bluuebunny/crossref_metadata_2025_split huggingface dataset:
The maizestriate leaves2(sr2) gene encodes a conserved DUF3732 domain homologous to the riceyss1gene
Authors: Brady Meghan J. , Cheam Maya , Gent Jonathan I. , Dawe R. Kelly 
Published: October 2023

ABSTRACTMaize striate leaves2(sr2) is a mutant that causes white stripes on leaves that has been used in mapping studies for decades, though the underlying gene has not been identified. Thesr2locus has been previously mapped to small regions of the normal chromosome 10 (N10) and a rearranged variant called Abnormal Chromosome 10 (Ab10). A comparison of assembled genomes carrying N10 and Ab10 revealed only five candidatesr2genes. Analysis of a stock carrying thesr2reference allele (sr2-ref) showed that one of the five genes has a transposon insertion that disrupts its protein sequence and has a severe reduction in mRNA. An independent Mutator transposon insertion in the gene (sr2-Mu) failed to complement thesr2-refmutation, and plants homozygous forsr2-Mushowed white striped leaf margins. Thesr2gene encodes a DUF3732 protein with strong homology to a rice gene with a similar mutant phenotype calledyoung seedling stripe1(yss1). These and other published data suggest thatsr2may have a function in plastid gene expression.
The commonTMEM173 HAQ, AQalleles rescue CD4 T cellpenia, restore T-regs, and preventSAVI (N153S)inflammatory disease in mice
Authors: Aybar-Torres Alexandra , Saldarriaga Lennon A , Pham Ann T. , Emtiazjoo Amir M. , Sharma Ashish K , Bryant Andrew J. , Jin Lei 
Published: October 2023

AbstractThe significance of STING (encoded by theTMEM173gene) in tissue inflammation and cancer immunotherapy has been increasingly recognized. Intriguingly, common humanTMEM173alleles R71H-G230A-R293Q (HAQ)and G230A-R293Q (AQ) are carried by ∼60% of East Asians and ∼40% of Africans, respectively. Here, we examine the modulatory effects ofHAQ, AQalleles on STING-associated vasculopathy with onset in infancy (SAVI), an autosomal dominant, fatal inflammatory disease caused by gain-of-function humanSTINGmutations. CD4 T cellpenia is evident in SAVI patients and mouse models. Using STING knock-in mice expressing common humanTMEM173allelesHAQ,AQ, andQ293, we found thatHAQ, AQ, andQ293splenocytes resist STING-mediated cell deathex vivo,establishing a critical role of STING residue 293 in cell death. TheHAQ/SAVI(N153S)andAQ/SAVI(N153S)mice did not have CD4 T cellpenia. TheHAQ/SAVI(N153S), AQ/SAVI(N153S)mice have more (∼10-fold, ∼20-fold, respectively) T-regs thanWT/SAVI(N153S)mice. Remarkably, while they have comparable TBK1, IRF3, and NFκB activation as theWT/SAVI, theAQ/SAVImice have no tissue inflammation, regular body weight, and normal lifespan. We propose that STING activation promotes tissue inflammation by depleting T-regs cellsin vivo. Billions of modern humans have the dominantHAQ, AQalleles. STING research and STING-targeting immunotherapy should considerTMEM173heterogeneity in humans.TeaserCommon humanHAQ, AQ TMEM173alleles dominate the gain-of-functionSAVI(N154S) TMEM173mutant in mice.
Photosynthesis is led by stomatal circadian rhythm and not by starch depletion after a long period of darkness
Authors: Dresch Cédric , Vidal Véronique , Suchail Séverine , Sallanon Huguette , Charles Florence , Truffault Vincent 
Published: October 2023

AbstractThe circadian rhythm is an endogenous rhythm, defined by repeated metabolic oscillations every 24 hours under constant parameters. In plants, the circadian rhythm regulates the growth through photosynthesis and the management of carbohydrates. In indoor farming, the photoperiod is independent from the sunlight and is of interest to increase energy savings. In this work, we studied the effects of modifications of photoperiods on indoor-grown lettuces (L. sativa), which were then not tuned with the circadian rhythm. The pattern of photoperiods applied was: 16/12-16/8-16/8. A mutant-free study was carried out to avoid genes shutdown unintended side effects and to evaluate the impact of the circadian rhythm under marketable production conditions. We observed that the circadian regulation of the stomatal conductance was the main limiting factor of net photosynthesis when the photoperiod is exceptionally not tuned with the circadian rhythm. In our experiment, the disruption of the circadian rhythm decreased the photosynthetic activity by 6.2% throughout the light period, with no alteration of the yield, morphology or light and water use efficiencies. Furthermore, starch depletion induced by the changes in the photoperiod could not explain variations of the net photosynthetic activity during the following light period. Interestingly, disrupting the circadian rhythm saved 5% of lighting time compared to the control, which can be converted into energy savings. Consequently, the circadian rhythm can be defined as a limiting factor for reducing energy consumption in indoor farming. Further characterization of the links between the photosynthesis-carbohydrates-growth continuum and the circadian rhythm is thus required.
Human GM-CSF/IL-3 enhance tumor immune infiltration in humanized HCC patient-derived xenografts
Authors: Weinfurtner Kelley , Tischfield David , McClung George , Crainic Jennifer , Gordan John , Jiao Jing , Furth Emma E. , Li Wuyan , Tuzneen Supan Erena , Nadolski Gregory J. , Hunt Stephen J. , Kaplan David E. , Gade Terence P.F. 
Published: October 2023

ABSTRACTBackground & AimsResponses to immunotherapies in hepatocellular carcinoma (HCC) are suboptimal with no biomarkers to guide patient selection. “Humanized” mice represent promising models to address this deficiency but are limited by variable chimerism and underdeveloped myeloid compartments. We hypothesized that expression of human GM-CSF and IL-3 increases tumor immune cell infiltration, especially myeloid-derived cells, in humanized HCC patient-derived xenografts (PDXs).Material and MethodsNOG (NOD/Shi-scid/IL-2Rnull) and NOG-EXL (huGM-CSF/huIL-3 NOG) mice conditioned with Busulfan underwent i.v. injection of human CD34+ cells. HCC PDX tumors were then implanted subcutaneously (SQ) or orthotopically (OT). Following serial blood sampling, mice were euthanized at defined tumor sizes. Tumor, blood, liver, and spleen were analyzed by flow cytometry and immunohistochemistry.ResultsHumanized NOG-EXL mice demonstrated earlier and increased human chimerism compared to humanized NOG mice (82.1% vs 43.8%, p<0.0001) with increased proportion of human monocytes (3.2% vs 1.1%, p=0.001) and neutrophils (0.8% vs 0.3%, p=0.02) in circulation. HCC tumors in humanized NOG-EXL mice had increased human immune cell infiltration (57.6% vs 30.2%, p=0.04), noting increased regulatory T cells (14.6% vs 6.8%, p=0.04), CD4+ PD-1 expression (84.7% vs 32.0%, p<0.01), macrophages (1.2% vs 0.6%, p=0.02), and neutrophils (0.5% vs 0.1%, p<0.0001). No differences were observed in tumor engraftment or growth latency in SQ tumors, but OT tumors required implantation at two rather than four weeks post-humanization for successful engraftment. Finally, utilizing adult bone marrow instead of fetal livers enabled partial HLA-matching to HCC tumors but required more CD34+ cells.ConclusionsHuman GM-CSF and IL-3 expression in humanized mice resulted in features more closely approximating the immune microenvironment of human disease, providing a promising model for investigating critical questions in immunotherapy for HCC.Impact and ImplicationsThis study introduces a unique mouse model at a critical point in the evolution of treatment paradigms for patients with hepatocellular carcinoma (HCC). Immunotherapies have become first line treatment for advanced HCC; however, response rates remain low with no clear predictors of response to guide patient selection. In this context, animal models that recapitulate human disease are greatly needed. Leveraging xenograft tumors derived from patients with advanced HCCs and a commercially available immunodeficient mouse strain that expresses human GM-CSF and IL-3, we demonstrate a novel but accessible approach for modeling the HCC tumor microenvironment.
Methanotroph phenotypic heterogeneity in a methane-oxygen counter gradient
Authors: Beals Delaney G. , Puri Aaron W. 
Published: October 2023

ABSTRACTConnecting genes to phenotypic traits in bacteria is often challenging because of a lack of environmental context in laboratory settings. Laboratory-based model ecosystems offer a means to better account for environmental conditions compared to standard planktonic cultures, and can help link genotypes and phenotypes. Here, we present a simple, cost-effective, laboratory-based model ecosystem to study aerobic methane-oxidizing bacteria (methanotrophs) within the methane-oxygen counter gradient typically found in the natural environment of these organisms. Culturing the methanotrophMethylomonassp. strain LW13 in this system resulted in formation of a distinct horizontal band at the intersection of the counter gradient, which we discovered was not due to increased numbers of viable bacteria at this location but instead to an increased amount of polysaccharides. We also discovered that different methanotrophic taxa form polysaccharide bands with distinct locations and morphologies when grown in the methane-oxygen counter gradient. By comparing transcriptomic data from LW13 growing within and surrounding this band, we identified genes upregulated within the band and validated their involvement in growth and band formation within the model ecosystem using knockout strains. Notably, deletion of these genes did not negatively affect growth using standard laboratory conditions. This work highlights the use of a laboratory-based model ecosystem that more closely mimics the natural environment to uncover methanotroph phenotypes missing from standard planktonic cultures, and to link these phenotypes with their genetic determinants.
Differential encoding of odor and place in mouse piriform and entorhinal cortex
Authors: Mena Wilson , Baker Keeley , Rubin Alon , Kohli Shaun , Yoo Yun , Bathellier Brice , Ziv Yaniv , Rezaei-Mazinani Shahab , Fleischmann Alexander 
Published: October 2023

AbstractThe integration of olfactory and spatial information is critical for guiding animal behavior. The lateral entorhinal cortex (LEC) is reciprocally interconnected with cortical areas for olfaction and the hippocampus and thus ideally positioned to encode odor-place associations. Here, we used mini-endoscopes to record neural activity in the mouse piriform cortex (PCx) and LEC. We show that in head-fixed mice, odor identity could be decoded from LEC ensembles, but less accurately than from PCx. In mice freely navigating a linear track, LEC ensemble activity at the odor ports was dominated by spatial information. Spatial position along the linear track could be decoded from LEC and PCx activity, however, PCx but not LEC exhibited strong behavior-driven modulation of positional information. Together, our data reveal that information about odor cues and spatial context is differentially encoded along the PCx-LEC axis.Significance statementFor most animals, the sense of smell is essential for successfully navigating the environment to find food, shelter, and mates. However, how olfactory and spatial information is integrated in the brain to support olfactory-guided behaviors remains poorly understood. In mammals, candidate brain regions thought to support odor-place associations include the olfactory (piriform, PCx) cortex, entorhinal cortex, and hippocampus. We here characterize the activity of cells in the PCx and lateral entorhinal cortex (LEC) of freely moving mice in response to odor cues presented in a linear track. Using mini-endoscope microscopy and population coding analyses, we find that information about odors, spatial location, and behavior is differentially encoded along the PCx-LEC axis.
Large-scale imputation models for multi-ancestry proteome-wide association analysis
Authors: Wu Chong , Zhang Zichen , Yang Xiaochen , Zhao Bingxin 
Published: October 2023

AbstractProteome-wide association studies (PWAS) decode the intricate proteomic landscape of biological mechanisms for complex diseases. Traditional PWAS model training relies heavily on individual-level reference proteomes, thereby restricting its capacity to harness the emerging summary-level protein quantitative trait loci (pQTL) data in the public domain. Here we introduced a novel framework to train PWAS models directly from pQTL summary statistics. By leveraging extensive pQTL data from the UK Biobank, deCODE, and ARIC studies, we applied our approach to train large-scale European PWAS models (totaln= 88,838 subjects). Furthermore, we developed PWAS models tailored for Asian and African ancestries by integrating multi-ancestry summary and individual-level data resources (totaln= 914 for Asian and 3,042 for African ancestries). We validated the performance of our PWAS models through a systematic multi-ancestry analysis of over 700 phenotypes across five major genetic data resources. Our results bridge the gap between genomics and proteomics for drug discovery, highlighting novel protein-phenotype links and their transferability across diverse ancestries. The developed PWAS models and data resources are freely available atwww.gcbhub.org.
Modelling termites’ tunnelling and decision-making behaviors
Authors: Mandal Sajib , Oberst Sebastian , Lai Joseph C. S. 
Published: October 2023

AbstractTermites’ digging and construction behavior plays an important role in understanding termites’ foraging and nesting strategies. Termites build galleries when they tunnel that building behavior is different from ants. Therefore, termite tunnelling behavior such as tunnelling networks (tunnel growth and branching), and direction-changing when generating new branches and encountering obstacles require more research. Measurement of termites’ tunnel growth in the experimental arena is often conducted manually by comparing photo sequences. Here, we observe the tunnelling behaviors of the small-sized desert subterranean termite (Heterotermes aureus) and the larger arid land subterranean termite (Reticulitermes tibialis) and develop a mathematical model to describe termites’ tunnelling behavior in the arena. The model can estimate the possible tunnel length with respect to termite body length over a certain time based on three data inputs. Another advantage of this model is that it takes only a few seconds to show results. The results of the model are verified numerically. A behavioral model based on a decision tree is also developed to investigate termites’ direction-changing mechanisms in tunnelling when generating branches and encountering obstacles. Thus, this study demonstrates methods to characterize and model termites’ tunnelling mechanism and direction-changing behavior, which might be applicable to other insects’ behavior and algorithm mimicking digging and tunneling behavior of ants.
Profiling Chromatin Accessibility in Humans Using Adenine Methylation and Long-Read Sequencing
Authors: Akbari Vahid , Leelakumari Sreeja , Jones Steven J.M. 
Published: October 2023

AbstractChromatin accessibility demonstrates accessible DNA regions that usually have regulatory function. Several studies have demonstrated DNA accessibility profiling using nanopore sequencing and GpC or adenine modification. However, the GpC dinucleotide is not evenly distributed across the genome and there are regions sparse in GpC. 6mA studies have demonstrated chromatin accessibility in yeast using nanopore based sequencing, although a high-false positive in 6mA detection rate and low coverage have previously precluded the effective use in mammalian sized genomes. Here, we have developed accurate 6mA base calling and demonstrated high-resolution profiling of accessible regions and simultaneous CpG methylation detection in humans using long read sequencing.
The role of family and environment in determining the skin microbiome of captive aquatic frogs,Xenopus laevis
Authors: Chapman Phoebe A. , Hudson Daniel , Morgan Xochitl C. , Beck Caroline W. 
Published: October 2023

AbstractBackgroundThe amphibian skin microbiome has drawn interest due to the ecological threat posed by chytridiomycosis, which drives changes in symbiotic microbial communities and may be inhibited by certain bacterial taxa. However, skin microbes also play a role in amphibian tissue regeneration.Xenopusspp. are well-established model organisms used to study development, regeneration, genetics and disease. Husbandry protocols, including use of antibiotics and other sterilising agents, may affect experimental outcomes by altering microbiomes. It is therefore essential to improve our understanding ofXenopusmicrobiome characteristics and inheritance. We undertook bacterial 16S rRNA based sampling of a captive, closedXenopus laeviscolony. A total of 16 female frogs, their eggs, and tadpoles were sampled, covering multiple aquarium systems and tanks, along with testes from males used for in vitro fertilisation and a range of environmental samples.ResultsTank environments supported the most complex microbial communities. Mother frogs harboured the most diverse microbial communities of the frog life stages, with tadpole skin microbiomes being relatively simple. Frog samples were dominated by Proteobacteria and Bacteroidota.RhizobiumandChryseobacteriumwere dominant in tadpoles, whereas mothers supported high proportions ofVogesellaandAcinetobacteras well asChryseobacterium. While the mothers’ habitats contained low levels of these taxa, the tadpole’s environmental microbes were very similar to those on tadpole skin. A total of 34 genera were found to be differentially abundant between the mothers and tadpoles. Analysis of Bray-Curtis distances indicated that mother and tadpole microbiomes varied according to the mothers’ aquarium system, the tanks within them, and the individual mother. Source tracking analyses showed that egg jelly and tadpoles received a mean of approximately two thirds of their microbiomes via vertical transmission, although a sizeable proportion came from unknown sources at all life stages.ConclusionsThe skin of mother frogs appears to select for certain taxa that are otherwise present at low abundances in the environment. While tadpoles inherit a proportion of their microbiomes from their mothers via the egg, they support a distinct and less diverse microbial community than adult frogs. The microbiome varies between individual mothers, and is also affected by the aquarium system and individual tank within that the mother occupies.
Immune response and resistance of clear cell renal cell carcinoma patients following immune checkpoint blockade
Authors: Mestrallet Guillaume 
Published: October 2023

Abstract175,000 patients die because of renal cell carcinoma (RCC) each year. Clear cell renal cell carcinoma (ccRCC or KIRC) is the most frequent subtype of RCC. Current therapies include immune checkpoint inhibitors (ICB) or VEGFR tyrosine kinase inhibitors (TKIs). However, many patients did not respond to ICB and immune resistance still occurred. Immune resistance may be explained by expression of various immune checkpoints and immunosuppressive pathways in KIRC patients. Thus, it is important to identify mechanisms driving immune response and resistance following ICB. To address this question, we performed an analysis of 3 KIRC cohorts treated with 3 different ICB. Overall, 20-30% of KIRC patients respond to ICB. Responders with metastasized stage IV cancer with tumorectomy prior to anti-PD-L1 are characterized by an increase in CD4+ and CD8+ T cell infiltration, and by better antigen presentation and T cell responses (BTN3A1, PRF1andCD27genes). However, the expression of CTLA4, TIGIT and BTLA in Th1, Th17 and M2 subsets may limit complete response in responders. Importantly, non-responders patients are characterized by higher infiltration by macrophages, and by overexpression of regulatory gene (ADORA2A) in Th2, CD8+ T cell, M1 and M2 clusters. Targeting these pathways may help to develop combination therapies to improve KIRC patient outcomes.
A customizable multiplex protein microarray for antibody testing and its application for tick-borne and other infectious diseases
Authors: Krishnamurthy Hari Krishnan , Jayaraman Vasanth , Krishna Karthik , Wang Tianhao , Bei Kang , Suresh Chithra , Matilda Shiny , Rai Alex J , Welc-Falęciak Renata , Pawełczyk Agnieszka , Blanton Lucas S. , Chrdle Aleš , Fořtová Andrea , Růžek Daniel , Nasrallah Gheyath K. , Abu-Raddadi Laith J. , Al-Sadeq Duaa W. , Abdallah Marah Abed Alhakim , Lilleri Daniele , Fornara Chiara , D’Angelo Piera , Furione Milena , Venermo Maria Söderlund- , Hedman Klaus , Chochlakis Dimosthenis , Psaroulaki Anna , Makridaki Eirini , Ntoula Artemis , Rajasekaran John J. 
Published: October 2023

AbstractTick-borne infections are the most common vector-borne diseases in the USA. Ticks harbor and spread several infections with Lyme disease being the most common tickborne infection in the US and Europe. Lack of awareness about tick populations, specific diagnostic tests, and overlapping symptoms of tick-borne infections can often lead to misdiagnosis affecting treatment and the prevalence data reported especially for non-Lyme tick-borne infections. The diagnostic tests currently available for tick-borne diseases are severely limited in their ability to provide accurate results and cannot detect multiple pathogens in a single run. The multiplex protein microarray developed at Vibrant was designed to detect multiple serological antibodies thereby detecting exposure to multiple pathogens simultaneously. Our microarray in its present form can accommodate 400 antigens and can multiplex across antigen types, whole cell sonicates, recombinant proteins, and peptides. A designed array containing multiple antigens of several microbes includingBorrelia burgdorferi,the Lyme disease spirochete, was manufactured and evaluated. The immunoglobulin M (IgM) and G (IgG) responses against several tick-borne microbes and other infectious agents were analyzed for analytical and clinical performance. The microarray improved IgM and IgG sensitivities and specificities of individual microbes when compared with the respective gold standards. The testing was also performed in a single run in comparison to multiple runs needed for comparable testing standards. In summary, our study presents a flexible multiplex microarray platform that can provide quick results with high sensitivity and specificity for evaluating exposure to varied infectious agents especially tick-borne infections.