bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying the potential for sustainable human–wildlife coexistence by integrating willingness to coexist with habitat suitability models
Authors: Vogel Susanne Marieke , Vasudev Divya , Ogutu Joseph O. , Taek Purity , Berti Emilio , Goswami Varun R. , Kaelo Michael , Buitenwerf Robert , Munk Michael , Li Wang , Wall Jake , Gelete Desalegn Chala , Amoke Irene , Odingo Alice , Svenning Jens-Christian 
Published: September 2022

AbstractPersistence of large mammals in the Anthropocene depends on human willingness to coexist with them, but this is rarely incorporated into habitat suitability or conservation priority assessments. We propose a framework that integrates human willingness-to-coexist with habitat suitability assessments to identify areas of high potential for sustainable coexistence. We demonstrate its applicability for elephants and rhinos in the socio-ecological system of Maasai Mara, Kenya, by integrating spatial distributions of people’s willingness-to-coexist based on Bayesian hierarchical models using 556 household interviews, with socio-ecological habitat suitability mapping validated with long-term elephant observations from aerial surveys. Willingness-to-coexist was higher if people had little personal experience with a species, and strongly reduced by experiencing a species as a threat to humans. The sustainable coexistence potential framework highlights areas of low socio-ecological suitability, and areas that require more effort to increase positive stakeholder engagement to achieve long-term persistence of large herbivores in human-dominated landscapes.
Regulation of neuropathic pain by microglial Orai1 channels
Authors: Tsujikawa Shogo , DeMeulenaere Kaitlyn E , Centeno Marivi V , Ghazisaeidi Shahrzad , Martin Megan E. , Tapies Martinna R. , Maneshi Mohammad M , Yamashita Megumi , Stauderman Kenneth A , Apkarian Apkar V , Salter Michael W , Prakriya Murali 
Published: September 2022

ABSTRACTMicroglia are important mediators of neuroinflammation that underlies neuropathic pain. However, the molecular checkpoints controlling microglial reactivity are not well-understood. We investigated the role of Orai1 channels for microglia-mediated neuroinflammation following nerve injury and find that deletion of Orai1 in microglia attenuates Ca2+ signaling and the production of inflammatory cytokines by proalgesic agonists. Conditional deletion of Orai1 attenuated microglia proliferation in the dorsal horn, spinal cytokines levels, and potentiation of excitatory neurotransmission following peripheral nerve injury. These cellular effects were accompanied by mitigation of pain hyperalgesia in Orai1 knockout mice. A small-molecule Orai1 inhibitor, CM4620, similarly mitigated allodynia in male mice. Surprisingly, these protective effects were not seen in female mice, revealing striking sexual dimorphism in Orai1 regulation of microglial reactivity and hyperalgesia. These findings indicate that Orai1 channels are key regulators of the sexually dimorphic role of microglia for the neuroinflammation that underlies neuropathic pain.
Molecular Dynamics Simulations Show How Antibodies May Rescue HIV-1 Mutants Incapable of Infecting Host Cells
Authors: Rajendra Dharanish , Maroli Nikhil , Dixit Narendra M , Maiti Prabal K 
Published: September 2022

AbstractHigh mutation and replication rates of HIV-1 result in the continuous generation of variants, allowing it to adapt to changing host environments. Mutations often have deleterious effects, but variants carrying them are rapidly purged. Surprisingly, a particular variant incapable of entering host cells was found to be rescued by host antibodies targeting HIV-1. Understanding the molecular mechanism of this rescue is important to develop and improve antibody-based therapies. To unravel the underlying mechanisms, we performed fully atomistic molecular dynamics simulations of the HIV-1 gp41 trimer responsible for viral entry into host cells, its entry-deficient variant, and its complex with the rescuing antibody. We find that the Q563R mutation, which the entry-deficient variant carries, prevents the native conformation of the gp41 6-helix bundle required for entry and stabilizes an alternative conformation instead. This is the consequence of substantial changes in the secondary structure and interactions between the domains of gp41. Binding of the antibody F240 to gp41 reverses these changes and re-establishes the native conformation, resulting in rescue. To test the generality of this mechanism, we performed simulations with the entry-deficient L565A variant and antibody 3D6. We find that 3D6 binding was able to reverse structural and interaction changes introduced by the mutation and restore the native gp41 conformation. Viral variants may not only escape antibodies but be aided by them in their survival, potentially compromising antibody-based therapies, including vaccination and passive immunization. Our simulation framework could serve as a tool to assess the likelihood of such resistance against specific antibodies.
Gas modulating microcapsules for spatiotemporal control of hypoxia
Authors: Molley Thomas G. , Jiang Shouyuan , Kopecky Chantal , Ranaweera Chavinya D. , Jalandhra Gagan K. , Rnjak-Kovacina Jelena , Kilian Kristopher A. 
Published: September 2022

AbstractOxygen is a vital molecule involved in regulating development, homeostasis, and disease. The oxygen levels in tissue vary from 1 to 8% with deviations having major biological consequences. In this work, we developed an approach to encapsulate enzymes and nanozymes, at an unprecedented loading capacity, which precisely controls the oxygen content in cell culture. Here, a single microcapsule is able to locally perturb the oxygen balance, and varying the concentration and distribution of matrix embedded microcapsules provides spatiotemporal control. We demonstrate attenuation of hypoxia signaling in populations of stem cells, cancer cells, endothelial cells, and cancer spheroids. Capsule containing hydrogel films applied to chick chorioallantoic membranes encourage neovascularization, providing scope for topical treatments or hydrogel wound dressings. We further demonstrate versatility by loading capsules with ceria nanorods as “nanozymes” to modulate active oxygen species with potential as a cytoprotective treatment. The approach can be used in multiple formats, including deposition in hydrogels, as granular solids for 3D bioprinting, and as injectable biomaterials. Overall, this platform’s simplicity and flexibility will prove useful for fundamental studies of oxygen-mediated processes in virtually any in vitro or in vivo format, with scope for inclusion in biomedical materials where controlling hypoxia may be clinically advantageous.
Structural basis of the transcription termination factor Rho engagement with transcribing RNA polymerase
Authors: Murayama Yuko , Ehara Haruhiko , Aoki Mari , Goto Mie , Yokoyama Takeshi , Sekine Shun-ichi 
Published: September 2022

AbstractTranscription termination is an essential step in transcription by RNA polymerase (RNAP) and crucial for gene regulation. For many bacterial genes, transcription termination is mediated by the ATP-dependent RNA translocase/helicase Rho, which causes the dissociation of RNA/DNA from RNAP elongation complex (EC). However, structural basis of the interplay between Rho and RNAP remains obscure. Here we report the cryo-electron microscopy structure of the Rho-engaged EC. The Rho hexamer binds RNAP through the C-terminal domains, which surround the RNA-exit site of RNAP, directing the nascent RNA seamlessly from the RNA exit to the Rho central channel. The β-flap tip at the RNA exit is critical to the Rho-dependent RNA release, and its deletion causes an alternative Rho-RNAP binding mode, which is irrelevant to termination. The Rho-binding site overlaps with the binding sites of other macromolecules, such as ribosomes, providing a general basis of gene regulation.TeaserCryo-EM captures the structure of an RNA polymerase elongation complex engaged with the termination factor Rho.
Contrasting genomic evolution between domesticated and wild Kluyveromyces lactis yeast populations
Authors: Friedrich Anne , Gounot Jean-Sébastien , Tsouris Andreas , Bleykasten Claudine , Freel Kelle , Caradec Claudia , Schacherer Joseph 
Published: September 2022

AbstractThe process of domestication has variable consequences on genome evolution leading to different phenotypic signatures. Access to the complete genome sequences of a large number of individuals makes it possible to explore the different facets of this domestication process. Here, we sought to explore the genome evolution of the Kluyveromyces lactis yeast species, a well-known species for its involvement in dairy processes but also present in natural environments. Using a combination of short and long-read sequencing strategies, we investigated the genomic variability of 41 Kluyveromyces lactis isolates and found that the overall genetic diversity of this species is very high (π = 2.9 x 10-2) compared to other species such as Saccharomyces cerevisiae (π = 3 x 10-3). However, the domesticated dairy population shows a reduced level of diversity (π = 7 x 10-4), probably due to a domestication bottleneck. In addition, this entire population is characterized by the introgression of the LAC4 and LAC12 genes, responsible for lactose fermentation and coming from the closely related species, Kluyveromyces marxianus, as previously described. Our results also highlighted that the LAC4/LAC12 gene cluster was acquired through multiple and independent introgression events. Finally, we also identified several genes that could play a role in adaptation to dairy environments through copy number variation. These genes are involved in sugar consumption, flocculation and drug resistance, and may play a role in dairy processes. Overall, our study illustrates contrasting genomic evolution and sheds new light on the impact of domestication processes on it.
Construction of epithelial-mesenchymal transition related miRNAs signatures as prognostic biomarkers in gastric cancer patients
Authors: Xiao Jun , Zhang Fan , Liu Wenju , Zang Weidong 
Published: September 2022

AbstractAimTo identify the potential post-healing EMT related miRNAs associated with lymph node metastatic gastric cancer (LNMGC).MethodsBoth RNA expression and clinical medical data were obtained from the TCGA dataset. We performed differential expression and normalization analysis of miRNAs. Cox linear regression model confirmed the differentially expressed miRNAs (DEmiRNAs) and clinical medical parameters related to overall survival (OS). The role of target genes of DEmiRNAs was determined according to the role enrichment analysis.ResultsWe obtained a total of 7531 DEmRNAs and 267 DEmRNAs, of which 185 DEmRNAs were down-regulated and 82 DEmRNAs were up-regulated. We randomly divided the LMNGC cases (n=291) into a training group (n=207) and a test group (n=84). The results showed that a total of 103, 11, 13 and 83 overlapping genes were associated with hsa-mir-141-3p, hsa-mir-4664-3p, hsa-mir-125b-5p and hsa-mir-7-5p, respectively. Kaplan-Meier determined that these four miRNAs can effectively distinguish high-risk and low-risk groups, and have a good indicator role (all p<0.05). Multivariate cox regression analysis also showed that EMT-related miRNA predictive model and lymph node metastasis were both prognostic risk factors (all p<0.05). The ROC curve showed that this feature had high accuracy (AUC>0.7, p<0.05). In addition, KEGG analysis showed that EMT-related pathways were mainly enriched in HIF-1 signaling pathway and focal adhesion.ConclusionsOur study demonstrated that EMT-related miRNAs could serve as independent prognostic markers in pN1-3 GC patients.
WDFY4 deficiency in NOD mice abrogates autoimmune diabetes and insulitis
Authors: Ferris Stephen T. , Chen Jing , Ohara Ray A. , Ou Feiya , Wu Renee , Kim Sunkyung , Liu Tiantian , Murphy Theresa L. , Murphy Kenneth M. 
Published: September 2022

AbstractThe events that initiate autoimmune diabetes in NOD mice remain poorly understood. CD4 and CD8 T cells are both required but whether either cell initiates disease is unclear. To test whether CD4 T cell infiltration into islet required damage to β cells induced by autoreactive CD8 T cells, we selectively inactivated Wdfy4 in NOD mice (NOD.Wdfy4-/-) using CRISPR/Cas9 targeting. Similar to C57BL/6 Wdfy4-/- mice NOD.Wdfy4-/- mice develop type 1 conventional dendritic cells (cDC1) that are unable to cross-present cell-associated antigens required to activate CD8 T cells. By contrast, cDC1 from heterozygous Wdfy4+/- mice can cross-present normally. Heterozygous NOD.Wdfy4+/- mice develop diabetes similar to NOD mice, but NOD.Wdfy4-/- mice neither develop diabetes nor prime autoreactive CD8 T cells in vivo. By contrast, NOD.Wdfy4-/- mice can process and present MHC-II-restricted autoantigens and can activate β cell specific CD4 T cells in lymph nodes, and yet do not develop CD4 T cell infiltration in islets. These results indicate that the priming of autoreactive CD8 T cells in NOD mice requires cross-presentation by cDC1. Further, autoreactive CD8 T cells are required not only to develop diabetes, but to recruit autoreactive CD4 T cells into islets of NOD mice, perhaps in response to progressive β cell damage.
Elevated levels of lamin A promote HR and NHEJ-mediated repair mechanisms in etoposide-treated ovarian cancer cells
Authors: Sengupta Duhita , Sengupta Kaushik 
Published: September 2022

AbstractLamins are emerging as major regulators in the maintenance of nuclear architecture and genome organization. Extensive research for the last two decades has enormously contributed to understanding the roles of lamins in various signaling mechanisms which are drastically modified in neoplasia. It is interesting to record that alteration in lamin A/C expression and distribution drives tumorigenesis of almost all tissues of human bodies. One of the important signatures of a cancer cell is its inability to repair DNA damage which befalls several genomic events that transform the cells to be sensitive to chemotherapeutic agents. This genomic and chromosomal instability is the most common feature found in cases of high-grade ovarian serous carcinoma. Here, we report elevated levels of lamins in OVCAR3 cells (High grade ovarian serous carcinoma cell line) in comparison to IOSE (Immortalised ovarian surface epithelial cells) and consequently altered damage repair machinery in OVCAR3. We have analyzed the changes in global gene expression as a sequel to DNA damage induced by etoposide in ovarian carcinoma where lamin A is particularly elevated in expression and reported some differentially expressed genes associated with pathways conferring cellular proliferation and chemoresistance. We highlight new avenues unraveling the role of upregulated lamin A in confronting chemically induced genomic instability in the context of high grade ovarian serous cancer through a combination of HR and NHEJ mechanisms.
Length-limitation of astral microtubules orients cell divisions in intestinal crypts
Authors: Jad Saleh , Marc-Antoine Fardin , Olivia Frenoy , Matis Soleilhac , Cécile Gaston , Hongyue Cui , Tien Dang , Gaudin Noémie , Audrey Vincent , Nicolas Minc , Delphine Delacour 
Published: September 2022

SUMMARYPlanar spindle orientation is critical for epithelial tissue organization, and generally instructed from the long cell shape axis or cortical polarity domains. We introduced mouse intestinal organoid crypts to study spindle orientation in a monolayered mammalian epithelium. Although spindles were planar in this tissue, mitotic cells remained elongated along the apico-basal axis and polarity complexes were segregated to basal poles, so that spindles oriented in an unconventional manner, orthogonal to both polarity and geometric cues. Using high-resolution 3D imaging, simulations, cell shape and cytoskeleton manipulations, we show that planar divisions resulted from a length-limitation in mitotic-phase astral microtubules which precludes them from interacting with basal polarity, and oriented spindles from the local geometry of apical domains. Accordingly, lengthening microtubules affected spindle planarity, cell positioning and crypt arrangement. We conclude that microtubule length regulation may serve as a key mechanism for spindles to sense local cell shapes and tissue forces to preserve mammalian epithelial architecture.
Altered litter and cellulose decomposition across an anthropogenic habitat modification gradient in Sulawesi, Indonesia
Authors: Holle Mukhlish J. M. , Lewis Owen T. 
Published: September 2022

AbstractMany tropical regions in Southeast Asia have experienced extensive habitat modification, creating a mosaic of forested and agricultural land. The capacity of these human-modified tropical landscapes to support biodiversity and ecosystem functions and services is of considerable practical interest.Decomposition of plant material is a key process maintaining the nutrient cycle in both natural and agro-ecosystems, but few studies have documented the relative contributions of different guilds of decomposers, acting on different plant substrates, across different tropical land-uses.We measured decomposition of leaf litter and cellulose across a gradient of anthropogenic habitat modification (forest, shrubland, and corn farmland) within Panua Nature Reserve, Sulawesi, Indonesia. The influence of fungi and the litter invertebrate community were investigated experimentally.Decomposition of both substrates was significantly lower in corn plantations than in forest sites. Partial exclusion of litter invertebrates, but not fungi, significantly reduced decomposition, but the feeding guild composition of the litter invertebrate community did not differ significantly across habitat types.Our results confirm that even small-scale agricultural areas adjacent to forest fragments can experience impaired ecosystem functions. These changes can be linked to reduced invertebrate activity, apparently independent of the functional structure of the litter invertebrate community. Effective management of human-modified landscapes will be needed to maintain nutrient cycling, even in areas where agroecosystems and tropical forests occur in close proximity.HighlightsHabitat modification alters litter and cellulose decompositionSmall-scale agriculture near forest fragments can impair ecosystem functions.Exclusion of litter invertebrates, but not fungi, significantly reduced decomposition.Maintaining nutrient cycling requires effective management of human-altered landscapes.
Var|Decrypt: a novel and user-friendly tool to explore and prioritize variants in whole-exome sequencing data
Authors: Salma Mohammad , Alaterre Elina , Moreaux Jérôme , Soler Eric 
Published: September 2022

AbstractMotivationHigh throughput sequencing (HTS) offers unprecedented opportunities for the discovery of causative gene variants in multiple human disorders including cancers, and has revolutionized clinical diagnostics. However, despite more than a decade of use of HTS-based assays, extracting relevant functional information from whole exome sequencing (WES) data remains challenging, especially for non-specialists lacking in-depth bioinformatic skills.ResultsTo address this limitation, we developed Var|Decrypt, a web-based tool designed to greatly facilitate WES data browsing and analysis. Var|Decrypt offers a wide range of gene and variant filtering possibilities, clustering and enrichment tools, providing an efficient way to derive patient-specific functional information and to prioritize gene variants for functional analyses. We applied Var|Decrypt on WES datasets of 10 acute erythroid leukemia patients, a rare and aggressive form of leukemia, and recovered known disease oncogenes in addition to novel putative drivers. We additionally benchmarked Var|Decrypt on an independent dataset of ~90 multiple myeloma WES, recapitulating the identified deregulated genes and pathways, showing the general applicability and versatility of Var|Decrypt for WES analysis.
Impaired baroreceptor reflex sensitivity in pelvic suspension rats is associated with sympathovagal imbalance but not with carotid artery structural change
Authors: Bhatnaagar A , Deepak KK , Roy A , Anil AK , Sharma B , Singh A , Netam RK 
Published: September 2022

AbstractIntroductionIn space, cephalad shift of body fluid equalizes the blood pressure throughout the body leading to various cardiovascular disturbances in space and upon return on earth. Effects of microgravity on humans can be simulated on earth by hindlimb unloading (HU) rat models l. This study was planned to examine the Effect of 15 days hindlimb unloading on baroreflex sensitivity, Herat rate variability (HRV) and carotid artery structure in rats.Material and methods18 male Wistar rats weighing 250-300 gm were randomly divided into control and hindlimb unloading groups and housed in separate cages for 15 days. Body weight, food and water intake was measured every day. The pelvic suspension method was used to simulate effects of microgravity. To record HRV, ECG was recorded in lead II configuration on the 15th day. Then blood pressure was recorded directly from the carotid artery. Linear regression of arterial pressure and RR interval used to derive the Baroreflex sensitivity. Vessel wall thickness, intimal thickness, smooth muscle cell layer thickness &amp; luminal diameter were compared after H&E staining. Ultrathin sectioning and counter-staining was done for electron microscopy and Changes in endothelial thickness, elastic lamina, and deeper artery structures were observed. Statistical analysis was done using Graphpad Prism (version 9.0). Unpaired t-test, Mann Whitney and 2 way ANOVA were used according to groups and distribution of parameters.ResultsWe found significant differences in Food intake (p □0.001), Body weight (p □0.001), Heart rate (p=0.031), BRS (p= 0.026), R-R interval (p=0.0246), heart rate variability parameters {SDSD (p=0.0001), RMSD (p= 0.0001), VLF(p=0.001),HF (p=0.0054), LF/HF Ratio (p= 0.0001)}. We did not found significant changes in Water intake, MAP, SBP, DBP, Vessel wall thickness, Luminal Diameter, Intimal thickness, Smooth muscle thickness, in H&E staining and in electron microscopy.ConclusionChronic microgravity simulation using pelvic suspension showed a decrease in BRS after 15 days of HU; however 15 days of HU was not insufficient to produce any structural changes in the carotid artery. BRS changes were accompanied by change in vascular vasoconstriction and vasodilation properties which were due to alteration in the sympathetic and parasympathetic outflow.
Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2
Authors: Haji Shojiro , Ito Taiki , Guenther Carla , Nakano Miyako , Shimizu Takashi , Mori Daiki , Chiba Yasunori , Tanaka Masato , Mishra Sushil K , Willment Janet A. , Brown Gordon D. , Nagae Masamichi , Yamasaki Sho 
Published: September 2022

AbstractC-type lectin receptors (CLRs) elicit immune responses upon recognition of glycoconjugates present on pathogens and self-components. While Dectin-1 is the best-characterized CLR recognizing β-glucan on pathogens, the endogenous targets of Dectin-1 are not fully understood. Herein, we report that human Dectin-1 is a ligand for CLEC-2, another CLR expressed on platelets. Biochemical analyses revealed that Dectin-1 is a mucin-like protein as its stalk region is highly O-glycosylated. A sialylated core 1 glycan attached to the EDxxT motif of human Dectin-1, which is absent in mouse Dectin-1, provides a ligand moiety for CLEC-2. Strikingly, the expression of human Dectin-1 in mice rescued the lethality and lymphatic defect resulting from a deficiency of Podoplanin, a known CLEC-2 ligand. This finding is the first example of an innate immune receptor also functioning as a physiological ligand to regulate ontogeny upon glycosylation.