bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lacking social support is associated with structural divergences in hippocampus-default network co-variation patterns
Authors: Zajner Chris , Spreng Nathan , Bzdok Danilo 
Published: August 2021

AbstractElaborate social interaction is a pivotal asset of the human species. The complexity of people’s social lives may constitute the dominating factor in the vibrancy of many individuals’ environment. The neural substrates linked to social cognition thus appear especially susceptible when people endure periods of social isolation: here, we zoom in on the systematic inter-relationships between two such neural substrates, the allocortical hippocampus (HC) and the neocortical default network (DN). Previous human social neuroscience studies have focused on the DN, while HC subfields have been studied in most detail in rodents and monkeys. To bring into contact these two separate research streams, we directly quantified how DN subregions are coherently co-expressed with specific HC subfields in the context of social isolation. A two-pronged decomposition of structural brain scans from ∼40,000 UK Biobank participants linked lack of social support to mostly lateral subregions in the DN patterns. This lateral DN association co-occurred with HC patterns that implicated especially subiculum, presubiculum, CA2, CA3, and dentate gyrus. Overall, the subregion divergences within spatially overlapping signatures of HC-DN co-variation followed a clear segregation divide into the left and right brain hemispheres. Separable regimes of structural HC-DN co-variation also showed distinct associations with the genetic predisposition for lacking social support at the population level.
Pancreatic ductal adenocarcinoma cells employ integrin α6β4 to form hemidesmosomes and regulate cell proliferation
Authors: Humphries Jonathan D. , Zha Junzhe , Burns Jessica , Askari Janet A. , Below Christopher R. , Chastney Megan R. , Jones Matthew C. , Mironov Aleksandr , Knight David , O’Reilly Derek A. , Dunne Mark J. , Garrod David R. , Jorgensen Claus , Humphries Martin J. 
Published: August 2021

AbstractPancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis due to its aggressive progression, late detection and lack of druggable driver mutations, which often combine to result in unsuitability for surgical intervention. Together with activating mutations of the small GTPase KRas, which are found in over 90% of PDAC tumours, a contributory factor for PDAC tumour progression is formation of a rigid extracellular matrix (ECM) and associated desmoplasia. This response leads to aberrant integrin signalling, and accelerated proliferation and invasion. To identify the integrin adhesion systems that operate in PDAC, we analysed a range of pancreatic ductal epithelial cell models using 2D, 3D and organoid culture systems. Proteomic analysis of isolated integrin receptor complexes from human pancreatic ductal epithelial (HPDE) cells predominantly identified integrin α6β4 and hemidesmosome components, rather than classical focal adhesion components. Electron microscopy, together with immunofluorescence, confirmed the formation of hemidesmosomes by HPDE cells, both in 2D and 3D culture systems. Similar results were obtained for the human PDAC cell line, SUIT-2. Analysis of HPDE cell secreted proteins and cell-derived matrices (CDM) demonstrated that HPDE cells secrete a range of laminin subunits and form a hemidesmosome-specific, laminin 332-enriched ECM. Expression of mutant KRas (G12V) did not affect hemidesmosome composition or formation by HPDE cells. Cell-ECM contacts formed by mouse and human PDAC organoids were also assessed by electron microscopy. Organoids generated from both the PDAC KPC mouse model and human patient-derived PDAC tissue displayed features of acinar-ductal cell polarity, and hemidesmosomes were visible proximal to prominent basement membranes. Furthermore, electron microscopy identified hemidesmosomes in normal human pancreas. Depletion of integrin β4 using siRNA reduced cell proliferation in both SUIT-2 and HPDE cells, reduced the number of SUIT-2 cells in S-phase, and induced G1 cell cycle arrest, indicating a requirement for α6β4-mediated adhesion for cell cycle progression and growth. Taken together, these data suggest that laminin-binding adhesion mechanisms in general, and hemidesmosome-mediated adhesion in particular, may be under-appreciated in the context of PDAC.Proteomic data are available via ProteomeXchange with the identifiers PXD027803, PXD027823 and PXD027827.
Ethology of morphogenesis reveals the design principles of cnidarian size and shape development
Authors: Stokkermans Anniek , Chakrabarti Aditi , Wang Ling , Moghe Prachiti , Subramanian Kaushikaram , Steenbergen Petrus , Mönke Gregor , Hiiragi Takashi , Prevedel Robert , Mahadevan L. , Ikmi Aissam 
Published: August 2021

SummaryDuring development, organisms interact with their natural habitats while undergoing morphological changes, yet it remains unclear whether the interplay between developing systems and their environments impacts animal morphogenesis. Here, we use the cnidarianNematostella vectensisas a developmental model to uncover a mechanistic link between organism size, shape and behavior. Using quantitative live imaging, including extensive behavioral profiling, combined with molecular and biophysical experiments, we demonstrate that the muscular hydraulic machinery that controls body movement directly drives larva-polyp morphogenesis. Unexpectedly, size and shape development are differentially controlled by antagonistic muscles. A simple theoretical model shows how a combination of slow-priming and fast-pumping pressures generated by muscular hydraulics acts as a global mechanical regulator that coordinates tissue remodeling. Altogether, our findings illuminate how dynamic behavioral modes in the environment can be harnessed to drive morphogenetic trajectories, establishing ethology as a critical component of organismal morphogenesis – termed ethology of morphogenesis.
GFAP splice variants fine-tune glioma cell invasion and tumour dynamics by modulating migration persistence
Authors: van Asperen Jessy V. , Uceda-Castro Rebeca , Vennin Claire , Sluijs Jacqueline , van Bodegraven Emma J. , Margarido Andreia S. , Robe Pierre A.J. , van Rheenen Jacco , Hol Elly M. 
Published: August 2021

AbstractGlioma is the most common form of malignant primary brain tumours in adults. Their highly invasive nature makes the disease incurable to date, emphasizing the importance of better understanding the mechanisms driving glioma invasion. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is characteristic for astrocyte- and neural stem cell-derived gliomas. Glioma malignancy is associated with changes in GFAP alternative splicing, as the canonical isoform GFAPα is downregulated in higher-grade tumours, leading to increased dominance of the GFAPδ isoform in the network. In this study, we used intravital imaging and anex vivobrain slice invasion model. We show that the GFAPδ and GFAPα isoforms differentially regulate the tumour dynamics of glioma cells. Depletion of either isoform increases the migratory capacity of glioma cells. Remarkably, GFAPδ-depleted cells migrate randomly through the brain tissue, whereas GFAPα-depleted cells show a directionally persistent invasion into the brain parenchyma. This study shows that distinct compositions of the GFAP-network lead to specific migratory dynamics and behaviours of gliomas.
New relationships are not necessarily more variable: female degus are more consistent with strangers, male degus are less
Authors: Thatcher Amber , Insel Nathan 
Published: August 2021

AbstractWhen an organism explores a new environment or stimulus it varies its behavior to ensure proper sampling. As contingencies are learned, variance can give-way to routines and stereotypies. This phenomenon is common across species but has not been well studied in the social domain, in which the stimulus an animal investigates, another individual, may react negatively to unexpected behaviors. Here we investigate the effects of social familiarity on interaction variability in degus, female members of which are predisposed to form relationships with new, same-sex individuals. Degus were presented with a series of 20 minute, dyadic “reunion” sessions across days, interleaving exposures to familiar and unfamiliar same-sex conspecifics. We found that session-to-session variability in males was higher between strangers compared with cagemates, suggesting males may establish relationships by testing different social roles. In contrast, following an initial exposure, female strangers showed lower session-to-session change compared with cagemates, potentially establishing new relationships by maintaining behavioral norms. Social novelty did not appear to affect variability of interaction timing within a session. Given ecological pressures on female degus to form large, stable social networks, the data are consistent with the notion that higher behavioral variability across encounters is maladaptive for establishing cooperative peer relationships.
A human stem cell resource to decipher the biochemical and cellular basis of neurodevelopmental defects in Lowe Syndrome
Authors: Akhtar Bilal M. , Bhatia Priyanka , Acharya Shubhra , Sharma Sanjeev , Sharma Yojet , Aswathy BS , Ganapathy Kavina , Vasudevan Anil , Raghu Padinjat 
Published: August 2021

AbstractHuman brain development is a complex process where multiple cellular and developmental events are co-ordinated to generate normal structure and function. Alteration in any of these events can impact brain development, manifesting clinically as neurodevelopmental disorders. Human genetic disorders of lipid metabolism often present with features of altered brain function. Lowe syndrome (LS), is a X-linked recessive disease with features of altered brain function. LS results from mutations in OCRL1 that encodes a phosphoinositide 5-phosphatase enzyme. However, the cellular mechanisms by which loss of OCRL1 leads to brain defects remain unknown. Human brain development involves several cellular and developmental features not conserved in other species and understanding such mechanisms remains a challenge. Rodent models of LS have been generated, but failed to recapitulate features of the human disease. Here we describe the generation of human stem cell lines from LS patients. Further, we present biochemical characterization of lipid metabolism in patient cell lines and demonstrate their use as a “disease-in-a-dish” model for understanding the mechanism by which loss of OCRL1 leads to altered cellular and physiological brain development.
Liquid-liquid phase separation of florigen activation complex induces flowering
Authors: Taoka Ken-ichiro , Tsuji Hiroyuki , Anzawa Suai , Enomoto Mayu , Koizumi Yuka , Nakamura Juri , Tanaka Mari , Fujita Akiko , Furuita Kyoko , Kodama Takashi S. , Fujimoto Masaru , Kurokawa Kazuo , Okamoto Takashi , Fujiwara Toshimichi , Nakano Akihiko , Kojima Chojiro 
Published: August 2021

AbstractFloral transition, regulated by the systemic action of the mobile florigen protein FLOWERING LOCUS T (FT), is essential for successful plant reproduction1. How FT controls downstream gene expression remains incompletely understood, although it relies on the florigen activation complex (FAC), a core component of FT function2–4. The FAC is a nucleus-localized transcriptional activator of genes encoding MADS-box transcription factors critical to reproductive development and consists of florigen FT; a scaffold 14-3-3 protein that is a key component for complex assembly; and FD, a basic leucine-zipper protein that recruits the FAC to DNA. Here we report that the FAC exhibits phase separation. In rice shoot apical meristem cells, rice florigen Heading date 3a (Hd3a) fused to the green fluorescent protein formed speckles in the nucleus. The FAC speckle is formed in a FAC-dependent manner in tobacco cells. Recombinant Hd3a, but not OsFD1, phase-separated in vitro, and this effect was enhanced in the presence of 14-3-3 protein. Furthermore, mutations affecting functionally important residues in the pocket region or C-terminal disordered region of Hd3a affected FAC phase separation, providing a biochemical framework for the protein’s effect on flowering. The ability to form condensates via phase transition represents a previously unknown mechanism for gene activation by the FAC.
A generic sequential stimulation adapter for reducing muscle fatigue during functional electrical stimulation
Authors: Ye Gongkai , Ali Saima , Bergquist Austin J. , Popovic Milos R. , Masani Kei 
Published: August 2021

AbstractBackgroundClinical applications of conventional functional electrical stimulation (FES) administered via a single electrode is limited by rapid onset neuromuscular fatigue. “Sequential” (SEQ) stimulation, involving rotation of pulses between multiple active electrodes, has been shown to reduce fatigue compared to conventional FES. However, there has been limited adoption of SEQ in research and clinical settings.MethodsThe SEQ adapter is a small, battery-powered device that transforms the output of any commercially available electrical stimulator into SEQ stimulation. We examined the output of the adaptor across a range of clinically relevant stimulation pulse parameters to verify the signal integrity preservation ability of the SEQ adapter. Pulse frequency, amplitude, and duration were varied across discrete states between 4-200 Hz, 10-100 mA, and 50-2000 μs, respectively.ResultsA total of 420 trials were conducted, with 80 stimulation pulses per trial. The SEQ adapter demonstrated excellent preservation of signal integrity, matching the pulse characteristics of the originating stimulator within 1% error. The SEQ adapter operates as expected at pulse frequencies up to 160 Hz, with a noted failure mode at 200 Hz.ConclusionThe SEQ adapter represents an effective and low-cost solution to increase the utilization of SEQ in existing rehabilitation paradigms.
Prospects of raising baobab (Adansonia digitata L.) to fruiting in two years
Authors: Egbadzor Kenneth Fafa , Akuaku Jones 
Published: August 2021

AbstractBaobab is a very important plant with several uses, serving as food security crop and has the potential to raise income of farmers. However, the plant is undomesticated. We have the objective of domesticating the plant and promote its cultivation and utilization. Seeds were treated with sulphuric acid for early germination and grafted with matured scions suspected to be fruiting for several years. Twenty-two of the seedlings were transplanted on the field at Ho Technical University campus. Unfortunately, only four survived bushfire and destruction by stray animals. Surprisingly, one of the four surviving trees anthesis within twenty-eight months after seed treatment (twenty months after transplanting). This is the earliest ever reported anthesis of baobab. With better agronomic practices such as supplementary irrigation, insect pest control, manuring and protection from stray animals, baobab could start fruiting within two years of planting. This would alleviate fear of long maturity period and motivate farmers to go into baobab plantation. This would help diversify agriculture in many African countries, increase income and food security and contribute towards the attainment of the sustainable development goals of the United Nations.
Analysis of migration of pathogenic drug-resistant bacteria to soils and groundwater after fertilization with sewage sludge
Authors: Stańczyk-Mazanek Ewa , Stępniak Longina 
Published: August 2021

AbstractThe paper discusses the analysis of the effect of using sewage sludge for fertilization on the level of soil and groundwater contamination with drug-resistant bacteria. Other sanitary contaminants in these environments were also analysed. Composted sewage sludge was introduced into the sandy soil over a period of 6 months. The examinations were conducted under conditions of a lysimetric experiment with the possibility of collecting soil leachates (in natural conditions). The following doses of sewage sludge were used: 0, 10, 20, 30 and 40 t/ha calculated per experimental object containing 10 kg of sandy soil. The research were carried out within the time frame of one year. Dactylis glomerata grass was grown on the fertilized soils. In soils and leachates from soils (which may have polluted groundwater) collected from fertilized experimental objects, the sanitary condition and quantity of drug-resistant bacteria (mainly from the families Enterobacteriaceae and Enterococcus) were analysed one year after fertilization. Their drug resistance to selected antibiotics was also analysed based on current recommendations.
An siRNA-guided Argonaute protein directs RNA Polymerase V to initiate DNA methylation
Authors: Sigman Meredith J. , Panda Kaushik , Kirchner Rachel , McLain Lauren L. , Payne Hayden , Peasari John Reddy , Husbands Aman Y. , Slotkin R. Keith , McCue Andrea D. 
Published: August 2021

AbstractIn mammals and plants, cytosine DNA methylation is essential for the epigenetic repression of transposable elements and foreign DNA. In plants, DNA methylation is guided by small interfering RNAs (siRNAs) in a self-reinforcing cycle termed RNA-directed DNA methylation (RdDM). RdDM requires the specialized RNA Polymerase V (Pol V), and the key unanswered question is how Pol V is first recruited to new target sites without preexisting DNA methylation. We find that Pol V follows and is dependent upon the recruitment of an AGO4-clade ARGONAUTE protein, and any siRNA can guide the ARGONAUTE protein to the new target locus independent of preexisting DNA methylation. These findings reject long-standing models of RdDM initiation and instead demonstrate that siRNA-guided ARGONAUTE targeting is necessary, sufficient and first to target Pol V recruitment and trigger the cycle of RdDM at a transcribed target locus, thereby establishing epigenetic silencing.
Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration
Authors: Senabouth Anne , Daniszewski Maciej , Lidgerwood Grace E. , Liang Helena H. , Hernández Damián , Mirzaei Mehdi , Zhang Ran , Han Xikun , Neavin Drew , Rooney Louise , Sanchez Isabel Lopez , Gulluyan Lerna , Paulo Joao A , Clarke Linda , Kearns Lisa S , Gnanasambandapillai Vikkitharan , Chan Chia-Ling , Nguyen Uyen , Steinmann Angela M , Zekanovic Rachael , Farbehi Nona , Gupta Vivek K. , Mackey David A , Bylsma Guy , Verma Nitin , MacGregor Stuart , Guymer Robyn H , Powell Joseph E. , Hewitt Alex W. , Pébay Alice 
Published: August 2021

AbstractInduced pluripotent stem cells generated from patients with geographic atrophy as well as healthy individuals were differentiated to retinal pigment epithelium (RPE) cells. By integrating transcriptional profiles of 127,659 RPE cells generated from 43 individuals with geographic atrophy and 36 controls with genotype data, we identified 439 expression Quantitative Trait (eQTL) loci in cis that were associated with disease status and specific to subpopulations of RPE cells. We identified loci linked to two genes with known associations with geographic atrophy - PILRB and PRPH2, in addition to 43 genes with significant genotype x disease interactions that are candidates for novel genetic associations for geographic atrophy. On a transcriptome-only level, we identified molecular pathways significantly upregulated in geographic atrophy-RPE including in extracellular cellular matrix reorganisation, neurodegeneration, and mitochondrial functions. We subsequently implemented a large-scale proteomics analysis, confirming modification in proteins associated with these pathways. We also identified six significant protein (p) QTL that regulate protein expression in the RPE cells and in geographic atrophy - two of which share variants with cis-eQTL. Transcriptome-wide association analysis identified genes at loci previously associated with age-related macular degeneration. Further analysis conditional on disease status, implicated statistically significant RPE-specific eQTL. This study uncovers important differences in RPE homeostasis associated with geographic atrophy.
GinJinn2: Object detection and segmentation for ecology and evolution
Authors: Ott Tankred , Lautenschlager Ulrich 
Published: August 2021

AbstractProper collection and preparation of empirical data still represent one of the most important, but also expensive steps in ecological and evolutionary/systematic research. Modern machine learning approaches, however, have the potential to automate a variety of tasks, which until recently could only be performed manually. Unfortunately, the application of such methods by researchers outside the field is hampered by technical difficulties, some of which, we believe, can be avoided.Here, we present GinJinn2, a user-friendly toolbox for deep learning-based object detection and instance segmentation on image data. Besides providing a convenient command-line interface to existing software libraries, it comprises several additional tools for data handling, pre- and postprocessing, and building advanced analysis pipelines.We demonstrate the application of GinJinn2 for biological purposes using four exemplary analyses, namely the evaluation of seed mixtures, detection of insects on glue traps, segmentation of stomata, and extraction of leaf silhouettes from herbarium specimens.GinJinn2 will enable users with a primary background in biology to apply deep learning-based methods for object detection and segmentation in order to automate feature extraction from image data.
Constitutive signal bias mediated by the human GHRHR splice variant 1
Authors: Cong Zhaotong , Zhou Fulai , Zhang Chao , Zou Xinyu , Zhang Huibing , Wang Yuzhe , Zhou Qingtong , Cai Xiaoqing , Liu Qiaofeng , Li Jie , Shao Lijun , Mao Chunyou , Wang Xi , Wu Jihong , Xia Tian , Zhao Lihua , Jiang Hualiang , Zhang Yan , Eric Xu H. , Cheng Xi , Yang Dehua , Wang Ming-Wei 
Published: August 2021

AbstractAlternative splicing of G protein-coupled receptors has been observed, but their functions are largely unknown. Here, we report that a splice variant (SV1) of the human growth hormone releasing hormone receptor (GHRHR) is capable of transducing biased signal. Differing only at the receptor N terminus, GHRHR predominantly activates Gs while SV1 selectively couples to β-arrestins. Based on the cryo-electron microscopy structures of SV1 in the apo state or in complex with the Gs protein, molecular dynamics simulations reveal that the N termini of GHRHR and SV1 differentiate the downstream signaling pathways, Gsvs. β-arrestins. Suggested by mutagenesis and functional studies, it appears that GHRH-elicited signal bias towards β-arrestin recruitment is constitutively mediated by SV1. The level of SV1 expression in prostate cancer cells is also positively correlated with ERK1/2 phosphorylation but negatively correlated with cAMP response. Our findings imply that constitutive signal bias may be a mechanism that ensures cancer cell proliferation.Significance StatementThe mechanism of functional changes induced by alternative splicing of GHRHR is largely unknown. Here, we demonstrate that GHRH-elicited signal bias towards β-arrestin recruitment is constitutively mediated by SV1. The cryo-electron microscopy structures of SV1 and molecular dynamics simulations reveal the different functionalities between GHRHR and SV1 at the near-atomic level, i.e., the N termini of GHRHR and SV1 differentiate the downstream signaling pathways, Gsvs. β-arrestins. Our findings provide valuable insights into functional diversity of class B1 GPCRs which may aid in the design of better therapeutic agents against certain cancers.