bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of prolonged captivity on the hemolymph profile ofTachypleus gigas
Authors: Akbar John B. , Sheikh Hassan I , Solachuddin J.A. Ichwan , Kamaruzzaaman B.Y. 
Published: April 2020

ABSTRACTHorseshoe crabs amebocyte cells degranulate to form a gel clot when in contact with endotoxins. This phenomenon is the basis of both Horseshoe crab immune system and detection of endotoxin in biologicals. The present study investigates the amebocyte cells quality inTachypleus gigaspre and post bleeding under captivity. Wild and captive horseshoe crabs (5 months captivity) were bled in 6 anticoagulant formulations (A, B, C, D, E and F). No profound difference in cell density between captive and wild groups with the mean value of 0.883×107a cells/mL and 0.917×107cells/mL, respectively. while, the cell viability of the captive group was significantly lower than the wild crabs (F=808.075, p<0.001). Anticoagulant formulation significantly affected cell viability and cell morphology in both captive and wild groups (p<0.001). Amebocyte cells collected from the wildT. gigasusing optimum anticoagulant (formula C) showed 0.6 ×107cells/mL cell density and 86.9% cell viability, while morphology analysis revealed the percentage of contracted, granular flattened and degranulated flattened cells were 14.62%, 71.39% and 14%, respectively. The anticoagulant formulations showed varying capabilities in maintaining cell viability due to its buffering and chelating capacity. We conclude that captivity has a negative effect on the amebocyte cell quality.HIGHLIGHTSCaptivity has a negative impact on amebocyte quality in horseshoe crab (Tachypleus gigas).No significant difference in cell density between captive and wild crabs.Anticoagulant formulations have significant impact on the cell density, viability and morphologyCaptive crabs were immunocompromised due to single specific feed intake.
Complementary α-arrestin - Rsp5 ubiquitin ligase complexes control selective nutrient transporter endocytosis in response to amino acid availability
Authors: Ivashov Vasyl , Zimmer Johannes , Schwabl Sinead , Kahlhofer Jennifer , Weys Sabine , Gstir Ronald , Jakschitz Thomas , Kremser Leopold , Bonn Günther K. , Lindner Herbert , Huber Lukas A. , Léon Sébastien , Schmidt Oliver , Teis David 
Published: April 2020

AbstractHow cells adjust transport across their membranes is incompletely understood. Previously, we have shown thatS.cerevisiaebroadly re-configures the nutrient transporters at the plasma membrane in response to amino acid availability, through selective endocytosis of sugar- and amino acid transporters (AATs) (Müller et al., 2015). A genome-wide screen now revealed that Art2/Ecm21, a member of the α-arrestin family of Rsp5 ubiquitin ligase adaptors, is required for the simultaneous endocytosis of four AATs and induced during starvation by the general amino acid control pathway. Art2 uses a basic patch to recognize C-terminal acidic sorting motifs in these AATs and instructs Rsp5 to ubiquitinate proximal lysine residues. In response to amino acid excess, Rsp5 instead uses TORC1-activated Art1 to detect N-terminal acidic sorting motifs within the same AATs, which initiates exclusive substrate-induced endocytosis of individual AATs. Thus, amino acid availability activates complementary α-arrestin-Rsp5-complexes to control selective endocytosis for nutrient acquisition.
Gene expression in the cardiovascular system of the domestic sheep (Ovis aries); a new tool to advance our understanding of cardiovascular disease
Authors: Tsang Hiu-Gwen , Clark Emily L. , Markby Greg R. , Bush Stephen J. , Hume David A. , Corcoran Brendan M. , MacRae Vicky E. , Summers Kim M. 
Published: April 2020

AbstractLarge animal models are of increasing importance in cardiovascular disease research as they demonstrate more similar cardiovascular features (in terms of anatomy, physiology and size) to humans than do rodent species. The maintenance of a healthy cardiovascular system requires expression of genes that contribute to essential biological activities and repression of those that are associated with functions likely to be detrimental to cardiovascular homeostasis. In this study we have used the transcriptome of the sheep, which has been utilised extensively to model human physiology and disease, to explore genes implicated in the process of vascular calcification. Vascular calcification is a major disruption to cardiovascular homeostasis where tissues of the cardiovascular system undergo ectopic calcification and consequent dysfunction. We investigate the gene expression profiles of genes involved in vascular calcification in a wide array of cardiovascular tissues and across multiple developmental stages, using RT-qPCR. The majority of transcriptomic studies on the mammalian cardiovascular system to date have focused on regional expression of specific genes. Here we also use RNA sequencing results from the sheep heart and cardiac valves to further explore the transcriptome of the cardiovascular system in this large animal. Our results demonstrate that there is a balance between genes that promote and those that suppress mineralisation during development and across cardiovascular tissues. We show extensive expression of genes encoding proteins involved in formation and maintenance of the extracellular matrix in cardiovascular tissues, and high expression of haematopoietic genes in the cardiac valves. Our analysis will support future research into the functions of implicated genes in the development of vascular calcification, and increase the utility of the sheep as a large animal model for understanding cardiovascular disease. This study provides a foundation to explore the transcriptome of the developing cardiovascular system and is a valuable resource for the fields of mammalian genomics and cardiovascular research.
TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration
Authors: Qiao Wei , Wong Karen H.M. , Shen Jie , Wang Wenhao , Wu Jun , Li Jinhua , Lin Zhengjie , Chen Zetao , Matinlinna Jukka P. , Zheng Yufeng , Wu Shuilin , Liu Xuanyong , Lai Keng Po , Chen Zhuofan , Lam Yun Wah , Cheung Kenneth M.C. , Yeung Kelvin W.K. 
Published: April 2020

AbstractThe use of magnesium ion (Mg2+)-modified biomaterials in bone regeneration is a promising and cost-effective therapeutic. Despite the widespread observation on the osteogenic effects of Mg2+, the diverse roles played by Mg2+in the complex biological process of bone healing have not been systematically dissected. Here, we reveal a previously unknown biphasic mode of action of Mg2+in bone repair. In the early inflammation phase, Mg2+primarily targets the monocyte-macrophage lineage to promote their recruitment, activation, and polarization. We showed that an increase in extracellular Mg2+contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7) and a TRPM7-dependent influx of Mg2+in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines like IL-8, leading to the formation of a pro-osteogenic immune microenvironment. In the later active repair/remodeling phase of bone healing, however, continued exposure of Mg2+and IL-8 leads to over activation of NF-κB signaling in macrophages, turning the immune microenvironment into pro-osteoclastogenesis. Moreover, the presence of Mg2+at this stage also decelerates bone maturation through the suppression of hydroxyapatite precipitation. The negative effects of Mg2+on osteogenesis can override the initial pro-osteogenic benefits of Mg2+, as we found prolonged delivery of Mg2+compromises overall bone formation. Taken together, this study establishes a paradigm shift in understanding the diverse and multifaceted roles of Mg2+in bone healing.
Comparison of the Hi-C, GAM and SPRITE methods by use of polymer models of chromatin
Authors: Fiorillo Luca , Musella Francesco , Kempfer Rieke , Chiariello Andrea M. , Bianco Simona , Kukalev Alexander , Irastorza-Azcarate Ibai , Esposito Andrea , Conte Mattia , Prisco Antonella , Pombo Ana , Nicodemi Mario 
Published: April 2020

AbstractPowerful technologies have been developed to probe chromatin 3D physical interactions genome-wide, such as Hi-C, GAM and SPRITE. Due to their intrinsic differences and without a benchmarking reference, it is currently difficult to assess how well each method represents the genome 3D structure and their relative performance. Here, we develop a computational approach to implement Hi-C, GAM and SPRITEin-silicoto compare the three methods in a simplified, yet controlled framework against known polymer 3D structures. We test our approach on models of three 6-Mb genomic regions, around theSox9and theHoxDgenes in mouse ES cells, and around theEpha4gene in mouse CHLX-12 cells. The model-derived contact matrices consistently match Hi-C, GAM and SPRITE experiments. We show thatin-silicoHi-C, GAM and SPRITE average data are overall faithful to the 3D structures of the polymer models. We find that the inherent variability of model single-molecule 3D conformations and experimental efficiency differently affect the contact data of the different methods. Similarly, the noise-to-signal levels vary with genomic distance differently inin-silicoHi-C, SPRITE and GAM. We benchmark the performance of each technology in bulk and in single-cell experiments, and identify the minimal number of cells required for replicates to return statistically consistent chromatin contact measures. Under the same experimental conditions, SPRITE requires the lowest number of cells, Hi-C is close to SPRITE, while GAM is the most reproducible method to capture interactions at large genomic distances.
Myomegalin regulates Hedgehog pathway by controlling PDE4D at the centrosome
Authors: Peng Hualing , Zhang Jingyi , Ya Amanda , Ma Winston , Villa Sammy , Sukenik Shahar , Ge Xuecai 
Published: April 2020

AbstractMutations in the Hedgehog (Hh) signaling are implicated in birth defects and cancers, including medulloblastoma, one of the most malignant pediatric brain tumors. Current Hh inhibitors face the challenge of drug resistance and tumor relapse, urging new insights in the Hh pathway regulation. Our previous study revealed how PDE4D controls global levels of cAMP in the cytoplasm to positively regulate Hh signaling; in the present study we found that a specific isoform PDE4D3 is tethered to the centrosome by myomegalin, a centrosome/Golgi associated protein. Myomegalin loss dislocates PDE4D3 from the centrosome, leading to local PKA over-activation and inhibition of the Hh signaling, leaving other PKA-related pathways unaffected. Myomegalin loss suppresses the proliferation of granule neuron precursors, and blocks the growth of medulloblastoma in mouse model. Our findings specify a new regulatory mechanism of the Hh pathway, and highlight an exciting therapeutic avenue for Hh-related cancers with reduced side effects.
Closed loop enhancement and neural decoding of human cognitive control
Authors: Basu Ishita , Yousefi Ali , Crocker Britni , Zelmann Rina , Paulk Angelique C , Peled Noam , Ellard Kristen K , Weisholtz Daniel S , Cosgrove G. Rees , Deckersbach Thilo , Eden Uri T , Eskandar Emad N , Dougherty Darin D , Cash Sydney S , Widge Alik S 
Published: April 2020

AbstractCognitive control is the ability to withhold a default, prepotent response in favor of a more adaptive choice. Control deficits are common across mental disorders, including depression, anxiety, and addiction. Thus, a method for improving cognitive control could be broadly useful in disorders with few effective treatments. Here, we demonstrate closed-loop enhancement of one aspect of cognitive control by direct brain stimulation in humans. We stimulated internal capsule/striatum in participants undergoing intracranial epilepsy monitoring as they performed a cognitive control/conflict task. Stimulation enhanced performance, with the strongest effects from dorsal capsule/striatum stimulation. We then developed a framework to detect control lapses and stimulate in response. This closed-loop approach produced larger behavioral changes than open-loop stimulation, with a slight improvement in performance change per unit of energy delivered. Finally, we decoded task performance directly from activity on a small number of electrodes, using features compatible with existing closed-loop brain implants. Our findings are proof of concept for a new approach to treating severe mental disorders, based on directly remediating underlying cognitive deficits.
DIY-NAMIC behavior: A high-throughput method to measure complex phenotypes in the homecage
Authors: Lee Jun Ho , Capan Selin , Lacefield Clay , Shea Yvonne M. , Nautiyal Katherine M. 
Published: April 2020

AbstractComplex behavioral assessment is becoming increasingly necessary in order to comprehensively assessin vivomanipulations in rodent models. Using operant behavioral paradigms provides rich data sets allowing for the careful analysis of behavioral phenotypes. However, one major limitation in these studies is the expense and work-load that are required using traditional methods. The equipment for commercial operant boxes can be prohibitively expensive, and the daily experimenter effort and mouse costs required for these studies is extensive. Rodents are generally trained on task-specific paradigms for months, tested every day for 5-7 days per week. Additionally, appetitive paradigms usually require food restriction and are also commonly run in the non-active light phase of the rodent circadian rhythm. These limitations make operant behavioral testing especially difficult during adolescence, a time period of interest with regards to the development of adult-like phenotypes and a high-risk period for the development of neuropsychiatric disorders, including those which involve impulsive behavior. In order to address these issues, we developed an automated, inexpensive, open-source method which allows the implementation of most standard operant paradigms in the homecage of rodents in shorter time frames without food restriction, and with much less experimenter effort. All construction and code for the DIY Nautiyal Automated Modular Instrumental Conditioning (DIY-NAMIC) system are open source. We demonstrate their utility here by measuring impulsive behavior in a pharmacology experiment, as well as in adolescent mice.Significance statementRigorous behavioral assessment is critical to understand the neural basis of neuropsychiatric disorders using animal models. Operant behavioral paradigms provide the ability to measure complex phenotypes, however, traditional methods generally require time-consuming daily training for many weeks. We designed, built, and tested an open-source automated homecage system for appetitive instrumental conditioning that enables testing in shorter timeframes with reduced experimenter effort.Abstract Figure
Predicting the presence and titer of rabies virus neutralizing antibodies from low-volume serum samples in low-containment facilities
Authors: Meza Diana K. , Broos Alice , Becker Daniel J. , Behdenna Abdelkader , Willett Brian J. , Viana Mafalda , Streicker Daniel G. 
Published: April 2020

SummarySerology is a core component of the surveillance and management of viral zoonoses. Virus neutralization tests are a gold standard serological diagnostic, but requirements for large volumes of serum and high biosafety containment can limit widespread use. Here, focusing onRabies lyssavirus,a globally important zoonosis, we developed a pseudotype micro-neutralization rapid fluorescent focus inhibition test (pmRFFIT) that overcomes these limitations. Specifically, we adapted an existing micro-neutralization test to use a green fluorescent protein–tagged murine leukemia virus pseudotype in lieu of pathogenic rabies virus, reducing the need for specialized reagents for antigen detection and enabling use in low-containment laboratories. We further used statistical analysis to generate rapid, quantitative predictions of the probability and titer of rabies virus neutralizing antibodies from microscopic imaging of neutralization outcomes. Using 47 serum samples from domestic dogs with neutralizing antibody titers estimated using the fluorescent antibody virus neutralization test (FAVN), pmRFFIT showed moderate sensitivity (78.79%) and high specificity (84.62%). Despite small conflicts, titer predictions were correlated across tests repeated on different dates both for dog samples (r = 0.93), and for a second dataset of sera from wild common vampire bats (r = 0.72, N = 41), indicating repeatability. Our test uses a starting volume of 3.5 μL of serum, estimates titers from a single dilution of serum rather than requiring multiple dilutions and end point titration, and may be adapted to target neutralizing antibodies against alternative lyssavirus species. The pmRFFIT enables high-throughput detection of rabies virus neutralizing antibodies in low-biocontainment settings and is suited to studies in wild or captive animals where large serum volumes cannot be obtained.
Gap junctions deliver malonyl-CoA from soma to germline to support embryogenesis inCaenorhabditis elegans
Authors: Starich Todd A. , Greenstein David 
Published: April 2020

AbstractGap junctions are ubiquitous in metazoans and play critical roles in important biological processes, including electrical conduction and development. Yet, only a few defined molecules passing through gap junction channels have been linked to specific functions. We isolated gap junction channel mutants that reduce coupling between the soma and germ cells in theC. elegansgonad. We provide evidence that malonyl-CoA, the rate-limiting substrate for fatty acid synthesis (FAS), is produced in the soma and delivered through gap junctions to the germline; there it is used by fatty acid synthase to critically support embryonic development. Separation of malonyl-CoA production from its site of utilization facilitates somatic control of germline development. Additionally, we demonstrate that loss of malonyl-CoA production in the intestine negatively impacts germline development independently of FAS. Our results suggest that metabolic outsourcing of malonyl-CoA may be a strategy by which the soma communicates nutritional status to the germline.Impact StatementMalonyl-CoA, the rate-limiting substrate for fatty acid synthesis, is produced in the soma and delivered through gap junctions to the germline to promote reproduction and coordinate it with nutritional status.
HtsRC-mediated accumulation of F-actin regulates ring canal size during Drosophila melanogaster oogenesis
Authors: Gerdes Julianne A. , Mannix Katelynn M. , Hudson Andrew M. , Cooley Lynn 
Published: April 2020

AbstractRing canals in the female germline ofDrosophila melanogasterare supported by a robust filamentous actin (F-actin) cytoskeleton, setting them apart from ring canals in other species and tissues. Previous work has identified components required for the expansion of the ring canal actin cytoskeleton but has not identified the proteins responsible for F-actin recruitment or accumulation. Using a combination of CRISPR-Cas9 mediated mutagenesis and UAS-Gal4 overexpression, we show that HtsRC, a component specific to female germline ring canals, is both necessary and sufficient to drive F-actin accumulation. Absence of HtsRC in the germline resulted in ring canals lacking inner rim F-actin, while overexpression of HtsRC led to larger ring canals. HtsRC functions in combination with Filamin to recruit F-actin to ring-canal-like ectopic actin structures in somatic follicle cells. Finally, we present findings which indicate that HtsRC expression and robust female germline ring canal expansion are important for high fecundity in fruit flies but dispensable for their fertility, a result which is consistent with our understanding of HtsRC as a newly evolved gene specific to female germline ring canals.
Using B cell receptor lineage structures to predict affinity
Authors: Ralph Duncan K. , Matsen Frederick A. 
Published: April 2020

ABSTRACTWe are frequently faced with a large collection of antibodies, and want to select those with highest affinity for their cognate antigen. When developing a first-line therapeutic for a novel pathogen, for instance, we might look for such antibodies in patients that have recovered. There exist effective experimental methods of accomplishing this, such as cell sorting and baiting; how-ever they are time consuming and expensive. Next generation sequencing of B cell receptor (BCR) repertoires offers an additional source of sequences that could be tapped if we had a reliable method of selecting those coding for the best antibodies. In this paper we introduce a method that uses evolutionary information from the family of related sequences that share a naive ancestor to predict the affinity of each resulting antibody for its antigen. When combined with information on the identity of the antigen, this method should provide a source of effective new antibodies. We also introduce a method for a related task: given an antibody of interest and its inferred ancestral lineage, which branches in the tree are likely to harbor key affinity-increasing mutations? These methods are implemented as part of continuing development of the partis BCR inference package, available athttps://github.com/psathyrella/partis.Comments. Please post comments or questions on this paper as new issues athttps://git.io/Jvxkn.