bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scaffold Protein RACK1 inhibitor compounds prevent the Focal Adhesion Kinase mediated breast cancer cell migration and invasion potential
Authors: Ullah Hemayet , Ahsan Nagib , Dakshanamurthy Sivanesan 
Published: June 2021

ABSTRACTScaffold protein RACK1 mediates cancer cell migration mostly through regulation of focal adhesion (FA) assembly by promoting a focal adhesion kinase (FAK) activation downstream of the integrin clustering and adhesion at the extracellular matrix (ECM). Here we demonstrated the efficacy of our recently developed RACK1 Y246 phosphorylation inhibitor compounds (SD29 and SD29-14) to inhibit the migration and invasion of MCF7 and MDA-MB-231 breast cancer cell lines. Using multiple assays, our results confirmed that inhibitor compounds effectively prevent the filopodia/lamellipodia development and inhibits the migration of breast cancer cells. A mechanistic model of the inhibitor compounds has been developed. Migration and invasion capabilities of the cancer cells define the metastasis of cancer. Thus, our results suggest a potential therapeutic mechanism of the inhibitors to prevent metastasis in diverse cancers.
The atypical RNA-binding protein TAF15 regulates dorsoanterior neural development through diverse mechanisms in Xenopus tropicalis
Authors: DeJong Caitlin S. , Dichmann Darwin S. , Exner Cameron R. T. , Xu Yuxiao , Harland Richard M. 
Published: June 2021

ABSTRACTThe FET family of atypical RNA-binding proteins includes Fused in sarcoma (Fus), Ewing’s sarcoma (EWS), and the TATA-binding protein-associate factor 15 (TAF15). FET proteins are highly conserved, suggesting specialized requirements for each protein. Fus regulates splicing of transcripts required for mesoderm differentiation and cell adhesion in Xenopus, but roles that EWS and TAF15 play remain unknown. Here we analyze the roles of maternally deposited and zygotically transcribed TAF15, which is essential for the proper development of dorsoanterior neural tissues. By measuring changes in exon usage and transcript abundance from TAF15-depleted embryos we found TAF15 may regulate dorsoanterior neural development through fgfr4 and ventx2.1. TAF15 uses distinct mechanisms to downregulate FGFR4 expression: 1) retention of a single intron within fgfr4 when maternal and zygotic TAF15 is depleted, and 2) reduction of total fgfr4 transcript when zygotic TAF15 alone is depleted. The two mechanisms of gene regulation (post-transcriptional vs transcriptional) suggest TAF15-mediated gene regulation is target and cofactor-dependent, depending on the milieu of factors that are present at different times of development.
Transcriptomic analysis of dorsal and ventral subiculum after induction of acute seizures by electric stimulation of the perforant pathway in rats
Authors: Aoyama Beatriz B. , Zanetti Gabriel G. , Dias Elayne V. , Athié Maria C. P. , Lopes-Cendes Iscia , Vieira André S. 
Published: June 2021

AbstractPreconditioning is a mechanism in which injuries induced by non-lethal hypoxia or seizures trigger cellular resistance to subsequent events. Norwood et al., in a 2010 study, showed that an 8-hour-long period of electrical stimulation of the perforant pathway in rats is required for the induction of hippocampal sclerosis. However, in order to avoid generalized seizures, status epilepticus (SE), and death, a state of resistance to seizures must be induced in the hippocampus by a preconditioning paradigm consisting of 2 daily 30-minute stimulation periods. Due to the importance of the subiculum in the hippocampal formation, this study aims to investigate differential gene expression patterns in the dorsal and ventral subiculum using RNA-sequencing, after induction of a preconditioning protocol by electrical stimulation of the perforant pathway. The dorsal (dSub) and ventral (vSub) subiculum regions were collected by laser-microdissection 24 hours after preconditioning protocol induction in rats. RNA sequencing was performed in a Hiseq 4000 platform, reads were aligned using the STAR and DESEq2 statistics package was used to estimate gene expression. We identified 1176 differentially expressed genes comparing control to preconditioned subiculum regions, 204 genes were differentially expressed in dSub and 972 in vSub. The gene ontology enrichment analysis showed that the most significant common enrichment pathway considering up-regulated genes in dSub and vSub was Cholesterol Biosynthesis. In contrast, the most significant enrichment pathway considering down-regulated genes in vSub was Axon guidance. Our results indicate that preconditioning induces synaptic reorganization, increased cholesterol metabolism, and astrogliosis in both dSub and vSub. Both regions also presented a decrease in glutamatergic transmission, an increase in complement system activation, and increased in GABAergic transmission. The down-regulation of proapoptotic and axon guidance genes in the ventral subiculum suggests that preconditioning induces a neuroprotective environment in this region.
Gui Shao Di Huang Wan promotes angiogenesis and regulates oestrogen receptor α and progesterone receptor β in in vitro bioassays
Authors: O’Cleirigh Rebecca , Gibbs Roslyn 
Published: June 2021

AbstractBackground and aimThe formula Gui Shao Di Huang Wan (GSDW) is used frequently to treat female infertility. This study aims to investigate some of the possible mechanisms of action of GSDW using in vitro bioassays of angiogenesis in Human Uterine Microvascular Endothelial Cells (HUVEC) and Human Uterine Microvascular Endothelial Cells (HUtMEC) and ovarian steroid receptor expression in a human endometrial cell line (Ishikawa).Experimental procedureAqueous extracts of GSDW and its component herbs were tested for pro-angiogenic activity using both HUVEC and HUtMEC 2D differentiation assays performed on Matrigel and effects on HUVEC proliferation using the MTT assay. Effects on the expression of Estrogen Receptor α (ERα) and Progesterone Receptor β (PRβ) in Ishikawa cells were determined using immunoblotting.Results and ConclusionAll analysed parameters of differentiation were increased by GSDW in both the HUVEC and HUtMEC mesh. Furthermore, measures of total length, segment number, junction number were affected by some but not all component herbs.The MTT assay showed an increase in proliferation of HUVECs at concentrations of GSDW between 0.68 and 5.47 μg/mL at 48 and 72 hours.In Ishikawa cells downregulation of ERα and upregulation of PRβ was seen after 48 hours incubation with 4 of the 8 herbs in the formula.The findings in this study demonstrate that GSDW has the potential to affect key parameters (vascular, sex hormone receptor expression) in vitro. This offers a mechanism by which these herbs may enhance fertility through improved endometrial receptivity and pregnancy rates.
Peroxisomal ATP uptake is managed by the ABC transporters and two adenine nucleotide transporters
Authors: van Roermund Carlo , IJlst Lodewijk , Linka Nicole , Wanders Ronald J.A. , Waterham Hans R. 
Published: June 2021

AbstractPeroxisomes are essential organelles involved in various metabolic processes, including fatty acid β-oxidation. Their metabolic functions require a controlled exchange of metabolites and co-factors, including ATP across the peroxisomal membrane. We investigated which proteins are involved in the peroxisomal uptake of ATP in the yeast Saccharomyces cerevisiae. Using wild-type and targeted deletion strains, we measured ATP-dependent peroxisomal octanoate β-oxidation, intra-peroxisomal ATP levels employing peroxisome-targeted ATP-sensing reporter proteins, and ATP uptake in proteoliposomes prepared from purified peroxisomes. We show that intra-peroxisomal ATP levels are maintained by different peroxisomal membrane proteins each with different modes of action: (1) the previously reported Ant1p protein, which catalyzes ATP/AMP exchange (2) the ABC transporter protein complex Pxa1p/Pxa2p, which mediates both acyl-CoA and ATP uptake; and; (3) the mitochondrial Aac2p protein, which catalyzes ATP/ADP exchange and was shown to have a dual localization in both mitochondria and peroxisomes. Our results provide compelling evidence for an ingenious complementary system for the uptake of ATP in peroxisomes.
Regulation Network of Colorectal Cancer Specific Enhancers in Progression of Colorectal Cancer
Authors: Chen Bohan , Ma Yiping , Bi Jinfang , Wang Wenbin , He Anshun , Su Guangsong , Zhao Zhongfang , Shi Jiandang , Zhang Lei 
Published: June 2021

AbstractEnhancers regulate multiple genes through higher-order chromatin structure and further affect cancer progression. Epigenetic changes in cancer cells activate several cancer specific enhancers that are silenced in normal cells. These cancer specific enhancers are potential therapeutic targets of cancer. However, functions and regulation network of colorectal cancer specific enhancers are still unknown. Here in this study, we profile colorectal cancer specific enhancers and reveal the regulation network of these enhancers by analysis of HiChIP, Hi-C and RNA-seq data. We propose the regulation network of colorectal cancer specific enhancers plays important role in progression of colorectal cancer.
High resolution dynamic mapping of the C. elegans intestinal brush border
Authors: Bidaud-Meynard Aurélien , Demouchy Flora , Nicolle Ophélie , Pacquelet Anne , Suman Shashi Kumar , Plancke Camille , Robin François , Michaux Grégoire 
Published: June 2021

AbstractThe intestinal brush border is made of an array of microvilli that increases the membrane surface area for nutrient processing, absorption, and host defence. Studies on mammalian cultured epithelial cells uncovered some of the molecular players and physical constrains required to establish this apical specialized membrane. However, the building and maintenance of a brush border in vivo has not been investigated in detail yet. Here, we combined super-resolution imaging, transmission electron microscopy and genome editing in the developing nematode C. elegans to build a high-resolution and dynamic localization map of known and new markers of the brush border. Notably, we show that microvilli components are dynamically enriched at the apical membrane during microvilli outgrowth and maturation but become highly stable once microvilli are built. This new mapping tool will be instrumental to understand the molecular processes of microvilli growth and maintenance in vivo as well as the effect of genetic perturbations, notably in the context of disorders affecting brush border integrity.
Sniffing Out New Friends: Similarity in Body-Odor Predicts the Quality of Same-Sex Non-Romantic Dyadic Interactions
Authors: Ravreby Inbal , Snitz Kobi , Sobel Noam 
Published: June 2021

AbstractMost are familiar with the notion of socially “clicking” with someone, namely sensing an immediate bond that can lead to strong and often long-lasting friendships. The mechanisms underlying such rapid bonding remain unclear. Given that body-odor similarity is a critical cue for social interaction in non-human mammals, we tested the hypothesis that body-odor similarly contributes to bonding in same-sex non-romantic human dyads. We observed that objective ratings obtained with an electronic nose, and subjective ratings obtained from human smellers, converged to suggest that click-friends smell more similar to each other than random dyads. Remarkably, we then found that we could use the electronic nose to predict which strangers would later form better dyadic interactions. Thus, humans may literally sniff-out new friends based on similarities in body-odor.
Evolution of the nitric oxide synthase family in vertebrates and novel insights in gill development
Authors: Annona Giovanni , Sato Iori , Pascual-Anaya Juan , Braasch Ingo , Voss Randal , Stundl Jan , Soukup Vladimir , Kuratani Shigeru , Postlethwait John H. , D’Aniello Salvatore 
Published: June 2021

AbstractNitric oxide (NO) is an ancestral key signaling molecule essential for life and has enormous versatility in biological systems, including cardiovascular homeostasis, neurotransmission, and immunity. Although our knowledge of nitric oxide synthases (Nos), the enzymes that synthesize NO in vivo, is substantial, the origin of a large and diversified repertoire of nos gene orthologs in fish with respect to tetrapods remains a puzzle. The recent identification of nos3 in the ray-finned fish spotted gar, which was considered lost in the ray-finned fish lineage, changed this perspective. This prompted us to explore nos gene evolution and expression in depth, surveying vertebrate species representing key evolutionary nodes. This study provides noteworthy findings: first, nos2 experienced several lineage-specific gene duplications and losses. Second, nos3 was found to be lost independently in two different teleost lineages, Elopomorpha and Clupeocephala. Third, the expression of at least one nos paralog in the gills of developing shark, bichir, sturgeon, and gar but not in arctic lamprey, suggest that nos expression in this organ likely arose in the last common ancestor of gnathostomes. These results provide a framework for continuing research on nos genes’ roles, highlighting subfunctionalization and reciprocal loss of function that occurred in different lineages during vertebrate genome duplications.
Enhanced processing of aversive stimuli on embodied artificial limbs by the human amygdala
Authors: Fourcade Antonin , Schmidt Timo Torsten , Nierhaus Till , Blankenburg Felix 
Published: June 2021

AbstractBody perception has been extensively investigated, with one particular focus being the integration of vision and touch within a neuronal body representation. Previous studies have implicated a distributed network comprising the extrastriate body area (EBA), posterior parietal cortex (PPC) and ventral premotor cortex (PMv) during illusory self-attribution of a rubber hand. Here, we set up an fMRI paradigm in virtual reality (VR) to study whether and how threatening (artificial) body parts affects their self-attribution. Participants (N=30) saw a spider (aversive stimulus) or a toy-car (neutral stimulus) moving along a 3D-rendered virtual forearm positioned like their real forearm, while tactile stimulation was applied on the real arm in the same (congruent) or opposite (incongruent) direction. We found that the PPC was more activated during congruent stimulation; higher visual areas and the anterior insula (aIns) showed increased activation during aversive stimulus presentation; and the amygdala was more strongly activated for aversive stimuli when there was stronger multisensory integration of body-related information (interaction of aversiveness and congruency). Together, these findings suggest an enhanced processing of aversive stimuli within the amygdala when they represent a bodily threat.
Modularity and selection of nectar traits in the evolution of the selfing syndrome inIpomoea lacunosa(Convolvulaceae)
Authors: Liao Irene T. , Rifkin Joanna L. , Cao Gongyuan , Rausher Mark D. 
Published: June 2021

SUMMARYAlthough the evolution of the selfing syndrome often involves reductions in floral size, pollen, and nectar, few studies of selfing syndrome divergence have examined nectar. We investigate whether nectar traits have evolved independently of other floral size traits in the selfing syndrome, whether nectar traits diverged due to drift or selection, and the extent to which quantitative trait locus (QTL) analyses predict genetic correlations.We use F5 recombinant inbred lines (RILs) generated from a cross betweenIpomoea cordatotrilobaandI. lacunosa. We calculate genetic correlations to identify evolutionary modules, test whether traits have been under selection, identify QTLs, and perform correlation analyses to evaluate how well QTL properties reflect the genetic correlations.Nectar and floral size traits form separate genetic clusters. Directional selection has acted to reduce nectar traits in the selfingI. lacunosa. Calculations from QTL properties are consistent with observed genetic correlations.Floral trait divergence during mating system syndrome evolution reflects independent evolution of at least two evolutionary modules: nectar and floral size traits. This independence implies that adaptive change in these modules requires direct selection on both floral size and nectar traits. Our study also supports the expected mechanistic link between QTL properties and genetic correlations.
Accurate prediction of protein structures and interactions using a 3-track network
Authors: Baek Minkyung , DiMaio Frank , Anishchenko Ivan , Dauparas Justas , Ovchinnikov Sergey , Lee Gyu Rie , Wang Jue , Cong Qian , Kinch Lisa N. , Schaeffer R. Dustin , Millán Claudia , Park Hahnbeom , Adams Carson , Glassman Caleb R. , DeGiovanni Andy , Pereira Jose H. , Rodrigues Andria V. , van Dijk Alberdina A. , Ebrecht Ana C. , Opperman Diederik J. , Sagmeister Theo , Buhlheller Christoph , Pavkov-Keller Tea , Rathinaswamy Manoj K , Dalwadi Udit , Yip Calvin K , Burke John E , Garcia K. Christopher , Grishin Nick V. , Adams Paul D. , Read Randy J. , Baker David 
Published: June 2021

AbstractDeepMind presented remarkably accurate protein structure predictions at the CASP14 conference. We explored network architectures incorporating related ideas and obtained the best performance with a 3-track network in which information at the 1D sequence level, the 2D distance map level, and the 3D coordinate level is successively transformed and integrated. The 3-track network produces structure predictions with accuracies approaching those of DeepMind in CASP14, enables rapid solution of challenging X-ray crystallography and cryo-EM structure modeling problems, and provides insights into the functions of proteins of currently unknown structure. The network also enables rapid generation of accurate models of protein-protein complexes from sequence information alone, short circuiting traditional approaches which require modeling of individual subunits followed by docking. We make the method available to the scientific community to speed biological research.One-Sentence SummaryAccurate protein structure modeling enables rapid solution of structure determination problems and provides insights into biological function.
Mouse models of immune dysfunction: Their neuroanatomical differences reflect their anxiety-behavioural phenotype
Authors: Fernandes Darren J. , Spring Shoshana , Corre Christina , Tu Andrew , Qiu Lily R. , Hammill Christopher , Vousden Dulcie A. , Noakes T. Leigh Spencer , Nieman Brian J. , Bowdish Dawn M.E , Foster Jane A. , Palmert Mark R. , Lerch Jason P. 
Published: June 2021

AbstractExtensive evidence supports the role of the immune system in modulating brain function and behaviour. However, past studies have revealed striking heterogeneity in behavioural phenotypes produced from immune system dysfunction. Using magnetic resonance imaging (MRI), we studied the neuroanatomical differences among 11 distinct genetically-modified mouse lines (n=371), each deficient in a different element of the immune system. We found a significant and heterogeneous effect of immune dysfunction on the brains of both male and female mice. However, by imaging the whole brain and using bayesian hierarchical modelling, we were able to identify patterns within the heterogeneous phenotype. Certain structures -- such as the corpus callosum, midbrain, and thalamus -- were more likely to be affected by immune dysfunction. A notable brain-behaviour relationship was identified with neuroanatomy endophenotypes across mouse models clustering according to anxiety-like behaviour phenotypes reported in literature, such as altered volume in brains regions associated with promoting fear response (e.g., the lateral septum and cerebellum). Interestingly, genes with preferential spatial expression in the most commonly affected regions are also associated with multiple sclerosis and other immune-mediated diseases. In total, our data suggest that the immune system modulates anxiety behaviour through well-established brain networks.
Harnessing the power of metabarcoding in the ecological interpretation of plant-pollinator DNA data: strategies and consequences of reads filtering
Authors: Tommasi Nicola , Ferrari Andrea , Labra Massimo , Galimberti Andrea , Biella Paolo 
Published: June 2021

AbstractDNA metabarcoding approaches to analyse complex mixtures of pollen has become the standard in pollination biology, especially in the light of recent threats affecting pollination. In spite of the increasing adoption of High Throughput Sequencing (HTS) approaches, these studies generate huge numbers of raw reads, some of which might be associated to false positives or infrequently recorded species with potentially little biological information. If these reads are not discarded (i.e. pruned), they can lead to changes in the ecological findings and lead to biased conclusions. In this study we reviewed 42 papers in the recent pollen DNA metabarcoding literature and focused on the type of pruning applied. We also tested whether the different types of those cut off threshold may leave a mark on the DNA metabarcoding data. To do so, we compared for the first time community composition, species richness and networks of species interactions (i.e. Connectace, Modularity, Connectivity and Shannon entropy) associated with the most relevant ways of treating HTS outputs: no cut (no reads filtering), or cutting levels obtained as proportional 1% of sample total reads, or as fixed amount of 100 reads, or from ROC (Receiver operator characteristic). Results clearly indicated that pruning type shapes species composition and that to apply or not a threshold dramatically impacts ecological indices, potentially increasing the risk of misinterpreting DNA metabarcoding data under an ecological point of view. Given the high methodological heterogeneity from the revised literature, we discuss in what conditions filtering types may be more appropriate, and also recommend to biologically justify the pruning threshold when analysing DNA metabarcoding raw reads, and to develop shared approaches to make future studies more comparable.
seqgra: Principled Selection of Neural Network Architectures for Genomics Prediction Tasks
Authors: Krismer Konstantin , Hammelman Jennifer , Gifford David K. 
Published: June 2021

AbstractSequence models based on deep neural networks have achieved state-of-the-art performance on regulatory genomics prediction tasks, such as chromatin accessibility and transcription factor binding. But despite their high accuracy, their contributions to a mechanistic understanding of the biology of regulatory elements is often hindered by the complexity of the predictive model and thus poor interpretability of its decision boundaries. To address this, we introduce seqgra, a deep learning pipeline that incorporates the rule-based simulation of biological sequence data and the training and evaluation of models, whose decision boundaries mirror the rules from the simulation process. The method can be used to (1) generate data under the assumption of a hypothesized model of genome regulation, (2) identify neural network architectures capable of recovering the rules of said model, and (3) analyze a model’s predictive performance as a function of training set size, noise level, and the complexity of the rules behind the simulated data.