bluuebunny/crossref_metadata_2025_split huggingface dataset:
TORC1 regulates actin dynamics to control proteasome homeostasis
Authors: Williams Thomas , Rousseau Adrien 
Published: July 2022

The conserved protein kinase complex TORC1 is a central regulator of protein homeostasis. TORC1 is active under nutrient replete, unstressed conditions and promotes bulk protein synthesis, cell growth, and proliferation. Many stresses inactivate TORC1, including nutrient starvation. When TORC1 is inactivated, bulk protein synthesis is inhibited, and stress-responsive protein synthesis activated. Degradation of damaged or unwanted proteins is increased through autophagy activation and enhanced proteasome assembly.
The 26S proteasome is composed of the 20S core particle (CP), capped with one or two 19S regulatory particles (RP). Following TORC1 inhibition, the Mpk1 kinase is activated. Mpk1 facilitates increased translation of proteasome regulatory particle assembly chaperones (RPACs), leading to increased proteasome assembly. The mechanisms underlying the RPAC translation increase remain unclear, however.
Here, we show that actin depolarisation upon TORC1 inhibition causes RPAC mRNAs to associate more with actin patch structures. Increasing this interaction enhances translation further. We identified Ede1 as a protein which binds translating RPAC mRNA and show that Ede1 is required to increase RPAC mRNA association with actin patches, RPAC translation and proteasome assembly upon stress.
COVID-19 Neuropathology: evidence for SARS-CoV-2 invasion of Human Brainstem Nuclei
Authors: Emmi Aron , Rizzo Stefania , Barzon Luisa , Sandre Michele , Carturan Elisa , Sinigaglia Alessandro , Riccetti Silvia , della Barbera Mila , Boscolo-Berto Rafael , Cocco Patrizia , Macchi Veronica , Antonini Angelo , De Gaspari Monica , Basso Cristina , De Caro Raffaele , Porzionato Andrea 
Published: July 2022

AbstractNeurological manifestations are common in COVID-19, the disease caused by SARS-CoV-2. Despite reports of SARS-CoV-2 detection in the brain and cerebrospinal fluid of COVID-19 patients, it’s still unclear whether the virus can infect the central nervous system, and which neuropathological alterations can be ascribed to viral tropism, rather than immune-mediated mechanisms.Here, we assess neuropathological alterations in 24 COVID-19 patients and 18 matched controls who died due to pneumonia / respiratory failure. Aside from a wide spectrum of neuropathological alterations, SARS-CoV-2-immunoreactive neurons were detected in specific brainstem nuclei of 5 COVID-19 subjects. Viral RNA was also detected by real-time RT-PCR. Quantification of reactive microglia revealed an anatomically segregated pattern of inflammation within affected brainstem regions, and was higher when compared to controls. While the results of this study support the neuroinvasive potential of SARS-CoV-2, the role of SARS-CoV-2 neurotropism in COVID-19 and its long-term sequelae require further investigation.
Dendrite architecture determines mitochondrial distribution patterns in vivo
Authors: Donovan Eavan J. , Agrawal Anamika , Liberman Nicole , Kalai Jordan I. , Chua Nicholas J. , Koslover Elena F. , Barnhart Erin L. 
Published: July 2022

SUMMARYMitochondria are critical for neuronal function and must be reliably distributed through complex neuronal architectures. By quantifying in vivo mitochondrial transport and localization patterns in the dendrites of Drosophila visual system neurons, we show that mitochondria make up a dynamic system at steady-state, with significant transport of individual mitochondria within a stable global pattern. Mitochondrial motility patterns are unaffected by visual input, suggesting that neuronal activity does not directly regulate mitochondrial localization in vivo. Instead, we present a mathematical model in which four simple scaling rules enable the robust self-organization of the mitochondrial population. Experimental measurements of dendrite morphology validate key model predictions: to maintain equitable distribution of mitochondria across asymmetrically branched subtrees, dendritic branch points obey a parent-daughter power law that preserves cross-sectional area, and thicker trunks support proportionally bushier subtrees. Altogether, we propose that “housekeeping” requirements, including the need to maintain steady-state mitochondrial distributions, impose constraints on neuronal architecture.
Multi-scale Assessment of Brain Blood Volume and Perfusion in the APP/PS1 Mouse Model of Amyloidosis
Authors: Munting Leon P , Derieppe Marc PP , Voortman Lenard M , Khmelinskii Artem , Suidgeest Ernst , Hirschler Lydiane , Barbier Emmanuel L , de Senneville Baudouin Denis , van der Weerd Louise 
Published: July 2022

ABSTRACTVascular dysfunction is increasingly recognized to play a role in the development of Alzheimer’s disease (AD). The relation between vascular dysfunction and the neuropathological amyloid β accumulation characteristic for AD is however unclear. The limited resolution of in vivo imaging techniques, the intricate 3D structure of the microvasculature and the different co-occurring types of amyloid β accumulation in patients hamper studying this relation in patients. Here, we therefore employed the APP/PS1 mouse model, which develops parenchymal amyloid β plaques, to study the effect of parenchymal amyloid β plaques on the structure and function of the vasculature. Blood vessels and amyloid β plaques were fluorescently labeled in vivo with lectin-DyLight594 and methoxy XO4, respectively, in APP/PS1 mice at old age. The brain tissue was cleared post-mortem with the CUBIC clearing protocol, which allowed structural imaging at microscopic resolution of the vessels and plaques in a large 3D volume. Segmentation of the vasculature enabled mapping of the microvascular Cerebral Blood Volume (mCBV), which ranged from 2 % to 5 % in the white matter and the thalamus, respectively. No mCBV differences were observed between APP/PS1 mice and wild type (WT) control mice. The effect of the amyloid β plaques on vascular function was studied in vivo by measuring Cerebral Blood Flow (CBF) and Arterial Transit Time (ATT) with Arterial Spin Labeling (ASL) MRI. Similar to the mCBV findings, no differences were observed in CBF or ATT between APP/PS1 and control mice, indicating that brain vascular morphology and function in this mouse model are preserved in the presence of amyloid β plaques.
Droplet-based microfluidics as a media optimization tool for cyanobacteria
Authors: Cao Jialan , Russo David A. , Xie Ting , Groß G. Alexander , Zedler Julie A. Z. 
Published: July 2022

AbstractThe urgent need to increase sustainability in biotechnology has led to an increased interest in photosynthetic production platforms. Cyanobacteria are particularly attractive for their fast photoautotrophic growth and genetic accessibility. However, the lack of systematic strain optimization is holding back progress towards industrialization. To overcome this bottleneck, here we introduce a droplet-based microfluidics platform capable of one- (1D) and two-dimension (2D) screening of key parameters in cyanobacterial cultivation. We successfully grew three different unicellular, biotechnologically relevant cyanobacteria: Synechocystis sp. PCC 6803, Synechococcus elongatus UTEX 2973 and Synechococcus sp. UTEX 3154. Highly-resolved 1D screening of nitrate, phosphate, carbonate, and salt content show that nitrate and/or phosphate can be limiting in standard cultivation media. Finally, we show that 2D screening results from our microfluidic setup translate well to a laboratory scale high-density cultivation setup. This study demonstrates that droplet-based microfluidics by micro segmented-flow are a powerful tool for nanoscale high-throughput optimization of cyanobacterial cultivation.
A mutant bacterial O-GlcNAcase visualizes a progressive decline of protein O-GlcNAcylation in early Drosophila embryos critical for neurodevelopment
Authors: Zhang Yaowen , Wang Dandan , Yu Haibin , Lei Xiaoyun , Meng Yang , Zhang Na , Chen Fang , Lv Lu , Pan Qian , Qin Hongtao , Zhang Zhuohua , van Aalten Daan M.F. , Yuan Kai 
Published: July 2022

AbstractProtein O-GlcNAcylation, a monosaccharide posttranslational modification maintained by two evolutionarily conserved enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), is a major nutrient sensor integrating key metabolic pathways. While mutations in OGT have recently been associated with neurodevelopmental disorders, the dynamics and function of protein O-GlcNAcylation during early embryogenesis remain elusive. Here we develop a new fluorescent probe to visualize O-GlcNAcylation levels in live Drosophila early embryos. Our study shows that protein O-GlcNAcylation declines as the embryos develop to the mid-blastula transition when the facultative heterochromatin makes its first appearance. Lowering O-GlcNAcylation levels by exogenous OGA activity promotes the polycomb group O-GlcNAc protein Polyhomeotic (Ph) to form nuclear foci and K27 trimethylation of histone H3. This enhanced facultative heterochromatin formation fine-tunes the expression of several neurodevelopmental genes including short of gastrulation (sog). We provide evidence that perturbation of O-GlcNAcylation during early embryogenesis affects learning ability in adulthood, highlighting the importance of O-GlcNAcylation homeostasis for the development of the nervous system.
Trans-ancestry meta-analysis improves performance of genetic scores for multiple adiposity-related traits in East Asian populations
Authors: Fairhurst-Hunter Zammy , Lin Kuang , Millwood Iona Y , Pozarickij Alfred , Chen Tzu-Ting , Torres Jason M. , Lun Jian-an , Kartsonaki Christiana , Gan Wei , Mahajan Anubha , Du Huaidong , Sohoni Rajani , Guo Yu , Sansome Sam , Yang Ling , Yu Canqing , Chen Yiping , Lv Jun , Hemani Gibran , Koido Masaru , Kamatani Yoichiro , Spracklen Cassandra N. , Gordon-Larsen Penny , Koprulu Mine , Meng Xiangrui , Kuchenbaecker Karoline , Fatumo Segun , Bhatta Laxmi , Brumpton Ben , Alegre-Díaz Jesús , Kuri-Morales Pablo , Tapia-Conyer Roberto , Graham Sarah E. , Willer Cristen J. , Neville Matt J. , Karpe Fredrik , Graff Mariaelisa , North Kari E , Loos Ruth J.F. , Haiman Christopher A. , Peters Ulrike , Buskye Steve , Gignoux Christopher R. , Wojcik Genevieve , Ling Yen-Fen , Li Liming , McCarthy Mark I , Chen Zhengming , Holmes Michael V , Walters Robin G 
Published: July 2022

AbstractGenome-wide association studies (GWAS) in predominately European-ancestry (EUR) populations have identified numerous genetic variants associated with adiposity-related traits. An emerging challenge is the limited transferability of genetic scores constructed based on GWAS results from one ancestry for trait prediction in other ancestries. We performed trans-ancestry meta-analysis (TAMA) for eight adiposity-related traits using genetic data from 96,124 East Asian (EAS) and 443,359 EUR individuals. We identified >1400 genomic regions significantly associated with one or more traits. Despite EAS comprising only ∼20% of the study population, genetic scores constructed from the trans-ancestry (TA) results accounted for between 30% and 79% more variation in the adiposity traits in EAS compared with scores derived from the EUR GWAS alone. Furthermore, TA scores also modestly improved variance explained in African/African American, Hispanic and South Asian populations. Our findings highlight the utility of TAMA for increasing variance explained by genetic scores across populations of different ancestries.
Real-Time PCR-based diagnosis of human visceral leishmaniasis using urine samples
Authors: Rahim Samiur , Amin Md. Robed , Sharif Mohiuddin , Rahman Mohammad Tariqur , Karim Muhammad Manjurul 
Published: July 2022

AbstractBackgroundDiagnosis of visceral leishmaniasis (VL) through the detection of its causative agents namely Leishmania donovani and L. infantum is traditionally based on Giemsa-stained smears of bone marrow, spleen aspirates, liver or lymph node. Collection of these samples involve invasive procedures and carries the risk of fatal hemorrhage especially during splenic aspiration. Earlier, we reported a Polymerase Chain Reaction (PCR)-based diagnosis of L. donovani in peripheral blood using a novel set of PCR primers with absolute specificity (Khatun et al. 2017). Using the same set of primers and PCR conditions, here we describe diagnosis of L. donovani from urine, for a non-invasive, rapid and safe diagnosis.MethodsDiagnosis of L. donovani was carried out using urine samples collected from clinically diagnosed VL patients (n=23) of Bangladesh in Real Time PCR. Test results were validated by comparing blood samples from the same set of patients. Sensitivity and specificity of this diagnosis was analyzed using retrospective bone marrow samples, collected earlier from confirmed VL patients (n=19) (Khatun et al. 2017).ResultsThe method showed 100% sensitivity in detecting VL in urine and corresponding blood samples and bone marrow samples, as well as 100% specificity in control groups.ConclusionUrine-based diagnosis could be a patient-friendly, non-invasive approach for VL detection with precision and perfection.
Wheat NAM genes regulate the majority of early monocarpic senescence transcriptional changes including nitrogen remobilisation genes
Authors: Andleeb Tayyaba , Borrill Philippa 
Published: July 2022

AbstractSenescence enables the remobilisation of nitrogen and micronutrients from vegetative tissues of wheat (Triticum aestivum L.) into the grain. Understanding the molecular players in this process will enable the breeding of wheat lines with tailored grain nutrient content. The NAC transcription factor NAM-B1 is associated with earlier senescence and higher levels of grain protein, iron, and zinc content due to increased nutrient remobilisation. To investigate how related NAM genes control nitrogen remobilization at the molecular level, we carried out a comparative transcriptomic study at seven time points (3, 7, 10, 13, 19 and 26 days after anthesis) in wild type and NAM RNA interference (RNAi) lines with reduced NAM gene expression. Approximately 2.5 times more genes were differentially expressed in WT than NAM RNAi during this early senescence time course (6,508 vs 2,605 genes). In both genotypes, differentially expressed genes were enriched for GO terms related to photosynthesis, hormones, amino acid transport and nitrogen metabolism. However, nitrogen metabolism genes including glutamine synthetase (GS1 and GS2), glutamate decarboxylase (GAD), glutamate dehydrogenase (GDH) and asparagine synthetase (ASN1) showed stronger or earlier differential expression in WT than in NAM RNAi plants, consistent with higher nitrogen remobilisation. The use of time course data identified the dynamics of NAM-regulated and NAM-independent gene expression changes during senescence, and provides an entry point to functionally characterise the pathways regulating senescence and nutrient remobilisation in wheat.
Investigating genetic diversity within the most abundant and prevalent non-pathogenic leaf-associated bacteria interacting with Arabidopsis thaliana in natural habitats
Authors: Ramirez-Sanchez Daniela , Gibelin-Viala Chrystel , Mayjonade Baptiste , Duflos Rémi , Belmonte Elodie , Pailler Vincent , Bartoli Claudia , Carrere Sébastien , Vailleau Fabienne , Roux Fabrice , Vailleau Fabienne 
Published: July 2022

ABSTRACTPlants interact simultaneously with highly diversified microbes defined as the plant microbiota. Microbiota modulates plant health and appears as a promising lever to develop innovative, sustainable and eco-friendly agro-ecosystems. Key patterns of microbiota assemblages in plants have been revealed by an extensive number of studies based on taxonomic profiling by metabarcoding. However, understanding the functionality of microbiota and identifying the genetic and molecular mechanisms underlying the interplay between plants and their microbiota are still in its infancy and relies on reductionist approaches primarily based on the establishment of representative microbial collections. In Arabidopsis thaliana, most of these microbial collections include one strain per OTU isolated from a limited number of habitats, thereby neglecting the ecological potential of genetic diversity within microbial species to affect the plant-microbiota molecular dialog. With this study, we aimed at estimating the extent of genetic variation between strains within the most abundant and prevalent leaf-associated non-pathogenic bacterial species in 163 natural populations of A. thaliana located south-west of France. By combining a culture-based collection approach consisting of the isolation of more than 7,000 bacterial colonies with an informative-driven approach, we isolated 35 pure strains from eight non-pathogenic bacterial species. We detected significant intra-specific genetic variation at the genomic level and for growth rate in synthetic media. In addition, significant host genetic variation was detected in response to most bacterial strains in in vitro conditions, with the presence of both negative and positive responses on plant growth. Our study provides new genetic and genomic resources for a better understanding of the plant-microbe ecological interactions at the microbiota level. We also highlight the need of considering genetic variation in both non-pathogenic bacterial species and A. thaliana to decipher the genetic and molecular mechanisms involved in the ecologically relevant dialog between hosts and leaf microbiota.
Sleep-dependent structural neuroplasticity after a spatial navigation task: A diffusion imaging study
Authors: Villemonteix Thomas , Guerreri Michele , Deantoni Michele , Balteau Evelyne , Schmidt Christina , Stee Whitney , Zhang Hui , Peigneux Philippe 
Published: July 2022

AbstractEvidence for sleep-dependent changes in micro-structural neuroplasticity remains scarce, despite the fact that it is a mandatory correlate of the reorganization of learning-related functional networks. We investigated the effects of post-training sleep on structural neuroplasticity markers measuring standard diffusion tensor imaging (DTI) mean diffusivity (MD) and the revised biophysical neurite orientation dispersion and density imaging (NODDI) free water fraction (FWF) and neurite density (NDI) parameters that enable disentangling whether MD changes result from modifications in neurites or in other cellular components (e.g., glial cells). Thirty-four healthy young adults were scanned using diffusion weighted imaging [DWI] on Day1 before and after 40-minutes route learning (navigation) in a virtual environment, then were sleep deprived (SD) or slept normally (RS) for the night. After recovery sleep for 2 nights, they were scanned again (Day4) before and after 40-minutes route learning (navigation) in an extended environment. Sleep-related microstructural changes were computed on DTI (MD) and NODDI (NDI and FWF) parameters in the cortical ribbon and subcortical hippocampal and striatal regions of interest (ROIs). Results disclosed navigation learning-related decreased DWI parameters in the cortical ribbon (MD, FWF) and subcortical (MD, FWF, NDI) areas. Post-learning sleep-related changes were found at Day4 in the extended learning session (pre- to post-relearning percentage changes), suggesting a rapid sleep-related remodelling of neurites and glial cells subtending learning and memory processes in basal ganglia and hippocampal structures.
Comparing the evolutionary dynamics of predominant SARS-CoV-2 virus lineages co-circulating in Mexico
Authors: Castelán-Sánchez Hugo G. , Delaye Luis , Inward Rhys P. D. , Dellicour Simon , Gutierrez Bernardo , Martinez de la Vina Natalia , Boukadida Celia , Pybus Oliver G , de Anda Jáuregui Guillermo , Guzmán Plinio , Garrido Flores Marisol , Fontanelli Óscar , Rosales Maribel Hernández , Meneses Amilcar , Olmedo-Alvarez Gabriela , Herrera-Estrella Alfredo , Sanchez-Flores Alejandro , Muñoz-Medina José Esteban , Comas-García Andreu , Gómez-Gil Bruno , Zárate Selene , Taboada Blanca , López Susana , Arias Carlos F. , Kraemer Moritz U.G. , Lazcano Antonio , Escalera-Zamudio Marina 
Published: July 2022

ABSTRACTOver 200 different SARS-CoV-2 lineages have been observed in Mexico by November 2021. To investigate lineage replacement dynamics, we applied a phylodynamic approach and explored the evolutionary trajectories of five dominant lineages that circulated during the first year of local transmission. For most lineages, peaks in sampling frequencies coincided with different epidemiological waves of infection in Mexico. Lineages B.1.1.222 and B.1.1.519 exhibited similar dynamics, constituting clades that likely originated in Mexico and persisted for >12 months. Lineages B.1.1.7, P.1 and B.1.617.2 also displayed similar dynamics, characterized by multiple introduction events leading to a few successful extended local transmission chains that persisted for several months. For the largest B.1.617.2 clades, we further explored viral lineage movements across Mexico. Many clades were located within the south region of the country, suggesting that this area played a key role in the spread of SARS-CoV-2 in Mexico.
Assembly of von Willebrand Factor Tubules within VivoHelical Parameters Requires A1 Domain Insertion
Authors: Javitt Gabriel , Fass Deborah 
Published: July 2022

AbstractThe von Willebrand factor (VWF) glycoprotein is stored in tubular form in Weibel-Palade bodies (WPBs) prior to secretion from endothelial cells into the bloodstream. The organization of VWF in the tubules promotes formation of covalently linked VWF polymers and enables orderly secretion without polymer tangling. Recent studies have described the high-resolution structure of helical tubular cores formedin vitroby the D1D2 and D′D3 amino-terminal protein segments of VWF. Here we show that formation of tubules with the helical geometry observed for VWF in intracellular WPBs requires also the VWA1 (A1) domain. We reconstituted VWF tubules from segments containing the A1 domain and discovered it to be inserted between helical turns of the tubule, altering helical parameters and explaining the increased robustness of tubule formation when A1 is present. The conclusion from this observation is that the A1 domain has a direct role in VWF assembly, along with its known activity in hemostasis post-secretion.Key pointsA cryo-EM structure shows that the A1 domain is necessary for forming VWF helical tubules matching those in Weibel-Palade bodies.The A1 domain has a role in intracellular VWF supramolecular assembly in addition to platelet binding following secretion and activation.