bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of insulators and transcription in 3D chromatin organisation of flies
Authors: Chathoth Keerthi T , Mikheeva Liudmila A , Crevel Gilles , Wolfe Jareth C. , Hunter Ioni , Beckett-Doyle Saskia , Cotterill Sue , Dai Hongsheng , Harrison Andrew , Zabet Nicolae Radu 
Published: April 2021

AbstractThe DNA in many organisms, including humans, is shown to be organised in topologically associating domains (TADs). InDrosophila, several architectural proteins are enriched at TAD borders, but it is still unclear whether these proteins play a functional role in the formation and maintenance of TADs. Here, we show that depletion of BEAF-32, Cp190, Chro and Dref leads to changes in TAD organisation and chromatin loops. Their depletion predominantly affects TAD borders located in heterochromatin, while TAD borders located in euchromatin are resilient to these mutants. Furthermore, transcriptomic data has revealed hundreds of genes displaying differential expression in these mutants and showed that the majority of differentially expressed genes are located within reorganised TADs. Our work identifies a novel and functional role for architectural proteins at TAD borders inDrosophilaand a link between TAD reorganisation and subsequent changes in gene expression.
Dysregulation of NRSF/REST via EHMT1 is associated with psychiatric disorders
Authors: Alsaqati Mouhamed , Davis Brittany A , Wood Jamie , Jones Megan , Jones Lora , Westwood Aishah , Petter Olena , Isles Anthony R , Linden David , Van den Bree Marianne , Owen Michael , Hall Jeremy , Harwood Adrian J 
Published: April 2021

SummaryGenetic evidence indicates disrupted epigenetic regulation as a major risk factor for psychiatric disorders, but the molecular mechanisms that drive this association are undetermined. EHMT1 is an epigenetic repressor that is causal for Kleefstra Syndrome (KS), a neurodevelopmental disorder (NDD) leading to ID, and is associated with schizophrenia. Here, we show that reduced EHMT1 activity decreases NRSF/REST protein leading to abnormal neuronal gene expression and progression of neurodevelopment in human iPSC. We further show that EHMT1 regulates NRSF/REST indirectly via repression of miRNA leading to aberrant neuronal gene regulation and neurodevelopment timing. Expression of a NRSF/REST mRNA that lacks the miRNA-binding sites restores neuronal gene regulation to EHMT1 deficient cells. Importantly, the EHMT1-regulated miRNA gene set with elevated expression is enriched for NRSF/REST regulators with an association for ID and schizophrenia. This reveals a molecular interaction between H3K9 dimethylation and NSRF/REST contributing to the aetiology of psychiatric disorders.
Perivascular cells support folliculogenesis in the developing ovary
Authors: Li Shuyun , Bhandary Bidur , DeFalco Tony 
Published: April 2021

AbstractGranulosa cells, supporting cells of the ovary, are essential for ovarian differentiation by providing a nurturing environment for oogenesis. Sufficient numbers of granulosa cells are vital for establishment of follicles and the oocyte reserve; therefore, identifying the cellular source from which granulosa cells are derived is critical for understanding basic ovarian biology. One cell type that has received little attention in this field is the perivascular cell. Here we use lineage tracing and organ culture techniques in mice to identify ovarian Nestin+ perivascular cells as multipotent progenitors that contribute to granulosa, thecal, and pericyte lineages. Maintenance of these progenitors was dependent on vascular-mesenchymal Notch signaling. Ablation of postnatal Nestin+ cells resulted in a disruption of granulosa cell specification and an increased incidence of polyovular ovarian follicles, thus uncovering key roles for vasculature in ovarian differentiation. These findings may provide new insights into the origins of female gonad dysgenesis and infertility.
Beta bursting in the retrosplenial cortex is a neurophysiological correlate of environmental novelty which is disrupted in a mouse model of Alzheimer’s disease
Authors: Walsh Callum , Ridler Thomas , Garrido Maria Garcia , Witton Jonathan , Randall Andrew D. , Brown Jonathan T. 
Published: April 2021

AbstractThe retrosplenial cortex (RSC) plays a significant role in spatial learning and memory, and is functionally disrupted in the early stages of Alzheimer’s disease. In order to investigate neurophysiological correlates of spatial learning and memory in this region we employedin vivoelectrophysiology in awake, behaving mice, comparing neural activity between wild-type and J20 mice, a mouse model of Alzheimer’s disease-associated amyloidopathy. To determine the response of the RSC to environmental novelty local field potentials were recorded while mice explored novel and familiar recording arenas. In familiar environments we detected short, phasic bursts of beta (20-30 Hz) oscillations (beta bursts) which arose at a low but steady rate. Exposure to a novel environment rapidly initiated a dramatic increase in the rate, size and duration of beta bursts. Additionally, theta-beta cross-frequency coupling was significantly higher during novelty, and spiking of neurons in the RSC was significantly enhanced during beta bursts. Finally, aberrant beta bursting was seen in J20 mice, including increased beta bursting during novelty and familiarity, yet a loss of coupling between beta bursts and spiking activity. These findings, support the concept that beta bursting may be responsible for the activation and reactivation of neuronal ensembles underpinning the formation and maintenance of cortical representations, and that disruptions to this activity in J20 mice may underlie cognitive impairments seen in these animals.
Vascular and perivascular cell profiling reveals the molecular and cellular bases of blood-brain barrier heterogeneity
Authors: Pfau Sarah J. , Langen Urs H. , Fisher Theodore M. , Prakash Indumathi , Nagpurwala Faheem , Lozoya Ricardo A. , Lee Wei-Chung Allen , Wu Zhuhao , Gu Chenghua 
Published: April 2021

SUMMARYThe blood-brain barrier (BBB) is critical for protecting the brain and maintaining neuronal homeostasis. Although the BBB is a unique feature of the central nervous system (CNS) vasculature, not all brain regions have the same degree of impermeability. Differences in BBB permeability are important for controlling the local extracellular environment of specific brain regions to regulate the function and plasticity of particular neural circuits. However, how BBB heterogeneity occurs is poorly understood. Here, we demonstrate how regional specialization of the BBB is achieved. With unbiased cell profiling in small, defined brain regions, we compare the median eminence, which has a naturally leaky BBB, with the cortex, which has an impermeable BBB. We identify hundreds of molecular differences in endothelial cells (ECs) and demonstrate the existence of differences in perivascular astrocytes and pericytes in these regions, finding 3 previously unknown subtypes of astrocytes and several key differences in pericytes. By serial electron microscopy reconstruction and a novel, aqueous-based tissue clearing imaging method, we further reveal previously unknown anatomical specializations of these perivascular cells and their unique physical interactions with neighboring ECs. Finally, we identify ligand-receptor pairs between ECs and perivascular cells that may regulate regional BBB integrity in ECs. Using a bioinformatic approach we identified 26 and 26 ligand-receptor pairs underlying EC-pericyte and EC-astrocyte interactions, respectively. Our results demonstrate that differences in ECs, together with region-specific physical and molecular interactions with local perivascular cells, contribute to BBB functional heterogeneity. These regional cell inventories serve as a platform for further investigation of the dynamic and heterogeneous nature of the BBB in other brain regions. Identification of local BBB specializations provides insight into the function of different brain regions and will permit the development of region-specific drug delivery in the CNS.
The receptor kinase SRF3 coordinates iron-level and flagellin dependent defense and growth responses in plants
Authors: Platre Matthieu P. , Satbhai Santosh B. , Brent Lukas , Gleason Matias F. , Grison Magali , Glavier Marie , Zhang Ling , Cao Min , Gaillochet Christophe , Goeschl Christian , Giovannetti Marco , Enugutti Balaji , von Reth Marcel , Alcázar Ruben , Parker Jane E. , Vert Grégory , Bayer Emmanuelle , Busch Wolfgang 
Published: April 2021

SummaryIron is critical for host-pathogen interactions. While pathogens seek to scavenge iron to spread, the host aims at decreasing iron availability to reduce pathogen virulence. Thus, iron sensing and homeostasis are of particular importance to prevent host infection and part of nutritional immunity. While the link between iron homeostasis and immunity pathways is well established in plants, how iron levels are sensed and integrated with immune response pathways remain unknown. We identified a receptor kinase, SRF3 coordinating root growth, iron homeostasis and immunity pathways via regulation of callose synthase activity. These processes are modulated by iron levels and rely on SRF3 extracellular and kinase domain which tune its accumulation and partitioning at the cell surface. Mimicking bacterial elicitation with the flagellin peptide flg22 phenocopies SRF3 regulation upon low iron levels and subsequent SRF3-dependent responses. We propose that SRF3 is part of nutritional immunity responses involved in sensing external iron levels.
Comparison of the therapeutic effects of hUC-MSC intravenous delivery and intraperitoneal administration of MSCs encapsulated in alginate capsules for the treatment of rat liver cirrhosis
Authors: Rymar S. , Pikus P. , Buchek P. , Shuvalova N. , Pokholenko Ia. , Irodov D. , Kordium V. 
Published: April 2021

AbstractMesenchymal stem cells are the most promising regenerative medicine tool for the treatment of various diseases, including liver disease, although the exact mechanism of their therapeutic action remains unclear. It was found that MSCs are captured by the lungs after systemic transplantation, quickly disappear, and are not detected at the site of injury, but at the same time exhibit an obvious therapeutic effect. Comparison of the MSC efficiency depending on the route of their administration may shed light on the mechanisms involved in the implementation of MSC therapeutic potential. In this work, we compared the therapeutic effects of human umbilical cord MSCs (hUC-MSCs) administered systemically and intraperitoneally in the form of MSCs encapsulated in alginate capsules in a CCl4-induced model of liver cirrhosis in rats. Our study showed that both treatments resulted in liver recovery. MSC transplantation by two different routes led to a decrease in collagen deposition, the disappearance of the fibrous area by the 13th week, and normalization of the morphometric parameters of liver parenchyma cells. The expression of some genes (EGF, alpha SMA, GFAP) which is activated in liver injury, decreased to the level observed in negative control animals. However, a detailed study of liver recovery in dynamics showed that encapsulated MSCs led to faster normalization in several parameters of the liver tissue. Our results showed that human umbilical cord MSCs effectively exhibit their therapeutic properties when using both methods of transplantation, however, intraperitoneal administration of encapsulated MSCs accelerated the process of liver regeneration.
Mechanical control of innate immune responses against viral infection revealed in a human Lung Alveolus Chip
Authors: Bai Haiqing , Si Longlong , Jiang Amanda , Belgur Chaitra , Plebani Roberto , Oh Crystal , Rodas Melissa , Nurani Atiq , Gilpin Sarah , Powers Rani K. , Goyal Girija , Baun Rachelle Prantil- , Ingber Donald E. 
Published: April 2021

ABSTRACTMechanical forces associated with breathing play a fundamental role in lung development and disease but the molecular pathways remain largely unknown. Here, we used a mechanically actuatable Human Lung Alveolus Chip that recapitulates human lung alveolar type I and type II cell differentiation, alveolar-capillary interface formation, and genome-wide gene expression profiles characteristic of the distal lung to investigate the role of physical forces associated with cyclic breathing motions in lung innate immune responses to viral infection. When the mechanically active Alveolus Chips are infected with the influenza H3N2 virus, a cascade of host responses is elicited on-chip, including increased production of cytokines and expression of inflammation-associated genes in pulmonary epithelial and endothelial cells, resulting in enhanced recruitment of circulating immune cells as occurs during viral infection in vivo. Surprisingly, studies carried out in parallel with static chips revealed that physiological breathing motions suppress viral replication by activating protective innate immune responses in epithelial and endothelial cells. This is mediated at least in part through upregulation of S100 calcium-binding protein A7 (S100A7), which binds to the Receptor for Advanced Glycation End Products (RAGE), an inflammatory mediator that is most highly expressed in the lung alveolusin vivo. This mechano-immunological control mechanism is further supported by the finding that existing RAGE inhibitor drugs can suppress the production of inflammatory cytokines in response to influenza virus infection in this model. S100A7-RAGE interactions and modulation of mechanical ventilation parameters could therefore serve as new targets for therapeutic intervention in patients infected with influenza and other potential pandemic viruses that cause life-threatening lung inflammation.
EVALUATION OF TAURINE’S NEUROPROTECTIVE EFFECTS ON SH-SY5Y CELLS UNDER OXIDATIVE STRESS
Authors: Rossato Rafaella Carvalho , Granato Alessandro Eustaquio Campos , Pinto Jessica Cristina , de Oliveira Moraes Carlos Dailton Guedes , Salles Geisa Nogueira , Soares Cristina Pacheco 
Published: April 2021

ABSTRACTAlzheimer’s disease (AD) is a type of dementia that affects millions of people. Although there is no cure, several study strategies seek to elucidate the mechanisms of the disease. Recent studies address the benefits of taurine. Thus, the present study aims to analyze the neuroprotective effect of taurine on human neuroblastoma, using anin vitroexperimental model of oxidative stress induced by hydrocortisone in the SH-SY5Y cell line as a characteristic model of AD. The violet crystal assay was used for cell viability and the evaluation of cell morphology was performed by scanning electron microscopy (SEM). After pretreatment with taurine, the SH-SY5Y cell showed an improvement in cell viability in the face of oxidative stress and improved cell morphology. Thus, the treatment presented a neuroprotective effect.GRAPHICAL ABSTRACT
Seed banks alter metacommunity diversity: the interactive effects of competition, germination, and survival
Authors: Wisnoski Nathan I. , Shoemaker Lauren G. 
Published: April 2021

AbstractDispersal and dormancy are two common strategies allowing for species persistence and the maintenance of ecological diversity in variable environments. However, theory and empirical tests of spatial diversity patterns tend to examine either mechanism in isolation. Here, we developed a stochastic, spatially explicit metacommunity model incorporating seed banks with varying germination and survival rates. We found that dormancy and dispersal had interactive, nonlinear effects on the maintenance and distribution of metacommunity diversity, where scale-dependent effects of seed banks were modified by local competitive interactions and dispersal. The interplay between seed germination and survival regulated the benefits of seed banks for diversity. Our study shows that the role of seed banks depends critically on spatial processes, and that classic predictions for how dispersal affects metacommunity diversity can be strongly influenced by dormancy. Together, these results highlight the need to consider both temporal and spatial storage when predicting multi-scale patterns of diversity.
Sensory evidence accumulation using optic flow in a naturalistic navigation task
Authors: Alefantis Panos , Lakshminarasimhan Kaushik J. , Avila Eric , Noel Jean-Paul , Pitkow Xaq , Angelaki Dora E. 
Published: April 2021

AbstractSensory evidence accumulation is considered a hallmark of decision-making in noisy environments. Integration of sensory inputs has been traditionally studied using passive stimuli, segregating perception from action. Lessons learned from this approach, however, may not generalize to ethological behaviors like navigation, where there is an active interplay between perception and action. We designed a sensory-based sequential decision task in virtual reality in which humans and monkeys navigated to a memorized location by integrating optic flow generated by their own joystick movements. A major challenge in such closed-loop tasks is that subjects’ actions will determine future sensory input, causing ambiguity about whether they rely on sensory input rather than expectations based solely on a learned model of the dynamics. To test whether subjects performed sensory integration, we used three independent experimental manipulations: unpredictable optic flow perturbations, which pushed subjects off their trajectory; gain manipulation of the joystick controller, which changed the consequences of actions; and manipulation of the optic flow density, which changed the reliability of sensory evidence. Our results suggest that both macaques and humans relied heavily on optic flow, thereby demonstrating a critical role for sensory evidence accumulation during naturalistic action-perception closed-loop tasks.
Cdc42activity in Sertoli cells is essential for maintenance of spermatogenesis
Authors: Bhandary Bidur , Heinrich Anna , Potter Sarah J. , Ratner Nancy , DeFalco Tony 
Published: April 2021

SUMMARYSertoli cells are highly polarized testicular supporting cells that simultaneously nurture progressively maturing germ cells. Proper localization of polarity protein complexes within Sertoli cells, including those responsible for blood-testis barrier formation, are vital for successful spermatogenesis. However, the mechanisms and developmental timing that underlie the establishment of polarity are poorly understood. To investigate this aspect of testicular function, we conditionally deletedCdc42, encoding a Rho GTPase involved in regulating cell polarity, specifically in Sertoli cells.Cdc42deletion disrupted adult Sertoli cell maturation and localization of polarity proteins, but did not affect fetal and early postnatal testicular development, nor the onset of the first wave of spermatogenesis. By early adulthood, however, conditional knockout males exhibited a loss of spermatogenic cells, resulting in a complete lack of sperm. These findings demonstrate thatCdc42plays an essential role in establishing adult Sertoli cell polarity and, thus, maintaining steady-state spermatogenesis and healthy sperm production.
Ancient gene duplications, rather than polyploidization, facilitate diversification of petal pigmentation patterns inClarkia gracilis(Onagraceae)
Authors: Lin Rong-Chien , Rausher Mark D. 
Published: April 2021

AbstractIt has been suggested that gene duplication and polyploidization create opportunities for the evolution of novel characters. However, the connections between the effects of polyploidization and morphological novelties have rarely been examined. In this study, we investigated whether petal pigmentation patterning in an allotetraploidClarkia gracilishas evolved as a result of polyploidization.C.gracilisis thought to be derived through a recent polyploidization event with two diploid species,C.amoena huntianaand an extinct species that is closely related toC.lassenensis. We reconstructed phylogenetic relationships of theR2R3-MYBs (the regulators of petal pigmentation) from two subspecies ofC.gracilisand the two purported progenitors,C.a.huntianaandC.lassenensis. The gene tree reveals that theseR2R3-MYBgenes have arisen through duplications that occurred before the divergence of the two progenitor species, i.e., before polyploidization. After polyploidization and subsequent gene loss, only one of the two orthologous copies inherited from the progenitors was retained in the polyploid, turning it to diploid inheritance. We examined evolutionary changes in theseR2R3-MYBs and in their expression, which reveals that the changes affecting patterning (including expression domain contraction, loss-of-function mutation,cis-regulatory mutation) occurred after polyploidization within theC.gracilislineages. Our results thus suggest that polyploidization itself is not necessary in producing novel petal color patterns. By contrast, duplications ofR2R3-MYBgenes in the common ancestor of the two progenitors have apparently facilitated diversification of petal pigmentation patterns.
Attitude towards entrepreneurship development courses of MOOCs
Authors: Ahmed Md. Meraz , Sultana Naveed , Astri Dwi Jayanti Suhandoko , Mardoni Yosi , Helmiatin Helmiatin 
Published: April 2021

PurposeThe purpose of the study was to explore the attitude of faculty members and students of two open universities – Bangladesh Open University (BOU) and Universitas Terbuka (UT) (Open University of Indonesia) towards entrepreneurship development courses of massive open online courses (MOOCs).Design/methodology/approachThe mixed-method research design was employed for this study. A self-structured survey questionnaire and focus group discussions (FGDs) were used to collect quantitative and qualitative data. A total of 66 faculty members and 149 tertiary level students of BOU and UT were selected as respondents. These respondents were selected using purposive sampling techniques. Data were analysed using quantitative and qualitative data analysis techniques.FindingsThe findings revealed that both universities' faculty members and students possessed a positive attitude towards entrepreneurship development courses of MOOCs (EDCM). However, this positive attitude of both groups was significantly different.Originality/valueThe policy recommendations could provide a strategic approach to developing various types of courses within the MOOC, which are attractive as a means of developing entrepreneurship in Bangladesh and Indonesia. It also aggressively promotes EDCM for the academic community in particular and society, in general, to elaborate on their entrepreneurial spirit. Nevertheless, before introducing MOOCs, an empirical study regarding MOOCs readiness is essential for both universities.