bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perfect genetic biomarkers for cancer from a fresh view of gene dysregulation
Authors: Gil Gabriel , Gonzalez Augusto 
Published: July 2022

SummaryOver the last decades, a host of gene expression profiles of tumor and normal tissue samples have been recorded by many microarray and RNA-Seq projects. Much of this big data awaits a full understanding and exploitation for translational cancer research. In particular, the pressing need to discover gene panels for diagnosis and therapy have not received yet a definitive answer. Here, we tackle such a question through rigorous mining of some of the currently available data. Our mining scheme rests on formal concept analysis and rough set theory and allows us to identify perfect gene panels for twelve of the solid tumors reported in the TCGA database. We dub them ‘perfect gene panels’ because they perfectly discriminate between normal and tumor samples. To wit, testing the gene expression profiles against a tumor or normal pattern provides no false positive and no false negative cases (i.e., 100% sensitivity and 100% specificity). Hence, perfect gene panels might be useful genetic markers for cancer diagnosis. Furthermore, we stress that such panels come in many flavors depending on the gene expression levels we choose as a pattern to check. For instance, there are perfect panels where a single gene over-expression signals a tumor and others where a single non-silenced gene is an indication of a tumor-free sample, just to mention two out of eight possible cases. Remarkably, some panels also suggest suitable genetic targets for therapeutic interventions, since they define normal samples by tuning the expression level of a single gene.
Prior parental experience attenuates hormonal stress responses and alters hippocampal glucocorticoid receptors in both sexes of the biparental rock dove
Authors: Farrar Victoria S. , Gallardo Jaime Morales , Calisi Rebecca M. 
Published: July 2022

AbstractIn the face of challenges, animals must balance investments in reproductive effort versus their own survival. Physiologically, this tradeoff may be mediated by glucocorticoid release by the hypothalamic-pituitary-adrenal (HPA) axis and prolactin release from the pituitary to maintain parental care. The degree to which animals react to, and recover from, stressors likely affects their ability to maintain parental behavior and ultimately, fitness. However, less is known about how the stress response changes when animals gain parental experience, and what mechanisms may underlie any effect of experience on hormonal stress responses. To address these questions, we measured the corticosterone (CORT) and prolactin (PRL) stress response in both sexes of the biparental rock dove (Columba livia) that had never raised chicks versus birds that had fledged at least one chick. We measured both CORT and PRL at baseline and after an acute stressor (30 minutes restraint). We also measured negative feedback ability by administering dexamethasone, a synthetic glucocorticoid that suppresses CORT release, and measuring CORT and PRL after 60 minutes. All hormones we measured when birds were not actively nesting, allowing us to assess any lasting effects of parental experience beyond the parental care period. Birds with parental experience had lower stress-induced and negative-feedback CORT, and higher stress-induced PRL than inexperienced birds. In a separate experiment, we measured glucocorticoid receptor subtype expression in the hippocampus, a key site of negative feedback regulation. We found that experienced birds expressed higher glucocorticoid receptors than inexperienced controls, which may mediate their ability to attenuate the hormonal stress response. Together, these results shed light on potential mechanisms by which gaining experience may improve parental performance and fitness.Summary statementExperienced rock dove parents show lower corticosterone and higher prolactin levels after an acute stressor than birds without parental experience and increased glucocorticoid receptor expression in the hippocampus may mediate this effect.
Characterization of Mechanics Driven Heterogeneity in Mesenchymal Stromal Cells
Authors: Kaonis Samantha , Aboellail Zack , Ghosh Soham 
Published: July 2022

ABSTRACTMesenchymal stromal or stem cells (MSC) are one of the most promising candidates for a myriad of cell therapy applications because of their multipotency, trophic properties and immunomodulatory properties. Despite showing promises in numerous preclinical and clinical studies, MSC based therapy is not yet a reality for regenerative medicine due their suboptimal outcome at the clinical endpoint. Suboptimal function of MSC is often attributed to the monolayer expansion process on plastic which is a necessary condition to reach the therapeutically relevant number, and also to their response to a fibrotic environment post transplantation. In both scenarios of plastic culture and fibrotic conditions, the mechanical environment experienced by the MSC is completely different from the natural mechanical niche of the MSC. Accordingly, the role of mechanical environment has been shown to be a critical determinant of MSC gene expression and function. In this study we report that human bone marrow derived primary MSC population becomes phenotypically heterogenous when they experience an abnormal mechanical environment, compared to their native environment. Using a newly developed technique to quantify the heterogeneity, we provide the evidence of phenotypical heterogeneity of MSC through high resolution imaging and image analysis. Additionally, we provide mechanistic insight of the origin of such substrate mechanics driven heterogeneity, which is further determined by the cell-cell mechanical communication through the substrate. The outcome of this study might provide mechanism driven design principles to the molecular, cellular and tissue engineering researchers for rational design of MSC culture condition and biomaterials, thus improving their functional outcome.
Characterization of DNA processing protein A (DprA) of the radiation-resistant bacterium Deinococcus radiodurans
Authors: Sharma Dhirendra Kumar , Misra Hari S. , Rajpurohit Yogendra S. 
Published: July 2022

AbstractThe uptake of environmental DNA (eDNA) by certain bacteria and its integration into their genome creates genetic diversity and new phenotypes. A DNA processing protein A (DprA) is part of a multiprotein complex and facilitate natural transformation (NT) phenotype in most bacteria. The Deinococcus radiodurans, an extremely radioresistant bacterium, is efficient in N T, and its genome encodes nearly all the components of the natural competence complex. Here, we have characterized the DprA of this bacterium (DrDprA) for the known characteristics of DprA proteins in other bacteria and the mechanisms underlying its roles in the transformation of eDNA into the bacterial genome. DrDprA is found to be a unique domain organization implicating some unique functions compared with DprA of other bacteria. In vitro studies showed that the purified recombinant DrDprA binds to both ssDNA and dsDNA with nearly equal affinity and protects ssDNA from nucleolytic degradation. DrDprA showed a strong interaction with DrRecA indicating its role in RecA catalyzed functions in vivo. Mutational studies identified amino acid residues responsible for its oligomerization, interaction with DrRecA, and DNA binding characteristics of DrDprA. Further, we demonstrated that both oligomerization and DNA binding properties of DrDprA are integral to its support in DrRecA catalyzed strand exchange reaction (SER) in vitro. These results suggested that DrDprA is largely structurally conserved with DprA homologs but showed some unique structure-function features like additional domain, the same affinity to ss/ds DNA and both oligomerization and DNA binding domains collectively contribute to its support in DrRecA functions.
Characterization of rumen microbiome and metabolome from an oro-esophageal probe and fluid, particulate and fluid-particulate fractions from rumen fistula in Holstein dairy cows
Authors: da Cunha Lais L. , Monteiro Hugo F. , Canisso Igor F. , Bicalho Rodrigo C. , Cardoso Felipe C. , Weimer Bart C. , Lima Fabio S. 
Published: July 2022

ABSTRACTLess invasive rumen sampling methods such as oro-esophageal probes became widely popular to explore the rumen microbiome and metabolome. However, it remains unclear if such methods represent well the rumen contents from fluid and particulate fractions. Herein, we characterized the microbiome and metabolome in rumen content collected by an oro-esophageal probe and fluid, particulate, and the combined fluid-particulate fractions collected by rumen fistula in ten multiparous Holstein dairy cows. The 16S rRNA gene was amplified and sequenced using the Illumina MiSeq platform. Untargeted metabolome was characterized using gas chromatography of a time-of-flight mass spectrometer. Although the pH of oro-esophageal samples was greater than those of fluid, fluid-particulate, and particulate ones, we found no difference in alpha and beta-diversity of their microbiomes. Bacteroidetes, Firmicutes, and Proteobacteria were consistently the top three most abundant phyla representing ~90% of all detected phyla across all samples. The overall metabolome PLS-DA of oro-esophageal samples was similar to the fluid-particulate samples but differed from fluid and particulate. Enrichment analysis pathways revealed few differences between oro-esophageal and fluid-particulate samples, such as the synthesis of unsaturated fatty acids. The results of the current study suggest that oro-esophageal sampling can be a proxy to screen the rumen microbiome with the 16S platform and overall fluid-particulate metabolome for a single-time and diet context. Nonetheless, studies focusing specifically on fluid and particulate metabolomes and specific metabolic pathways should carefully consider the sampling method used.IMPORTANCEThe techniques used to collect the rumen contents (oro-esophageal probe and rumen fistula) suggested potential differences in the populations of rumen microbes, and the implications of these techniques for high throughput studies characterizing the rumen microbiome and metabolome need further elucidation. Ten rumen-fistulated Holstein dairy cows were used to characterize the microbiome and metabolome of samples collected using an oro-esophageal probe and the rumen-fistula fluid, particulate, and fluid-particulate fractions. The results of the current study suggest that oro-esophageal sampling represents well the rumen microbiome and overall fluid-particulate metabolome. However, fluid and particulate metabolomes and specific metabolic pathways across all types of rumen samples differed, indicating that studies focused on the characterization of rumen metabolome variable fractions should carefully consider the sampling method used.
Asymmetric dimethylarginine positively modulates Calcium-Sensing Receptor signalling to promote lipid accumulation and adiposity
Authors: Dowsett Laura , Duluc Lucie , Higgins Erin , Alghamdi Fatmah , Fast Walter , Salt Ian P. , Leiper James 
Published: July 2022

AbstractIrreversible methylation of arginine residues generates asymmetric dimethylarginine (ADMA). ADMA is a competitive inhibitor of nitric oxide (NO) synthase and an independent risk factor for cardiovascular disease. Plasma ADMA concentrations increase with obesity and fall following weight loss. Here, we demonstrate that ADMA drives lipid accumulation through a newly identified NO-independent pathway via the amino-acid sensitive calcium-sensing receptor (CaSR). ADMA treatment of 3T3-L1 and HepG2 cells activates mTOR signalling and upregulates a suite of lipogenic genes with an associated increase in triglyceride content. Pharmacological blockade of CaSR inhibits ADMA driven lipid accumulation and ADMA treatment potentiates CaSR signalling via both Gq and Gi/o pathways. Impairment of ADMA metabolism in adipocytes in vivo, by dimethylamine dimethylaminohydrolase-1 (DDAH1) deletion, increases visceral adiposity and adipocyte hypertrophy. This study identifies a signalling mechanism for ADMA as an endogenous ligand of the G protein-coupled receptor CaSR that potentially contributes to the impact of ADMA in cardiometabolic disease.
DNAffinity: A Machine-Learning Approach to Predict DNA Binding Affinities of Transcription Factors
Authors: Barissi Sandro , Sala Alba , Wieczor Milosz , Battistini Federica , Orozco Modesto 
Published: July 2022

ABSTRACTWe present a physics-based machine learning approach to predict in vitro transcription factor binding affinities from structural and mechanical DNA properties directly derived from atomistic molecular dynamics simulations. The method is able to predict affinities obtained with techniques as different as uPBM, gcPBM and HT-SELEX with an excellent performance, much better than existing algorithms. Due to its nature, the method can be extended to epigenetic variants, mismatches, mutations, or any non-coding nucleobases. When complemented with chromatin structure information, our in vitro trained method provides also good estimates of in vivo binding sites in yeast.
Significance of two transmembrane ion gradients for human erythrocyte volume stabilization
Authors: Ataullakhanov F.I. , Martinov M.V. , Shi Qiang , Vitvitsky V.M. 
Published: July 2022

SummaryFunctional completeness of erythrocytes depends on high deformability of these cells, that allows them to pass through narrow tissue capillaries. The erythrocytes high deformability is provided due to maintenance of discoid shape with an optimal cell surface area to volume ratio. This ratio can be maintained due to cell volume stabilization at a given cell surface area. We studied role of Na/K-ATPase and transmembrane Na+and K+gradients in human erythrocyte volume stabilization at non-selective increase in cell membrane permeability to cations by using mathematical simulation. The simulation took into account a contribution of glycolytic metabolites and adenine nucleotides to cytoplasm osmotic pressure in the cells. It was shown that in the presence of Na/K-ATPase activated by intracellular sodium ions and two oppositely directed gradients of Na+and K+ions in the cell, the volume of the erythrocyte deviates from the optimal value by no more than 10% with a change in the non-selective permeability of the cell membrane to cations from 50 to 200% of the normal value. The transport Na/K-ATPase, which sets the ratio of transmembrane fluxes of sodium and potassium ions equal to 3:2, provides the best stabilization of the erythrocyte volume exactly at a non-selective increase in the permeability of the cell membrane, when the permeability for sodium and potassium ions increases equally. Such increase in erythrocyte membrane permeability is caused by oxidation of the membrane components and by mechanical stress during circulation. In the case of only one transmembrane ion gradient (Na+), the cell loses the ability to stabilize the volume when the cell membrane is damaged. In this case even small variations of cell membrane permeability cause dramatic changes in the cell volume. Our results reveal that the presence of two oppositely directed transmembrane ion gradients (Na+and K+) and the transport Na/K-ATPase activated by intracellular sodium are fundamentally important conditions for the stabilization of cellular volume in human erythrocytes.
Glucose lowering effects by sago (Metroxylon sagu Rottb) resistant starches Type 2 and 4 in spontaneously type 2 diabetes, Goto kakizaki rat
Authors: Lokman Ezarul Faradianna , Bugam Sal Hazreen , Ibrahim Aina Shafiza , Yunus Nurleyna , Mansor Fazliana , Balasubramaniam Vimala , Mohamad Khairul Mirza , Lazim Rabizah Md , Seruji Awang Zulfikar Rizal Awang 
Published: July 2022

AbstractThe beneficial effects of resistant starch (RS) consumption on health in terms of reducing postprandial hyperglycemia are evident. However, the potential of local Sarawak sago RS in regulating glucose has not been extensively studied. This study aims to identify glucose lowering effects of Sarawak sago RS namely, native unmodified (RS2) and chemically modified (RS4). An oral glucose tolerance test was performed before and after one-month treatment with sago RS2 and RS4 in spontaneously type 2 diabetes, goto kakizaki rat. The mechanisms involved were further explored by screening the in vitro inhibitory activities of α-Glucosidase and DPP-IV. Histopathology examination for pancreas, kidney and liver tissues was performed in response to sago RS treatment using hematoxylin and eosin (H&E) staining.The blood glucose area under the curve (AUC) in RS-treated groups was decreased and significant in RS2-treated group (p<0.05). Improved insulin AUC and higher glucagon like peptide (GLP-1) levels were observed in all RS-treated groups (p<0.05). Sago RS2 and RS4 might have potential roles in regulating glucose via α-Glucosidase and DPP-IV inhibitory activities by reducing glucose absorption in the intestine. For histopathology study, although insignificant, sago RS2 and RS4 attenuated lesion scores of pancreatic tissue whereas the liver and kidney tissues significantly showed lesser lesion scores as compared to the control diabetic group suggesting the potential of RS in reducing cell degeneration which indeed requires further validation.Findings of this study suggests the therapeutic potential of sago RS in the T2D management which may justify further investigation to be done.
Network analysis of the human structural connectome including the brainstem: a new perspective on consciousness
Authors: Salhi Salma , Kora Youssef , Ham Gisu , Haghighi Hadi Zadeh , Simon Christoph 
Published: July 2022

AbstractThe underlying anatomical structure is fundamental to the study of brain networks and is likely to play a key role in the generation of conscious experience. We conduct a computational and graph-theoretical study of the human structural connectome incorporating a variety of subcortical structures including the brainstem, which is typically not considered in similar studies. Our computational scheme involves the use of Python DIPY and Nibabel libraries to develop an averaged structural connectome comprised of 100 healthy adult subjects. We then compute degree, eigenvector, and betweenness centralities to identify several highly connected structures and find that the brainstem ranks highest across all examined metrics. Our results highlight the importance of including the brainstem in structural network analyses. We suggest that structural network-based methods can inform theories of consciousness, such as global workspace theory (GWT), integrated information theory (IIT), and the thalamocortical loop theory.
Generation and propagation of network bursts in the basal ganglia exhibit dynamic changes during early postnatal development
Authors: Klavinskis-Whiting Sebastian , Bitzenhofer Sebastian , Hanganu-Opatz Ileana , Ellender Tommas 
Published: July 2022

AbstractThe neonatal brain is characterised by intermittent bursts of oscillatory activity interspersed by relative silence. While these bursts of activity are well characterised for many cortical areas much less is known whether and how these propagate and interact with subcortical regions. Here, early network activity was recorded using silicon probes from the developing basal ganglia, including the motor/somatosensory cortex, dorsal striatum and intralaminar thalamus, during the first two postnatal weeks in mice. Using an unsupervised detection and classification method, two main classes of bursting activity were found, consisting of spindle bursts (SB) and nested gamma spindle bursts (NGB), which were characterised by oscillatory activity at respectively ∼10 Hz and ∼30 Hz. These bursts were reliably identified across all three brain structures but differed in their structural, spectral, and developmental characteristics. Coherence and cross-correlation analyses revealed that burst events often occur synchronously across different brain regions and were mostly of a similar type, especially between cortex and striatum, which also exhibited the strongest interactions as compared to other brain regions. Interestingly, the preferred frequency for these interactions suggested a developmental shift from initial lower frequencies to higher frequencies across development. Together, these results provide the first detailed description of early network activity within the developing basal ganglia and suggests that distinct brain regions drive and coordinate burst activity at different developmental stages.
Transcriptional response of the xerotolerant Arthrobacter sp. Helios strain to PEG-induced drought stress
Authors: Hernández-Fernández G , Galán B , Carmona M , Castro L , García JL 
Published: July 2022

AbstractA new bacterial strain highly tolerant to desiccation and to UV radiation has been isolated from the microbiome of solar panels. This strain showed a high xerotolerance in the exponential and the stationary phase of growth and it has been classified as Arthrobacter sp. Helios according to its 16S rDNA, positioning this new strain in the ‘Arthrobacter citreus group’. The complete genome of Arthrobacter sp. Helios consists in a single circular chromosome of 3,895,998 bp, with a 66% GC content and no plasmids. A total of 3,586 genes were predicted, of which 2,275 protein-encoding genes were functionally assigned. The genome analysis suggests that it is motile, ecologically versatile, capable of growing in a variety of carbon sources and well poised to respond to environmental stresses. Using PEG6000 to mimic arid stress conditions, we have studied the transcriptional response of this strain to matric stress when cells are cultured on media containing 10% (PEG10) and 35% PEG (PEG35). The transcriptomic analysis revealed that cells can be easily adapted to moderate matric stress (PEG10) by modifying the expression of a small number of genes to maintain a high growth rate, while a higher matric stress (PEG35) altered the expression of many more genes. Remarkably, these metabolic changes do not confer the cells a higher tolerance to desiccation, suggesting that mechanisms to support matric stress and desiccation tolerance are different. The peculiar observation that Arthrobacter sp. Helios seems to be permanently prepared to handle the desiccation stress makes it an exciting chassis for biotechnological applications.
A simple thermodynamic description of phase separation of Nup98 FG domains
Authors: Ng Sheung Chun , Görlich Dirk 
Published: July 2022

AbstractThe permeability barrier of nuclear pore complexes (NPCs) controls nucleocytoplasmic transport. It retains inert macromolecules but allows facilitated passage of nuclear transport receptors that shuttle cargoes into or out of nuclei. The barrier can be described as a condensed phase assembled from cohesive FG repeat domains, including foremost the charge-depleted FG domain of Nup98. We found that Nup98 FG domains show an LCST-type phase separation, and we provide comprehensive and orthogonal experimental datasets for a quantitative description of this behaviour. A derived thermodynamic model correlates saturation concentration with repeat number, temperature, and ionic strength. It allows estimating the enthalpy, entropy, and ΔG (∼0.2 kJ/mol, 0.1 kB·T) contributions per repeat to phase separation and inter-repeat cohesion. While changing the cohesion strength strongly impacts the strictness of barrier, these numbers provide boundary conditions for in-depth modelling not only of barrier assembly but also of NPC passage.