bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-term exposure to intermittent hypoxia leads to changes in gene expression seen in chronic pulmonary disease
Authors: Wu Gang , Lee Yin Yeng , Gulla Evelyn M. , Potter Andrew , Kitzmiller Joseph , Ruben Marc D , Salomonis Nathan , Whitsett Jeffrey A. , Francey Lauren J , Hogenesch John B , Smith David F. 
Published: March 2020

AbstractObstructive sleep apnea (OSA) results from episodes of airway collapse and intermittent hypoxia and is associated with a host of health complications including dementia, diabetes, heart failure, and stroke. Although the lung is the first organ to sense changes in inspired oxygen levels, little is known about the consequences of IH to the lung hypoxia-inducible factor (HIF)-responsive pathways. Furthermore, cellular mechanisms causing disease progression across multiple systems in OSA are unknown. We hypothesized that exposure to IH would lead to up- and down-regulation of diverse expression pathways and that individual cell populations would show distinctive responses to IH. We identify changes in circadian and immune pathways in lungs from mice exposed to IH. Among all cell types, endothelial cells show the most prominent transcriptional changes. Interestingly, up-regulated genes in endothelial, fibroblast, and myofibroblast cells were enriched for genes associated with pulmonary fibrosis and pulmonary hypertension. These genes include targets of several drugs currently used to treat chronic pulmonary diseases. Our results reveal potential candidates for cell-targeted therapy seeking to minimize pulmonary effects of OSA. A better understanding of the pathophysiologic mechanisms underlying diseases associated with OSA could improve our therapeutic approaches, directing therapies to the most relevant cells and molecular pathways.
Increased FOXL2 Expression Alters Uterine Structures and Functions
Authors: Li Rong , Wu San-Pin , Zhou Lecong , Nicol Barbara , Lydon John P. , Yao Humphrey H-C , DeMayo Francesco J. 
Published: March 2020

AbstractTranscription factor FOXL2 exhibits an increase in mRNA levels in eutopic endometrial biopsy in endometriosis patients. While FOXL2 is known of regulating sex differentiation and reproductive function, the impact of elevated FOXL2 expression on uterine physiology remains unknown. To answer this question, we generated mice with over expression of FOXL2 (FOXL2OE) in the female reproductive tract by crossingFoxl2LsL/+with thePgrcremodel. FOXL2OEuterus showed severe morphological abnormality including abnormal epithelial stratification, blunted adenogenesis, increased endometrial fibrosis and disrupted myometrial morphology. In contrast, increasing FOXL2 levels specifically in uterine epithelium by crossing theFoxl2LsL/+with theLtficremice resulted in the eFOXL2OEmice with uterine epithelial stratification but without defects in endometrial fibrosis and adenogenesis, demonstrating a role of the endometrial stroma in the uterine abnormalities of the FOXL2OEmice. Transcriptomic analysis of 12 weeks oldPgrcreand FOXL2OEuterus at diestrus stage showed a positive correlation of FOXL2OEuterine transcriptome with human endometrium of endometriosis patients. Furthermore, we found FOXL2OEmice were sterile. The infertility was caused in part by a disruption of the hypophyseal ovarian axis resulting in an anovulatory phenotype. The FOXL2OEmice failed to show decidual responses during artificial decidualization in ovariectomized mice which demonstrates the uterine contribution to the infertility phenotype. These data supported that aberrantly increased FOXL2 expressions in the female reproductive tract can disrupt ovarian and uterine functions, particularly, may be involved in the progressions of endometriosis.
DNA methyltransferase 1 (DNMT1) function is implicated in the age-related loss of cortical interneurons
Authors: Hahn Anne , Bayer Cathrin , Pensold Daniel , Tittelmeier Jessica , Marx-Blümel Lisa , González-Bermúdez Lourdes , Linde Jenice , Groß Jonas , Salinas-Riester Gabriela , Lingner Thomas , von Maltzahn Julia , Spehr Marc , Pieler Tomas , Urbach Anja , Zimmer-Bensch Geraldine 
Published: March 2020

AbstractIncreased life expectancy in modern society comes at the cost of age-associated disabilities and diseases. Aged brains not only show reduced excitability and plasticity, but also a decline in inhibition. Age-associated defects in inhibitory circuits likely contribute to cognitive decline and age-related disorders. Molecular mechanisms that exert epigenetic control of gene expression, contribute to age-associated neuronal impairments. Both DNA methylation, mediated by DNA methyltransferases (DNMTs), and histone modifications maintain neuronal function throughout lifespan. Here we provide evidence that DNMT1 function is implicated in the age-related loss of cortical inhibitory interneurons. Deletion ofDnmt1in parvalbumin-positive interneurons attenuates their age-related decline in the cerebral cortex. Moreover, DNMT1-deficient mice show improved somatomotor performance and reduced aging-associated transcriptional changes. A decline in the proteostasis network, responsible for the proper degradation and removal of defective proteins, is suggested to be essentially implicated in age- and disease-related neurodegeneration. Our data suggest that DNMT1 acts indirectly on interneuron survival in aged mice by modulating the proteostasis network during life-time.
Bbs5 functions as the docking compartment of Bbsome binding to Klc3 regulated by Bbs5-Ser246PKC-phosphorylation during mouse spermatogenesis
Authors: Yu Dahai , He Lixia , Zhou Xin , Wang Xiuxia , Yu Bingzhi 
Published: March 2020

AbstractA mitochondrial and a fibrous sheath form the midpiece of the mammalian sperm flagellum encircling most of the axoneme. It has been documented that Kinesin light chain 3 (KLC3) was involved although the formation procedure remains unclear. Yeast-two-hybrid dataset showed an interaction between Klc3 and Bardet-Biedl Syndrome 5 (BBS5) Protein, another molecular associated with cilia and flagella forming. In this study, we presumed that the most conserved IFT complex BBsome was involved in spermatogenesis via the interaction of one of its subunits, Bbs5 with Klc3. Firstly, the interaction between Klc3 and Bbs5 was confirmed with Co-IP. Secondly, we identified PKC phosphorylation sitesin vitroby LC-MS/MS, Ser19and Ser246of Bbs5, examined the phosphorylation status of Bbs5 Ser19and Ser246in mouse testis. Co-IP was performed to find which PKC isoforms phosphorylate Bbs5. In addition, we tried to discuss the roles of Ser19and Ser246of Bbs5 in the Klc3-bbs5 interaction and in mouse spermatogenesis based on our early findings.
One-Day Construction Of Multiplex Arrays to Harness Natural CRISPR Systems
Authors: Cooper Robert M. , Hasty Jeff 
Published: March 2020

AbstractCRISPR-Cas systems are prokaryotic immune systems that have proliferated widely not only in bacteria and archaea, but also much more recently, in human biological research and applications. Much work to date has utilized synthetic sgRNAs along with the CRISPR nuclease Cas9, but the discovery of array-processing nucleases now allows the use of more compact, natural CRISPR arrays in heterologous hosts, in addition to organisms with endogenous systems. Unfortunately, the construction of multiplex natural CRISPR arrays remains technically challenging, expensive, and/or time-consuming. This limitation hampers research involving natural CRISPR arrays in both native and heterologous hosts. To address this problem, we present a method to assemble CRISPR arrays that is simple, rapid, affordable, and highly scalable – we assembled 9-spacer arrays with one day’s worth of work. We used this method to harness the endogenous CRISPR system of the highly competent bacteriumAcinetobacter baylyi, showing that while single spacers are not always completely effective at blocking DNA acquisition through natural competence, multiplex natural CRISPR arrays enable both nearly complete DNA exclusion and genome editing, including with multiple targets for both. In addition to demonstrating a CRISPR array assembly method that will benefit a variety of applications, we also find a potential bet-hedging strategy for balancing CRISPR defense vs. DNA acquisition in naturally competentA. baylyi.
Plasticity and Artificial Selection for Developmental Mode in a Poecilogonous Sea Slug
Authors: Caplins Serena A. 
Published: March 2020

AbstractDevelopmental mode describes the means by which larvae are provisioned with the nutrients they need to proceed through development and typically results in a trade-off between offspring size and number. The sacoglossan sea slugAlderia willowiexhibits intraspecific variation for developmental mode (= poecilogony) that is environmentally modulated with populations producing more yolk-feeding (lecithotrophic) larvae during the summer, and more planktonic feeding (planktotrophic) larvae in the winter. I found significant family level variation in the reaction norms between 17 maternal families ofA. willowiwhen reared in low (16 ppt) versus high (32 ppt) salinity. I documented a significant response to selection for lecithotrophic larvae, the proportion of which increased 32% after three generations of selection in high salinity, and 18% after 2 generations in low salinity (realized heritability: 0.365 ± 0.024). The slope of the reaction norm was maintained following one generation of selection for lecithotrophy and one generation of selfing. The rapid response to selection favoring one developmental mode may speak to the rarity of intraspecific variation for developmental mode, which could fix for one mode over another much more readily than has generally been assumed from studies of less plastic organisms.
A gut sensor for sugar preference
Authors: Buchanan Kelly L. , Rupprecht Laura E. , Sahasrabudhe Atharva , Kaelberer M. Maya , Klein Marguerita , Villalobos Jorge , Liu Winston W. , Yang Annabelle , Gelman Justin , Park Seongjun , Anikeeva Polina , Bohórquez Diego V. 
Published: March 2020

Summary Paragraph/AbstractAnimals innately prefer caloric sugars over non-caloric sweeteners. Such preference depends on the sugar entering the intestine.1–4Although the brain is aware of the stimulus within seconds,5–8how the gut discerns the caloric sugar to guide choice is unknown. Recently, we discovered an intestinal transducer, known as the neuropod cell.9,10This cell synapses with the vagus to inform the brain about glucose in the gut in milliseconds.10Here, we demonstrate that neuropod cells distinguish a caloric sugar from a non-caloric sweetener using the electrogenic sodium glucose co-transporter 1 (SGLT1) or sweet taste receptors. Activation of neuropod cells by non-caloric sucralose leads to ATP release, whereas the entry of caloric sucrose via SGLT1 stimulates glutamate release. To interrogate the contribution of the neuropod cell to sugar preference, we developed a method to record animal preferences in real time while using optogenetics to silence or excite neuropod cells. We discovered that silencing these cells, or blocking their glutamatergic signaling, renders the animals unable to recognize the caloric sugar. And, exciting neuropod cells leads the animal to consume the non-caloric sweetener as if it were caloric. By transducing the precise identity of the stimuli entering the gut, neuropod cells guide an animal’s internal preference toward the caloric sugar.
Oligomeric amyloid beta prevents myelination in a clusterin-dependent manner
Authors: Beiter Rebecca M. , Ennerfelt Hannah E. , Rivet-Noor Courtney , Merchak Andrea , Bai Robin , Johanson David M. , Slogar Erica , Sol-Church Katia , Phillips Jennifer L. , Bathe Tim , Overall Christopher C. , Lukens John R. , Prokop Stefan , Gaultier Alban 
Published: March 2020

AbstractWhite matter loss has been described as a common occurrence in Alzheimer’s disease (AD) patients for multiple decades. However, it remains unclear why oligodendrocyte progenitor cells (OPCs) fail to repair myelin deficits in these patients. Here, we show that clusterin, a risk factor for late-onset AD, is produced by OPCs and inhibits their differentiation into oligodendrocytes. Specifically, we demonstrate that a unique subset of OPCs produces clusterin. We show that phagocytosis of debris, including amyloid beta (Aβ) and myelin, drives the upregulation of clusterin in OPCs. We confirm,in vivo, that Aβ oligomers drive clusterin upregulation and that OPCs phagocytose Aβ. Furthermore, we show that clusterin is a potent inhibitor of OPC differentiation and prevents the production of myelin proteins. Finally, we demonstrate that clusterin inhibits OPC differentiation by significantly reducing the production of IL-9 by OPCs. Our data reveals that clusterin may be responsible for the lack of myelin repair observed in AD and is a promising therapeutic target for AD-associated cognitive decline.
Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer’s disease brain tissue
Authors: Ghosh Ujjayini , Thurber Kent R. , Yau Wai-Ming , Tycko Robert 
Published: March 2020

AbstractAmyloid-β (Aβ) fibrils exhibit self-propagating, molecular-level polymorphisms that may underlie variations in clinical and pathological characteristics of Alzheimer’s disease. We report the molecular structure of a specific brain-derived polymorph that has been identified as the most prevalent polymorph of 40-residue Aβ fibrils in cortical tissue of Alzheimer’s disease patients. This structure, developed from cryo-electron microscopy and supported by solid state NMR data, differs qualitatively from all previously described Aβ fibril structures, both in its molecular conformation and its organization of cross-β subunits. Knowledge of this brain-derived fibril structure may contribute to the development of structure-specific amyloid imaging agents and aggregation inhibitors with greater diagnostic and therapeutic utility.
Examining the relationship between social cognition and neural synchrony during movies in children with and without autism
Authors: Lyons KM , Stevenson RA , Owen AM , Stojanoski B 
Published: March 2020

AbstractChildren who have been diagnosed with autism spectrum disorder (ASD) often show a marked deficit in measures of social cognition. In autistic adults, measures of social cognition have been shown to relate to differences in brain synchronization (as measured by fMRI) when individuals are processing naturalistic stimuli, such as movies. However, whether children with social impairments, with or without a diagnosis of ASD, differ in their neural responses to movies has not yet been investigated. In the current study, neural synchrony, measured using fMRI, was examined in three groups of children aged 7 to 12, who differed with respect to scores on a measure of autistic traits associated with social impairment and whether or not they had been diagnosed with ASD. While watching the movie ‘Despicable Me’, those diagnosed with ASD had significantly less neural synchrony in areas that have been previously shown to be associated with social cognition (e.g. areas related to ‘theory of mind’), and plot following (e.g. the lateral prefrontal cortex), than those who did not have an ASD diagnosis. In contrast, two groups who differed in their degree of social impairment, but did not have a diagnosis of ASD, showed no significant differences in neural synchrony across the whole brain. These results shed some light on how autistic traits may contribute to an individual’s conscious experience of the world, and how, for children with ASD, that experience may differ markedly from that of those without ASD.
Single-Cell Atlas of Early Human Brain Development Highlights Heterogeneity of Human Neuroepithelial Cells and Early Radial Glia
Authors: Eze Ugomma C. , Bhaduri Aparna , Haeussler Maximilian , Nowakowski Tomasz J. , Kriegstein Arnold R. 
Published: March 2020

AbstractThe human cortex is comprised of diverse cell types that emerge from an initially uniform neuroepithelium that gives rise to radial glia, the neural stem cells of the cortex. To characterize the earliest stages of human brain development, we performed single-cell RNA-sequencing across regions of the developing human brain, including the telencephalon, diencephalon, midbrain, hindbrain, and cerebellum. We identify nine progenitor populations physically proximal to the telencephalon, suggesting more heterogeneity than previously described, including a highly prevalent mesenchymal-like population that disappears once neurogenesis begins. Comparison of human and mouse progenitor populations at corresponding stages identifies two progenitor clusters that are enriched in the early stages of human cortical development. We also find that organoid systems display low fidelity to neuroepithelial and early radial glia cell types, but improve as neurogenesis progresses. Overall, we provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development.
Endothelial Cells stimulate proliferation of CD140a sorted human Glial Progenitor Cells and their specification towards astrocytic lineage
Authors: Dasgupta Asmita 
Published: March 2020

AbstractHomeostasis in stem cell niche is established by fine-tuning between interacting signaling pathways of all resident cell types that constitute the niche. In this context, the exact contribution of human endothelial cells in biology of PDGFRα positive human glial progenitor cells (hGPCs) in niche environment is not well understood. Towards the same, insert co-culture system with human umbilical vein endothelial cells (HUVECs) has been adopted. In co-culture with HUVECs, under proliferative condition, hGPCs show increased proliferation and sphere formation, while under differentiating condition hGPCs show increased differentiation to astrocytes with concomitant decrease in differentiation to oligodendrocytes with respect to no co-culture controls. Transcript assay for selected humoral factors reveals bone morphogenic proteins (BMPs), endothelin1, growth arrest specific 6 and interleukin 6 to be in higher abundance in HUVECS than hGPCs, of which BMP4 transcripts were most abundant, indicating possibilities of its being the key mediator of endothelial mediated effects. Concurrently, noggin effectively attenuates HUVEC mediated astrocytic differentiation of PDGFRα sorted fetal hGPCs The results have implication towards safety of transplantation therapies with PDGFRα sorted fetal hGPCs. It is postulated that proliferation and differentiation response as seen in this co-culture system could have defining implications towards the genesis of glioma.
Converting lateral scanning into axial focusing to speed up 3D microscopy
Authors: Chakraborty Tonmoy , Chang Bo-Jui , Daetwyler Stephan , Sapoznik Etai , Chen Bingying , Dean Kevin M. , Fiolka Reto 
Published: March 2020

AbstractIn optical microscopy, the slow axial scanning rate of the objective or the sample has traditionally limited the speed of 3D volumetric imaging. Recently, by conjugating either a movable-mirror to the image plane or an electrotuneable lens (ETL) to the back-focal plane respectively, rapid axial scanning has been achieved. However, mechanical actuation of a mirror limits axial scanning rate (usually only 10-100 Hz for piezoelectric or voice coil based actuators), while ETLs introduce spherical and higher order aberrations, thereby preventing high-resolution imaging. Here, we introduce a novel optical design that can transform a lateral-scan motion into a spherical-aberration-free, high-resolution, rapid axial scan. Using a galvanometric mirror, we scan a laser beam laterally in a remote-focusing arm, which is then back-reflected from different heights of a mirror in image space. We characterize the optical performance of this remote focusing technique and use it to accelerate axially swept light-sheet microscopy (ASLM) by one order of magnitude, allowing the quantification of rapid vesicular dynamics in 3D.
Beyond endemism, expanding conservation efforts: a relictual Pleistocene distribution and first report of the prickly pear cactus,Opuntia bonaerensis,in Brazil and Uruguay
Authors: Köhler Matias , Esser Luíz F. , Font Fabián , Souza-Chies Tatiana T. , Majure Lucas C. 
Published: March 2020

AbstractGeographical range is one of the critical features for species conservation assessment. Nevertheless, species distribution is frequently unknown, undervalued or overlooked. During a broad taxonomic and floristic study of the southern South American prickly pear species (Opuntiaspp.), new records of a previously endemic Argentinian taxon have been found in Uruguay and Brazil. Molecular phylogenetic inference was carried out to further evaluate the identity of the new records, and ecological niche models were implemented to test how the new records would fit in the previous known distribution of the species. Through molecular and morphological evidence, we confirmed the new records ofOpuntia bonaerensisfor Brazilian and Uruguayan floras and discussed its phylogenetic relationship and morphologic similarities with closely related species. Our new records uncovered a distributional pattern congruent with the Neotropical Peripampasic Orogenic Arc, which must be further explored to better determine the biogeographic history of the species. Ecological niche models (ENM) revealed thatO. bonaerensishad a putative ancient distribution across the grasslands and shrublands in the Pampean region largely congruent with the populations found in Brazil and Uruguay, suggesting relictual Pleistocene populations of the species and the role of glacial/interglacial cycles on the distribution of the species. In a prospective climate change scenario, ENM suggests that the species would in general be more restricted to the southernmost limits of the Pampa region and previous outlying records from Mendoza (Argentina) are a putative future refuge forO. bonaerensis. The importance of these new records for biodiversity and conservation assessment efforts that are ongoing at different scales in Brazil and neighbor areas is highlighted.
Porcupine: Rapid and robust tagging of physical objects using nanopore-orthogonal DNA strands
Authors: Doroschak Kathryn , Zhang Karen , Queen Melissa , Mandyam Aishwarya , Strauss Karin , Ceze Luis , Nivala Jeff 
Published: March 2020

Molecular tagging is an approach to labeling physical objects using DNA or other molecules that can be used in cases where methods like RFID tags and QR codes are not suitable. No molecular tagging method exists that is inexpensive, fast and reliable to decode, and usable outside a lab setting to create or read tags. To address this, we present Porcupine, an end-user molecular tagging system that features DNA-based tags readable within seconds using a portable nanopore device. Porcupine’s digital bits are represented by the presence or absence of distinct, nanopore-orthogonal DNA strands, which we call molecular bits (molbits). We classify molbits directly from the raw nanopore signal, avoiding basecalling. To extend the tag’s shelf life, decrease readout time, and make tags robust to environmental contamination, molbits are prepared for readout during tag assembly and can be stabilized by dehydration. The result is an extensible, real time, high accuracy tagging system that includes a novel approach to developing nanopore-orthogonal barcodes.One sentence summaryPorcupine lets end-users label physical objects with custom DNA tags, without requiring a lab to create or read tags, and offers rapid readout using nanopore sequencing.