bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pangenomics provides insights into the role of synanthropy in barn swallow evolution
Authors: Secomandi Simona , Gallo Guido Roberto , Sozzoni Marcella , Iannucci Alessio , Galati Elena , Abueg Linelle , Balacco Jennifer , Caprioli Manuela , Chow William , Ciofi Claudio , Collins Joanna , Fedrigo Olivier , Ferretti Luca , Fungtammasan Arkarachai , Haase Bettina , Howe Kerstin , Kwak Woori , Lombardo Gianluca , Masterson Patrick , Messina Graziella , Møller Anders Pape , Mountcastle Jacquelyn , Mousseau Timothy A. , Ferrer-Obiol Joan , Olivieri Anna , Rhie Arang , Rubolini Diego , Saclier Marielle , Stanyon Roscoe , Stucki David , Thibaud-Nissen Françoise , Torrance James , Torroni Antonio , Weber Kristina , Ambrosini Roberto , Bonisoli-Alquati Andrea , Jarvis Erich D. , Gianfranceschi Luca , Formenti Giulio 
Published: March 2022

AbstractInsights into the evolution of non-model organisms are often limited by the lack of reference genomes. As part of the Vertebrate Genomes Project, we present a new reference genome and a pangenome produced with High-Fidelity long reads for the barn swallow Hirundo rustica. We then generated a reference-free multialignment with other bird genomes to identify genes under selection. Conservation analyses pointed at genes enriched for transcriptional regulation and neurodevelopment. The most conserved gene is CAMK2N2, with a potential role in fear memory formation. In addition, using all publicly available data, we generated a comprehensive catalogue of genetic markers. Genome-wide linkage disequilibrium scans identified potential selection signatures at multiple loci. The top candidate region comprises several genes and includes BDNF, a gene involved in stress response, fear memory formation, and tameness. We propose that the strict association with humans in this species is linked with the evolution of pathways typically under selection in domesticated taxa.
GLOBAL HOST RESPONSES TO THE MICROBIOTA AT SINGLE CELL RESOLUTION IN GNOTOBIOTIC ZEBRAFISH
Authors: Massaquoi Michelle S. , Kong Garth , Chilin Daisy , Hamilton Mary K. , Melancon Ellie , Eisen Judith S. , Guillemin Karen 
Published: March 2022

AbstractResident microbes are a feature of vertebrate animals that influence diverse aspects of their biology from tissue development to metabolism. Here we describe transcriptional responses to the microbiota across all the cells of a model developing vertebrate, the larval zebrafish. By performing single cell transcriptomic analysis of whole germ free and conventionalized larvae, we show that the impacts of the microbiota are sensed by all major organ systems but that responses are highly specific to different cell types. The presence of microbiota stimulates the expansion of progenitor-like cells in epithelial tissues and increases proliferation gene expression in progenitor-like cell populations of the immune and nervous systems. Across many cell types, including enterocytes, immune cells, and neurons, the microbiota upregulates expression of genes involved in microbial responses, cell type-specific activities, and cell type-specific deployment of ATP metabolism genes. These combined transcriptional patterns demonstrate how the microbiota simultaneously modulate cellular immune and metabolic programs. The impacts of the microbiota on tissue development are illustrated by the exocrine pancreas, which in the absence of the microbiota is smaller and composed of uniformly differentiated acinar cells. The presence of the microbiota results in exocrine pancreas enlargement and heterogeneous cellular expression of digestive enzyme and secretion genes, demonstrating how the microbiota promotes plasticity in tissue development and function. This single cell transcriptional dataset demonstrates the impacts of the microbiota on vertebrate development across the body and provides a foundation for dissecting cell type specific responses to microbial consortia members or molecules.SummaryAnimal development proceeds in the presence of intimate microbial associations, but the extent to which different host cells across the body respond to resident microbes remains to be fully explored. Using the vertebrate model organism, the larval zebrafish, we assessed transcriptional responses to the microbiota across the entire body at single cell resolution. We find that cell types across the body, not limited to tissues at host-microbe interfaces, respond to the microbiota. Responses are cell-type specific, but across many tissues the microbiota enhances cell proliferation, increases metabolism, and stimulates a diversity of cellular activities, revealing roles for the microbiota in promoting developmental plasticity. This work provides a resource for exploring transcriptional responses to the microbiota across all cell types of the vertebrate body and generating new hypotheses about the interactions between vertebrate hosts and their microbiota.
Lassa virus glycoprotein nanoparticles elicit a neutralizing antibody that defines a new site of vulnerability
Authors: Brouwer Philip J.M. , Antanasijevic Aleksandar , Ronk Adam J. , Müller-Kräuter Helena , Watanabe Yasunori , Claireaux Mathieu , Lloyd Nicole M. , Bijl Tom. P. L. , Perrett Hailee R. , Steijaert Thijs , Burger Judith A. , van Haaren Marlies M. , Sliepen Kwinten , van Gils Marit J. , Crispin Max , Strecker Thomas , Bukreyev Alexander , Ward Andrew B. , Sanders Rogier W. 
Published: March 2022

AbstractLassa virus is endemic in large parts of West Africa and causes a hemorrhagic fever. Recent years have seen several serious outbreaks of Lassa fever with high mortality rates. A vaccine to curtail infection is urgently needed. The development of a recombinant protein vaccine has been hampered by the instability of soluble Lassa virus glycoprotein complex (GPC) trimers, which disassemble into monomeric subunits after expression. Here we use two-component protein nanoparticles to stabilize GPC in a trimeric conformation and present twenty prefusion GPC trimers on the surface of an icosahedral nanoparticle. Cryo-EM studies of assembled GPC nanoparticles demonstrated a well-ordered structure and yielded a high-resolution structure of an unliganded GPC. These nanoparticles induced potent humoral immune responses in rabbits and protective immunity against a lethal Lassa virus challenge in guinea pigs. We isolated a neutralizing antibody which was mapped to the putative receptor-binding site, revealing a novel site of vulnerability on GPC.
Systemic ablation of Camkk2 impairs metastatic colonization and improves insulin sensitivity in TRAMP mice: Evidence for cancer cell-extrinsic CAMKK2 functions in prostate cancer
Authors: Pulliam Thomas L. , Awad Dominik , Han Jenny J. , Murray Mollianne M. , Ackroyd Jeffrey J. , Goli Pavithr , Oakhill Jonathan S. , Scott John W. , Ittman Michael M. , Frigo Daniel E. 
Published: March 2022

AbstractDespite early studies linking calcium-calmodulin protein kinase kinase 2 (CAMKK2) to prostate cancer cell migration and invasion, the role of CAMKK2 in metastasis in vivo remains unclear. Moreover, while CAMKK2 is known to regulate systemic metabolism, whether CAMKK2’s effects on whole body metabolism would impact prostate cancer progression and/or related comorbidities is not known. Here, we demonstrate that germline ablation of Camkk2 slows, but does not stop, primary prostate tumorigenesis in the TRansgenic Adenocarcinoma Mouse Prostate (TRAMP) genetic mouse model. Consistent with prior epidemiological reports supporting a link between obesity and prostate cancer aggressiveness, TRAMP mice fed a high-fat diet exhibited a pronounced increase in the colonization of lung metastases. We demonstrated that this effect on metastatic spread was dependent on CAMKK2. Notably, diet-induced lung metastases exhibited a highly aggressive neuroendocrine phenotype. Concurrently, Camkk2 deletion improved insulin sensitivity in the same mice. Histological analyses revealed that cancer cells were smaller in the TRAMP;Camkk2-/- mice compared to TRAMP;Camkk2+/+ controls. Given the differences in circulating insulin levels, a known regulator of cell growth, we hypothesized that systemic CAMKK2 could promote prostate cancer cell growth and disease progression in part through cancer cell-extrinsic mechanisms. Accordingly, host deletion of Camkk2 impaired the growth of syngeneic murine prostate tumors in vivo, confirming nonautonomous roles for CAMKK2 in prostate cancer. Cancer cell size and mTOR signaling was diminished in tumors propagated in Camkk2-null mice. Together, these data indicate that, in addition to cancer cell-intrinsic roles, CAMKK2 promotes prostate cancer progression via tumor-extrinsic mechanisms. Further, we propose that CAMKK2 inhibition may also help combat common metabolic comorbidities in men with advanced prostate cancer.
ACSF2: A MEDIUM-CHAIN ACYL-CoA SYNTHETASE WITH A POTENTIAL ROLE IN NEURONAL DIFFERENTIATION
Authors: Maiguel Dony , Morita Masashi , Pei Zhengtong , Jia Zhenzhen , Watkins Paul A. 
Published: March 2022

ABSTRACTBy activating fatty acids to their CoA derivatives, acyl-CoA synthetases (ACS) play an essential role in fatty acid metabolism. We previously identified ACSF2 as an ACS that was phylogenetically distinct from known families of short-chain, medium-chain, long-chain, very long-chain, and bubblegum ACSs. Functionally, ACSF2 preferentially activated medium-chain fatty acids. In this work, we provide further characterization of this unique ACS. ACSF2 mRNA expression was found in most tissues, although immunohistochemical analysis revealed differences in protein expression between various cell types in each tissue. Endogenous ACSF2 was found in the Golgi region in Neuro2a and P19 cells, and disruption of the Golgi in Neuro2a cells with nocodazole disrupted ACSF2 localization. In contrast, MA-10, HepG2, and skin fibroblasts had a mitochondrial ACSF2 localization. ACSF2 activated saturated fatty acids containing 6 to 10 carbons when overexpressed in COS-1 cells. The Kmapp for C10:0 was 24.4 μM and Vmaxapp was 385 nmol/20min/mg COS cell protein. Knockdown by RNA interference revealed that ACSF2 was responsible for most of the medium-chain ACS activity in Neuro2a cells. A lysine residue critical for activity in bacterial short-chain ACSs was found in ACSF2, and mutation of this residue to alanine abolished enzyme activity. Neurite outgrowth results when Neuro2a cells are induced to differentiate with retinoic acid, and ACSF2 migrated to nodes and points of neurite-neurite contact along with the presynaptic marker, synaptophysin. ACSF2-deficient Neuro2a cells showed significantly blunted neurite outgrowth in response to retinoic acid. These results suggest that this medium-chain ACS may play an important role in neuronal development.
Natural variation identifies new effectors of water use efficiency inArabidopsis
Authors: Bhaskara Govinal Badiger , Lasky Jesse R , Razzaque Samsad , Zhang Li , Haque Taslima , Bonnette Jason E , Civelek Guzide Zeynep , Verslues Paul E , Juenger Thomas E 
Published: March 2022

AbstractWater use efficiency (WUE) is the ratio of biomass gained per unit of water consumed; thus, it can be altered by genetic factors that affect either side of the ratio. In the present study, we exploited natural variation for WUE as an unbiased approach to discover loci affecting either biomass accumulation or water use as factors affecting WUE. Genome-wide association (GWAS) analysis using integrated WUE measured through carbon isotope discrimination (δ13C) ofArabidopsis thalianaaccessions identified genomic regions associated with WUE. Reverse genetic analysis of 70 candidate genes selected based on the GWAS results and transcriptome data identified 25 genes affecting WUE as measured by gravimetric and δ13C analyses. Mutants of four genes had higher WUE than wild type, while mutants of the other 21 genes had lower WUE. The differences in WUE were caused by either altered biomass or water consumption (or both). Stomatal density was not a primary cause of altered WUE in these mutants. Leaf surface temperatures indicated that transpiration differed for mutants of 16 genes, but generally biomass accumulation had greater effect on WUE. The genes we identified are involved in diverse cellular processes including hormone and calcium signaling, meristematic activity, photosynthesis, flowering time, leaf/vasculature development, and cell wall composition; however, none of them had been previously linked to WUE or traits related to plant water relations. Thus, our study successfully identified new effectors of WUE that can be used to understand the genetic basis of WUE and improve crop productivity.
Monitoring of urban ecological environment including air quality using satellite imagery
Authors: Wang Yuan , Cai Guoyin , Yang Liuzhong , Zhang Ning , Du Mingyi 
Published: March 2022

AbstractRapid urbanisation has highlighted problems in the urban ecological environment and stimulated research on the evaluation of urban environments. In previous studies, key factors such as greenness, wetness, and temperature were extracted from satellite images to assess the urban ecological environment. Although air pollution has become increasingly serious as urbanisation proceeds, information on air pollution is not included in existing models. The Sentinel-5P satellite launched by the European Space Agency in 2017 is a reliable data source for monitoring air quality. By making full use of images from Landsat 8, Sentinel-2A, and Sentinel-5P, this work attempts to construct a new remote sensing monitoring index for urban ecology by adding air quality information to the existing remote sensing ecological index. The proposed index was tested in the Beijing metropolitan area using satellite data from 2020. The results obtained using the proposed index differ greatly in the central urban region and near large bodies of water from those obtained using the existing remote sensing monitoring model, indicating that air quality plays a significant role in evaluating the urban ecological environment. Because the model constructed in this study integrates information on vegetation, soil, humidity, heat, and air quality, it can comprehensively and objectively reflect the quality of the urban ecological environment. Consequently, the proposed remote sensing index provides a new approach to effectively monitoring the urban ecological environment.
Deep selection shapes the intragenomic diversity of rRNA genes
Authors: Sultanov Daniel , Hochwagen Andreas 
Published: March 2022

ABSTRACTRibosome biogenesis in eukaryotes is supported by hundreds of ribosomal RNA (rRNA) gene copies that are encoded in the ribosomal DNA (rDNA). The multiple copies of rRNA genes are thought to have low sequence diversity within one species. Here, we present species-wide rDNA sequence analysis inSaccharomyces cerevisiaethat challenges this view. We show that rDNA copies in this yeast are far from homogeneous, both among and within isolates, and that many variants avoided fixation or elimination over evolutionary time. The sequence diversity landscape across the rDNA shows clear functional stratification, suggesting different copy-number thresholds for selection that shape rDNA diversity. Notably, nucleotide variants in the most conserved rDNA regions are sufficiently deleterious to exhibit signatures of purifying selection even when present in only a small fraction of rRNA gene copies. Our results portray a complex evolutionary landscape that shapes rDNA sequence diversity within a single species and reveal unexpectedly deep purifying selection of multi-copy genes.
An ALS-associated KIF5A mutant forms oligomers and aggregates and induces neuronal toxicity
Authors: Nakano Juri , Chiba Kyoko , Niwa Shinsuke 
Published: March 2022

AbstractKIF5A is a kinesin superfamily motor protein that transports various cargos in neurons. Mutations inKif5acause familial amyotrophic lateral sclerosis (ALS). These ALS mutations are in the intron ofKif5aand induce mis-splicing of KIF5A mRNA, leading to splicing out of exon 27, which in human KIF5A encodes the cargo-binding tail domain of KIF5A. Therefore, it has been suggested that ALS is caused by loss of function of KIF5A. However, the precise mechanisms regarding how mutations in KIF5A cause ALS remain unclear. Here, we show that an ALS-associated mutant of KIF5A, KIF5A(Δexon27), is predisposed to form oligomers and aggregates in cultured mouse cell lines. Interestingly, purified KIF5A(Δexon27) oligomers showed more active movement on microtubules than wild type KIF5Ain vitro. Purified KIF5A(Δexon27) was prone to form aggregatesin vitro. Moreover, KIF5A(Δexon27)-expressingCaenorhabditis elegansneurons showed morphological defects. These data collectively suggest that ALS-associated mutations of KIF5A are toxic gain-of-function mutations rather than simple loss-of-function mutations.
Safety assessment of insecticidal proteins: A case study utilizing His-tagged protein to determine the safety of Mpp75Aa1.1, a new ETX_MTX2 protein that controls western corn rootworm
Authors: Wang Cunxi , Bean Gregory J. , Chen Chun Ju , Kessenich Colton R. , Peng Jiexin , Visconti Nicolo R. , Milligan Jason S. , Moore Robert G. , Tan Jianguo , Edrington Thomas C. , Li Bin , Giddings Kara S. , Bowen David , Luo Jinhua , Ciche Todd , Moar William J. 
Published: March 2022

ABSTRACTThe recently discovered insecticidal protein Mpp75Aa1.1 from Brevibacillus laterosporus is one member of the ETX_MTX family of beta-pore forming proteins (β-PFPs) expressed in genetically modified (GM) maize to control western corn rootworm (WCR; Diabrotica virgifera virgifera LeConte). In this paper, bioinformatic analysis establishes that although Mpp75Aa1.1 shares varying degrees of similarity to members of the ETX_MTX2 protein family, it is unlikely to contribute to any allergenic, toxic, or otherwise adverse biological effects. The safety of Mpp75Aa1.1 is further supported by a weight of evidence including evaluation of history of safe use (HOSU) of ETX_MTX2 proteins. Assessments using either purified Mpp75Aa1.1 protein or a poly-histidine-tagged (His-tagged) variant of the Mpp75Aa1.1 protein demonstrate that both forms of the protein are heat labile at temperatures at or above 55 °C, degraded by gastrointestinal proteases within 0.5 min, and have no adverse effects in acute mouse oral toxicity studies at a dose level of 1920 or 2120 mg/kg body weight. Results also indicate that the domain-based protein characterization should be considered as part of the weight of evidence for the safe consumption of food or feed. Furthermore, these results support the use of His-tagged proteins as suitable surrogates for assessing the safety of their non-tagged parent proteins.
Glial dysregulation in human brain in Fragile X-related disorders
Authors: Dias Caroline M. , Talukdar Maya , Akula Shyam K. , Walsh Katherine , Walsh Christopher A. 
Published: March 2022

AbstractWhile large trinucleotide repeat expansions at the FMR1 locus cause Fragile X Syndrome (FXS), smaller “premutations” are associated with the late-onset condition Fragile X-associated tremor/ataxia syndrome (FXTAS), which shows very different clinical and pathological features, with no clear molecular explanation for these marked differences. One prevailing theory posits that the premutation uniquely causes neurotoxic increases in FMR1 mRNA (i.e., 4-8-fold increases), but evidence to support this hypothesis is largely derived from analysis of peripheral blood. We applied single- nucleus RNA-sequencing to post-mortem frontal cortex and cerebellum from 9 individuals with Fragile X mutations as well as age and sex matched controls (n=6) to assess cell-type specific molecular neuropathology. We found robust reduction of FMR1 mRNA in FXS as expected, with modest but significant upregulation (∼1.3 fold) of FMR1 in glial clusters associated with premutation expansions. In premutation cases we identified alterations in glia number in cortex and cerebellum. Differential expression analysis demonstrated altered cortical oligodendrocyte development, while gene ontology analysis revealed alterations in neuroregulatory roles of glia, such as glial modulation of neurotransmission and synaptic structure. We identified significant enrichment of known FMR1 protein target genes in differentially expressed gene lists in FXS as well as the premutation, suggesting FMR1 protein target pathways may represent a shared source of dysfunction in both conditions despite opposite FMR1 mRNA changes. These findings challenge existing dogma regarding FXTAS and implicate glial dysregulation as a critical facet of premutation pathophysiology, representing novel therapeutic targets directly derived from the human condition.
Does the perception of organizational justice determine employees' affective commitment? The mediating role of organizational trust
Authors: Malla Sweta Srivastava , Malla Sanjay 
Published: March 2022

PurposeThe purpose of this paper is to identify select antecedents for affective commitment (AC) and whether organizational trust (OT) mediates the relationship between dimensions of organizational justice (OJ) and AC.Design/methodology/approachUsing a survey-based design, data were collected from employees across industry verticals who were working in various organizations and participated in an executive management program at an Indian management institute. Analysis was carried out using a partial least square-based package of ADANCO 2.2.1.FindingsIn line with cross-cultural research, the results indicated that distributive and informational justice contribute toward employees' AC. In addition, the findings confirmed that OT mediates the justice-AC relationship for distributive, interpersonal and informational justice. The role of job satisfaction (JS) as an important antecedent was also identified.Practical implicationsThe evidence-based findings, as represented in importance–performance map analysis (IPMA), will help the organizational leaders understand the factors responsible for employees' AC. Leaders will appreciate the important role played by justice, fairness and OT in enhancing commitment. The importance of JS was also highlighted.Originality/valueThis is a pioneering study to provide empirical evidence of the moderating effect of trust on OJ and the AC relationship. It is also one of the first to consider all of the four dimensions of OJ as possible antecedents for AC in a non-Western context.