bluuebunny/crossref_metadata_2025_split huggingface dataset:
Erythroid precursors and progenitors suppress adaptive immunity and get invaded by SARS-CoV-2
Authors: Shahbaz Shima , Xu Lai , Osman Mohammad , Sligl Wendy , Shields Justin , Joyce Michael , Tyrrell Lorne , Oyegbami Olaide , Elahi Shokrollah 
Published: August 2020

AbstractSARS-CoV-2 infection is associated with lower blood oxygen levels even in patients without hypoxia requiring hospitalization. This discordance illustrates the need for a more unifying explanation as to whether SARS-CoV-2 directly or indirectly affects erythropoiesis. Here we show significantly enriched CD71+ erythroid precursors/progenitors in the blood circulation of COVID-19 patients that have distinctive immunosuppressive properties. A subpopulation of abundant erythroid cells, CD45+CD71+cells, co-express ACE2, TMPRSS2, CD147, CD26 and these can be infected with SARS-CoV-2. In turn, pre-treatment of erythroid cells with dexamethasone significantly diminished ACE2/TMPRSS2 expression and subsequently reduced their infectivity with SARS-CoV-2. Taken together, pathological abundance of erythroid cells might reflect stress erythropoiesis due to the invasion of erythroid progenitors by SARS-CoV-2. This may provide a novel insight into the impact of SARS-CoV-2 on erythropoiesis and hypoxia seen in COVID-19 patients.
Arabidopsis Myosin XIK Interacts with the Exocyst Complex to Facilitate Vesicle Tethering during Exocytosis
Authors: Zhang Weiwei , Huang Lei , Zhang Chunhua , Staiger Christopher J. 
Published: August 2020

ABSTRACTMyosin motors are essential players in secretory vesicle trafficking and exocytosis in yeast and mammalian cells; however, similar roles in plants remain a matter for debate, at least for diffusely-growing cells. Here, we demonstrate that Arabidopsis (Arabidopsis thaliana) myosin XIK, via its globular tail domain (GTD), participates in the vesicle tethering step of exocytosis through direct interactions with the exocyst complex. Specifically, myosin XIK GTD bound directly to the SEC5B subunit of exocyst in vitro and functional fluorescently-tagged XIK colocalized with multiple exocyst subunits at plasma membrane (PM)-associated stationary foci. Moreover, genetic and pharmacological inhibition of myosin XI activity reduced the frequency and lifetime of stationary exocyst complexes at the PM. By tracking single exocytosis events of cellulose synthase (CESA) complexes (CSCs) with high spatiotemporal resolution imaging and pair-wise colocalization analysis of myosin XIK, exocyst subunits and CESA6, we demonstrated that XIK associates with secretory vesicles earlier than exocyst and is required for the recruitment of exocyst to the PM tethering site. This study reveals an important functional role for myosin XI in secretion and provides new insights about the dynamic regulation of exocytosis in plants.
Trophic shift and the origin of birds
Authors: Wu Yonghua 
Published: August 2020

AbstractBirds are characterized by evolutionary specializations of both locomotion (e.g., flapping flight) and digestive system (toothless, crop, and gizzard), while the potential selection pressures responsible for these evolutionary specializations remain unclear. Here we used a recently developed molecular phyloecological method to reconstruct the diets of the ancestral archosaur and of the common ancestor of living birds (CALB). Our results showed that the ancestral archosaur exhibited a predominant Darwinian selection of protein and fat digestion and absorption, whereas the CALB showed a marked enhanced selection of carbohydrate and fat digestion and absorption, suggesting a trophic shift from carnivory to herbivory (fruit, seed, and/or nut-eater) at the archosaur-to-bird transition. The evolutionary shift of the CALB to herbivory may have essentially made them become a low-level consumer and, consequently, subject to relatively high predation risk from potential predators such as gliding maniraptorans, from which birds descended. Under the relatively high predation pressure, ancestral birds with gliding capability may have then evolved not only flapping flight as a possible anti-predator strategy against gliding predatory maniraptorans but also the specialized digestive system as an evolutionary tradeoff of maximizing foraging efficiency and minimizing predation risk. Our results suggest that the powered flight and specialized digestive system of birds may have evolved as a result of their tropic shift-associated predation pressure.
A Large-scale Comparison of Cortical and Subcortical Structural Segmentation Methods in Alzheimer’s Disease: a Statistical Approach
Authors: Zamani Jafar , Sadr Ali , Javadi Amir-Homayoun 
Published: August 2020

AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative disease that leads to anatomical atrophy, as evidenced by magnetic resonance imaging (MRI). Automated segmentation methods are developed to help with the segmentation of different brain areas. However, their reliability has yet to be fully investigated. To have a more comprehensive understanding of the distribution of changes in AD, as well as investigating the reliability of different segmentation methods, in this study we compared volumes of cortical and subcortical brain segments, using automated segmentation methods in more than 60 areas between AD and healthy controls (HC).MethodsA total of 44 MRI images (22 AD and 22 HC, 50% females) were taken from the minimal interval resonance imaging in Alzheimer’s disease (MIRIAD) dataset. HIPS, volBrain, CAT and BrainSuite segmentation methods were used for the subfields of hippocampus, and the rest of the brain.ResultsWhile HIPS, volBrain and CAT showed strong conformity with the past literature, BrainSuite misclassified several brain areas. Additionally, the volume of the brain areas that successfully discriminated between AD and HC showed a correlation with mini mental state examination (MMSE) scores. The two methods of volBrain and CAT showed a very strong correlation. These two methods, however, did not correlate with BrainSuite.ConclusionOur results showed that automated segmentation methods HIPS, volBrain and CAT can be used in the classification of AD and HC. This is an indication that such methods can be used to inform researchers and clinicians of underlying mechanisms and progression of AD.
Thyroid hormone regulates proximodistal identity in the fin skeleton
Authors: Hu Yinan , Harper Melody , Acosta Benjamin , Donahue Joan , Bui Hoa , Lee Hyungwoo , Nguyen Stacy , McMenamin Sarah 
Published: August 2020

AbstractAcross the ∼30,000 species of ray-finned fish, fins show incredible diversity in overall shape and in the patterning of the supportive bony rays. Fin length mutant zebrafish have provided critical insights into the developmental pathways that regulate relative fin size. However, the processes that govern skeletal patterning along the proximodistal axis of the fin have remained less well understood. Here, we show that thyroid hormone regulates proximodistal identity of fin rays, distalizing gene expression profiles, morphogenetic processes during outgrowth, and ultimate morphology of the fin. This role for thyroid hormone in specifying proximodistal identity appears conserved between development and regeneration, in all the fins, and between species. We demonstrate that proximodistal identity is regulated independently from pathways that determine size, and we show that modulating proximodistal patterning relative to growth can recapitulate the spectrum of fin ray diversity found in nature.
Respiratory complex and tissue lineage drive mutational patterns in the tumor mitochondrial genome
Authors: Gorelick Alexander N. , Kim Minsoo , Chatila Walid K. , La Konnor , Hakimi A. Ari , Taylor Barry S. , Gammage Payam A. , Reznik Ed 
Published: August 2020

AbstractMitochondrial DNA (mtDNA) encodes essential protein subunits and translational machinery for four distinct complexes of oxidative phosphorylation (OXPHOS). Using repurposed whole-exome sequencing data, we demonstrate that pathogenic mtDNA mutations arise in tumors at a rate comparable to the most common cancer driver genes. We identify OXPHOS complexes as critical determinants shaping somatic mtDNA mutation patterns across tumor lineages. Loss-of-function mutations accumulate at an elevated rate specifically in Complex I, and often arise at specific homopolymeric hotspots. In contrast, Complex V is depleted of all non-synonymous mutations, suggesting that mutations directly impacting ATP synthesis are under negative selection. Both common truncating mutations and rarer missense alleles are associated with a pan-lineage transcriptional program, even in cancer types where mtDNA mutations are comparatively rare. Pathogenic mutations of mtDNA are associated with substantial increases in overall survival of colorectal adenocarcinoma patients, demonstrating a clear functional relationship between genotype and phenotype. The mitochondrial genome is therefore frequently and functionally disrupted across many cancers, with significant implications for patient stratification, prognosis and therapeutic development.
Post-interval EEG activity is related to task-goals in temporal discrimination
Authors: Bueno Fernanda D. , Cravo André M. 
Published: August 2020

AbstractStudies investigating the neural mechanisms of time perception often measure brain activity while participants perform a temporal task. However, several of these studies are based exclusively on tasks in which time is relevant, making it hard to dissociate activity related to decisions about time from other task-related patterns. In the present study, human participants performed a temporal or color discrimination task of visual stimuli. Participants were informed which magnitude they would have to judge before or after presenting the two stimuli (S1 and S2) in different blocks. Our behavioral results showed, as expected, that performance was better when participants knew beforehand which magnitude they would judge. Electrophysiological data (EEG) was analyzed using Linear Discriminant Contrasts (LDC) and a Representational Similarity Analysis (RSA) approach to investigate whether and when information about time and color was encoded. During the presentation of S1, we did not find consistent differences in EEG activity as a function of the task. On the other hand, during S2, we found that temporal and color information was encoded in a task-relevant manner. Taken together, our results suggest that task goals strongly modulate decision-related information in EEG activity.
ABbs5mouse model reveals pituitary cilia contributions to developmental abnormalities
Authors: Bentley Melissa R. , Engle Staci E. , Haycraft Courtney J. , Andersen Reagan S. , Croyle Mandy J. , Clearman Kelsey R. , Rains Addison B. , Berbari Nicolas F. , Yoder Bradley K. 
Published: August 2020

AbstractPrimary cilia are critical sensory and signaling compartments present on most mammalian cell types. These specialized structures require a unique signaling protein composition relative to the rest of the cell to carry out their functions. Defects in ciliary structure and signaling result in a broad group of disorders collectively known as ciliopathies. One ciliopathy, Bardet-Biedl Syndrome (BBS; OMIM 209900), presents with diverse clinical features, many of which are attributed to defects in ciliary signaling during both embryonic development and postnatal life. For example, patients exhibit obesity, polydactyly, hypogonadism, developmental delay, and skeletal abnormalities along with sensory and cognitive deficits, but for many of these phenotypes it is uncertain which are developmental in origin. A subset of BBS proteins assembles into the BBSome complex, which is responsible for mediating transport of membrane proteins into and out of the cilium, establishing it as a sensory and signaling hub. Here we describe two new mouse models for BBS resulting from a congenital null and conditional allele ofBbs5.Bbs5null mice develop a complex phenotype including craniofacial defects, skeletal shortening, ventriculomegaly, infertility, and pituitary anomalies. Utilizing the conditional allele, we show that the male fertility defects, ventriculomegaly, and pituitary abnormalities are only found whenBbs5is mutated prior to P7 indicating a developmental origin. In contrast, mutation ofBbs5results in obesity independent of the age ofBbs5loss. Compared to other animal models of BBS,Bbs5mutant mice exhibit pathologies that suggest a specialized role for Bbs5 in ciliary function.
Endothelial Barrier Function is co-regulated at Vessel Bifurcations by Fluid Forces and Sphingosine-1-Phosphate
Authors: Akbari Ehsan , Spychalski Griffin B. , Menyhert Miles M. , Rangharajan Kaushik K. , Prakash Shaurya , Song Jonathan W. 
Published: August 2020

AbstractSphingosine-1-phosphate (S1P) is a blood-borne bioactive lipid mediator of endothelial barrier function. Prior studies have implicated mechanical stimulation due to intravascular laminar shear stress in co-regulating S1P signaling in endothelial cells (ECs). Yet, vascular networksin vivoconsist of vessel bifurcations, and this geometry produces hemodynamic forces that are distinct from laminar shear stress. However, the role of these forces at vessel bifurcations in regulating S1P-dependent endothelial barrier function is not known. In this study, we implemented a microfluidic platform that recapitulates the flow dynamics of vessel bifurcations within situquantification of the permeability of microvessel analogues. Co-application of S1P with impinging bifurcated fluid flow, which was characterized by approximately zero shear stress and 38 dyn cm-2stagnation pressure at the vessel bifurcation point, promotes vessel stabilization. Similarly, co-treatment of carrier-free S1P with 3 dyn cm-2laminar shear stress is also protective of endothelial barrier function. Moreover, it is shown that vessel stabilization due to laminar shear stress, but not bifurcated fluid flow, is dependent on S1P receptor 1 or 2 signaling. Collectively, these findings demonstrate the endothelium-protective function of fluid forces at vessel bifurcations and their involvement in coordinating S1P-dependent regulation of vessel permeability.
Hexosamine biosynthetic pathway integrates circadian and metabolic signals to regulate daily rhythms in protein O-linked N-acetylglucosaminylation
Authors: Liu Xianhui , Blaženović Ivana , Contreras Adam J. , Pham Thu M. , Tabuloc Christine A. , Li Ying H. , Ji Jian , Fiehn Oliver , Chiu Joanna C. 
Published: August 2020

SUMMARYThe integration of circadian and metabolic signals is essential for maintaining robust circadian rhythms and ensuring efficient metabolism and energy use. UsingDrosophilaas an animal model, we showed that cellular protein O-linked N-acetylglucosaminylation (O-GlcNAcylation) exhibits robust 24-hour rhythm and is a key post-translational mechanism that regulates circadian physiology. We observed strong correlation between protein O-GlcNAcylation rhythms and clock-controlled feeding-fasting cycles, suggesting that O-GlcNAcylation rhythms are primarily driven by nutrient input. Interestingly, daily O-GlcNAcylation rhythms were severely dampened when we subjected flies to time-restricted feeding (TRF) at unnatural feeding time. This suggests the presence of a clock-regulated buffering mechanism that prevents excessive O-GlcNAcylation at non-optimal times of the day-night cycle. We found that this buffering mechanism is mediated by glutamine-fructose-6-phosphate amidotransferase (GFAT) activity, which is regulated through integration of circadian and metabolic signals. Finally, we generated a mathematical model to describe the key factors that regulate daily O-GlcNAcylation rhythm.
Genetics of mouse behavioral and peripheral neural responses to sucrose
Authors: Lin Cailu , Inoue Masashi , Li Xia , Bosak Natalia P. , Ishiwatari Yutaka , Tordoff Michael G. , Beauchamp Gary K. , Bachmanov Alexander A. , Reed Danielle R. 
Published: August 2020

AbstractMice of the C57BL/6ByJ (B6) strain have higher consumption of, and stronger peripheral neural responses to, sucrose solution than do mice of the 129P3/J (129) strain. To identify quantitative trait loci (QTLs) responsible for this strain difference and evaluate the contribution of peripheral taste responsiveness to individual differences in sucrose intake, we produced an intercross (F2) of 627 mice, measured their sucrose consumption in two-bottle choice tests, recorded the electrophysiological activity of the chorda tympani nerve elicited by sucrose in a subset of F2mice, and genotyped the mice with DNA markers distributed in every mouse chromosome. We confirmed a sucrose consumption QTL (Scon2, or Sac) on mouse chromosome (Chr) 4, harboring theTas1r3gene, which encodes the sweet taste receptor subunit T1R3 and affects both behavioral and neural responses to sucrose. For sucrose consumption, we also detected five new main-effect QTLsScon6(Chr2),Scon7(Chr5),Scon8(Chr8),Scon3(Chr9) and a sex-specific QTLScon9(Chr15), and an interacting QTL pairScon4(Chr1)and Scon3(Chr9). No additional QTLs for the taste nerve responses to sucrose were detected besides the previously known one on Chr4 (Scon2). Identification of the causal genes and variants for these sucrose consumption QTLs may point to novel mechanisms beyond peripheral taste sensitivity that could be harnessed to control obesity and diabetes.
Chronic oxytocin-driven alternative splicing of CRFR2α induces anxiety
Authors: Winter Julia , Meyer Magdalena , Berger Ilona , Peters Sebastian , Royer Melanie , Bianchi Marta , Stang Simone , Langgartner Dominik , Reber Stefan O. , Kuffner Kerstin , Schmidtner Anna K. , Hartmann Finn , Bludau Anna , Bosch Oliver J. , Slattery David A. , van den Burg Erwin H. , Neumann Inga D. , Jurek Benjamin 
Published: August 2020

SUMMARYRecently, oxytocin (OXT) has generated considerable interest as potential treatment for psychiatric disorders, including general anxiety disorder or autism spectrum disorder. Therefore, knowledge on the involved molecular processes downstream of OXT receptor (OXTR) activation is indispensable. We reveal that alternative splicing of corticotropin releasing factor receptor 2α (CRFR2α) parallels increased anxiety-like behavior following chronic OXT treatment, contrasting the well-known anxiolysis of acute OXT. In detail, chronic OXT shifts the splicing ratio between membrane-bound (mCRFR2α) and soluble CRFR2α (sCRFR2α) in favor of the latter via ERK1/2-MEF2A signaling. Targeted manipulations ofCrfr2αsplicing mimic the effect of chronic OXT, confirming its role in the regulation of anxiety-like behavior. Furthermore, chronic OXT triggers cytoplasmic distribution and extracellular release of sCRFR2α into the cerebrospinal fluid, with sCRFR2α levels positively correlating with anxiety-like behavior. Concluding, the dichotomy between anxiolytic mCRFR2α and anxiogenic sCRFR2α is the basis for the deleterious effects of chronic OXT on anxiety.Graphical Abstract
Intranasal Administration of Functionalized Soot Particles Disrupts Olfactory Sensory Neuron Progenitor Cells in the Neuroepithelium
Authors: Norwood Jordan N. , Gharpure Akshay P. , Kumal Raju , Turner Kevin L. , Pistone Lauren Ferrer , Vander Wal Randy , Drew Patrick J. 
Published: August 2020

AbstractExposure to air pollution has been linked to the development of neurodegenerative diseases and anosmia, but the underlying mechanism is not known. Additionally, the loss of olfactory function often precedes the onset of neurodegenerative diseases. Chemical ablation of olfactory sensory neurons blocks the drainage of cerebrospinal fluid (CSF) through the cribriform plate and alters normal CSF production and/or circulation. Damage to this drainage pathway could contribute to the development of neurodegenerative diseases and could link olfactory sensory neuron health and neurodegeneration. Here, we investigated the impact of intranasal treatment of combustion products (laboratory-generated soots) and their oxygen functionalized derivatives on mouse olfactory sensory neurons, olfactory nerve cell progenitors, and the behavior of the mouse. We found that after a month of every-other-day intranasal treatment of soots, there was minimal effect on olfactory sensory neuron anatomy or exploratory behavior in the mouse. However, oxygen-functionalized soot caused a large decrease in globose basal cells, which are olfactory progenitor cells. These results suggest that exposure to air pollution damages the olfactory neuron progenitor cells, and could lead to decreases in the number of olfactory neurons, potentially disrupting CSF drainage.
A Minimally Destructive Protocol for DNA Extraction from Ancient Teeth
Authors: Harney Éadaoin , Cheronet Olivia , Fernandes Daniel M. , Sirak Kendra , Mah Matthew , Bernardos Rebecca , Adamski Nicole , Broomandkhoshbacht Nasreen , Callan Kimberly , Lawson Ann Marie , Oppenheimer Jonas , Stewardson Kristin , Zalzala Fatma , Anders Alexandra , Candilio Francesca , Constantinescu Mihai , Coppa Alfredo , Ciobanu Ion , Dani János , Gallina Zsolt , Genchi Francesco , Nagy Emese Gyöngyvér , Hajdu Tamás , Hellebrandt Magdolna , Horváth Antónia , Király Ágnes , Kiss Krisztián , Kolozsi Barbara , Kovács Péter , Köhler Kitti , Lucci Michaela , Pap Ildikó , Popovici Sergiu , Raczky Pál , Simalcsik Angela , Szeniczey Tamás , Vasilyev Sergey , Virag Cristian , Rohland Nadin , Reich David , Pinhasi Ron 
Published: August 2020

ABSTRACTAncient DNA sampling methods—although optimized for efficient DNA extraction—are destructive, relying on drilling or cutting and powdering (parts of) bones and teeth. As the field of ancient DNA has grown, so have concerns about the impact of destructive sampling of the skeletal remains from which ancient DNA is obtained. Due to a particularly high concentration of endogenous DNA, the cementum of tooth roots is often targeted for ancient DNA sampling, but standard destructive sampling methods often result in the loss of at least one entire root. Here, we present a minimally destructive method for extracting ancient DNA from dental cementum present on the surface of tooth roots. This method does not require destructive drilling or grinding, and, following extraction, the tooth remains safe to handle and suitable for most morphological studies, as well as other biochemical studies, such as radiocarbon dating. We extracted and sequenced ancient DNA from 30 teeth (and 9 corresponding petrous bones) using this minimally destructive extraction method in addition to a typical tooth sampling method. We find that the minimally destructive method can provide ancient DNA that is of comparable quality to extracts produced from teeth that have undergone destructive sampling processes. Further, we find that a rigorous cleaning of the tooth surface combining diluted bleach and UV light irradiation seems sufficient to minimize external contaminants usually removed through the physical removal of a superficial layer when sampling through regular powdering methods.
Mechanism of negative membrane curvature generation by I-BAR domains
Authors: Nepal Binod , Sepehri Aliasghar , Lazaridis Themis 
Published: August 2020

AbstractThe membrane sculpting ability of BAR domains has been attributed to the intrinsic curvature of their banana-shaped dimeric structure. However, there is often a mismatch between this intrinsic curvature and the diameter of the membrane tubules generated. I-BAR domains have been especially mysterious: they are almost flat but generate high negative membrane curvature. Here, we use atomistic implicit-solvent computer modeling to show that the membrane bending of the IRSP53 I-BAR domain is dictated by its higher oligomeric structure, whose curvature is completely unrelated to the intrinsic curvature of the dimer. Two other I-BARs gave similar results, whereas a flat F-BAR sheet developed a concave membrane binding interface, consistent with its observed positive membrane curvature generation. Laterally interacting helical spirals of I-BAR dimers on tube interiors are stable and have an enhanced binding energy that is sufficient for membrane bending to experimentally observed tubule diameters at a reasonable surface density.