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Martins, Jéssica Santa Cruz de Carvalho, Thiago das Chagas Sousa, Maria de Lourdes de Aguiar Oliveira, Etel Rodrigues Pereira Gimba, Marilda Mendonça Siqueira e Aline da Rocha Matos. "Total Osteopontin and Its Isoform OPN4 Are Differently Expressed in Respiratory Samples during Influenza A(H1N1)pdm09 Infection and Progression". Microorganisms 11, n. 5 (20 maggio 2023): 1349. http://dx.doi.org/10.3390/microorganisms11051349.
Testo completoAbstract (sommario):
Influenza A virus (IAV) infection affects the human respiratory tract, causing an acute and highly contagious disease. Individuals with comorbidities and in the extremes of age are classified as risk groups for serious clinical outcomes. However, part of the severe infections and fatalities are observed among young healthy individuals. Noteworthy, influenza infections lack specific prognostic biomarkers that would predict the disease severity. Osteopontin (OPN) has been proposed as a biomarker in a few human malignancies and its differential modulation has been observed during viral infections. However, OPN expression levels in the primary site of IAV infection have not been previously investigated. Therefore, we evaluated the transcriptional expression patterns of total OPN (tOPN) and its splicing isoforms (OPNa, OPNb, OPNc, OPN4, and OPN5) in 176 respiratory secretion samples collected from human influenza A(H1N1)pdm09 cases and a group of 65 IAV-negative controls. IAV samples were differentially classified according to their disease severity. tOPN was more frequently detected in IAV samples (34.1%) when compared with the negative controls (18.5%) (p < 0.05), as well as in fatal (59.1%) versus non-fatal IAV samples (30.5%) (p < 0.01). OPN4 splice variant transcript was more prevalent in IAV cases (78.4%) than in the negative controls (66.1%) (p = 0.05) and in severe cases (85.7%) in relation to the non-severe ones (69.2%) (p < 0.01). OPN4 detection was also associated with severity symptoms such as dyspnea (p < 0.05), respiratory failure (p < 0.05), and oxygen saturation < 95% (p < 0.05). In addition, the OPN4 expression level was increased in the fatal cases of respiratory samples. Our data indicated that tOPN and OPN4 had a more pronounced expression pattern in IAV respiratory samples, pointing to the potential use of these molecules as biomarkers to evaluate disease outcomes.
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Ferreira, Luciana, Raquel Lima, Ana Bastos, Andreia Silva, Catarina Tavares, Ana Pestana, Elisabete Rios et al. "OPNa Overexpression Is Associated with Matrix Calcification in Thyroid Cancer Cell Lines". International Journal of Molecular Sciences 19, n. 10 (30 settembre 2018): 2990. http://dx.doi.org/10.3390/ijms19102990.
Testo completoAbstract (sommario):
Osteopontin (OPN) spliced variants (OPN-SV: OPNa, OPNb, and OPNc) are aberrantly expressed in tumors and frequently associated with cancer progression. This holds true for papillary thyroid carcinoma (PTC), which is the most common type of thyroid cancer (TC). PTC often presents with desmoplasia and dystrophic calcification, including psammoma bodies (PB). This work aimed to investigate total OPN (tOPN) and OPN-SV expression and their association with the presence of PB in the PTC classical variants (cPTC), as well as the involvement of OPN-SV in matrix calcification of TC cell lines. We found that cPTC samples presenting PB showed higher OPN expression levels. In TC cell lines, OPNa overexpression promotes higher matrix calcification and collagen synthesis when compared to that of clones overexpressing OPNb or OPNc. In response to OPN knockdown, calcification was inhibited, paralleled with the downregulation of calcification markers. In conclusion, our data evidenced that OPN expression is associated with the presence of PB in cPTC samples. Among the OPN-SV, OPNa is the main contributor to matrix calcification in tested TC cells, providing clues to a better understanding on the biology and ethiopathogenesis of the calcification process in TC cells.
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Zhang, Ziyu, Liangliang Zheng, Wei Xu, Tan Gao, Xiaobin Wu e Biao Yang. "Blind Remote Sensing Image Deblurring Based on Overlapped Patches’ Non-Linear Prior". Sensors 22, n. 20 (16 ottobre 2022): 7858. http://dx.doi.org/10.3390/s22207858.
Testo completoAbstract (sommario):
The remote sensing imaging environment is complex, in which many factors cause image blur. Thus, without prior knowledge, the restoration model established to obtain clear images can only rely on the observed blurry images. We still build the prior with extreme pixels but no longer traverse all pixels, such as the extreme channels. The features are extracted in units of patches, which are segmented from an image and partially overlap with each other. In this paper, we design a new prior, i.e., overlapped patches’ non-linear (OPNL) prior, derived from the ratio of extreme pixels affected by blurring in patches. The analysis of more than 5000 remote sensing images confirms that OPNL prior prefers clear images rather than blurry images in the restoration process. The complexity of the optimization problem is increased due to the introduction of OPNL prior, which makes it impossible to solve it directly. A related solving algorithm is established based on the projected alternating minimization (PAM) algorithm combined with the half-quadratic splitting method, the fast iterative shrinkage-thresholding algorithm (FISTA), fast Fourier transform (FFT), etc. Numerous experiments prove that this algorithm has excellent stability and effectiveness and has obtained competitive processing results in restoring remote sensing images.
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Bastos, Ana Clara Ana Clara Santos da Fonseca, Luciana Bueno Ferreira, Mariana Emerenciano e Etel Rodrigues Pereira Gimba. "Abstract 6719: Osteopontin-c is worse prognostic marker and mediate key steps associated with central nervous system infiltration in B-cell acute lymphoblastic leukemia cells". Cancer Research 83, n. 7_Supplement (4 aprile 2023): 6719. http://dx.doi.org/10.1158/1538-7445.am2023-6719.
Testo completoAbstract (sommario):
Abstract B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignance, but 35% of patients still relapse after chemotherapy treatment, mainly in the central nervous system (CNS). In order to search for new biomarkers that could predict CNS infiltration and relapse, many studies are trying to find gene products aberrantly expressed in these patients, including osteopontin (OPN). The OPN primary transcript undergoes alternative splicing, generating at least five OPN splicing isoforms (OPN-SI), named OPNa, OPNb, OPNc, OPN4 and OPN5, that have tumor specific roles and have been reported as biomarkers in solid tumors. However, knowledge regarding OPN-SI in B-ALL is scarce. This study aimed to investigate the expression patterns and roles of OPN-SI in CNS infiltration in B-ALL. OPN-SI transcript levels were analyzed by quantitative real time PCR (qRT-PCR) assays using RNA extracted from 54 B-ALL pediatric patient blood samples or from RS4,11 cell line. OPNc transcript knock-down in RS4;11 cells (a B-ALL cell line containing the MLL gene fusion) was performed using anti-OPNc or control scrambled antisense DNA oligomers (anti-OPNc-ASOs and Scbl-ASO, respectively). These oligomers were transfected in RS4;11 cells and the in vitro effects of OPNc knock-down were evaluated by several functional assays, such as cell viability by MTT analysis, cell adhesion, and transmigration and invasion assays using a boyden chamber device. Among tested OPN-SI, OPNc is the most highly expressed OPN-SI in B-ALL patient samples containing the MLL fusion gene, when compared to those samples harboring the ETV6-RUNX1 fusion gene (p<0,005). High OPNc expression levels were significantly associated with poor prognostic features, such as high-risk classification (p<0,005), CNS infiltration and high white blood cell counting (p<0,05). The RS4;11 cells in which OPNc was knocked-down decreased their OPNc expression levels in 85% in relation to control Scbl-ASO transfected cells (p<0,005). These cells decreased their viability in 41% (p<0,05), besides displaying a 55% decrease in RS4;11 cell adhesion to matrigel. In addition, these cells decreased their capacity to transmigrate (54%) and invade the matrigel (51%) in comparison to control cells. In summary, these results suggest that OPNc transcript levels are associated with B-ALL worse prognostic features and that it may mediate some key steps involved on CNS infiltration mechanistic. Hence, our data provide important basis for the potential use of OPNc as a biomarker for B-ALL CNS relapse and for the involvement of this isoform on some steps that can mediate CNS invasion, opening new opportunities to improve B-ALL pediatric patients’ survival rates and quality of life. Citation Format: Ana Clara Ana Clara Santos da Fonseca Bastos, Luciana Bueno Ferreira, Mariana Emerenciano, Etel Rodrigues Pereira Gimba. Osteopontin-c is worse prognostic marker and mediate key steps associated with central nervous system infiltration in B-cell acute lymphoblastic leukemia cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6719.
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Ferreira, Luciana Bueno, Catarina Eloy, Ana Pestana, Joana Lyra, Margarida Moura, Hugo Prazeres, Catarina Tavares, Manuel Sobrinho-Simões, Etel Gimba e Paula Soares. "Osteopontin expression is correlated with differentiation and good prognosis in medullary thyroid carcinoma". European Journal of Endocrinology 174, n. 4 (aprile 2016): 551–61. http://dx.doi.org/10.1530/eje-15-0577.
Testo completoAbstract (sommario):
BackgroundOsteopontin (OPN) or secreted phosphoprotein 1 (SPP1) is a matricellular glycoprotein whose expression is elevated in various types of cancer and has been shown to be involved in tumourigenesis and metastasis in many malignancies, including follicular cell-derived thyroid carcinomas. Its role in C-cell-derived thyroid lesions and tumours remains to be established.ObjectiveThe objective of this study is to clarify the role of OPN expression in the development of medullary thyroid carcinoma (MTC).MethodsOPN expression was analysed in a series of 116 MTCs by immunohistochemistry and by qPCR mRNA quantification of the 3 OPN isoforms (OPNa, OPNb and OPNc) in six cases from which fresh frozen tissue was available. Statistical tests were used to evaluate the relationship of OPN expression and the clinicopathological and molecular characteristics of patients and tumours.ResultsOPN expression was detected in 91 of 116 (78.4%) of the MTC. We also observed high OPN expression in C-cell hyperplasia as well as in C-cells scattered in the thyroid parenchyma adjacent to the tumours. OPN expression was significantly associated with smaller tumour size, PTEN nuclear expression and RAS status, and suggestively associated with non-invasive tumours. OPNa isoform was expressed significantly at higher levels in tumours than in non-tumour samples. OPNb and OPNc presented similar levels of expression in all samples. Furthermore, OPNa isoform overexpression was significantly associated with reduced growth and viability in the MTC-derived cell line (TT).ConclusionThe expression of OPN in normal C-cells and C-cell hyperplasia suggests that OPN is a differentiation marker of C-cells, rather than a marker of biological aggressiveness in this setting. At variance with other cancers, OPN expression is associated with good prognostic features in MTC.
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Ho, Nguyen-Tuong, Shu-Wei Lin, Yi-Rong Lee, Chii-Ruey Tzeng e Shu-Huei Kao. "Osteopontin Splicing Isoforms Contribute to Endometriotic Proliferation, Migration, and Epithelial-Mesenchymal Transition in Endometrial Epithelial Cells". International Journal of Molecular Sciences 23, n. 23 (5 dicembre 2022): 15328. http://dx.doi.org/10.3390/ijms232315328.
Testo completoAbstract (sommario):
Osteopontin (OPN) isoforms, including OPNb and OPNc, promote malignancy and may contribute to the pathogenesis of endometriosis, a benign disorder with multiple characteristics resembling malignant tumors. In our experiments, OPNb and OPNc were significantly overexpressed in both endometriosis and adenomyosis compared to the normal endometrium. Upregulation of CD44v and the epithelial–mesenchymal transition (EMT) process was also present in endometriotic lesions. Overexpression of OPNb and OPNc splicing variants in endometriotic cells evoked morphological changes, actin remodeling, cell proliferation, cell migration, and EMT through binding OPN ligand receptors CD44 and αvβ3, subsequently activating the PI3K and NF-ĸB pathways. We elucidated the causal role of OPN splice variants in regulating endometriotic cell growth, which may promote the development of OPN-targeted therapies for patients suffering from endometriotic disorders.
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Buhr, Ethan D., Wendy W. S. Yue, Xiaozhi Ren, Zheng Jiang, Hsi-Wen Rock Liao, Xue Mei, Shruti Vemaraju et al. "Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea". Proceedings of the National Academy of Sciences 112, n. 42 (21 settembre 2015): 13093–98. http://dx.doi.org/10.1073/pnas.1516259112.
Testo completoAbstract (sommario):
The molecular circadian clocks in the mammalian retina are locally synchronized by environmental light cycles independent of the suprachiasmatic nuclei (SCN) in the brain. Unexpectedly, this entrainment does not require rods, cones, or melanopsin (OPN4), possibly suggesting the involvement of another retinal photopigment. Here, we show that the ex vivo mouse retinal rhythm is most sensitive to short-wavelength light but that this photoentrainment requires neither the short-wavelength–sensitive cone pigment [S-pigment or cone opsin (OPN1SW)] nor encephalopsin (OPN3). However, retinas lacking neuropsin (OPN5) fail to photoentrain, even though other visual functions appear largely normal. Initial evidence suggests that OPN5 is expressed in select retinal ganglion cells. Remarkably, the mouse corneal circadian rhythm is also photoentrainable ex vivo, and this photoentrainment likewise requires OPN5. Our findings reveal a light-sensing function for mammalian OPN5, until now an orphan opsin.
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Upton, Brian A., Nicolás M. Díaz, Shannon A. Gordon, Russell N. Van Gelder, Ethan D. Buhr e Richard A. Lang. "Evolutionary Constraint on Visual and Nonvisual Mammalian Opsins". Journal of Biological Rhythms 36, n. 2 (25 marzo 2021): 109–26. http://dx.doi.org/10.1177/0748730421999870.
Testo completoAbstract (sommario):
Animals have evolved light-sensitive G protein–coupled receptors, known as opsins, to detect coherent and ambient light for visual and nonvisual functions. These opsins have evolved to satisfy the particular lighting niches of the organisms that express them. While many unique patterns of evolution have been identified in mammals for rod and cone opsins, far less is known about the atypical mammalian opsins. Using genomic data from over 400 mammalian species from 22 orders, unique patterns of evolution for each mammalian opsins were identified, including photoisomerases, RGR-opsin (RGR) and peropsin (RRH), as well as atypical opsins, encephalopsin (OPN3), melanopsin (OPN4), and neuropsin (OPN5). The results demonstrate that OPN5 and rhodopsin show extreme conservation across all mammalian lineages. The cone opsins, SWS1 and LWS, and the nonvisual opsins, OPN3 and RRH, demonstrate a moderate degree of sequence conservation relative to other opsins, with some instances of lineage-specific gene loss. Finally, the photoisomerase, RGR, and the best-studied atypical opsin, OPN4, have high sequence diversity within mammals. These conservation patterns are maintained in human populations. Importantly, all mammalian opsins retain key amino acid residues important for conjugation to retinal-based chromophores, permitting light sensitivity. These patterns of evolution are discussed along with known functions of each atypical opsin, such as in circadian or metabolic physiology, to provide insight into the observed patterns of evolutionary constraint.
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Karthikeyan, Ramanujam, Wayne I. L. Davies e Lena Gunhaga. "Non-image-forming functional roles of OPN3, OPN4 and OPN5 photopigments". Journal of Photochemistry and Photobiology 15 (giugno 2023): 100177. http://dx.doi.org/10.1016/j.jpap.2023.100177.
Testo completo
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Guido, Mario. "Illuminating the Inner Retina of Vertebrates: Multiple Opsins and Non-Visual Photoreceptors". Science Reviews - from the end of the world 2, n. 1 (18 dicembre 2020): 7–17. http://dx.doi.org/10.52712/sciencereviews.v2i1.35.
Testo completoAbstract (sommario):
Throughout evolution, the need to detect light has generated highly specialized photoreceptor cells that in vertebrates are mainly located in the retina. The most studied photodetectors within these cells are the visual photoreceptors “cones and rods” responsible for day and night vision, respectively. These cells contain photosensitive molecules consisting of a protein part called “opsin” that binds a chromophore derived from vitamin A, retinaldehyde, capable of photoisomerizing from 11-cis retinal to all-trans retinal form, and triggering the light responses that lead to vision. However, other cells of the inner retina of vertebrates [retinal ganglion cells (RGCs), horizontal cells (HCs), and Muller’s glial cells] are currently known to express non-visual photopigments such as melanopsin (Opn4), encephalopsin (Opn3) and neuropsin (Opn5), which would be involved in diverse functions not associated with imaging. Melanopsin is the most widely studied of them, it is expressed in intrinsically photosensitive RGCs (ipRGCs) and HCs of the chicken retina and participates in setting the biological clock, the pupillary light reflex, and presumably in other reflex and subconscious functions, in addition to the lateral interaction between visual photoreceptors and HCs. It is noteworthy that these non-visual photopigments (Opn3, Opn4 and Opn5) respond to blue and/or near violet region light. This particular photosensitivity may provide individuals with a broader spectrum of response to light stimulation within the visible beyond the scope of the visual photoreceptors, regulating an important number of functions not yet completely identified. We can conclude that “a constellation of cells and photoreceptor molecules are present in the inner retina of vertebrates, and from very early stages of development, even before any sign of vision may occur.”
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Prusik, Magdalena. "Avian central clocking system". Medycyna Weterynaryjna 74, n. 1 (2018): 6043–2018. http://dx.doi.org/10.21521/mw.6043.
Testo completoAbstract (sommario):
In birds many life processes runs in diurnal (e.g. locomotor activity, feeding, melatonin secretion) and seasonal rhythms (e.g. reproduction, song, feathering, migration) depending on the environmental light and the activity of the central clock system (CCS). The structure and mechanisms of the activity of the avian CCS are the most complex among vertebrates. CCS consists of three oscillators (in the retina, SCN and pineal gland) possessing own sensory input system (photopigments) and effective output system (products for direct biological effects). So far in the CCS in birds 14 forms of photopigments (Opn1, Opn2, Opn3, TMT, Opn4x, Opn4m, Opn5, RGR, RRH, VA-opsins, pinopsin, Cry1, Cry2 i Cry4) and 12 clock genes making up oscillators (Bmal1, Bmal2, Clock, NPas2 called also Mop4 and Rorα – positive genes and Cry1, Cry2, Cry4, Per2, Per3, E4bp4 and Rev-erbα – negative genes) have been described. Photopigments are placed in all layers of the retina; in brain - mainly in regions of nuclei: septalis lateralis, premammillaris, habenularis and paraventricularis; in the pineal gland - in all kinds of pinealocytes. Most photopigments belonging to the opsin family are linked with nucleotide phototransduction path, typical for vertebrates, but in avian CCS also phosphoinositol phototransduction path, characteristic for invertebrates, is existing and concerns Opn4x and Opn5. Oscilators are placed in nuclei of cells of all layers of the retina, in mSCN and vSCN (with great species variability) and in pinealocytes. It is supposing, that all nonvisual photopigments have a direct role in the synchronization of the oscillator activity with the environmental light, but molecular mechanisms of the interaction between photopigments and the oscillator remain unknown. The impact of each of the three oscillators of CCS in generating of biological rhythms in birds show great species differentiation. The differences concern both the domination of one of oscillators over the others and the assignation of biological processes which individual oscillator synchronizes rhythmically with the environmental light..
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Warren, W. C., R. Liang, G. G. Krivi, N. R. Siegel e R. V. Anthony. "Purification and structural characterization of ovine placental lactogen". Journal of Endocrinology 126, n. 1 (luglio 1990): 141–49. http://dx.doi.org/10.1677/joe.0.1260141.
Testo completoAbstract (sommario):
ABSTRACT Discrepancies exist in the reported purity and biological activity of ovine placental lactogen (oPL), and little structural characterization has been reported. Ovine PL was purified from fetal cotyledonary tissue (day 100 of gestation) by monitoring activity with a recombinant bovine GH (bGH) liver radioreceptor assay. Two hundred grams of tissue yielded 4·2 mg of oPL, with an ∼ 1000-fold purification of oPL specific activity following initial tissue extraction. The oPL was radioiodinated and used in an ovine fetal liver (day 100 of gestation) radioreceptor assay to examine competitive displacement of oPL, ovine GH (oGH) and ovine prolactin (oPRL). The potency of oPL (ED50 = 0·18 nmol/l; ED50 is the quantity of ligand necessary to displace 50% of specifically bound 125I-labelled oPL) was greater than that of oGH (ED50 = 4·1 nmol/l) and oPRL (ED50 = 1·1 μmol/l) in competing for 125I-labelled oPL-binding sites. Attempts to sequence the NH2 terminus of oPL by vapour-phase sequencing indicated that the NH2 terminus was blocked. Purified oPL was subjected to trypsin and CnBr digestion, and two CnBr and six tryptic peptides were sequenced. The peptide sequences were compared with other PLs, oPRL and bGH for sequence similarity, and found to be most similar to bovine PL (bPL; 68% overall identity) and oPRL (47% overall identity). Complementary DNA (cDNA) clones were isolated for oPL by screening a λZAP cDNA library with a cDNA coding for bPL. Three cDNAs were nucleotide sequenced, and their combined sequence included 41 nucleotides of 5'-untranslated region, the complete coding region of pre-oPL (708 nucleotides) and a portion of the 3' untranslated region (158 nucleotides). The predicted amino acid sequence derived from the nucleotide sequence confirmed homology to bPL (67%) and oPRL (48%). Little amino acid sequence existed with other PLs (≤29%) or GH proteins (≤27%). These results suggest that oPL and oGH are more biologically similar in their ability to compete for fetal liver binding sites, but that oPL is structurally more similar to oPRL. Elucidation of exact structure–function relationships for oPL will, however, require further investigation. Journal of Endocrinology (1990) 126, 141–149
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Schultz, K. P., C. R. Williams e C. Busettini. "Macaque Pontine Omnipause Neurons Play No Direct Role in the Generation of Eye Blinks". Journal of Neurophysiology 103, n. 4 (aprile 2010): 2255–74. http://dx.doi.org/10.1152/jn.01150.2009.
Testo completoAbstract (sommario):
We recorded the activity of pontine omnipause neurons (OPNs) in two macaques during saccadic eye movements and blinks. As previously reported, we found that OPNs fire tonically during fixation and pause about 15 ms before a saccadic eye movement. In contrast, for blinks elicited by air puffs, the OPNs paused <2 ms before the onset of the blink. Thus the burst in the agonist orbicularis oculi motoneurons (OOMNs) and the pause in the antagonist levator palpabrae superioris motoneurons (LPSMNs) necessarily precede the OPN pause. For spontaneous blinks there was no correlation between blink and pause onsets. In addition, the OPN pause continued for 40–60 ms after the time of the maximum downward closing of the eyelids, which occurs around the end of the OOMN burst of firing. LPSMN activity is not responsible for terminating the OPN pause because OPN resumption was very rapid, whereas the resumption of LPSMN firing during the reopening phase is gradual. OPN pause onset does not directly control blink onset, nor does pause offset control or encode the transition between the end of the OOMN firing and the resumption of the LPSMNs. The onset of the blink-related eye transients preceded both blink and OPN pause onsets. Therefore they initiated while the saccadic short-lead burst neurons were still fully inhibited by the OPNs and cannot be saccadic in origin. The abrupt dynamic change of the vertical eye transients from an oscillatory behavior to a single time constant exponential drift predicted the resumption of the OPNs.
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Hattori, Toshio, Hiroko Iwasaki-Hozumi, Gaowa Bai, Haorile Chagan-Yasutan, Ashwnini Shete, Elizabeth Freda Telan, Atsushi Takahashi, Yugo Ashino e Takashi Matsuba. "Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases". Biomedicines 9, n. 8 (13 agosto 2021): 1006. http://dx.doi.org/10.3390/biomedicines9081006.
Testo completoAbstract (sommario):
Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, Mycobacterium tuberculosis (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and coronavirus disease 2019 (COVID-19). Proteolysis of OPN by thrombin, matrix metalloproteases, caspase 8/3, cathepsin D, plasmin, and enterokinase generates various cleaved OPNs with a variety of bioactivities by binding to different target cells. Moreover, OPN is susceptible to gradual proteolysis. During inflammation, one of the cleaved fragments, N-terminal thrombin-cleaved OPN (trOPN or OPN-Arg168 [OPN-R]), induces dendritic cell (DC) adhesion. Further cleavage by carboxypeptidase B2 or carboxypeptidase N removes Arg168 from OPN-R to OPN-Leu167 (OPN-L). Consequently, OPN-L decreases DC adhesion. In particular, the differences in plasma level over time are observed between FL-OPN and its cleaved OPNs during inflammation. We found that the undefined OPN levels (mixture of FL-OPN and cleaved OPN) were elevated in plasma and reflected the pathology of TB and COVID-19 rather than FL-OPN. These infections are associated with elevated levels of various proteases. Inhibition of the cleavage or the activities of cleaved products may improve the outcome of the therapy. Research on the metabolism of OPN is expected to create new therapies against infectious diseases.
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Barreto Ortiz, Sebastian, Daijiro Hori, Yohei Nomura, Xin Yun, Haiyang Jiang, Hwanmee Yong, James Chen et al. "Opsin 3 and 4 mediate light-induced pulmonary vasorelaxation that is potentiated by G protein-coupled receptor kinase 2 inhibition". American Journal of Physiology-Lung Cellular and Molecular Physiology 314, n. 1 (1 gennaio 2018): L93—L106. http://dx.doi.org/10.1152/ajplung.00091.2017.
Testo completoAbstract (sommario):
We recently demonstrated that blue light induces vasorelaxation in the systemic mouse circulation, a phenomenon mediated by the nonvisual G protein-coupled receptor melanopsin (Opsin 4; Opn4). Here we tested the hypothesis that nonvisual opsins mediate photorelaxation in the pulmonary circulation. We discovered Opsin 3 (Opn3), Opn4, and G protein-coupled receptor kinase 2 (GRK2) in rat pulmonary arteries (PAs) and in pulmonary arterial smooth muscle cells (PASMCs), where the opsins interact directly with GRK2, as demonstrated with a proximity ligation assay. Light elicited an intensity-dependent relaxation of PAs preconstricted with phenylephrine (PE), with a maximum response between 400 and 460 nm (blue light). Wavelength-specific photorelaxation was attenuated in PAs from Opn4−/− mice and further reduced following shRNA-mediated knockdown of Opn3. Inhibition of GRK2 amplified the response and prevented physiological desensitization to repeated light exposure. Blue light also prevented PE-induced constriction in isolated PAs, decreased basal tone, ablated PE-induced single-cell contraction of PASMCs, and reversed PE-induced depolarization in PASMCs when GRK2 was inhibited. The photorelaxation response was modulated by soluble guanylyl cyclase but not by protein kinase G or nitric oxide. Most importantly, blue light induced significant vasorelaxation of PAs from rats with chronic pulmonary hypertension and effectively lowered pulmonary arterial pressure in isolated intact perfused rat lungs subjected to acute hypoxia. These findings show that functional Opn3 and Opn4 in PAs represent an endogenous “optogenetic system” that mediates photorelaxation in the pulmonary vasculature. Phototherapy in conjunction with GRK2 inhibition could therefore provide an alternative treatment strategy for pulmonary vasoconstrictive disorders.
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Eric Almeida Xavier, Anelise Freitas Sandei e Isabela Canavezzi Matias. "Human and animal cells under influence of different lighting and stimulus". GSC Advanced Research and Reviews 18, n. 3 (30 marzo 2024): 291–307. http://dx.doi.org/10.30574/gscarr.2024.18.3.0097.
Testo completoAbstract (sommario):
Circadian rhythms, are the basis of homeostasis of organisms like human and other mammals. Violation of circadian rhythms leads to the development of pathological conditions and severe course of preexisting pathologies. For example some work with B16-F1O cells (B16) has shown that molecules like opsins, Circadian Locomotor Output Cycles Kaput (CLOCK) and clock genes are changed after a white light pulse (WLP). Like this, melanopsin (OPN4) and rhodopsin (OPN2) through UVA irradiation induced B16 pigmentation. Thus, heat shock reduces secreted rhodopsin expression in normal Melan-a melanocytes, while the opposite effect is found in malignant B16 cells. In both cell lines UVA radiation increases the expression of melanopsin and melanin, interfering with several clock genes, and also increasing the DNA repair enzyme xeroderma pigmentosum, complementation group A (XPA). Furthermore, B16 are more responsive to UVA radiation when compared to normal cells. Thereby, opsins are involved in animal camouflage. And their functions in humans involve different wavelengths, for example in skin the keratinocyte differentiation by (410 nm) involved cone opsin (OPN1) and rhodopsin (OPN2), like this in epidermal keratinocytes irradiation by (447 nm) accelerates closure in wound-healing and violet light (415 nm) induced hyperpigmentation. Furthermore, in B16 cell culture certain wavelengths induce proliferation or inhibition like signs of apoptosis and necrosis. Finally understanding the response of opsins and clock genes to different wavelengths in the skin, we could attribute a therapeutic of photobiomodulation (PBM) to approach various dermatological conditions, such as psoriasis, atopic dermatitis, hair growth, wound healing and tissue regeneration.
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Christensen, Brian, Albert J. Buitenhuis, Lotte N. Jacobsen, Marie S. Ostenfeld e Esben S. Sørensen. "The Effect of Human and Bovine Milk Osteopontin on Intestinal Caco-2 Cells: A Transcriptome Comparison". Nutrients 15, n. 5 (25 febbraio 2023): 1166. http://dx.doi.org/10.3390/nu15051166.
Testo completoAbstract (sommario):
Osteopontin (OPN) is a multifunctional protein abundantly present in human milk, whereas the concentration is significantly lower in bovine milk. Human and bovine milk OPN are structurally similar and both proteins resist gastric digestion and reach the intestines in a bioactive form. Intervention studies have indicated the beneficial effects of supplementing infant formula with bovine milk OPN and several in vivo and in vitro studies have shown that bovine milk OPN positively influences intestinal development. To investigate the functional relationship, we compared the effect of simulated gastrointestinal digested human and bovine milk OPN on gene expression in Caco-2 cells. After incubation, total RNA was extracted and sequenced and transcripts were mapped to the human genome. Human and bovine milk OPN regulated the expression of 239 and 322 genes, respectively. A total of 131 genes were similarly regulated by the OPNs. As a control, a whey protein fraction with a high content of alpha-lactalbumin had a very limited transcriptional impact on the cells. Enrichment data analysis showed that biological processes related to the ubiquitin system, DNA binding, and genes associated with transcription and transcription control pathways were affected by the OPNs. Collectively, this study shows that human and bovine milk OPN have a significant and highly comparable effect on the intestinal transcriptome.
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Everling, Stefan, Martin Paré, Michael C. Dorris e Douglas P. Munoz. "Comparison of the Discharge Characteristics of Brain Stem Omnipause Neurons and Superior Colliculus Fixation Neurons in Monkey: Implications for Control of Fixation and Saccade Behavior". Journal of Neurophysiology 79, n. 2 (1 febbraio 1998): 511–28. http://dx.doi.org/10.1152/jn.1998.79.2.511.
Testo completoAbstract (sommario):
Everling, Stefan, Martin Paré, Michael C. Dorris, and Douglas P. Munoz. Comparison of the discharge characteristics of brain stem omnipause neurons and superior colliculus fixation neurons in monkey: implications for control of fixation and saccade behavior. J. Neurophysiol. 79: 511–528, 1998. Fixation neurons (SCFNs) in the rostral pole of the superior colliculus (SC) and omnipause neurons (OPNs) in the nucleus raphe interpositus (rip) in the pons share similar discharge properties. Both types of neurons discharge tonically during periods of visual fixation and pause for saccadic eye movements, and their activation by electrical stimulation suppresses saccade generation. On the basis of these similarities and the projection from the rostral SC to the rip, it was hypothesized that SCFNs provide a major excitatory input to OPNs. We investigated the role and relationship of SCFNs and OPNs with respect to both fixation behavior and saccade generation by comparing their activity recorded in the same monkeys performing a gap saccade task. In this task, the central fixation point was extinguished 200 ms before the presentation of an eccentric saccadic target, and the discharges of OPNs and SCFNs were contrasted during visual fixation, nonvisual (gap) fixation, and saccade generation. During visual fixation, the mean discharge rate of OPNs was higher and more regular than that of SCFNs. During the gap period, SCFNs decreased their discharge rate before target appearance, whereas no change in discharge rate was observed in OPNs. For both SCFNs and OPNs, the activity level before target appearance was not correlated to saccadic reaction time. In contrast to SCFNs, several OPNs responded with a transient phasic increase in discharge immediately after the target presentation. Before their saccade-related pause, there was a gradual reduction in the activity of SCFNs, whereas OPNs had an abrupt cessation of discharge. SCFNs paused earlier than OPNs, but the OPN pause onset was better synchronized to saccade onset than the SCFN pause onset. OPNs resumed firing after their pause in activity earlier than SCFNs, and the OPN pause end was better synchronized to saccade end than the SCFN pause end. These physiological data reveal differences in the discharge properties of SCFNs and OPNs that are irreconcilable with the hypothesis that the discharge pattern of OPNs reflects simply the excitatory input from SCFNs. It is most likely that additional inputs to OPNs compensate for the reduction in discharge of SCFNs during these periods.
19
Gandhi, Neeraj J., e Edward L. Keller. "Activity of the Brain Stem Omnipause Neurons During Saccades Perturbed by Stimulation of the Primate Superior Colliculus". Journal of Neurophysiology 82, n. 6 (1 dicembre 1999): 3254–67. http://dx.doi.org/10.1152/jn.1999.82.6.3254.
Testo completoAbstract (sommario):
Stimulation of the rostral ∼2 mm of the superior colliculus (SC) during a large, visual target-initiated saccade produces a spatial deviation of the ongoing saccade and then stops it in midflight. After the termination of the stimulation, the saccade resumes and ends near the location of the flashed target. The density of collicular projections to the omnipause neuron (OPN) region is greatest from the rostral SC and decreases gradually for the more caudal regions. It has been hypothesized that the microstimulation excites the OPNs through these direct connections, and the reactivation of OPNs, which are normally silent during saccades, stops the initial component in midflight by gating off the saccadic burst generator. Two predictions emerge from this hypothesis: 1) for microstimulation triggered on the onset of large saccades, the time from stimulation onset to resumption of OPN discharge should decrease as the stimulation site is moved rostral and 2) the lead time from reactivation of OPNs to the end of the initial saccade on stimulation trials should be equal to the lead time of pause end with respect to the end of control saccades. We tested this hypothesis by recording OPN activity during saccades perturbed by stimulation of the rostral ∼2 mm of the SC. The distance of the stimulation site from the most rostral extent of the SC and the time of reactivation with respect to stimulation onset were not significantly correlated. The mean lead of reactivation of OPNs relative to the end of the initial component of perturbed saccades (6.5 ms) was significantly less than the mean lead with respect to the end of control (9.6 ms) and resumed saccades (10.4 ms). These results do not support the notion that the excitatory input from SC neurons—in particular, the fixation neurons in the rostral SC—provide the major signal to reactivate OPNs and end saccades. An alternative, conceptual model to explain the temporal sequence of events induced by stimulation of the SC during large saccades is presented. Other OPN activity parameters also were measured and compared for control and stimulation conditions. The onset of pause with respect to resumed saccade onset was larger and more variable than the onset of pause with respect to control saccades, whereas pause end with respect to the end of resumed and control saccades was similar. The reactivated discharge of OPNs during the period between the end of the initial and the onset of the resumed saccades was at least as strong as that following control movements. This latter observation is interpreted in terms of the resettable neural integrator hypothesis.
20
Van Wyk, Brooke, e Gregory Fraley. "Ontogeny of OPN4, OPN5, GnRH and GnIH mRNA Expression in the Posthatch Male and Female Pekin Duck (Anas platyrhynchos domesticus) Suggests OPN4 May Have Additional Functions beyond Reproduction". Animals 11, n. 4 (14 aprile 2021): 1121. http://dx.doi.org/10.3390/ani11041121.
Testo completoAbstract (sommario):
The hypothalamic–pituitary–gonadal axis (HPG) is known to be regulated by daylength through the deep brain photoreceptor (DBP) system. The post-hatch ontogeny is not known for any of the DBPs. We set out to determine the ontogeny of OPN4 and OPN5 gene expression relative to GnRH and GnIH using qRT-PCR. Brains and serum were collected from five drakes and five hens on the day of hatching (Day 0) and again at 2, 4, 6, 10, 14, 19, 25 and 31 weeks of age and analyzed by qRT-PCR. Hen and drake serum was assayed for circulating levels of estradiol and testosterone, respectively. Data were analyzed between sexes over time using a repeated measures two-way ANOVA. Interestingly, the results show that on the day of hatching (Day 0), ducks showed adult-like levels of relative OPN4, but not OPN5, gene expression. During week 10, DBP levels increased, achieving highest relative expression levels at week 19 that maintained through week 31, typically peak fertility in ducks. GnRH mRNA levels increased following the DBP expression at the onset of puberty, and gonadal steroids increased after GnRH at week 14 while estradiol preceded testosterone. GnIH mRNA levels did not appreciably change during the time course of this experiment. These observations suggest that OPN4 may be active during the peri-hatch period and may have physiological roles beyond puberty and fertility.
21
PAMPENA, David A., Karen A. ROBERTSON, Olga LITVINOVA, Gilles LAJOIE, Harvey A. GOLDBERG e Graeme K. HUNTER. "Inhibition of hydroxyapatite formation by osteopontin phosphopeptides". Biochemical Journal 378, n. 3 (15 marzo 2004): 1083–87. http://dx.doi.org/10.1042/bj20031150.
Testo completoAbstract (sommario):
Osteopontin (OPN) is an acidic phosphoglycoprotein that is believed to function in the prevention of soft tissue calcification. In vitro studies have shown that OPN can inhibit the formation of hydroxyapatite (HA) and other biologically relevant crystal phases, and that this inhibitory activity requires phosphorylation of the protein; however, it is not known which phosphorylated residues are involved. We have synthesized peptides corresponding to four phosphoserine-containing sequences in rat OPN: OPN7–17, containing phosphoserines 10 and 11; OPN41–52, containing phosphoserines 46 and 47; OPN248–264, containing phosphoserines 250, 257 and 262; and OPN290–301, containing phosphoserines 295–297. The abilities of these peptides to inhibit de novo HA formation were determined using a constant-composition autotitration assay. All four OPN phosphopeptides caused a dose-dependent increase in nucleation lag time, but did not significantly affect subsequent formation of the crystals. However, OPN41–52 (inhibitory constant 73.5 min/µM) and OPN290–301 (72.2 min/µM) were approx. 4 times more potent inhibitors than OPN7–17 (19.7 min/µM) and OPN247–264 (16.3 min/µM). ‘Scrambling’ the amino acid sequence of OPN290–301 resulted in decreased potency (45.6 min/µM), whereas omission of the phosphate groups from this peptide caused a greater decrease (5.20 min/µM). These findings have identified phosphorylated sequences that are important for the ability of rat bone OPN to inhibit HA crystal formation, and suggest that negative-charge density is an important factor in this activity.
22
Plesa, Maria, Abdelaziz Kholti, Karen Vermis, Peter Vandamme, Stavroula Panagea, Craig Winstanley e Pierre Cornelis. "Conservation of the opcL gene encoding the peptidoglycan-associated outer-membrane lipoprotein among representatives of the Burkholderia cepacia complex". Journal of Medical Microbiology 53, n. 5 (1 maggio 2004): 389–98. http://dx.doi.org/10.1099/jmm.0.05504-0.
Testo completoAbstract (sommario):
Members of the Burkholderia cepacia complex are Gram-negative β-proteobacteria that are classified into nine genomic species or genomovars. Some representatives of this group of bacteria, such as Burkholderia multivorans (genomovar II) and Burkholderia cenocepacia (genomovar III), are considered to be dangerous pathogens for cystic fibrosis (CF) patients because of their capacity to colonize CF lungs. The opcL gene, which encodes the peptidoglycan-associated outer-membrane lipoprotein (PAL), was detected in the genome of Burkholderia sp. LB 400 by a similarity search that was based on the sequence of the Pseudomonas aeruginosa PAL, OprL. Primers that could amplify part of opcL from B. multivorans LMG 13010T were designed. This PCR fragment was used as a probe for screening of a B. multivorans genomic bank, allowing cloning of the complete opcL gene. The complete opcL gene could be PCR-amplified from DNA from all genomovars. The sequences of these opcL genes showed a high degree of conservation (> 95 %) among different species of the B. cepacia complex. OpcL protein that was purified from B. multivorans LMG 13010T was used to generate mouse polyclonal antisera against OpcL. The OpcL protein could be produced in Escherichia coli and detected in outer-membrane fractions by Western blot. Burkholderia cells were labelled by immunofluorescence staining using antibodies against OpcL, but only after treatment with EDTA and SDS. The opcL gene could be amplified directly from the sputa of 15 CF patients who were known to be colonized by B. cepacia; sequence data derived from the amplicons identified the colonizing strains as B. cenocepacia (genomovar III, n = 14) and B. multivorans (n = 1).
23
Fay, Li-Yu, Chao-Hung Kuo, Hsuan-Kan Chang, Mei-Yin Yeh, Chih-Chang Chang, Chin-Chu Ko, Tsung-Hsi Tu et al. "Comparative Study of the Cytokine Profiles of Serum and Tissues from Patients with the Ossification of the Posterior Longitudinal Ligament". Biomedicines 11, n. 7 (18 luglio 2023): 2021. http://dx.doi.org/10.3390/biomedicines11072021.
Testo completoAbstract (sommario):
Background: The ossification of the posterior longitudinal ligament (OPLL) is one of the contributing factors leading to severe cervical spondylotic myelopathy (CSM). The mechanism causing ossification is still unclear. The current study was designed to analyze the specimens of patients with or without OPLL. Methods: The study collected 51 patients with cervical spondylosis. There were six serum samples in both the non-OPLL (NOPLL) and OPLL groups. For tissue analysis, there were seven samples in the NOPLL group and five samples in the OPLL group. The specimens of serum and tissue were analyzed by using Human Cytokine Antibody Arrays to differentiate biomarkers between the OPLL and NOPLL groups, as well as between serum and OPLL tissue. Immunohistochemical staining of the ligament tissue was undertaken for both groups. Results: For OPLL vs. NOPLL, the serum leptin levels are higher in the OPLL group, corroborating others’ observations that it may serve as a disease marker. In the tissue, angiogenin (ANG), osteopontin (OPN), and osteopro-tegerin (OPG) are higher than they are in the OPLL group (p < 0.05). For serum vs. OPLL tissue, many chemotactic cytokines demonstrated elevated levels of MIP1 delta, MCP-1, and RANTES in the serum, while many cytokines promoting or regulating bone genesis were up-regulated in tissue (oncostatin M, FGF-9, LIF, osteopontin, osteoprotegerin, TGF-beta2), as well as the factor that inhibits osteoclastogenesis (IL-10), with very few cytokines responsible for osteoclastogenesis. Molecules promoting angiogenesis, including angiotensin, vEGF, and osteoprotegerin, are abundant in the OPLL tissue, which paves the way for robust bone growth.
24
Bergeron, André, e Daniel Guitton. "In Multiple-Step Gaze Shifts: Omnipause (OPNs) and Collicular Fixation Neurons Encode Gaze Position Error; OPNs Gate Saccades". Journal of Neurophysiology 88, n. 4 (1 ottobre 2002): 1726–42. http://dx.doi.org/10.1152/jn.2002.88.4.1726.
Testo completoAbstract (sommario):
The superior colliculus (SC), via its projections to the pons, is a critical structure for driving rapid orienting movements of the visual axis, called gaze saccades, composed of coordinated eye-head movements. The SC contains a motor map that encodes small saccade vectors rostrally and large ones caudally. A zone in the rostral pole may have a different function. It contains superior colliculus fixation neurons (SCFNs) with probable projections to omnipause neurons (OPNs) of the pons. SCFNs and OPNs discharge tonically during visual fixation and pause during single-step gaze saccades. The OPN tonic discharge inhibits saccades and its cessation (pause) permits saccade generation. We have proposed that SCFNs control the OPN discharge. We compared the discharges of SCFNs and OPNs recorded while cats oriented horizontally, to the left and right, in the dark to a remembered target. Cats used multiple-step gaze shifts composed of a series of small gaze saccades, of variable amplitude and number, separated by periods of variable duration (plateaus) in which gaze was immobile or moving at low velocity (<25°/s). Just after contralaterally (ipsilaterally) presented targets, the firing frequency of SCFNs decreased to almost zero (remained constant at background). As multiple-step gaze shifts progressed in either direction in the dark, these activity levels prevailed until the distance between gaze and target [gaze position error (GPE)] reached ∼16°. At this point, firing frequency gradually increased, without saccade-related pauses, until a maximum was reached when gaze arrived on target location (GPE = 0°). SCFN firing frequency encoded GPE; activity was not correlated to characteristics or occurrence of gaze saccades. By comparison, after target presentation to left or right, OPN activity remained steady at pretarget background until first gaze saccade onset, during which activity paused. During the first plateau, activity resumed at a level lower than background and continued at this level during subsequent plateaus until GPE ∼8° was reached. As GPE decreased further, tonic activity during plateaus gradually increased until a maximum (greater than background) was reached when gaze was on goal (GPE = 0°). OPNs, like SCFNs, encoded GPE, but they paused during every gaze saccade, thereby revealing, unlike for SCFNs, strong coupling to motor events. The firing frequency increase in SCFNs as GPE decreased, irrespective of trajectory characteristics, implies these cells get feedback on GPE, which they may communicate to OPNs. We hypothesize that at the end of a gaze-step sequence, impulses from SCFNs onto OPNs may suppress further movements away from the target.
25
Gandhi, Neeraj J., e Edward L. Keller. "Spatial Distribution and Discharge Characteristics of Superior Colliculus Neurons Antidromically Activated From the Omnipause Region in Monkey". Journal of Neurophysiology 78, n. 4 (1 ottobre 1997): 2221–25. http://dx.doi.org/10.1152/jn.1997.78.4.2221.
Testo completoAbstract (sommario):
Gandhi, Neeraj J. and Edward L. Keller. Spatial distribution and discharge characteristics of superior colliculus neurons antidromically activated from the omnipause region in monkey. J. Neurophysiol. 78: 2221–2225, 1997. One proposed role of the superior colliculus (SC) in oculomotor control is to suppress or excite the activity of brain stem omnipause neurons (OPNs) to initiate or terminate saccades, respectively. Although connections from the SC to the OPNs have been demonstrated, the spatial distribution and discharge characteristics of the projecting neurons from the SC remain unknown. We mapped the spatial distribution of the deeper-layer neurons of the SC by stimulating the region of the OPNs to identify antidromic projections and found that the density of direct projections from the SC to the OPNs was greatest in the most rostral region and decreased gradually for more caudal sites. On the basis of saccade-related discharge characteristics, the antidromically driven neurons were predominantly fixation and buildup neurons. The spatially distributed SC projections to the OPNs and the discharge characteristics of the SC neurons suggest that the direct projections from SC to OPNs are excitatory. Finally, we propose how excitation and disfacilitation from SC activity can contribute to modulation of OPN response and control saccades.
26
Phillips, James O., Leo Ling e Albert F. Fuchs. "Action of the Brain Stem Saccade Generator During Horizontal Gaze Shifts. I. Discharge Patterns of Omnidirectional Pause Neurons". Journal of Neurophysiology 81, n. 3 (1 marzo 1999): 1284–95. http://dx.doi.org/10.1152/jn.1999.81.3.1284.
Testo completoAbstract (sommario):
Action of the brain stem saccade generator during horizontal gaze shifts. I. Discharge patterns of omnidirectional pause neurons. Omnidirectional pause neurons (OPNs) pause for the duration of a saccade in all directions because they are part of the neural mechanism that controls saccade duration. In the natural situation, however, large saccades are accompanied by head movements to produce rapid gaze shifts. To determine whether OPNs are part of the mechanism that controls the whole gaze shift rather than the eye saccade alone, we monitored the activity of 44 OPNs that paused for rightward and leftward gaze shifts but otherwise discharged at relatively constant average rates. Pause duration was well correlated with the duration of either eye or gaze movement but poorly correlated with the duration of head movement. The time of pause onset was aligned tightly with the onset of either eye or gaze movement but only loosely aligned with the onset of head movement. These data suggest that the OPN pause does not encode the duration of head movement. Further, the end of the OPN pause was often better aligned with the end of the eye movement than with the end of the gaze movement for individual gaze shifts. For most gaze shifts, the eye component ended with an immediate counterrotation owing to the vestibuloocular reflex (VOR), and gaze ended at variable times thereafter. In those gaze shifts where eye counterrotation was delayed, the end of the pause also was delayed. Taken together, these data suggest that the end of the pause influences the onset of eye counterrotation, not the end of the gaze shift. We suggest that OPN neurons act to control only that portion of the gaze movement that is commanded by the eye burst generator. This command is expressed by driving the saccadic eye movement directly and also by suppressing VOR eye counterrotation. Because gaze end is less well correlated with pause end and often occurs well after counterrotation onset, we conclude that elements of the burst generator typically are not active till gaze end, and that gaze end is determined by another mechanism independent of the OPNs.
27
Paré, Martin, e Daniel Guitton. "Brain Stem Omnipause Neurons and the Control of CombinedEye-Head Gaze Saccades in the Alert Cat". Journal of Neurophysiology 79, n. 6 (1 giugno 1998): 3060–76. http://dx.doi.org/10.1152/jn.1998.79.6.3060.
Testo completoAbstract (sommario):
Paré, Martin and Daniel Guitton. Brain stem omnipause neurons and the control of combined eye-head gaze saccades in the alert cat. J. Neurophysiol. 79: 3060–3076, 1998. When the head is unrestrained, rapid displacements of the visual axis—gaze shifts (eye-re-space)—are made by coordinated movements of the eyes (eye-re-head) and head (head-re-space). To address the problem of the neural control of gaze shifts, we studied and contrasted the discharges of omnipause neurons (OPNs) during a variety of combined eye-head gaze shifts and head-fixed eye saccades executed by alert cats. OPNs discharged tonically during intersaccadic intervals and at a reduced level during slow perisaccadic gaze movements sometimes accompanying saccades. Their activity ceased for the duration of the saccadic gaze shifts the animal executed, either by head-fixed eye saccades alone or by combined eye-head movements. This was true for all types of gaze shifts studied: active movements to visual targets; passive movements induced by whole-body rotation or by head rotation about stationary body; and electrically evoked movements by stimulation of the caudal part of the superior colliculus (SC), a central structure for gaze control. For combined eye-head gaze shifts, the OPN pause was therefore not correlated to the eye-in-head trajectory. For instance, in active gaze movements, the end of the pause was better correlated with the gaze end than with either the eye saccade end or the time of eye counterrotation. The hypothesis that cat OPNs participate in controlling gaze shifts is supported by these results, and also by the observation that the movements of both the eyes and the head were transiently interrupted by stimulation of OPNs during gaze shifts. However, we found that the OPN pause could be dissociated from the gaze-motor-error signal producing the gaze shift. First, OPNs resumed discharging when perturbation of head motion briefly interrupted a gaze shift before its intended amplitude was attained. Second, stimulation of caudal SC sites in head-free cat elicited large head-free gaze shifts consistent with the creation of a large gaze-motor-error signal. However, stimulation of the same sites in head-fixed cat produced small “goal-directed” eye saccades, and OPNs paused only for the duration of the latter; neither a pause nor an eye movement occurred when the same stimulation was applied with the eyes at the goal location. We conclude that OPNs can be controlled by neither a simple eye control system nor an absolute gaze control system. Our data cannot be accounted for by existing models describing the control of combined eye-head gaze shifts and therefore put new constraints on future models, which will have to incorporate all the various signals that act synergistically to control gaze shifts.
28
Busettini, C., e L. E. Mays. "Saccade–Vergence Interactions in Macaques. I. Test of the Omnipause Multiply Model". Journal of Neurophysiology 94, n. 4 (ottobre 2005): 2295–311. http://dx.doi.org/10.1152/jn.01336.2004.
Testo completoAbstract (sommario):
Horizontal vergence eye movements are movements in opposite directions used to change fixation between far and near targets. The occurrence of a saccade during vergence causes vergence velocity to be transiently enhanced. The goal of this study was to test in the monkey the previously described Multiply Model (Zee et al. 1992) that holds that, in humans, the speeding of vergence during a saccade may be the result of the disinhibition of a subgroup of vergence-related neurons by the saccadic omnipause neurons (OPNs). In agreement with the Multiply Model: 1) the onset of the enhancement was closely related to saccadic onset, and thus linked to the onset of the OPN pause; 2) the magnitude of the vergence velocity enhancement was strongly dependent on saccade–vergence timing. Contrary to the Multiply Model: 1) the peak of the vergence velocity enhancement was dependent on saccadic peak velocity; 2) the dependency on saccadic peak velocity was not the indirect result of a dependency on saccadic duration and therefore on the duration of the OPN pause; 3) the decline of the vergence enhancement, identified by the time of the peak of the enhancement velocity, occurred too early to be linked to the end of the OPN pause; 4) vergence enhancement had a saccadic-like peak-velocity/size main sequence. Overall, the evidence is incompatible with the OPN Multiply hypothesis of vergence enhancement. Alternative models are described in an accompanying paper.
29
Gandhi, Neeraj J., e David L. Sparks. "Dissociation of Eye and Head Components of Gaze Shifts by Stimulation of the Omnipause Neuron Region". Journal of Neurophysiology 98, n. 1 (luglio 2007): 360–73. http://dx.doi.org/10.1152/jn.00252.2007.
Testo completoAbstract (sommario):
Natural movements often include actions integrated across multiple effectors. Coordinated eye-head movements are driven by a command to shift the line of sight by a desired displacement vector. Yet because extraocular and neck motoneurons are separate entities, the gaze shift command must be separated into independent signals for eye and head movement control. We report that this separation occurs, at least partially, at or before the level of pontine omnipause neurons (OPNs). Stimulation of the OPNs prior to and during gaze shifts temporally decoupled the eye and head components by inhibiting gaze and eye saccades. In contrast, head movements were consistently initiated before gaze onset, and ongoing head movements continued along their trajectories, albeit with some characteristic modulations. After stimulation offset, a gaze shift composed of an eye saccade, and a reaccelerated head movement was produced to preserve gaze accuracy. We conclude that signals subject to OPN inhibition produce the eye-movement component of a coordinated eye-head gaze shift and are not the only signals involved in the generation of the head component of the gaze shift.
30
Gandhi, Neeraj J., e Desiree K. Bonadonna. "Temporal Interactions of Air-Puff–Evoked Blinks and Saccadic Eye Movements: Insights Into Motor Preparation". Journal of Neurophysiology 93, n. 3 (marzo 2005): 1718–29. http://dx.doi.org/10.1152/jn.00854.2004.
Testo completoAbstract (sommario):
Following the initial, sensory response to stimulus presentation, activity in many saccade-related burst neurons along the oculomotor neuraxis is observed as a gradually increasing low-frequency discharge hypothesized to encode both timing and metrics of the impending eye movement. When the activity reaches an activation threshold level, these cells discharge a high-frequency burst, inhibit the pontine omnipause neurons (OPNs) and trigger a high-velocity eye movement known as saccade. We tested whether early cessation of OPN activity, prior to when it ordinarily pauses, acts to effectively lower the threshold and prematurely trigger a movement of modified metrics and/or dynamics. Relying on the observation that OPN discharge ceases during not only saccades but also blinks, air-puffs were delivered to one eye to evoke blinks as monkeys performed standard oculomotor tasks. We observed a linear relationship between blink and saccade onsets when the blink occurred shortly after the cue to initiate the movement but before the average reaction time. Blinks that preceded and overlapped with the cue increased saccade latency. Blinks evoked during the overlap period of the delayed saccade task, when target location is known but a saccade cannot be initiated for correct performance, failed to trigger saccades prematurely. Furthermore, when saccade and blink execution coincided temporally, the peak velocity of the eye movement was attenuated, and its initial velocity was correlated with its latency. Despite the perturbations, saccade accuracy was maintained across all blink times and task types. Collectively, these results support the notion that temporal features of the low-frequency activity encode aspects of a premotor command and imply that inhibition of OPNs alone is not sufficient to trigger saccades.
31
Iwamoto, Yoshiki, Hitoshi Kaneko, Kaoru Yoshida e Hiroshi Shimazu. "Role of Glycinergic Inhibition in Shaping Activity of Saccadic Burst Neurons". Journal of Neurophysiology 101, n. 6 (giugno 2009): 3063–74. http://dx.doi.org/10.1152/jn.90565.2008.
Testo completoAbstract (sommario):
The immediate premotor signals for saccades are created at the level of medium-lead burst neurons (MLBNs). During fixations, MLBNs receive tonic inhibition from omnipause neurons (OPNs), which use glycine as a neurotransmitter. To elucidate the role of this inhibition, we studied discharge patterns of horizontal MLBNs following iontophoretic application of strychnine, a glycine-receptor antagonist, in alert cats. Three-barrel micropipettes were used for extracellular recording and iontophoresis. After application of strychnine, MLBNs exhibited spontaneous discharge and visual responses during intersaccadic intervals. Spikes were evoked by single-pulse stimulation of the contralateral superior colliculus (SC). These results show that MLBNs receive substantial excitatory input during intersaccadic intervals and that inhibitory action of OPNs is indeed necessary to prevent MLBNs from firing. Strychnine also affected saccade-related activity of MLBNs. The burst of activity, as in normal conditions, declined rapidly before the end of saccades but was followed by low rate spike activity, which continued beyond the end of saccades. This suggests that in normal conditions, the termination of saccades is determined by resumed inhibitory action of OPNs and not by termination of excitatory input to MLBNs. In addition, the firing rate and the number of spikes during saccades increased after strychnine application, suggesting that MLBNs receive glycinergic inhibition of non-OPN origin as well. We conclude that glycinergic inhibition plays essential roles in the maintenance of stable fixation, the termination of saccades, and the regulation of saccade size and velocity.
32
Prsa, Mario, e Henrietta L. Galiana. "Visual-Vestibular Interaction Hypothesis for the Control of Orienting Gaze Shifts by Brain Stem Omnipause Neurons". Journal of Neurophysiology 97, n. 2 (febbraio 2007): 1149–62. http://dx.doi.org/10.1152/jn.00856.2006.
Testo completoAbstract (sommario):
Models of combined eye-head gaze shifts all aim to realistically simulate behaviorally observed movement dynamics. One of the most problematic features of such models is their inability to determine when a saccadic gaze shift should be initiated and when it should be ended. This is commonly referred to as the switching mechanism mediated by omni-directional pause neurons (OPNs) in the brain stem. Proposed switching strategies implemented in existing gaze control models all rely on a sensory error between instantaneous gaze position and the spatial target. Accordingly, gaze saccades are initiated after presentation of an eccentric visual target and subsequently terminated when an internal estimate of gaze position becomes nearly equal to that of the target. Based on behavioral observations, we demonstrate that such a switching mechanism is insufficient and is unable to explain certain types of movements. We propose an improved hypothesis for how the OPNs control gaze shifts based on a visual-vestibular interaction of signals known to be carried on anatomical projections to the OPN area. The approach is justified by the analysis of recorded gaze shifts interrupted by a head brake in animal subjects and is demonstrated by implementing the switching mechanism in an anatomically based gaze control model. Simulated performance reveals that a weighted sum of three signals: gaze motor error, head velocity, and eye velocity, hypothesized as inputs to OPNs, successfully reproduces diverse behaviorally observed eye-head movements that no other existing model can account for.
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Weber, Georg F., e Piotr Ziolkowski. "Abstract P2-11-36: Osteopontin splice variants indicate prognosis in premalignant breast lesions". Cancer Research 83, n. 5_Supplement (1 marzo 2023): P2–11–36—P2–11–36. http://dx.doi.org/10.1158/1538-7445.sabcs22-p2-11-36.
Testo completoAbstract (sommario):
Abstract BACKGROUND: Premalignant breast lesions pose variable risks for transformation, raising the question who should receive treatment to counteract the potential progression to breast cancer. Prognostic indicators will spare low-risk patients the burden of substantial treatment side effects and will enable high-risk patients to comfortably take preemptive action. Osteopontin (OPN) is a secreted mediator of breast cancer progression, which is subject to alternative splicing in transformed tissues and has been known to be a marker for breast cancer aggressiveness. Here, we test the variants OPN-a and OPN-c as potential prognosticators for the transformation of premalignant breast lesions. The presence of spliced Osteopontin-c in these lesions does reflect the risk for cancer development within 5 years. METHODS: By immunohistochemistry, we analyze the association of Osteopontin variant expression in healthy breasts, hyperplasias, radial scars, lobular and ductal carcinomas in situ from 434 women as well as papillomas from 114 women to assess a) staining for OPN exon 4 (present in OPN-a and OPNb) and OPN-c in low-risk to high-risk lesions b) correlations between staining and progression to cancer or survival. RESULTS: The staining intensity for OPN-c correlates with risk, and it is prognostic for ensuing invasive disease and survival. About 10% of OPN-c pathology score 0–1 (intensity), vs. 40% of score 3 experience cancer over 5 years. More than 90% of women, who progress, had pathology scores of 2–3 for OPN-c intensity at the time of initial diagnosis. When combining OPN-c and OPN exon 4 staining, all of the low intensity patients are alive after 5 years, whereas women in the high category have a close to 30% chance to die within 5 years. Of patients who succumb, close to 80% had a high combined score at the time of initial diagnosis. In the papilloma patients, fewer than 5% of OPN-c pathology score 0-1 (intensity), versus almost 18% of score 2-3 experienced cancer in follow-up. 9 of 12 women, who progressed, had pathology scores of 2-3 for OPN-c intensity at the time of initial diagnosis, none had a score of 0. When developing a combined risk score from intensity plus percent positivity for OPN-c, the progression risk for patients with low score was 3.2%, for intermediate score was 5.7%, and for high score was 18.8%. Papillomas in patients, who were later diagnosed with cancer in the contralateral breast, displayed stronger staining positivity than non-progressors. CONCLUSION: The information of OPN-c immunohistochemistry can provide a foundation for very reliable prognostication and has the potential to aid decision making in the treatment or watchful waiting of early breast lesions. The addition of OPN-a refines the prognostication of survival. The staining intensity for OPN variants may also inform on the cancer risk in the unaffected breast, which may reflect a genetic predisposition for Osteopontin expression and splicing. OPN splice variant immunohistochemistry on breast biopsies will allow counseling of the patients on their risk to develop breast cancer at a later time. Citation Format: Georg F. Weber, Piotr Ziolkowski. Osteopontin splice variants indicate prognosis in premalignant breast lesions [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-36.
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Biener, Eva, Cyril Martin, Nathalie Daniel, Stuart J. Frank, Victoria E. Centonze, Brian Herman, Jean Djiane e Arieh Gertler. "Ovine Placental Lactogen-Induced Heterodimerization of Ovine Growth Hormone and Prolactin Receptors in Living Cells Is Demonstrated by Fluorescence Resonance Energy Transfer Microscopy and Leads to Prolonged Phosphorylation of Signal Transducer and Activator of Transcription (STAT)1 and STAT3". Endocrinology 144, n. 8 (1 agosto 2003): 3532–40. http://dx.doi.org/10.1210/en.2003-0096.
Testo completoAbstract (sommario):
Abstract HEK-293T cells transiently transfected with ovine (o) GH receptor (GHR) and prolactin receptor (PRLR) constructs respectively tagged downstream with cyan or yellow fluorescent proteins were used to study ovine placental lactogen (oPL)-stimulated heterodimerization by fluorescence resonance energy transfer (FRET) microscopy. The oPL-stimulated transient heterodimerization of GHR and PRLR had a peak occurring 2.5–3 min after oPL application, whereas oGH or oPRL had no effect at all. The results indicate none or only little dimerization occurring before the hormonal stimulation. The effect of heterodimerization was studied by comparing activation of Janus kinase 2, signal transducer and activator of transcription (STAT)1, STAT3, STAT5, and MAPK in Chinese hamster ovary cells stably transfected with chimeric genes encoding receptors consisting of cytosolic and transmembrane parts of oGHR and oPRLR, extracellular domains of human granulocyte and macrophage colony-stimulating factor (hGM-CSF) receptor α or β, and cells transfected with the two forms (α or β) of PRLR and GHR. Functionality of those proteins was verified by hGM-CSF-induced phosphorylation of both intracellular PRLR and GHR domains and hGM-CSF-induced heterodimerization was documented by chimeric receptor coimmunoprecipitation. Homodimerization or heterodimerization of PRLRs and GHRs had no differential effect on activation of STAT5 and MAPK. However, heterodimerization resulted in a prolonged phosphorylation of STAT1 and in particular STAT3, suggesting that the heterodimerization of α-oGHR and β-oPRLR is able to transduce a signal, which is distinct from that occurring on homodimeric associations.
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Chimoto, S., Y. Iwamoto, H. Shimazu e K. Yoshida. "Monosynaptic activation of medium-lead burst neurons from the superior colliculus in the alert cat". Journal of Neurophysiology 75, n. 6 (1 giugno 1996): 2658–61. http://dx.doi.org/10.1152/jn.1996.75.6.2658.
Testo completoAbstract (sommario):
1. Extracellular recordings were made from medium-lead burst neurons (MLBNs) in the paramedian pontomedullary reticular formation rostral and caudal to the abducens nucleus in the alert cat. 2. Single-pulse stimulation of the contralateral superior colliculus during intersaccadic intervals evoked no response in most MLBNs. When collicular stimulation was applied at the beginning of saccades, spikes of MLBNs were consistently evoked with short latencies. The shortest latency was 0.8 ms, indicating monosynaptic activation of MLBNs from the superior colliculus. 3. Results suggest that monosynaptic excitatory effects from the colliculus are concealed by inhibitory input from omnipause neurons (OPNs) during intersaccadic intervals and that the monosynaptic collicular activation is disclosed when this inhibition is removed by a pause in OPN activity at the beginning of saccades.
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Byun, Jun-Hwan, Ji-Yeon Hyeon, Eun-Su Kim, Byeong-Hoon Kim, Hiroshi Miyanishi, Hirohiko Kagawa, Yuki Takeuchi, Se-Jae Kim, Akihiro Takemura e Sung-Pyo Hur. "Gene expression patterns of novel visual and non-visual opsin families in immature and mature Japanese eel males". PeerJ 8 (27 febbraio 2020): e8326. http://dx.doi.org/10.7717/peerj.8326.
Testo completoAbstract (sommario):
This study was carried out to identify and estimate physiological function of a new type of opsin subfamily present in the retina and whole brain tissues of Japanese eel using RNA–Seq transcriptome method. A total of 18 opsin subfamilies were identified through RNA–seq. The visual opsin family included Rh2, SWS2, FWO, DSO, and Exo-Rhod. The non-visual opsin family included four types of melanopsin subfamily (Opn4x1, Opn4x2, Opn4m1, and Opn4m2), peropsin, two types of neuropsin subfamily (Opn5-like, Opn5), Opn3, three types of TMT opsin subfamily (TMT1, 2, 3), VA-opsin, and parapinopsin. In terms of changes in photoreceptor gene expression in the retina of sexually mature and immature male eels, DSO mRNA increased in the maturation group. Analysis of expression of opsin family gene in male eel brain before and after maturation revealed that DSO and SWS2 expression in terms of visual opsin mRNA increased in the sexually mature group. In terms of non-visual opsin mRNA, parapinopsin mRNA increased whereas that of TMT2 decreased in the fore-brain of the sexually mature group. The mRNA for parapinopsin increased in the mid-brain of the sexually mature group, whereas those of TMT1 and TMT3 increased in the hind-brain of the sexually mature group. DSO mRNA also increased in the retina after sexual maturation, and DSO and SWS2 mRNA increased in whole brain part, suggesting that DSO and SWS2 are closely related to sexual maturation.
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Smith, Audrey L., Alexandria P. Eiken, Sydney A. Skupa, Christopher R. D'Angelo, Avyakta Kallam, Matthew A. Lunning, Gregory Bociek et al. "Abstract 6396: BET inhibition alleviates T-cell dysfunction in chronic lymphocytic leukemia". Cancer Research 83, n. 7_Supplement (4 aprile 2023): 6396. http://dx.doi.org/10.1158/1538-7445.am2023-6396.
Testo completoAbstract (sommario):
Abstract Background: The chronic lymphocytic leukemia (CLL) tumor microenvironment (TME) is laden with hyporesponsive T-cells that permit disease persistence. Yet, redundant TME immunosuppressive mechanisms and epigenetic maintenance of T-cell exhaustion limit the efficacy of T-cell targeted therapies in CLL. Bromodomain and extra-terminal (BET) proteins regulate key pathways contributing to CLL pathogenesis and TME interactions, including T-cell function and differentiation. We hypothesize that blocking BET protein function can reverse T-cell exhaustion to yield durable tumor elimination in CLL. Methods: WT C57BL/6 mice were engrafted with Eμ-TCL1 spleen-derived lymphocytes, then treated daily with the novel pan-BET inhibitor, OPN-51107 (OPN5; 20mg/kg PO) for up to 4 weeks. Splenic gene expression was evaluated with the NanoString PanCancer iO360 panel. T-cell differentiation status, immune inhibitory receptor (IR) expression, proliferation (72 h ex vivo α-CD3/α-CD28 stimulation), and cytokine production (6 h ex vivo PMA/ionomycin stimulation) was measured via flow cytometry. CLL patient and healthy donor PBMCs were used for validation studies and to assess T-cell transcription factor (TF) expression via flow cytometry. Evaluation of BRD4 occupancy at select T-cell TFs via ChIP qPCR is ongoing. Results: OPN5 significantly increased cytotoxic cell signatures and reduced exhaustion-associated cell signatures in leukemic mice through inhibition of T-cell exhaustion signaling, as well as activation of Th1, natural killer cell, and IL-7 signaling pathways. Correspondingly, T-cells from OPN5-treated mice demonstrated greater ex vivo proliferative capacity and effector response to stimuli. A greater proportion of CD8+ T-cells from OPN5-treated mice were classified as naïve, and OPN5 significantly reduced KLRG1 expression on antigen-experienced CD8+ T-cells. Importantly, OPN5 curtailed IR co-expression (PD-1, PD-L1, VISTA, CD244, CD160, and LAG3) on splenic T-cells. These findings were confirmed with primary CLL cells ex vivo. OPN5 also impaired expression of terminal differentiation-associated TFs in CLL patient-derived T-cells, enriching for a TCF1+ progenitor T-cell population. While BTK inhibitors are known to similarly improve T-cell function in CLL, ibrutinib treatment was inadequate to revert CLL T-cell terminal differentiation. Future ATAC-sequencing analysis will inform how BET inhibition alleviates exhaustion-associated chromatin organization in CLL T-cells. Conclusion: BET inhibition dismantles immunosuppressive mechanisms in the CLL TME, alleviating CLL-induced T-cell dysfunction and terminal differentiation. These findings suggest that BET inhibition may be a useful component of combination strategies for the treatment of CLL to yield lasting anti-cancer immune memory and prevent relapsed/refractory disease. Citation Format: Audrey L. Smith, Alexandria P. Eiken, Sydney A. Skupa, Christopher R. D'Angelo, Avyakta Kallam, Matthew A. Lunning, Gregory Bociek, Julie M. Vose, Ben Powell, Gideon Bollag, Dalia El-Gamal. BET inhibition alleviates T-cell dysfunction in chronic lymphocytic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6396.
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Gertler, Arieh, Eva Biener, Krishnan V. Ramanujan, Jean Djiane e Brian Herman. "Fluorescence resonance energy transfer (FRET) microscopy in living cells as a novel tool for the study of cytokine action". Journal of Dairy Research 72, S1 (28 luglio 2005): 14–19. http://dx.doi.org/10.1017/s0022029905001123.
Testo completoAbstract (sommario):
Fluorescence resonance energy transfer (FRET) microscopy was used to study interactions between proteins in intact cells. We showed that growth hormone (GH) causes transient homodimerization of GH receptors tagged with yellow or cyan fluorescent proteins. The peak of FRET signaling occurred 2 to 4 min after hormonal stimulation and was followed by a decrease in FRET signal. Repeating those experiments in cells pretreated with the inhibitor of internalization methyl-β-cyclodextrin, or in potassium-depleted cells showed no difference in the kinetics of FRET signaling as compared with the non-treated cells, indicating that the decrease in FRET signal does not result from receptor internalization by the pathways inhibited by methyl-β-cyclodextrin or potassium depleted but might occur by other pathways of internalization. Using a similar methodology, we also demonstrated that ovine placental lactogen (oPL) causes transient heterodimerization of GH and prolactin (PRL) receptors 2·5 to 3 min after oPL application. On the other hand, oGH or oPRL had no effect at all, further substantiating the finding the oPL, which lacks a specific receptor, acts in homologous systems by heterodimerization of GH and PRL receptors. We also demonstrated that both PRL and leptin (LEP) are capable of transactivation of the oncogenic receptors erbB2 and erbB3. Upon PRL or LEP stimulation of HEK-293T cells transfected with LEP or PRL receptors and erbB2 or erbB3, erbB proteins are first phosphorylated and then activate MAPK (erk1/erk2). However, the FRET experiments failed to document any evidence of a direct interaction between erbB2 and the PRL or LEP receptors, suggesting that erbB activation probably occurs via activated JAK2, translocated from the respective receptors to erbB2.
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Kasiyati, _. "Regulasi Fotodeteksi: Peran Cahaya Pada Performa Produksi Telur Unggas". Buletin Anatomi dan Fisiologi 3, n. 2 (30 dicembre 2018): 150–60. http://dx.doi.org/10.14710/baf.3.2.2018.150-160.
Testo completoAbstract (sommario):
Cahaya merupakan salah satu faktor lingkungan yang esensial bagi kehidupan aves. Signal cahaya yang diterima oleh hipotalamus dapat mengontrol sekresi gonadotropin releasing hormone (GnRH) yang berperan dalam menstimulasi pitutari melepaskan follicle stimulating hormone (FSH) dan luteinizing hormone (LH). Peningkatan konsetrasi dan waktu sekresi gonadotropin berpengaruh pada umur dewasa kelamin, siklus ovulasi, serta performa produksi telur pada aves. Tujuan dari ulasan artikel ini fokus pada peran cahaya yang melibatkan sistem sensori pada performa produksi telur unggas. Organ fotoreseptor vertebrata non-mamalia termasuk aves selain mata adalah organ pineal dan fotoreseptor otak bagian dalam (deep brain photoreceptors). Beberapa molekul fotoreseptor deep brain, yaitu rodopsin (RH), melanopsin (OPN4), dan vertebrate ancient (VA)-opsin, serta protein opsin 5 (OPN5 atau neuropsin). Paparan cahaya yang lebih lama pada siang hari yang panjang menstimulasi peningkatan ekspresi mRNA GnRH sehingga menginduksi dewasa (matang) kelamin unggas. Peningkatan performa reproduksi walaupun kecil tetap berpengaruh pada produksi telur. Lebih dari 33% peningkatan performa reproduksi dan produksi telur merupakan kontribusi dari penggunaan cahaya. Intisari dari ulasan ini adalah mengetahui peran fotoreseptor pada unggas.
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Banerjee, Arun, e Thomas Wenzel. "Black opal from Honduras". European Journal of Mineralogy 11, n. 2 (19 aprile 1999): 401–8. http://dx.doi.org/10.1127/ejm/11/2/0401.
Testo completo
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Doi, Toru, Ryuji Sakamoto, Chiaki Horii, Naoki Okamoto, Koji Nakajima, Shima Hirai, Fumihiko Oguchi et al. "Risk factors for progression of ossification of the posterior longitudinal ligament in asymptomatic subjects". Journal of Neurosurgery: Spine 33, n. 3 (settembre 2020): 316–22. http://dx.doi.org/10.3171/2020.3.spine2082.
Testo completoAbstract (sommario):
OBJECTIVEThe incidence and risk factors for the progression of ossification of the posterior longitudinal ligament (OPLL) have been previously reported in surgically and nonsurgically treated symptomatic patients. However, the correlates of OPLL progression in asymptomatic subjects with OPLL are not well characterized. This study aimed to clarify the incidence and risk factors for OPLL progression in asymptomatic subjects based on whole-body CT.METHODSThe authors retrospectively reviewed 2585 healthy subjects who underwent whole-body CT at a single health center from September 2007 to December 2011. This study included asymptomatic subjects with OPLL who underwent CT scans twice with an interval of at least 5 years. Progression of OPLL was assessed based on initial and final CT scan. Subjects were divided into two groups: nonprogression (OPLL-NP) and progression (OPLL-P) groups. Clinical characteristics, bone mineral density status, OPLL types, and OPLL involvement of multiple vertebral levels between the two groups were compared. Risk factors for progression of OPLL were identified by logistic regression analysis after propensity score adjustment.RESULTSOf the 109 subjects with OPLL (91 men and 18 women), 20 (18.3%) exhibited OPLL progression (OPLL-P group). Subjects in the OPLL-P group were significantly younger (p = 0.031), had higher prevalence of multilevel OPLL involvement (p = 0.041) and continuous type of OPLL (p = 0.015), and had higher uric acid (UA) levels (p = 0.004) at the time of initial CT examination compared to the OPLL-NP group. Younger age (adjusted odds ratio [aOR] 0.95, 95% CI 0.90–0.99), OPLL involvement of multiple vertebral levels (aOR 2.88, 95% CI 1.06–7.83), continuous type of OPLL (aOR 4.21, 95% CI 1.35–13.10), and higher UA levels (aOR 2.09, 95% CI 1.24–3.53) were significant risk factors for OPLL progression.CONCLUSIONSYounger age, OPLL involvement of multiple vertebral levels, continuous type of OPLL, and higher UA levels are significant risk factors for OPLL progression in asymptomatic subjects.
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Curtis, Neville J., Jason R. Gascooke, Martin R. Johnston e Allan Pring. "A Review of the Classification of Opal with Reference to Recent New Localities". Minerals 9, n. 5 (15 maggio 2019): 299. http://dx.doi.org/10.3390/min9050299.
Testo completoAbstract (sommario):
Our examination of over 230 worldwide opal samples shows that X-ray diffraction (XRD) remains the best primary method for delineation and classification of opal-A, opal-CT and opal-C, though we found that mid-range infra-red spectroscopy provides an acceptable alternative. Raman, infra-red and nuclear magnetic resonance spectroscopy may also provide additional information to assist in classification and provenance. The corpus of results indicated that the opal-CT group covers a range of structural states and will benefit from further multi-technique analysis. At the one end are the opal-CTs that provide a simple XRD pattern (“simple” opal-CT) that includes Ethiopian play-of-colour samples, which are not opal-A. At the other end of the range are those opal-CTs that give a complex XRD pattern (“complex” opal-CT). The majority of opal-CT samples fall at this end of the range, though some show play-of-colour. Raman spectra provide some correlation. Specimens from new opal finds were examined. Those from Ethiopia, Kazakhstan, Madagascar, Peru, Tanzania and Turkey all proved to be opal-CT. Of the three specimens examined from Indonesian localities, one proved to be opal-A, while a second sample and the play-of-colour opal from West Java was a “simple” Opal-CT. Evidence for two transitional types having characteristics of opal-A and opal-CT, and “simple” opal-CT and opal-C are presented.
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Mello, Kivvi Duarte, Tatiana Martins Tilli, Ana Carolina S. Ferreira, Claudete Esteves Klumb e Etel Rodrigues Pereira Gimba. "Abstract B58: OPNc and OPNb osteopontin splicing isofoms activate prostate cancer prosurvival features through PI3K/AKT/BIM signaling pathway". Cancer Research 72, n. 4 Supplement (6 febbraio 2012): B58. http://dx.doi.org/10.1158/1538-7445.prca2012-b58.
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Harpham, Wendy S. "Opal". Oncology Times 29, n. 3 (febbraio 2007): 33. http://dx.doi.org/10.1097/01.cot.0000266375.91332.de.
Testo completo
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Park, Jinyoung, Yong Eun Cho, Kyung Hyun Kim, Sanghoon Shin, Sungjun Kim, Chae Hwan Lim, Seok Young Chung e Yoon Ghil Park. "Correlation Between the Severity of Multifidus Fatty Degeneration and the Size of Ossification of Posterior Longitudinal Ligament at Each Spinal Level". Neurospine 20, n. 3 (30 settembre 2023): 921–30. http://dx.doi.org/10.14245/ns.2346506.253.
Testo completoAbstract (sommario):
Objective: This study aimed to investigate the correlation between ossification of the posterior longitudinal ligament (OPLL) size and multifidus fatty degeneration (MFD), hypothesizing that larger OPLL sizes are associated with worse MFD.Methods: One hundred four patients with cervical OPLL who underwent surgery were screened. OPLL occupying diameter and area ratios, the severity of MFD using the Goutallier classification, and range of motion (ROM) of cervical flexion-extension (ΔCobb) were measured. Correlation analyses between OPLL size, MFD severity, and ΔCobb were conducted. MFD severity was compared for each OPLL type using one-way analysis of variance.Results: The final clinical data from 100 patients were analyzed. The average Goutallier grade of C2–7 significantly correlated with the average OPLL diameter and area occupying ratios, and OPLL involved vertebral level (r = 0.58, p < 0.01; r = 0.40, p < 0.01; r = 0.47, p < 0.01, respectively). The OPLL size at each cervical level significantly correlated with MFD of the same or 1–3 adjacent levels. ΔCobb angle was negatively correlated with the average Goutallier grade (r = -0.31, p < 0.01) and average OPLL occupying diameter and area ratios (r = -0.31, p < 0.01; r = -0.35, p < 0.01, respectively). Patients with continuous OPLL exhibited worse MFD than those with segmental OPLL (p < 0.01).Conclusion: OPLL size is clinically correlated with MFD and cervical ROM. OPLL at one spinal level affects MFD at the same and 1–3 adjacent spinal levels. The worsening severity of MFD is associated with the longitudinal continuity of OPLL.
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Mills, D. E., e R. B. Woods. "Interaction of prolactin with adrenal hormones in blood pressure regulation in rats". American Journal of Physiology-Endocrinology and Metabolism 249, n. 6 (1 dicembre 1985): E614—E618. http://dx.doi.org/10.1152/ajpendo.1985.249.6.e614.
Testo completoAbstract (sommario):
This study examined the role of the adrenals in the systolic blood pressure (BP) response to ovine prolactin (oPRL) administration as well as the interaction of oPRL with epinephrine (EPI), norepinephrine (NOR), and corticosterone (CORT) on BP in the rat. After intraperitoneal implantation of 7-day osmotic minipumps releasing 0.6 micrograms oPRL/h in 0.9% NaCl on day 1, BP was measured via tail cuff on days 1, 4, and 7 in adrenalectomized (ADX) and sham-ADX male rats (n = 8/group). BP was also measured in ADX rats receiving CORT (27.0 micrograms/h), EPI (1.7 micrograms/h), NOR (5.0 micrograms/h), CORT + oPRL, EPI + oPRL, and NOR + oPRL by osmotic pump (n = 8/group). All ADX rats not receiving CORT were given 1.0% NaCl replacement for drinking water. oPRL increased BP over 17 days in sham-ADX rats (P less than 0.01) but had no effect in ADX rats. BP also increased over 7 days in ADX animals receiving CORT, EPI (P less than 0.01), and NOR (P less than 0.01). BP responses to CORT + oPRL and EPI + oPRL were similar to those of CORT and EPI alone, respectively. However, the BP response to NOR + oPRL on day 4 was 250% (P less than 0.01) that to NOR alone and similar to NOR alone on day 7. Replacement of CORT + NOR + oPRL did not prolong the oPRL-induced sensitization to NOR. In no instance did oPRL, by itself, alter heart rate. These data suggest that the pressor response to oPRL requires the presence of the adrenal glands and that oPRL transiently potentiates the pressor response to NOR in vivo.
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Won, Young Il, Chang-Hyun Lee, Woon Tak Yuh, Shin Won Kwon, Chi Heon Kim e Chun Kee Chung. "Genetic Odyssey to Ossification of the Posterior Longitudinal Ligament in the Cervical Spine: A Systematic Review". Neurospine 19, n. 2 (30 giugno 2022): 299–306. http://dx.doi.org/10.14245/ns.2244038.019.
Testo completoAbstract (sommario):
Despite numerous studies, the pathogenesis of ossification of the posterior longitudinal ligament (OPLL) is still unclear. Previous genetic studies proposed variations in genes related to bone and collagen as a cause of OPLL. It is unclear whether the upregulations of those genes are the cause of OPLL or an intermediate result of endochondral ossification process. Causal variations may be in the inflammation-related genes supported by clinical and updated genomic studies. OPLL demonstrates features of genetic diseases but can also be induced by mechanical stress by itself. OPLL may be a combination of various diseases that share ossification as a common pathway and can be divided into genetic and idiopathic. The phenotype of OPLL can be divided into continuous (including mixed) and segmental (including localized) based on the histopathology, prognosis, and appearance. Continuous OPLL shows substantial overexpression of osteoblast-specific genes, frequent upper cervical involvement, common progression, and need for surgery, whereas segmental OPLL shows moderate-to-high expression of these genes and is often clinically silent. Genetic OPLL seems to share clinical features with the continuous type, while idiopathic OPLL shares features with the segmental type. Further genomic studies are needed to elucidate the relationship between genetic OPLL and phenotype of OPLL.
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Curtis, Neville J., Jason R. Gascooke, Martin R. Johnston e Allan Pring. "29Si Solid-State NMR Analysis of Opal-AG, Opal-AN and Opal-CT: Single Pulse Spectroscopy and Spin-Lattice T1 Relaxometry". Minerals 12, n. 3 (4 marzo 2022): 323. http://dx.doi.org/10.3390/min12030323.
Testo completoAbstract (sommario):
Single pulse, solid-state 29Si nuclear magnetic resonance (NMR) spectroscopy offers an additional method of characterisation of opal-A and opal-CT through spin-lattice (T1) relaxometry. Opal T1 relaxation is characterised by stretched exponential (Weibull) function represented by scale (speed of relaxation) and shape (form of the curve) parameters. Relaxation is at least an order of magnitude faster than for silica glass and quartz, with Q3 (silanol) usually faster than Q4 (fully substituted silicates). 95% relaxation (Q4) is achieved for some Australian seam opals after 50 s though other samples of opal-AG may take 4000 s, while some figures for opal-AN are over 10,000 s. Enhancement is probably mostly due to the presence of water/silanol though the presence of paramagnetic metal ions and molecular motion may also contribute. Shape factors for opal-AG (0.5) and opal-AN (0.7) are significantly different, consistent with varying water and silanol environments, possibly reflecting differences in formation conditions. Opal-CT samples show a trend of shape factors from 0.45 to 0.75 correlated to relaxation rate. Peak position, scale and shape parameter, and Q3 to Q4 ratios offer further differentiating feature to separate opal-AG and opal-AN from other forms of opaline silica. T1 relaxation measurement may have a role for provenance verification. In addition, definitively determined Q3/Q4 ratios are in the range 0.1 to 0.4 for opal-AG but considerably lower for opal-AN and opal-CT.
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Murakami, Motoaki, Atsushi Seichi, Hirotaka Chikuda, Katsushi Takeshita, Kozo Nakamura e Atsushi Kimura. "Long-term follow-up of the progression of ossification of the posterior longitudinal ligament". Journal of Neurosurgery: Spine 12, n. 5 (maggio 2010): 577–79. http://dx.doi.org/10.3171/2010.1.spine09452.
Testo completoAbstract (sommario):
The authors report the case of a man with cervical ossification of the posterior longitudinal ligament (OPLL) who was observed for more than 26 years. Initial symptoms consisted of subtle numbness of the hands, and initial radiography showed small, segmental-type OPLL in the cervical spine. Lateral radiography of the cervical spine was performed every few years. Ossification accelerated for about 4 years during the follow-up. Segmental-type OPLL developed into mixed-type extensive OPLL. This case shows an accelerating maturation process of OPLL over the course of a few years. Segmental-type OPLL appears to represent an initial stage of extensive OPLL.
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Choi, Byung-Wan, Dong-Hoon Baek, Lindsey C. Sheffler e Han Chang. "Analysis of progression of cervical OPLL using computerized tomography: typical sign of maturation of OPLL mass". Journal of Neurosurgery: Spine 23, n. 5 (novembre 2015): 539–43. http://dx.doi.org/10.3171/2015.1.spine131167.
Testo completoAbstract (sommario):
OBJECT The progression of cervical ossification of the posterior longitudinal ligament (OPLL) can lead to increase in the size of the OPLL mass and aggravation of neurological symptoms. In the present study, the authors aimed to analyze the progression of cervical OPLL by using CT imaging, elucidate the morphology of OPLL masses, and evaluate the factors associated with the progression of cervical OPLL. METHODS Sixty patients with cervical OPLL were included. All underwent an initial CT examination and had at least 24 months’ follow-up with CT. The mean duration of follow-up was 29.6 months. Fourteen patients (Group A) had CT evidence of OPLL progression, and 46 (Group B) did not show evidence of progression on CT. The 2 groups were compared with respect to the following variables: sex, age, number of involved segments, type of OPLL, and treatment methods. The CT findings, such as the connection of an OPLL mass with the vertebral body and formation of trabeculation in the mass, were evaluated. RESULTS Sex and treatment modality were not associated with OPLL progression. The mean age of the patients in Group A was significantly lower than that in Group B (p = 0.03). The mean number of involved segments was 5.3 in Group A and 3.6 in Group B (p = 0.002). Group A had a higher proportion of cases with the mixed type of OPLL, whereas Group B had a higher proportion of cases with the segmental type (p = 0.02). A connection between the vertebral body and OPLL mass and trabeculation formation were more common in Group B (p < 0.01). CONCLUSIONS Progression of cervical OPLL is associated with younger age, involvement of multiple levels, and mixed-type morphology. OPLL masses that are contiguous with the vertebral body and have trabecular formation are useful findings for identifying masses that are less likely to progress.