bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive astrocytes associated with prion disease impair the blood brain barrier
Authors: Kushwaha Rajesh , Li Yue , Makarava Natallia , Pandit Narayan P. , Molesworth Kara , Birukov Konstantin G. , Baskakov Ilia V. 
Published: March 2023

AbstractBackgroundImpairment of the blood-brain barrier (BBB) is considered to be a common feature among neurodegenerative diseases, including Alzheimer’s, Parkinson’s and prion diseases. In prion disease, increased BBB permeability was reported 40 years ago, yet the mechanisms behind the loss of BBB integrity have never been explored. Recently, we showed that reactive astrocytes associated with prion diseases are neurotoxic. The current work examines the potential link between astrocyte reactivity and BBB breakdown.ResultsIn prion-infected mice, the loss of BBB integrity and aberrant localization of aquaporin 4 (AQP4), a sign of retraction of astrocytic endfeet from blood vessels, were noticeable prior to disease onset. Gaps in cell-to-cell junctions along blood vessels, together with downregulation of Occludin, Claudin-5 and VE-cadherin, which constitute tight and adherens junctions, suggested that loss of BBB integrity is linked with degeneration of vascular endothelial cells. In contrast to cells isolated from non-infected adult mice, endothelial cells originating from prion-infected mice displayed disease-associated changes, including lower levels of Occludin, Claudin-5 and VE-cadherin expression, impaired tight and adherens junctions, and reduced trans-endothelial electrical resistance (TEER). Endothelial cells isolated from non-infected mice, when co-cultured with reactive astrocytes isolated from prion-infected animals or treated with media conditioned by the reactive astrocytes, developed the disease-associated phenotype observed in the endothelial cells from prion-infected mice. Reactive astrocytes were found to produce high levels of secreted IL-6, and treatment of endothelial monolayers originating from non-infected animals with recombinant IL-6 alone reduced their TEER. Remarkably, treatment with extracellular vesicles produced by normal astrocytes partially reversed the disease phenotype of endothelial cells isolated from prion-infected animals.ConclusionsTo our knowledge, the current work is the first to illustrate early BBB breakdown in prion disease and to document that reactive astrocytes associated with prion disease are detrimental to BBB integrity. Moreover, our findings suggest that the harmful effects are linked to proinflammatory factors secreted by reactive astrocytes.
Spatial Signatures of Biological Soil Crusts and Community Level Self-Organization in Drylands
Authors: Kozar Daniel , Weber Bettina , Zhang Yu , Dong Xiaoli 
Published: March 2023

AbstractIn dryland landscapes, patches of vascular plants can respond to environmental stress by adjusting their spatial pattern to intercept runoff more effectively, i.e., spatially self-organize, and maintain productivity. However, vegetation patch dynamics in drylands often assumes interspaces of plant patches are composed only of bare soil. Biological soil crusts (BSCs) are complex communities, largely of cyanobacteria, algae, lichens, and bryophytes, living in the soil surface in drylands and often cover more area than vascular plants. BSCs often occur in patches of light cyanobacteria and dark-mixed aggregates and can significantly affect and respond to ecohydrological feedbacks in dryland ecosystems. However, little is known about their spatial patterns and dynamics. In this study, we investigate spatial attributes of BSC patches, their spatial interactions with vascular plants, and factors that drive variation in these attributes. We collected ultra-high-resolution (1-cm) data on spatial patterns of BSCs and vascular plants at 26 sites across three ecoregions of the Southwest of the United States of America. Our analysis shows that light cyanobacterial BSCs vary most in their patch shape complexity along the aridity gradient, while dark-mixed BSCs vary strongly in their abundance. The abundance of dark-mixed BSCs is significantly affected by the soil template, namely soil texture and calcareousness, as well as vascular plants to persist under stress. Furthermore, species associations also change with environmental stress. Light cyanobacteria BSCs, likely a significant source of runoff, may act as a buffer for woody plants against drying, as spatial interactions between these biota become more positive (i.e., spatially aggregated) with greater aridity. While dark-mixed BSCs rely significantly on soil conditions and reduce in abundance as a response to aridity stress, we find evidence that they may have some capacity to spatially adjust under conditions of constant aridity. The interaction of dark-mixed BSCs with light cyanobacteria patches becomes more positive with slope. We conclude that light cyanobacteria BSCs can likely change patch shape in response to water limitation, while dark-mixed BSCs have a reduced capacity to do so – providing further evidence that the abundance of dark-mixed BSCs will decline in the future under drying. BSCs and vascular plants coordinate in space in response to resource availability, suggesting the need to consider self-organization of multiple assemblages to fully understand dryland response to climatic change.
Representations of carbon dioxide in the mosquito antennal lobe
Authors: Goyal Shefali , Singh Pranjul , Gupta Mudit , Gupta Smith , Singh Swikriti Saran , Gupta Arjit Kant , Gupta Nitin 
Published: March 2023

AbstractCarbon dioxide (CO2) is one of the prominent sensory cues used by mosquitoes to find hosts for blood-feeding. CO2is detected on the maxillary palps by capitate peg sensory neurons, whose axons project to the antennal lobe in the brain. Behavioral studies have shown that mosquitoes prefer non-homogenous plumes of CO2over homogenous plumes and CO2greatly enhances the attractiveness of lactic acid, a skin volatile. However, the neural mechanisms underlying these behavioral preferences are not known. Usingin vivointracellular recordings from projection neurons and local neurons in the antennal lobe, along with single sensillum recordings from the maxillary palps, we checked the representations of CO2in the first two layers of theAedes aegyptiolfactory system. We found that the preference to non-homogeneous plumes of CO2and its synergistic attraction with lactic acid are encoded in the PN population responses. Our results provide a foundation for understanding CO2-mediated host-attraction in mosquitoes.
A unifying account of replay as context-driven memory reactivation
Authors: Zhou Zhenglong , Kahana Michael J. , Schapiro Anna C. 
Published: March 2023

AbstractDuring rest and sleep, sequential neural activation patterns corresponding to awake experience re-emerge, and this replay has been shown to benefit subsequent behavior and memory. Whereas some studies show that replay directly recapitulates recent experience, others demonstrate that replay systematically deviates from the temporal structure, the statistics, and even the content of recent experience. Given these disparate characteristics, what is the nature and purpose of replay? Here, we offer a theoretical framework in which replay reflects simple context-guided processes that facilitate memory. We suggest that, during awake learning, the brain associates experiences with the contexts in which they are encoded, at encoding rates that vary according to the salience of each experience. During quiescence, replay emerges as the result of a cascade of autonomous bidirectional interactions between contexts and their associated experiences, which in turn facilitates memory consolidation. A computational model instantiating this proposal explains numerous replay phenomena, including findings that existing models fail to account for and observations that have been predominantly construed through the lens of reinforcement learning. Our theory provides a unified, mechanistic framework of how the brain initially encodes and subsequently replays experiences in the service of memory consolidation.
Host and microbiome jointly contribute to adaptation to a complex environment
Authors: Petersen Carola , Hamerich Inga K. , Adair Karen L. , Griem-Krey Hanne , Oliva Montserrat Torres , Hoeppner Marc P. , Bohannan Brendan J.M. , Schulenburg Hinrich 
Published: March 2023

AbstractMost animals and plants have associated microorganisms, collectively referred to as their microbiomes, which can provide essential functions. Given their importance, host-associated microbiomes have the potential to contribute substantially to adaptation of the host-microbiome assemblage (the “metaorganism”). Microbiomes may be especially important for rapid adaptation to novel environments because microbiomes can change more rapidly than host genomes. However, it is not well understood how hosts and microbiomes jointly contribute to metaorganism adaptation. We developed a model system with which to disentangle the contributions of hosts and microbiomes to metaorganism adaptation. We established replicate mesocosms containing the nematodeCaenorhabditis elegansco-cultured with microorganisms in a novel complex environment (laboratory compost). After approximately 30 nematode generations (100 days), we harvested worm populations and associated microbiomes, and subjected them to a common garden experiment designed to unravel the impacts of microbiome composition and host genetics on metaorganism adaptation. We observed that adaptation took different trajectories in different mesocosm replicates, with some increasing in fitness and others decreasing, and that interactions between host and microbiome played an important role in these contrasting evolutionary paths. We chose two exemplary mesocosms (one with a fitness increase and one with a decrease) for detailed study. For each example, we identified specific changes in both microbiome composition (for both bacteria and fungi) and nematode gene expression associated with each change in fitness. Our study provides experimental evidence that adaptation to a novel environment can be jointly influenced by host and microbiome.
Extensive variation in germlinede novomutations inPoecilia reticulata
Authors: Lin Yuying , Darolti Iulia , van der Bijl Wouter , Morris Jake , Mank Judith E. 
Published: March 2023

AbstractThe rate of germline mutation is fundamental to evolutionary processes, as it generates the variation upon which selection acts. The guppy,Poecilia reticulata, is a model of rapid adaptation, however the relative contribution of standing genetic variation versusde novomutation to evolution in this species remains unclear. Here, we use pedigree-based approaches to quantify and characterizede novomutations (DNMs) in three large guppy families. Our results suggest germline mutation rate in the guppy varies substantially across individuals and families. Most DNMs are shared across multiple siblings, suggesting they arose during early zygotic development. DNMs are randomly distributed throughout the genome, and male-biased mutation rate is low, as would be expected from the short guppy generation time. Overall, our study demonstrates remarkable variation in germline mutation rate and provides insights into rapid evolution of guppies.
The translocation mechanism of calcitriol throughHelicobacter pylorilipid membrane and influence on water permeability
Authors: Cao Zanxia , Zhao Liling , Chen Mingcui , Liu Lei 
Published: March 2023

AbstractHelicobacter pyloriexhibits a unique membrane lipid composition, including dimyristoyl phosphatidylethanolamine (DMPE) and cholesterol, unlike other Gram-negative bacteria. Calcitriol has antimicrobial activity againstH. pylori, but cholesterol enhances antibiotics resistance inH. pylori. This study explored the changes in membrane structure and the molecular mechanisms of cholesterol/calcitriol translocation using well-tempered metadynamics (WT-MetaD) simulations and microsecond conventional molecular dynamics simulations. Our results showed that the average area per lipid and sterol tilt angles were slightly lower, while DP-P, DCG-CG, DAC-AC, and SCDwere higher in cholesterol membrane systems than in calcitriol membrane systems. Cholesterol membrane systems were more ordered than calcitriol-containing membranes. Calcitriol facilitated water transport across the membrane, while cholesterol had the opposite effect. The differing effects might result from the tail 25-hydroxyl group and a wider range of orientations of calcitriol in the DMPE/ dimyristoyl phosphatidylglycerol (DMPG) (3:1) membrane. Calcitriol moves across the bilayer center without changing its orientation along the membrane Z-axis, becomes parallel to the membrane surface at the membrane-water interface, and then rotates approximately 90º in this interface. The translocation mechanism of calcitriol is quite different from the flip-flop of cholesterol. Moreover, calcitriol crossed from one layer to another more easily than cholesterol, causing successive perturbations to the hydrophobic core and increasing water permeation. These results improve our understanding of the relationship between cholesterol/ calcitriol concentrations and the lipid bilayer structure and the role of lipid composition in water permeation.
Supervised learning of high-confidence phenotypic subpopulations from single-cell data
Authors: Ren Tao , Chen Canping , Danilov Alexey V. , Liu Susan , Guan Xiangnan , Du Shunyi , Wu Xiwei , Sherman Mara H. , Spellman Paul T. , Coussens Lisa M. , Adey Andrew C. , Mills Gordon B. , Wu Ling-Yun , Xia Zheng 
Published: March 2023

AbstractAccurately identifying phenotype-relevant cell subsets from heterogeneous cell populations is crucial for delineating the underlying mechanisms driving biological or clinical phenotypes. Here, by deploying a learning with rejection strategy, we developed a novel supervised learning framework called PENCIL to identify subpopulations associated with categorical or continuous phenotypes from single-cell data. By embedding a feature selection function into this flexible framework, for the first time, we were able to select informative features and identify cell subpopulations simultaneously, which enables the accurate identification of phenotypic subpopulations otherwise missed by methods incapable of concurrent gene selection. Furthermore, the regression mode of PENCIL presents a novel ability for supervised phenotypic trajectory learning of subpopulations from single-cell data. We conducted comprehensive simulations to evaluate PENCIL’s versatility in simultaneous gene selection, subpopulation identification and phenotypic trajectory prediction. PENCIL is fast and scalable to analyze 1 million cells within 1 hour. Using the classification mode, PENCIL detected T-cell subpopulations associated with melanoma immunotherapy outcomes. Moreover, when applied to scRNA-seq of a mantle cell lymphoma patient with drug treatment across multiple time points, the regression mode of PENCIL revealed a transcriptional treatment response trajectory. Collectively, our work introduces a scalable and flexible infrastructure to accurately identify phenotype-associated subpopulations from single-cell data.
Artificially cultivated duckweed: a high-efficiency starch producer
Authors: Fang Yang , Guo Ling , Wang Songhu , Xiao Yao , Ding Yanqiang , Jin Yanling , Tian Xueping , Du Anping , Liao Zhihua , He Kaize , Chen Shuang , Zhao Yonggui , Tan Li , Yi Zhuolin , Che Yuqing , Chen Lanchai , Li Jinmeng , Zhao Leyi , Zhang Peng , Gu Zhengbiao , Zhang Fangyuan , Hong Yan , Zhang Qing , Zhao Hai 
Published: March 2023

AbstractThe increasing demand for starch has been a social struggle. We report a new technology that efficiently produces starch from duckweed. AlthoughLandoltia punctatahas a dramatic contraction of gene families, its starch content and productivity reached 72.2% (dry basis) and 10.4 g m-2d-1in 10 days, equivalent to a yield of 38.0 t ha-1y-1under nutrient limitation and CO2elevation treatment. Meanwhile, we also examined the mechanism of duckweed’s high starch accumulation. This is exhibited in the regulation of DNA methylation and transcription factors as well as the significantly up-regulated transcription levels and the increased enzyme activities of key genes in starch biosynthesis. Meantime, while nitrogen redistribution was enhanced, sucrose biosynthesis and transportation, and lignocellulose biosynthesis were all reduced. These alterations led to a reduction in lignocellulose and protein content and ultimately an increase in an accumulation of starch in the chloroplast. This work demonstrates duckweed’s potential of being a highly efficient starch producer.
A simple method to dramatically increaseC. elegansgermline microinjection efficiency
Authors: Gibney Theresa V. , Favichia Michelle , Latifi Laila , Medwig-Kinney Taylor N. , Matus David Q. , McIntyre Daniel C. , Arrigo Angelo B. , Branham Kendall R. , Bubrig Louis T. , Ghaddar Abbas , Jiranek Juliana A. , Liu Kendra E. , Marcucci Charles G. , Porter Robert J. , Pani Ariel M. 
Published: March 2023

AbstractGenome manipulation methods inC. elegansrequire microinjecting DNA or ribonucleoprotein complexes into the microscopic core of the gonadal syncytium. These microinjections are technically demanding and represent a key bottleneck for all genome engineering and transgenic approaches inC. elegans. While there have been steady improvements in the ease and efficiency of genetic methods forC. elegansgenome manipulation, there have not been comparable advances in the physical process of microinjection. Here, we report a simple and inexpensive method for handling worms using a paintbrush during the injection process that nearly tripled average microinjection rates compared to traditional worm handling methods. We found that the paintbrush increased injection throughput by substantially increasing both injection speeds and post-injection survival rates. In addition to dramatically and universally increasing injection efficiency for experienced personnel, the paintbrush method also significantly improved the abilities of novice investigators to perform key steps in the microinjection process. We expect that this method will benefit theC. eleganscommunity by increasing the speed at which new strains can be generated and will also make microinjection-based approaches less challenging and more accessible to personnel and labs without extensive experience.
Coexistence of many species under a random competition-colonization trade-off
Authors: Miller Zachary R. , Clenet Maxime , Libera Katja Della , Massol François , Allesina Stefano 
Published: March 2023

ABSTRACTThe competition-colonization trade-off is a well-studied coexistence mechanism for metacommunities. In this setting, it is believed that coexistence of all species requires their traits to satisfy restrictive conditions limiting their similarity. To investigate whether diverse metacommunities can assemble in a competition-colonization trade-off model, we study their assembly from a probabilistic perspective. From a pool of species with parameters (corresponding to traits) sampled at random, we compute the probability that any number of species coexist and characterize the set of species that emerges through assembly. Remarkably, almost exactly half of the species in a large pool typically coexist, with no saturation as the size of the pool grows, and with little dependence on the underlying distribution of traits. Through a mix of analytical results and simulations, we show that this unlimited niche packing emerges as assembly actively moves communities toward overdispersed configurations in niche space. Our findings also apply to a realistic assembly scenario where species invade one-at-a-time from a fixed regional pool. When diversity arises de novo in the metacommunity, richness still grows without bound, but more slowly. Together, our results suggest that the competition-colonization trade-off can support the robust emergence of diverse communities, even when coexistence of the full species pool is exceedingly unlikely.
Genetic structure and diversity ofrfblocus of pathogenic species of genusLeptospira
Authors: Ferreira L. C. A. , Ferreira Filho L. F. A. , Cosate M. R. V. , Sakamoto T. 
Published: March 2023

AbstractConsidered a globally important zoonotic bacterial disease, leptospirosis affects both humans and commercially important animals. It is transmitted through direct or indirect exposure to the urine of infected animals and is a major public health challenge in regions with heavy rainfall, floods, and poor socioeconomic conditions. The genusLeptospirahas 67 species, which can be grouped into pathogenic and saprophytic groups. Serological classification based on antigenic characteristics is important in epidemiology and clinical analysis but is laborious, requires infrastructure and specialized labor, and takes days to obtain results. In this study, we aimed to find genetic patterns associated with the serological classification ofLeptospirato propose molecular markers for classifyingLeptospirasamples at the serogroup level. For this, we used genomic data of 722 samples distributed in 67 species in public databases and compared the gene composition of theirrfblocus. Clustering analysis was able to group samples into five major classes that share similarities in both the serological and genetic composition of therfblocus. We also identified some syntenic blocks in the internal region of therfblocus and patterns of presence and absence of these blocks which can be used to determine the serogroup of a sample. Our findings can assist the development of molecular strategies for the serological identification ofLeptospirasamples, which could be more rapid and accurate than the current method.
Piperidine CD4-mimetic compounds expose vulnerable Env epitopes sensitizing HIV-1-infected cells to ADCC
Authors: Ding Shilei , Tolbert William D. , Zhu Huile , Lee Daniel , Higgins Tyler , Zhao Xuchen , Nguyen Dung , Sherburn Rebekah , Richard Jonathan , Lepage Gabrielle-Gendron , Medjahed Halima , Mohammadi Mohammadjavad , Abrams Cameron , Pazgier Marzena , Smith Amos B. , Finzi Andrés 
Published: March 2023

ABSTRACTThe ability of HIV-1 accessory proteins Nef and Vpu to decrease CD4 levels contributes to the protection of infected cells from antibody-dependent cellular cytotoxicity (ADCC) by preventing the exposure of Env vulnerable epitopes. Small-molecule CD4 mimetics (CD4mc) based on the indane and piperidine scaffolds such as (+)-BNM-III-170 and (S)-MCG-IV-210 sensitize HIV-1 infected cells to ADCC by exposing CD4-induced (CD4i) epitopes recognized by non-neutralizing antibodies abundantly present in plasma from people living with HIV. Here, we characterize a new family of CD4mc, (S)-MCG-IV-210 derivatives, based on the piperidine scaffold which engage the gp120 within the Phe43 cavity by targeting the highly-conserved Asp368Env residue. We utilized structure-based approaches and developed a series of piperidine analogs with improved activity to inhibit infection of difficult-to-neutralize tier-2 viruses and sensitize infected cells to ADCC mediated by HIV+ plasma. Moreover, the new analogs formed an H-bond with the α-carboxylic acid group of Asp368, opening a new avenue to enlarge the breadth of this family of anti-Env small molecules. Overall, the new structural and biological attributes of these molecules make them good candidates for strategies aimed at the elimination HIV-1-infected cells.