bluuebunny/crossref_metadata_2025_split huggingface dataset:
REPRODUCTIVE SENESCENCE IMPAIRS THE ENERGY METABOLISM OF HUMAN GRANULOSA CELLS
Authors: Cecchino Gustavo Nardini , García-Velasco Juan A. , Rial Eduardo 
Published: March 2021

AbstractFemale age is the single greatest factor influencing reproductive performance. It is widely known that mitochondrial dysfunction plays a key role in reproductive senescence. Ovarian bioenergetics includes a sophisticated metabolic synergism between oocytes and human mural granulosa cells (GCs), which is crucial for oocyte maturation during follicular growth. These cells are believed to be potential biomarkers of oocyte quality. It has been proposed that alterations in their energy metabolism could lead to infertility. We investigated if there is an age-related effect on the energy metabolism of human mural granulosa cells. We performed an observational prospective cohort and experimental study including 127 women that underwent in vitro fertilization cycles allocated to two groups: a control group comprising oocyte donors aged less than 35 years and a group of infertile women aged over 38 years. The bioenergetics of cumulus cells and purified mural GCs were determined from oxidative phosphorylation parameters, aerobic glycolysis and adenine nucleotide levels. We have found that human mural GCs and cumulus cells present a high glycolytic profile and that the follicular fluid is critical to sustain their energy metabolism. GCs from older women present lower mitochondrial respiration and glycolysis than those from young donors which is not accompanied by a lower respiratory capacity. The diminished energy metabolism leads to a decrease in the total cellular energy charge. We conclude that, as women age, mural granulosa cells exhibit a reduction in their energy metabolism that is likely to influence female reproductive potential.
Refget: standardised access to reference sequences
Authors: Yates Andrew D , Adams Jeremy , Chaturvedi Somesh , Davies Robert M. , Laird Matthew , Leinonen Rasko , Nag Rishi , Sheffield Nathan C. , Hofmann Oliver , Keane Thomas 
Published: March 2021

ABSTRACTReference sequences are essential in creating a baseline of knowledge for many common bioinformatics methods, especially those using genomic sequencing. We have created refget, a Global Alliance for Genomics and Health API specification to access reference sequences and sub-sequences using an identifier derived from the sequence itself. We present four reference implementations across in-house and cloud infrastructure, a compliance suite and a web report used to ensure specification conformity across implementations.https://w3id.org/ga4gh/refget.
Chronic exercise protects against the progression of renal cyst growth and dysfunction in rats with polycystic kidney disease
Authors: Qiu Jiahe , Sato Yoichi , Xu Lusi , Miura Takahiro , Kohzuki Masahiro , Ito Osamu 
Published: March 2021

AbstractIntroductionPolycystic kidney disease (PKD) is a genetic disorder characterized by the progressive enlargement of renal epithelial cysts and renal dysfunction. Previous studies have reported the beneficial effects of chronic exercise on chronic kidney disease. However, the effects of chronic exercise have not been fully examined in PKD patients or models. The effects of chronic exercise on the progression of PKD were investigated in a polycystic kidney (PCK) rat model.MethodsSix-week-old male PCK rats were divided into a sedentary group and an exercise group. The exercise group underwent forced treadmill exercise for 12 weeks (28 m/min, 60 min/day, 5 days/week). After 12 weeks, kidney function and histology were examined, protein expressions were analyzed, and signaling cascades of PKD were examined.ResultsChronic exercise reduced the excretion of urinary protein, liver-type fatty acid-binding protein, plasma creatinine, urea nitrogen, and increased plasma irisin and urinary arginine vasopressin (AVP) excretion. Chronic exercise also slowed renal cyst growth, glomerular damage, and interstitial fibrosis, and led to reduced Ki-67 expression. Chronic exercise had no effect on cAMP content but decreased the renal expression of B-Raf and reduced the phosphorylation of extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), and S6.ConclusionChronic exercise slows renal cyst growth and damage in PCK rats, despite increasing AVP, with down-regulation of the cAMP/B-Raf/ERK and mTOR/S6 pathways in the kidney of PCK rats.
Adipocyte Tribbles1 Regulates Plasma Adiponectin and Plasma Lipids in Mice
Authors: Ha Elizabeth E. , Quartuccia Gabriella I. , Ling Ruifeng , Xue Chenyi , Hernandez-Ono Antonio , Imam Rami , Cui Jian , Soni Rajesh K. , Bauer Robert C. 
Published: March 2021

AbstractMultiple GWAS have identified SNPs in the 8q24 locus near theTRIB1gene that significantly associate with plasma lipids and coronary artery disease. While subsequent studies have uncovered roles for hepatic and myeloidTrib1in contributing to either plasma lipids or atherosclerosis, the causal tissue for these GWAS associations remains unclear. The same 8q24 SNPs significantly associate with plasma adiponectin levels in humans as well, suggesting a role forTRIB1in adipose tissue. Here, we report that adipocyte-specificTrib1knockout mice (Trib1_ASKO) have increased plasma adiponectin levels and decreased plasma cholesterol and triglycerides. We demonstrate that loss ofTrib1increases adipocyte production and secretion of adiponectin independent of the known TRIB1 function of regulating proteasomal degradation. RNA-seq analysis of adipocytes and livers from Trib1_ASKO mice suggests that alterations in adipocyte function underlie the plasma lipid changes observed in these mice. Secretomics and RNA-seq analysis revealed that Trib1_ASKO mice have increased production of Lpl and decreased production of Angptl4 in adipose tissue, and fluorescent substrate assays confirm an increase in adipose tissue Lpl activity, which likely underlies the observed triglyceride phenotype. In summary, we demonstrate here a novel role for adipocyteTrib1in regulating plasma adiponectin, total cholesterol, and triglycerides in mice, confirming previous genetic associations observed in humans and providing a novel avenue through whichTrib1regulates plasma lipids and coronary artery disease.
Relevance of Circulating Hybrid Cells as a Non-Invasive Biomarker for Myriad Solid Tumors
Authors: Dietz Matthew S. , Sutton Thomas L. , Walker Brett S. , Gast Charles E. , Zarour Luai , Sengupta Sidharth K. , Swain John R. , Eng Jennifer , Parappilly Michael , Limbach Kristen , Sattler Ariana , Burlingame Erik , Chin Yuki , Gower Austin , Montoya Mira Jose L. , Sapre Ajay , Chiu Yu-Jui , Clayburgh Daniel R. , Pommier SuEllen J. , Cetnar Jeremy P. , Fischer Jared M. , Jaboin Jerry J. , Han Seunggu J. , Nazemi Kellie J. , Pommier Rodney F. , Billingsley Kevin G. , Sheppard Brett C. , Tsikitis V. Liana , Skalet Alison H. , Mayo Skye C. , Lopez Charles D. , Gray Joe W. , Mills Gordon B. , Mitri Zahi , Hwan Chang Young , Chin Koei , Wong Melissa H. 
Published: March 2021

AbstractMetastatic progression defines the final stages of tumor evolution and underlies the majority of cancer-related deaths. The heterogeneity in disseminated tumor cell populations capable of seeding and growing in distant organ sites contributes to the development of treatment resistant disease. We recently reported the identification of a novel tumor-derived cell population, circulating hybrid cells (CHCs), harboring attributes from both macrophages and neoplastic cells, including functional characteristics important to metastatic spread. These disseminated hybrids outnumber conventionally defined circulating tumor cells (CTCs) in cancer patients. It is unknown if CHCs represent a generalized cancer mechanism for cell dissemination, or if this population is relevant to the metastatic cascade. Herein, we detect CHCs in the peripheral blood of patients with cancer in myriad disease sites encompassing epithelial and non-epithelial malignancies. Further, we demonstrate that in vivo-derived hybrid cells harbor tumor-initiating capacity in murine cancer models and that CHCs from human breast cancer patients express stem cell antigens, features consistent with the ability to seed and grow at metastatic sites. Finally, we reveal heterogeneity of CHC phenotypes reflect key tumor features, including oncogenic mutations and functional protein expression. Importantly, this novel population of disseminated neoplastic cells opens a new area in cancer biology and renewed opportunity for battling metastatic disease.Simple SummaryThere is an incomplete understanding of circulating neoplastic cell populations and the fundamental mechanisms that drive dissemination, immune evasion, and growth —all critical information to more effectively prevent and treat cancer progression. A novel disseminated tumor cell population, circulating hybrid cells, are detected across many cancer types and carry functional tumor-initiating properties. Additionally, circulating hybrid cells are found at significantly higher levels than conventionally defined circulating tumor cells. Our study demonstrates that neoplastic hybrid cells harbor phenotypic and genetic characteristics of tumor and immune cells, display stem features, and are a generalizable phenomenon in solid tumors. Circulating hybrid cells therefore have relevance as a novel biomarker and open a new field of study in malignancy.
The mutational signatures of formalin fixation on the human genome
Authors: Guo Qingli , Lakatos Eszter , Al Bakir Ibrahim , Curtius Kit , Graham Trevor A. , Mustonen Ville 
Published: March 2021

AbstractBackgroundFormalin fixation and paraffin embedding (FFPE) of patient material remains standard practice in clinical pathology labs around the world. Clinical archives of patient material near-exclusively consist of FFPE blocks. The ability to perform high quality genome sequencing on FFPE-derived DNA would accelerate a broad spectrum of medical research. However, formalin is a recognised mutagen and sequencing of DNA derived from FFPE material is known to be riddled with artefactual mutations.ResultsHere we derive genome-wide mutational signatures caused by formalin fixation, and provide a computational method to correct mutational profiles for these formalin-induced artefacts. We show that the FFPE-signature is dominated by C>T transitions caused by cytosine deamination, and has very high similarity to COSMIC signature SBS30 (base excision repair deficiency due to inactivation mutations inNTHL1). Further, we demonstrate that chemical repair of formalin-induced DNA lesions, a process that is routinely performed as part of sequencing library preparation, leads to a signature highly similar to COSMIC signature SBS1 (spontaneous deamination of methylated cytosine). Next, we design FFPEsig, a computational method to remove the formalin-induced artefacts from mutational counts. We prove the efficacy of this method by generating synthetic FFPE samples using 2,780 cancer genomes from the Pan-Cancer Analysis of Whole Genome (PCAWG) project, and via analysis of FFPE-derived genome sequencing data from colorectal cancers.ConclusionsFormalin fixation leaves a predictable mutational footprint across the genome. The application of our FFPEsig software corrects the mutational profile for the influence of formalin, enabling robust mutational signature analysis in FFPE-derived patient material.
A meta-analysis of effects of feeding seaweed on beef and dairy cattle performance and methane yield
Authors: Lean Ian J. , Golder Helen M. , Grant Tianna M. D. , Moate Peter J. 
Published: March 2021

AbstractThere has been considerable interest in the use of red seaweed, and in particularAsparagopsis taxiformis, to increase production of cattle and to reduce greenhouse gas emissions. We hypothesized that feeding seaweed or seaweed derived products would increase beef or dairy cattle performance as indicated by average daily gain (ADG), feed efficiency measures, milk production, and milk constituents, and reduce methane emissions. We used meta-analytical methods to evaluate these hypotheses. A comprehensive search of Google Scholar, Pubmed and ISI Web of Science produced 14 experiments from which 23 comparisons of treatment effects could be evaluated. Red seaweed (A. taxiformis) and brown seaweed (Ascophyllum nodosum) were the dominant seaweeds used. There were no effects of treatment on ADG or dry matter intake (DMI). There was an increase in efficiency for feed to gain by 0.41 ± 0.22 kg per kg [standardized mean difference (SMD) = 0.70 ± 0.35; P = 0.001], but not for gain to feed (P = 0.215), although the direction of the change was for improved efficiency. The type of seaweed used was not a significant covariable for ADG and DMI. Milk production was increased with treatment on weighted mean difference (WMD; 1.35 ± 0.44 kg/d; P <0.001); however, the SMD of 0.45 was not significant (P = 0.111). Extremely limited data suggest the possibility of increased percentages of milk fat (P = 0.040) and milk protein (P = 0.001) on DerSimonian and Laird (D&L) WMD evaluation. The limited data available indicate dietary supplementation with seaweed produced a significant and substantial reduction in methane yield by 5.28 ± 3.5 g/kg DMI (P = 0.003) on D&L WMD evaluation and a D&L SMD of −1.70 (P = 0.001); however, there was marked heterogeneity in the results (I2> 80%). In one comparison, methane yield was reduced by 97%. We conclude that while there was evidence of potential for benefit from seaweed use to improve production and reduce methane yield morein vivoexperiments are required to strengthen the evidence of effect and identify sources of heterogeneity in methane response, while practical applications and potential risks are evaluated for seaweed use.
Egocentric Asymmetric Coding in Sensory Cortical Border Cells
Authors: Long Xiaoyang , Deng Bin , Cai Jing , Chen Zhe Sage , Zhang Sheng-Jia 
Published: March 2021

ABSTRACTBoth egocentric and allocentric representations of space are essential to spatial navigation. Although some studies of egocentric coding have been conducted within and around the hippocampal formation, externally anchored egocentric spatial representations have not yet been fully explored. Here we record and identify two subtypes of border cell in the rat primary somatosensory cortex (S1) and secondary visual cortex (V2). Subpopulations of S1 and V2 border cells exhibit rotation-selective asymmetric firing fields in an either clockwise (CW) or counterclockwise (CCW) manner. CW- and CCW-border cells increase their firing rates when animals move unidirectionally along environmental border(s). We demonstrate that both CW- and CCW-border cells fire in an egocentric reference frame relative to environmental borders, maintain preferred directional tunings in rotated, stretched, dark as well as novel arenas, and switch their directional firings in the presence of multi-layer concentric enclosures. These findings may provide rotation-selective egocentric reference frames within a larger spatial navigation system, and point to a common computational principle of spatial coding shared by multiple sensory cortical areas.HighlightsEgocentric border cells are present in rat S1 and V2Subtypes of border cells display egocentric asymmetric codingEgocentric and allocentric streams coexist in sensory corticesRotation-selective asymmetric firing is robust with environmental manipulations
Optimal immune specificity at the intersection of host life history and parasite epidemiology
Authors: Downie A. E. , Mayer A. , Metcalf C. J. E. , Graham A. L. 
Published: March 2021

AbstractEpidemiology and life history are commonly hypothesized to influence host immune strategy, and the pairwise relationships between immune strategy and each factor have been extensively investigated. But the interaction of these two is rarely considered, despite evidence that this interaction might produce emergent effects on optimal immune strategy. Here we investigate the confluence of epidemiology and life history as it affects immune strategy through a demographically-framed model of sensitivity and specificity in parasite recognition and response. We find that variation in several different life history traits associated with both reproduction and longevity alters optimal immune strategies – but the direction and magnitude of these effects depends on how epidemiological risks vary across life. Drawing on published life history data, we also find that our predictions apply across chordate taxa. Our results shed light on the complex interactions shaping immune strategy and may prove valuable in interpreting empirical results in ecoimmunology.
Combination adjuvants enhance recombinant protein vaccine protection against fungal infection
Authors: Wuethrich Marcel , Dobson Hannah E. , Taira Cleison Ledesma , Okaa Uju Joy , Petrovsky Nikolai , Klein Bruce S. 
Published: March 2021

ABSTRACTThe development of effective vaccines against fungal infections requires the induction of protective, pathogen-specific cell mediated immune responses. Here, we asked whether combination adjuvants based on delta inulin (Advax) formulated with TLR agonists could improve vaccine protection mediated by a fungal recombinant protein, Bl-Eng2, which itself harbors an immunodominant antigen and Dectin-2 agonist/adjuvant. We found that Bl-Eng2 formulated with Advax3 containing TLR9 agonist or Advax8, containing TLR4 agonist, provided the best protection against pulmonary infection withBlastomyces dermatitidis, being more effective than Freund’s complete adjuvant or Adjuplex. Advax3 was most efficient in inducing IFN-γ and IL-17 producing antigen-specific T cells that migrated to the lung uponBlastomyces dermatitidisinfection. Mechanistic studies revealed Bl-Eng2/Advax3 protection was tempered by neutralization of IL-17 and particularly IFN-γ. Likewise, greater numbers of lung-resident T cells producing IFN-γ, IL-17, or IFN-γ+and IL-17+correlated with fewer fungi recovered from lung. Protection was maintained after depletion of CD4+T cells, partially reduced by depletion of CD8+T cells, and completely eliminated after depletion of both CD4+and CD8+T cells. We conclude that Bl-Eng2 formulated with Advax3 is promising for eliciting vaccine-induced antifungal immunity, through a previously uncharacterized mechanism involving CD8+and also CD4+T cells producing IFN-γ and/or IL-17. Although no licensed vaccine exists as yet against any fungal disease, these findings indicate the importance of adjuvant selection for the development of effective fungal vaccines.IMPORTANCEFungal disease remains a challenging clinical and public health problem. Despite medical advances, invasive fungal infections have skyrocketed over the last decade and pose a mounting health threat in immune-competent and -deficient hosts with worldwide mortality rates ranking 7th, even ahead of tuberculosis. The development of safe, effective vaccines remains a major hurdle for fungi. Critical barriers to progress include the lack of defined fungal antigens and suitable adjuvants. Our research is significant in identifying adjuvant combinations that elicit optimal vaccine-induced protection when formulated with a recombinant protective antigen and uncovering the mechanistic bases of the underlaying vaccine protection, which will foster the strategic development of anti-fungal vaccines.
Baseline power of theta oscillations predicts mystical-type experiences induced by DMT
Authors: Tagliazucchi Enzo , Zamberlan Federico , Cavanna Federico , de la Fuente Laura , Romero Celeste , Perl Yonatan Sanz , Pallavicini Carla 
Published: March 2021

AbstractN,N-Dimethyltryptamine (DMT) is a classic psychedelic capable of inducing short-lasting but profound changes in consciousness. As with other psychedelics, the experience induced by DMT strongly depends upon contextual factors, yet the neurobiological determinants of this variability remain unknown. We combined wireless electroencephalography and source imaging to map changes in neural oscillations elicited by inhaled DMT. Furthermore, we found that the power of frontal and temporal theta oscillations was inversely correlated with scales indexing feelings of unity and transcendence, which are an integral part of the phenomenology of mystical-type experiences. Finally, we established the robustness of these results using a machine learning model for regression trained and tested following a cross-validation procedure. Our results are consistent with the observation that the state of mind prior to consuming a psychedelic drug influences the ensuing subjective experience of the user. We also suggest that priming subjects to reduce their theta power before administration of a serotonergic psychedelic could enhance the likelihood of inducing mystical-type experiences, leading to sustained positive effects in well-being and improving the outcome of therapeutic interventions.
A conserved BAH module within mammalian BAHD1 connects H3K27me3 to Polycomb gene silencing
Authors: Fan Huitao , Guo Yiran , Tsai Yi-Hsuan , Storey Aaron J. , Kim Arum , Gong Weida , Edmondson Ricky D. , Mackintosh Samuel G. , Li Haitao , Byrum Stephanie D. , Tackett Alan J. , Cai Ling , Wang Gang Greg 
Published: March 2021

ABSTRACTTrimethylation of histone H3 lysine 27 (H3K27me3) is important for gene silencing and imprinting, (epi)genome organization and organismal development. In a prevalent model, the functional readout of H3K27me3 in mammalian cells is achieved through the H3K27me3-recognizing chromodomain harbored within the chromobox (CBX) component of canonical Polycomb repressive complex 1 (cPRC1), which induces chromatin compaction and gene repression. Here, we report that binding of H3K27me3 by a Bromo Adjacent Homology (BAH) domain harbored within BAH domain-containing protein 1 (BAHD1) is required for overall BAHD1 targeting to chromatin and for optimal repression of the H3K27me3-demarcated genes in mammalian cells. Disruption of direct interaction between BAHD1BAHand H3K27me3 by point mutagenesis leads to chromatin remodeling, notably, increased histone acetylation, at its Polycomb gene targets. Mice carrying an H3K27me3-interaction-defective mutation of Bahd1BAHcauses marked embryonic lethality, showing a requirement of this pathway for normal development. Altogether, this work demonstrates an H3K27me3-initiated signaling cascade that operates through a conserved BAH “reader” module within BAHD1 in mammals.Key PointsBAHD1BAHis a functionally validated mammalian “reader” of H3K27me3, mediating BAHD1 targeting for gene silencing.BAHD1BAHconnects H3K27me3 together with histone deacetylation, an integral step of gene silencing.BAHD1BAH-mediated functional readout of H3K27me3 is essential for organismal development.Graphic abstractA mammalian H3K27me3-transduction pathway operates through an H3K27me3-specific ‘reader’ module (BAH) of BAHD1, which assembles a complex with corepressors (HDACs and others) for suppressing histone acetylation and repressing expression at Polycomb target genes.