bluuebunny/crossref_metadata_2025_split huggingface dataset:
Somatosensory corticospinal tract axons sprout within the cervical cord following a dorsal root/dorsal column spinal injury in the rat
Authors: McCann Margaret M. , Fisher Karen M. , Ahloy-Dallaire Jamie , Darian-Smith Corinna 
Published: October 2019

AbstractThe corticospinal tract (CST) is the major descending pathway controlling voluntary hand function in primates, and though less dominant, it mediates voluntary paw movements in rats. As with primates, the CST in rats originates from multiple (albeit fewer) cortical sites, and functionally different motor and somatosensory subcomponents terminate in different regions of the spinal gray matter. We recently reported in monkeys that following a combined cervical dorsal root/dorsal column lesion (DRL/DCL), both motor and S1 CSTs sprout well beyond their normal terminal range. The S1 CST sprouting response is particularly dramatic, indicating an important, if poorly understood, somatosensory role in the recovery process. As rats are used extensively to model spinal cord injury (SCI), we asked if the S1 CST response is conserved in rodents. Rats were divided into sham controls, and two groups surviving post-lesion for ~6 and 10 weeks. A DRL/DCL was made to partially deafferent one paw. Behavioral testing showed a post-lesion deficit and recovery over several weeks. Three weeks prior to ending the experiment, S1 cortex was mapped electrophysiologically, for tracer injection placement to determine S1 CST termination patterns within the cord. Synaptogenesis was also assessed for labeled S1 CST terminals within the dorsal horn. Our findings show that the affected S1 CST sprouts well beyond its normal range in response to a DRL/DCL, much as it does in macaque monkeys. This, along with evidence for increased synaptogenesis post-lesion, indicates that CST terminal sprouting following a central sensory lesion, is a robust and conserved response.
Deformability based sorting of stored red blood cells reveals donor-dependent aging curves
Authors: Islamzada Emel , Matthews Kerryn , Guo Quan , Santoso Aline T. , Duffy Simon P. , Scott Mark D. , Ma Hongshen 
Published: October 2019

AbstractA fundamental challenge in the transfusion of red blood cells (RBCs) is that a subset of donated RBC units may not provide optimal benefit to transfusion recipients. This variability stems from the inherent ability of donor RBCs to withstand the physical and chemical insults of cold storage, which ultimately dictate their survival in circulation. The loss of RBC deformability during cold storage is well-established and has been identified as a potential biomarker for the quality of donated RBCs. While RBC deformability has traditionally been indirectly inferred from rheological characteristics of the bulk suspension, there has been considerable interest in directly measuring the deformation of RBCs. Microfluidic technologies have enabled single cell measurement of RBC deformation but have not been able to consistently distinguish differences between RBCs between healthy donors. Using the microfluidic ratchet mechanism, we developed a method to sensitively and consistently analyze RBC deformability. We found that the aging curve of RBC deformability varies significantly across donors, but is consistent for each donor over multiple donations. Specifically, certain donors seem capable of providing RBCs that maintain their deformability during two weeks of cold storage in standard test tubes. The ability to distinguish between RBC units with different storage potential could provide a valuable opportunity to identify donors capable of providing RBCs that maintain their integrity, in order to reserve these units for sensitive transfusion recipients.
Oxygenation properties of hemoglobin and the evolutionary origins of isoform multiplicity in an amphibious air-breathing fish, the blue-spotted mudskipper (Boleophthalmus pectinirostris)
Authors: Storz Jay F. , Natarajan Chandrasekhar , Grouleff Magnus K. , Vandewege Michael , Hoffmann Federico G. , You Xinxin , Venkatesh Byrappa , Fago Angela 
Published: October 2019

ABSTRACTAmong the numerous lineages of teleost fish that have independently transitioned from obligate water-breathing to facultative air-breathing, evolved properties of hemoglobin (Hb)-O2transport may have been shaped by the prevalence and severity of aquatic hypoxia (which influences the extent to which fish are compelled to switch to aerial respiration) as well as the anatomical design of air-breathing structures and the cardiovascular system. Here we examine the structure and function of Hbs in an amphibious, facultative air-breathing fish, the blue-spotted mudskipper (Boleophthalmus pectinirostris). We also characterized the genomic organization of the globin gene clusters of the species and we integrated phylogenetic and comparative genomic analyses to unravel the duplicative history of the genes that encode the subunits of structurally distinct mudskipper Hb isoforms (isoHbs). TheB. pectinirostrisisoHbs exhibit high intrinsic O2-affinities, similar to those of hypoxia-tolerant, water-breathing teleosts, and remarkably large Bohr effects. Genomic analysis of conserved synteny revealed that the genes that encode the α-type subunits of the two main adult isoHbs are members of paralogous gene clusters that represent products of the teleost-specific whole-genome duplication. Experiments revealed no appreciable difference in the oxygenation properties of co-expressed isoHbs in spite of extensive amino acid divergence between the alternative α-chain subunit isoforms. It therefore appears that the ability to switch between aquatic and aerial respiration does not necessarily require a division of labor between functionally distinct isoHbs with specialized oxygenation properties.Summary statementThe blue-spotted mudskipper routinely switches between aquatic and aerial respiration. This respiratory versatility is associated with properties of hemoglobin-oxygen transport that are similar to those found in hypoxia-adapted water-breathing fishes.
Bacterial secondary metabolite biosynthetic potential in soil varies with phylum, depth, and vegetation type
Authors: Sharrar Allison M. , Crits-Christoph Alexander , Méheust Raphaël , Diamond Spencer , Starr Evan P. , Banfield Jillian F. 
Published: October 2019

AbstractBacteria isolated from soils are major sources of specialized metabolites, including antibiotics and other compounds with clinical value that likely shape interactions among microbial community members and impact biogeochemical cycles. Yet, isolated lineages represent a small fraction of all soil bacterial diversity. It remains unclear how the production of specialized metabolites varies across the phylogenetic diversity of bacterial species in soils, and whether the genetic potential for production of these metabolites differs with soil type. We sampled soils and saprolite from three sites in a northern California Critical Zone Observatory with varying vegetation and bedrock characteristics and used metagenomic sequencing and assembly to reconstruct 1,334 microbial genomes containing diverse biosynthetic gene clusters (BGCs) for secondary metabolite production. We obtained genomes for prolific producers of secondary metabolites, including novel groups within the Actinobacteria, Chloroflexi and candidate phylum Dormibactereota. Surprisingly, one genome of a Candidate Phyla Radiation bacterium encoded for a ribosomally synthesized linear azole/azoline-containing peptide, a capacity we found in other publicly available CPR bacterial genomes. Overall, bacteria with higher biosynthetic potential were enriched in shallow soils and grassland soils, with patterns of abundance of BGC type varying by taxonomy.
AP-1B facilitates endocytosis during cell migration
Authors: Kell Margaret Johnson , Ang Su Fen , Pigati Lucy , Halpern Abby , Fölsch Heike 
Published: October 2019

ABSTRACTThe epithelial cell-specific clathrin adaptor AP-1B has a well-established role in polarized sorting of cargos to the basolateral membrane. Here we demonstrate a novel function for AP-1B during collective cell migration of epithelial sheets. We show that AP-1B colocalized with β1 integrin in focal adhesions during cell migration using confocal microscopy and total internal reflection fluorescence (TIRF) microscopy on fixed specimens. Further, AP-1B labeling in cell protrusion was distinct from labeling for the canonical endocytic adaptor complex AP-2. Using stochastic optical reconstruction microscopy (STORM) and live TIRF imaging we identified numerous AP-1B-coated structures at or close to the plasma membrane in cell protrusions. Importantly, immuno-electron microscopy (EM) showed AP-1B in clathrin-coated pits and budding vesicles at the plasma membrane during cell migration. Our data therefore established a novel function for AP-1B in endocytosis. We further show that β1 integrin was dependent on AP-1B and its co-adaptor, autosomal recessive hypercholesterolemia protein (ARH), for sorting to the basolateral membrane. Notably, we found that expression of AP-1B (and ARH) slowed epithelial-cell migration, and qRT-PCR analysis of human epithelial-derived cell lines revealed a loss of AP-1B expression in highly metastatic cancer cells indicating that AP-1B-facilitated endocytosis during cell migration might be an anti-cancer mechanism.
Glucocorticoids mediate egg rejection in a brood parasite host
Authors: Abolins-Abols Mikus , Hauber Mark E. 
Published: October 2019

AbstractAvian brood parasites and their hosts are engaged in a coevolutionary battle that can result in the evolution of sophisticated trickery by parasites and novel defence behaviours in hosts. Despite the clear evolutionary and ecological significance of host behaviour, however, we know very little about the mechanisms that regulate host defences, which limits our understanding of both inter- and intraspecific variation in host responses to parasitism. Here we tested whether corticosterone, a hormone known to be upregulated in hosts exposed to parasitism, also mediates one of the most frequent host defences – the rejection of foreign eggs. We experimentally reduced corticosterone levels in free-living brood parasite hosts, American robins Turdus migratorius, using mitotane and found that the likelihood of model egg rejection was significantly lower in the mitotane-treated birds relative to the sham-treated birds. These results demonstrate a causal link between glucocorticoids and egg rejection in hosts of avian brood parasites, but the physiological and sensory-cognitive pathways that regulate this effect remain unknown.
Cre-assisted Fine-mapping of Neural Circuits using Orthogonal Split Inteins
Authors: Luan Haojiang , Kuzin Alexander , Odenwald Ward F. , White Benjamin H. 
Published: October 2019

Summary:Genetic methods for targeting small numbers of neurons of a specific type are critical for mapping the brain circuits underlying behavior. Existing methods can provide exquisite targeting precision in favorable cases, but for many cases alternative techniques will be required. Here, we introduce a new step-wise combinatorial method for sequentially refining neuronal targeting: Depending on the restriction achieved at the first step, a second step can be easily implemented to further refine expression. For both steps, the new method relies on two independent intersections. The primary intersection targets neurons based on their developmental origins (i.e. lineage) and terminal identities, while the second intersection limits the number of lineages represented in the primary intersection by selecting lineages with overlapping activity of two distinct enhancers during neurogenesis. Our method relies critically on two libraries of 134 transgenic fly lines that express fragments of a split Cre recombinase under the control of distinct neuroblast enhancers. The split Cre fragments are fused to non-interacting pairs of split inteins, which ensure reconstitution of full-length and active Cre when all fragments are expressed in the same cell. Our split Cre system, together with its open source libraries, represent off-the-shelf components that should facilitate the targeting and characterization of brain circuits inDrosophila. Our methodology may also prove useful in other genetic model organisms.
Synthetic lethality across normal tissues is strongly associated with cancer risk, onset, and tumor suppressor specificity
Authors: Cheng Kuoyuan , Nair Nishanth Ulhas , Lee Joo Sang , Ruppin Eytan 
Published: October 2019

AbstractVarious characteristics of cancers exhibit tissue-specificity, including lifetime cancer risk, onset age and cancer driver genes. Previously, the large variation in cancer risk across human tissues was found to strongly correlate with the number of stem cell divisions and abnormal DNA methylation levels occurring in them. Here we study the role of another potentially important factor, synthetic lethality, in cancer risk. Analyzing transcriptomics data in the GTEx compendium we quantify the extent of co-inactivation of cancer synthetic lethal (cSL) gene pairs in normal tissues and find that normal tissues with more down-regulated cSL gene pairs have lower and delayed cancer risk. We also show that the tissue-specificity of numerous tumor suppressor genes is strongly associated with the expression of their cSL partner genes in the corresponding normal tissues. Overall, our findings uncover the role of synthetic lethality as a novel important factor involved in tumorigenesis.
Meta-analytic clustering dissociates brain activity and behavior profiles across reward processing paradigms
Authors: Flannery Jessica S. , Riedel Michael C. , Bottenhorn Katherine L. , Poudel Ranjita , Salo Taylor , Hill-Bowen Lauren D. , Laird Angela R. , Sutherland Matthew T. 
Published: October 2019

ABSTRACTReward learning is a ubiquitous cognitive mechanism guiding adaptive choices and behaviors, and when impaired, can lead to considerable mental health consequences. Reward-related functional neuroimaging studies have begun to implicate networks of brain regions essential for processing various peripheral influences (e.g., risk, subjective preference, delay, social context) involved in the multifaceted reward processing construct. To provide a more complete neurocognitive perspective on reward processing that synthesizes findings across the literature while also appreciating these peripheral influences, we utilized emerging meta-analytic techniques to elucidate brain regions, and in turn networks, consistently engaged in distinct aspects of reward processing. Using a data-driven, meta-analytic,k-means clustering approach, we dissociated seven meta-analytic groupings (MAGs) of neuroimaging results (i.e., brain activity maps) from 749 experimental contrasts across 176 reward processing studies involving 13,358 healthy participants. We then performed an exploratory functional decoding approach to gain insight into the putative functions associated with each MAG. We identified a seven-MAG clustering solution which represented dissociable patterns of convergent brain activity across reward processing tasks. Additionally, our functional decoding analyses revealed that each of these MAGs mapped onto discrete behavior profiles that suggested specialized roles in predicting value (MAG-1 & MAG-2) and processing a variety of emotional (MAG-3), external (MAG-4 & MAG-5), and internal (MAG-6 & MAG-7) influences across reward processing paradigms. These findings support and extend aspects of well-accepted reward learning theories and highlight large-scale brain network activity associated with distinct aspects of reward processing.
ROS production by localized SCHENGEN receptor module drives lignification at subcellular precision
Authors: Fujita Satoshi , De Bellis Damien , Edel Kai H. , Köster Phillipp , Andersen Tonni Grube , Schmid-Siegert Emanuel , Dénervaud Tendon Valérie , Pfister Alexandre , Marhavý Peter , Ursache Robertas , Doblas Verónica G. , Daraspe Jean , Creff Audrey , Ingram Gwyneth , Kudla Jörg , Geldner Niko 
Published: October 2019

AbstractProduction of reactive-oxygen species (ROS) by NADPH oxidases (NOXs) impacts many processes in animals and plants and many plant receptor pathways involve rapid, NOX-dependent increases of ROS. Yet, their general reactivity has made it challenging to pinpoint the precise role and direct cellular targets of ROS. A well-understood ROS target in plants are lignin peroxidases in the cell wall. Lignin can be deposited with exquisite spatial control, but the underlying mechanisms have remained elusive. Here we establish a full kinase signaling relay that exerts direct, spatial control over ROS production and lignification within the cell wall. We show that polar localization of a single kinase component is crucial for pathway function. Our data indicates that an intersection of more broadly localized components allows for micrometer-scale precision of lignification and that this system is triggered through initiation of ROS production as a critical peroxidase co-substrate.
Genome-wide association study of cryptosporidiosis in infants implicatesPRKCA
Authors: Wojcik Genevieve L. , Korpe Poonum , Marie Chelsea , Mychaleckyj Josyf , Kirkpatrick Beth D. , Rich Stephen S. , Concannon Patrick , Faruque A. S. G. , Haque Rashidul , Petri William A. , Duggal Priya 
Published: October 2019

AbstractDiarrhea is a major cause of both morbidity and mortality worldwide, especially among young children. Cryptosporidiosis is a leading cause of diarrhea in children, particularly in South Asia and Sub-Saharan Africa where it is responsible for over 200,000 deaths per year. Beyond the initial clinical presentation of diarrhea, it is associated with long term sequelae such as malnutrition and neurocognitive developmental deficits. Risk factors include poverty and overcrowding, yet not all children with these risk factors and exposure are infected, nor do all infected children develop symptomatic disease. One potential risk factor to explain these differences is their human genome. To identify genetic variants associated with symptomatic cryptosporidiosis, we conducted a genome-wide association study (GWAS) examining 6.5 million single nucleotide polymorphisms (SNPs) in 873 children from three independent cohorts in Dhaka, Bangladesh: the Dhaka Birth Cohort (DBC), the Performance of Rotavirus and Oral Polio Vaccines in Developing Countries (PROVIDE) study, and the Cryptosporidiosis Birth Cohort (CBC). Associations were estimated separately for each cohort under an additive model, adjusting for height-for-age Z-score at 12 months of age, the first two principal components to account for population substructure, and genotyping batch. The strongest meta-analytic association was with rs58296998 (P=3.73×10−8), an intronic SNP and eQTL ofPRKCA. Each additional risk allele conferred 2.4 times the odds of cryptosporidiosis in the first year of life. This genetic association suggests a role for protein kinase C alpha in pediatric cryptosporidiosis and warrants further investigation. This article was submitted to an online preprint archive.(1)ImportanceGlobally, one of the major causes of pediatric morbidity and mortality remains diarrhea. The initial symptoms of diarrhea can often lead to long term consequences for the health of young children, such as malnutrition and neurocognitive developmental deficits. Despite many children having similar exposures to infectious causes of diarrhea, not all develop symptomatic disease, indicating a possible role for human genetic variation. Here we conducted a genetic study of susceptibility to symptomatic disease associated with Cryptosporidium infection (a leading cause of diarrhea) in three independent cohorts of infants from Dhaka, Bangladesh. We identified a genetic variant within protein kinase c alpha (PRKCA) associated with higher risk of cryptosporidiosis in the first year of life. These results indicate a role for human genetics in susceptibility to cryptosporidiosis and warrant further research to elucidate the mechanism.
High-Throughput Translational Profiling with riboPLATE-seq
Authors: Metz Jordan B. , Hornstein Nicholas J. , Das Sharma Sohani , Worley Jeremy , Gonzalez Christian , Sims Peter A. 
Published: October 2019

ABSTRACTProtein synthesis is dysregulated in many diseases, but we lack a systems-level picture of how signaling molecules and RNA binding proteins interact with the translational machinery, largely due to technological limitations. Here we present riboPLATE-seq, a scalable method for generating paired libraries of ribosome-associated and total mRNA. As an extension of the PLATE-seq protocol, riboPLATE-seq utilizes barcoded primers for pooled library preparation, but additionally leverages rRNA immunoprecipitation on whole polysomes to measure ribosome association (RA). We compare RA to its analogue in ribosome profiling and RNA sequencing, translation efficiency, and demonstrate both the performance of riboPLATE-seq and its utility in detecting translational alterations induced by specific inhibitors of protein kinases.
Fibrotic scar after experimental autoimmune encephalomyelitis inhibits oligodendrocyte differentiation
Authors: Yahn Stephanie L. , Li Jiajun , Goo Irene , Gao Han , Brambilla Roberta , Lee Jae K. 
Published: October 2019

AbstractRemyelination failure is a crucial component of disease progression in the autoimmune demyelinating disease Multiple Sclerosis (MS). The regenerative capacity of oligodendrocyte progenitor cells (OPCs) to replace myelinating oligodendrocytes is likely influenced by many aspects of the lesion environment including inflammatory signaling and extracellular matrix (ECM) deposition. These features of MS lesions are typically attributed to infiltrating leukocytes and reactive astrocytes. Here we demonstrate that fibroblasts also contribute to the inhibitory environment in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Using Col1α1GFPtransgenic mice, we show that perivascular fibroblasts are activated in the spinal cord at EAE onset, and infiltrate the parenchyma by the peak of behavioral deficits where they are closely associated with areas of demyelination, myeloid cell accumulation, and ECM deposition. We further show that both fibroblast conditioned media and fibroblast ECM inhibit the differentiation of OPCs into mature oligodendrocytes. Taken together, our results indicate that the fibrotic scar is a major component of EAE pathology that leads to an inhibitory environment for remyelination, thus raising the possibility that anti-fibrotic mechanisms may serve as novel therapeutic targets for MS.
Synthetic biogenesis of chromoplasts from leaf chloroplasts
Authors: Llorente Briardo , Torres-Montilla Salvador , Morelli Luca , Florez-Sarasa Igor , Ezquerro Miguel , D’andrea Lucio , Majer Eszter , Troncoso Adrian , Fernie Alisdair R. , Daròs José A. , Rodriguez-Concepcion Manuel 
Published: October 2019

AbstractPlastids, the defining organelles of plant cells, undergo physiological and morphological changes to fulfill distinct biological functions. In particular, the differentiation of chloroplasts into chromoplasts results in an enhanced storage capacity for carotenoids with industrial and nutritional value such as beta-carotene (pro-vitamin A). Here, we show that synthetically inducing a burst in the production of phytoene, the first committed intermediate of the carotenoid pathway, elicits an artificial chloroplast-to-chromoplast differentiation in leaves. Phytoene overproduction initially interferes with photosynthesis, acting as a metabolic threshold switch mechanism that weakens chloroplast identity. In a second stage, phytoene conversion into downstream carotenoids is required for the differentiation of chromoplasts. Our findings reveal that lowering the photosynthetic capacity of chloroplasts and increasing the production of carotenoids are not just the consequence but an absolute requirement for chromoplast differentiation, which additionally involves a concurrent reprogramming of nuclear gene expression and plastid morphology for improved carotenoid storage.