Journal articles on the topic 'Human functional fingerprint'
To see the other types of publications on this topic, follow the link: Human functional fingerprint.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Human functional fingerprint.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Vamanu, Emanuel. "Complementary Functional Strategy for Modulation of Human Gut Microbiota." Current Pharmaceutical Design 24, no. 35 (January 24, 2019): 4144–49. http://dx.doi.org/10.2174/1381612824666181001154242.
Full textAbstract:
Two pathologies commonly associated with gut microbiota dysbiosis are type 2 diabetes and cardiovascular diseases. Since diet and medication are two important causes of microbiome fingerprint modifications, new complementary and alternative methods can include wild edible mushrooms, which serve as functional products, given their properties in modulating the microbial pattern at the colon level. A disturbance in microbial balance translates into the occurrence of degenerative dysfunctions that are also associated with other pathologies, such as obesity, colon cancer. The metagenomic study has enabled the identification of some competitive microbiological and biochemical biomarkers which allow the development of innovative strategies in controling microbial disbalance from human gut. Thus, the aim of this review was to present the significant findings related to human microbiome modulation via the prebiotic effects of wild edible mushrooms as a complementary strategy to modern treatment. Certain mushroom species have been approached and their effects on the microbiota fingerprint of two major target groups are highlighted.
2
Le Du, Marie-Hélène, and José Luis Millán. "Structural Evidence of Functional Divergence in Human Alkaline Phosphatases." Journal of Biological Chemistry 277, no. 51 (October 7, 2002): 49808–14. http://dx.doi.org/10.1074/jbc.m207394200.
Full textAbstract:
The evolution of the alkaline phosphatase (AP) gene family has lead to the existence in humans of one tissue-nonspecific (TNAP) and three tissue-specific isozymes,i.e.intestinal (IAP), germ cell (GCAP), and placental AP (PLAP). To define the structural differences between these isozymes, we have built models of the TNAP, IAP, and GCAP molecules based on the 1.8-Å structure of PLAP (1) and have performed a comparative structural analysis. We have examined the monomer-monomer interface as this area is crucial for protein stability and enzymatic activity. We found that the interface allows the formation of heterodimers among IAP, GCAP, and PLAP but not between TNAP with any of the three tissue-specific isozymes. Secondly, the active site cleft was mapped into three regions,i.e.the active site itself, the roof of the cleft, and the floor of the cleft. This analysis led to a structural fingerprint of the active site of each AP isozyme that suggests a diversification in substrate specificity for this isozyme family.
3
Toh, K. A., and W. Y. Yau. "Fingerprint and Speaker Verification Decisions Fusion Using a Functional Link Network." IEEE Transactions on Systems, Man and Cybernetics, Part C (Applications and Reviews) 35, no. 3 (August 2005): 357–70. http://dx.doi.org/10.1109/tsmcc.2005.848184.
Full text
4
Zhao, Zheng, Li Xie, Lei Xie, and Philip E. Bourne. "Delineation of Polypharmacology across the Human Structural Kinome Using a Functional Site Interaction Fingerprint Approach." Journal of Medicinal Chemistry 59, no. 9 (March 17, 2016): 4326–41. http://dx.doi.org/10.1021/acs.jmedchem.5b02041.
Full text
5
Gomez-Fuentes, Sandra, Sarah Hernández-de la Fuente, Valeria Morales-Ruiz, Dina López-Recinos, Adrián Guevara-Salinas, María Cristina Parada-Colin, Clara Espitia, et al. "A novel, sequencing-free strategy for the functional characterization of Taenia solium proteomic fingerprint." PLOS Neglected Tropical Diseases 15, no. 2 (February 18, 2021): e0009104. http://dx.doi.org/10.1371/journal.pntd.0009104.
Full textAbstract:
The flatworm Taenia solium causes human and pig cysticercosis. When cysticerci are established in the human central nervous system, they cause neurocysticercosis, a potentially fatal disease. Neurocysticercosis is a persisting public health problem in rural regions of Mexico and other developing countries of Latin America, Asia, and Africa, where the infection is endemic. The great variability observed in the phenotypic and genotypic traits of cysticerci result in a great heterogeneity in the patterns of molecules secreted by them within their host. This work is aimed to identify and characterize cysticercal secretion proteins of T. solium cysticerci obtained from 5 naturally infected pigs from Guerrero, Mexico, using 2D-PAGE proteomic analysis. The isoelectric point (IP) and molecular weight (MW) of the spots were identified using the software ImageMaster 2D Platinum v.7.0. Since most secreted proteins are impossible to identify by mass spectrometry (MS) due to their low concentration in the sample, a novel strategy to predict their sequence was applied. In total, 108 conserved and 186 differential proteins were identified in five cysticercus cultures. Interestingly, we predicted the sequence of 14 proteins that were common in four out of five cysticercus cultures, which could be used to design vaccines or diagnostic methods for neurocysticercosis. A functional characterization of all sequences was performed using the algorithms SecretomeP, SignalP, and BlastKOALA. We found a possible link between signal transduction pathways in parasite cells and human cancer due to deregulation in signal transduction pathways. Bioinformatics analysis also demonstrated that the parasite release proteins by an exosome-like mechanism, which could be of biological interest.
6
Amico, Enrico, and Joaquín Goñi. "Mapping hybrid functional-structural connectivity traits in the human connectome." Network Neuroscience 2, no. 3 (September 2018): 306–22. http://dx.doi.org/10.1162/netn_a_00049.
Full textAbstract:
One of the crucial questions in neuroscience is how a rich functional repertoire of brain states relates to its underlying structural organization. How to study the associations between these structural and functional layers is an open problem that involves novel conceptual ways of tackling this question. We here propose an extension of the Connectivity Independent Component Analysis (connICA) framework to identify joint structural-functional connectivity traits. Here, we extend connICA to integrate structural and functional connectomes by merging them into common “hybrid” connectivity patterns that represent the connectivity fingerprint of a subject. We tested this extended approach on the 100 unrelated subjects from the Human Connectome Project. The method is able to extract main independent structural-functional connectivity patterns from the entire cohort that are sensitive to the realization of different tasks. The hybrid connICA extracts two main task-sensitive hybrid traits. The first trait encompasses the within and between connections of dorsal attentional and visual areas, as well as frontoparietal circuits. The second trait mainly encompasses the connectivity between visual, attentional, default mode network (DMN), and subcortical network. Overall, these findings confirm the potential of the hybrid connICA for the compression of structural/functional connectomes into integrated patterns from a set of individual brain networks.
7
Uddin, Lucina Q., Joshua Kinnison, Luiz Pessoa, and Michael L. Anderson. "Beyond the Tripartite Cognition–Emotion–Interoception Model of the Human Insular Cortex." Journal of Cognitive Neuroscience 26, no. 1 (January 2014): 16–27. http://dx.doi.org/10.1162/jocn_a_00462.
Full textAbstract:
Functional MRI studies report insular activations across a wide range of tasks involving affective, sensory, and motor processing, but also during tasks of high-level perception, attention, and control. Although insular cortical activations are often reported in the literature, the diverse functional roles of this region are still not well understood. We used a meta-analytic approach to analyze the coactivation profiles of insular subdivisions—dorsal anterior, ventral anterior, and posterior insula—across fMRI studies in terms of multiple task domains including emotion, memory, attention, and reasoning. We found extensive coactivation of each insular subdivision, with substantial overlap between coactivation partners for each subdivision. Functional fingerprint analyses revealed that all subdivisions cooperated with a functionally diverse set of regions. Graph-theoretical analyses revealed that the dorsal anterior insula was a highly “central” structure in the coactivation network. Furthermore, analysis of the studies that activate the insular cortex itself showed that the right dorsal anterior insula was a particularly “diverse” structure in that it was likely to be active across multiple task domains. These results highlight the nuanced functional profiles of insular subdivisions and are consistent with recent work suggesting that the dorsal anterior insula can be considered a critical functional hub in the human brain.
8
Khymenets, Olha, Cristina Andres-Lacueva, Mireia Urpi-Sarda, Rosa Vazquez-Fresno, Mercè Mercader Mart, Guillermo Reglero, Mireia Torres, and Rafael Llorach. "Metabolic fingerprint after acute and under sustained consumption of a functional beverage based on grape skin extract in healthy human subjects." Food & Function 6, no. 4 (2015): 1288–98. http://dx.doi.org/10.1039/c4fo00684d.
Full text
9
Bua, Rosaria Ornella, Angela Messina, Luisa Sturiale, Rita Barone, Domenico Garozzo, and Angelo Palmigiano. "N-Glycomics of Human Erythrocytes." International Journal of Molecular Sciences 22, no. 15 (July 28, 2021): 8063. http://dx.doi.org/10.3390/ijms22158063.
Full textAbstract:
Glycosylation is a complex post-translational modification that conveys functional diversity to glycoconjugates. Cell surface glycosylation mediates several biological activities such as induction of the intracellular signaling pathway and pathogen recognition. Red blood cell (RBC) membrane N-glycans determine blood type and influence cell lifespan. Although several proteomic studies have been carried out, the glycosylation of RBC membrane proteins has not been systematically investigated. This work aims at exploring the human RBC N-glycome by high-sensitivity MALDI-MS techniques to outline a fingerprint of RBC N-glycans. To this purpose, the MALDI-TOF spectra of healthy subjects harboring different blood groups were acquired. Results showed the predominant occurrence of neutral and sialylated complex N-glycans with bisected N-acetylglucosamine and core- and/or antennary fucosylation. In the higher mass region, these species presented with multiple N-acetyllactosamine repeating units. Amongst the detected glycoforms, the presence of glycans bearing ABO(H) antigens allowed us to define a distinctive spectrum for each blood group. For the first time, advanced glycomic techniques have been applied to a comprehensive exploration of human RBC N-glycosylation, providing a new tool for the early detection of distinct glycome changes associated with disease conditions as well as for understanding the molecular recognition of pathogens.
10
Baranova, Margarita N., Arsen M. Kudzhaev, Yuliana A. Mokrushina, Vladislav V. Babenko, Maria A. Kornienko, Maja V. Malakhova, Victor G. Yudin, et al. "Deep Functional Profiling of Wild Animal Microbiomes Reveals Probiotic Bacillus pumilus Strains with a Common Biosynthetic Fingerprint." International Journal of Molecular Sciences 23, no. 3 (January 21, 2022): 1168. http://dx.doi.org/10.3390/ijms23031168.
Full textAbstract:
The biodiversity of microorganisms is maintained by intricate nets of interactions between competing species. Impaired functionality of human microbiomes correlates with their reduced biodiversity originating from aseptic environmental conditions and antibiotic use. Microbiomes of wild animals are free of these selective pressures. Microbiota provides a protecting shield from invasion by pathogens in the wild, outcompeting their growth in specific ecological niches. We applied ultrahigh-throughput microfluidic technologies for functional profiling of microbiomes of wild animals, including the skin beetle, Siberian lynx, common raccoon dog, and East Siberian brown bear. Single-cell screening of the most efficient killers of the common human pathogen Staphylococcus aureus resulted in repeated isolation of Bacillus pumilus strains. While isolated strains had different phenotypes, all of them displayed a similar set of biosynthetic gene clusters (BGCs) encoding antibiotic amicoumacin, siderophore bacillibactin, and putative analogs of antimicrobials including bacilysin, surfactin, desferrioxamine, and class IId cyclical bacteriocin. Amicoumacin A (Ami) was identified as a major antibacterial metabolite of these strains mediating their antagonistic activity. Genome mining indicates that Ami BGCs with this architecture subdivide into three distinct families, characteristic of the B. pumilus, B. subtilis, and Paenibacillus species. While Ami itself displays mediocre activity against the majority of Gram-negative bacteria, isolated B. pumilus strains efficiently inhibit the growth of both Gram-positive S. aureus and Gram-negative E. coli in coculture. We believe that the expanded antagonistic activity spectrum of Ami-producing B. pumilus can be attributed to the metabolomic profile predetermined by their biosynthetic fingerprint. Ultrahigh-throughput isolation of natural probiotic strains from wild animal microbiomes, as well as their metabolic reprogramming, opens up a new avenue for pathogen control and microbiome remodeling in the food industry, agriculture, and healthcare.
11
Adejumobi, O. K., M. A. Adedoyin, A. A. Adenowo, O. O. Shoewu, and A. I. O. Yussuff. "DEVELOPMENT OF A FINGERPRINT-BASED ATTENDANCE NOTIFICATION SYSTEM USING SIMPLE MAIL TRANSFER PROTOCOL." Engineering and Technology Research Journal 6, no. 1 (March 24, 2021): 39–49. http://dx.doi.org/10.47545/etrj.2021.6.1.076.
Full textAbstract:
The concept of attendance monitoring has since evolved to become an integral part of every functional society. Today, in most educational institutions, students’ attendance is being taken manually by lecturers on paper-based attendance registers. However, this method is time-consuming, inaccurate and may not be available for analysis when needed because the collected data has not been stored in any database. Hence, in this paper, a fingerprintbased, wireless students’ attendance system using C# and MYSQL is developed to address the problem of truancy, human error in taking attendance and impersonation. Also, a fingerprint device with the Graphical User Interface (GUI) is modelled using C#, which was used for both enrolment and verification while MYSQL was used to model the database. The Simple Mail Transfer Protocol (SMTP) is then used to send the PDF version of the attendance records to relevant stakeholders to ascertain the students’ levels of attendance. The developed system is simple, secure and cost-effective to implement. The developed system worked efficiently when experimented.
12
Langlois, M. R., and J. R. Delanghe. "Biological and clinical significance of haptoglobin polymorphism in humans." Clinical Chemistry 42, no. 10 (October 1, 1996): 1589–600. http://dx.doi.org/10.1093/clinchem/42.10.1589.
Full textAbstract:
Abstract Haptoglobin is a hemoglobin-binding protein expressed by a genetic polymorphism as three major phenotypes: 1-1, 2-1, and 2-2. Most attention has been paid to determining haptoglobin phenotype as a genetic fingerprint used in forensic medicine. More recently, several functional differences between haptoglobin phenotypes have been demonstrated that appear to have important biological and clinical consequences. Haptoglobin polymorphism is associated with the prevalence and clinical evolution of many inflammatory diseases, including infections, atherosclerosis, and autoimmune disorders. These effects are explained by a phenotype-dependent modulation of oxidative stress and prostaglandin synthesis. Recent evidence is growing that haptoglobin is involved in the immune response as well. The strong genetic pressure favoring the 2-2 phenotype suggests an important role of haptoglobin in human pathology.
13
Bartels, Andreas, and Semir Zeki. "The chronoarchitecture of the cerebral cortex." Philosophical Transactions of the Royal Society B: Biological Sciences 360, no. 1456 (April 29, 2005): 733–50. http://dx.doi.org/10.1098/rstb.2005.1627.
Full textAbstract:
We review here a new approach to mapping the human cerebral cortex into distinct subdivisions. Unlike cytoarchitecture or traditional functional imaging, it does not rely on specific anatomical markers or functional hypotheses. Instead, we propose that the unique activity time course (ATC) of each cortical subdivision, elicited during natural conditions, acts as a temporal fingerprint that can be used to segregate cortical subdivisions, map their spatial extent, and reveal their functional and potentially anatomical connectivity. We argue that since the modular organisation of the brain and its connectivity evolved and developed in natural conditions, these are optimal for revealing its organisation. We review the concepts, methodology and first results of this approach, relying on data obtained with functional magnetic resonance imaging (fMRI) when volunteers viewed traditional stimuli or a James Bond movie. Independent component analysis (ICA) was used to identify voxels belonging to distinct functional subdivisions, based on their differential spatio-temporal fingerprints. Many more regions could be segregated during natural viewing, demonstrating that the complexity of natural stimuli leads to more differential responses in more functional modules. We demonstrate that, in a single experiment, a multitude of distinct regions can be identified across the whole brain, even within the visual cortex, including areas V1, V4 and V5. This differentiation is based entirely on the differential ATCs of different areas during natural viewing. Distinct areas can therefore be identified without any a priori hypothesis about their function or spatial location. The areas we identified corresponded anatomically across subjects, and their ATCs showed highly area-specific inter-subject correlations. Furthermore, natural conditions led to a significant de-correlation of interregional ATCs compared to rest, indicating an increase in regional specificity during natural conditions. In contrast, the correlation between ATCs of distant regions of known substantial anatomical connections increased and reflected their known anatomical connectivity pattern. We demonstrate this using the example of the language network involving Broca's and Wernicke's area and homologous areas in the two hemispheres. In conclusion, this new approach to brain mapping may not only serve to identify novel functional subdivisions, but to reveal their connectivity as well.
14
Zhuo, Degen, Wei D. Zhao, Fred A. Wright, Hee-Yung Yang, Jian-Ping Wang, Russell Sears, Troy Baer, et al. "Assembly, Annotation, and Integration of UNIGENE Clusters into the Human Genome Draft." Genome Research 11, no. 5 (April 11, 2001): 904–18. http://dx.doi.org/10.1101/gr.164501.
Full textAbstract:
The recent release of the first draft of the human genome provides an unprecedented opportunity to integrate human genes and their functions in a complete positional context. However, at least three significant technical hurdles remain: first, to assemble a complete and nonredundant human transcript index; second, to accurately place the individual transcript indices on the human genome; and third, to functionally annotate all human genes. Here, we report the extension of the UNIGENE database through the assembly of its sequence clusters into nonredundant sequence contigs. Each resulting consensus was aligned to the human genome draft. A unique location for each transcript within the human genome was determined by the integration of the restriction fingerprint, assembled genomic contig, and radiation hybrid (RH) maps. A total of 59,500 UNIGENE clusters were mapped on the basis of at least three independent criteria as compared with the 30,000 human genes/ESTs currently mapped in Genemap'99. Finally, the extension of the human transcript consensus in this study enabled a greater number of putative functional assignments than the 11,000 annotated entries in UNIGENE. This study reports a draft physical map with annotations for a majority of the human transcripts, called the Human Index of Nonredundant Transcripts (HINT). Such information can be immediately applied to the discovery of new genes and the identification of candidate genes for positional cloning.
15
Watanabe, Tomoya, DeAnna Baker Frost, Logan Mlakar, Jonathan Heywood, Willian A. da Silveira, Gary Hardiman, and Carol Feghali-Bostwick. "A Human Skin Model Recapitulates Systemic Sclerosis Dermal Fibrosis and Identifies COL22A1 as a TGFβ Early Response Gene that Mediates Fibroblast to Myofibroblast Transition." Genes 10, no. 2 (January 22, 2019): 75. http://dx.doi.org/10.3390/genes10020075.
Full textAbstract:
: Systemic sclerosis (SSc) is a complex multi-system autoimmune disease characterized by immune dysregulation, vasculopathy, and organ fibrosis. Skin fibrosis causes high morbidity and impaired quality of life in affected individuals. Animal models do not fully recapitulate the human disease. Thus, there is a critical need to identify ex vivo models for the dermal fibrosis characteristic of SSc. We identified genes regulated by the pro-fibrotic factor TGFβ in human skin maintained in organ culture. The molecular signature of human skin overlapped with that which was identified in SSc patient biopsies, suggesting that this model recapitulates the dermal fibrosis characteristic of the human disease. We further characterized the regulation and functional impact of a previously unreported gene in the setting of dermal fibrosis, COL22A1, and show that silencing COL22A1 significantly reduced TGFβ-induced ACTA2 expression. COL22A1 expression was significantly increased in dermal fibroblasts from patients with SSc. In summary, we identified the molecular fingerprint of TGFβ in human skin and demonstrated that COL22A1 is associated with the pathogenesis of fibrosis in SSc as an early response gene that may have important implications for fibroblast activation. Further, this model will provide a critical tool with direct relevance to human disease to facilitate the assessment of potential therapies for fibrosis.
16
Lee, Jinyoung, Sarah Fung, Robin Yong, Sarbin Ranjitkar, John Kaidonis, Alistair R. Evans, and Luca Fiorenza. "Tooth wear development in the Australian Aboriginal dentition from Yuendumu: A longitudinal study." PLOS ONE 16, no. 7 (July 9, 2021): e0254151. http://dx.doi.org/10.1371/journal.pone.0254151.
Full textAbstract:
The analysis of dental wear, at both the microscopic and macroscopic scale, is one of the most widely used tools in archeology and anthropology to reconstruct the diet and lifestyle of past human populations. Biomechanical studies have indicated that tooth wear helps to dissipate the mechanical load over the crown surface, thus reducing the risk of tooth fracture. To date, there are only a few studies that have examined functional tooth wear variation in modern humans. Here we propose to study masticatory efficiency through the use of the Occlusal Fingerprint Analysis method, a well-developed digital approach that allows the reconstruction of the occlusal dynamics occurring during mastication. The aim of this study is to provide the first longitudinal quantitative data of molar and premolar macrowear patterns within a functional context. We examined the mixed and permanent dentition of one Australian Aboriginal child (from ages 8 to 17) from Yuendumu, using high-resolution surface scans of dental casts including both upper and lower arches. Our results suggest that the occlusal macrowear patterns of this individual did not significantly change through time. Occlusal contact parameters such as functional area, inclination and direction remain relatively unaltered throughout childhood and adolescence, indicating little change in the masticatory function of this individual. The functional tooth wear pattern in this individual did not change longitudinally indicating the degree of masticatory efficiency has most probably remained unaltered.
17
Nie, Pengcheng, Chengyong Cai, Fangfang Qu, Lei Lin, Tao Dong, and Yong He. "Study of 2,4-D Spectral Characteristics and Its Detection in Zizania Latifolia Using Terahertz Time-Domain Spectroscopy." Applied Sciences 9, no. 11 (May 31, 2019): 2248. http://dx.doi.org/10.3390/app9112248.
Full textAbstract:
2,4-Dichlorophenoxyacetic acid (2,4-D) is a common plant growth regulator, which can remain in food and, with long-term consumption, threaten human health. Therefore, it is necessary to propose an effective detection method. Terahertz time-domain spectroscopy technique (THz-TDS) has good advantages in the quantitative and qualitative analysis of most biomolecules due to its rich fingerprint characteristics. In this paper, density functional theory (DFT) was applied to geometry optimization and frequency vibration calculation of 2,4-D, and THz-TDS was used to quantitatively detect 2,4-D in Zizania latifolia. The results showed that there were three characteristic absorption peaks of 2,4-D at 1.36, 1.60, and 2.38 THz, respectively, and the theoretical spectra were in good consistency with experimental spectra, with slight discrepancies. Additionally, the absorption peak at 1.36 THz had the best absorption characteristics and was chosen as the main peak for 2,4-D quantitative analysis. It was demonstrated that the limits of detection (LOD) of 2,4-D in Zizania latifolia were found to be as low as 5%, the absorbance intensity at 1.36 THz showed a good linear relationship (R2 = 0.9854) with 2,4-D concentration from 5% to 30%, and the recovery was 93.29%–98.75%. Overall, this work enriched the fingerprint database of pesticide molecules on the basis of terahertz spectroscopy and could provide a technical support for the detection of 2,4-D in food by terahertz spectroscopy.
18
Mori, Miki, Zhongzhong Chen, Aaron Boudreau, Laura van't Veer, and Jean-Philippe Coppe. "Kinase-sensing system to identify the oncogenic phospho-fingerprint of breast cancer." Journal of Clinical Oncology 31, no. 26_suppl (September 10, 2013): 23. http://dx.doi.org/10.1200/jco.2013.31.26_suppl.23.
Full textAbstract:
23 Background: Kinases and their substrates harness myriad critical molecular pathways. A new highly valuable assay would be one detecting the true active state of phospho-signaling networks. To address this technological and knowledge gap, we developed a semi-high throughput sensing system that monitors the catalytic activity of kinases using peptides as phosphorylation targets/probes. We used this assay to evaluate the presence of dysfunctional kinases in biological extracts and identify oncogenic phospho-signatures prevalent in breast cancer. Methods: We developed a human kinase protein and peptide repertoire computationally curated from thousands of publications. Out of the 2,702 validated peptide targets and 6,173 kinase-substrate nodes we compiled, we chose a subset of 151 biological peptides predicted to specifically report on tyrosine / serine / threonine kinases, including EGFR, ERK, AKT, SRC, ABL. Along with 91 control peptides, we tested a total of 242 peptides in a luminescence ATP-consumption assay for their ability to report on the kinases’ activity. The assay was further validated using an isogenic culture model of basal like breast cancer (HMT-3522 S1 and T4-2), and cell lines harboring various oncogenic alterations (MDA-MB-231, MCF7, T47D, AU565, ZR75.1, SKBR3). Results: The differential phosphorylation activity of recombinant kinase enzymes was successfully detected in time course, dilution and inhibitor experiments. The increased presence of (hyper-) activated SRC, EGFR, AKT or ABL kinases observed by western blots in subsets of breast cancer cells, was selectively, repeatedly and specifically detected using the peptide-based kinase assay. Significantly altered peptide-phosphorylation patterns were successfully integrated into signatures using gene expression microarray-like analysis, revealing the breast cancer-associated map of phosphorylation circuits. Conclusions: This assay is suitable to comprehensively capture the activity of kinase signaling networks. We will now use this functional proteomic assay to identify the active, oncogenic kinome of breast cancer, with the objective to improve clinical guidance and individualize breast cancer patients’ therapy.
19
Schall, Sonja, Stefan J. Kiebel, Burkhard Maess, and Katharina von Kriegstein. "Voice Identity Recognition: Functional Division of the Right STS and Its Behavioral Relevance." Journal of Cognitive Neuroscience 27, no. 2 (February 2015): 280–91. http://dx.doi.org/10.1162/jocn_a_00707.
Full textAbstract:
The human voice is the primary carrier of speech but also a fingerprint for person identity. Previous neuroimaging studies have revealed that speech and identity recognition is accomplished by partially different neural pathways, despite the perceptual unity of the vocal sound. Importantly, the right STS has been implicated in voice processing, with different contributions of its posterior and anterior parts. However, the time point at which vocal and speech processing diverge is currently unknown. Also, the exact role of the right STS during voice processing is so far unclear because its behavioral relevance has not yet been established. Here, we used the high temporal resolution of magnetoencephalography and a speech task control to pinpoint transient behavioral correlates: we found, at 200 msec after stimulus onset, that activity in right anterior STS predicted behavioral voice recognition performance. At the same time point, the posterior right STS showed increased activity during voice identity recognition in contrast to speech recognition whereas the left mid STS showed the reverse pattern. In contrast to the highly speech-sensitive left STS, the current results highlight the right STS as a key area for voice identity recognition and show that its anatomical-functional division emerges around 200 msec after stimulus onset. We suggest that this time point marks the speech-independent processing of vocal sounds in the posterior STS and their successful mapping to vocal identities in the anterior STS.
20
Camponeschi, Francesca, Angelo Gallo, Mario Piccioli, and Lucia Banci. "The long-standing relationship between paramagnetic NMR and iron–sulfur proteins: the mitoNEET example. An old method for new stories or the other way around?" Magnetic Resonance 2, no. 1 (April 26, 2021): 203–21. http://dx.doi.org/10.5194/mr-2-203-2021.
Full textAbstract:
Abstract. Paramagnetic NMR spectroscopy and iron–sulfur (Fe–S) proteins have maintained a synergic relationship for decades. Indeed, the hyperfine shifts with their temperature dependencies and the relaxation rates of nuclei of cluster-bound residues have been extensively used as a fingerprint of the type and of the oxidation state of the Fe–S cluster within the protein frame. The identification of NMR signals from residues surrounding the metal cofactor is crucial for understanding the structure–function relationship in Fe–S proteins, but it is generally impaired in standard NMR experiments by paramagnetic relaxation enhancement due to the presence of the paramagnetic cluster(s). On the other hand, the availability of systems of different sizes and stabilities has, over the years, stimulated NMR spectroscopists to exploit iron–sulfur proteins as paradigmatic cases to develop experiments, models, and protocols. Here, the cluster-binding properties of human mitoNEET have been investigated by 1D and 2D 1H diamagnetic and paramagnetic NMR, in its oxidized and reduced states. The NMR spectra of both oxidation states of mitoNEET appeared to be significantly different from those reported for previously investigated [Fe2S2]2+/+ proteins. The protocol we have developed in this work conjugates spectroscopic information arising from “classical” paramagnetic NMR with an extended mapping of the signals of residues around the cluster which can be taken, even before the sequence-specific assignment is accomplished, as a fingerprint of the protein region constituting the functional site of the protein. We show how the combined use of 1D NOE experiments, 13C direct-detected experiments, and double- and triple-resonance experiments tailored using R1- and/or R2-based filters significantly reduces the “blind” sphere of the protein around the paramagnetic cluster. This approach provided a detailed description of the unique electronic properties of mitoNEET, which are responsible for its biological function. Indeed, the NMR properties suggested that the specific electronic structure of the cluster possibly drives the functional properties of different [Fe2S2] proteins.
21
Altieri, Fabio, Francesco Cairone, Flavia Giamogante, Simone Carradori, Marcello Locatelli, Silvia Chichiarelli, and Stefania Cesa. "Influence of Ellagitannins Extracted by Pomegranate Fruit on Disulfide Isomerase PDIA3 Activity." Nutrients 11, no. 1 (January 17, 2019): 186. http://dx.doi.org/10.3390/nu11010186.
Full textAbstract:
Pomegranate fruit is a functional food of high interest for human health due to its wide range of phytochemicals with antioxidant properties are implicated in the prevention of inflammation and cancer. Ellagitannins, such as punicalagin and ellagic acid, play a role as anti-atherogenic and neuroprotective molecules in the complex fighting against the degenerative diseases. The aim of this work was to evaluate the composition in punicalagins and ellagic acid of differently obtained extracts from whole fruit, peels and juices, prepared by squeezing or by centrifugation, of pomegranate belonging to different cultivars. Moreover, a wider phenolic fingerprint was also determined. The bioactivity of the extracts was tested on the redox activity of PDIA3 disulfide isomerase, an enzyme involved in the regulation of several cellular functions and associated with different diseases such as cancer, prion disorders, Alzheimer’s and Parkinson’s diseases. The results demonstrate that the different ratios between punicalagin and ellagic acid modulate the enzyme activity and other ellagitannins could interfere with this activity.
22
Mastrangelo, Annalaura, María I. Panadero, Laura M. Pérez, Beatriz G. Gálvez, Antonia García, Coral Barbas, and Francisco J. Rupérez. "New insight on obesity and adipose-derived stem cells using comprehensive metabolomics." Biochemical Journal 473, no. 14 (July 12, 2016): 2187–203. http://dx.doi.org/10.1042/bcj20160241.
Full textAbstract:
Obesity affects the functional capability of adipose-derived stem cells (ASCs) and their effective use in regenerative medicine through mechanisms that are still poorly understood. In the present study we used a multiplatform [LC/MS, GC/MS and capillary electrophoresis/MS (CE/MS)], metabolomics, untargeted approach to investigate the metabolic alteration underlying the inequalities observed in obesity-derived ASCs. The metabolic fingerprint (metabolites within the cells) and footprint (metabolites secreted in the culture medium), from obesity- and non-obesity-derived ASCs of humans or mice, were characterized to provide valuable information. Metabolites associated with glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway and the polyol pathway were increased in the footprint of obesity-derived human ASCs, indicating alterations in carbohydrate metabolism, whereas, from the murine model, deep differences in lipid and amino acid catabolism were highlighted. Therefore, new insights on the ASCs’ metabolome were provided that enhance our understanding of the processes underlying ASCs’ stemness capacity and its relationship with obesity, in different cell models.
23
Vanhoutte, Tom, Vicky De Preter, Evie De Brandt, Kristin Verbeke, Jean Swings, and Geert Huys. "Molecular Monitoring of the Fecal Microbiota of Healthy Human Subjects during Administration of Lactulose and Saccharomyces boulardii." Applied and Environmental Microbiology 72, no. 9 (September 2006): 5990–97. http://dx.doi.org/10.1128/aem.00233-06.
Full textAbstract:
ABSTRACT Diet is a major factor in maintaining a healthy human gastrointestinal tract, and this has triggered the development of functional foods containing a probiotic and/or prebiotic component intended to improve the host's health via modulation of the intestinal microbiota. In this study, a long-term placebo-controlled crossover feeding study in which each subject received several treatments was performed to monitor the effect of a prebiotic substrate (i.e., lactulose), a probiotic organism (i.e., Saccharomyces boulardii), and their synbiotic combination on the fecal microbiota of three groups of 10 healthy human subjects differing in prebiotic dose and/or intake of placebo versus synbiotic. For this purpose, denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA gene amplicons was used to detect possible changes in the overall bacterial composition using the universal V3 primer and to detect possible changes at the subpopulation level using group-specific primers targeting the Bacteroides fragilis subgroup, the genus Bifidobacterium, the Clostridium lituseburense group (cluster XI), and the Clostridium coccoides-Eubacterium rectale group (cluster XIVa). Although these populations remained fairly stable based on DGGE profiling, one pronounced change was observed in the universal fingerprint profiles after lactulose ingestion. Band position analysis and band sequencing revealed that a band appearing or intensifying following lactulose administration could be assigned to the species Bifidobacterium adolescentis. Subsequent analysis with real-time PCR (RT-PCR) indicated a statistically significant increase (P < 0.05) in total bifidobacteria in one of the three subject groups after lactulose administration, whereas a similar but nonsignificant trend was observed in the other two groups. Combined RT-PCR results from two subject groups indicated a borderline significant increase (P = 0.074) of B. adolescentis following lactulose intake. The probiotic yeast S. boulardii did not display any detectable universal changes in the DGGE profiles, nor did it influence the bifidobacterial levels. This study highlighted the capacity of an integrated approach consisting of DGGE analysis and RT-PCR to monitor and quantify pronounced changes in the fecal microbiota of healthy subjects upon functional food administration.
24
Su, Shan, Cristina Di Poto, Rabindra Roy, Xuefeng Liu, Wanxing Cui, Alexander Kroemer, and Habtom W. Ressom. "Long-term culture and characterization of patient-derived primary hepatocytes using conditional reprogramming." Experimental Biology and Medicine 244, no. 11 (June 11, 2019): 857–64. http://dx.doi.org/10.1177/1535370219855398.
Full textAbstract:
Cultivation of primary human hepatocytes (PHHs) often faces obstacles including failure of long-term in vitro culture, weak proliferation ability, rapid loss of liver-specific function and morphology, and tendency of fibrosis. Previous research focused on immortalization methods, such as telomerase and viral, to culture immortalized primary human hepatocytes, which may lose some of the normal properties. However, non-immortalized PHHs often fail to maintain long-term viability and functionality. These highlight the urgent need for developing new culture strategy for PHHs. In the present study, we isolated PHHs from fresh human liver tissues representing different liver diseases and age groups. We used conditional reprogramming, without permanent immortalization, for long-term in vitro primary human hepatocytes cultivation and characterization. For functional characterization, we assessed CYP3A4, 1A1 and 2C9 activities and measured the mRNA expression of albumin, s100a4, krt8, krt18, cyp1a1, cyp3a4, cyp2b6, cyp2c8, cyp2c9, and cyp2d6. Additionally, we compared the DNA fingerprint of the cells against their original liver tissues using short tandem repeat (STR) analysis. We found that PHHs-derived from young patients can survive for more than three months, while the lifespan of primary human hepatocytes derived from adult patients ranges from two to three months, which is longer than most commercial primary hepatocytes. Importantly, the cells at early passages retain strong CYP3A4, 1A1 and 2C9 activities and the DNA fingerprints are identical with their original tissues. Through conditional programming, we achieved, for the first time, a high level of success rate in the long-term in vitro cultivation of primary human hepatocytes-derived patients representing diverse liver disease. Moreover, the conditional programming cell culture technology reported in this paper requires neither co-culture with additive cells, nor complex and expensive components, such as collagen sandwich or spheroid culture. We thus believe that the patient-derived PHHs cultivation using conditional programming may provide a viable and valuable cell model to study liver disease-related mechanisms. Impact statement Commercially available primary human hepatocytes rapidly lose their proliferative ability and liver-specific functions over a few cultivation days. The demand for pharmaceutical toxicity screening and liver disease research requires the development of long-term primary hepatocyte culture methods. This manuscript addresses this challenge by introducing for the first time successful long-term in vitro cultivation of primary human hepatocytes from a range of liver transplantation patients using conditional reprogramming technique. The beauty of this technique is that it is not a permanent immortalization and does not require co-culture with additive cells. The primary human hepatocytes retain proliferative capacity, genetic stability, and hepatocyte-specific functions at early passages. In view of these, we believe that scientists and researchers will benefit from using these highly valuable cell models to study diverse liver diseases.
25
Imran, Ali, Brandon S. Moyer, Ashley J. Canning, Dan Kalina, Thomas M. Duncan, Kelsey J. Moody, Aaron J. Wolfe, Michael S. Cosgrove, and Liviu Movileanu. "Kinetics of the multitasking high-affinity Win binding site of WDR5 in restricted and unrestricted conditions." Biochemical Journal 478, no. 11 (June 11, 2021): 2145–61. http://dx.doi.org/10.1042/bcj20210253.
Full textAbstract:
Recent advances in quantitative proteomics show that WD40 proteins play a pivotal role in numerous cellular networks. Yet, they have been fairly unexplored and their physical associations with other proteins are ambiguous. A quantitative understanding of these interactions has wide-ranging significance. WD40 repeat protein 5 (WDR5) interacts with all members of human SET1/MLL methyltransferases, which regulate methylation of the histone 3 lysine 4 (H3K4). Here, using real-time binding measurements in a high-throughput setting, we identified the kinetic fingerprint of transient associations between WDR5 and 14-residue WDR5 interaction (Win) motif peptides of each SET1 protein (SET1Win). Our results reveal that the high-affinity WDR5-SET1Win interactions feature slow association kinetics. This finding is likely due to the requirement of SET1Win to insert into the narrow WDR5 cavity, also named the Win binding site. Furthermore, our explorations indicate fairly slow dissociation kinetics. This conclusion is in accordance with the primary role of WDR5 in maintaining the functional integrity of a large multisubunit complex, which regulates the histone methylation. Because the Win binding site is considered a key therapeutic target, the immediate outcomes of this study could form the basis for accelerated developments in medical biotechnology.
26
Ferrante, Claudio, Gokhan Zengin, Luigi Menghini, Alina Diuzheva, József Jekő, Zoltán Cziáky, Lucia Recinella, et al. "Qualitative Fingerprint Analysis and Multidirectional Assessment of Different Crude Extracts and Essential Oil from Wild Artemisia santonicum L." Processes 7, no. 8 (August 7, 2019): 522. http://dx.doi.org/10.3390/pr7080522.
Full textAbstract:
Artemisia species are used as folk medicines in several countries. This work was aimed to shed more light on the effect of methanol, water, ethyl acetate extracts, and essential oil (EO) of A. santonicum on selected enzymes (cholinesterase, tyrosinase α-amylase, and α-glucosidase) as well of their antioxidant and pharmacological effects. The chemical profile of the essential oil was determined using gas chromatography coupled to mass spectrometry (GC-MS) analysis, while the extracts were chemically characterized by high performance liquid chromatography coupled to mass spectrometry (HPLC-MS). Forty-nine constituents were identified and camphor (36.6%), 1,8-cineole (10.2%), α-thujone (10.1%), borneol (4.5%), and β-thujone (3.6%) were the major components. Overall, 45, 74, and 67 components were identified from the ethyl acetate, methanol, and water extracts, respectively. The EO and extracts showed significant antioxidant properties, in a cell-free model; particularly, methanol and water extracts revealed promising sources of antioxidant compounds. Additionally, we evaluated protective effects of EO and extracts in isolated rat colon tissue challenged with lipopolysaccharide (LPS), as an ex vivo model of colon inflammation, and human colon cancer HCT116 cell line. Particularly, we observed that, among all tested samples, A. santonicum ethyl acetate displayed the best pharmacological profile, being able to blunt LPS-induced levels of all tested biomarkers of inflammation and oxidative stress, including colon nitrites, lactate dehydrogenase, prostaglandin E2, and serotonin. Additionally, this extract was also able to reduce HCT116 cell viability, thus suggesting potential antiproliferative effects against colon cancer cells. Based on our results, A. santonicum has great potential for developing novel functional agents including pharmaceuticals, cosmeceuticals, and nutraceuticals.
27
Quiros-Gonzalez, Isabel, Michal R. Tomaszewski, Monika A. Golinska, Emma Brown, Laura Ansel-Bollepalli, Lina Hacker, Dominique-Laurent Couturier, Rosa M. Sainz, and Sarah E. Bohndiek. "Abstract LB057: Bevacizumab leaves a photoacoustic fingerprint in breast cancer mouse models." Cancer Research 82, no. 12_Supplement (June 15, 2022): LB057. http://dx.doi.org/10.1158/1538-7445.am2022-lb057.
Full textAbstract:
Abstract Background: Photoacoustic tomography (PAT) provides a direct readout of tumor haemoglobin (Hb) concentration and oxygenation. This readout could be used to provide an early indication of response to anti-angiogenic drugs, thus optimizing the management of these therapies. Experimental Procedures: Two cohorts of nude Balb/c were inoculated with either estrogen-dependent MCF-7 (n=7) or estrogen-independent MDA-MB-231 (n=19) cells. Mice were randomly split into Control (Ctrl) and Bevacizumab (Bev,10 mg/Kg, IP, weekly) groups. PAT was performed weekly, starting just before enrolment. Oxy- and deoxy-Hb were quantified in the tumour and reference areas. Total Hb (THb) and O2 saturation (SO2) were calculated. Blood samples and tissues were collected after imaging. Hypoxia (Hypoxyprobe and CA-IX) and vascular density/maturity (CD31 and ASMA) were analyzed by immunohistochemistry. Circulating levels of human and mouse vascular endothelial growth factor (hVEGF and mVEGF) and Hb were measured. Summary of New Data: Reflecting clinical observations, the MCF-7 Bev group and most of the mice from the MDA-MB-231 Bev group (8/11) showed no improvement in survival with Bev treatment. All resistant tumours (Bev MCF-7 and Bev MDA-MB-231 non-responders (Bev-NR)) showed an increase in hVEGF production (Ctrl vs Bev; 73.0513.06 vs. 497103.9 for MCF-7; 247.984.81 vs. 330.4 85.97 for Bev NR). MDA-MB-231 responders (Bev-R) showed a significant decrease in hVEGF (247.984.81 vs. 80.53 26.13). These results indicate that VEGF was only successfully sequestered in a small subset of animals (3/11) and that VEGF overload might be a resistance mechanism. At the final time point, PAT showed no difference between Ctrl and Bev-NR in THb for either group (THbMDA-MB-231 7.2±1.3 vs. 5.5±1.2). THb was found significantly increased in the Bev-R group by PAT (13.9±3.3 p-valuevs.Crtl=0.0339; p-valuevs.Bev=0.0072) and biochemical measurements. SO2 showed a slight but significant decrease between Ctrl and Bev-NR (0.58±0.03 vs. 0.48±0.01). A dramatic decrease was seen in the Bev-R group (0.31±0.07) and significantly different from Ctrl and Bev-NR. SO2 was sensitive to early changes, SO2 values increased in Ctrl and Bev-NR 48h after enrolment (p-values paired t-test pCtrl= 0.0134; pNR=0.0268) while Bev-R shows a trend (p=0.0649). Analysis of SO2MSOT over time shows a significant (p<0.0001) change in slope at 3 weeks after enrolment in the Bev-R group compared to either of the Ctrl or Bev-NR groups. Our results indicate that PAT SO2 can differentiate responders at very early stages of the treatment. Histologically, we observed fewer blood vessels but better structured in Bev-NR than in Bev-R, which showed higher vascular density and also higher levels of hypoxia makers. Statement of the Conclusions: Our results postulates PAT as a low-cost, label-free and non-invasive candidate to monitor response to Bevacizumab over time. Our results also indicate that tumours with functional vasculature may be resistant to Bevacizumab treatment. Citation Format: Isabel Quiros-Gonzalez, Michal R. Tomaszewski, Monika A. Golinska, Emma Brown, Laura Ansel-Bollepalli, Lina Hacker, Dominique-Laurent Couturier, Rosa M. Sainz, Sarah E. Bohndiek. Bevacizumab leaves a photoacoustic fingerprint in breast cancer mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB057.
28
Bertrand, Carol A., Ruilin Zhang, Joseph M. Pilewski, and Raymond A. Frizzell. "SLC26A9 is a constitutively active, CFTR-regulated anion conductance in human bronchial epithelia." Journal of General Physiology 133, no. 4 (March 16, 2009): 421–38. http://dx.doi.org/10.1085/jgp.200810097.
Full textAbstract:
Human bronchial epithelial (HBE) cells exhibit constitutive anion secretion that is absent in cells from cystic fibrosis (CF) patients. The identity of this conductance is unknown, but SLC26A9, a member of the SLC26 family of CF transmembrane conductance regulator (CFTR)-interacting transporters, is found in the human airway and exhibits chloride channel behavior. We sought differences in the properties of SLC26A9 and CFTR expressed in HEK 293 (HEK) cells as a fingerprint to identify HBE apical anion conductances. HEK cells expressing SLC26A9 displayed a constitutive chloride current that was inhibited by the CFTR blocker GlyH-101 (71 ± 4%, 50 µM) and exhibited a near-linear current–voltage (I-V) relation during block, while GlyH-101–inhibited wild-type (wt)CFTR exhibited a strong inward-rectified (IR) I-V relation. We tested polarized HBE cells endogenously expressing either wt or ΔF508-CFTR for similar activity. After electrical isolation of the apical membrane using basolateral α-toxin permeabilization, wtCFTR monolayers displayed constitutive chloride currents that were inhibited by GlyH-101 (68 ± 6%) while maintaining a near-linear I-V relation. In the absence of blocker, the addition of forskolin stimulated a current increase having a linear I-V; GlyH-101 blocked 69 ± 7% of the current and shifted the I-V relation IR, consistent with CFTR activation. HEK cells coexpressing SLC26A9 and wtCFTR displayed similar properties, as well as forskolin-stimulated currents that exceeded the sum of those in cells separately expressing SLC26A9 or wtCFTR, and an I-V relation during GlyH-101 inhibition that was moderately IR, indicating that SLC26A9 contributed to the stimulated current. HBE cells from CF patients expressed SLC26A9 mRNA, but no constitutive chloride currents. HEK cells coexpressing SLC26A9 with ΔF508-CFTR also failed to exhibit SLC26A9 current. We conclude that SLC26A9 functions as an anion conductance in the apical membranes of HBE cells, it contributes to transepithelial chloride currents under basal and cAMP/protein kinase A–stimulated conditions, and its activity in HBE cells requires functional CFTR.
29
Casal-Beiroa, Paula, Vanesa Balboa-Barreiro, Natividad Oreiro, Sonia Pértega-Díaz, Francisco J. Blanco, and Joana Magalhães. "Optical Biomarkers for the Diagnosis of Osteoarthritis through Raman Spectroscopy: Radiological and Biochemical Validation Using Ex Vivo Human Cartilage Samples." Diagnostics 11, no. 3 (March 18, 2021): 546. http://dx.doi.org/10.3390/diagnostics11030546.
Full textAbstract:
Osteoarthritis (OA) is the most common rheumatic disease, characterized by progressive articular cartilage degradation. Raman spectroscopy (RS) has been recently proposed as a label-free tool to detect molecular changes in musculoskeletal tissues. We used cartilage samples derived from human femoral heads to perform an ex vivo study of different Raman signals and ratios, related to major and minor molecular components of articular cartilage, hereby proposed as candidate optical biomarkers for OA. Validation was performed against the radiological Kellgren–Lawrence (K-L) grading system, as a gold standard, and cross-validated against sulfated glycosaminoglycans (sGAGs) and total collagens (Hyp) biochemical contents. Our results showed a significant decrease in sGAGs (SGAGs, A1063 cm−1/A1004 cm−1) and proteoglycans (PGs, A1375 cm−1/A1004 cm−1) and a significant increase in collagen disorganization (ColD/F, A1245 cm−1/A1270 cm−1), with OA severity. These were correlated with sGAGs or Hyp contents, respectively. Moreover, the SGAGs/HA ratio (A1063 cm−1/A960 cm−1), representing a functional matrix, rich in proteoglycans, to a mineralized matrix-hydroxyapatite (HA), was significantly lower in OA cartilage (K-L I vs. III–IV, p < 0.05), whilst the mineralized to collagenous matrix ratio (HA/Col, A960 cm−1/A920 cm−1) increased, being correlated with K-L. OA samples showed signs of tissue mineralization, supported by the presence of calcium crystals-related signals, such as phosphate, carbonate, and calcium pyrophosphate dihydrate (MGP, A960 cm−1/A1004 cm−1, MGC, A1070 cm−1/A1004 cm−1 and A1050 cm−1/A1004 cm−1). Finally, we observed an increase in lipids ratio (IL, A1450 cm−1/A1670 cm−1) with OA severity. As a conclusion, we have described the molecular fingerprint of hip cartilage, validating a panel of optical biomarkers and the potential of RS as a complementary diagnostic tool for OA.
30
Sacchini, Simona, Pedro Herráez, Manuel Arbelo, Antonio Espinosa de los Monteros, Eva Sierra, Miguel Rivero, Cristiano Bombardi, and Antonio Fernández. "Methodology and Neuromarkers for Cetaceans’ Brains." Veterinary Sciences 9, no. 2 (January 21, 2022): 38. http://dx.doi.org/10.3390/vetsci9020038.
Full textAbstract:
Cetacean brain sampling may be an arduous task due to the difficulty of collecting and histologically preparing such rare and large specimens. Thus, one of the main challenges of working with cetaceans’ brains is to establish a valid methodology for an optimal manipulation and fixation of the brain tissue, which allows the samples to be viable for neuroanatomical and neuropathological studies. With this in view, we validated a methodology in order to preserve the quality of such large brains (neuroanatomy/neuropathology) and at the same time to obtain fresh brain samples for toxicological, virological, and microbiological analysis (neuropathology). A fixation protocol adapted to brains, of equal or even three times the size of human brains, was studied and tested. Finally, we investigated the usefulness of a panel of 20 antibodies (neuromarkers) associated with the normal structure and function of the brain, pathogens, age-related, and/or functional variations. The sampling protocol and some of the 20 neuromarkers have been thought to explore neurodegenerative diseases in these long-lived animals. To conclude, many of the typical measures used to evaluate neuropathological changes do not tell us if meaningful cellular changes have occurred. Having a wide panel of antibodies and histochemical techniques available allows for delving into the specific behavior of the neuronal population of the brain nuclei and to get a “fingerprint” of their real status.
31
Chen, Qian, Shengyao Jia, Jianyuan Qin, Yong Du, and Zongshan Zhao. "A Feasible Approach to Detect Pesticides in Food Samples Using THz-FDS and Chemometrics." Journal of Spectroscopy 2020 (May 31, 2020): 1–10. http://dx.doi.org/10.1155/2020/3859076.
Full textAbstract:
The use of pesticides will have an impact on food, organisms, and environment. Specifically, pesticide residues in food will damage human health. Because of its high permeability, low energy, high spectral resolution, and fingerprint characteristics, terahertz frequency-domain spectroscopy has been introduced into the determination of pesticides (imidacloprid, acetamiprid, and triadimefon) residues in food samples (glutinous rice flour, wheat flour, and corn flour) in our present study. These three pesticides exhibit their own absorption peaks in the region of 0.4–1.7 THz. For understanding the origins of these peaks, the experimental data are interpreted by using density functional theory calculations at the level of B3LYP/6-31G (d). It is found that these absorption peaks come from the intramolecular and intermolecular interactions. The absorption peaks of pesticides are still detectable in a mixture of pesticides and food samples when they reach a certain concentration. The results from chemometrics analysis show that quantitative detection of pesticides in food samples is feasible. The partial least squares regression models have high correlation coefficient (>0.99), low root-mean-square error of calibration (<1.5%), low root-mean-square error of cross-validation (<2.4%), and low root-mean-square error of prediction (<2.3%), indicating good quality of prediction for pesticides concentration. Our results prove that the terahertz frequency-domain spectrum combined with chemometrics can be used for the detection of pesticides in food samples.
32
Jyotsana, Nidhi, Amit Sharma, Anuhar Chaturvedi, Colin Walsh, Anitha Thomas, Michaela Scherr, Matthias Eder, et al. "Effective Treatment of Human CML By RNAi In Vivo in a Xenotransplantation Mouse Model." Blood 126, no. 23 (December 3, 2015): 1261. http://dx.doi.org/10.1182/blood.v126.23.1261.1261.
Full textAbstract:
Abstract Background: Considering the heterogeneity of leukemic cells in patients, current treatment regimens of chemotherapy and bone marrow transplantation lack specificity and are associated with frequent relapses and severe adverse effects. Hence, there is a need to develop novel therapeutics that can target the disease by its molecular fingerprint with minimal side effects.Despite the wide potential of RNA interference (RNAi) for translational therapeutics, systemic application of siRNA is hampered by rapid renal clearance, degradation by serum nucleases or associated immune responses. Lipid nanoparticles (LNPs) containing ionizable cationic lipids, when mixed with siRNA, embody the most advanced delivery platform for systemic administration of siRNA based therapeutics. Here, we established and employed the BCR-ABL dependent K562-CML xenotransplantation model as a proof of principle to validate LNP mediated siRNA functional delivery in vivo. Methods and Results: A microfluidic mixing technology was used to obtain reproducible ionizable cationic LNPs loaded with anti-BCR-ABL or CTRL siRNA. To determine the delivery efficiency of LNP-siRNA formulations, human leukemic K562 cells were incubated with siRNA-containing LNPs at various concentrations. Almost 100% of cells had taken up siRNA containing LNPs even at the lowest concentration of 0.0625µg/ml with stable uptake kinetics. We also observed near 100% uptake of LNP-siRNA in hard to transfect primary patient cells (CML, AML, ALL and MDS). Looking at the on-target functional efficacy of LNP-siRNA formulations, we observed a time and dose dependent increase in apoptosis (annexin V assay) and decrease in cell viability (alamar blue assay) of K562 cells treated with anti-BCR-ABL siRNA but not CTRL siRNA. A robust knockdown in BCR-ABL mRNA levels (65-90%) at 72 hours and protein at 96 hours was observed which confirmed that cell death was an on-target effect. Colony-forming potential of primary human CD34+ CML cells was significantly reduced when treated with anti-BCR-ABL siRNA compared to CTRL siRNA and to CD34+ cells from healthy donors. To translate our findings in vivo, we evaluated the safety profile, delivery potential and functional efficacy of LNP-siRNA in mice. A total dose of 15mg/kg (3 injections of 5mg/kg at day 0, 1 and 2) in healthy NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice resulted in 100% LNP positive cells in peripheral blood up to day 10. The formulations were highly tolerable in vivo with no significant differences in body weight and complete blood counts between treated and control mice. Moreover, serum analysis showed no significant toxicity in mice following LNP-siRNA treatment. With a focus on hematopoietic tissues following systemic administration, NSG mice received transplants of human K562 cells (stably expressing GFP and luciferase) intrafemorally and were injected intravenously for 3 consecutive injections of LNP-siRNA (1 or 5mg/kg body weight) at 8 hours interval. Interestingly, almost 100% LNP uptake was observed in xenograft leukemic cells in bone marrow at 48 hours at both doses. The leukemic burden of luciferase expressing K562 cells in mice was quantified using in vivo imaging before and during treatment. Treatment with anti-BCR-ABL siRNA for 10 days (n=7) resulted in a 0.5 fold decrease, whereas CTRL siRNA (n=7) resulted in a net 5-fold increase of luciferase signal, thus proving the efficacy of our approach in vivo. Conclusion: We show a highly efficient and non-toxic delivery in vitro and in vivo with nearly 100% uptake of LNP-siRNA formulations in bone marrow of leukemic mice. By inhibiting BCR-ABL we show a reduction of leukemic burden in our xenotransplant model, while leukemic cells expanded in CTRL siRNA treated mice. Our study provides a proof-of-principle that the combined use of lipid nanoparticles and RNAi technology can be used to target leukemia cells in vivo with promising therapeutic implications. Disclosures Walsh: Precision Nanosystems Inc.: Employment. Thomas:Precision Nanosystems Inc.: Employment. Ramsay:Precision Nanosystems Inc.: Employment. Heuser:Karyopharm: Research Funding.
33
Freamat, Mihael, Hiroshi Kawauchi, Masumi Nozaki, and Stacia A. Sower. "Identification and cloning of a glycoprotein hormone receptor from sea lamprey, Petromyzon marinus." Journal of Molecular Endocrinology 37, no. 1 (August 2006): 135–46. http://dx.doi.org/10.1677/jme.1.02064.
Full textAbstract:
A full-length transcript encoding a functional lamprey glycoprotein hormone receptor I (lGpH-R I, GenBank AY750688) was cloned from the testes of the sea lamprey, Petromyzon marinus, using the GpH-R protein fingerprint GLYCHORMONER from the PRINTS database. The present study is the first to identify a GpH-R transcript in an agnathan, which is one of the only two representatives of the oldest lineage of vertebrates. The 719-amino acid full-length cDNA encoding lGpH-R I is highly similar and is likely a homolog of the vertebrate GpH-Rs (including LH, FSH, and TSH receptors). The key motifs, sequence comparisons, and characteristics of the identified GpH-R reveal a mosaic of features common to all other classes of GpH-Rs in vertebrates. The lGpH-R I was shown to activate the cAMP signaling system using human chorionic gonadotropin in transiently transfected COS-7 cells. The highest expression of the receptor transcript was demonstrated in the testes using reverse transcriptase-PCR. Lower levels of the receptor transcript were also detected in brain, heart, intestine, kidney, liver, muscle, and thyroid. The high expression of lGpH-R I in the testis and the high similarity with gnathostome gonadotropin hormone receptors suggest that lGpH-R I functions as a receptor for lamprey gonadotropin hormones. We hypothesize from these data that there is lower specificity of gonadotropin and its receptor in agnathans and that during co-evolution of the ligand and its receptor in gnathostomes, there were increased specificities of interactions between each GpH (TSH, LH, and FSH) and its receptor.
34
de Haan, Willeke, Cristina Øie, Mohammed Benkheil, Wouter Dheedene, Stefan Vinckier, Giulia Coppiello, Xabier López Aranguren, et al. "Unraveling the transcriptional determinants of liver sinusoidal endothelial cell specialization." American Journal of Physiology-Gastrointestinal and Liver Physiology 318, no. 4 (April 1, 2020): G803—G815. http://dx.doi.org/10.1152/ajpgi.00215.2019.
Full textAbstract:
Liver sinusoidal endothelial cells (LSECs) are the first liver cells to encounter waste macromolecules, pathogens, and toxins in blood. LSECs are highly specialized to mediate the clearance of these substances via endocytic scavenger receptors and are equipped with fenestrae that mediate the passage of macromolecules toward hepatocytes. Although some transcription factors (TFs) are known to play a role in LSEC specialization, information about the specialized LSEC signature and its transcriptional determinants remains incomplete. Based on a comparison of liver, heart, and brain endothelial cells (ECs), we established a 30-gene LSEC signature comprising both established and newly identified markers, including 7 genes encoding TFs. To evaluate the LSEC TF regulatory network, we artificially increased the expression of the 7 LSEC-specific TFs in human umbilical vein ECs. Although Zinc finger E-box-binding protein 2, homeobox B5, Cut-like homolog 2, and transcription factor EC (TCFEC) had limited contributions, musculoaponeurotic fibrosarcoma (C-MAF), GATA binding protein 4 (GATA4), and MEIS homeobox 2 (MEIS2) emerged as stronger inducers of LSEC marker expression. Furthermore, a combination of C-MAF, GATA4, and MEIS2 showed a synergistic effect on the increase of LSEC signature genes, including liver/lymph node-specific ICAM-3 grabbing non-integrin ( L-SIGN) (or C-type lectin domain family member M ( CLEC4M)), mannose receptor C-Type 1 ( MRC1), legumain ( LGMN), G protein-coupled receptor 182 ( GPR182), Plexin C1 ( PLXNC1), and solute carrier organic anion transporter family member 2A1 ( SLCO2A1). Accordingly, L-SIGN, MRC1, pro-LGMN, GPR182, PLXNC1, and SLCO2A1 protein levels were elevated by this combined overexpression. Although receptor-mediated endocytosis was not significantly induced by the triple TF combination, it enhanced binding to E2, the hepatitis C virus host-binding protein. We conclude that C-MAF, GATA4, and MEIS2 are important transcriptional regulators of the unique LSEC fingerprint and LSEC interaction with viruses. Additional factors are however required to fully recapitulate the molecular, morphological, and functional LSEC fingerprint. NEW & NOTEWORTHY Liver sinusoidal endothelial cells (LSECs) are the first liver cells to encounter waste macromolecules, pathogens, and toxins in the blood and are highly specialized. Although some transcription factors are known to play a role in LSEC specialization, information about the specialized LSEC signature and its transcriptional determinants remains incomplete. Here, we show that Musculoaponeurotic Fibrosarcoma (C-MAF), GATA binding protein 4 (GATA4), and Meis homeobox 2 (MEIS2) are important transcriptional regulators of the unique LSEC signature and that they affect the interaction of LSECs with viruses.
35
Gerotziafas, Grigoris T., Tahar Chakroun, Vassiliki Galea, Meyer Michel Samama, and Ismail Elalamy. "Structural Determinants of Enoxaparin Oligosaccharides for the Down-Regulation of Tissue Factor Induced Factor VIIa Generation In Human Plasma." Blood 116, no. 21 (November 19, 2010): 1106. http://dx.doi.org/10.1182/blood.v116.21.1106.1106.
Full textAbstract:
Abstract Abstract 1106 Introduction. Low molecular weight heparins are multitargeted drugs that exert their antithrombotic effect primarily via the binding of pentasaccharide domain on antithrombin. The structural and functional fingerprint of enoxaparin regarding the affinity for AT and the inhibition of FXa and thrombin has been extensively studied. The depolymerization process used for manufacturing enoxaparin results in the formation of a 1,6 anhydro ring (bicyclic) structure at the reducing end of all oligosaccharides bearing 6-0-sulfo-groups on the glucosamine moiety. The influence of this particular structure on the antithrombotic activity of enoxaparin is not known. In previous studies our group demonstrated that enoxaparin and the synthetic pentasaccharide inhibit factor VIIa generation after triggering tissue factor pathway in human plasma. In patients suffering from acute coronary syndromes treatment with enoxaparin induces inhibition of FVIIa in plasma. Aim. We investigated the effect of structural characteristics of enoxaparin oligosaccharide on the generation of FVIIa. Methods. Oligosaccharides (hexa- octa- dodeca- saccharides) with the 1,6 anhydro ring structure (40%-50%) or without it (<7%) and one octasaccharide with high affinity for antithrombin (AT) were provided by Sanofi-Aventis France. Normal platelet poor plasma (PPP) from 5 healthy donors was spiked with increasing concentrations of the studied oligosaccharides (0.625 to 10 μg/ml) or enoxaparin or saline (control). Factor VIIa generation was studied after TF pathway activation in PPP according to previously described assay sensitive to detect the inhibitory effect of low concentrations of enoxaparin and pentasaccharide (Gerotziafas et al Blood Coagul Fibrinolysis. 2003;14:633-8). Briefly in polystyrene tubes containing one volume of normal human PPP was added one volume of diluted (1:250) non calcified thromboplastin (Recombiplastin). After a 3 min incubation, coagulation was triggered by adding one volume of CaCl2 solution (0.025 M). FVIIa levels were determined with the one-stage clotting assay using recombinant thromboplastin (TF1–218) truncated to interact only with FVIIa (Staclot FVIIa-rTF; Diagnostica Stago, Asnières, France), with clotting times determined by chronometric method. Results. At 2.5 μg/ml enoxaparin all studied oligosaccharide significantly inhibited FVIIa generation. The octasaccharide with the higher affinity for AT inhibited FVIIa generation significantly more than enoxaparin or the other oligosaccharides. Oligosaccharides possessing the 1,6 anhydro ring structure induced more pronounced inhibition of FVIIa generation compared to those without this structure. Octa- and dodeca- saccharides induced higher inhibition of FVIIa generation compared to the hexasaccharide. This difference was not influenced by the presence of the 1,6 anhydro ring structure. Conclusion. The FVIIa generation in PPP is a sensitive experimental system for the evaluation of structural/functional relationships in oligosaccharides contained in LMWH preparations. The present study is the first to report that the length of the oligosaccharide chain the affinity to AT and the presence of the 1,6 anhydro ring structure are structural characteristics enoxaparin which in addition to the pentasaccharide domain dowregulate TF triggered factor VIIa generation. Disclosures: No relevant conflicts of interest to declare.
36
Chitteti, Brahmananda Reddy, Bradley Poteat, Mu Wang, Yunlong Liu, and Edward F. Srour. "Genetic and Proteomic Analysis of Functionally Distinct Human Hematopoietic Stem Cells from Bone Marrow, Mobilized Peripheral Blood, and Cord Blood." Blood 112, no. 11 (November 16, 2008): 1324. http://dx.doi.org/10.1182/blood.v112.11.1324.1324.
Full textAbstract:
Abstract The bone marrow (BM) repopulating potential of hematopoietic stem cells (HSCs) is directly related to the cell cycle status of these cells. In general, only mitotically quiescent HSCs retain the ability to engraft and sustain long-term multilineage reconstitution in conditioned recipients. In a series of studies, our laboratory previously examined the effect of cell cycle status on the engraftment potential of human HSC from three different hematopoietic tissues. Only CD34+ cells in G0 phase of cell cycle (G0CD34+) from adult human BM or mobilized peripheral blood (MPB) engrafted successfully in conditioned NOD/SCID mice whereas those in G1 phase of cell cycle (G1CD34+) failed to do so. In contrast, both G0CD34+ and G1CD34+ cells from cord blood (CB) engrafted effectively. In the present study, we used the distinct in vivo behavior of these groups of adult and neonatal cells as the basis for genotypic and proteomic analyses in which it was possible to align multiple profiles of functional and non-functional HSC and therefore derive a genetic and protein fingerprint that may be associated with Engraftment potential of human stem cells. Human CD34+ cells from BM, MPB, and CB were sorted into G0 and G1 phases of cell cycle and the cell cycle status of each isolated fraction was further confirmed by the expression or lack thereof of Ki67 by qRT-PCR. Agilent Whole Human Genome Oligo Microarrays were used for genotyping (three independent samples from each tissue for a total of 18 groups) and a Linear Mixed Effect Model was used to identify differentially expressed genes, with at least a two-fold increase in expression and false discovery rate <0.05. An LC-MS/MS proteomic analysis of the same 18 groups of cells in addition to 6 others (total of four independent samples from each tissue) was also conducted in parallel. Differential expression of cellular proteins was calculated using a proprietary algorithm. A total of 190 genes were highly expressed in engrafting cells (all three groups of G0CD34+ cells and CB-derived G1CD34+ cells) whereas 1039 genes were highly expressed in non-engrafting cells (BM- and MPB-derived G1CD34+ cells). Out of the 190 differentially regulated genes in engrafting cells, 161 genes have a known function. Of these, 84 are present in the nucleus and 23 are transcription regulators including ARNTL, BCL6B, DMTF1, HES1, HLF, IFI16, and ZNF326. System Biology modeling indicated that the top four signaling pathways associated with these genes are Wnt signaling, PPARα/RXRα activation, Amyloid processing, and IGF1 signaling. Of the 1039 differentially regulated genes in non-engrafting cells, 273 are present in the nucleus and 69 are transcription regulators including CALR, CyclinE1, CEBPB, CIITA, MYC, MAPK1, and NOTCH4. System Biology modeling implicated these genes in multiple signaling pathways with the top four being the antigen presentation pathway, role of BRCA1 in DNA damage response, IL4 signaling, and the G1/S checkpoint regulation. However, proteomic analysis identified a total of 646 proteins that were detected in the lysates of all six groups of cells. Of these, 70 proteins had a significant differential expression with less than 5% false discovery rate between paired groups. The genes of only 9 proteins were differentially expressed in either the engrafting or non-engrafting cells including TPT1 (in the engrafting group) and ALDOA, MPO, TUBB, CALR, ACTB, ACTG1, PRTN3, ANXA1 (in the non-engrafting group). Functional studies aimed at discerning the roles of these proteins in stem cell function are underway. These studies demonstrate that the overlap between genomic and proteomic analysis of the same groups of engrafting and non-engrafting hematopoietic cells is rather limited but that simultaneous analysis with both protocols may identify unique modulators of stem cell function. Furthermore, protein expression analysis may be more useful in identifying pathways, the activation of which results in the loss of stem cell function since these pathways remain inactive in the mitotically and metabolically inactive engrafting cells.
37
Lee, Sanggyu, Jianjun Chen, Goulin Zhou, Run Shi, Masha Kocherginsky, Theodore G. Karrison, Yeong Cheol Kim, et al. "Gene Expression Profiles in Acute Myeloid Leukemia (AML): From Diagnosis to Prognosis." Blood 106, no. 11 (November 16, 2005): 2996. http://dx.doi.org/10.1182/blood.v106.11.2996.2996.
Full textAbstract:
Abstract Chromosome translocations are among the most common genetic abnormalities in human leukemia. The abnormally expressed genes from each translocation can be used to identify specific markers for clinical diagnosis of each translocation. Microarrays have identified genes differentially expressed in different translocations but the results between laboratories are not always compatible. We used SAGE to quantitate gene expression in bone marrow(BM) samples from 22 patients with four types of AML, [de novo AML M2 with t(8;21), AML M3 or M3V with t(15;17), AML M4Eo with inv(16), AML M5 with t(9;11) or secondary t(9;11)].We made SAGE libraries from CD15+ leukemic myeloid progenitor cells, collecting over 106 SAGE tags, of which 209,486 were unique tags; 136,010 were known genes and ESTs, and 73,476 were novel transcripts. SAGE tags for further analysis were selected based on a 5-fold difference between patient’s samples and normal CD15+ BM; they were also statistically significantly different at the 5% level. Using these strict criteria, we identified 2,381 unique tags, of which 2,053 were known genes and ESTs, and 328 were novel transcripts that were either specific for each translocation or were common(55) SAGE tags for all 4 translocations. The major change in all translocations was a decrease in expression in leukemia cells compared with normal cells; the decrease was least in the t(8;21) cells. Changes in expression of these known genes, which fall into different gene ontology functional categories, varied by translocation. Those associated with macromolecular biosynthesis, transport and transcription were most altered in the t(8;21); those related to defense response and apoptosis were altered in the t(15;17); cell proliferation genes were most affected by the t(9;11). From this analysis, we identified the functional molecular signature of each translocation. We designed a custom microarray to validate our SAGE data analysis. Our initial microarray contained 349 probes including 212 known genes, 61 ESTs, 28 novel sequences based on our data and 48 genes reported by others. We have now included 65 additional probes that appeared to be correlated with survival. Using 63 samples with the four translocations [16 inv(16), 4 t(9;11), 20 t(15;17), 4 t(8;21) and 19 other translocations], we are validating which genes provide a robust, reproducible “fingerprint” for each translocation, for all translocations, and which ones provide reliable information related to prognosis and survival. Our results will provide new insights into genes that collaborate with each translocation to lead to a fully leukemic phenotype as well as which genes appear to provide valid prognostic information.
38
Ferrari, Ivan Vito, Riccardo Narducci, Giuseppe Prestopino, Ferdinando Costantino, Alessio Mattoccia, Lina Di Giamberardino, Morena Nocchetti, et al. "Layered Double Hydroxides as a Drug Delivery Vehicle for S-Allyl-Mercapto-Cysteine (SAMC)." Processes 9, no. 10 (October 14, 2021): 1819. http://dx.doi.org/10.3390/pr9101819.
Full textAbstract:
The intercalations of anionic molecules and drugs in layered double hydroxides (LDHs) have been intensively investigated in recent years. Due to their properties, such as versatility in chemical composition, good biocompatibility, high density and protection of loaded drugs, LDHs seem very promising nanosized systems for drug delivery. In this work, we report the intercalation of S-allyl-mercapto-cysteine (SAMC), which is a component of garlic that is well-known for its anti-tumor properties, inside ZnAl-LDH (hereafter LDH) nanostructured crystals. In order to investigate the efficacy of the intercalation and drug delivery of SAMC, the intercalated compounds were characterized using X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The increase in the interlayer distance of LDH from 8.9 Å, typical of the nitrate phase, to 13.9 Å indicated the intercalation of SAMC, which was also confirmed using FT-IR spectra. Indeed, compared to that of the pristine LDH precursor, the spectrum of LDH-SAMC was richly structured in the fingerprint region below 1300 cm−1, whose peaks corresponded to those of the functional groups in the SAMC molecular anion. The LDH-SAMC empirical formula, obtained from UV-Vis spectrophotometry and thermogravimetric analysis, was [Zn0.67Al0.33(OH)2]SAMC0.15(NO3)0.18·0.6H2O. The morphology of the sample was investigated using SEM: LDH-SAMC exhibited a more irregular size and shape of the flake-like crystals in comparison with the pristine LDH, with a reduction in the average crystallite size from 3 µm to about 2 µm. In vitro drug release studies were performed in a phosphate buffer solution at pH 7.2 and 37 °C and were analyzed using UV-Vis spectrophotometry. The SAMC release from LDH-SAMC was initially characterized by a burst effect in the first four hours, during which, 32% of the SAMC is released. Subsequently, the release percentage increased at a slower rate until 42% after 48 h; then it stabilized at 43% and remained constant for the remaining period of the investigation. The LDH-SAMC complex that was developed in this study showed the improved efficacy of the action of SAMC in reducing the invasive capacity of a human hepatoma cell line.
39
Guedj, Carole, and Patrik Vuilleumier. "Functional connectivity fingerprints of the human pulvinar: Decoding its role in cognition." NeuroImage 221 (November 2020): 117162. http://dx.doi.org/10.1016/j.neuroimage.2020.117162.
Full text
40
Lee, Sanggyu, JianJun Chen, Guolin Zhou, Edward Touma, Run Shi, Miao Sun, Masha Kocherginsky, et al. "Gene Expression Profiles in Acute Myeloid Leukemias (AML): A Novel Approach Using SAGE and Custom Microarray." Blood 104, no. 11 (November 16, 2004): 197. http://dx.doi.org/10.1182/blood.v104.11.197.197.
Full textAbstract:
Abstract Chromosome translocations are among the most common genetic abnormalities in human leukemia. Each translocation may affect a different pair of genes. The abnormally expressed genes that result from the different translocations provide a rich source for identifying specific markers for clinical diagnosis of each translocation. Microarrays have identified genes differentially expressed in different translocations but the results between laboratories are not always compatible. We used SAGE to quantitate gene expression in bone marrow (BM) samples from 22 patients with four types of AML, namely de novo AML M2 with t(8;21), AML M3 or M3V with t(15;17), AML M4Eo with inv(16), AML M5 with t(9;11) or secondary t(9;11).We generated SAGE libraries from CD15+ leukemic myeloid progenitor cells, collecting over 106 SAGE tags, of which 209,486 were unique tags; 136,010 were known genes and ESTs, and 73,476 were novel transcripts. SAGE tags for further analysis were selected based on a 5-fold difference between patients’ samples and normal CD15+ BM; they were also statistically significantly different at the 5 % level. Using these strict criteria, we identified 1,571 unique tags, of which 1,405 were known genes and ESTs, and 166 were novel transcripts that were either specific for each translocation or were common for all four translocations. Changes in expression of these known genes which fall into different gene ontogeny functional categories varied by translocation. For example, those associated with macromolecular biosynthesis, transport and transcription were most altered in the t(8;21); those related to defense response and apoptosis were altered in the t(15;17); cell proliferation genes were most affected by the t(9;11). Cell surface receptor signaling, intracellular signaling and RNA processing were altered in treatment related but not in de novo t(9;11). From this analysis, we identified the functional molecular signature of each translocation. We designed a custom microarray to validate our SAGE data analysis. Our initial pilot microarray experiment with 96 genes that were specific for each translocation or common for all translocations used mononuclear cells from normal and patient BM and translocation cell lines, ME-1, THP-1, Mono Mac-6, Kasumi 1, NB-4; the array data from BM matched the SAGE data for 48-75 % of genes and the majority of cell lines, except ME-1, matched at least 70 % with the SAGE results for the appropriate translocation. We have now designed a full-scale microarray that contains over 400 probes including 250 known genes, 61 ESTs, 45 novel sequences and 48 genes reported by others. We will test at least 100 patients’ samples with the four translocations to validate which genes provide a robust, reproducible “fingerprint” for each translocation and for all translocations. We will correlate our microarray data with age, sex, race, response to treatment, survival and other mutations (FLT3, MLL ITD, etc) to identify any transcripts that might reliably define these categories. Our results will provide new insights into genes that collaborate with each translocation to lead to a fully leukemic phenotype.
41
Ghezzi, Chiara, Edurne Gorraitz, Bruce A. Hirayama, Donald D. F. Loo, Rolf Grempler, Eric Mayoux, and Ernest M. Wright. "Fingerprints of hSGLT5 sugar and cation selectivity." American Journal of Physiology-Cell Physiology 306, no. 9 (May 1, 2014): C864—C870. http://dx.doi.org/10.1152/ajpcell.00027.2014.
Full textAbstract:
Sodium glucose cotransporters (SGLTs) mediate the translocation of carbohydrates across the brush border membrane of different organs such as intestine, kidney, and brain. The human SGLT5 (hSGLT5), in particular, is localized in the kidney were it is responsible for mannose and fructose reabsorption from the glomerular filtrate as confirmed by more recent studies on hSGLT5 knockout mice. Here we characterize the functional properties of hSGLT5 expressed in a stable T-Rex-HEK-293 cell line using biochemical and electrophysiological assays. We confirmed that hSGLT5 is a sodium/mannose transporter that is blocked by phlorizin. Li+ and H+ ions were also able to drive mannose transport, and transport was electrogenic. Our results moreover indicate that substrates require a pyranose ring with an axial hydroxyl group (–OH) on carbon 2 (C-2). Compared with Na+/glucose cotransport, the level of function of Na+/mannose cotransport in rat kidney slices was low.
42
Hernandez, Tina, and Pierre Hainaut. "Tumor‐specific mutation spectra in the human p53 gene: From carcinogen “fingerprints” to functional consequences." Journal of Environmental Science and Health, Part C 16, no. 1 (May 1998): 31–45. http://dx.doi.org/10.1080/10590509809373497.
Full text
43
Zilles, K. "Architectonics of the human cerebral cortex and transmitter receptor fingerprints: reconciling functional neuroanatomy and neurochemistry." European Neuropsychopharmacology 12, no. 6 (December 2002): 587–99. http://dx.doi.org/10.1016/s0924-977x(02)00108-6.
Full text
44
Rajapandian, Meenusree, Enrico Amico, Kausar Abbas, Mario Ventresca, and Joaquín Goñi. "Uncovering differential identifiability in network properties of human brain functional connectomes." Network Neuroscience 4, no. 3 (January 2020): 698–713. http://dx.doi.org/10.1162/netn_a_00140.
Full textAbstract:
The identifiability framework (𝕀 f) has been shown to improve differential identifiability (reliability across-sessions and -sites, and differentiability across-subjects) of functional connectomes for a variety of fMRI tasks. But having a robust single session/subject functional connectome is just the starting point to subsequently assess network properties for characterizing properties of integration, segregation, and communicability, among others. Naturally, one wonders whether uncovering identifiability at the connectome level also uncovers identifiability on the derived network properties. This also raises the question of where to apply the 𝕀 f framework: on the connectivity data or directly on each network measurement? Our work answers these questions by exploring the differential identifiability profiles of network measures when 𝕀 f is applied (a) on the functional connectomes, and (b) directly on derived network measurements. Results show that improving across-session reliability of functional connectomes (FCs) also improves reliability of derived network measures. We also find that, for specific network properties, application of 𝕀 f directly on network properties is more effective. Finally, we discover that applying the framework, either way, increases task sensitivity of network properties. At a time when the neuroscientific community is focused on subject-level inferences, this framework is able to uncover FC fingerprints, which propagate to derived network properties.
45
Pham, Thu-Hang, Christopher Benner, Monika Lichtinger, Lucia Schwarzfischer, Yuhui Hu, Reinhard Andreesen, Wei Chen, and Michael Rehli. "Dynamic epigenetic enhancer signatures reveal key transcription factors associated with monocytic differentiation states." Blood 119, no. 24 (June 14, 2012): e161-e171. http://dx.doi.org/10.1182/blood-2012-01-402453.
Full textAbstract:
Abstract Cellular differentiation is orchestrated by lineage-specific transcription factors and associated with cell type–specific epigenetic signatures. In the present study, we used stage-specific, epigenetic “fingerprints” to deduce key transcriptional regulators of the human monocytic differentiation process. We globally mapped the distribution of epigenetic enhancer marks (histone H3 lysine 4 monomethylation, histone H3 lysine 27 acetylation, and the histone variant H2AZ), describe general properties of marked regions, and show that cell type–specific epigenetic “fingerprints” are correlated with specific, de novo–derived motif signatures at all of the differentiation stages studied (ie, hematopoietic stem cells, monocytes, and macrophages). We validated the novel, de novo–derived, macrophage-specific enhancer signature, which included ETS, CEBP, bZIP, EGR, E-Box and NF-κB motifs, by ChIP sequencing for a subset of motif corresponding transcription factors (PU.1, C/EBPβ, and EGR2), confirming their association with differentiation-associated epigenetic changes. We describe herein the dynamic enhancer landscape of human macrophage differentiation, highlight the power of genome-wide epigenetic profiling studies to reveal novel functional insights, and provide a unique resource for macrophage biologists.
46
Miller, Gregory E., Edith Chen, Jasmen Sze, Teresa Marin, Jesusa M. G. Arevalo, Richard Doll, Roy Ma, and Steve W. Cole. "A Functional Genomic Fingerprint of Chronic Stress in Humans: Blunted Glucocorticoid and Increased NF-κB Signaling." Biological Psychiatry 64, no. 4 (August 2008): 266–72. http://dx.doi.org/10.1016/j.biopsych.2008.03.017.
Full text
47
Tinti, M. G., T. Mazza, L. D’agruma, and A. De Cata. "AB0171 THE IMMUNOMODULATORY AND ANTI-INFLAMMATORY EFFECTS OF BOSENTAN IN SYSTEMIC SCLEROSIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1385.2–1386. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6606.
Full textAbstract:
Background:Plasma endothelin-1 (ET-1) levels are increased in patients with systemic sclerosis (SSc), playing a central role in the development of fibrosis, vasoconstriction and inflammation1. While the beneficial effect of Bosentan, the endothelin receptor antagonists, have been demonstrated on vasoconstriction and fibrosis, its potential anti-inflammatory and immunomodulatory activity needs to be further investigated.Objectives:To assess whether Bosentan can modulate the gene expression profile of immune cells in sample of patients with limited and diffuse SSc and active digital ulcers.Methods:We enrolled 34 patients affected by SSc. Twenty-four patients were affected by limited SSc and 12 by diffuse SSc. Blood samples were collected from patients before and after 24 weeks of treatment with Bosentan, in the absence of immunosuppressive therapies. All patients received Bosentan 125 mg twice a day for 24 weeks. Gene expression profiles were assessed by GeneChip® Human Transcriptome Array 2.0 microarray technology. Significantly (p-value<0.05) and differentially (|FC|>1.5) expressed genes pre/post treatment were obtained by paired t-statistics, as implemented in Partek Genomics Suite ver. 6.6. These genes were subjected to functional enrichment analysis by Ingenuity Pathway Analysis. The effect of Bosentan on patients was studied on the “diffuse” and “limited” sub-cohorts, individually, as well as on the whole cohort.Results:Contrary to the limited cohort where differentially expressed genes resulted to be all non-coding genes which are almost all over-expressed before treatment, the diffuse cohort was characterized by 19 differentially expressed genes that enrich biological functions and pathways related to the immune system and its organic response (in particular T-cells). Comparing the limited to the diffuse cohort, pre- and post- treatment, a distinct genetic fingerprint emerges, that characterizes the response to Bosentan by the latter cohort as increased apoptosis of lymphocytes (z-score=3.28) and a decreased quantity of antigen presenting cells (from z-score=1.06 (pre) to -0.75 (post)).Conclusion:The presence of an inflammatory microenvironment, as occur in SSc, influence the relative expression of ET-1 receptors on immune cells, which in turn further contribute to the amplification of cellular responses to inflammation. The observed difference response to therapy between the two cohorts of patients was attributed to influence of ET-1 levels on the relative expression of ET-1 receptors on immune cells surface. Interestingly Bosentan, beside the already-known effect on promoting antigen presenting cells apoptosis, seem to exert its immunomodulatory activity also by deregulating functions that mainly involves the T cells and by promoting their apoptosis, which in turn reflect also its anti-inflammatory proprieties.References:[1]Tinazzi E, Puccetti A, Patuzzo G, et al. Endothelin receptors expressed by immune cells are involved in modulation of inflammation and in fibrosis: relevance to the pathogenesis of systemic sclerosis. J Immunol Res. 2015;2015:147616.Disclosure of Interests:None declared
48
Lewintre, Eloisa Jantus, Miguel Marin, Cristina Reinoso, David Montaner, Joaquín Dopazo, Juan Jose Calvete, and Javier Garcia-Conde. "Analysis of B-CLL Transcriptomic and Proteomic Profiles: Differences between Molecular Subgroups." Blood 108, no. 11 (November 1, 2006): 2088. http://dx.doi.org/10.1182/blood.v108.11.2088.2088.
Full textAbstract:
Abstract INTRODUCTION: B cell chronic lymphocytic leukemia (B-CLL) is a lymphoproliferative disorder with a variable clinical course. Patients (pts) with unmutated (unmut) IgVH gene show a shorter progression free survival and overall survival than the patients with IgVH mutated (mut). To understand the differences between molecular subgroups of B-CLL we have studied transcriptomic and proteomic profiles on samples from 40 B-CLL pts (Binet stage A). MATERIAL AND METHODS: 100 μg of total PBMC proteins were used for IEF followed by 2D electrophoresis. Image analysis of scanned gels was used to identify statistically differentially expressed proteins. Image acquisition and analysis were performed using the Ludesi software (http://www.ludesi.com). Selected spots were subjected to automatic digestion and the proteins were identified by MALDI-TOF (Voyager DE-Pro, Applied Biosystems) peptide mass fingerprint using the Protein Prospector software. To confirm the initial results, sequencing of selected peptide ions was carried out by collision-induced dissociation (CID) with a nESI-QTRAP mass spectrometer from Applied Biosystems. Eight proteins were validated by Western Blot. Total RNA from B cells was used to analyze the expression profile by hybridization with Whole Human Genome U133 Plus 2.0 Array from Affymetrix. Normalization, differential gene expression and functional annotations were analyzed using the GEPAS suite (http://www.gepas.org). qPCR using TaqMan primers/probes was used for validation of the microarray data RESULTS: When we compared IgVH mut vs unmut transcriptomic and proteomic profiles, we found more than 600 differentially expressed genes and 12 proteins ( fdr <0.05 adjusted for multiple test contrast and p<0.05, Mann-Whitney’s test, for gene and proteins, respectively). In tables 1 and 2 we show some of the most differentially expressed gene/proteins in each group of pts. Validation of results from microarrays and proteomic data using qPCR and Western blot are in progress. We obtained positive correlation between transcriptomic and proteomic profiles, (corr=0.21, p=0.04, Pearson’s correation test) suggesting that common features are found using both approximations. CONCLUSION: We found a number of interesting gene/proteins that could be able to differentiate molecular subgroups of B-CLL pts. The study of these proteins and genes may lead to better understand the different clinical behaviour of IgVH mut and unmut B-CLL forms, but validation with a larger group of pts is still necessary. Table 1: Genes differentially expressed IgVH mut IgVH unmut Genes annotated using their gene symbol BCL11A MGC9913 DUSP22 RGS4 PDLIM5 CRY1 RDH13 GGT2 PHF15 DMD SVH TUBB6 ADAM29 LPL ITPKB ITGA9 RBKS BCL7A NFATC1 MYEOV RIN3 PPP1R9A Table 2: Proteins differentially expressed IgVH mut IgVH unmut Proteins were annotated according to their gene symbol VIM ERP29 COTL1 CCT2 S100A9 PSMB10 HSPD1
49
Betzel, Richard F., John D. Medaglia, Lia Papadopoulos, Graham L. Baum, Ruben Gur, Raquel Gur, David Roalf, Theodore D. Satterthwaite, and Danielle S. Bassett. "The modular organization of human anatomical brain networks: Accounting for the cost of wiring." Network Neuroscience 1, no. 1 (February 2017): 42–68. http://dx.doi.org/10.1162/netn_a_00002.
Full textAbstract:
Brain networks are expected to be modular. However, existing techniques for estimating a network’s modules make it difficult to assess the influence of organizational principles such as wiring cost reduction on the detected modules. Here we present a modification of an existing module detection algorithm that allowed us to focus on connections that are unexpected under a cost-reduction wiring rule and to identify modules from among these connections. We applied this technique to anatomical brain networks and showed that the modules we detected differ from those detected using the standard technique. We demonstrated that these novel modules are spatially distributed, exhibit unique functional fingerprints, and overlap considerably with rich clubs, giving rise to an alternative and complementary interpretation of the functional roles of specific brain regions. Finally, we demonstrated that, using the modified module detection approach, we can detect modules in a developmental dataset that track normative patterns of maturation. Collectively, these findings support the hypothesis that brain networks are composed of modules and provide additional insight into the function of those modules.
50
Tang, Joseph Kuo-Hsiang, Le You, Robert E. Blankenship, and Yinjie J. Tang. "Recent advances in mapping environmental microbial metabolisms through 13 C isotopic fingerprints." Journal of The Royal Society Interface 9, no. 76 (August 15, 2012): 2767–80. http://dx.doi.org/10.1098/rsif.2012.0396.
Full textAbstract:
After feeding microbes with a defined 13 C substrate, unique isotopic patterns (isotopic fingerprints) can be formed in their metabolic products. Such labelling information not only can provide novel insights into functional pathways but also can determine absolute carbon fluxes through the metabolic network via metabolic modelling approaches. This technique has been used for finding pathways that may have been mis-annotated in the past, elucidating new enzyme functions, and investigating cell metabolisms in microbial communities. In this review paper, we summarize the applications of 13 C approaches to analyse novel cell metabolisms for the past 3 years. The isotopic fingerprints (defined as unique isotopomers useful for pathway identifications) have revealed the operations of the Entner–Doudoroff pathway, the reverse tricarboxylic acid cycle, new enzymes for biosynthesis of central metabolites, diverse respiration routes in phototrophic metabolism, co-metabolism of carbon nutrients and novel CO 2 fixation pathways. This review also discusses new isotopic methods to map carbon fluxes in global metabolisms, as well as potential factors influencing the metabolic flux quantification (e.g. metabolite channelling, the isotopic purity of 13 C substrates and the isotopic effect). Although 13 C labelling is not applicable to all biological systems (e.g. microbial communities), recent studies have shown that this method has a significant value in functional characterization of poorly understood micro-organisms, including species relevant for biotechnology and human health.