bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation ofTH-Cre knock-in cell lines for detection and specific targeting of stem cell-derived dopaminergic neurons
Authors: Fiorenzano A , Nelander Wahlestedt J , Parmar M 
Published: July 2020

AbstractThe focal and progressive degeneration of dopaminergic (DA) neurons in ventral midbrain has made Parkinson’s disease (PD) a particularly interesting target of cell-based therapies. However, ethical issues and limited tissue availability have so far hindered the widespread use of human fetal tissue in cell-replacement therapy. DA neurons derived from human pluripotent stem cells (hPSCs) offer unprecedented opportunities to access a renewable source of cells suitable for PD therapeutic applications. To better understand the functional properties of stem-cell derived DA neurons, we generated targeted hPSC lines with the gene coding for Cre recombinase knocked into theTHlocus. When combined with flexed GFP, they serve as reporter cell lines able to identify and isolate TH+ neuronsin vitroand after transplantationin vivo. TheseTH-Cre lines provide a valuable genetic tool to manipulate DA neurons useful for the design of more precise DA differentiation protocols and the study of these cells after transplantation in pre-clinical animal models of PD.
Intermolecular Channels Direct Crystal Orientation in Mineralized Collagen
Authors: Xu YiFei , Nudelman Fabio , Eren E. Deniz , Wirix Maarten J. M. , Cantaert Bram , Nijhuis Wouter H. , Hermida-Merino Daniel , Portale Giuseppe , Bomans Paul H. H. , Ottmann Christian , Friedrich Heiner , Bras Wim , Akiva Anat , Orgel Joseph P. R. O. , Meldrum Fiona C. , Sommerdijk Nico A. J. M. 
Published: July 2020

ABSTRACTThe mineralized collagen fibril is the basic building block of bone, commonly pictured as a parallel array of ultrathin carbonated hydroxyapatite (HAp) platelets distributed throughout the collagen. This orientation is often attributed to an epitaxial relationship between the HAp and collagen molecules inside 2D voids within the fibril. Although recent studies have questioned this model, the structural relationship between the collagen matrix and HAp, and the mechanisms by which collagen directs mineralization remain unclear. Here, we use XRD to reveal that the voids in the collagen are in fact cylindrical pores with diameters of ∼2 nm, while electron microscopy shows that the HAp crystals in bone are only uniaxially oriented with respect to the collagen. Fromin vitromineralization studies with HAp, CaCO3and γ-FeOOH we conclude that confinement within these pores, together with the anisotropic growth of HAp, dictates the orientation of HAp crystals within the collagen fibril.
KLF4 Recruits SWI/SNF to Increase Chromatin Accessibility and Reprogram the Endothelial Enhancer Landscape under Laminar Shear Stress
Authors: Moonen Jan-Renier A.J. , Chappell James , Shi Minyi , Shinohara Tsutomu , Li Dan , Mumbach Maxwell R. , Zhang Fan , Nasser Joseph , Mai Daniel H. , Taylor Shalina , Wang Lingli , Metzger Ross J. , Chang Howard Y. , Engreitz Jesse M. , Snyder Michael P. , Rabinovitch Marlene 
Published: July 2020

AbstractPhysiologic laminar shear stress (LSS) induces an endothelial gene expression profile that is vasculo-protective. In this report, we delineate how LSS mediates changes in the epigenetic landscape to promote this beneficial response. We show that under LSS, KLF4 interacts with the SWI/SNF nucleosome remodeling complex to increase accessibility at enhancer sites that promote expression of homeostatic endothelial genes. By combining molecular and computational approaches we discovered enhancers that loop to promoters of known and novel KLF4- and LSS-responsive genes that stabilize endothelial cells and suppress inflammation, such asBMPR2andDUSP5. By linking enhancers to genes that they regulate under physiologic LSS, our work establishes a foundation for interpreting how non-coding DNA variants in these regions might disrupt protective gene expression to influence vascular disease.
Phylogeny and biogeography ofCeibaMill. (Malvaceae, Bombacoideae)
Authors: Pezzini Flávia Fonseca , Dexter Kyle G. , de Carvalho-Sobrinho Jefferson G. , Kidner Catherine A. , Nicholls James A. , de Queiroz Luciano P. , Pennington R. Toby 
Published: July 2020

ABSTRACTThe Neotropics is the most species-rich area in the world and the mechanisms that generated and maintain its biodiversity are still debated. This paper contributes to the debate by investigating the evolutionary and biogeographic history of the genusCeibaMill. (Malvaceae: Bombacoideae).Ceibacomprises 18 mostly neotropical species endemic to two major biomes, seasonally dry tropical forests (SDTFs) and rain forests and its species are one of the most characteristic elements of neotropical SDTF, one of the most threatened biomes in the tropics. Phylogenetic analyses of DNA sequence data from the nuclear ribosomal internal transcribed spacers (ITS) for 30 accessions representing 14 species ofCeibarecovered the genus as monophyletic and showed geographical and ecological structure in three main clades: (i) a rain forest lineage of nine accessions ofC. pentandrasister to the remaining species; (ii) a highly supported clade composed ofC. schottiiandC. aesculifoliafrom Central American and Mexican SDTF plus two accessions ofC. samaumafrom inter Andean valleys from Peru; and (iii) a highly supported South American SDTF clade including 10 species showing little sequence variation. Within this South American clade, no species represented by multiple accessions were resolved as monophyletic. We demonstrate that the patterns of species age, monophyly and geographical structure previously reported for SDTF species within the Leguminosae family are not shared byCeiba, suggesting that further phylogenetic studies of unrelated groups are required.HIGHLIGHTSThis paper provides a well sampled phylogeny of the iconic genusCeiba, one of the most characteristic tree genera of neotropical Seasonally Dry Tropical Forest (SDTF).There is a clear phylogenetic signal for biome preference and geographic structure inCeiba.We estimate a mid Miocene origin forCeiba, with the stem node age of the genus estimated at 21.1 Ma and the crown node age at 12.7 Ma.Ceibaspecies have young stem ages in the SDTF clade but old stem ages in rain forest species.Patterns of species age, monophyly, ecological and geographical structure reported for SDTF species are only partially shared byCeiba, an iconic genus of neotropical SDTF.
Metabolic features of mouse and human retinas: rods vs. cones, macula vs. periphery, retina vs. RPE
Authors: Li Bo , Zhang Ting , Liu Wei , Wang Yekai , Xu Rong , Zeng Shaoxue , Zhang Rui , Zhu Siyan , Gillies Mark C , Zhu Ling , Du Jianhai 
Published: July 2020

AbstractPhotoreceptors, especially cones, which are enriched in the human macula, have high energy demands, making them vulnerable to metabolic stress. Metabolic dysfunction of photoreceptors and their supporting retinal pigment epithelium (RPE) is an important underlying cause of degenerative retinal diseases. However, how cones and the macula support their exorbitant metabolic demand and communicate with RPE is unclear. By profiling metabolite uptake and release and analyzing metabolic genes, we have found cone-rich retinas and human macula share specific metabolic features with upregulated pathways in pyruvate metabolism, mitochondrial TCA cycle and lipid synthesis. Human neural retina and RPE have distinct but complementary metabolic features. Retinal metabolism centers on NADH production and neurotransmitter biosynthesis. The retina needs aspartate to sustain its aerobic glycolysis and mitochondrial metabolism. RPE metabolism is directed toward NADPH production and biosynthesis of acetyl-rich metabolites, serine and others. RPE consumes multiple nutrients, including proline, to produce metabolites for the retina.
ThePeroxiredoxin 6gene plays a critical role in the homeostatic regulation of fear response
Authors: Phasuk Sarayut , Pairojana Tanita , Suresh Pavithra , Huang Shun-Ping , Pakaprot Narawut , Chompoopong Supin , Yang Chee-Hing , Chang Hsueh-Kai , Chen Chien-Chang , Liu Ingrid Y. 
Published: July 2020

AbstractPeroxiredoxin 6 (PRDX6) is a multifunctional enzyme implicated in redox regulation and expressed in many organs including the brain. It is known to participate in many psychiatric functions, but its role in fear memory is unknown. The present study demonstrates thatPRDX6plays a critical role in the regulation of fear response. UsingPrdx6knockout (Prdx6−/−) mice, we identified that PRDX6 acts as a suppressor in fear memory formation. Lack ofPrdx6leads to the faster fear acquisition and enhanced contextual fear response. This phenomenon was confirmed by the fact that injection of lentivirus-carried human PRDX6-V5 into the hippocampus ofPrdx6−/−mice restored the enhanced fear response to the wild-type level. In the hippocampus ofPrdx6−/−mice, calcium-dependent PLA2 level was increased, which may compensate for the lack of aiPLA2 function to maintain normal synaptic membranes. On the other hand, reactive oxygen species (ROS) levels did not change, indicating loss of peroxidase function did not affect the regulation of fear response.
ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain
Authors: Lim Jormay , Chu Ya-Cherng , Hao Chen-Ming , Liao Wei-Hao , Lin Shao-Shien , Hsu Sherry , Tai Hsiao-Hsin , Chien Ya-Chih , Lai Dar-Ming , Chen Wen-Shiang , Chen Chih-Cheng , Wang Jaw-Lin 
Published: July 2020

ABSTRACTAccumulating evidence has shown transcranial low-intensity ultrasound can be potentially a non-invasive neural modulation tool to treat brain diseases. However, the underlying mechanism remains elusive, because the majority of studies on animal models applying rather high-intensity ultrasound that cannot be safely used in humans. Here we showed low-intensity ultrasound was able to activate neurons in the mouse brain and repeated ultrasound stimulation resulted in adult neurogenesis in specific brain regions.In vitrocalcium imaging studies showed that a specific ultrasound stimulation mode, which combined with both ultrasound-induced pressure and acoustic streaming mechanotransduction, is required to activate cultured cortical neurons. ASIC1a and the tether-mode mechanotransduction were involved in the low-intensity ultrasound-mediated mechanotransduction and cultured neuron activation, which was inhibited by ASIC1a blockade and cytoskeleton-modified agents. In contrast, the inhibition of mechanical sensitive channels involved in bilayer-model mechanotransduction like Piezo or TRP proteins did not affect the ultrasound-mediated neuronal activation.SIGNIFICANCECNS neurons have no sensory function, protected by the skull. For this reason, brain neuromodulation by ultrasound were either done at a high intensity or through auditory nerves. We demonstrate in this study CNS neurons react to ultrasound stimulation at an intensity (5 mW/cm2) far lower than typical therapeutic ultrasound (>30 mW/cm2). Using micropipette ultrasound in calcium imaging, we show the reactions of CNS neurons to ultrasound is through ASIC1a channels, pointing to the molecular basis for direct ultrasound neuromodulation at low intensity. Furthermore, we also show evidence of neurogenesis with the same ultrasound stimulation, suggesting potential therapeutic translation.
Species coexistence and overlapping distributions in a metacommunity are compatible with niche differences and competition at a local scale
Authors: Dubart Maxime , David Patrice , Ben-Ami Frida , Haag Christoph R. , Pajunen V. Ilmari , Ebert Dieter 
Published: July 2020

AbstractNiche partitioning is the most studied factor structuring communities of competing species. In fragmented landscapes, however, a paradox can exist: different taxa may competitively dominate different types of habitat patches, resulting in a form of spatial niche partitioning, yet differences in long-term distributions among species can appear surprisingly small. This paradox is illustrated by an emblematic metacommunity - that ofDaphniaspp. in rockpools on the Finnish Baltic coast, where three species compete with each other, have distinct ecological preferences, yet largely overlap in long-term distributions. Here we examine how metacommunity models that explicitly estimate species-specific demographic parameters can solve the apparent paradox. Our research confirms previous studies that local extinction rates are influenced by environmental variables in a strong and species-specific way and are considerably increased by interspecific competition. Yet, our simulations show that this situation exists alongside interspecific differences in realized niches that are, overall, small, and identified three main explanations for this compatibility. Our results illustrate how state-space modelling can clarify complex metacommunity dynamics and explain why local competition and niche differentiation do not always scale up to the landscape level.
Acoel single-cell transcriptomics: cell-type analysis of a deep branching bilaterian
Authors: Duruz Jules , Kaltenrieder Cyrielle , Ladurner Peter , Bruggmann Rémy , Martìnez Pedro , Sprecher Simon G. 
Published: July 2020

AbstractBilaterian animals display a wide variety of cell types, organized into defined anatomical structures and organ systems, which are mostly absent in pre-bilaterian animals. Xenacoelomorpha are an early-branching bilaterian phylum displaying an apparently relatively simple anatomical organization that have greatly diverged from other bilaterian clades. In this study, we use whole-body single-cell transcriptomics on the acoelIsodiametra pulchrato identify and characterize different cell types. Our analysis identifies the existence of ten major cell-type categories in acoels all contributing to main biological functions of the organism: metabolism, locomotion and movements, behavior, defense and development. Interestingly, while most cell clusters express core fate markers shared with other animal clades, we also describe a surprisingly large number of clade-specific marker genes, suggesting the emergence of clade-specific common molecular machineries functioning in distinct cell types. Together, these results provide novel insight into the evolution of bilaterian cell-types and open the door to a better understanding of the origins of the bilaterian body plan and their constitutive cell types.
Profiling the initial burst of beneficial genetic diversity in clonal cell populations to anticipate evolution
Authors: Deatherage Daniel E. , Barrick Jeffrey E. 
Published: July 2020

AbstractClonal populations of cells continuously evolve new genetic diversity, but it takes a significant amount of time for the progeny of a single cell with a new beneficial mutation to outstrip both its ancestor and competitors to fully dominate a population. If these driver mutations can be discovered earlier—while they are still extremely rare—and profiled in large numbers, it may be possible to anticipate the future evolution of similar cell populations. For example, one could diagnose the likely course of incipient diseases, such as cancer and bacterial infections, and better judge which treatments will be effective, by tracking rare drug-resistant variants. To test this approach, we replayed the first 500 generations of a >70,000-generationEscherichia coliexperiment and examined the trajectories of new mutations in eight genes known to be under positive selection in this environment in six populations. By employing a deep sequencing procedure using unique molecular identifiers and target enrichment we were able to track 301 beneficial mutations at frequencies as low as 0.01% and infer the fitness effects of 240 of these. Distinct molecular signatures of selection on protein structure and function were evident for the three genes in which beneficial mutations were most common (nadR, pykF,andtopA). We detected mutations hundreds of generations before they became dominant and tracked beneficial alleles in genes that were not mutated in the long-term experiment until thousands of generations had passed. This type of targeted adaptome sequencing approach could function as an early warning system to inform interventions that aim to prevent undesirable evolution.
Natural variation in the sequestosome-related gene,sqst-5, underlies zinc homeostasis inCaenorhabditis elegans
Authors: Evans Kathryn S. , Zdraljevic Stefan , Stevens Lewis , Collins Kimberly , Tanny Robyn E. , Andersen Erik C. 
Published: July 2020

AbstractZinc is an essential trace element that acts as a co-factor for many enzymes and transcription factors required for cellular growth and development. Altering intracellular zinc levels can produce dramatic effects ranging from cell proliferation to cell death. To avoid such fates, cells have evolved mechanisms to handle both an excess and a deficiency of zinc. Zinc homeostasis is largely maintained via zinc transporters, permeable channels, and other zinc-binding proteins. Variation in these proteins might affect their ability to interact with zinc, leading to either increased sensitivity or resistance to natural zinc fluctuations in the environment. We can leverage the power of the roundworm nematodeCaenorhabditis elegansas a tractable metazoan model for quantitative genetics to identify genes that could underlie variation in responses to zinc. We found that the laboratory-adapted strain (N2) is resistant and a natural isolate from Hawaii (CB4856) is sensitive to micromolar amounts of exogenous zinc supplementation. Using a panel of recombinant inbred lines, we identified two large-effect quantitative trait loci (QTL) on the left arm of chromosome III and the center of chromosome V that are associated with zinc responses. We validated and refined both QTL using near-isogenic lines (NILs) and identified a naturally occurring deletion insqst-5, a sequestosome-related gene, that is associated with resistance to high exogenous zinc. We found that this deletion is relatively common across strains within the species and that variation insqst-5is associated with zinc resistance. Our results offer a possible mechanism for how organisms can respond to naturally high levels of zinc in the environment and how zinc homeostasis varies among individuals.Author summaryZinc, although an essential metal, can be toxic if organisms are exposed to concentrations that are too high or too low. To prevent toxicity, organisms have evolved mechanisms to regulate zinc uptake from the environment. Here, we leveraged genetic variation between two strains of the roundwormCaenorhabditis eleganswith different responses to high exogenous zinc to identify genes that might be involved in maintaining proper zinc levels. We identified four loci that contributed to differential zinc responses. One of these loci was the sequestosome-related genesqst-5. We discovered that targeted deletions ofsqst-5caused an increase in resistance to zinc. Although SQST-5 contains a conserved zinc-binding protein domain, it has yet to be directly implicated in theC. eleganszinc response pathway. We identified two common forms of genetic variation insqst-5among 328 distinct strains, suggesting that variation insqst-5must have emerged multiple times, perhaps in response to an environment of high zinc. Overall, our study suggests a natural context for the evolution of zinc response mechanisms.
Stable isotope (C, N, O, and H) study of a comprehensive set of feathers from twoSetophaga citrina
Authors: Deme Samiksha , Yeung Laurence Y. , Sun Tao , Lee Cin-Ty A. 
Published: July 2020

AbstractOxygen, hydrogen, carbon and nitrogen stable isotopes were measured on a comprehensive sampling of feathers from two spring Hooded Warblers (Setophaga citrina) in Texas to evaluate isotopic variability between feathers and during molt. Isotopic homogeneity within each bird was found across all four isotopic systems, supporting the hypothesis that molt in these neotropical migrants is fully completed on the breeding grounds. Moreover, this homogeneity suggests that the isotopic composition of a single feather is typically representative of the whole songbird. However, each bird also has outlier feathers, which could signify regrowth of lost feathers after prebasic molt.
Phenotyping cowpea accessions at the seedling stage for drought tolerance using the pot method
Authors: Nkomo Gabriel V. , Sedibe Moosa M. , Mofokeng Maletsema A. 
Published: July 2020

AbstractOne of the most important screening techniques used in cowpea selection for drought tolerance is screening at the seedling stage. The objective of this study was to phenotype 60 cowpea genotypes for seedling drought tolerance in screen houses (glasshouse and greenhouse). A triplicated 6 × 10 alpha lattice design with four blocks was used for the experiments. After planting, pots were watered to field capacity, thereafter watering was completely withheld for 4 weeks after planting (WAP), when plants were at the three-leaf stage. Principal component analysis revealed that of the 14 variables, the first four expressed more than 1 eigenvalue. Data showed that PC1, PC2, and PC3 contributed 39.3%, 15.2%, and 10% respectively, with 64.68% total variation. Bartlett’s test of sphericity was significant at p<0.05, while the Kaiser-Meyer-Olkin measure of sampling adequacy was 77. A PCA plot and biplot showed that the number of pods (NP), seeds per pod (SP), survival count (SC), pod weight (PWT), and stem wilting in week one (WWK1) had the most significant contributions to genetic variability to drought tolerance and to yield after stress imposition Based on the PCA, biplot, and cluster plot, the accessions IT 07-292-10, IT 07-274-2-9, IT90K-59, 835-911, RV 343, and IT 95K-2017-15 had the maximum variability in terms of number of pods, seeds per pod, survival count, pod weight and wilting in week one after drought imposition. Cowpea accessions 835-911, IT 07-292-10, RV 344, Kangorongondo, and IT 90K-59 were the major individuals that contributed mainly to domain information model (DIM) 1 and 2. The accessions that contributed the least were IT 89KD288, Chibundi mavara, and TVU12746. Thirty-six cowpea accessions from both screen houses were tolerant to drought, 15 were moderately tolerant, while 23 were susceptible. The findings of the study provided a useful tool for screening and determining drought-tolerant and susceptible accessions at the seedling stage. Thirty-six cowpea accessions from both screen houses were tolerant to drought as well as those that showed great variability can be used as parents in future cowpea breeding programmes.