bluuebunny/crossref_metadata_2025_split huggingface dataset:
Galectin-3-binding protein inhibits extracellular heparan 6-O-endosulfatse Sulf-2
Authors: Panigrahi Aswini , Benicky Julius , Aljuhani Reem , Mukherjee Pritha , Nováková Zora , Bařinka Cyril , Goldman Radoslav 
Published: December 2023

AbstractHuman extracellular 6-O-endosulfatases Sulf-1 and Sulf-2 are the only enzymes that post-synthetically alter the 6-Osulfation of heparan sulfate proteoglycans (HSPG), which regulates interactions of HSPG with many proteins. Oncogenicity of Sulf-2 in different cancers has been documented and we have shown that Sulf-2 is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC). In spite of its importance, limited information is available on direct protein-protein interactions of the Sulf-2 protein in the tumor microenvironment. In this study, we used monoclonal antibody (mAb) affinity purification and mass spectrometry to identify galectin-3-binding protein (LG3BP) as a highly specific binding partner of Sulf-2 in the secretome of HNSCC cell lines. We validated their direct interactionin vitrousing recombinant proteins and have shown that the chondroitin sulfate (CS) covalently bound to the Sulf-2 influences the binding to LG3BP. We confirmed importance of the CS chain for the interaction by generating a mutant Sulf-2 protein that lacks the CS. Importantly, we have shown that the LG3BP inhibits Sulf-2 activityin vitroin a concentration dependent manner. As a consequence, the addition of LG3BP to a spheroid cell culture inhibited invasion of the HNSCC cells into Matrigel. Thus, Sulf-2 interaction with LG3BP has functional relevance, and may regulate physiological activity of the Sulf-2 enzyme as well as its activity in the tumor microenvironment.
Mind the gap: A systematic review and meta-analysis of how social memory is studied
Authors: Cum Meghan , Pérez Jocelyn Santiago , Wangia Erika , Lopez Naeliz , Wright Elizabeth S. , Iwata Ryo L. , Li Albert , Chambers Amelia R. , Padilla-Coreano Nancy 
Published: December 2023

AbstractSocial recognition is crucial for survival in social species, and necessary for group living, selective reproduction, pair bonding, and dominance hierarchies. Mice and rats are the most commonly used animal models in social memory research, however current paradigms do not account for the complex social dynamics they exhibit in the wild. To assess the range of social memories being studied, we conducted a systematic analysis of neuroscience articles testing the social memory of mice and rats published within the past two decades and analyzed their methods. Our results show that despite these rodent’s rich social memory capabilities, the majority of social recognition papers explore short-term memories and short-term familiarity levels with minimal exposure between subject and familiar stimuli – a narrow type of social memory. We have identified several key areas currently understudied or underrepresented: kin relationships, mates, social ranks, sex variabilities, and the effects of aging. Additionally, reporting on social stimulus variables such as housing history, strain, and age, is limited, which may impede reproducibility. Overall, our data highlight large gaps in the diversity of social memories studied and the effects social variables have on social memory mechanisms.
Single-cell transcriptomic profiling of the neonatal oviduct and uterus reveals new insights into upper Müllerian duct regionalization
Authors: Jia Shuai , Zhao Fei 
Published: December 2023

AbstractThe upper Müllerian duct (MD) is patterned and specified into two morphologically and functionally distinct organs, the oviduct and uterus. It is known that this regionalization process is instructed by inductive signals from the adjacent mesenchyme. However, the interaction landscape between epithelium and mesenchyme during upper MD development remains largely unknown. Here, we performed single-cell transcriptomic profiling of mouse neonatal oviducts and uteri at the initiation of MD epithelial differentiation (postnatal day 3). We identified major cell types including epithelium, mesenchyme, pericytes, mesothelium, endothelium, and immune cells in both organs with established markers. Moreover, we uncovered region-specific epithelial and mesenchymal subpopulations and then deduced region-specific ligand-receptor pairs mediating mesenchymal-epithelial interactions along the craniocaudal axis. Unexpectedly, we discovered a mesenchymal subpopulation marked by neurofilaments with specific localizations at the mesometrial pole of both the neonatal oviduct and uterus. Lastly, we analyzed and revealed organ-specific signature genes of pericytes and mesothelial cells. Taken together, our study enriches our knowledge of upper Müllerian duct development, and provides a manageable list of potential genes, pathways, and region-specific cell subtypes for future functional studies.
Activation of Store-Operated Calcium Entry and Mitochondrial Respiration by Enterovirus 71 Is Essential for Efficient Virus Replication
Authors: Hsu Bang-Yan , Tsai Ya-Hui , Weng Ta-Chou , Kung Szu-Hao 
Published: December 2023

ABSTRACTEnterovirus (EV) infections disrupt cellular calcium (Ca2+) homeostasis. The EV protein 2B is localized to the endoplasmic reticulum (ER) and causes depletion of ER Ca2+stores. This depletion coincides with a substantial increase in cytosolic Ca2+levels driven by extracellular Ca2+influx. However, the precise mechanism underlying this influx remains elusive. In the present study, we demonstrated that EV71 infections induce store-operated Ca2+entry (SOCE) by activating the Ca2+sensor stromal interaction molecule 1 (STIM1), which subsequently interacts with Orai1, a plasma membrane (PM) Ca2+channel. This finding was supported by confocal imaging, which revealed that STIM1, typically localized in the ER, becomes active and colocalizes with Orai1 at the PM in EV71-infected cells. Pharmacological inhibition of the STIM1–Orai1 interaction and knockdown of either STIM1 or Orai1 significantly reduced virus-induced cytosolic Ca2+levels and viral replication. Global transcriptome analysis revealed that differentially expressed genes are primarily associated with the mitochondrial electron transport chain (ETC) upon SOCE activation, contributing to enhanced ATP generation and oxygen consumption. This increase in mitochondrial Ca2+levels is correlated with the mid-stage of virus infection. Furthermore, we demonstrated that high levels of mitochondrial Ca2+influx led to apoptotic cell death favoring viral release at the late stage of virus infection. Finally, SOCE-dependent EV replication was observed in a mouse intestinal organoid culture, a more physiologically relevant cell system. Our results provide valuable insights into the mechanism through which EV infections induce SOCE-mediated spatial and temporal control of Ca2+signaling, substantially affecting the virus life cycle.IMPORTANCEHost cell Ca2+signals play crucial roles in various steps of virus life cycles, including entry, replication, and exit. EV requires increased cytosolic Ca2+levels for efficient replication, but the precise mechanisms underlying the association between Ca2+levels and EV replication remain elusive. Using EV71 as a model virus, we demonstrated that EV71 infection elevated cytosolic Ca2+levels through store-operated Ca2+entry activation and progressive Ca2+mobilization to mitochondria. This led to the upregulation of electron transport chain activity, which is essential for efficient virus replication and apoptotic cell death, facilitating viral release during the mid and late stages of the infectious cycle, respectively. These findings substantially enhance the understanding of how EVs co-opt host cell mechanisms to promote their own life cycle. STIM1 and Orai1 may be novel targets for broad-spectrum host-directed therapeutics against EVs and other viruses that employ similar replication mechanisms.
Metagenomic Detection and Genetic Characterization of Human Sapovirus among Children in Nigeria
Authors: Uwem George Etop , Temitope Faleye O. C. , Lander De Coninck , Sheriff Agbaje Tunde , Ijeoma Ifeorah Maryjoy , Bernard Onoja Anyebe , Elijah Oni Igbekele , Oluseyi Olayinka Adebowale , Toluwani Ajileye Goodnews , Arthur Oragwa Obinna , Toluwanimi Akinleye Emmanuel , Bolutife Popoola Olubukola , Oluwadamilola Osasona Gideon , Olaitan Olayinka Titilola , Oluwadamilola George Adefunke , Ahmed Muhammad Iluoreh , Isaac Komolafe , Adekunle Adeniji Johnson , Jelle Matthijnssens , Olubusuyi Adewumi Moses 
Published: December 2023

AbstractUsing a metagenomic sequencing approach on stool samples from children with Acute Flaccid Paralysis (AFP), we describe the genetic diversity of Sapoviruses (SaVs) in children in Nigeria. We identified six near-complete genome sequences and two partial genome sequences. Multiple SaV genogroups and genotypes were detected, including GII (GII.4 and GII.8), GIV (GIV.1) and GI (GI.2 and GI.7). Sequence identity and phylogenetic analysis showed that the Nigerian SaVs were related to previously documented gastroenteritis outbreaks associated strains from China and Japan. Minor variations in the functional motifs of the nonstructural proteins NS3 and NS5 were confirmed in the Nigerian strains. To adequately understand the effect of such amino acid changes, a better understanding of the biological function of these proteins is vital. The identification of distinct SaVs reinforces the need for robust surveillance in acute gastroenteritis (AGE) and non-AGE cohorts to better understand SaVs genotype diversity, evolution, and its role in disease burden in Nigeria.
Persistence of an infectious form of SARS-CoV-2 post protease inhibitor treatment of permissive cells in vitro
Authors: Nair Manoj S. , Luck Maria I. , Huang Yaoxing , Sabo Yosef , Ho David D. 
Published: December 2023

SummaryReports have described SARS-CoV-2 rebound in COVID-19 patients treated with nirmatrelvir, a 3CL protease inhibitor. The cause remains a mystery, although drug resistance, re-infection, and lack of adequate immune responses have been excluded. We now present virologic findings that provide a clue to the cause of viral rebound, which occurs in ∼20% of the treated cases. The persistence of an intermediary form of infectious SARS-CoV-2 was experimentally documented in vitro after treatment with nirmatrelvir or another 3CL protease inhibitor, but not with a polymerase inhibitor, remdesivir. This infectious intermediate decayed slowly with a half-life of ∼1 day, suggesting that its persistence could outlive the treatment course to re-ignited SARS-CoV-2 infection as the drug is eliminated. Additional studies are needed to define the nature of this viral intermediate, but our findings point to a particular direction for future investigation and offer a specific treatment recommendation that should be tested clinically.
Profiling cellular heterogeneity and fructose transporter expression in the rat nephron by integrating single-cell and microdissected tubule segment transcriptomes
Authors: Zhang Ronghao , Jadhav Darshan Aatmaram , Kramer Benjamin , Gonzalez-Vicente Agustin ,   the Kidney Precision Medicine Project
Published: December 2023

AbstractSingle-cell RNA sequencing (scRNAseq) is a crucial tool in kidney research. These technologies cluster cells according to transcriptome similarity, irrespective of the anatomical location and ordering within the nephron. Thus, a cluster transcriptome may obscure heterogeneity of the cell population within a nephron segment. Elevated dietary fructose leads to salt-sensitive hypertension, in part by fructose reabsorption in the proximal tubule (PT). However, organization of the four known fructose transporters in apical PTs (SGLT4, SGLT5, GLUT5 and NaGLT1) remains poorly understood. We hypothesized that cells within each subsegment of the proximal tubule exhibit complex, heterogenous fructose transporter expression patterns. To test this hypothesis we analyzed rat and kidney transcriptomes and proteomes from publicly available scRNAseq and tubule microdissection databases. We found that microdissected PT-S1 segments consist of 81±12% cells with scRNAseq-derived transcriptional characteristics of S1, whereas PT-S2 express a mixture of 18±9% S1, 58±8% S2, and 19±5% S3 transcripts, and PT-S3 consists of 75±9% S3 transcripts. The expression of all four fructose transporters was detectable in all three PT segments, but key fructose transporters SGLT5 and GLUT5 progressively increased from S1 to S3, and both were significantly upregulated in S3 vs. S1/S2 (Slc5a10: 1.9 log2FC, p<1×10-299; Scl2a5: 1.4 log2FC, p<4×10-105). A similar distribution was found in human kidneys. These data suggest that S3 is the primary site of fructose reabsorption in both humans and rats. Finally, because of the multiple scRNAseq transcriptional phenotypes found in each segment our findings also imply that anatomic labels applied to scRNAseq clusters may be misleading.
AlphaFold2 structures template ligand discovery
Authors: Lyu Jiankun , Kapolka Nicholas , Gumpper Ryan , Alon Assaf , Wang Liang , Jain Manish K. , Barros-Álvarez Ximena , Sakamoto Kensuke , Kim Yoojoong , DiBerto Jeffrey , Kim Kuglae , Tummino Tia A. , Huang Sijie , Irwin John J. , Tarkhanova Olga O. , Moroz Yurii , Skiniotis Georgios , Kruse Andrew C. , Shoichet Brian K. , Roth Bryan L. 
Published: December 2023

AbstractAlphaFold2 (AF2) and RosettaFold have greatly expanded the number of structures available for structure-based ligand discovery, even though retrospective studies have cast doubt on their direct usefulness for that goal. Here, we tested unrefined AF2 modelsprospectively, comparing experimental hit-rates and affinities from large library docking against AF2 models vs the same screens targeting experimental structures of the same receptors. Inretrospectivedocking screens against the σ2and the 5-HT2A receptors, the AF2 structures struggled to recapitulate ligands that we had previously found docking against the receptors’ experimental structures, consistent with published results.Prospectivelarge library docking against the AF2 models, however, yielded similar hit rates for both receptors versus docking against experimentally-derived structures; hundreds of molecules were prioritized and tested against each model and each structure of each receptor. The success of the AF2 models was achieved despite differences in orthosteric pocket residue conformations for both targets versus the experimental structures. Intriguingly, against the 5-HT2A receptor the most potent, subtype-selective agonists were discovered via docking against the AF2 model, not the experimental structure. To understand this from a molecular perspective, a cryoEM structure was determined for one of the more potent and selective ligands to emerge from docking against the AF2 model of the 5-HT2A receptor. Our findings suggest that AF2 models may sample conformations that are relevant for ligand discovery, much extending the domain of applicability of structure-based ligand discovery.
Engineered Skin Microbiome Reduces Mosquito Attraction to Mice
Authors: Liu Feng , Coutinho-Abreu Iliano V. , Raban Robyn , Nguyen Tam Thuy Dan , Dimas Alejandra R. , Merriman Joseph A. , Akbari Omar S. 
Published: December 2023

AbstractThe skin microbiome plays a pivotal role in the production of attractive cues detected by mosquitoes. Here we leveraged recent advances in genetic engineering to significantly reduce the production of L-(+)-lactic acid as a strategy to reduce mosquito attraction to the highly prominent skin commensalsStaphylococcus epidermidisandCorynebacterium amycolatum. Engraftment of these engineered bacteria onto the skin of mice reduced mosquito attraction and feeding for up to 11 uninterrupted days, which is considerably longer than the several hours of protection conferred by the leading chemical repellent DEET. Taken together, our findings demonstrate engineering the skin microbiome to reduce attractive volatiles represents an innovative untapped strategy to reduce vector attraction, preventing bites, and pathogen transmission setting the stage for new classes of long-lasting microbiome-based repellent products.One-Sentence SummaryModified microbes make skin less attractive to mosquitoes
STOPGAP, an open-source package for template matching, subtomogram alignment, and classification
Authors: Wan William , Khavnekar Sagar , Wagner Jonathan 
Published: December 2023

AbstractCryo-electron tomography (cryo-ET) enables molecular-resolution 3D imaging of complex biological specimens such as viral particles, cellular sections, and in some cases, whole cells. This enables the structural characterization of molecules in their near-native environments, without the need for purification or separation, thereby preserving biological information such as conformational states and spatial relationships between different molecular species. Subtomogram averaging is an image processing workflow that allows users to leverage cryo-ET data to identify and localize target molecules, determine high-resolution structures of repeating molecular species, and classifying different conformational states. Here we describe STOPGAP, an open-source package for subtomogram averaging designed to provide users with fine control over each of these steps. In providing detailed descriptions of the image processing algorithms that STOPGAP uses, we intend for this manuscript to also serve as a technical resource to users as well as further community-driven software development.
CD4+T cells are homeostatic regulators duringMtbreinfection
Authors: Bromley Joshua D. , Ganchua Sharie Keanne C. , Nyquist Sarah K. , Maiello Pauline , Chao Michael , Borish H. Jacob , Rodgers Mark , Tomko Jaime , Kracinovsky Kara , Mugahid Douaa , Nguyen Son , Wang Dennis , Rosenberg Jacob M. , Klein Edwin C. , Gideon Hannah P. , Floyd-O’Sullivan Roisin , Berger Bonnie , Scanga Charles A , Lin Philana Ling , Fortune Sarah M. , Shalek Alex K. , Flynn JoAnne L. 
Published: December 2023

ABSTRACTImmunological priming – either in the context of prior infection or vaccination – elicits protective responses against subsequentMycobacterium tuberculosis(Mtb) infection. However, the changes that occur in the lung cellular milieu post-primaryMtbinfection and their contributions to protection upon reinfection remain poorly understood. Here, using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrate that priorMtbinfection elicits a long-lasting protective response against subsequentMtbexposure and that the depletion of CD4+T cells prior toMtbrechallenge significantly abrogates this protection. Leveraging microbiologic, PET-CT, flow cytometric, and single-cell RNA-seq data from primary infection, reinfection, and reinfection-CD4+T cell depleted granulomas, we identify differential cellular and microbial features of control. The data collectively demonstrate that the presence of CD4+T cells in the setting of reinfection results in a reduced inflammatory lung milieu characterized by reprogrammed CD8+T cell activity, reduced neutrophilia, and blunted type-1 immune signaling among myeloid cells, mitigatingMtbdisease severity. These results open avenues for developing vaccines and therapeutics that not only target CD4+and CD8+T cells, but also modulate innate immune cells to limitMtbdisease.
Climate change decreases the likelihood of tropical forest community persistence with a strong mediation of plant-plant network structures
Authors: Luo Zijing , Liu Hanlun , Li Yuanzhi , Wang Weimin , Mayfield Margaret M. , Chu Chengjin 
Published: December 2023

AbstractClimate change is known to negatively impact tropical forests; yet how climate change impacts tree community persistence at local scales remains less clear. Using data from a long-term tropical forest census plot over 25 years, we constructed plant- plant interaction networks based on tree growth. We then quantified community persistence as feasibility domain of constituent species using recently developed frameworks of structural stability. We found a decrease in structural stability under warming and precipitation changes over time as evidenced by both direct environmental effects and indirect effects via network structure; and indirect effects were stronger than direct effects. Among these structures, facilitation:competition degree ratio and competitive transitivity were most positively related with structural stability. Our study highlights how the lens of plant-plant interaction networks can identify novel details about risk to tropical forest diversity under climate change at local scales. Insights from this work will be helpful for aligning forest management activities with areas under the greatest risk of species loss.
Development and validation of allele specificRLKgene markers for banana bunchy top disease (BBTD) resistance in banana
Authors: Caro Reina Esther S. , Manohar Anand Noel C. , Gardoce Roanne R. , Dela Cueva Fe M. , Gueco Lavernee S. , Manuel Ma. Carmina C. , Lantican Darlon V. 
Published: December 2023

ABSTRACTAs global demand for bananas rises, the threat of banana bunchy top disease (BBTD), caused bybanana bunchy top virus(BBTV), poses a significant constraint to sustainable banana production. To circumvent this, it is critical to fast-track the development of BBTV-resistant banana cultivars. In a dataset of differentially expressed genes between BBTV-resistant and susceptible bananas, sixRLKgenes involved in plant defense against pathogens were exclusively upregulated in the BBTV-resistant wildMusa balbisianacompared to the BBTV-susceptibleMusa acuminatacv. ’Lakatan’. Here, two genic variants ofRLKs, single nucleotide polymorphisms (SNPs) and simple sequence repeats (SSR), were identified in 10 banana accessions representing major genomic groupings. Nine gene-specific markers were developed using three marker systems: SSR, allele-specific PCR, and tetra primer amplification refractory mutation system PCR markers. Six of these were polymorphic and successfully discriminated 117Musagenotypes at the NPGRL-IPBex situgermplasm, with an average polymorphism information content of 0.36 for SNP markers and 0.49 for SSR marker, both of which are moderately informative. These markers facilitated the construction of a dendrogram using the Unweighted Neighbor-Joining (UNJ) method with 1000 bootstrap iterations, identifying four major clades:M. acuminataspp. and otherMusaspp. (I), wildM. balbisiana(BBw) and other accessions with high-proportion of B-genome (II & III), hybrid bananas (triploids and tetraploids) (IV), which revealed the genetic diversity and relationships amongMusaaccessions. Ultimately, this genomic resource will aid in positioning the Philippines as a key player in banana disease resistance breeding towards a food-secure banana industry.
Metabolic scaling in small life forms
Authors: Ritchie Mark E. , Kempes Christopher P. 
Published: December 2023

AbstractMetabolic scaling is one of the most important patterns in biology. Theory explaining the 3/4-power size-scaling of biological metabolic rate does not predict the non-linear scaling observed for smaller life forms. Here we present a new model for cells < 10−8m3that maximizes power from the reaction-displacement dynamics of enzyme-catalyzed reactions. Maximum metabolic rate is achieved through an allocation of cell volume to optimize a ratio of reaction velocity to molecular movement. Small cells < 10−17m3generate power under diffusion by diluting enzyme concentration as cell volume increases. Larger cells require bulk flow of cytoplasm generated by molecular motors. These outcomes predict curves with literature-reported parameters that match the observed scaling of metabolic rates for unicells, and predicts the volume at which Prokaryotes transition to Eukaryotes. We thus reveal multiple size-dependent physical constraints for microbes in a model that extends prior work to provide a parsimonious hypothesis for how metabolism scales across small life.