bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of Polysubstance use in young Black and Latinx sexual minority men and transgender women in its association with sexual partnership factors: The PUSH study
Authors: Arrington-Sanders Renata , Galai Noya , Falade-Nwulia Oluwaseun , Hammond Christopher , Wirtz Andrea , Beyrer Christopher , Celentano David 
Published: November 2022

ABSTRACTBackgroundYoung Black and Latinx sexual minority men (SMM) and transgender women (TW) continue to suffer some of the highest burdens of HIV in the United States. Disparities are partly attributed to suboptimal uptake of HIV prevention and treatment services negatively impacted by substance use. Adult studies have demonstrated that polysubstance use increases HIV acquisition risk through increased sexual behaviors, however there are few studies that have examined polysubstance in this population and how polysubstance use might increase young SMM and TW’s risk for HIV.MethodsCross-sectional data from 466 young Black and Latinx SMM and TW living in four US high HIV-burden cities enrolled in the PUSH Study, a status neutral randomized control trial to increase uptake of pre-exposure prophylaxis and treatment adherence. Examined data for patterns of polysubstance use comparing age differences of use; and exploring associations between substance use and HIV risk behaviors focusing on three core partnership factors - inconsistent condom use, pressure to have anal sex without a condom, and older partner.ResultsMost participants described prior substance use with alcohol and cannabis being most common (76%, respectively) and 23% describing other describing prior alcohol use, 76% (n=353) described cannabis use, and 23% described other illicit drug use (including stimulants, cocaine, hallucinogens, sedatives, opioids, and inhalants). Polysubstance use was common with nearly half (47%) of participants reported alcohol and cannabis use, 20% reporting alcohol, cannabis, and one other illicit drug use, and 19% reporting alcohol or cannabis use plus one other illicit drug use. Polysubstance use was associated with greater adjusted odds of pressure to have anal sex without a condom, having an older partner (> 5 years older), and inconsistent condom use.ConclusionsHigh levels of substance use, polysubstance use and strong associations with high-risk sexual practices and sexual partnerships that are known to be predictors of HIV acquisition or transmission among Black and Latinx sexual and gender minority youth, call for combination interventions that include substance use treatment alongside ARV-based prevention and treatment and partner-based interventions.
Does the visual word form area split in bilingual readers? A millimeter-scale 7T fMRI study
Authors: Zhan Minye , Pallier Christophe , Dehaene Stanislas , Cohen Laurent 
Published: November 2022

AbstractIn expert readers, a brain region known as the visual word form area (VWFA) is highly sensitive to written words, exhibiting a posterior-to-anterior gradient of increasing sensitivity to orthographic stimuli whose statistics match those of real words. Using high-resolution 7T fMRI, we ask whether, in bilingual readers, distinct cortical patches specialize for different languages. In 21 English-French bilinguals, unsmoothed 1.2 mm fMRI revealed that the VWFA is actually composed of several small cortical patches highly selective for reading, with a posterior-to-anterior word similarity gradient, but with near-complete overlap between the two languages. In 10 English-Chinese bilinguals, however, while most word-specific patches exhibited similar reading specificity and word-similarity gradients for reading in Chinese and English, additional patches responded specifically to Chinese writing and, surprisingly, to faces. Our results show that the acquisition of multiple writing systems can indeed tune the visual cortex differently in bilinguals, sometimes leading to the emergence of cortical patches specialized for a single language.
WITHDRAWN: SETD2 deficiency promotes the transition from PKD to ccRCC by dysregulation of sphingomyelin metabolism
Authors: Zhang Yu , Liu Changwei , Ye Tianbao , Chen Lu , Yang Xiaoqun , Zhou Luting , An Huimin 
Published: November 2022

Withdrawal StatementbioRxiv has withdrawn this preprint as it was submitted and made public without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Quantifying spatial dynamics and regulators ofMycobacterium tuberculosisphagocytosis by primary human macrophages using microfabricated patterns
Authors: Savulescu Anca F. , Peton Nashied , Oosthuizen Delia , Hazra Rudranil , Mhlanga Musa. M. , Coussens Anna K. 
Published: November 2022

AbstractMacrophages provide a first line of defense against invading pathogens, including the leading cause of bacterial mortality,Mycobacterium tuberculosis(Mtb). Phagocytosing extracellular organisms mediate pathogen clearanceviaa multitude of antimicrobial mechanisms, uniquely designed against an array of pathogens. Macrophages are able to execute different programs of activation in response to pathogenic challenge with host mediators, polarizing them to a variety of differentiation states, including the pro-inflammatory M1 and anti-inflammatory M2 states. The functional polarization of a macrophage prior to infection, thus impacts the outcome of host-pathogen interaction. One of the limitations when usingin vitrodifferentiated human primary monocyte-derived macrophages (MDMs) is the heterogeneous nature of the mature population, which presents a challenge for quantitative characterization of various host-pathogen processes. Here, we describe an approach to minimize this heterogeneity, based on micropatterning of cells to reintroduce aspects of cellular homogeneity lost in a 2D tissue culture. Micropatterning consists of growing cells at the single cell level on microfabricated patterns, to constrain the size and shape of the cell, reducing cell-to-cell variation and mimicking the physiological spatial confinement that cells experience in tissues. We infected micropatterned GM-CSF- (M1) and M-CSF- (M2) derived human MDMs withMtb, which allowed us to study host-pathogen interactions at a single cell level, at high resolution and in a quantitative manner, across tens to hundreds of cells in parallel. Using our approach, we were able to quantify phagocytosis ofMtbin MDMs, finding phagocytic contraction is increased by interferon-gamma stimulation, whilst contraction and bacterial uptake is decreased following silencing of phagocytosis regulatorNHLRC2or Tween80 removal of bacterial surface lipids. We also identify alterations in host organelle position withinMtbinfected MDMs, as well as identifying differences inMtbsubcellular localization in relation to the microtubule organizing center (MTOC) and in line with the cellular polarity in M1 and M2 MDMs. Our approach described here can be adapted to study other host-pathogen interactions and co-infections in MDMs and can be coupled with downstream automated analytical approaches.
Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes
Authors: Casado Pedro , Rio-Machin Ana , Miettinen Juho J. , Bewicke-Copley Findlay , Rouault-Pierre Kevin , Krizsan Szilvia , Parsons Alun , Rajeeve Vinothini , Miraki-Moud Farideh , Taussig David C , Bödör Csaba , Gribben John , Heckman Caroline , Fitzgibbon Jude , Cutillas Pedro R. 
Published: November 2022

ABSTRACTAcute myeloid leukaemia (AML) patients harbouring certain chromosome abnormalities have particularly adverse prognosis. For these patients, targeted therapies have not yet made a significant clinical impact. To understand the molecular landscape of poor prognosis AML we profiled 74 patients from two different centres (in UK and Finland) at the proteomic, phosphoproteomic and drug response phenotypic levels. These data were complemented with transcriptomics analysis for 39 cases. Data integration highlighted a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia, which we term MLLGA and MLLGB. MLLGA presented increased DOT1L phosphorylation, HOXA gene expression, CDK1 activity and phosphorylation of proteins involved in RNA metabolism, replication and DNA damage when compared to MLLGB and no KMT2A rearranged samples. MLLGA was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and inosine-5-monosphosphate dehydrogenase (IMPDH) relative to other cases. Intermediate-risk KMT2A-MLLT3 cases were mainly represented in a third group closer to MLLGA than to MLLGB. The expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia, suggesting a role of the nucleolar activity in sensitivity to treatment. In summary, our multilayer molecular profiling of AML with poor prognosis and KMT2A-MLLT3 karyotypes identified a phosphoproteomics signature that defines two biologically and phenotypically distinct groups of KMT2A rearranged leukaemia. These data provide a rationale for the potential development of specific therapies for AML patients characterised by the MLLGA phosphoproteomics signature identified in this study.
SEN1 is responsible for molybdate transport into nodule symbiosomes for nitrogen fixation inLotus japonicus
Authors: Chu Qingnan , Hakoyama Tsuneo , Hayashi Makoto , Toyooka Kiminori , Sato Mayuko , Kamiya Takehiro , Fujiwara Toru 
Published: November 2022

AbstractSymbiotic nitrogen fixation (SNF) in legume root nodules requires a steady supply of molybdenum (Mo) for synthesis of the iron-Mo cofactor for nitrogenase in bacteroids. For this nutrient to be exported by the host plant it must cross the peribacteroid membrane (PBM), however, the molybdate transporter responsible has not yet been identified. ALotus japonicussymbiotic mutant,sen1, forms nodules that do not fix nitrogen; it has nodule defects and bacteroid degradation. The biochemical function and subcellular localization of SEN1 protein remains to be elucidated. Here, we found a new phenotype in which theSEN1mutation resulted in increased Mo accumulation in the nodule host fractions but decreased Mo accumulation in the bacteroids at 10 days post inoculation. We identified the molybdate efflux transport activity of SEN1 via heterologous expression in yeast.SEN1was expressed exclusively in nodules, and its expression was stable in response to varying Mo supply in nutrient solution.In situimmunostaining verified that the SEN1 protein is localized, in part, to the PBM in the rhizobium-infected cells. Taken together, these results confirmed that SEN1 is responsible for mediating molybdate efflux from the cytosol of nodule host cells to the symbiosomes for SNF. Furthermore,SEN1mutation reduced the expression ofnifDandnifK, suggesting thatSEN1may be pertinent to iron-Mo-cofactor assembly. This work fills the knowledge gap regarding how molybdate is allocated from the host plant to the bacteroids; such knowledge is critical for developing new SNF biological systems in non-legume plants.One-sentence summarySEN1 is localized partly in the peribacteroid membrane of nodule cells and mediates the molybdate exportation from the host plant cytosol to the symbiosomes for symbiotic nitrogen fixation.
The Arabidopsis ARID-HMG protein AtHMGB15 modulates JA signalling by regulating MYC2 during pollen development
Authors: Sachdev Sonal , Biswas Ruby , Roy Adrita , Chaudhuri Shubho 
Published: November 2022

ABSTRACTIn flowering plants, jasmonic acid (JA) signalling regulates the complex process of male gametophyte development. JA signalling initiates with the activation of MYC2 transcription factor, for the expression of several JA responsive genes throughout stamen development and pollen maturation. However, the regulation of JA signalling during different developmental stages of male gametophytes is still less understood. In this study we have characterized T-DNA insertion line of AtHMGB15. Phenotypic characterization ofathmgb15-4mutant plants showed delayed bolting, shorter siliques and reduced seed set compared to wildtype. Moreover, deletion of AtHMGB15 resulted in defective pollen morphology, delayed pollen germination, abberant pollen tube growth and a higher percentage of non-viable pollen population inathmgb15-4compared to wildtype. Molecular analysis indicated down-regulation of JA-biosynthesis and JA-signalling genesvizMYC2, MYB21 and MYB24 inathmgb15-4mutant. Furthermore, jasmonic acid and its derivatives were found almost ten-fold lower inathmgb15-4flowers. However, exogenous application of jasmonate could restore pollen morphology and pollen germination, suggesting that impaired JA signalling is responsible for the pollen phenotype inathmgb15mutant. AtHMGB15 physically interacts with MYC2 protein to form the transcription activation complex for promoting transcription of genes responsible for JA signalling during stamen and pollen development. Collectively, our findings indicate that AtHMGB15, a plant specific DNA binding protein of the ARID-HMG group, acts as a positive regulator of JA signalling to control the spatiotemporal expression of key regulators responsible for stamen and pollen development.
Cell autonomous requirement of imprinted XCI in extra-embryonic polar trophoblast cells
Authors: Wang Feng , Chander Ashmita , Yoon Yeonsoo , Wallingford Mary C. , Espejo-Serrano Carmen , Bustos Francisco , Findlay Greg M. , Mager Jesse , Bach Ingolf 
Published: November 2022

SummaryIn female mice the gene dosage from X chromosomes is adjusted by a process called X chromosome inactivation (XCI) that occurs in two steps. An imprinted form of XCI (iXCI) silencing the paternally inherited X chromosome (Xp) is initiated at the 2-4 cell stages. As extraembryonic cells including trophoblasts keep the Xp silenced, epiblast cells that give rise to the embryo proper reactivate the Xp and undergo a random form of XCI (rXCI) during peri-implantation stages. Lack of X dosage compensation leads to peri-implantation lethality due to inhibition of trophoblast stem cells. However, as the epiblast regulates the trophoblast lineage, the roles of iXCI vs rXCI in the early lethal phenotype remains unclear. We have investigated functions and expression of Rlim (Rnf12), an E3 ubiquitin ligase, and its target protein Rex1 (Zfp42) that control iXCI. Consistent with functions specifically for iXCI, we show an inverse correlation in the expression of Rlim and Rex1 throughout pre-implantation development, but anRlim-independent downregulation of Rex1 in epiblast cells upon implantation. Moreover, disturbing the functional Rlim-Rex1 dynamics in females leads to cell fate confusion and premature differentiation specifically of the polar trophoblast stem cell pool. Thus, controlled by the Rlim-Rex1 axis, female mouse development requires iXCI in the polar trophoblast cell lineage.
Development of a mouse model for postresectional liver failure
Authors: van Mierlo Kim M.C. , Van Himbeeck Cathy , Lebrun Valérie , Jansen Peter L.M. , Dejong Cornelius H.C. , Leclercq Isabelle A. , Olde Damink Steven W.M. , Schaap Frank G. 
Published: November 2022

AbstractBackgroundPostresectional liver failure (PLF) is a dreaded complication after extended liver resection. Post-operative hyperbilirubinemia suggests that impaired hepatobiliary transport with intrahepatic accumulation of harmful cholephiles plays an etiological role. Bile salts serve dual roles as signaling molecules engaged in liver regeneration after partial hepatectomy (PH) and biological detergents.AimIn this study we tested the hypothesis that excessive accumulation of bile salts in the regenerating liver results in PLF.MethodsTwelve weeks old male C57BL6/J mice were subjected to 70% PH and post-operatively challenged with a diet supplemented with cholic acid (CA, 0.5 or 1.0%; n=5-6 per group) or a control diet. After 48 hours mice were sacrificed, and liver injury, secretory function, and regenerative indices were assessed.ResultsMice fed a 1.0% CA diet displayed more pronounced weight loss following PH and had a deranged post-operative glucose course. Liver injury (aminotransferase elevations) and impaired hepatobiliary transport function (hyperbilirubinemia) were apparent in the group fed a 1.0% CA diet, but not in animals fed a 0.5% CA diet. No differences in liver mass recovery were observed among groups. However, the percentage of hepatocytes staining positive for the proliferation marker Ki-67 were reduced in mice receiving a 1.0% CA diet relative to animals fed a 0.5% CA diet. PH-induced expression of key factors involved in cell cycle progression (e.g. Foxm1b, Cdc25b) was abrogated in the 1.0% CA group.ConclusionA postresectional challenge with a 1.0% CA diet induces signs of liver injury and defective liver regeneration. A longer duration of the dietary challenge and/or secondary hits may further improve the model. Once validated, it can be used to evaluate pharmaceutical strategies to prevent or treat PLF.
Medicago truncatulaABCG40 is a cytokinin importer that negatively regulates lateral root density and nodule number
Authors: Jamruszka Tomasz , Banasiak Joanna , Pawela Aleksandra , Jarzyniak Karolina , Xia Jian , Biała-Leonhard Wanda , Plačková Lenka , Tsering Tashi , Iacobini Francesca Romana , Novák Ondřej , Geisler Markus , Jasiński Michał 
Published: November 2022

AbstractNumerous studies suggest that cytokinin (CK) distribution plays a relevant role in shaping plant morphology in changing environments. Nonetheless, our knowledge about the involvement of short-distance CK translocation in root mineral nutrition remains scarce, and the specific role of CK transporters in root morphology has yet to be established. Therefore, the molecular identity of CK transporters should be determined to increase knowledge on root plasticity during soil fertility, as well as more frequently encountered plant nutrient deficiencies. In this work, we identified and characterized theMedicago truncatulafull-size ATP-binding cassette (ABC) transporter of the G subfamily MtABCG40 as a plasma membrane CK importer. Its expression is root-specific and is induced by nitrogen deprivation and CKs. Our analyses indicate that MtABCG40 exerts a negative impact on lateral root density by decreasing lateral root initiation and enhancing primary root elongation. Moreover, we also observed that this transporter negatively influenced the nodule number. Our results suggest that MtABCG40 action affects CK signalling, which impacts the cellular response to auxin. In summary, we identified a novel ABCG-type CK transporter that regulates lateral root density and nodule number.
Aliphatic residues contribute significantly to the phase separation of TDP-43 C-terminal domain
Authors: Mohanty Priyesh , Shenoy Jayakrishna , Rizuan Azamat , Ortiz José F Mercado , Fawzi Nicolas L. , Mittal Jeetain 
Published: November 2022

AbstractTAR DNA binding protein 43 (TDP-43) is involved in key processes in RNA metabolism such as splicing, stability and transcription. TDP-43 dysfunction is frequently implicated in many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD). The prion-like, disordered C-terminal domain (CTD) of TDP-43 is aggregation-prone and harbors the majority (~90%) of all ALS-related mutations. Recent studies have established that TDP-43 CTD can undergo liquid-liquid phase separation (LLPS) in isolation and is important for phase separation (PS) of the full-length protein under physiological conditions. While a short conserved helical region (CR, spanning residues 319-341) promotes oligomerization and is essential for LLPS, aromatic residues in the flanking disordered regions (IDR1/2) have also been found to play a critical role in PS and aggregation. However, TDP-43 CTD has a distinct sequence composition compared with other phase separating proteins, including many aliphatic residues. These residues have been suggested to modulate the apparent viscosity of the resulting phases, but their direct contribution to phase separation has been relatively ignored. Here, we utilized a multiscale simulation and experimental approach to assess the residue-level determinants of TDP-43 CTD phase separation. Single chain and condensed phase simulations performed at the atomistic and coarse-grained level respectively, identified the importance of aromatic residues (previously established) while also suggesting an essential role for aliphatic methionine residues in LLPS.In vitroexperiments confirmed the role of phenylalanine, methionine, and leucine (but not alanine) residues in driving the phase separation of CTD, which have not been previously considered essential for describing the molecular grammar of PS. Finally, NMR experiments also showed that phenylalanine residues in the disordered flanking regions and methionine residues both within and outside the CR contribute important contacts to CTD interactions. Broadly, our work highlights the importance of non-alanine aliphatic residues such as methionine and leucine, and potentially valine and isoleucine, in determining the LLPS propensity, expanding the molecular grammar of protein phase separation to include critical contributions from aliphatic residues.
Mutations Affecting Polar Nuclei Number, Antipodal Cell Cluster Size, Cellularization, and Nuclear Localization in Maize Embryo Sacs
Authors: Chettoor Antony M. , Yang Bing , Evans Matthew M. S. 
Published: November 2022

AbstractThe maize female gametophyte is comprised of four cell types: two synergids, an egg cell, a central cell, and a variable number of antipodal cells. In maize, these cells are produced after three rounds of free-nuclear divisions followed by cellularization, differentiation, and proliferation of the antipodal cells. Cellularization of the eight-nucleate syncytium produces seven cells with two polar nuclei in the central cell. Nuclear localization is tightly controlled in the embryo sac as evidenced by the regular, stereotypical position of the nuclei in all syncytial stages of female gametophyte development. This leads to precise allocation of the nuclei into the cells upon cellularization. Nuclear positioning within the syncytium is highly correlated with their identity after cellularization. Two mutants are described with extra polar nuclei, abnormal antipodal cell morphology, and reduced antipodal cell number, which is correlated with a frequent loss of auxin signaling in the antipodal cell cluster. Mutations in one of these genes,indeterminate gametophyte2encoding a MICROTUBULE ASSOCIATED PROTEIN65-3 homolog, shows a requirement for MAP65-3 in cellularization of the syncytial embryo sac and that the identity of the nuclei in the syncytial female gametophyte can be changed very late before cellularization.