bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-dependent interactions between prodromal intestinal inflammation and LRRK2 G2019S in mice promote symptoms of Parkinson’s disease
Authors: Fang Ping , Espey Hannah , Yu Lewis W. , Agirman Gulistan , Li Kai , Deng Yongning , Lee Jamie , Hrncir Haley , Arnold Arthur P. , Hsiao Elaine Y. 
Published: December 2022

AbstractGastrointestinal (GI) disruptions, such as inflammatory bowel disease (IBD), are common prodromal symptoms of Parkinson’s disease (PD), but how they may impact risk for PD remains poorly understood. Herein, we provide evidence that prodromal intestinal inflammation expedites and exacerbates PD symptoms in rodent carriers of the human PD risk allele LRRK2 G2019S in a sex-dependent manner. Chronic intestinal damage in genetically predisposed male, but not female, mice promotes α-synuclein aggregation in the substantia nigra, elevated α-synuclein loads in microglia, loss of dopaminergic neurons, and motor impairment. This male bias in gene-environment interaction is preserved in gonadectomized males, and similarly conferred by sex chromosomal complement in gonadal females expressing human LRRK2 G2019S, revealing that XY chromosomes, not testicular hormones, mediate the male bias in the gut-brain-driven risk for endophenotypes of PD. The early onset and heightened severity of neuropathological and behavioral outcomes in male LRRK2 G2019S mice is preceded by the accumulation of α-synuclein in the colon, increases in α-synuclein-positive macrophages in the colonic lamina propria, and elevations in α-synuclein loads within microglia in the substantia nigra. Taken together, these data reveal that prodromal intestinal inflammation promotes the pathogenesis of PD symptoms in male carriers of LRRK2 G2019S, through mechanisms that depend on genotypic sex and involve early accumulation of α-synuclein in myeloid cells within the gut and brain.
Trade-offs between baseline thermal tolerance and thermal tolerance plasticity are much less common than it appears
Authors: Gunderson Alex R. 
Published: December 2022

AbstractThermal tolerance plasticity is a core mechanism by which organisms can mitigate the effects of climate change. As a result, there is a need to understand how variation in tolerance plasticity arises. The Baseline Tolerance/Plasticity Trade-off Hypothesis (hereafter referred to as the Trade-off Hypothesis, TOH) has recently emerged as a potentially powerful explanation. The TOH posits that organisms with high baseline thermal tolerance have reduced thermal tolerance plasticity relative to those with low baseline tolerance. Many studies have found support for the TOH. However, this support must be regarded cautiously because the most common means of testing the TOH can yield spurious ‘trade-offs’ due to regression to the mean. I acquired data for 25 previously-published analyses that supported the TOH at the intraspecific level and reanalyzed them after applying a method that adjusts plasticity estimates for regression to the mean. Only six of the 25 analyses remained statistically significant after adjustment, and effect size and variance explained decreased in all cases. The few data sets in which support for the TOH was maintained after adjustment point to areas of future study, but are too few to make generalizations at this point. In sum, regression to the mean has led to a substantial overestimation of support for the TOH and must be accounted for in future tests of the hypothesis.
Effect of D128N mutation on OsSERK2 in Xa21 mediated immune complex: anin-silicostudy
Authors: Alvy Raghib Ishraq , Mubassir M H M 
Published: December 2022

ABSTRACTReceptor-like kinases (RLKs) are plant proteins that form signaling circuits to transduce information through the plant cell membrane to the nucleus and activate processes that direct growth, development, stress response, and disease resistance. Upon sensing various environmental stress stimuli, RLKs interact with specific targets and recruits several other proteins to initiate the defense mechanism. Among many RLK subfamilies, leucine-rich repeat RLKs (LRR-RLKs) are the largest. Xa21, a member of LRR-RLK, is a vital receptor protein in rice plants that binds with bacterial RaxX21-sY, whereas OsSERK2 is a somatic embryogenic receptor kinase (SERK) acts as a coreceptor. This study focuses on the effect of a substitution mutation of aspartate128 with asparagine128 (D128N) in OsSERK2 on the interdependent binding pattern of the mentioned Xa21, RaxX21-sY, and OsSERK2 D128N proteins. The results showed that the D128N mutation in OsSERK2 can significantly change the interaction pattern of the critical residues of the OsSERK2 and affects its receptor-ligand (Xa21-RaxX21-sY) interaction in the complex.
Mycobacterium tuberculosis-specific CD4 T cells expressing transcription factors associate with bacterial control in granulomas
Authors: Grant Nicole L. , Kelly Kristen , Maiello Pauline , Abbott Helena , O’Connor Shelby , Lin Philana Ling , Scanga Charles A. , Flynn JoAnne L. 
Published: December 2022

ABSTRACTDespite the extensive research on CD4 T cells within the context ofMycobacterium tuberculosis(Mtb) infection, few studies have focused on identifying and investigating the profile of Mtb-specific T cells within lung granulomas. To facilitate identification of Mtb-specific CD4 T cells, we identified immunodominant epitopes for two Mtb proteins, Rv1196 and Rv0125, using a Mauritian cynomolgus macaque model of Mtb infection, providing data for the synthesis of MHC Class II tetramers. Using tetramers, we identified Mtb-specific cells within different immune compartments post-infection. We found that granulomas were enriched sites for Mtb-specific cells and that tetramer+cells had increased frequencies of the activation marker CD69, and transcription factors T-bet and RORγT, compared to tetramer negative cells within the same sample. Our data revealed that while the frequency of Rv1196 tetramer+cells was positively correlated with granuloma bacterial burden, the frequency of RORγT or T-bet within tetramer+cells was inversely correlated with granuloma bacterial burden highlighting the importance of having activated, functional Mtb-specific cells for control of Mtb in lung granulomas.
Analysis of the ARTIC V4 and V4.1 SARS-CoV-2 primers and their impact on the detection of Omicron BA.1 and BA.2 lineage defining mutations
Authors: Ulhuq Fatima R. , Barge Madhuri , Falconer Kerry , Wild Jonathan , Fernandes Goncalo , Gallagher Abbie , McGinley Suzie , Sugadol Ahmad , Tariq Muhammad , Maloney Daniel , Kenicer Juliet , Dewar Rebecca , Templeton Kate , McHugh Martin 
Published: December 2022

AbstractThe ARTIC protocol uses a multiplexed PCR approach with two primer pools tiling the entire SARS-CoV-2 genome. Primer pool updates are necessary for accurate amplicon sequencing of evolving SARS-CoV-2 variants with novel mutations. The suitability of the ARTIC V4 and updated V4.1 primer scheme was assessed using whole genome sequencing of Omicron from clinical samples using Oxford Nanopore Technology. Analysis of Omicron BA.1 genomes revealed that 93.22% of clinical samples generated improved genome coverage at 50x read depth with V4.1 primers when compared to V4 primers. Additionally, the V4.1 primers improved coverage of BA.1 across amplicons 76 and 88, which resulted in the detection of the variant defining mutations G22898A, A26530G and C26577G. The Omicron BA.2 sub-variant (VUI-22JAN-01) replaced BA.1 as the dominant variant by March 2022, and analysis of 168 clinical samples showed reduced coverage across amplicons 15 and 75. Upon further interrogation of primer binding sites, a mutation at C4321T (present in 163/168, 97% of samples) was identified as a possible cause of complete dropout of amplicon 15. Furthermore, two mutations were identified within the primer binding regions for amplicon 75: A22786C (present in 90% of samples) and C22792T (present in 12.5% of samples). Together, these mutations may result in reduced coverage of amplicon 75 and further primer updates would allow the identification of the two BA.2 defining mutations present in amplicon 75; A22688G and T22679C. This work highlights the need for ongoing surveillance of primer matches as circulating variants evolve and change.
Genetic risk factor clustering within and across neurodegenerative diseases
Authors: Koretsky Mathew J. , Alvarado Chelsea , Makarious Mary B , Vitale Dan , Levine Kristin , Bandres-Ciga Sara , Dadu Anant , Scholz Sonja W. , Sargent Lana , Faghri Faraz , Iwaki Hirotaka , Blauwendraat Cornelis , Singleton Andrew , Nalls Mike , Leonard Hampton 
Published: December 2022

AbstractOverlapping symptoms and copathologies are common in closely related neurodegenerative diseases (NDDs). Investigating genetic risk variants across these NDDs can give further insight into disease manifestations. In this study we have leveraged genome-wide single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) summary statistics to cluster patients based on their genetic status across identified risk variants for five NDDs (Alzheimer’s disease [AD], Parkinson’s disease [PD], amyotrophic lateral sclerosis [ALS], Lewy body dementia [LBD], and frontotemporal dementia [FTD]). The multi-disease and disease-specific clustering results presented here provide evidence that NDDs have more overlapping genetic etiology than previously expected and how neurodegeneration should be viewed as a spectrum of symptomology. These clustering analyses also show potential subsets of patients with these diseases that are significantly depleted for any known common genetic risk factors suggesting environmental or other factors at work. Establishing that NDDs with overlapping pathologies share genetic risk loci, future research into how these variants might have different effects on downstream protein expression, pathology and NDD manifestation in general is important for refining and treating NDDs.
Stress and resilience during pregnancy: a comparative study between pregnant and non-pregnant women in Ethiopia
Authors: Abera Mubarek , Hanlon Charlotte , Fedlu Hikma , Fewtrell Mary , Tesfaye Markos , Wells Jonathan 
Published: December 2022

AbstractBackgroundStress occurring during pregnancy is associated with perturbances in maternal psychology and physiology, and results in adverse pregnancy and birth outcomes. However, little attention has been given to understand maternal stress and its potential negative consequences in many low- and middle-income countries. We aimed to investigate whether pregnancy is associated with greater stress and lower psychological resilience among women living in Jimma, Southwest Ethiopia.MethodAn institution-based comparative cross-sectional study design was implemented in Jimma University Medical Center from 15 September to 30 November 2021. Women attending antenatal care and family planning services were invited to participate in the study. Participants were interviewed using the Perceived Stress Scale (PSS-10), Brief Resilience Scale (BRS), distress questionnaire-5, and the Household Food Insecurity Access Scale (HFIAS). Linear regression analysis was used to test associations of pregnancy (exposure) with outcomes of stress and resilience scores, while adjusting for potential confounders. Stress and resilience were mutually adjusted for one another in the final model.ResultsA total of 166 pregnant and 154 non-pregnant women participated, with mean age of 27.0 SD 5.0 and 29.5 SD 5.3 years respectively. Pregnancy was associated with increased stress score by 4.1 points (β=4.1; 95% CI: 3.0, 5.2), and with reduced resilience by 3.3 points (β=3.3; 95% CI: -4.5, -2.2) in a fully adjusted model. In mutually-adjusted models, pregnancy was independently associated with greater stress (β=2.9, 95% CI 1.8, 3.9) and lower resilience (β=-1.3, 95% CI: -2.5, -0.2) compared to non-pregnant women.ConclusionIn this low income setting, pregnancy is associated with greater vulnerability in the mental health of women, characterized by greater perceived stress and diminished resilience. Context-relevant interventions to improve resilience and reduce stress could help improve the health and wellbeing of mothers, with potential benefits for their offspring.
H3.1Cys96oxidation by mitochondrial ROS promotes chromatin remodeling, breast cancer progression to metastasis and multi-drug resistance
Authors: Palma Flavio R. , Ogata Fernando T. , Coelho Diego R. , Pulakanti Kirthi , Meyer Alison , Huang Yunping , Danes Jeanne M. , Schipma Matthew J. , Furdui Cristina M. , Spitz Douglas R. , Gantner Benjamin N. , Rao Sridhar , Backman Vadim , Bonini Marcelo G. 
Published: December 2022

ABSTRACTTranscription stability enforces cellular identity and is tightly controlled by restrictions imposed on both transcription factor function and target gene accessibility. Progression of cancer to metastasis and multi-drug resistance requires fluid transcriptional programs that can explore different genomic landscapes to enable clonal expansion of aggressive and treatment resistant phenotypes. Here, we show that increased levels of H2O2produced in mitochondria leads to H3.1 oxidation at Cys96, a distinctive redox sensitive amino acid residue restricted to this histone variant, in the nucleus. The oxidation of Cys96 promotes the eviction of H3.1 from chromatin and its exchange with H3.3, thereby opening silenced portions of the chromatin. Mutation of Cys96 by an oxidation-resistant serine residue or quenching nuclear H2O2reversed chemotherapy resistance and drove established metastatic disease into remission. Together, these results show that increased mitochondrial H2O2production, characteristic of metabolic dysfunction, promotes transcriptional plasticity by removing structural chromatin restrictions imposed by the redox sensitive histone variant H3.1. We suggest that this new regulatory nexus between cancer metabolism and chromatin remodeling controls chromatin states that enable cancer progression and drug resistance acquisition.
The plant nuclear lamina disassembles to regulate genome folding in stress conditions
Authors: Wang Nan , Wang Zhidan , Tzourtzou Sofia , Wang Xu , Bi Xiuli , Leimeister Julia , Xu Linhao , Sakamoto Takuya , Matsunaga Sachihiro , Schaller Andreas , Jiang Hua , Liu Chang 
Published: December 2022

AbstractThe nuclear lamina (NL) is a complex network of nuclear lamins and lamin-associated nuclear membrane proteins, which scaffold the nucleus to maintain structural integrity. InArabidopsisthaliana, Nuclear Matrix Constituent Proteins (NMCPs) are essential components of the NL and are required to maintain the structural integrity of the nucleus and specific perinuclear chromatin anchoring. At the nuclear periphery, suppressed chromatin overlapping with repetitive sequences and inactive protein coding genes are enriched. At a chromosomal level, plant chromatin organization in interphase nuclei displays flexibilities in response to various developmental cues and environmental stimuli. Based on these observations inArabidopsis, and given the role ofAtNMCPgenes (CRWN1andCRWN4) in organizing chromatin positioning at the nuclear periphery, one can expect considerable changes in chromatin-NL interactions when the global chromatin organization patterns are being altered in plants. Here, we report the highly flexible nature of plant nuclear lamina, which disassembles substantially under various stress conditions. Particularly, under heat stress, we reveal that chromatin domains, initially tethered to the nuclear envelope, remain largely associated with CRWN1 and become scattered in the inner nuclear space. Via investigating the three-dimensional chromatin contact network, we further reveal that CRWN1 proteins play a structural role in shaping the changes in genome folding under heat stress. Also, CRWN1 acts as a negative transcriptional co-regulator to modulate the shift of the plant transcriptome profile in response to heat stress.
Assessing the Nucleotide-Level Impact of Spaceflight Stress using RNA-Sequencing Data
Authors: Knight Montana S. , Doherty Colleen J. , Nielsen Dahlia M. 
Published: December 2022

AbstractUnderstanding the effects of space radiation and microgravity on DNA integrity is critical to assess the impact of long-term spaceflight. However, studying spaceflight’s effect on terrestrial life is difficult. NASA created GeneLab, a public Omics database for spaceflight-related data, to help combat these limitations. While GeneLab has very few DNA-based data sets, transcriptome information is abundant. This study used RNA-Seq data from GeneLab to examine DNA sequence variants linked to spaceflight stress exposure. More mutations were observed in spaceflight samples than in the ground control samples. This increase in variants was not reduced in samples grown under artificial gravity in space, suggesting that microgravity did not significantly affect the amount of DNA damage in this experiment. There was also an increase in transversion mutations, consistent with known forms of radiation-induced damage. This work demonstrates that RNA-Seq data is a useful resource for evaluating DNA damage from spaceflight and provides a baseline for the types of mutations that could be detected.
Mercury contamination of an introduced generalist fish of intermediate trophic level
Authors: Gedig D. P. , Hauger M. , Armstrong D. A. , Jeffries K. M. 
Published: December 2022

AbstractMercury contamination is a global issue because mercury concentrations in aquatic systems are influenced by both natural and anthropogenic pathways, including the burning of fossil fuels and flooding during hydroelectric development. Mercury biomagnifies in aquatic ecosystems, leading to higher concentrations in piscivore fishes than those at lower trophic levels. Here, liver and muscle total mercury (THg) concentrations in black crappiePomoxis nigromaculatusfrom three lakes in southeastern Manitoba, Canada were related to age, morphology and physiological traits to better understand the dynamics of mercury accumulation in an introduced generalist fish species. Black crappie liver and muscle samples from Big Whiteshell Lake (relatively large lake, 17.5 km2; n=30), Caddy Lake (small lake surrounded by wetlands, 3.1 km2; n=42) and Lac du Bonnet (river widening influenced by hydroelectric dams, 84.0 km2; n=29) were analyzed for THg content. These THg concentrations were then compared to black crappie mercury concentrations in other Canadian water bodies to assess within species relative contamination levels, as well as to mercury concentrations in other freshwater fishes to examine biomagnification. Age and size had strong positive correlations (r>0.60) with muscle mercury concentrations. No evidence of acute point source contamination was found in the study area when compared to black crappie muscle mercury concentrations in other water bodies, and tissue THg concentration was not correlated with a reduction in gonadosomatic index (GSI) or hepatosomatic index (HSI). Analysis of liver THg in addition to muscle THg revealed the possible impacts of seasonal and ontogenetic differences in diet on exposure. Furthermore, THg analysis of liver and muscle tissue showed how generalist foraging techniques of black crappie may curb the progressively greater mercury exposure and resultant physiological consequences expected from ontogenetic diet shifts from invertebrates to fishes. Although there appeared to be temporally varied levels of mercury exposure (i.e., liver THg) by sex, there was no sex effect observed in long-term accumulation in the muscle. Flood risk is believed to be a key driver of differences in black crappie THg concentrations between lakes in the region. Black crappie bioaccumulated less mercury at age than primary piscivore species in the region. These results will help foster a better understanding of mercury biomagnification in boreal shield lakes within a region impacted by legacy mercury.
Deficiency in hyaluronan synthase 3 attenuates ruptures in a murine model of abdominal aortic aneurysms by reduced aortic monocyte infiltration
Authors: Suvorava Tatsiana , Brack Fedor , Kaczur Janet , Petzsch Patrick , Köhrer Karl , Quast Christine , Gerdes Nobert , Voigt Katharina , Krüger Martina , Fischer Jens W. , Brückner Alexander , Fleischmann Bernd K. , Wenzel Daniela , Zimmermann Laura-Maria A. , Sengle Gerhard , Flögel Ulrich , Grandoch Maria 
Published: December 2022

AbstractAbdominal aortic aneurysms (AAA) are a common vascular disorder with a high mortality due to the prevalence of aortic ruptures. The underlying pathomechanisms are complex and involve immune cell infiltration and degradation of the vascular extracellular matrix (ECM). Hyaluronan (HA), synthesized at the plasma membrane by three HA synthase isoenzymes (HAS1-3), is not only a major constituent of the ECM but also known to directly affect the phenotype of vascular smooth muscle cells as well as immunological responses. Specifically, the HAS3 isoenzyme has been reported to play a major role in various inflammatory conditions. Therefore, the aim of the present study was to elucidate the role of HAS3-derived HA in the pathogenesis of abdominal aortic aneurysm. To this end, we used a murine model of Angiotensin II (AngII)-induced abdominal aortic aneurysms and dissections (AAAs/AADs) and could demonstrate that genetic depletion ofHas3improves survival inApoe/Has3double deficient (Apoe/Has3-DKO) mice via the reduced occurrence of aortic ruptures. Mechanistically, fewer elastica breaks were observed inApoe/Has3-DKO mice compared toApoe-KO littermates. This was associated with a decreased infiltration of myeloid immune cells into the vessel wall ofHas3-deficient mice while in parallel elevated numbers of circulating leukocytes were detected. RNA seq analysis from aortic tissue pointed towards a disturbed endothelial-myeloid cell communication as a cause for the diminished recruitment of immune cells to the aortic wall. While endothelial cells were unaffected, upregulation of adhesion receptors as well as the HA receptor CD44, known to mediate leukocyte adhesion to the endothelium, was blunted in monocytes fromApoe/Has3-DKO mice in response to AngII treatment. These findings underline the pivotal detrimental role of monocyte’s HAS3-dependent pericellular HA matrix for an exaggerated immune cell recruitment to inflammatory foci giving here rise for an increased incidence of ruptured aortic aneurysms.