bluuebunny/crossref_metadata_2025_split huggingface dataset:
Commensal fungi Candida albicans modulates dietary high-fat induced alterations in metabolism, immunity, and gut microbiota
Authors: Peroumal Doureradjou , Sahu Satya Ranjan , Kumari Premlata , Utkalaja Bhabasha , Acharya Narottam 
Published: March 2022

AbstractObesity and its associated diseases represent a growing health concern. Despite a strong correlation between gut microbiota and obesity, a limited study is available to suggest the direct involvement of fungus in host physiology. Candida albicans survives as a commensal fungus in the gastrointestinal tract, and its excessive growth causing infections in immune-suppressed individuals is widely accepted. However, any mutualistic relationship that may exist between C. albicans and the host remains outstanding. Here we show that the dietary C. albicans do not cause any noticeable infections, and our metagenomics analyses suggest that it colonizes in the gut and modulates microbiome dynamics which in turn negates the high-fat diet induced uncontrolled body weight gain, metabolic hormonal imbalances, and inflammatory response. Interestingly, adding C. albicans to a non-obesogenic diet stimulates the appetite regulated hormones and helped the mice gain healthy body weight. In concert, our results suggest a mutualism between C. albicans and the host, therefore, contrary to the notion, C. albicans is not always an adversary rather a bonafide admirable companion of the host. Finally, we discuss its potential translational implication as a probiotic especially in obese people or people dependent on high fat calorie intakes to manage obesity and associated complications.
Epigenetic clocks for mice based on age-associated regions that are conserved between mouse strains and human
Authors: Perez-Correa Juan , Tharmapalan Vithurithra , Geiger Hartmut , Wagner Wolfgang 
Published: March 2022

AbstractAging of mice can be tracked by DNA methylation changes at specific sites in the genome. In this study, we used the recently released Infinium Mouse Methylation BeadChip to compare such epigenetic modifications in C57BL/6 (B6) and DBA/2J (DBA) mice. We observed marked differences in age-associated DNA methylation in these commonly used inbred mouse strains, indicating that epigenetic clocks for one strain cannot be simply applied to other strains without further verification. In B6 mice age-associated hypomethylation prevailed with focused hypermethylation at CpG islands, whereas in DBA mice CpG islands revealed rather hypomethylation upon aging. Interestingly, the CpGs with highest age-correlation were still overlapping in B6 and DBA mice and included the genesHsf4,Prima1,Aspa, andWnt3a. Notably,Hsf4andPrima1were also top candidates in previous studies based on whole genome deep sequencing approaches. Furthermore,Hsf4,Aspa, andWnt3arevealed highly significant age-associated DNA methylation in the homologous regions in human. Subsequently, we used pyrosequencing of the four relevant regions to establish a targeted epigenetic clock that provided very high correlation with chronological age in independent cohorts of B6 (R2= 0.98) and DBA (R2= 0.91). Taken together, the methylome differs extensively between B6 and DBA mice, while prominent age-associated changes are conserved among these strains and even in humans. Our new targeted epigenetic clock with 4 CpGs provides a versatile tool for other researchers analyzing aging in mice.
Long-read-resolved, ecosystem-wide exploration of nucleotide and structural microdiversity of lake bacterioplankton genomes
Authors: Okazaki Yusuke , Nakano Shin-ichi , Toyoda Atsushi , Tamaki Hideyuki 
Published: March 2022

AbstractReconstruction of metagenome-assembled genomes (MAGs) has become a fundamental approach in microbial ecology. However, an MAG is hardly complete and overlooks genomic microdiversity because metagenomic assembly fails to resolve microvariants among closely related genotypes. Aiming at understanding the universal factors that drive or constrain prokaryotic genome diversification, we performed an ecosystem-wide high-resolution metagenomic exploration of microdiversity by combining spatiotemporal (2 depths × 12 samples) sampling from a pelagic freshwater system, MAG reconstruction using long- and short-read metagenomic sequences, and profiling of single nucleotide variants (SNVs) and structural variants (SVs) through mapping of short and long reads to the MAGs, respectively. We reconstructed 575 MAGs, including 29 circular assemblies, providing high-quality reference genomes of freshwater bacterioplankton. Read mapping against these MAGs identified 100–101,781 SNVs/Mb, 0–305 insertions, 0–467 deletions, 0–41 duplications, and 0–6 inversions for each MAG. Nonsynonymous SNVs were accumulated in genes potentially involved in cell surface structural modification to evade phage recognition. Most (80.2%) deletions overlapped with a gene-coding region, and genes of prokaryotic defense systems were most frequently (>8% of the genes) involved in a deletion. Some such deletions exhibited a monthly shift in their allele frequency, suggesting a rapid turnover of genotypes in response to phage predation. MAGs with extremely low microdiversity were either rare or opportunistic bloomers, suggesting that population persistency is key to their genomic diversification. The results lead to the conclusion that prokaryotic genomic diversification is primarily driven by viral load and constrained by a population bottleneck.
A wheat resistosome defines common principles of immune receptor channels
Authors: Förderer Alexander , Li Ertong , Lawson Aaron , Deng Ya-nan , Sun Yue , Logemann Elke , Zhang Xiaoxiao , Wen Jie , Han Zhifu , Chang Junbiao , Chen Yuhang , Schulze-Lefert Paul , Chai Jijie 
Published: March 2022

AbstractPlant intracellular nucleotide-binding leucine-rich repeat (NLRs) receptors detect pathogen effectors to trigger immune responses. Indirect recognition of a pathogen effector by the dicotyledonous Arabidopsis thaliana coiled-coil (CC) domain containing NLR (CNL) ZAR1 induces the formation of a large hetero-oligomeric protein complex, termed the ZAR1 resistosome, which functions as a calcium channel required for ZAR1-mediated immunity (1–3). Whether the resistosome and channel activities are conserved among plant CNLs remains unknown. We report here a cryogenic electron microscopy (cryo-EM) structure of the wheat CNL Sr35 in complex with the effector AvrSr35 of the wheat stem rust pathogen at 3.0 Å resolution. Direct effector binding to the leucine-rich repeats (LRRs) of Sr35 results in the formation of a pentameric Sr35-AvrSr35 complex, which we designate the Sr35 resistosome. Wheat Sr35 and Arabidopsis ZAR1 resistosomes bear striking structural similarity, including a previously unnoticed arginine cluster in the LRR domain that co-occurs and forms intramolecular interactions with the ‘EDVID’ motif in the CC domain. Electrophysiological measurements show that the Sr35 resistosome exhibits non-selective cation channel activity. These structural insights allowed us to generate novel variants of closely related wheat and barley orphan NLRs that recognize AvrSr35. Our data support the evolutionary conservation of CNL resistosomes in plants and demonstrate proof of principle for structure-based engineering of NLRs for crop improvement.
Cdk1-mediated threonine phosphorylation of Sam68 modulates its RNA binding, alternative splicing activity, and cellular functions
Authors: Malki Idir , Liepina Inara , Kogelnik Nora , Lightfoot Adam , Gonchar Oksana , Watmuff Hollie , Bottrill Andrew , Fry Andrew M. , Dominguez Cyril 
Published: March 2022

ABSTRACTSam68 is a member of the STAR family of proteins that directly link signal transduction with post-transcriptional gene regulation. Sam68 controls the alternative splicing of many oncogenic proteins and its role is modulated by post-translational modifications, including serine/threonine phosphorylation, that differ at various stages of the cell cycle. However, the molecular basis and mechanisms of these modulations remain largely unknown. Here, we combined mass spectrometry, NMR spectroscopy, and cell biology techniques to provide a comprehensive post-translational modification (PTM) mapping of Sam68 at different stages of the cell cycle in HEK293 and HCT116 cells. We established that Sam68 is specifically phosphorylated at T33 and T317 by Cdk1, and demonstrated that these phosphorylation events reduce the binding of Sam68 to RNA, control its cellular localization, and reduce its alternative splicing activity, leading to a reduction in the induction of apoptosis and an increase in the proliferation of HCT116 cells.
SUMO4 promotes SUMO deconjugation required for DNA double-strand break repair
Authors: Garvin Alexander J. , Lanz Alexander J. , Starowicz Katarzyna , Ronson George E , Mackintosh Matthew J.W. , Walker Alexandra K. , Aghabi Yara , MacKay Hannah , Densham Ruth M. , Leney Aneika C. , Morris Joanna R. 
Published: March 2022

AbstractThe amplitudes of small-modifier protein signalling through ubiquitin and the Small Ubiquitin-like Modifiers, SUMO1-3, are critical to the correct phasing of DNA repair protein accumulation, activity, and clearance, and for the completion of mammalian DNA double-strand break (DSB) repair. However, how SUMO-conjugate signalling in the response is delineated is poorly understood. At the same time, the role of the non-conjugated SUMO protein, SUMO4, has remained enigmatic. Here we reveal that SUMO4 is required to prevent excessive DNA-damage-induced SUMOylation and deleterious over-accumulation of RAP80. Mechanistically we show SUMO4 acts independently of its conjugation and potentiates SENP1 catalytic activity. These data identify SUMO4 as a SUMO deconjugation component and show SUMO4:SENP1 are critical regulators of DNA-damage-induced SUMO signalling.HighlightsThe roles of the SUMO family members, SUMO1-4, in DSB repair are not redundant.SUMO4 conjugation is deleterious.SUMO4 promotes SENP1 catalytic activity.SUMO4:SENP1 restrict SUMO-signalling and accumulation of the BRCA1-A complex.
Population genetic analysis of Ophidiomyces ophidiicola, the causative agent of snake fungal disease, indicates recent introductions to the USA
Authors: Ladner Jason T. , Palmer Jonathan M. , Ettinger Cassandra L. , Stajich Jason E. , Farrell Terence M. , Glorioso Brad M. , Lawson Becki , Price Steven J. , Stengle Anne G. , Grear Daniel A. , Lorch Jeffrey M. 
Published: March 2022

ABSTRACTSnake fungal disease (SFD; ophidiomycosis), caused by the pathogen Ophidiomyces ophidiicola (Oo), has been documented in wild snakes in North America and Eurasia, and is considered an emerging disease in the eastern USA. However, a lack of historical disease data has made it challenging to determine whether Oo is a recent arrival to the USA or whether SFD emergence is due to other factors. Here, we examined the genomes of 82 Oo strains to determine the pathogen’s history in the eastern USA. Oo strains from the USA formed a clade (Clade II) distinct from European strains (Clade I), and molecular dating indicated that these clades diverged too recently (∼2,000 years ago) for transcontinental dispersal of Oo to have occurred via natural snake movements across Beringia. A lack of nonrecombinant intermediates between clonal lineages in Clade II indicates that Oo has actually been introduced multiple times to North America from an unsampled source population, and molecular dating indicates that several of these introductions occurred within the last few hundred years. Molecular dating also indicated that the most common Clade II clonal lineages have expanded recently in the USA, with time of most recent common ancestor mean estimates ranging from 1985-2007 CE. The presence of Clade II in captive snakes worldwide demonstrates a potential mechanism of introduction and highlights that additional incursions are likely unless action is taken to reduce the risk of pathogen translocation and spillover into wild snake populations.
Geographical indications' prices and marketing margins: the role of group size, longevity and production decisions
Authors: Bimbo Francesco , Bonanno Alessandro , Viscecchia Rosaria 
Published: March 2022

PurposeGeographical indication (GI) labels aim to improving farmers' and processors' income. This article studies how characteristics related to GI groups and their reputation (e.g. the producer group size, longevity and production decisions) are related to prices at the origin, final (consumption) prices and marketing margins.Design/methodology/approach The authors use 8 years of annual data for the Italian Extra Virgin Olive Oil (EVOO) GI market encompassing 46 GI EVOOs. Estimated parameters characterizing the relationship between the GI's group features and prices (at origin and at consumption) are obtained via Three-Stage Least Squares (3SLS).FindingsResults show that the number of GI operators is related to consumption prices, while is weakly related to prices at the origin. GIs' age is not associated with higher consumption prices, while origin prices are lower for older GIs compared to younger ones. Higher farmers' olive/oil conversion rate is associated with lower origin and consumption prices, whereas the extent of vertical integration is related to higher prices at the origin and a higher share of the marketing margins going to producers.Originality/valueTo the best of their knowledge, the authors offer the first empirical evidence on how structural characteristics and production decisions of a GI group relate to prices and marketing margins.
Give play to strengths or overcome weaknesses? The impact of family involvement on exploitative and exploratory OFDI
Authors: Yang Xuelei , Shang Hangbiao , Li Weining 
Published: March 2022

Purpose This study explores the impact of family ownership and management on exploitative and exploratory outward foreign direct investment (OFDI) in family businesses in emerging economies, as well as the moderating effects of intra-family successions and founder CEOs.Design/methodology/approach The authors empirically tested the hypotheses based on the data of Chinese listed manufacturing family enterprises from 2009 to 2018.Findings Family ownership does not significantly reduce exploitative OFDI but significantly increases exploratory OFDI. When family offspring have succession intentions, these relationships are strengthened. Additionally, family management is negatively associated with exploitative OFDI and positively associated with exploratory OFDI. Founder CEOs have a positive moderating effect on the relationship between family management and exploitative and exploratory OFDI.Originality/value This study is the first attempt to introduce exploitative and exploratory OFDI into the internationalization of family enterprises. The research goes beyond internationalization as a single concept and provides new evidence to solve the controversy about how family involvement affects family firms’ internationalization. On the other hand, the authors respond to the call to understand the impact of family heterogeneity on internationalization by systematically examining the influence of four important family heterogeneity characteristics on family firms’ OFDI choice.
Work site food purchases among healthcare staff: Relationship with healthy eating and opportunities for intervention
Authors: Utter Jennifer , McCray Sally , Denny Simon 
Published: March 2022

AbstractAimThe current study describes food‐purchasing behaviours of healthcare staff, determines whether purchasing food at work is associated with overall indicators of healthy eating, and explores opportunities for improving the hospital food environment.MethodsA secondary analysis of a health and wellbeing survey of healthcare workers (n = 501) in Queensland, Australia. Multiple regression models describe the associations between food purchases and indicators of healthy eating, while controlling for age, gender and work role.ResultsMore than 60% of staff purchased food/drinks at work in the past week, and this was inversely associated with indicators of healthy eating. For example, among those purchasing food/drinks at work on most days, only 18% reported their overall diet as excellent or very good, compared to 50% of those who do not purchase food/drink at work (odds ratio [OR] = 0.24; 95% confidence interval [CI] = [0.12,0.48] in adjusted models). Staff feedback prioritised strategies to make healthy meals more accessible and affordable.ConclusionImprovements to the retail food environment in hospitals could have a positive impact on the overall nutritional wellbeing of staff.
A quantitative framework to infer the effect of traits, diversity and environment on dispersal and extinction rates from fossils
Authors: Hauffe Torsten , Pires Mathias M. , Quental Tiago B. , Wilke Thomas , Silvestro Daniele 
Published: March 2022

Abstract

Speciation, dispersal and extinction govern the spatial and temporal dynamics of biodiversity. The fossil record offers the opportunity to directly estimate range expansion and contraction via dispersal and extinction, respectively. However, due to the incomplete occurrence record, determining the dynamics of these processes and the biotic and abiotic factors influencing them remains challenging.

The dispersal–extinction–sampling (DES) model infers dispersal and extinction rates from present and past geographical ranges of taxa while accounting for the incompleteness of the fossil record via jointly estimated sampling rates. Here, we expand the DES framework to a new suite of models that (a) incorporate heterogeneity in fossil sampling across taxa, (b) reconstruct diversity trajectories through time and across regions, and (c) link rates of range evolution with biotic and abiotic covariates. These models integrate the effects of competitive interaction, traits and environmental change on dispersal and extinction while controlling for phylogenetic effects through higher level taxonomy.

We validate our framework through simulations and find that likelihood‐based model testing has the power to discriminate among models with or without biotic and abiotic effects on dispersal and extinction. Among the tested models, we found that trait‐dependent models yielded the most accurate parameter estimates. We then assess the factors influencing geographical range evolution for Eurasian and North American terrestrial carnivores. We identify substantial variation in the fossil sampling rates of carnivore genera and find that global cooling increased their extinction risk while their dispersal rate varied among families and increased with larger body size.

The expanded suite of DES models for fossil biogeography is a powerful tool to test hypotheses about the factors influencing geographical range evolution using fossil data.
Clozapine and COVID‐19 Vaccination: Effects on blood levels and leukocytes. An observational cohort study
Authors: Veerman Selene R. T. , Moscou Timo , Bogers Jan P. A. M. , Cohen Dan , Schulte Peter F. J. 
Published: March 2022

AbstractObjectiveTo investigate the safety of COVID‐19 vaccination in patients on clozapine as regards plasma clozapine concentration and haematological parameters.MethodsWe conducted a multicentre observational cohort study from 22 February 2021 to 2 September 2021. Primary outcomes were clinically relevant increase in clozapine blood levels (>100 μg/L increase compared to baseline) and clozapine alert levels (>1000 μg/L). Secondary outcomes were granulocytopenia, leukocytopenia and lymphocytopenia. Outcomes were measured approximately 5 days after the first and (where applicable) second dose of COVID‐19 vaccine.ResultsThis study included 139 patients. Compared to baseline, clozapine blood levels increased significantly (ES = 0.28, p = 0.003) after the second vaccination. Clinically relevant increases in clozapine blood levels occurred in 20/92 patients (22%) and in 16/56 patients (29%) during the first and second phases, respectively. Clozapine alert levels developed in one patient (1%) following the first dose and in three patients (5%) after the second dose. In both phases, changes in white blood cells (WBC) were limited to mild granulocytopenia (3% and 5%), moderate granulocytopenia (1% and 0%) and leukocytopenia (2% and 3%) without cause for extra monitoring according to the guideline.ConclusionIn general, as regards WBC counts COVID‐19 vaccination seems to be safe in patients with SMI. Changes in WBC had no clinical implications. Psychoeducation on the symptoms of clozapine intoxication is recommended, especially in patients with clozapine blood levels approaching the upper limit of the therapeutic range. Increase in the C‐reactive protein (CRP) level can signal inflammation rapidly and help to prevent clozapine intoxication following vaccination.
Influence of mental health professionals’ attitudes and personality traits on decision‐making around coercion: Results from an experimental quantitative survey using case vignettes
Authors: Efkemann Simone Agnes , Scholten Matthé , Bottlender Ronald , Juckel Georg , Gather Jakov 
Published: March 2022

AbstractObjectiveResearch on coercion in mental healthcare has recently shifted to the investigation of subjective aspects, both on the side of the people with mental disorders affected and the staff members involved. In this context, the role of personality traits and attitudes of staff members in decision‐making around coercion is increasingly being assessed. This study aimed to examine the role of staff attitudes towards coercion and staff members’ personality traits in decision‐making around coercion in an experimental setting.MethodsWe assessed the attitudes towards coercion and (general) personality traits of mental health professionals in psychiatric hospitals with a quantitative survey. Furthermore, we developed case vignettes representing cases in a ‘grey zone’ and included them in the survey to assess staff members’ decisions about coercion in specific situations.ResultsA general approving attitude towards coercion significantly influenced decisions around coercion in individual cases—resulting in a more likely approval of applying coercion in the cases described in the vignettes. Personality traits did not seem to be relevant in this regard.ConclusionStrategies to reduce coercion in mental healthcare institutions should focus more on the role of staff attitudes and encourage staff members to reflect on them critically.