bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity and biotechnological potential of filamentous fungi isolated from sediments of Basque estuaries
Authors: Otamendi A. , Agirrezabala Z. , Perez-Cruz C. , Liébana R. , Berregi I. , Alonso-Sáez L. , Dueñas M.T. , Lanzén A. , Etxebeste O. 
Published: July 2023

AbstractMarine environments harbor a vast diversity of microorganisms, which have developed multiple strategies to adapt to stress conditions such as high salt concentrations and nutrient scarcity and, thus, are a source of natural products and high-value enzymes, as they have the ability to degrade complex polymeric substrates. These features make marine microorganisms a valuable source for the development of new biotechnological tools. Here, we focused on the isolation of filamentous fungi, using sediment samples collected from estuaries of the Basque Country in the Bay of Biscay. The phenotype of these isolates was characterized based on the potential to grow on complex marine polysaccharides or to secrete pigments to the culture medium. Based on this screening, the genomes of two isolates of the order Hypocreales,Marquandomyces marquandiiandAlbophoma yamanashiensis, were sequenced and are described here for the first time. The analysis of their CAZYme (carbohydrate-active enzyme) and secondary metabolite gene-cluster repertoires suggest that these estuarine isolates could be used as a source of novel enzymatic activities and secondary metabolites.One-sentence summaryIsolation and characterization of filamentous fungi from sediments of Basque estuaries and an assessment of their biotechnological potential.ImportanceMarine microbes are considered an unlimited source of molecules for biotechnology in fields such as pharmaceutics, biomedicine, cosmetics, nutraceutics, food, feed or agriculture. Thus, it is believed that blue biotechnology will make a significant contribution to the sustainability of global economy. However, the study of marine fungi lags behind that of marine bacteria and it is considered that the potential impact of fungi at the biotechnological level is underestimated. In this work, filamentous fungi from sediment samples of estuaries of the Basque Country have been isolated and the genomes of the Sordariomycete fungiMarquandomyces marquandiiandAlbophoma yamanashiensissequenced and analyzed. Their characterization will contribute to the inventory of the genomic diversity within filamentous fungi and the identification of species and activities with biotechnological potential.
Investigating Brain Alterations in the Dp1Tyb Mouse Model of Down Syndrome
Authors: Serrano Maria Elisa , Kim Eugene , Siow Bernard , Ma Da , Rojo Loreto , Simmons Camilla , Hayward Darryl , Gibbins Dorota , Singh Nisha , Strydom Andre , Fisher Elizabeth M. C. , Tybulewicz Victor L. J. , Cash Diana 
Published: July 2023

ABSTRACTDown syndrome (DS) is one of the most common birth defects and the most prevalent genetic form of intellectual disability. DS arises from trisomy of chromosome 21, but its molecular and pathological consequences are not fully understood. In this study, we compared Dp1Tyb mice, a DS model, against their wild-type (WT) littermates of both sexes to investigate the impact of DS-related genetic abnormalities on the brain phenotype.We performedin vivowhole brain magnetic resonance imaging (MRI) and hippocampal1H magnetic resonance spectroscopy (MRS) on the animals at 3 months of age. Subsequently,ex vivoMRI scans and histological analyses were conducted post-mortem. Our findings unveiled distinct neuroanatomical and biochemical alterations in the Dp1Tyb brains.Dp1Tyb brains exhibited a smaller surface area and a rounder shape compared to WT brains. Regional volumetric analysis revealed significant changes in 26 out of 72 examined brain regions, including the medial prefrontal cortex and dorsal hippocampus. These alterations were consistently observed in bothin vivoandex vivoimaging data. Additionally, high-resolutionex vivoimaging enabled us to investigate cerebellar layers and hippocampal subregions, revealing selective areas of decrease and remodelling in these structures.An analysis of hippocampal metabolites revealed an elevation in glutamine and the glutamine/glutamate ratio in the Dp1Tyb mice compared to controls, suggesting a possible imbalance in the excitation/inhibition ratio. This was accompanied by the decreased levels of taurine. Histological analysis revealed fewer neurons in the hippocampal CA3 and DG layers, along with an increase in astrocytes and microglia. These findings recapitulate multiple neuroanatomical and biochemical features associated with DS, enriching our understanding of the potential connection between chromosome 21 trisomy and the resultant phenotype.
EEG-fMRI in awake rat and whole-brain simulations show decreased brain responsiveness to sensory stimulations during absence seizures
Authors: Stenroos Petteri , Guillemain Isabelle , Tesler Federico , Montigon Olivier , Collomb Nora , Stupar Vasile , Destexhe Alain , Coizet Véronique , David Olivier , Barbier Emmanuel L. 
Published: July 2023

AbstractIn patients suffering absence epilepsy, recurring seizures can significantly decrease their quality of life and lead to yet untreatable comorbidities. Absence seizures are characterized by spike-and- wave discharges on the electroencephalogram associated with a transient alteration of consciousness. However, it is still unknown how the brain responds to external stimuli during and outside of seizures.This study aimed to investigate responsiveness to visual and somatosensory stimulation in GAERS, a well-established rat model for absence epilepsy. Animals were imaged under non-curarized awake state using a quiet, zero-echo-time, functional magnetic resonance imaging (fMRI) sequence. Sensory stimulations were applied during interictal and ictal periods. Whole brain hemodynamic responses were compared between these two states. Additionally, a mean-field simulation model was used to explain the changes of neural responsiveness to visual stimulation between states.During a seizure, whole-brain responses to both sensory stimulations were suppressed and spatially hindered. In the cortex, hemodynamic responses were negatively polarized during seizures, despite the application of a stimulus. The mean-field simulation revealed restricted propagation of activity due to stimulation and agreed well with fMRI findings. Results suggest that sensory processing is hindered or even suppressed by the occurrence of an absence seizure, potentially contributing to decreased responsiveness during this absence epileptic process.
Tillering structures the genetic variability of wheat vegetative growth and its plasticity under water deficit
Authors: Leveau Stéphane , Parent Boris , Giunta Francesco , Luchaire Nathalie , Cabrera-Bosquet Llorenç , Beauchêne Katia , Jezequel Stéphane , Motzo Rosella , Martre Pierre 
Published: July 2023

AbstractLeaf expansion under drought drives the trade-off between water saving for later grain production and canopy photosynthesis. Fine-tuning leaf expansion could therefore become a target of genetic progress for drought-prone environments. However, its components (branching, leaf production and elongation) may have their own genetic variability and plasticity under drought, making hard to calibrate crop simulation models and specify breeding targets. In this study, we focused on the genetic diversity of bread wheat and durum wheat to determine the links and trade-offs between the underlying processes of leaf growth under drought and how it translates to leaf expansion at the whole plant and canopy level. For that, we used non-destructive imaging both in the field and controlled condition platforms to determine the dynamics of the components of shoot expansion and analyze their relative contribution to the genetic variability of whole-plant shoot expansion under drought. Results show that leaf expansion measured at plant level in controlled environment was associated with that measured at canopy level in the field, indicating that controlled phenotyping platforms can capture the genetic variability of growth in the field. Both whole-plant and canopy expansion were associated with tillering rate. In addition, the sensitivity of shoot growth and tillering to soil water deficit were correlated, indicating that both tillering ability and sensitivity to water deficit drive the genetic variability of shoot expansion. Overall, dissecting leaf expansion dynamics allowed determining the links between shoot expansion traits under drought, and provides key targets in phenotyping, modelling and breeding for drought environments.
Acquisition of drug resistance in basal cell nevus syndrome tumors through basal to squamous cell carcinoma transition
Authors: Jussila Anna R. , Haensel Daniel , Gaddam Sadhana , Oro Anthony E. 
Published: July 2023

ABSTRACTWhile basal cell carcinomas (BCCs) arise from ectopic hedgehog pathway activation and can be treated with pathway inhibitors, sporadic BCCs display high resistance rates while tumors arising in Gorlin syndrome patients with germline Patched (PTCH1) mutations are uniformly suppressed by inhibitor therapy. In rare cases, Gorlin syndrome patients on long-term inhibitor therapy will develop individual resistant tumor clones that rapidly progress, but the basis of this resistance remains unstudied. Here we report a case of an SMOi-resistant tumor arising in a Gorlin patient on suppressive SMOifor nearly a decade. Using a combination of multi-omics and spatial transcriptomics, we define the tumor populations at the cellular and tissue level to conclude that Gorlin tumors can develop resistance to SMOithrough the previously described basal to squamous cell carcinoma transition (BST). Intriguingly, through spatial whole exome genomic analysis, we nominate PCYT2, ETNK1, and the phosphatidylethanolamine biosynthetic pathway as novel genetic suppressors of BST resistance. These observations provide a general framework for studying tumor evolution and provide important clinical insight into mechanisms of resistance to SMOifor not only Gorlin syndrome but sporadic BCCs as well.
Cytokinins control secondary cell wall formation in the inflorescence stem of Arabidopsis
Authors: Didi Vojtech , Arnaud Dominique , Pacinková Anna , Jupa Radek , Cegan Radim , Melnikava Alesia , Vasickova Jana , Benitez Mariana , Unda Faride , Dobisova Tereza , Riber Willi , Dostalova Zuzana , Mansfield Shawn D. , Novak Ondrej , Strnad Miroslav , Hobza Roman , Gloser Vít , Budinska Eva , Hejatko Jan 
Published: July 2023

AbstractSpatiotemporal control over developmental programs is vital to all organisms. Here we show that cytokinin (signaling) deficiency leads to early secondary cell wall (SCW) formation in Arabidopsis inflorescence stem that associates with precocious upregulation of a SCW transcriptional cascade controlled by NAC TFs (NSTs). We demonstrate that cytokinin signaling through the AHK2/3 and the ARR1/10/12 suppresses the expression of severalNSTsand SCW formation in the apical portions of stems. Exogenous cytokinin application reconstituted both proper development and apical-basal gradient ofNST1andNST3in a cytokinin biosynthesis-deficient mutant. We show thatAHK2andAHK3required functionalNST1orNST3to control SCW initiation in the interfascicular fibers, further evidencing that cytokinins act upstream ofNSTs transcription factors. The premature onset of a rigid SCW biosynthesis and altered expression ofNST1/3andVND6/7due to cytokinin deficiency led to the formation of smaller tracheary elements (TEs) and impaired hydraulic conductivity. We conclude that cytokinins downregulateNSTsto inhibit premature SCW formation in the apical part of the inflorescence stem, facilitating thus the development of fully functional TEs and interfascicular fibers.Summary statementCytokinins attenuate premature secondary cell wall (SCW) formation via downregulating the expression of NAC TFs, the master switches of SCW transcriptional cascade, thus affecting the tracheary elements size and conductivity.
Megakaryocyte maturation involves activation of the adaptive unfolded protein response
Authors: Faiz M. , Kalev-Zylinska M.L , Dunstan-Harrison C. , Singleton D.C , Hay M.P. , Ledgerwood E.C. 
Published: July 2023

AbstractEndoplasmic reticulum stress triggers the unfolded protein response (UPR) to promote cell survival or apoptosis. Transient endoplasmic reticulum stress activation has been reported to trigger megakaryocyte production, and UPR activation has been reported as a feature of megakaryocytic cancers. However, the role of UPR signaling in megakaryocyte biology is not fully understood. We studied the involvement of UPR in human megakaryocytic differentiation using PMA (phorbol 12-myristate 13-acetate)-induced maturation of megakaryoblastic cell lines and thrombopoietin-induced differentiation of human peripheral blood-derived progenitors. Our results demonstrate that an adaptive UPR is a feature of megakaryocytic differentiation, and that this response is not associated with ER stress-induced apoptosis. Differentiation did not alter the response to the canonical endoplasmic reticulum stressors DTT or thapsigargin. However, thapsigargin, but not DTT, inhibited differentiation, consistent with the involvement of Ca2+signaling in megakaryocyte differentiation.
Drug screening in human physiologic medium identifies uric acid as an inhibitor of rigosertib efficacy
Authors: Rawat Vipin , DeLear Patrick , Prashanth Prarthana , Ozgurses Mete Emir , Tebeje Anteneh , Burns Philippa A. , Conger Kelly O. , Solís Christopher , Hasnain Yasir , Novikova Anna , Endress Jennifer E. , González-Sánchez Paloma , Dong Wentao , Stephanopoulos Greg , DeNicola Gina M. , Harris Isaac S. , Sept David , Mason Frank M. , Coloff Jonathan L. 
Published: July 2023

ABSTRACTThe non-physiological nutrient levels found in traditional culture media have been shown to affect numerous aspects of cancer cell physiology, including how cells respond to certain therapeutic agents. Here, we comprehensively evaluated how physiological nutrient levels impact therapeutic response by performing drug screening in human plasma-like medium (HPLM). We observed dramatic nutrient-dependent changes in sensitivity to a variety of FDA-approved and clinically trialed compounds, including rigosertib, an experimental cancer therapeutic that has recently failed in phase 3 clinical trials. Mechanistically, we found that the ability of rigosertib to destabilize microtubules is strongly inhibited by the purine metabolism waste product uric acid, which is uniquely abundant in humans relative to traditionalin vitroandin vivocancer models. Structural modelling studies suggest that uric acid interacts with the tubulin-rigosertib complex and may act as an uncompetitive inhibitor of rigosertib. These results offer a possible explanation for the failure of rigosertib in clinical trials and demonstrate the utility of physiological media to achievein vitroresults that better represent human therapeutic responses.
Life and death in Trypillia times: Interdisciplinary analyses of the exceptional human remains from the settlement of Kosenivka, Ukraine (3700–3600 BCE)
Authors: Fuchs Katharina , Hofmann Robert , Shatilo Liudmyla , Schlütz Frank , Storch Susanne , Chabanyuk Vladislav , Kirleis Wiebke , Müller Johannes 
Published: July 2023

AbstractWe present an interdisciplinary analysis of finds from the Trypillia settlement of Kosenivka, Ukraine (ca. 3700–3600 BCE, Trypillia C1), that links information on human, faunal, and botanical remains with archaeological data to provide exceptionally detailed insights into life and death at a Trypillia mega-site. We obtained osteological, palaeopathological, and histotaphonomic data from human bone fragments; performed carbon and nitrogen stable isotopic analysis of human and animal bone to calculate food webs with the software FRUITS; and modelled newly generated radiocarbon dates to refine the site’s chronology. The biological profile of seven identified individuals, some of whom suffered from disease symptoms common in the Chalcolithic, represents a demographic cross-section of the population. The analysis of perimortem cranial trauma suffered by two individuals suggest cases of interpersonal conflict. Food web calculations demonstrate the large contribution of cereals to the protein component of the human diet, which is supported by dental observations, and we suggest that livestock were a major manure producer for crop cultivation.The most probable scenario for the formation of the Kosenivka find assemblage is a deathly fire event. This makes the site a rare example where the archaeological and osteological results can be used to reconstruct a minimum number of house inhabitants. Following a literature review, we contextualise our analysis by discussing the general lack of human remains from Early and Middle Trypillia sites. The individuals from Kosenivka form part of the less than 0.05% of the total estimated Trypillia population that is represented skeletally; its members were deposited within settlements in the Middle Trypillia stage (until C1), preceding the shift to extramural burials in its late phase (C2).Our detailed results indicate the huge explanatory potential that has yet to be unlocked in the rare and often poorly preserved bioarchaeological archives of the Cucuteni–Trypillia phenomenon.
BRCA1 and BRCA2 germline mutations driven signaling pathway alterations are sufficient to initiate breast tumorigenesis by the PIK3CAH1047Roncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna 
Published: July 2023

AbstractSingle cell transcriptomics studies have begun to identify breast epithelial cell and stromal cell specific transcriptome differences between BRCA1/2 mutation carriers and non-carriers. We generated a single cell transcriptome atlas of breast tissues from BRCA1, BRCA2 mutation carriers and compared this single cell atlas of mutation carriers with our previously described single cell breast atlas of healthy non-carriers. We observed that BRCA1 but not BRCA2 mutations altered the ratio between basal, luminal progenitor and mature luminal cells in breast tissues. A unique subcluster of cells within luminal progenitors is underrepresented in case of BRCA1 and BRCA2 mutation carriers compared to non-carriers. Both BRCA1 and BRCA2 mutations specifically altered transcriptomes in epithelial cells which are an integral part of NF-κB, LARP1, and MYC signaling. Reduction of MYC signaling and translational machinery in BRCA1/2 mutant epithelial cells is reminiscent of embryonic diapause-like adaptation that occurs in drug tolerant populations of cells. Signaling pathway alterations in epithelial cells unique to BRCA1 mutations included STAT3, BRD4, SMARCA4, HIF2A/EPAS1, and Inhibin-A signaling. BRCA2 mutations were associated with upregulation of IL-6, PDK1, FOXO3, and TNFSF11 signaling. These signaling pathway alterations are sufficient to alter sensitivity of BRCA1/BRCA2-mutant breast epithelial cells to transformation as epithelial cells from BRCA1 mutation carriers overexpressing hTERT + PIK3CAH1047Rgenerated adenocarcinomas, whereas similarly modified mutant BRCA2 cells generated basal carcinomas in NSG mice. Thus, our studies provide a high-resolution transcriptome atlas of breast epithelial cells of BRCA1 and BRCA2 mutation carriers and reveal their susceptibility to PIK3CA mutation-driven transformation.Statement of SignificanceThis study provides a single cell atlas of breast tissues of BRCA1/2 mutation carriers and demonstrates that aberrant signaling due to BRCA1/2 mutations sufficient to initiate breast cancer by mutant PIK3CA.
A Proxitome–RNA–capture Approach Reveals that Processing Bodies Repress Co–Regulated Hubs
Authors: Liu Chen , Mentzelopoulou Andriani , Hatzianestis Ioannis H. , Tzagkarakis Epameinondas , Scaltsoyiannes Vassilis , Ma Xuemin , Michalopoulou Vassiliki A. , Romero–Campero Francisco J. , Romero–Losada Ana B. , Sarris Panagiotis F. , Marhavy Peter , Bölter Bettina , Kanterakis Alexandros , Gutierrez–Beltran Emilio , Moschou Panagiotis N. 
Published: July 2023

AbstractCellular condensates are usually ribonucleoprotein assemblies with liquid– or solid–like properties. Because they lack a delineating membrane, the compositional determination of condensates is laborious. Here we set up a pipeline for proximity–biotinylation–dependent capture of RNA to investigate the RNA composition of the condensate in Arabidopsis known as the processing bodies (PBs). Using this pipeline together within situprotein–protein interaction and RNA detection,in silico, and high–resolution imaging approaches, we studied PBs under normal and heat stress conditions. The composition of PBs in RNAs is much more dynamic than that of the total transcriptome. RNAs involved in cell wall development and regeneration, hormonal signaling, secondary metabolism/defense, and RNA metabolism were enriched in PBs. RNA binding proteins and liquid–to–solid phase transitions modulated specificity of RNA recruitment in PBs. Surprisingly, RNAs were sometimes recruited together with their encoded proteins. In PBs RNAs follow distinct fates, with small liquid-like PBs modulating RNA decay while larger ones storage. The size and properties of PBs are regulated by the actin polymerization cAMP receptor (SCAR)–WASP family verprolin homologous (WAVE) complex. SCAR/WAVE modulates signaling by shuttling RNAs between PBs and the translational machinery adjusting the ethylene signaling pathway. Heat stress leads to the storage of immunity–related RNAs in PBs by reducing PBs dynamics, suggesting why processes such as immunity malfunction under heat stress. In summary, we provide a method to identify RNAs in condensates which allowed us to reveal a mechanism for RNA fate regulation.
Self-targeting spacers reveal new functions of CRISPR systems
Authors: Tangarife Cardona Miguel Angel , Arboleda Rivera Juan Camilo 
Published: July 2023

AbstractThe CRISPR systems enable bacteria and archaea to defend from bacteriophages or mobile genetic elements by inserting portions of the DNA of these elements into its own genome in sequences known as spacers that will later trigger the complementarity-based degradation of invading sequences. The presence of self-targeting spacers is widespread in prokaryotes; however, its functional role is still unclear. In this study, we analyzed self-targeting spacers of CRISPR systems and found a high presence of membrane proteins, aminoacyl-tRNA synthetases and ATP-binding proteins. This is a novel report that supports other research linking CRISPR systems to membrane proteins and could explain the reported relationships between antibiotic resistance and presence of CRISPR systems.