Artykuły w czasopismach: „Mirror activation pattern”

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Slade, Justin M., Daniel M. Landers i Philip E. Martin. "Muscular Activity during Real and Imagined Movements: A Test of Inflow Explanations". Journal of Sport and Exercise Psychology 24, nr 2 (czerwiec 2002): 151–67. http://dx.doi.org/10.1123/jsep.24.2.151.

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Based on inflow explanations, the predictions related to EMG activity during imagery of a dumbbell and manipulandum curl were that EMG activity: (a) increases, relative to baseline, in both the biceps and triceps of the active arm; (b) is localized to muscles used in executing the real movement; and (c) mirrors the pattern of activity observed during the real movement. Based on literature which suggests that EMG activity during imagery may be due to expectancy effects, it was also hypothesized that EMG activity would be greater during imagery for those who were aware of the predictions of inflow explanations than for those who were unaware of those predictions. Undergraduate students (N = 60) completed a series of real and imagined dumbbell and manipulandum curls. For both movements, biceps and triceps EMG activity was measured in both the passive and active arms during baseline, imagery, and real movement conditions. No EMG differences were found between those who were aware or unaware of the predictions derived from inflow explanations. For both curls, average EMG biceps and triceps activity was significantly greater in the active arm during imagery than during baseline. Pattern analysis showed that the EMG activation patterns for biceps and triceps did not mirror the triphasic EMG pattern observed during the real movement. Results did not support the mirroring hypothesis (e.g., the psychoneuro-muscular theory), as the pattern of increased activation during imagery did not reflect that observed during the real movement.

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Sawada, Yukihiro, Yuichiro Nagano i Gohichi Tanaka. "Mirror Tracing and the Provocation of Vascular-Dominant Reaction Pattern Through Heightened Attention". Journal of Psychophysiology 16, nr 4 (grudzień 2002): 201–10. http://dx.doi.org/10.1027//0269-8803.16.4.201.

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Abstract After a hint from Lang et al.'s (1997) defence cascade, researchers considered cognitive process experienced when encountering mental stress to be composed of four elements: (serially) first attention (Attent), second unpleasant affect (UnplAff) and sometimes pleasant affect (PlAff), and third cognitive coping (CogCop). The present study investigates the effect of each cognitive element on the provocation of the well-known vascular-dominant reaction pattern during mirror tracing: elevation of mean blood pressure mainly because of increases in total peripheral resistance. Twenty-four male students first underwent four computer-simulated mirror-tracing practices of 3 min each, then a 7 min adaptation followed by a 3 min baseline, and further four kinds of actual mirror tracing trials (Attent, UnplAff, PlAff, and CogCop) of 3 min each. Results on the cardiovascular measures indicated that every mirror-tracing trial indisputably provoked the vascular-dominant reaction pattern. An alpha-adrenergic vascular sympathetic activation was heightened. Self-report measures on the four cognitive elements suggested that heightened Attent seemed to contribute to provoking the reaction pattern. Although the UnplAff and PlAff trials had an active coping feature in a narrow sense, they could not provoke the cardiac-dominant reaction pattern. Differences in task difficulty among the mirror tracings could not explain the results. The implications of these results are discussed in order to better understand cardiovascular hemodynamics during mental stress.

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Fernandez-Teran, M., M. E. Piedra, I. S. Kathiriya, D. Srivastava, J. C. Rodriguez-Rey i M. A. Ros. "Role of dHAND in the anterior-posterior polarization of the limb bud: implications for the Sonic hedgehog pathway". Development 127, nr 10 (15.05.2000): 2133–42. http://dx.doi.org/10.1242/dev.127.10.2133.

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dHAND is a basic helix-loop-helix (bHLH) transcription factor essential for cardiovascular development. Here we analyze its pattern of expression and functional role during chick limb development. dHAND expression was observed in the lateral plate mesoderm prior to emergence of the limb buds. Coincident with limb initiation, expression of dHAND became restricted to the posterior half of the limb bud. Experimental procedures that caused mirror-image duplications of the limb resulted in mirror-image duplications of the pattern of dHAND expression along the anterior-posterior axis. Retroviral overexpression of dHAND in the limb bud produced preaxial polydactyly, corresponding to mild polarizing activity at the anterior border. At the molecular level, misexpression of dHAND caused ectopic activation of members of the Sonic hedgehog (Shh) pathway, including Gli and Patched, in the anterior limb bud. A subset of infected embryos displayed ectopic anterior activation of Shh. Other factors implicated in anterior-posterior polarization of the bud such as the most 5′ Hoxd genes and Bmp2 were also ectopically activated at the anterior border. Our results indicate a role for dHAND in the establishment of anterior-posterior polarization of the limb bud.

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D'Ausilio, A., L. Maffongelli, E. Bartoli, M. Campanella, E. Ferrari, J. Berry i L. Fadiga. "Listening to speech recruits specific tongue motor synergies as revealed by transcranial magnetic stimulation and tissue-Doppler ultrasound imaging". Philosophical Transactions of the Royal Society B: Biological Sciences 369, nr 1644 (5.06.2014): 20130418. http://dx.doi.org/10.1098/rstb.2013.0418.

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The activation of listener's motor system during speech processing was first demonstrated by the enhancement of electromyographic tongue potentials as evoked by single-pulse transcranial magnetic stimulation (TMS) over tongue motor cortex. This technique is, however, technically challenging and enables only a rather coarse measurement of this motor mirroring. Here, we applied TMS to listeners’ tongue motor area in association with ultrasound tissue Doppler imaging to describe fine-grained tongue kinematic synergies evoked by passive listening to speech. Subjects listened to syllables requiring different patterns of dorso-ventral and antero-posterior movements (/ki/, /ko/, /ti/, /to/). Results show that passive listening to speech sounds evokes a pattern of motor synergies mirroring those occurring during speech production. Moreover, mirror motor synergies were more evident in those subjects showing good performances in discriminating speech in noise demonstrating a role of the speech-related mirror system in feed-forward processing the speaker's ongoing motor plan.

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Wongprasert, Y., R. Muanghlua i K. Sato. "The Diamond Crystal Nucleation by Combustion Activation CVD". Advanced Materials Research 55-57 (sierpień 2008): 557–60. http://dx.doi.org/10.4028/www.scientific.net/amr.55-57.557.

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This paper presents the diamond nucleation using combustion activation chemical vapor deposition (CACVD) by 0.95 volumetric ratio of O2 /C2H2 under atmospheric pressure. The main point of our work is to develop the CACVD technique for synthesize the semiconductor materials, which is developed for electronic devices application. The surface nucleation of substrate was studied by using surface pretreatment. The results of surface nucleation on mirror-silicon, polished silicon by diamond powder, silicon-dioxide (SiO2), and polished SiO2 by diamond powder, are significantly different. It can be concluded that the silicon-dioxide mask technique is useful for nucleated diamond protection whereas the polished silicon by diamond powder is suitable for nucleated diamond generation. These techniques are applied for the pattern fabrication.

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Kim, Sunah, Ryan A. Stevenson i Thomas W. James. "Visuo-haptic Neuronal Convergence Demonstrated with an Inversely Effective Pattern of BOLD Activation". Journal of Cognitive Neuroscience 24, nr 4 (kwiecień 2012): 830–42. http://dx.doi.org/10.1162/jocn_a_00176.

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We investigated the neural substrates involved in visuo-haptic neuronal convergence using an additive-factors design in combination with fMRI. Stimuli were explored under three sensory modality conditions: viewing the object through a mirror without touching (V), touching the object with eyes closed (H), or simultaneously viewing and touching the object (VH). This modality factor was crossed with a task difficulty factor, which had two levels. On the basis of an idea similar to the principle of inverse effectiveness, we predicted that increasing difficulty would increase the relative level of multisensory gain in brain regions where visual and haptic sensory inputs converged. An ROI analysis focused on the lateral occipital tactile–visual area found evidence of inverse effectiveness in the left lateral occipital tactile–visual area, but not in the right. A whole-brain analysis also found evidence for the same pattern in the anterior aspect of the intraparietal sulcus, the premotor cortex, and the posterior insula, all in the left hemisphere. In conclusion, this study is the first to demonstrate visuo-haptic neuronal convergence based on an inversely effective pattern of brain activation.

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Duprez, D. M., K. Kostakopoulou, P. H. Francis-West, C. Tickle i P. M. Brickell. "Activation of Fgf-4 and HoxD gene expression by BMP-2 expressing cells in the developing chick limb". Development 122, nr 6 (1.06.1996): 1821–28. http://dx.doi.org/10.1242/dev.122.6.1821.

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Bone morphogenetic protein-2 (BMP-2) has been implicated in the polarizing region signalling pathway, which specifies pattern across the antero-posterior of the developing vertebrate limb. Retinoic acid and Sonic Hedgehog (SHH) can act as polarizing signals; when applied anteriorly in the limb bud, they induce mirror-image digit duplications and ectopic Bmp-2 expression in anterior mesenchyme. In addition, the two signals can activate Fgf-4 expression in anterior ridge and HoxD expression in anterior mesenchyme. We tested the role of BMP-2 in this signalling cascade by ectopically expressing human BMP-2 (hBMP-2) at the anterior margin of the early wing bud using a replication defective retroviral vector, and found that ectopic expression of Fgf-4 was induced in the anterior part of the apical ectodermal ridge, followed later by ectopic expression of Hoxd-11 and Hoxd-13 in anterior mesenchyme. This suggests that BMP-2 is involved in regulating Fgf-4 and HoxD gene expression in the normal limb bud. Ectopically expressed hBMP-2 also induced duplication of digit 2 and bifurcation of digit 3, but could not produce the mirror-image digit duplications obtained with SHH-expressing cells. These results suggest that BMP-2 may be involved primarily in maintenance of the ridge, and in the link between patterning and outgrowth of the limb bud.

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Zhao, Shulei, Fang-Cheng Hung, Jennifer S. Colvin, Andrew White, Weilie Dai, Frank J. Lovicu, David M. Ornitz i Paul A. Overbeek. "Patterning the optic neuroepithelium by FGF signaling and Ras activation". Development 128, nr 24 (15.12.2001): 5051–60. http://dx.doi.org/10.1242/dev.128.24.5051.

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During vertebrate embryogenesis, the neuroectoderm differentiates into neural tissues and also into non-neural tissues such as the choroid plexus in the brain and the retinal pigment epithelium in the eye. The molecular mechanisms that pattern neural and non-neural tissues within the neuroectoderm remain unknown. We report that FGF9 is normally expressed in the distal region of the optic vesicle that is destined to become the neural retina, suggesting a role in neural patterning in the optic neuroepithelium. Ectopic expression of FGF9 in the proximal region of the optic vesicle extends neural differentiation into the presumptive retinal pigment epithelium, resulting in a duplicate neural retina in transgenic mice. Ectopic expression of constitutively active Ras is also sufficient to convert the retinal pigment epithelium to neural retina, suggesting that Ras-mediated signaling may be involved in neural differentiation in the immature optic vesicle. The original and the duplicate neural retinae differentiate and laminate with mirror-image polarity in the absence of an RPE, suggesting that the program of neuronal differentiation in the retina is autonomously regulated. In mouse embryos lacking FGF9, the retinal pigment epithelium extends into the presumptive neural retina, indicating a role of FGF9 in defining the boundary of the neural retina.

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Nacharova, M. A., A. A. Mikhailova, Ya Yu Govorun, A. A. Portugalskaia i V. B. Pavlenko. "NEUROPHYSIOLOGICAL MECHANISMS OF SPEECH PERCEPTION AND THEIR PERCULARITIES IN HEALTHY CHILDREN AND CHILDREN WITH DEVELOPMENTAL DISORDERS". Scientific Notes of V.I. Vernadsky Crimean Federal University. Biology. Chemistry 6(72), nr 3 (2021): 146–62. http://dx.doi.org/10.37279/2413-1725-2020-6-3-146-162.

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Neuronal synchronization, reflected in the EEG pattern, is the mechanism by which the brain integrates different types of information contained in a speech message and presented in different areas of the brain (for example, phonological, spelling, semantic and syntactic information). The process of understanding a sentence consists of two groups of interrelated cognitive operations: it begins with searching in memory for phonological, syntactic and semantic properties of words, which is followed by integrating information into a general idea of the sentence meaning. The stage of searching for words in adults results in an increase in the theta rhythm power. The stage of integrating words into a sentence results in the growth of theta, beta, and gamma rhythms. At the same time, the growth of theta rhythm is more typical for children than for adults. Higher rhythms reactivity during speech perception indicates better developed speech skills in children. Under conditions of relative relaxation, the EEG of children with a high level of speech development is characterized by a moderate power level of theta and beta rhythms and a high level of alpha and mu rhythms. It is assumed that a key role in the process of understanding speech is played by the so-called «action perception circuits», surrounding the Sylvian sulcus of the left hemisphere. The «action perception circuits» are composed of nerve cells capable of providing the speech signals perception and generation. The most important subgroup of neurons included in the «action perception circuits» are mirror neurons that are activated when performing and observing actions. The desynchronization of the EEG mu rhythm is considered as mirror neurons activation marker. In several studies, it revealed that the level of mirror neurons activation and the level of speech understanding in children are connected. It is a topic of great interest to research the mu rhythm alpha and beta components reactivity both during the production of speech and during the perception of another person speech. At present, it is becoming obvious that analyzing the EEG rhythms power changes during the speech understanding in different scenarios could be used to identify the mechanisms of the brain language network and speech disorders. The revealed patterns make it possible to propose ways of correcting the children speech development using EEG biological feedback methods.

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COSTA, LUCIANO DA FONTOURA, i OLAF SPORNS. "DIVERSITY OF CORTICAL STATES AT NONEQUILIBRIUM SIMULATED BY THE ANTI-FERROMAGNETIC ISING MODEL UNDER METROPOLIS DYNAMICS". International Journal of Bifurcation and Chaos 17, nr 07 (lipiec 2007): 2387–98. http://dx.doi.org/10.1142/s0218127407018464.

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This article investigates the relationship between the interconnectivity and simulated dynamics of the thalamocortical system from the specific perspective of attempting to maximize the diversity of cortical states. This is achieved by designing the dynamics such that they favor opposing activity between adjacent regions, thus promoting dynamic diversity while avoiding widespread activation or de-activation. The anti-ferromagnetic Ising model with Metropolis dynamics is adopted and applied to four variations of the large-scale connectivity of the cat thalamocortical system: (a) considering only cortical regions and connections; (b) considering the entire thalamocortical system; (c) the same as in (b) but with the thalamic connections rewired so as to maintain the statistics of node degree and node degree correlations; and (d) as in (b) but with attenuated weights of the connections between cortical and thalamic nodes. A series of interesting findings are obtained, including the identification of specific substructures revealed by correlations between the activity of adjacent regions in case (a) and a pronounced effect of the thalamic connections in splitting the thalamocortical regions into two large groups of nearly homogenous opposite activation (i.e. cortical regions and thalamic nuclei, respectively) in cases (b) and (c). The latter effect is due to the existence of dense connections between cortical and thalamic regions and the lack of interconnectivity between the latter. Another interesting result regarding case (d) is the fact that the pattern of thalamic correlations tend to mirror that of the cortical regions. The possibility to control the level of correlation between the cortical regions by varying the strength of thalamocortical connections is also identified and discussed.

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Kopp, A., i I. Duncan. "Control of cell fate and polarity in the adult abdominal segments of Drosophila by optomotor-blind". Development 124, nr 19 (1.10.1997): 3715–26. http://dx.doi.org/10.1242/dev.124.19.3715.

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In an accompanying report (Kopp, A., Muskavitch, M. A. T. and Duncan, I. (1997) Development 124, 3703–3714), we show that Hh protein secreted by posterior compartment cells patterns the posterior portion of the anterior compartment in adult abdominal segments. Here we show that this function of hh is mediated by optomotor-blind (omb). omb- mutants mimic the effects of loss-of-function alleles of hh: structures from the posterior of the anterior compartment are lost, and often this region develops as a mirror image of the anterior portion. Structures from the anterior part of the posterior compartment are also lost. In the pupa, omb expression in abdominal histoblasts is highest at or near the compartment boundary, and decreases in a shallow gradient toward the anterior. This gradient is due to activation of omb by Hh secreted by posterior compartment cells. In contrast to imaginal discs, this Hh signaling is not mediated by dpp or wg. We describe several gain-of-function alleles that cause ectopic expression of omb in the anterior of the segment. Most of these cause the anterior region to develop with posterior characteristics without affecting polarity. However, an allele that drives high level ubiquitous expression of omb (QdFab) causes the anterior tergite to develop as a mirror-image duplication of the posterior tergite, a pattern opposite to that seen in omb- mutants. Ubiquitous expression of hh causes similar double-posterior patterning. We find that omb- alleles suppress this effect of ectopic hh expression and that posterior patterning becomes independent of hh in the QdFab mutant. These observations indicate that omb is the primary target of hh signaling in the adult abdomen. However, it is clear that other targets exist. One of these is likely Scruffy, a novel gene that we describe, which acts in parallel to omb. To explain the effects of omb alleles, we propose that both anterior and posterior compartments in the abdomen are polarized by underlying symmetric gradients of unknown origin. We suggest that omb has two functions. First, it specifies the development of appropriate structures both anterior and posterior to the compartment boundary. Second, it causes cells to reverse their interpretation of polarity specified by the underlying symmetric gradients.

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Ruiz, Marta, Marco Puthenparampil, Marta Campagnolo, Francesca Castellani, Alessandro Salvalaggio, Susanna Ruggero, Elisabetta Toffanin i in. "Oligoclonal IgG bands in chronic inflammatory polyradiculoneuropathies". Journal of Neurology, Neurosurgery & Psychiatry 92, nr 9 (13.04.2021): 969–74. http://dx.doi.org/10.1136/jnnp-2020-325868.

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BackgroundCerebrospinal fluid (CSF) albumincytologic dissociation represents a supportive diagnostic criterion of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).Few studies have investigated possible systemic or intrathecal humoral immune response activation in CIDP.Aim of our study was to investigate whether the search of oligoclonal IgG bands (OCBs) might provide additional data helpful in CIDP diagnostic work-up.MethodsForty-eight consecutive patients with CIDP (34 men, mean age 59.4, range 16–83) were recruited. CSF analysis included nephelometric measurement of albumin and IgG concentrations, calculation of QALB, QAlbLIM and intrathecal IgG synthesis, and OCBs detection with isoelectric focusing. Data were compared with those from CSF and serum of 32 patients with Guillain-Barré syndrome (GBS), 18 patients with anti-myelin associated glycoprotein (MAG) antibody neuropathy, 4 patients with multifocal motor neuropathy and 32 patients with non-inflammatory neuropathies (NINPs).ResultsPatients with CIDP and anti-MAG antibody neuropathy had significantly higher CSF albumin concentrations and QALB values than NINPs (p=0.0003 and p=0.0095, respectively). A total of 9 (19%) patients with CIDP presented identical serum and CSF OCBs (‘mirror pattern’) versus 3 patients (16.6%) with anti-MAG antibody neuropathy, 13 patients (40.6%) with GBS and 12.5% patients with NINPs. Only one patient with CIDP showed unique-to-CSF OCBs. First-line therapy was effective in 80.4% of patients with CIDP, irrespective of CSF findings.ConclusionsCompared with NINP, CIDP, GBS and anti-MAG antibody neuropathies had a significantly increased CSF protein and blood–spinal nerve root barrier damage. Intrathecal humoral immune response is rare in our patients with CIDP. Systemic oligoclonal activation is more frequent, but not significantly different from what was detected in the control groups.

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Lai, Yu-Heng, Gilbert Audira, Sung-Tzu Liang, Petrus Siregar, Michael Edbert Suryanto, Huan-Chau Lin, Omar Villalobos i in. "Duplicated dnmt3aa and dnmt3ab DNA Methyltransferase Genes Play Essential and Non-Overlapped Functions on Modulating Behavioral Control in Zebrafish". Genes 11, nr 11 (7.11.2020): 1322. http://dx.doi.org/10.3390/genes11111322.

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DNA methylation plays several roles in regulating neuronal proliferation, differentiation, and physiological functions. The major de novo methyltransferase, DNMT3, controls the DNA methylation pattern in neurons according to environmental stimulations and behavioral regulations. Previous studies demonstrated that knockout of Dnmt3 induced mouse anxiety; however, controversial results showed that activation of Dnmt3 causes anxiolytic behavior. Thus, an alternative animal model to clarify Dnmt3 on modulating behavior is crucial. Therefore, we aimed to establish a zebrafish (Danio rerio) model to clarify the function of dnmt3 on fish behavior by behavioral endpoint analyses. We evaluated the behaviors of the wild type, dnmt3aa, and dnmt3ab knockout (KO) fish by the novel tank, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm locomotor activity, color preference, and short-term memory tests. The results indicated that the dnmt3aa KO fish possessed abnormal exploratory behaviors and less fear response to the predator. On the other hand, dnmt3ab KO fish displayed less aggression, fear response to the predator, and interests to interact with their conspecifics, loosen shoaling formation, and dysregulated color preference index ranking. Furthermore, both knockout fishes showed higher locomotion activity during the night cycle, which is a sign of anxiety. However, changes in some neurotransmitter levels were observed in the mutant fishes. Lastly, whole-genome DNA methylation sequencing demonstrates a potential network of Dnmt3a proteins that is responsive to behavioral alterations. To sum up, the results suggested that the dnmt3aa KO or dnmt3ab KO fish display anxiety symptoms, which supported the idea that Dnmt3 modulates the function involved in emotional control, social interaction, and cognition.

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Bello, Umar M., Stanley J. Winser i Chetwyn C. H. Chan. "Role of kinaesthetic motor imagery in mirror-induced visual illusion as intervention in post-stroke rehabilitation". Reviews in the Neurosciences 31, nr 6 (27.08.2020): 659–74. http://dx.doi.org/10.1515/revneuro-2019-0106.

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AbstractMirror-induced visual illusion obtained through mirror therapy is widely used to facilitate motor recovery after stroke. Activation of primary motor cortex (M1) ipsilateral to the moving limb has been reported during mirror-induced visual illusion. However, the mechanism through which the mirror illusion elicits motor execution processes without movements observed in the mirrored limb remains unclear. This study aims to review evidence based on brain imaging studies for testing the hypothesis that neural processes associated with kinaesthetic motor imagery are attributed to ipsilateral M1 activation. Four electronic databases were searched. Studies on functional brain imaging, investigating the instant effects of mirror-induced visual illusion among stroke survivors and healthy participants were included. Thirty-five studies engaging 78 stroke survivors and 396 healthy participants were reviewed. Results of functional brain scans (n = 20) indicated that half of the studies (n = 10, 50%) reported significant changes in the activation of ipsilateral M1, which mediates motor preparation and execution. Other common neural substrates included primary somatosensory cortex (45%, kinaesthesia), precuneus (40%, image generation and self-processing operations) and cerebellum (20%, motor control). Similar patterns of ipsilateral M1 activations were observed in the two groups. These neural substrates mediated the generation, maintenance, and manipulation of motor-related images, which were the key processes in kinaesthetic motor imagery. Relationships in terms of shared neural substrates and mental processes between mirror-induced visual illusion and kinaesthetic motor imagery generate new evidence on the role of the latter in mirror therapy. Future studies should investigate the imagery processes in illusion training for post-stroke patients.

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Knezevic, V., R. De Santo, K. Schughart, U. Huffstadt, C. Chiang, K. A. Mahon i S. Mackem. "Hoxd-12 differentially affects preaxial and postaxial chondrogenic branches in the limb and regulates Sonic hedgehog in a positive feedback loop". Development 124, nr 22 (15.11.1997): 4523–36. http://dx.doi.org/10.1242/dev.124.22.4523.

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Several 5′ members of the Hoxd cluster are expressed in nested posterior-distal domains of the limb bud suggesting a role in regulating anteroposterior pattern of skeletal elements. While loss-of-function mutants have demonstrated a regulatory role for these genes in the developing limb, extensive functional overlaps between various different Hox genes has hampered elucidation of the roles played by individual members. In particular, the function of Hoxd-12 in the limb remains obscure. Using a gain-of-function approach, we find that Hoxd-12 misexpression in transgenic mice produces apparent transformations of anterior digits to posterior morphology and digit duplications, while associated tibial hemimelia and other changes indicate that formation/growth of certain skeletal elements is selectively inhibited. If the digital arch represents an anterior bending of the main limb axis, then the results are all reconcilable with a model in which Hoxd-12 promotes formation of postaxial chondrogenic condensations branching from this main axis (including the anteriormost digit) and selectively antagonizes formation of ‘true’ preaxial condensations that branch from this main axis (such as the tibia). Hoxd-12 misexpression can also induce ectopic Sonic hedgehog (Shh) expression, resulting in mirror-image polydactyly in the limb. Misexpression of Hoxd-12 in other lateral plate derivatives (sternum, pelvis) likewise phenocopies several luxoid/luxate class mouse mutants that all share ectopic Shh signalling. This suggests that feedback activation of Shh expression may be a major function of Hoxd-12. Hoxd-12 can bind to and transactivate the Shh promoter in vitro. Furthermore, expression of either exogenous Hoxd-11 or Hoxd-12 in cultured limb bud cells, together with FGF, induces expression of the endogenous Shh gene. Together these results suggest that certain 5′ Hoxd genes directly amplify the posterior Shh polarizing signal in a reinforcing positive feedback loop during limb bud outgrowth.

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Sommer, Iris, Nick Ramsey, Doortje Graafmans, Rene Mandl, Anke Bouma i Rene Kahn. "Mirror-imaged language activation patterns in healthy monozygotic twins". NeuroImage 13, nr 6 (czerwiec 2001): 607. http://dx.doi.org/10.1016/s1053-8119(01)91950-0.

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Patten, Piers E. M., Shih-Shih Chen, Davide Bagnara, Rita Simone, Sonia Marsilio, Xiao-Jie Yan, Jacqueline C. Barrientos i in. "CLL Cells Can Diversify, Switch, and Differentiate in Response to Autologous T Cell Stimuli Present in a Murine Adoptive Transfer Model". Blood 120, nr 21 (16.11.2012): 315. http://dx.doi.org/10.1182/blood.v120.21.315.315.

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Abstract Abstract 315 Adoptive transfer of primary patient CLL cells into NOD/SCID/γcnull(NSG) mice results in engraftment and proliferation of CLL cells if autologous T cells are present. Formation of splenic follicles consisting of B cells interspersed and surrounded by T cells indicates engraftment. However, ultimately these CD20+ cells are lost several weeks later. We describe one of the mechanisms for this apparent loss: differentiation to plasma cells. Peripheral blood cells from 9 IgM+ CLL patients (6 U-CLL and 3 M-CLL) were adoptively transferred into NSG mice with enriched autologous CD3+ cells pre-activated with anti-CD3/28 beads. B and T cell engraftment and subset distributions were analyzed for 47 mice by immunohistochemistry (IHC) and flow cytometry (FC) at the time of sacrifice. The earliest and latest times of assessment were 12 and 124 days, respectively, after CLL cell injection. In some cases, CLL cells were labeled with CFSE to track cell division. At sacrifice, 3 engraftment patterns were observed. Pattern 1 (observed up to day 56) showed small follicles of CD20+ cells with low-moderate numbers of surrounding T cells. Intensely positive CD38 cells were inconspicuous. FC showed CD19+CD5+ cells with no increase in CD38 and variable CFSE dilution indicating lower levels of proliferation. Pattern 2 (observed throughout the study period) showed much higher T and B cell numbers. CD20+ cells were interspersed with and surrounded by principally CD4+ cells which were activated and functional as indicated by expression of Ki-67, PD-1, CD57, and T cell derived cytokines IFNγ and IL5 in plasma. Follicles contained CD20 and cytoplasmic Ig+ (cIg+) cells that double stained for IRF-4 and Blimp-1, transcription factors required for B cell differentiation. While Bcl-6 staining in these cells was minimal or absent, follicles from all 9 patients contained activation-induced deaminase (AID)+ cells. Cells with dim IgM expression localized to follicles; however, cells with intense IgM, IgA, or IgG were present both within, surrounding, and outside follicles matched by similar CD38 staining. Smaller populations of CD138+ cells surrounded follicles and were interspersed throughout non-follicular splenic areas. FC showed a novel CD19+CD5-CFSE-CD38++ population containing a CD138+ subset. Pattern 3 (observed in a limited subset of cases not before day 63) had minimal CD20+ cells by IHC, but noticeable populations of cIg+CD38+ and CD138+ cells interspersed amongst plentiful T cells. Such cells corresponded with cells with plasma cell morphology. Confirmation that differentiated cells were from the patient clone was achieved in 3 ways. First, in FACS sorted CD19+CD5+ and CD19+CD5-38++ cells from a subset of pattern 2 cases, RT-PCR revealed that all fractions contained both IGHC unswitched and switched clones identical to those found in the patients. Second, cases with pattern 3 engraftment generated CLL clonal switched and unswitched cDNA sequences. Finally, adoptive transfer of highly purified CD5+CD19+ patient cells generated IRF-4+Blimp-1+CD138+ cells. The generation of switched cells from all 9 patients indicated functional AID. In one U- CLL case, ultra-deep sequencing on pre-transfer and post-transfer human cells taken from mouse spleen revealed a significant number of new IGHVDJ mutations in spleen-derived cells. Such mutations targeted nucleotides typical for AID's action. In conclusion, CLL cells can diversify, switch, and differentiate in NSG mice in response to autologous T cell signals. The extent of this maturation is a function of T cell numbers and activity and the duration of the experiment. Differentiation without significant Bcl-6 expression suggests that follicles in NSG mice are not recapitulating classic germinal center reactions, possibly giving clues to the origin of CLL. Several features of poor prognosis disease were demonstrated (e.g., increased CD38 and AID expression with the development of clonally related switched transcripts) that might mirror clinical disease features. AID expressed by CLL cells is fully functional as indicated by de novo somatic hypermutation and class switch recombination. Both U-CLL and M-CLL clones respond in a similar manner in this model, suggesting the importance of T– B cell interactions in all types of CLL. Finally, the demonstration that cells can differentiate when appropriately induced may lead to novel therapeutic options for CLL. Disclosures: No relevant conflicts of interest to declare.

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Jang, Seon Hee, i Frank E. Pollick. "Experience Influences Brain Mechanisms of Watching Dance". Dance Research 29, supplement (listopad 2011): 352–77. http://dx.doi.org/10.3366/drs.2011.0024.

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The study of dance has been helpful to advance our understanding of how human brain networks of action observation are influenced by experience. However previous studies have not examined the effect of extensive visual experience alone: for example, an art critic or dance fan who has a rich experience of watching dance but negligible experience performing dance. To explore the effect of pure visual experience we performed a single experiment using functional Magnetic Resonance Imaging (fMRI) to compare the neural processing of dance actions in 3 groups: a) 14 ballet dancers, b) 10 experienced viewers, c) 12 novices without any extensive dance or viewing experience. Each of the 36 participants viewed short 2-second displays of ballet derived from motion capture of a professional ballerina. These displays represented the ballerina as only points of light at the major joints. We wished to study the action observation network broadly and thus included two different types of display and two different tasks for participants to perform. The two different displays were: a) brief movies of a ballet action and b) frames from the ballet movies with the points of lights connected by lines to show a ballet posture. The two different tasks were: a) passively observe the display and b) imagine performing the action depicted in the display. The two levels of display and task were combined factorially to produce four experimental conditions (observe movie, observe posture, motor imagery of movie, motor imagery of posture). The set of stimuli used in the experiment are available for download after this paper. A random effects ANOVA was performed on brain activity and an effect of experience was obtained in seven different brain areas including: right Temporoparietal Junction (TPJ), left Retrosplenial Cortex (RSC), right Primary Somatosensory Cortex (S1), bilateral Primary Motor Cortex (M1), right Orbitofrontal Cortex (OFC), right Temporal Pole (TP). The patterns of activation were plotted in each of these areas (TPJ, RSC, S1, M1, OFC, TP) to investigate more closely how the effect of experience changed across these areas. For this analysis, novices were treated as baseline and the relative effect of experience examined in the dancer and experienced viewer groups. Interpretation of these results suggests that both visual and motor experience appear equivalent in producing more extensive early processing of dance actions in early stages of representation (TPJ and RSC) and we hypothesise that this could be due to the involvement of autobiographical memory processes. The pattern of results found for dancers in S1 and M1 suggest that their perception of dance actions are enhanced by embodied processes. For example, the S1 results are consistent with claims that this brain area shows mirror properties. The pattern of results found for the experienced viewers in OFC and TP suggests that their perception of dance actions are enhanced by cognitive processes. For example, involving aspects of social cognition and hedonic processing – the experienced viewers find the motor imagery task more pleasant and have richer connections of dance to social memory. While aspects of our interpretation are speculative the core results clearly show common and distinct aspects of how viewing experience and physical experience shape brain responses to watching dance.

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Molenberghs, Pascal, Lydia Hayward, Jason B. Mattingley i Ross Cunnington. "Activation patterns during action observation are modulated by context in mirror system areas". NeuroImage 59, nr 1 (styczeń 2012): 608–15. http://dx.doi.org/10.1016/j.neuroimage.2011.07.080.

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Shieh, Angell C., i Kevin M. Shannon. "Role of Downstream Effectors in Kras-Driven Myeloproliferative Disease." Blood 110, nr 11 (16.11.2007): 1617. http://dx.doi.org/10.1182/blood.v110.11.1617.1617.

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Abstract Mutations that deregulate Ras signaling are highly prevalent in myeloid malignancies. Previous work has shown that expressing oncogenic KrasG12D in hematopoietic cells from the endogenous Kras promoter leads to growth factor-independent and hypersensitive myeloid progenitor colony formation, and causes a fatal myeloproliferative disorder (MPD) (Braun et al PNAS101:597, 2004; Chan et al JCI113:528, 2004). These characteristics mirror the human juvenile and chronic myelomonocytic leukemias (JMML and CMML) - diseases that are associated with Ras pathway mutations. Oncogenic Ras accumulates in its active GTP-bound form and constitutively activates a number of downstream effectors. However, it is unclear which effectors are necessary for the maintenance of disease as well as how they contribute to specific phenotypes such as enhanced proliferation and defective apoptosis. We constructed second site mutants - secondary mutations on a backbone of KrasG12D(G12D) that prevent K-RasG12D from binding to a subset of effectors - to begin to elucidate the individual contributions of downstream effector pathways to hematologic disease. Murine fetal liver cells engineered to express KrasG12D,E37G(E37G) and KrasG12D,Y64G(Y64G) second site mutants maintain a hypersensitive pattern of colony-forming unit granulocyte-macrophage (CFU-GM) colony growth in response to granulocyte-macrophage colony-stimulating factor (GM-CSF), but are no longer able to grow in the absence of GM-CSF. Interestingly, both mutant proteins that display hypersensitivity also hyperactivate two major Ras effector pathways, as opposed to other second site mutants tested which only hyperactivate one major Ras effector pathway and do not show growth factor hypersensitivity. Whereas E37G activates both PI3 kinase and Ral-GDS but not Raf, Y64G stimulates Raf/MEK/ERK and PI3 kinase but not Ral-GDS. Consistent with the idea that activation of at least two effector cascades is required for aberrant in vitro growth, expression of activated effectors BrafV600E, p110a-CAAX, and RalGDS-CAAX did not confer GM-CSF hypersensitivity on CFU-GM colonies. We transplanted bone marrow cells transduced with MSCV-E37G-IRES-GFP or MSCV-Y64G-IRES-GFP retroviruses into lethally irradiated Balb/c mice. Seven of 8 mice that received Y64G cells died of T lineage acute lymphoid leukemia/lymphoma (T-ALL/L) with a median survival of 112 days. Diseased animals showed very high levels of GFP in the thymus, spleen, peripheral blood and bone marrow. Four of 9 mice injected with E37G-expressing cells mice also died of T-ALL/L with a median survival of 106 days and three of 9 died of anemia. None of the MIG mice (n=8) have died of leukemia/lymphoma. The Y64G and E37G T ALL/Ls studied to date are transplantable into sublethally irradiated recipients. We conclude that second site mutations in the KrasG12D oncogene that are defective for activation of either PI3 kinase or Raf/MEK/ERK are able to deregulate the growth of primary hematopoietic cells in vitro and in vivo. These data argue that targeting a single effector pathway downstream of oncogenic Ras may not be effective in many hematologic malignancies. We are interrogating Ras signaling networks in T-ALL/L cells and cloning MSCV integration sites to further characterize the effects of these second site mutant alleles.

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Dreyer, Alexander M., i Jochem W. Rieger. "High-gamma mirror activity patterns in the human brain during reach-to-grasp movement observation, retention, and execution—An MEG study". PLOS ONE 16, nr 12 (2.12.2021): e0260304. http://dx.doi.org/10.1371/journal.pone.0260304.

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While the existence of a human mirror neuron system is evident, the involved brain areas and their exact functional roles remain under scientific debate. A number of functionally different mirror neuron types, neurons that selectively respond to specific grasp phases and types for example, have been reported with single cell recordings in monkeys. In humans, spatially limited, intracranially recorded electrophysiological signals in the high-gamma (HG) range have been used to investigate the human mirror system, as they are associated with spiking activity in single neurons. Our goal here is to complement previous intracranial HG studies by using magnetoencephalography to record HG activity simultaneously from the whole head. Participants performed a natural reach-to-grasp movement observation and delayed imitation task with different everyday objects and grasp types. This allowed us to characterize the spatial organization of cortical areas that show HG-activation modulation during movement observation (mirroring), retention (mnemonic mirroring), and execution (motor control). Our results show mirroring related HG modulation patterns over bilateral occipito-parietal as well as sensorimotor areas. In addition, we found mnemonic mirroring related HG modulation over contra-lateral fronto-temporal areas. These results provide a foundation for further human mirror system research as well as possible target areas for brain-computer interface and neurorehabilitation approaches.

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Lee, Mi Young, Jin Ho Choi, Rae Joon Park, Yong Hyun Kwon, Jong Sung Chang, Jun Lee, Sang Ho Ahn i Sung Ho Jang. "Clinical Characteristics and Brain Activation Patterns of Mirror Movements in Patients with Corona Radiata Infarct". European Neurology 64, nr 1 (2010): 15–20. http://dx.doi.org/10.1159/000313979.

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Weiss, Erica J., i Martha Flanders. "Muscular and Postural Synergies of the Human Hand". Journal of Neurophysiology 92, nr 1 (lipiec 2004): 523–35. http://dx.doi.org/10.1152/jn.01265.2003.

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Because humans have limited ability to independently control the many joints of the hand, a wide variety of hand shapes can be characterized as a weighted combination of just two or three main patterns of covariation in joint rotations, or “postural synergies.” The present study sought to align muscle synergies with these main postural synergies and to describe the form of membership of motor units in these postural/muscle synergies. Seventeen joint angles and the electromyographic (EMG) activities of several hand muscles (both intrinsic and extrinsic muscles) were recorded while human subjects held the hand statically in 52 specific shapes (i.e., shaping the hand around 26 commonly grasped objects or forming the 26 letter shapes of a manual alphabet). Principal-components analysis revealed several patterns of muscle synergy, some of which represented either coactivation of all hand muscles, or reciprocal patterns of activity (above and below average levels) in the intrinsic index finger and thumb muscles or (to a lesser extent) in the extrinsic four-tendoned extensor and flexor muscles. Single- and multiunit activity was generally a multimodal function of whole hand shape. This implies that motor-unit activation does not align with a single synergy; instead, motor units participate in multiple muscle synergies. Thus it appears that the organization of the global pattern of hand muscle activation is highly distributed. This organization mirrors the highly fractured somatotopy of cortical hand representations and may provide an ideal substrate for motor learning and recovery from injury.

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Coudé, Gino, i Pier Francesco Ferrari. "Reflections on the differential organization of mirror neuron systems for hand and mouth and their role in the evolution of communication in primates". Interaction Studies 19, nr 1-2 (17.09.2018): 38–53. http://dx.doi.org/10.1075/is.17037.cou.

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Abstract It is now generally accepted that the motor system is not purely dedicated to the control of behavior, but also has cognitive functions. Mirror neurons have provided a new perspective on how sensory information regarding others’ actions and gestures is coupled with the internal cortical motor representation of them. This coupling allows an individual to enrich his interpretation of the social world through the activation of his own motor representations. Such mechanisms have been highly preserved in evolution as they are present in humans, apes and monkeys. Recent neuroanatomical data showed that there are two different connectivity patterns in mirror neuron networks in the macaque: one is concerned with sensorimotor transformation in relation to reaching and hand grasping within the traditional parietal-premotor circuits; the second one is linked to the mouth/face motor control and the new data show that it is connected with limbic structures. The mouth mirror sector seems to be wired not only for ingestive behaviors but also for orofacial communicative gestures and vocalizations. Notably, the hand and mouth mirror networks partially overlap, suggesting the importance of hand-mouth synergies not only for sensorimotor transformation, but also for communicative purposes in order to better convey and control social signals.

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Colantonio, Lucia, Andrea Iellem, Barbara Clissi, Ruggero Pardi, Lars Rogge, Francesco Sinigaglia i Daniele D’Ambrosio. "Upregulation of Integrin 6/β1 and Chemokine Receptor CCR1 by Interleukin-12 Promotes the Migration of Human Type 1 Helper T Cells". Blood 94, nr 9 (1.11.1999): 2981–89. http://dx.doi.org/10.1182/blood.v94.9.2981.

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Abstract CD4+ T helper 1 (Th1) cells and Th2 cells are distinguished based on the pattern of cytokines they are able to produce. Selectin ligands and chemokine receptors are differentially expressed in Th1 and Th2 cells, providing a basis for tissue-specific recruitment of helper T-cell subsets. However, the modes and mechanisms regulating tissue-specific localization of Th1 and Th2 cells are still largely unknown. Here, we show the preferential expression on Th1 cells of the integrin 6/β1, which is distinctly regulated by the Th1-inducing cytokines interleukin-12 (IL-12) and interferon-alfa (IFN-). The pattern of integrin 6/β1 regulation closely mirrors that of the chemokine receptor CCR1. Analysis of signal transducer and activator of transcription 4 (Stat4) activation by IL-12 and IFN- shows distinct signaling kinetics by these cytokines, correlating with the pattern of CCR1 and integrin 6/β1 expression. Unlike IFN-, the ability of IL-12 to generate prolonged intracellular signals appears to be critical for inducing integrin 6/β1 upregulation in Th1 cells. The expression and upregulation of CCR1 and 6/β1 integrin promotes the migration of Th1 cells. These findings suggest that the exquisite regulation of integrin 6/β1 and CCR1 may play an important role in tissue-specific localization of Th1 cells.

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Colantonio, Lucia, Andrea Iellem, Barbara Clissi, Ruggero Pardi, Lars Rogge, Francesco Sinigaglia i Daniele D’Ambrosio. "Upregulation of Integrin 6/β1 and Chemokine Receptor CCR1 by Interleukin-12 Promotes the Migration of Human Type 1 Helper T Cells". Blood 94, nr 9 (1.11.1999): 2981–89. http://dx.doi.org/10.1182/blood.v94.9.2981.421k27_2981_2989.

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CD4+ T helper 1 (Th1) cells and Th2 cells are distinguished based on the pattern of cytokines they are able to produce. Selectin ligands and chemokine receptors are differentially expressed in Th1 and Th2 cells, providing a basis for tissue-specific recruitment of helper T-cell subsets. However, the modes and mechanisms regulating tissue-specific localization of Th1 and Th2 cells are still largely unknown. Here, we show the preferential expression on Th1 cells of the integrin 6/β1, which is distinctly regulated by the Th1-inducing cytokines interleukin-12 (IL-12) and interferon-alfa (IFN-). The pattern of integrin 6/β1 regulation closely mirrors that of the chemokine receptor CCR1. Analysis of signal transducer and activator of transcription 4 (Stat4) activation by IL-12 and IFN- shows distinct signaling kinetics by these cytokines, correlating with the pattern of CCR1 and integrin 6/β1 expression. Unlike IFN-, the ability of IL-12 to generate prolonged intracellular signals appears to be critical for inducing integrin 6/β1 upregulation in Th1 cells. The expression and upregulation of CCR1 and 6/β1 integrin promotes the migration of Th1 cells. These findings suggest that the exquisite regulation of integrin 6/β1 and CCR1 may play an important role in tissue-specific localization of Th1 cells.

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Schild, J. H., J. W. Clark, C. C. Canavier, D. L. Kunze i M. C. Andresen. "Afferent synaptic drive of rat medial nucleus tractus solitarius neurons: dynamic simulation of graded vesicular mobilization, release, and non-NMDA receptor kinetics". Journal of Neurophysiology 74, nr 4 (1.10.1995): 1529–48. http://dx.doi.org/10.1152/jn.1995.74.4.1529.

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1. We have developed a comprehensive mathematical model of an afferent synaptic connection to the soma of a medial nucleus tractus solitarius (mNTS) neuron. Model development is based on numerical fits to quantitative data recorded in our laboratory. This work is part of a continuing collaborative effort aimed at identifying and characterizing the mechanisms responsible for the non-linear integrative properties of this first synapse in the baroreceptor reflex. 2. The complete model consists of three major parts: 1) a Hodgkin-Huxley (HH)-type membrane model of the prejunctional sensory terminal bouton; 2) a multistage model describing vesicular storage, adenosine 3',5'-cyclic monophosphate (cAMP)- and Ca(2+)-dependent mobilization, release and recycling; and 3) a HH-type membrane model of the postjunctional mNTS cell that includes descriptions for a desensitizing non-N-methyl-D-aspartate (NMDA) ionic current that is responsible for the fast excitatory postsynaptic potentials (EPSPs) observed in mNTS cells. The membrane models for both the terminal bouton and the mNTS neuron are coupled to separate lumped fluid compartment models describing intracellular Ca2+ ion concentration dynamics. 3. Our modeling strategy is twofold. The first is to validate model performance by reproducing a wide variety of experimental data both from our laboratory and from the literature. The second is to explore the functional aspects of the model in order to gain a greater appreciation for the balance between presynaptic mechanisms (e.g., terminal membrane properties and vesicular dynamics) and postsynaptic mechanisms (e.g., non-NMDA receptor kinetics and neuronal dynamics) that underlie the afferent synaptic drive of mNTS neurons. 4. The model accurately reproduces EPSP dynamics recorded with the use of a wide range of stimulus protocols. The model can also mirror the unique pattern of graded frequency- and use-dependent reduction in peak EPSP magnitude observed experimentally through 60 s of constant, suprathreshold synaptic activation. We demonstrate how vesicular mobilization, recycling, and receptor kinetics can function synergistically in establishing synaptic transfer. Furthermore, we show that by allowing the aggregate rate of vesicle mobilization to respond in a use-dependent manner, it is possible to compensate for the attenuating affects of desensitization at elevated rates of stimulation. 5. Our simulations indicate that the low-frequency characteristics of this synapse are dominated by vesicular dynamics, whereas the high-frequency properties arise from a combination of Ca(2+)-dependent vesicular mobilization and the kinetics of the non-NMDA receptor. Desensitization can influence the peak magnitude and decay time of the EPSP, thereby affecting synaptic throughput. However, we demonstrate that, as the time course of neurotransmitter in the synaptic cleft decreases, the influence of desensitization should be somewhat diminished. As a result, the effective bandwidth of the synapse increases and becomes limited by the gating characteristics of the non-NMDA channel. 6. The model also includes a neuromodulatory aspect in that the frequency response of the synapse can be modulated by an adenylate cyclase-mediated regulatory mechanism. Although our simulations indicate the behavior of a limited number of possible neuromodulatory agents, the results demonstrate the pivotal role such agents could play in modifying synaptic transfer characteristics presynaptically. 7. Both continuous and burst-mode tract stimulation evoke patterns of action potentials in spontaneously active mNTS neurons that are mimicked very well by our model. Our simulations demonstrate that, as the rate of stimulation increases beyond approximately 20-30 Hz, the inherent low-pass frequency-response characteristics of the synapse limit the overall dynamic range of the mNTS neuron, causing the postsynaptic cell to “entrain” at frequencies within its normal operating range.

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Ali, Robert A., Yonette Paul, Robert Forestal McCauley, Miriam Yaniz, Martha Q. Gonzalez, Lawrence L. Horstman, Wenche Jy i Yeon S. Ahn. "Cell Derived Microparticles (MP) in Different Phases of Thrombotic Thrombocytopenic Purpura (TTP) and Effect of Exchange Plasmapheresis (EPP) on Their Profiles". Blood 132, Supplement 1 (29.11.2018): 3736. http://dx.doi.org/10.1182/blood-2018-99-115651.

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Abstract BACKGROUND: Cell derived MPs are small membrane vesicles released during cell activation or apoptosis. They express an inside-out membrane, which exposes the negatively charged phospholipid layer outside, allowing clotting factors to be anchored and generate thrombin. Among various species of MPs, RMP (red cell MPs), PMP (platelet MPs), LMP (leukocytes), EMP (endothelial cells) are of special interest. They play an important role in hemostasis, thromboses, and inflammation. MPs mirror early injury of parent cells and are sensitive early biomarkers of underlying disorders. TTP is a microangiopathy mediated by antibody-induced depletion of ADAMTS13, a von Willebrand factor-cleaving protease. Endothelial injury promotes platelet clumping and formation of platelet rich microthrombi in the microcirculation. Subsequent platelet sequestration leads to impaired microcirculation, thrombocytopenia and red cell fragmentation with a microangiopathic hemolytic anemia. Exchange plasmapheresis (EPP) is the standard therapy. It removes antibodies to ADAMTS13, replacing it with ADAMTS13 rich plasma. It is possible that EPP removes thrombogenic MPs to improve the clinical course of TTP. In this study, we investigated MP profiles in active and remission phase of TTP and the effect of EPP on MP profiles. We also aimed to determine if MP profiles may be a useful measure for monitoring clinical course and tracking progress of therapy. METHODS: A retrospective study was conducted evaluating MP assays in patients with TTP. MP profiles were reviewed in acute and remission phases of TTP. Acute phase was defined as thrombocytopenia, clinical evidence of microangiopathy and hemolytic anemia and low ADAMTS13 activity. Remission was defined as sustained normalization of laboratory parameters and no further microangiopathy for at least one month. Patients were studied longitudinally, with MP assays before and after EPP. EMP were measured by CD31+/CD42b− (EMP31), CD62E+ (EMP62); PMP by CD31+/CD42b+ (PMP42) and CD41+ (PMP41). All were measured in platelet-poor plasma by flow cytometry. All MP data are presented in units of x105/µL. The differences in MP patterns among TTP patients in active and remission phases of disease, as well as the effect of EPP on MP profiles were assessed. RESULTS: Among 20 patients with TTP, 8 (40%) were in acute phase and 12 (60%) in remission. An average of 10.7 EPP were performed. The average platelet count prior to EPP was 50.6x103/µL, which increased to 248 x103/µL following the last EPP. ADAMTS13 activity was generally <10% at the onset. For patients in the acute phase, PMPs were low: PMP41 0.32 (±0.11), PMP42 3.11 (±2.56), but consistently increased following EPP to the point of statistical significance at the last treatment: PMP41 1.26 (±0.71), p=0.005 and PMP42 7.65 (±5.03), p=0.039. Moreover, levels were higher in the remission phase for both PMPs, but only statistically significant for PMP41: 1.39, p=0.034. Conversely, EMP62E was initially elevated on presentation, but declined with successive EPP: 6.07 (±3.02) prior to initiation of EPP to 4.5 (±3.1) upon the last day of EPP. Furthermore, this pattern continued into remission, with EMP62E of 2.72 (±2.11), p=0.009. Similar to the trend in EMP62E, RMP was elevated in the acute phase (25.1 [±18.5]) before steadily declining with EPP (19.65 [±12.53]). This progressive drop in RMP persisted for those in remission phase of TTP 10 (±5.42), p=0.015. DISCUSSION/CONCLUSION: Taken collectively, cell derived MP's were found to reflect disease activity and response to therapy. There was a linear correlation between PMP levels and platelet count. Low PMPs in the acute phase reflects the initial thrombocytopenia characteristic of TTP. When EPP was initiated, the disease improved and there was a rise in PMP which mirrored the rise in platelets. This rise was sustained in the remission phase. Conversely, EMP62E and RMP are increased in acute phase TTP due to endothelial activation, microthrombi deposition and red cell fragmentation. After EPP the disease is quiescent, hence the progressive decline of EMP62E and RMP. These results show promising utility of cell derived MP profiles as a clinical tool to surveil chronic TTP patients and to predict disease relapse at an early stage. After EPP is initiated, change in MP Profiles may be used to monitor response to therapy and determine the appropriate time to wean EPP. Disclosures No relevant conflicts of interest to declare.

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Petersen, Julie, Clarissa W. Ong, Allison S. Hancock, Ronald B. Gillam, Michael E. Levin i Michael P. Twohig. "An Examination of the Relationship Between Perfectionism and Neurological Functioning". Journal of Cognitive Psychotherapy 35, nr 3 (1.08.2021): 195–211. http://dx.doi.org/10.1891/jcpsy-d-20-00037.

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Clinical perfectionism is the rigid pursuit of high standards, interfering with functioning. Little research has explored neural patterns in clinical perfectionism. The present study explores neural correlates of clinical perfectionism, before and after receiving ten 50-minute, weekly sessions of acceptance and commitment therapy (ACT), as compared to low-perfectionist controls, in specific cortical structures: the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), right inferior parietal lobule (IPL). Participants in the perfectionist condition (n = 43) were from a randomized controlled trial evaluating ACT for clinical perfectionism and low-perfectionist controls were undergraduate students (n = 12). Participants completed three tasks (editing a passage, mirror image tracing, circle tracing) using functional near-infrared spectroscopy (fNIRS) to measure neural activation. Results indicate that ḥin the DLPFC and MPFC of the perfectionists whereas activation in the other tasks were relatively similar. There were no differences were observed in the right DLPFC, MPFC, and right IPL between the posttreatment perfectionist and nonperfectionist control groups. Our findings suggest an unclear relationship between neural activation and perfectionism.

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Ferrucci, Michela, Francesca Biagioni, Larisa Ryskalin, Fiona Limanaqi, Stefano Gambardella, Alessandro Frati i Francesco Fornai. "Ambiguous Effects of Autophagy Activation Following Hypoperfusion/Ischemia". International Journal of Molecular Sciences 19, nr 9 (13.09.2018): 2756. http://dx.doi.org/10.3390/ijms19092756.

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Autophagy primarily works to counteract nutrient deprivation that is strongly engaged during starvation and hypoxia, which happens in hypoperfusion. Nonetheless, autophagy is slightly active even in baseline conditions, when it is useful to remove aged proteins and organelles. This is critical when the mitochondria and/or proteins are damaged by toxic stimuli. In the present review, we discuss to that extent the recruitment of autophagy is beneficial in counteracting brain hypoperfusion or, vice-versa, its overactivity may per se be detrimental for cell survival. While analyzing these opposite effects, it turns out that the autophagy activity is likely not to be simply good or bad for cell survival, but its role varies depending on the timing and amount of autophagy activation. This calls for the need for an appropriate autophagy tuning to guarantee a beneficial effect on cell survival. Therefore, the present article draws a theoretical pattern of autophagy activation, which is hypothesized to define the appropriate timing and intensity, which should mirrors the duration and severity of brain hypoperfusion. The need for a fine tuning of the autophagy activation may explain why confounding outcomes occur when autophagy is studied using a rather simplistic approach.

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Durand, Edith, i Ana Inès Ansaldo. "Recovery from anomia following Semantic Feature Analysis". Neural Correlates of Lexical Processing 8, nr 2 (15.11.2013): 195–215. http://dx.doi.org/10.1075/ml.8.2.04dur.

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Our previous work (Marcotte et al., 2012) reported neurofunctional changes associated with recovery from anomia following Semantic Feature Analysis (SFA) in a group of participants with moderate to severe chronic anomia, providing evidence of therapy-induced neuroplasticity in chronic aphasia. The activation patterns observed concurrently with the recovery of naming suggest that SFA triggers the recruitment of an alternative pathway involving the left precentral gyrus and the left inferior parietal lobule, both of which are part of the Mirror Neuron System (MNS). SFA’s potential role in triggering the recruitment of the MNS is discussed, in line with Embodied Cognition Theory and other theoretical frameworks opening a window on aphasia therapy issues and the intricate links between motor and language processing.

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Blackburn, James A. "Noise activated transitions among periodic states of a pendulum with a vertically oscillating pivot, mediated by a chaotic attractor". Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences 462, nr 2067 (17.01.2006): 1043–52. http://dx.doi.org/10.1098/rspa.2005.1630.

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It is well known that by harmonically displacing the point of suspension of a simple pendulum in a vertical direction, it is possible to produce a stable inverted state. Under certain conditions, this inverted state bifurcates into two distinct oscillations that mirror each other about the vertical. For some parameter values these two states, together with a third periodic oscillation that is symmetric about the downward direction, become embedded within a chaotic attractor. With added noise, the system dynamics can consist of endless patterns of escape from a given periodic attractor followed by capture by one of the three. After each escape and before the next capture, the system travels on the chaotic attractor. It is confirmed that the escape process is consistent with a picture of noise induced activation from the effective potential wells associated with each of the attractors.

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Castaneyra-Ruiz, Leandro, Diego M. Morales, James P. McAllister, Steven L. Brody, Albert M. Isaacs, Jennifer M. Strahle, Sonika M. Dahiya i David D. Limbrick. "Blood Exposure Causes Ventricular Zone Disruption and Glial Activation In Vitro". Journal of Neuropathology & Experimental Neurology 77, nr 9 (17.08.2018): 803–13. http://dx.doi.org/10.1093/jnen/nly058.

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Abstract Intraventricular hemorrhage (IVH) is the most common cause of pediatric hydrocephalus in North America but remains poorly understood. Cell junction-mediated ventricular zone (VZ) disruption and astrogliosis are associated with the pathogenesis of congenital, nonhemorrhagic hydrocephalus. Recently, our group demonstrated that VZ disruption is also present in preterm infants with IVH. On the basis of this observation, we hypothesized that blood triggers the loss of VZ cell junction integrity and related cytopathology. In order to test this hypothesis, we developed an in vitro model of IVH by applying syngeneic blood to cultured VZ cells obtained from newborn mice. Following blood treatment, cells were assayed for N-cadherin-dependent adherens junctions, ciliated ependymal cells, and markers of glial activation using immunohistochemistry and immunoblotting. After 24–48 hours of exposure to blood, VZ cell junctions were disrupted as determined by a significant reduction in N-cadherin expression (p < 0.05). This was also associated with significant decrease in multiciliated cells and increase in glial fibrillary acid protein-expressing cells (p < 0.05). These observations suggest that, in vitro, blood triggers VZ cell loss and glial activation in a pattern that mirrors the cytopathology of human IVH and supports the relevance of this in vitro model to define injury mechanisms.

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Usenko, Alex, Shailesh Dhungana, Anthony N. Caruso i Stteven L. Bellinger. "Electroless Nickel Plating for Ohmic Contacts to Silicon Power Devices". ECS Meeting Abstracts MA2022-02, nr 23 (9.10.2022): 960. http://dx.doi.org/10.1149/ma2022-0223960mtgabs.

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Silicon diodes, FETs, IGBTs still keep the majority of power device market, being much cheaper compared to SiC and GaN wide band gap-based devices. To keep the Si devices competitive, their manufacturing processes must be significantly improved. This includes forming Ohmic contacts. Currently the common process is PVD – physical vapor deposition of metal stacks. This process is not efficient: not selective and wasteful - metal sputtered or evaporated from target coats entire vacuum chamber, not just wafer being processed. Electroless deposition can be potentially used for metallization of Si power devices. The electroless process can be designed selective, so the metal deposits only on silicon surface, not on areas protected by dielectric films. The deposited layer must have good adhesion to silicon surface, make Ohmic contact, and preferably converts into silicide upon anneal. Nickel satisfies all these requirements, thus is a good candidate. A major issue in Nickel plating on Si is that it does not deposits well onto very smooth polished surface of Si. Several approaches are known how to overcome this issue. Dubin [1] suggested adding pretreatment with Palladium. The Pd reacts autocatalytically on silicon surface forming Pd islands. Upon switching to Ni bath, Ni deposits on Pd first, then forms a continuous film when the islands merge. One issue in the Pd/Ni process are that the native oxide on silicon must be removed so Pd can reach Si. In Dubin’ process this is resolved by adding HF to Pd bath. Another issue is bad process repeatability – a consequence of autocatalytic nature of the Pd plating reaction. The autocatalytic processes have uncontrollable “incubation” time, therefore repeating Pd plating with same recipe (same time) does not produce the same results. We describe a new approach as to plate Nickel directly on polished Silicon surface. In our process the Pd activation of Si surface is replaced by a stain etch process. The stain etch is a process where crystalline Silicon is converted into porous Si layer [2]. Technically the stain etch is simply processing in a wet bath – mixture of concentrated nitric and hydrofluoric acids in a ratio around 1:1000. Same as in the Pd/Ni case, the process must be designed to exclude native Si oxide. We achieve this by direct switching from the stain bath to Ni bath, no water rinsing in between. The surface of wafer retrieved from the stain bath is highly hydrophobic (hydrogen terminated) thus there is no liquid drops on surface. A brief nitrogen gun drying is still performed, thus preventing contamination of Ni bath with HF. The hydrogen termination protects the surface. We tried both traditional Ni plating recipes – alkaline, and acidic [3], and found that Ni plating is good in both cases. However, the resulting Ni layer is heavily non-uniform in thickness. We observe that the Ni pattern repeats the visual pattern after the stain etch. A byproduct of the stain etch reaction is hydrogen. The hydrogen forms bubbles that stick to Si surface and cause local masking, eventually non-uniformity. Thus, the key to Ni plating uniformity is the uniform stain etch. Known approaches [2] - adding surfactants to the bath, etc. happen to be only partially efficient. Therefore, we tried new stain etch recipe: add glacial acetic acid thus getting HNA mixture 1000:1:1000. The hydrogen bubbles in the old recipe were about 2 mm in diameter and kept on Si surface for many seconds. In our recipe, the bubbles get released from Si surface as soon as they reach about 0.1 mm size. The eventual Si porous layer shows uniform color appearance across entire wafers. Notice, etching in the nitric/hydrofluoric mixture is also autocatalytic process, thus the topic of repeatability arises too. However, we use Si surface color change as the signal to finish the stain etch. Thus, we can get the same thickness porous film every time despite the incubation time varies uncontrollably. Direct Ni plating onto blanket polished Silicon wafers with the HNA 1000:1:1000 pretreatment shows uniform mirror like appearance. Very high surface area of the porous Si enables the Ni plating. Nano scale sizes of porous Si with plated Ni result in uniform silicide upon anneal. References Dubin, V.M., "Selective electroless Ni deposition onto Pd-activated Si for integrated circuit fabrication" Thin Solid Films 226,no.1(1993):94-98. Kolasinski, K.W. "Porous Si formation by galvanic etching." Handbook of Porous Silicon2 (2014). Delaunois, F. Electroless nickel plating: fundamentals to applications. CRC Press, 2019.

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Yan, Qing, Conner J. Rogan i Jeffrey C. Anderson. "Development of a Pseudomonas syringae–Arabidopsis Suspension Cell Infection System for Investigating Host Metabolite-Dependent Regulation of Type III Secretion and Pattern-Triggered Immunity". Molecular Plant-Microbe Interactions® 32, nr 5 (maj 2019): 527–39. http://dx.doi.org/10.1094/mpmi-10-18-0295-fi.

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The importance of pattern-triggered immunity (PTI) in plant defense has been clearly established through genetic studies of mutants lacking functional pattern recognition receptors (PRRs) and signaling components downstream of PRR activation. Despite extensive knowledge of PRR-mediated signaling responses to pathogen-associated molecular patterns (PAMPs), little is known about which of these responses, if any, are directly responsible for limiting bacterial growth. In this work, we established a protocol for coculturing the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 and Arabidopsis suspension cells. The system closely mirrors infection processes that occur in leaves, with bacteria relying on the type III secretion system (T3SS) for maximal growth and PAMP-induced plant defenses effectively limiting bacterial growth. To demonstrate the utility of this system, we investigated the molecular basis of PAMP-induced growth inhibition and discovered that T3SS-associated genes are inhibited when DC3000 is cocultured with PAMP-treated plant suspension cells. To determine the underlying mechanism of decreased T3SS gene expression, we performed metabolomics and biochemical analyses of suspension cell exudates and identified 14 metabolites that significantly increased or decreased following PAMP treatment. Citric acid, a known inducer of T3SS gene expression in DC3000, was among several organic acids decreased in exudates from PAMP-treated plant cells. Exogenous addition of citric acid increased T3SS gene expression and partially recovered growth of DC3000 in the presence of PAMP-treated cells, indicating that a portion of PAMP-induced defense in this system is decreased extracellular release of this metabolite. We envision that the well-defined infection conditions of this coculture system will be valuable for quantitative studies of type III effector delivery by P. syringae. Furthermore, this system provides a unique ‘top-down’ approach to unravel the molecular basis of PTI against P. syringae.

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De Piano, Maria, Andrea Cacciamani, Bijorn Omar Balzamino, Fabio Scarinci, Pamela Cosimi, Concetta Cafiero, Guido Ripandelli i Alessandra Micera. "Biomarker Signature in Aqueous Humor Mirrors Lens Epithelial Cell Activation: New Biomolecular Aspects from Cataractogenic Myopia". Biomolecules 13, nr 9 (29.08.2023): 1328. http://dx.doi.org/10.3390/biom13091328.

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Inflammatory, vasculogenic, and profibrogenic factors have been previously reported in vitreous (VH) and aqueous (AH) humors in myopic patients who underwent cataract surgery. In light of this, we selected some mediators for AH and anterior-capsule-bearing lens epithelial cell (AC/LEC) analysis, and AH expression was correlated with LEC activation (epithelial–mesenchymal transition and EMT differentiation) and axial length (AL) elongation. In this study, AH (97; 41M/56F) and AC/LEC samples (78; 35M/43F) were collected from 102 patients who underwent surgery, and biosamples were grouped according to AL elongation. Biomolecular analyses were carried out for AH and LECs, while microscopical analyses were restricted to whole flattened AC/LECs. The results showed increased levels of interleukin (IL)-6, IL-8, and angiopoietin-2 (ANG)-2 and decreased levels of vascular endothelium growth factor (VEGF)-A were detected in AH depending on AL elongation. LECs showed EMT differentiation as confirmed by the expression of smooth muscle actin (α-SMA) and transforming growth factor (TGF)-βR1/TGFβ isoforms. A differential expression of IL-6R/IL-6, IL-8R/IL-8, and VEGF-R1/VEGF was observed in the LECs, and this expression correlated with AL elongation. The higher VEGF-A and lower VEGF-D transcript expressions were detected in highly myopic LECs, while no significant changes were monitored for VEGF-R transcripts. In conclusion, these findings provide a strong link between the AH protein signature and the EMT phenotype. Furthermore, the low VEGF-A/ANG-2 and the high VEGF-A/VEGF-D ratios in myopic AH might suggest a specific inflammatory and profibrogenic pattern in high myopia. The highly myopic AH profile might be a potential candidate for rating anterior chamber inflammation and predicting retinal distress at the time of cataract surgery.

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Walsh, Scott W., Marwah Al Dulaimi, Kellie J. Archer i Jerome F. Strauss. "Patterns of Maternal Neutrophil Gene Expression at 30 Weeks of Gestation, but Not DNA Methylation, Distinguish Mild from Severe Preeclampsia". International Journal of Molecular Sciences 22, nr 23 (28.11.2021): 12876. http://dx.doi.org/10.3390/ijms222312876.

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Neutrophils are activated and extensively infiltrate blood vessels in preeclamptic women. To identify genes that contribute to neutrophil activation and infiltration, we analyzed the transcriptomes of circulating neutrophils from normal pregnant and preeclamptic women. Neutrophils were collected at 30 weeks’ gestation and RNA and DNA were isolated for RNA sequencing and 5-hydroxy-methylcytosine (5-hmC) sequencing as an index of dynamic changes in neutrophil DNA methylation. Women with normal pregnancy who went on to develop mild preeclampsia at term had the most uniquely expressed genes (697) with 325 gene ontology pathways upregulated, many related to neutrophil activation and function. Women with severe preeclampsia who delivered prematurely had few pathways up- or downregulated. Cluster analysis revealed that gene expression in women with severe preeclampsia was an inverse mirror image of gene expression in normal pregnancy, while gene expression in women who developed mild preeclampsia was remarkably different from both. DNA methylation marks, key regulators of gene expression, are removed by the action of ten-eleven translocation (TET) enzymes, which oxidize 5-methylcytosines (5mCs), resulting in locus-specific reversal of DNA methylation. DNA sequencing for 5-hmC revealed no differences among the three groups. Genome-wide DNA methylation revealed extremely low levels in circulating neutrophils suggesting they are de-methylated. Collectively, these data demonstrate that neutrophil gene expression profiles can distinguish different preeclampsia phenotypes, and in the case of mild preeclampsia, alterations in gene expression occur well before clinical symptoms emerge. These findings serve as a foundation for further evaluation of neutrophil transcriptomes as biomarkers of preeclampsia phenotypes. Changes in DNA methylation in circulating neutrophils do not appear to mediate differential patterns of gene expression in either mild or severe preeclampsia.

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Connolly, Jason D., Melvyn A. Goodale, Joseph F. X. Desouza, Ravi S. Menon i Tutis Vilis. "A Comparison of Frontoparietal fMRI Activation During Anti-Saccades and Anti-Pointing". Journal of Neurophysiology 84, nr 3 (1.09.2000): 1645–55. http://dx.doi.org/10.1152/jn.2000.84.3.1645.

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An anti-saccade, which is a saccade directed toward a mirror-symmetrical position in the opposite visual field relative to the visual stimulus, involves at least three separate operations: covert orienting, response suppression, and coordinate transformation. The distinction between pro- and anti-saccades can also be applied to pointing. We used fMRI to compare patterns of brain activation during pro- and anti-movements, to determine whether or not additional areas become active during the production of anti-movements. In parietal cortex, an inferior network was active during both saccades and pointing that included three foci along the intraparietal sulcus: 1) a posterior superior parietal area (pSPR), more active during the anti-tasks; 2) a middle inferior parietal area (mIPR), active only during the anti-tasks; and 3) an anterior inferior parietal area (aIPR), equally active for pro- and anti-movement. A superior parietal network was active during pointing but not saccades and included the following: 1) a medial region, active during anti- but not pro-pointing (mSPR); 2) an anterior and medial region, more active during pro-pointing (aSPR); and 3) an anterior and lateral region, equally active for pro- and anti-pointing (lSPR). In frontal cortex, areas selectively active during anti-movement were adjacent and anterior to areas that were active during both the anti- and pro-tasks, i.e., were anterior to the frontal eye field and the supplementary motor area. All saccade areas were also active during pointing. In contrast, foci in the dorsal premotor area, the anterior superior frontal region, and anterior cingulate were active during pointing but not saccades. In summary, pointing with central gaze activates a frontoparietal network that includes the saccade network. The operations required for the production of anti-movements recruited additional frontoparietal areas.

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Kumar, Anoop, Karen S. Hawkins, Meredith A. Hannan i Michael B. Ganz. "Activation of PKC-βIin glomerular mesangial cells is associated with specific NF-κB subunit translocation". American Journal of Physiology-Renal Physiology 281, nr 4 (1.10.2001): F613—F619. http://dx.doi.org/10.1152/ajprenal.2001.281.4.f613.

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Changes in expression and activity of protein kinase C (PKC) isoforms and early transcription factors may account for alterations in cell behavior seen in diabetes. We studied the expression of PKC-βIin rat glomerular mesangial cells (MCs) cultured in normal or high glucose and compared it with the temporal and spatial expression of dimeric transcription factor (NF-κB) p50 and p65. The results show that in unstimulated cells PKC-βIand NF-κB p50 are distributed in the cytosol and, on stimulation, their distribution is perinuclear and they are localized to the membrane. Serum-starved MCs cultured in high-glucose medium exhibit a predominantly cytosolic localization of PKC-βIand both p50 and p65 NF-κB. However, phorbol 12-myristate 13-acetate (PMA) stimulation of cells grown in the presence of high glucose resulted in membrane translocation of PKC-βIthat was associated with nuclear translocation of NF-κB p65, but not NF-κB p50. Moreover, the translocation to the nucleus for NF-κB p65 was significantly higher in MCs exposed to high glucose compared with those exposed to normal glucose. These observations indicate that the NF-κB p65, but not NF-κB p50, expression and translocation pattern mirrors that of PKC-βI, which may be one important pathway by which signaling is enhanced in the high-glucose state.

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Tian, Dongting, Shin-ichi Izumi i Eizaburo Suzuki. "Modulation of Interhemispheric Inhibition between Primary Motor Cortices Induced by Manual Motor Imitation: A Transcranial Magnetic Stimulation Study". Brain Sciences 11, nr 2 (19.02.2021): 266. http://dx.doi.org/10.3390/brainsci11020266.

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Imitation has been proven effective in motor development and neurorehabilitation. However, the relationship between imitation and interhemispheric inhibition (IHI) remains unclear. Transcranial magnetic stimulation (TMS) can be used to investigate IHI. In this study, the modification effects of IHI resulting from mirror neuron system (MNS) activation during different imitations are addressed. We measured IHI between homologous primary motor cortex (M1) by analyzing the ipsilateral silent period (iSP) evoked by single-pulse focal TMS during imitation and analyzed the respective IHI modulation during and after different patterns of imitation. Our main results showed that throughout anatomical imitation, significant time-course changes of iSP duration through the experiment were observed in both directions. iSP duration declined from the pre-imitation time point to the post-imitation time point and did not return to baseline after 30 min rest. We also observed significant iSP reduction from the right hemisphere to the left hemisphere during anatomical and specular imitation, compared with non-imitative movement. Our findings indicate that using anatomical imitation in action observation and execution therapy promotes functional recovery in neurorehabilitation by regulating IHI.

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Mousavi, Fatemeh, Christopher L. Pin, Mickenzie B. Martin i Parisa Shooshtari. "Abstract B074: Loss of ATF3 affects the molecular response and epigenetic reprogramming to KRAS-dependent pancreatic ductal adenocarcinoma". Cancer Research 82, nr 22_Supplement (15.11.2022): B074. http://dx.doi.org/10.1158/1538-7445.panca22-b074.

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Abstract Introduction: With a five-year survival rate <10%, Pancreatic Ductal Adenocarcinoma (PDAC) is the 3rd leading cause of cancer-related deaths in North America. Over 90% of PDAC patients harbor a KRAS mutation, the most common form being KRASG12D. However, without additional genetic mutations or environmental events, such as chronic pancreatitis, KRAS mutations do not lead to PDAC. Our laboratory showed Activating Transcription Factor 3 (ATF3) is required for loss of the acinar cell phenotype in response to experimentally induced pancreatitis and for KRASG12D-driven progression to advanced PanIN lesions. However, the mechanism(s) by which ATF3 affects PDAC progression are unknown. The goal of this work is to determine the transcriptional mechanisms by which ATF3 contributes to PDAC progression. We have previously shown ATF3 affects histone acetylation during pancreatic injury and hypothesize that ATF3 affects transcription following KRASG12D activation by altering histone acetylation program and gene expression. Methods: C57Bl/6l mice with acinar-inducible KRASG12D combined with (Ptf1acrertERTKrasLSL-KRASG12D; PK) or without (Ptf1acrertERTKrasLSL-KRASG12DAtf3-/-; APK) ATF3 deletion were gavage with tamoxifen for 5 consecutive days and sacrificed 22 days after initial tamoxifen treatment. Acinar cells were isolated using a standard collagenase protocol, and RNA and chromatin were obtained for RNA-seq or ChIP-seq (for acetylated histone 3 (H3K27ac)). The sequenced datasets were quality checked with FastQC, aligned to the mm10 genome using STAR (for RNA-seq) or Bowtie2 (for ChIP-seq). Differential expression and differential binding analyses were performed using DESeq2 (for RNA-seq) or DiffBind (for ChIP-seq). H3K27ac enrichment patterns were compared to RNA expression profiles in PK and APK cells to identify potential genes/pathways that ATF3 works through to affect acetylation and gene expression in KrasG12D activated mice. Results: Preliminary data indicates that absence of ATF3 alters the pathway activated by KRASG12D and differentially enriches pathways that are directly linked to KRAS signaling. Moreover, comparing PK to wildtype acini, H3K27ac ChIP-seq shows a shift in acetylation patterns at the transcription start site. This change in acetylation patterns in response to KRASG12D is not observed to the same extent with deletion of ATF3. Conclusions: This work indicates that significant H3K27 acetylation occurs in response to KRASG12D activation, even in the absence of significant morphological changes, and that ATF3 seems to alter KRASG12D’s ability to affect changes in histone acetylation patterns. Epigenetic changes appear to mirror changes in the transcriptome but provide more information. Future studies will investigate the epigenetic profiles in pancreatic tumor samples and the potential for HDAC inhibitors as a possible therapeutic target for PDAC patients. Citation Format: Fatemeh Mousavi, Christopher L. Pin, Mickenzie B. Martin, Parisa Shooshtari. Loss of ATF3 affects the molecular response and epigenetic reprogramming to KRAS-dependent pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B074.

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Schocker, Frauke, Skadi Kull, Christian Schwager, Jochen Behrends i Uta Jappe. "Individual Sensitization Pattern Recognition to Cow’s Milk and Human Milk Differs for Various Clinical Manifestations of Milk Allergy". Nutrients 11, nr 6 (14.06.2019): 1331. http://dx.doi.org/10.3390/nu11061331.

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Cow’s milk allergy (CMA) belongs to one of the most common food allergies in early childhood affecting 2–3% of children under 3 years of age. However, approximately 1% of adults remain allergic to cow’s milk, often showing severe reactions even to traces of milk. In our study, we recruited patients with different clinical manifestations of CMA, including patients with anaphylaxis and less severe symptoms. We assessed the sensitization patterns and allergic responses of these subgroups through different immunological and cell-based methods. Sera of patients were investigated for IgE against whole cow’s milk and its single allergens by CAP- FEIA. In a newly developed in-house multiplex dot assay and a basophil activation test (BAT), cow’s milk allergens, in addition to human breast milk and single allergens from cow’s and human milk were analyzed for IgE recognition and severity of CMA in the included patients. Both the CAP-FEIA routine diagnostic and the multiplex dot test could differentiate CMA with severe from milder allergic reactions by means of the patients’ casein sensitization. The BAT, which mirrors the clinical response in vitro, confirmed that basophils from patients with severe reactions were more reactive to caseins in contrast to the basophils from more moderate CMA patients. By means of this improved component-resolved diagnosis of CMA, individual sensitization patterns could be assessed, also taking sensitization against human milk into consideration.

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Bhat, Pangala V., Mieczyslaw Marcinkiewicz, Yuan Li i Sylvie Mader. "Changing Patterns of Renal Retinal Dehydrogenase Expression Parallel Nephron Development in the Rat". Journal of Histochemistry & Cytochemistry 46, nr 9 (wrzesień 1998): 1025–32. http://dx.doi.org/10.1177/002215549804600906.

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We have recently characterized a cytosolic aldehyde dehydrogenase from rat kidney that functions as a retinal dehydrogenase (RALDH) and have cloned the corresponding gene. RALDH catalyzes the oxidation of retinal to retinoic acid, which regulates cell growth and differentiation by activating retinoic acid receptors. In situ hybridization demonstrates that RALDH mRNA expression is prominent in kidney in 2-day-old rats, is detected in lung and in epithelia of several tissues, but is not found in liver tissue. Retinal dehydrogenase activity peaks in kidney at Day 2 after birth and decreases gradually until adulthood, correlating well with RALDH expression. Weaker activity is also detectable in lungs but not in liver. Notably, distribution patterns of RALDH in kidney tissues are dramatically altered during postnatal development (P). From P0 to P6, hybridization is essentially concentrated within the marginal nephrogenic zone of the cortex. Expression progresses to deeper cortical layers from P12 to P16 and is intense in the medulla at P42, and focal expression is still detectable in the cortex. Immunocytochemical localization of RALDH in neonatal kidney shows staining mostly in cortical zone convoluted tubules and in adult rat shows staining in segments of distal and proximal tubules. These data suggest an important role for RALDH in modulating retinoic acid levels in different cell types during rat kidney development. The changing patterns of RALDH expression mirror stages of nephron formation in the developing rat kidney, strongly suggesting a central role for RALDH and thus for retinoids in controlling kidney development.

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Coats, Timothy J., i Mohamed Morsy. "Biological mechanisms and individual variation in fibrinolysis after major trauma". Emergency Medicine Journal 37, nr 3 (30.01.2020): 135–40. http://dx.doi.org/10.1136/emermed-2019-209181.

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ObjectiveTo understand more about the individual variation in the time course of fibrinolysis following major injury and to assess the potential for stratification of trauma patients for tranexamic acid (TXA) therapy.MethodsA historical dataset (from 2004) was used, consisting of samples from 52 injured patients attended by a medical prehospital system. Blood samples were taken at the incident scene, on arrival in the emergency department, 2.5 hours after hospital arrival and 5 hours after hospital arrival. From the study database, we extracted values for tissue-type plasminogen activator (tPA; an activator of fibrinolysis), one of the plasminogen activator inhibitors (PAI-1; as a natural inhibitor of fibrinolysis) and D-dimer (as a marker of the extent of fibrinolysis).ResultsThe changes over time in median tPA and PAI-1 were mirror images, with initial high tPA levels which then rapidly decreased and low initial PAI-1 levels which slowly increased. There were high levels of fibrinolytic activity (D-dimer) throughout. This pattern was present in patients across a broad range of injury severities.ConclusionsAfter major trauma, there seems to be an early ‘antifibrinolytic gap’ with the natural antifibrinolytic system lagging several hours behind the natural profibrinolytics. An early dose of exogenous antifibrinolytic (TXA) might have its effect by filling this gap. The finding that tPA and subsequent clot breakdown (illustrated by D-dimer formation) are raised in a broad range of patients, with little correlation between the initial fibrinolytic response and markers of injury severity, may be the reason that TXA is effective across a broad range of injured patients.

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Calautti, Cinzia, Francois Leroy, Jean Yves Guincestre, Rose Marie Marie, Fausto Viader i Jean Claude Baron. "Motor recovery after striato-capsular stroke (SCS) depends on normal laterality of brain activation: a longitudinal PET study". Stroke 32, suppl_1 (styczeń 2001): 334. http://dx.doi.org/10.1161/str.32.suppl_1.334-d.

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101 Introduction: Although bilateral motor network overactivations during finger motion are documented after stroke, their relation with actual recovery is unknown. One longitudinal study reported a shift of activations from the affected to the unaffected hemisphere with elapsing time (Marshall et al, Stroke , 2000;31:656), but whether this shift was related to recovery was not assessed. Subjects and Methods: In this prospective, longitudinal study of 5 R-handed pts (59±13 yrs) with R-sided hemiparesis due to first-ever left SCS, we obtained two 3D-PET H 2 O 15 studies(ECAT HR+), the 1 st at 1–4 and the 2 nd at ∼8 months after onset (PET1 and PET2, respectively), replicating 4 times 2 conditions: i) rest with eyes closed, metronome on; ii) metronome-cued right thumb-to-index tapping (TIT) at fixed-rate (1.26 Hz). Data were assessed individually with SPM96 and p< 0.05, corrected; controls were 7 healthy age-matched R-handed subjects. We computed correlations between R hand motor performance (max number of TITs in 15 s) and Laterality Index (LI = the affected-to-unaffected-hemisphere ratio of activated voxels, Cramer et al, Stroke , 1997;28:2518). Results and comments: motor scores significantly improved from PET1 to PET2 (18±4 and 29±5, respectively, p<0.05, paired t-test); 2 pts exhibited mirror movement at PET1 and 1 at PET2. Significant overactivations at PET1 affected the whole motor network bilaterally, but were considerably less extensive at PET2, with a significant LI shift (.69±.11 and .08±.54, respectively, p<0.05). Shift magnitude was negatively correlated (Spearman rho= -.975, p<0.05) with clinical recovery (expressed as motor score changes), that is, the more the laterality shifted (i.e., deviated from normality), the lesser the recovery. Conclusion: The shift towards the unaffected hemisphere confirms earlier report, though performance was fixed here. This study is the first to document a correlation between recovery and brain activation patterns after stroke, such that the greater the shift, the worse the recovery.

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Boulay, Aude, Sara Trabanelli, Stéphanie Boireau, Myriam Boyer-Clavel, Sébastien Nisole, Pedro Romero, Camilla Jandus, Anne-Sophie Beignon i Nathalie J. Arhel. "Assessing the Impact of Persistent HIV Infection on Innate Lymphoid Cells Using In Vitro Models". ImmunoHorizons 7, nr 3 (1.03.2023): 243–55. http://dx.doi.org/10.4049/immunohorizons.2300007.

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Abstract Pathogens that persist in their host induce immune dysfunctions even in the absence of detectable replication. To better understand the phenotypic and functional changes that persistent infections induce in sentinel innate immune cells, we developed human PBMC-based HIV models of persistent infection. Autologous nonactivated PBMCs were cocultured with chronically infected, acutely infected, or uninfected cells and were then analyzed by unsupervised high-dimensional flow cytometry. Using this approach, we identified prevalent patterns of innate immune dysfunctions associated with persistent HIV infections that at least in part mirror immune dysfunctions observed in patients. In one or more models of chronic infection, bystander CD16+ NK cells expressing markers of activation, such as CD94, CD45RO, CD62L, CD69, CD25, and immune checkpoints PD1, Tim3, TIGIT, NKG2A and Lag3, were significantly reduced. Conversely, helper ILC subsets expressing PDL1/PDL2 were significantly enriched in chronic infection compared with either uninfected or acute infection, suggesting that chronic HIV-1 infection was associated with an inhibitory environment for bystander ILC and NK subsets. The cell-based models of persistent infection that we describe here provide versatile tools to explore the molecular mechanisms of these immune dysfunctions and unveil the contribution of innate immunity in sustaining pathogen persistence.

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Guillaume, Alain, Jason R. Fuller, Riju Srimal i Clayton E. Curtis. "Cortico-cerebellar network involved in saccade adaptation". Journal of Neurophysiology 120, nr 5 (1.11.2018): 2583–94. http://dx.doi.org/10.1152/jn.00392.2018.

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Saccade adaptation is the learning process that ensures that vision and saccades remain calibrated. The central nervous system network involved in these adaptive processes remains unclear because of difficulties in isolating the learning process from the correlated visual and motor processes. Here we imaged the human brain during a novel saccade adaptation paradigm that allowed us to isolate neural signals involved in learning independent of the changes in the amplitude of corrective saccades usually correlated with adaptation. We show that the changes in activation in the ipsiversive cerebellar vermis that track adaptation are not driven by the changes in corrective saccades and thus provide critical supporting evidence for previous findings. Similarly, we find that activation in the dorsomedial wall of the contraversive precuneus mirrors the pattern found in the cerebellum. Finally, we identify dorsolateral and dorsomedial cortical areas in the frontal and parietal lobes that encode the retinal errors following inaccurate saccades used to drive recalibration. Together, these data identify a distributed network of cerebellar and cortical areas and their specific roles in oculomotor learning. NEW & NOTEWORTHY The central nervous system constantly learns from errors and adapts to keep visual targets and saccades in registration. We imaged the human brain while the gain of saccades adapted to a visual target that was displaced while the eye was in motion, inducing retinal error. Activity in the cerebellum and precuneus tracked learning, whereas parts of the dorsolateral and dorsomedial frontal and parietal cortex encoded the retinal error used to drive learning.

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Tagaris, Georgios A., Seong-Gi Kim, John P. Strupp, Peter Andersen, Kamil Uğurbil i Apostolos P. Georgopoulos. "Mental Rotation Studied by Functional Magnetic Resonance Imaging at High Field (4 Tesla): Performance and Cortical Activation". Journal of Cognitive Neuroscience 9, nr 4 (lipiec 1997): 419–32. http://dx.doi.org/10.1162/jocn.1997.9.4.419.

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We studied the performance and cortical activation patterns during a mental rotation task (Shepard & Metzler, 1971) using functional magnetic resonance imaging (fMlU) at high field (4 Tesla). Twenty-four human subjects were imaged (fMRI group), whereas six additional subjects performed the task without being imaged (control group). All subjects were shown pairs of perspective drawings of 31, objects and asked to judge whether they were the same or mirror images. The measures of performance examined included (1) the percentage of errors, (2) the speed of performance, calculated as the inverse of the average response time, and (3) the rate of rotation for those object pairs correctly identified as “same.” We found the following: (1) Subjects in the fMRI group performed well outside and inside the magnet, and, in the latter case, before and during data acquisition. Moreover, performance over time improved in the same manner as in the control group. These findings indicate that exposure to high magnetic fields does not impair performance in mental rotation. (2) Functional activation data were analyzed from 16 subjects of the fMRI goup. Several cortical areas were activated during task performance. The relations between the measures of performance above and the magnitude of activation of specific cortical areas were investigated by anatomically demarcating these areas of interest and calculating a normalized activation for each one of them. (3) We used the multivariate technique of hierarchical tree modeling to determine functional clustering among areas of interest and performance measures. Two main branches were distinguished: One comprised areas in the right hemisphere and the extrastriate and superior parietal lobules bilaterally, whereas the other comprised areas of the left hemisphere and the frontal pole bilaterally; all three performance measures above clustered with the former branch. Specifically, performance outcome (“percentage of errors”) clustered with the parieto-occipital subcluster, whereas both the speed of performance and the rate of mental rotation clustered with the right precentral gyms. We conclude that the mental rotation paradigm used involves the cooperative interaction of functional groups of cortical areas of which some are probably more specifically associated with performance, whereas others may serve a more general function within the task constraints.

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Smith, Graeme C. M., Fabrizio d’adda di Fagagna, Nicholas D. Lakin i Stephen P. Jackson. "Cleavage and Inactivation of ATM during Apoptosis". Molecular and Cellular Biology 19, nr 9 (1.09.1999): 6076–84. http://dx.doi.org/10.1128/mcb.19.9.6076.

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ABSTRACT The activation of the cysteine proteases with aspartate specificity, termed caspases, is of fundamental importance for the execution of programmed cell death. These proteases are highly specific in their action and activate or inhibit a variety of key protein molecules in the cell. Here, we study the effect of apoptosis on the integrity of two proteins that have critical roles in DNA damage signalling, cell cycle checkpoint controls, and genome maintenance—the product of the gene defective in ataxia telangiectasia, ATM, and the related protein ATR. We find that ATM but not ATR is specifically cleaved in cells induced to undergo apoptosis by a variety of stimuli. We establish that ATM cleavage in vivo is dependent on caspases, reveal that ATM is an efficient substrate for caspase 3 but not caspase 6 in vitro, and show that the in vitro caspase 3 cleavage pattern mirrors that in cells undergoing apoptosis. Strikingly, apoptotic cleavage of ATM in vivo abrogates its protein kinase activity against p53 but has no apparent effect on the DNA binding properties of ATM. These data suggest that the cleavage of ATM during apoptosis generates a kinase-inactive protein that acts, through its DNA binding ability, in a trans-dominant-negative fashion to prevent DNA repair and DNA damage signalling.

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Dr. Amit Kumar Chandrana. "Correlating Language and Music for the Activation of Human Mind". Creative Launcher 8, nr 2 (30.04.2023): 65–69. http://dx.doi.org/10.53032/tcl.2023.8.2.09.

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As Heinrich Heine puts it, “Where words leave off, music begins”. Music and language belong to a common origin i.e. sound, a form of energy. In other words, language and music are two sons of the same mother. Language and music both engage the auditory system, utilizing similar neural pathways to process sound and rhythm. Just as language relies on patterns of sounds and syntax to convey meaning, music utilizes melody, harmony, and structure to evoke emotions and communicate messages. A language always talks about the speech sounds that are produced by the vocal cords while music is the outcome of non-oral sounds or sometimes may be the oral sounds. Both language and music have the ability to elicit powerful emotional responses in individuals, stirring feelings of joy, sadness, or nostalgia. The rhythmic and melodic elements in music can enhance language processing by providing a rhythmic framework that aids in memorization and comprehension. Though language and music are not always complementary to each other but one seems incomplete in absence of the other. Language and music share the capacity to convey complex ideas and narratives, allowing us to express our thoughts and experiences in nuanced and creative ways. Studies have shown that exposure to music can improve language skills, including vocabulary acquisition, syntax comprehension, and verbal fluency. The use of prosody, intonation, and rhythm in language mirrors the melodic and rhythmic components of music, highlighting their interconnectedness. Musical training has been found to enhance linguistic abilities, as musicians often demonstrate better pitch discrimination, phonological awareness, and language learning skills. Language and music can both serve as cultural markers, reflecting and preserving the traditions, values, and identities of different communities. The shared neural processes involved in language and music suggest a deep-rooted correlation, as they tap into fundamental mechanisms of auditory perception and cognitive processing. The present research article is a descriptive study on the relationship between language and music and their effects on the mind and body of the human beings. In the first section of this paper, the linguistic aspects that are akin to music have been attempted to be pointed out. Similarly, in the following section, the core of the music has been discussed in context to language. In the third section, a comparative study of language and music has been done on the basis of the points discussed in the preceding sections. Finally, the paper also discusses as how the amalgamation of the two i.e. language and music can be helpful in activating the human mind and the body.

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