bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metacommunity framework and its core terms entanglement
Authors: Kolasa Jurek , Hammond Matthew P. , Yan Joyce 
Published: September 2021

ABSTRACTThe metacommunity framework links space and ecological processes but is vulnerable to complex entanglement among its integral components. Most ecological processes are context-dependent. However, when ecological theories show it, they may be seriously crippled unless they explicitly tackle it. Otherwise, findings emerging from accumulated cases will be of limited value and likely remain ambiguous or misleading. Specifically, interactions among the core terms of metacommunity theory interact in complex ways that we identify as entanglement. We employ four core dimensions to alleviate this issue and create a space where various studies converse and effectively complement each other irrespective of the case specifics. The dimensions encompass the metacommunity empirical domain: (1) inter-habitat differences, (2) species habitat specialization, (3) effective dispersal, and (4) species interactions (negative to positive). Then, we assess the entanglement effects by testing that (a)changing values in one dimension, with others constant, alters study conclusions, and (b)these effects increase and dominate when integral dimensions interact reciprocally. As a metric, we analyzed species diversity in a stochastic, agent-based, unified metacommunity model, UMM, where species move, select habitats, reproduce, and interact. In the simulations, each dimension has four or five levels spanning a broad spectrum of conditions. The exercise strongly supports both hypotheses. It also suggests that positive interactions, in contrast to the popular emphasis, promote biodiversity more than negative ones like competition or predation. The proposed integrated conceptual system can expand to include meta-ecosystems, habitat gradients, and other processes. Thus, it can offer a unified approach to spatial processes in ecology. Finally, by combining the four dimensions into one interactive system, we identify a rich array of lower-level hypotheses that inevitably emerge from this system. The hypotheses’ shared origin anchors individual studies in coherent structure to advance sound generalizations.
Backward masking in mice requires visual cortex
Authors: Gale Samuel D , Strawder Chelsea , Bennett Corbett , Mihalas Stefan , Koch Christof , Olsen Shawn R 
Published: September 2021

AbstractVisual masking is used to infer the timescale of conscious perception in humans; yet the underlying circuit mechanisms are not understood. Here we describe a two-alternative choice backward masking task in mice and humans, in which the location of a briefly presented grating is effectively masked within a 50 ms window after stimulus onset. Importantly, human subjects reported reduced perceptual visibility during masking that closely corresponded with behavior deficits. In mice, optogenetic silencing of visual cortex reduces performance over a similar time course as masking. However, response rates and accuracy do not match masking, demonstrating that cortical silencing and masking are distinct phenomena. Spiking responses recorded in primary visual cortex (V1) are consistent with masked behavior when quantified over long, but not short, time windows, indicating masking involves further downstream processing. Behavioral performance can be quantitatively recapitulated by a dual accumulator model constrained by V1 activity. The model and the animal’s performance for the earliest decisions imply that the initial spike arriving from the periphery can trigger a correct response, but subsequent V1 spikes, evoked by the mask, degrade performance for longer decisions. To test the necessity of visual cortex for backward masking, we optogenetically silenced mask-evoked cortical activity which fully restored discrimination of target location. Together, these results demonstrate that mice, like humans, are susceptible to backward visual masking and that visual cortex has a crucial role in this process.
Innate immune signaling drives late cardiac toxicity following DNA damaging cancer therapies
Authors: Shamseddine Achraf , Patel Suchit H. , Chavez Valery , Adnan Mutayyaba , Bona Melody Di , Li Jun , Dang Chau T. , Ramanathan Lakshmi V. , Oeffinger Kevin C. , Liu Jennifer E. , Steingart Richard M. , Piersigilli Alessandra , Socci Nicholas D. , Chan Angel T. , Yu Anthony F. , Bakhoum Samuel F. , Schmitt Adam M. 
Published: September 2021

AbstractLate cardiac toxicity is a potentially lethal complication of cancer therapy, yet the pathogenic mechanism remains largely unknown, and few treatment options exist. Here we report DNA damaging agents such as radiation and anthracycline chemotherapies induce delayed cardiac inflammation following therapy due to activation of cGAS and STING-dependent type I interferon signaling. Genetic ablation of cGAS-STING-signaling in mice inhibits DNA damage induced cardiac inflammation, rescues late cardiac functional decline, and prevents death from cardiac events. Treatment with a STING antagonist suppresses cardiac interferon signaling following DNA damaging therapies and effectively mitigates cardiotoxicity. These results identify a therapeutically targetable, pathogenic mechanism for one of the most vexing treatment-related toxicities in cancer survivors.
A structural biology community assessment of AlphaFold 2 applications
Authors: Akdel Mehmet , Pires Douglas E V , Porta Pardo Eduard , Jänes Jürgen , Zalevsky Arthur O , Mészáros Bálint , Bryant Patrick , Good Lydia L. , Laskowski Roman A , Pozzati Gabriele , Shenoy Aditi , Zhu Wensi , Kundrotas Petras , Ruiz Serra Victoria , Rodrigues Carlos H M , Dunham Alistair S , Burke David , Borkakoti Neera , Velankar Sameer , Frost Adam , Lindorff-Larsen Kresten , Valencia Alfonso , Ovchinnikov Sergey , Durairaj Janani , Ascher David B , Thornton Janet M , Davey Norman E , Stein Amelie , Elofsson Arne , Croll Tristan I , Beltrao Pedro 
Published: September 2021

AbstractMost proteins fold into 3D structures that determine how they function and orchestrate the biological processes of the cell. Recent developments in computational methods have led to protein structure predictions that have reached the accuracy of experimentally determined models. While this has been independently verified, the implementation of these methods across structural biology applications remains to be tested. Here, we evaluate the use of AlphaFold 2 (AF2) predictions in the study of characteristic structural elements; the impact of missense variants; function and ligand binding site predictions; modelling of interactions; and modelling of experimental structural data. For 11 proteomes, an average of 25% additional residues can be confidently modelled when compared to homology modelling, identifying structural features rarely seen in the PDB. AF2-based predictions of protein disorder and protein complexes surpass state-of-the-art tools and AF2 models can be used across diverse applications equally well compared to experimentally determined structures, when the confidence metrics are critically considered. In summary, we find that these advances are likely to have a transformative impact in structural biology and broader life science research.
The Impact of Body Mass Index on Physical Activity and Cardiac Workload
Authors: Bloom Myra Jane , Brown Lakin Mckenzie , Jost Scarlet Rae , Lang Andrew Stuart Ian Donald , Mankin Nancy Viola , Mast Zachary William , McMahan Ericka Rachel , Merheb Jonathan Abdou , Nelson Philip Paul , Nnaji Joshua Chinweoke , Valderrama Enrique Francisco 
Published: September 2021

AbstractBackgroundHaving an abnormal body mass index (BMI) adversely affects cardiac workload and level of physical activity.ObjectiveTo examine the relationship between cardiac workload, physical activity, Sex, and BMI.MethodsThe number of steps taken per day (Steps) and minutes per week spent in targeted heart rate zones were collected from primarily first and second year university students (n = 1,801; 62% female) over a standard, 15-week long semester. Other data collected included BMI, Sex, Age, and Class Standing. Sex differences in BMI, Steps, and training heart rate zone (heart rates above 50% of max) minutes (THR) were evaluated, correlations between the study parameters were analyzed, and one-way ANOVA was used to test between competing models. The values p < .05 were considered statistically significant.ResultsStatistically significant (p < .05) differences between males and females were found for Steps, THR, and BMI. Males were more physically active but spent 18% less time with heart rates above 50% of max. Students who had abnormal BMI values, both low and high, experienced greater cardiac workload (p < .05), even though they were found to be less physically active (p < .05).ConclusionOur study revealed that university students with abnormal BMI values experienced greater cardiac workload, even though they are less physically active. Thus, physical fitness and healthy lifestyle interventions should also include underweight students in addition to students who are overweight or obese.
Using causality and correlation analysis to decipher microbial interactions in activated sludge
Authors: Cai Weiwei , Han Xiangyu , Yao Hong 
Published: September 2021

ABSTRACTNetwork theory is widely used to understand microbial interactions in activated sludge and numerous other artificial and natural environments. However, when using correlation-based methods, it is not possible to identify the directionality of interactions within microbiota. Based on the classic Granger test of sequencing-based time-series data, a new Microbial Causal Correlation Network (MCCN) was constructed with distributed ecological interaction on the directed, associated links. As a result of applying MCCN to a time series of activated sludge data, we found that the hub species OTU56, classified as belonging the genus Nitrospira, was responsible for completing nitrification in activated sludge, and mainly interacted with Proteobacteria and Bacteroidetes in the form of amensal and commensal relationships, respectively. Phylogenetic tree suggested a mutualistic relationship between Nitrospira and denitrifiers. Zoogloea displayed the highest ncf value within the classified OTUs of the MCCN, indicating that it could be a foundation for activated sludge through forming the characteristic cell aggregate matrices into which other organisms embed during floc formation. Overall, the introduction of causality analysis greatly expands the ability of a network to shed a light on understanding the interactions between members of a microbial community.
The longevity response to warm temperature is neurally controlled via the regulation of collagen genes
Authors: Palani Sankara Naynar , Sellegounder Durai , Liu Yiyong 
Published: September 2021

AbstractStudies in diverse species have associated higher temperatures with shorter lifespan and lower temperatures with longer lifespan. However, the mechanisms behind these inverse effects of temperature on longevity are not well understood. Here, we demonstrate that in Caenorhabditis elegans, functional loss of NPR-8, a G protein-coupled receptor related to mammalian neuropeptide Y receptors, increases worm lifespan at 25°C but not at 20°C or 15°C, and that the lifespan increase at 25°C is regulated by the NPR-8-expressing AWB and AWC chemosensory neurons as well as AFD thermosensory neurons. RNA sequencing revealed that both warm temperature and old age profoundly alter gene expression. Further investigation uncovered that the NPR-8-dependent longevity response to warm temperature is achieved by regulating the expression of a subset of collagen genes. As elevated collagen expression is a common feature of many lifespan-extending interventions and enhanced stress resistance, collagen expression could be critical for healthy aging.
Tuft cell-produced cysteinyl leukotrienes and IL-25 synergistically initiate lung type 2 inflammation
Authors: Ualiyeva Saltanat , Lemire Evan , Aviles Evelyn C. , Boyd Amelia A. , Wong Caitlin , Lai Juying , Liu Tao , Matsumoto Ichiro , Barrett Nora A. , Boyce Joshua A. , Haber Adam L. , Bankova Lora G. 
Published: September 2021

ABSTRACTAeroallergen sensing by airway epithelial cells can trigger pathogenic immune responses leading to chronic type 2 inflammation, the hallmark of airway diseases such as asthma. Airway tuft cells are specialized chemosensory epithelial cells and the dominant source of the epithelial cytokine IL-25 in the trachea and of cysteinyl leukotrienes (CysLTs) in the naïve murine nasal mucosa. The interaction of IL-25 and CysLTs and the contribution of tuft cell-derived CysLTs to the development of allergen-triggered inflammation in the airways has not been clarified. Here we show that inhalation of LTC4 in combination with a subthreshold dose of IL-25 leads to dramatic synergistic induction of type 2 inflammation throughout the lungs, causing rapid eosinophilia, dendritic cell (DC) and inflammatory type 2 innate lymphoid cell (ILC2) expansion, and goblet cell metaplasia. While lung eosinophilia is dominantly mediated through the classical CysLT receptor CysLT1R, type 2 cytokines and activation of innate immune cells require signaling through both CysLT1R and CysLT2R. Tuft cell-specific deletion of the terminal enzyme requisite for CysLT production, Ltc4s, was sufficient to reduce both the innate immune response in the lung – eosinophilia, KLRG1+ ILC2 activation and DC recruitment – and the systemic immune response in the draining lymph nodes after inhalation of the mold aeroallergen Alternaria. Our findings identify surprisingly potent synergy of CysLTs and IL-25 downstream of aeroallergen-trigged activation of airway tuft cells leading to a highly polarized type 2 immune response and further implicate airway tuft cells as powerful modulators of type 2 immunity in the lungs.One Sentence SummaryTuft cells produce two highly synergistic mediators: LTC4 and IL-25 to cooperatively induce allergen-driven airway inflammation.
Remotely-sensed slowing down in spatially patterned dryland ecosystems
Authors: Veldhuis Michiel P. , Martinez-Garcia Ricardo , Deblauwe Vincent , Dakos Vasilis 
Published: September 2021

AbstractRegular vegetation patterns have been predicted to indicate a system slowing down and possibly desertification of drylands. However, these predictions have not yet been observed in dryland vegetation due to the inherent logistic difficulty to gather longer-term in situ data. Here, we use recently developed methods using remote-sensing EVI time-series in combination with classified regular vegetation patterns along a rainfall gradient in Sudan to test these predictions. Overall, three temporal indicators (responsiveness, temporal autocorrelation, variance) show slowing down as vegetation patterns change from gaps to labyrinths to spots towards more arid conditions, confirming predictions. However, this transition exhibits non-linearities, specifically when patterns change configuration. Model simulations reveal that the transition between patterns temporarily slows down the system affecting the temporal indicators. These transient states when vegetation patterns reorganize thus affect the systems resilience indicators in a non-linear way. Our findings suggest that spatial self-organization of dryland vegetation is associated with critical slowing down, but this transition towards reduced resilience happens in a non-linear way. Future work should aim to better understand transient dynamics in regular vegetation patterns in dryland ecosystems, because long transients make regular vegetation patterns of limited use for management in anticipating critical transitions.
Drought Stress Induces Morpho-physiological and Proteome Changes ofPandanus amaryllifolius
Authors: Mohd Amnan Muhammad Asyraf , Aizat Wan Mohd , Khaidizar Fiqri Dizar , Tan Boon Chin 
Published: September 2021

AbstractDrought is one of the significant threats to the agricultural sector. However, there is limited knowledge on the plant response to drought stress and post-drought recovery.Pandanus amaryllifolius, a moderate drought-tolerant plant, is well known for its ability to survive in low-level soil moisture conditions. Understanding the molecular regulation of drought stress signaling in this plant could help guide the rational design of crop plants to counter this environmental challenge. This study aimed to determine the morpho-physiological, biochemical and protein changes ofP. amaryllifoliusin response to drought stress and during recovery. Drought significantly reduced leaf relative water content ofP. amaryllifolius. In contrast, relative electrolyte leakage, proline and malondialdehyde contents, and the activities of antioxidant enzymes in the drought-treated and recovered samples were relatively higher than the well-watered sample. The protein changes between drought-stressed, well-watered, and recovered plants were evaluated using tandem mass tags (TMT)-based quantitative proteomics. Of the 1,415 differentially abundant proteins, 74 were significantly altered. The majority of proteins differing between them were related to carbon metabolism, photosynthesis, stress response, and antioxidant activity. This is the first study that reports the protein changes in response to drought stress inPandanus. The data generated provide an insight into the drought-responsive mechanisms inP. amaryllifolius.
Inhibition of Kallikrein-related peptidases 7 restrains pancreatic tumor growth through induction of ferroptosis
Authors: Wang Yueqing , Xiang Fengyi , Deng Hao , Leng Shuang , Zhao Dengze , Chen Yue , Xie Donghui , Li Qingyun , Cao Chunyu , Zheng Weihong , Liu Wei , Liu Xiaowen , Zheng Jun , Tan Xiao 
Published: September 2021

AbstractPancreatic cancer is one of the most aggressive and lethal malignancies with extremely poor prognosis, and KLK7 was considered as a potential therapeutic target. In this study, we analyzed the expression of KLK7 in TCGA and GTEx databases and found that KLK7 had a negative correlation to long-term survival rate (>1.5 years) of pancreatic cancer patients. Compound 42 is a coumarinic derivative, a suicide substrate inhibitor of KLK7, which has been proved to inhibit the proliferation of PANC-1 cells in vitro effectively in our previous study. In this study, we further investigated the inhibition ability of Compound 42 in tumor formation and development in CDX and PDX tumor models of pancreatic cancer subsequently. Besides, we studied the inhibitory mechanism of Compound 42 and the result showed that Compound 42 arrested the pancreatic cancer cell cycle in G0/G1 phase and induced ferroptosis through down-regulation of GPX4 protein level and accumulation of iron ion. Thus, these experiments demonstrate that Compound 42, suppressing pancreatic cancer in vivo, is expected to become a novel drug for pancreatic cancer treatment.
Prospective isolation of mouse and human hematopoietic stem cells using Plexin domain containing 2
Authors: Tanaka Yosuke , Kubota Yasushi , Lieberam Ivo , Barlow Jillian L. , Bramley Josh W. , Sakuma Chiaki , Shibata Takashi , Nakagawa Masataka , Kurosawa Yasunori , Maruyama Toshiaki , Okumura C.J. , Akuta Teruo , Kent David G. , Jessell Thomas M , Goyama Susumu , Kimura Shinya , Kitamura Toshio 
Published: September 2021

AbstractNumerous strategies exist to isolate hematopoietic stem cells (HSCs) using complex combinations of markers and flow cytometry. However, robust identification of HSCs using imaging techniques is substantially more challenging which has prompted the recent development of HSC reporter mice. To date, none of the molecules used in these reporters have been useful for human HSC identification. Here we report that PLXDC2 is a useful marker for both mouse and human HSCs. Using a green fluorescent protein (GFP) knock-in at the Plxdc2 locus in mice (hereafter denoted as Plxdc2-GFP), we showed that Plxdc2-GFP is highly expressed in HSCs with 1 in 2.8 Plxdc2-GFP+CD150+ cells giving long-term multi-lineage reconstitution in transplantation. Moreover, we developed a novel human PLXDC2 antibody and showed that human PLXDC2+ HSCs have stronger long-term multilineage reconstitution ability compared with PLXDC2- HSCs in a xenograft model. Thus, our study identifies PLXDC2 as a highly relevant molecule in HSC identification, potentially allowing greater purity and live in vivo tracking of these cells.SummaryTo date, few molecules are available for isolation of HSCs across species. The present study shows that PLXDC2 is a highly useful molecule for isolation of HSCs, which works across mouse and human.
GABAB receptor/HCN channel complexes in VTA dopamine neurons limit synaptic inhibition and prevent anxiety-like behavior
Authors: Pérez-Garci Enrique , Rizzi Giorgio , Fritzius Thorsten , Porcu Alessandra , Besseyrias Valerie , Gassmann Martin , Tan Kelly R. , Bettler Bernhard 
Published: September 2021

AbstractAversive stimuli inhibiting dopamine neurons in the ventral tegmental area (DAVTA neurons) induce anxiety-like behaviors. The inhibition of DAVTA neurons is prolonged by GABAB receptor (GBR)-activated K+-currents, which exhibit a rapid desensitization of unknown physiological relevance. We now report that GBRs associate via auxiliary KCTD16 subunits with HCN channels, which facilitates activation of hyperpolarization- activated currents (Ih) by GBR-activated K+ currents. Activation of Ih underlies rapid K+ current desensitization in DAVTA neurons and limits GBR-mediated inhibition. Disruption of the GBR/HCN complex in KCTD16-/- mice or blockade of Ih prolongs optogenetically driven inhibition of DAVTA neuron firing. KCTD16-/- mice exhibit an increased anxiety-like behavior in response to stressful stimuli, which is reproduced by in vivo CRISPR/Cas9-mediated KCTD16 ablation in DAVTA neurons or intra-VTA infusion of HCN antagonist to wild-type mice. Our data reveal that GBR-induced Ih protect DAVTA neurons from prolonged GBR- mediated inhibition in response to stressors, which moderates anxiety-like behaviors.