bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-read Data Revealed Structural Diversity in Human Centromere Sequences
Authors: Suzuki Yuta , Myers Gene , Morishita Shinichi 
Published: September 2019

ABSTRACTCentromeres invariably serve as the loci of kinetochore assembly in all eukaryotic cells, but their underlying DNA sequences evolve rapidly. Human centromeres are characterized by their extremely repetitive structures, i.e., higher-order repeats, rendering the region one of the most difficult parts of the genome to assess. Consequently, our understanding of centromere sequence variations across human populations is limited. Here, we analyzed chromosomes 11, 17, and X using long sequencing reads of two European and two Asian genomes, and our results show that human centromere sequences exhibit substantial structural diversity, harboring many novel variant higher-order repeats specific to individuals, while frequent single-nucleotide variants are largely conserved. Our findings add another dimension to our knowledge of centromeres, challenging the notion of stable human centromeres. The discovery of such diversity prompts further deep sequencing of human populations to understand the true nature of sequence evolution in human centromeres.
Single-cell genomics of uncultured bacteria reveals dietary fiber responders in the mouse gut microbiota
Authors: Chijiiwa Rieka , Hosokawa Masahito , Kogawa Masato , Nishikawa Yohei , Ide Keigo , Sakanashi Chikako , Takahashi Kai , Takeyama Haruko 
Published: September 2019

AbstractBackgroundThe gut microbiota can have dramatic effects on host metabolism; however, current genomic strategies for uncultured bacteria have several limitations that hinder their ability to identify responders to metabolic changes in the microbiota. In this study, we describe a novel single-cell genomic sequencing technique that can identify metabolic responders at the species level without the need for reference genomes, and apply this method to identify bacterial responders to an inulin-based diet in the mouse gut microbiota.ResultsInulin feeding changed the mouse fecal microbiome composition to increase Bacteroides spp., resulting in the production of abundant succinate in the mouse intestine. Using our massively parallel single-cell genome sequencing technique, named SAG-gel platform, we obtained 346 single-amplified genomes (SAGs) from mouse gut microbes before and after dietary inulin supplementation. After quality control, the SAGs were classified as 267 bacteria, spanning two phyla, four classes, seven orders, and 14 families, and 31 different strains of SAGs were graded as high- and medium-quality draft genomes. From these, we have successfully obtained the genomes of the dominant inulin-responders, Bacteroides spp., and identified their polysaccharide utilization loci and their specific metabolic pathways for succinate production.ConclusionsOur single-cell genomics approach generated a massive amount of SAGs, enabling a functional analysis of uncultured bacteria in the intestinal microbiome. This enabled us to estimate metabolic lineages involved in the bacterial fermentation of dietary fiber and metabolic outcomes such as short-chain fatty acid production in the intestinal environment based on the fibers ingested. The technique allows the in-depth isolation and characterization of uncultured bacteria with specific functions in the microbiota and could be exploited to improve human and animal health.
Rhythmic variations in prefrontal inter-neuronal correlations, their underlying mechanisms and their behavioral correlates
Authors: Ben Hadj Hassen S. , Gaillard C. , Astrand E. , Wardak C. , Ben Hamed S. 
Published: September 2019

SummaryFunctional neuronal correlations between pairs of neurons are thought to play an important role in neuronal information processing and optimal neuronal computations during attention, perception, decision-making and learning. These noise correlations are often assumed to be stable in time. However, recent studies suggest that cognitive processes are rhythmic, this rhythmicity accounting for variations in overt behavioral performance. Whether this rhythmicity coincides with variations in shared noise variability is unknown. Here, we perform simultaneous recordings from the macaque frontal eye fields, while animals are engaged in a spatial memory task. We report that noise correlations in prefrontal cortex fluctuate rhythmically in the high alpha (10-16Hz) and beta (20-30Hz) frequency ranges. Importantly, these rhythmic modulations in shared neuronal variability account for dynamic changes in overt behavioral performance. They also coincide with increased spike-LFP phase coupling in these specific frequency ranges, the spatial profile of which vary between superficial and deep cortical layers. Finally, we demonstrate, using an artificial neuronal model, that rhythmic variations in noise correlation oscillations parsimoniously arise from long range (LFP) and local spike-LFP phase coupling mechanisms. Thus a significant portion of noise correlation fluctuations can be attributed to long-range global network rhythmicity.
Design and Optimization Protocol for High-Dimensional Immunophenotyping Assays using Spectral Flow Cytometry
Authors: Ferrer-Font L , Pellefigues C , Mayer JU , Small S , Jaimes MC , Price KM 
Published: September 2019

ABSTRACTTechnological advances in fluorescence flow cytometry and an ever-expanding understanding of the complexity of the immune system has led to the development of large 20+ flow cytometry panels. Yet, as panel complexity and size increases, so does the difficulty involved in designing a high-quality panel, accessing the instrumentation capable of accommodating large numbers of parameters, and in analysing such high-dimensional data.A recent advancement is spectral flow cytometry, which in contrast to conventional flow cytometry distinguishes the full emission spectrum of each fluorochrome across all lasers, rather than identifying only the peak of emission. Fluorochromes with a similar emission maximum but distinct off-peak signatures can therefore be accommodated within the same flow cytometry panel, allowing greater flexibility in terms of panel design and fluorophore detection.Here, we highlight the specific characteristics regarding spectral flow cytometry and aim to guide users through the process of building, designing and optimising high-dimensional spectral flow cytometry panels using a comprehensive step-by-step protocol. Special considerations are also given for using highly-overlapping dyes and a logical selection process an optimal marker-fluorophore assignment is provided.
Responses of global waterbird populations to climate change vary with latitude
Authors: Amano Tatsuya , Székely Tamás , Wauchope Hannah S. , Sandel Brody , Nagy Szabolcs , Mundkur Taej , Langendoen Tom , Blanco Daniel , Michel Nicole L. , Sutherland William J. 
Published: September 2019

AbstractWhile climate change continues to present a major threat to global biodiversity and ecosystems, most research on climate change impacts do not have the resolution to detect changes in species abundance and are often limited to temperate ecosystems. This limits our understanding of global responses in species abundance—a determinant of ecosystem function and services—to climate change including in the highly-biodiverse tropics. We address this knowledge gap by quantifying abundance responses to climate change in waterbirds, an indicator taxon of wetland biodiversity, at 6,822 sites between −55° and 64°. Using 1,303,651 count records since 1990 of 390 species, we show that with temperature increase, the abundance of species and populations decreased at lower latitudes, particularly in the tropics, but increased at higher latitudes. These contrasting responses to temperature increase according to latitude indicate potential global-scale poleward shifts of species abundance under climate change, providing empirical support for predictions by earlier studies. The negative responses to temperature increase in tropical species and populations are of conservation concern, as they are often also threatened by other anthropogenic factors. Our results suggest that existing biases in studies towards temperate regions could underestimate the impact of climate change on waterbirds and other species.
Positive relation between arcuate fasciculus white matter fiber structure and severity of auditory hallucinations: A DTI tractography study
Authors: Falkenberg Liv E. , Westerhausen René , Johnsen Erik , Kroken Rune , Løberg Else-Marie , Beresniewicz Justyna , Kazimierczak Katarzyna , Kompus Kristiina , Ersland Lars , Hugdahl Kenneth 
Published: September 2019

AbstractThe arcuate fasciculus (AF) has been implicated in the pathology behind schizophrenia and auditory verbal hallucinations (AVHs). White matter tracts forming the arcuate fasciculus can be quantified and visualized using diffusion tensor imaging (DTI) tractography. Although there have been a number of studies on this topic, the results have been conflicting. Studying the underlying white matter structure of the AF could shed light on functional connectivity between temporal and frontal language areas in AVHs. The participants were 66 patients with a schizophrenia diagnosis, where AVHs were defined from the Positive and Negative Syndrome Scale (PANSS), and compared with a healthy control group. DTI was performed on a 3T MR scanner, and tensor estimation was done using deterministic streamline tractography. Statistical analysis of the data showed significantly longer tracts along the AF in patients with severe and frequent AVHs, as well as an overall significant asymmetry with longer fibers on the left side. In addition, there were significant positive correlations between PANSS scores and tract length, tract volume, and number of streamlines for the posterior AF segment on the left side. It is concluded that the present structural results complement previous functional findings of fronto-temporal connectivity in AVH patients.
The Brazilian Amazon Protected Area Network was largely unaffected by recent satellite-detectable fires
Authors: Bebber Daniel P. 
Published: September 2019

AbstractAugust 2019 saw dramatic increases in wildfires in the Brazilian Amazon, leading to arguments between Brazil and G7 leaders and widespread concern among conservationists. Popular media reports suggested that ‘swathes of the Amazon rainforest in Brazil are on fire’. Here we investigate the spatial distribution of fires through August 2019, showing that fires were largely restricted to deforested regions and areas with low canopy cover, particularly in unprotected areas that comprise half the region. In contrast, Brazil’s protected areas had one third as many fires, and forest in protected areas with high canopy cover was almost entirely unaffected by fire. Protected areas reduce deforestation and carbon emissions, and have proved largely untouched by recent fires. However, fires in closed-canopy forest cannot readily be detected by satellite remote-sensing and so this analysis likely underestimates the burned area in intact forest, both in protected and unprotected areas.
A quantitative binding model for the Apl protein, the dual purpose recombination-directionality factor and lysis-lysogeny regulator of bacteriophage 186
Authors: Cutts Erin , Egan J. Barry , Dodd Ian , Shearwin Keith 
Published: September 2019

AbstractThe Apl protein of bacteriophage 186 functions both as an excisionase and as a transcriptional regulator; binding to the phage attachment site (att), and also between the major early phage promoters (pR-pL). Like other recombination directionality factors (RDFs), Apl binding sites are direct repeats spaced one DNA helix turn apart. Here, we use in vitro binding studies with purified Apl and pR-pL DNA to show that Apl binds to multiple sites with high cooperativity, bends the DNA, and spreads from specific binding sites into adjacent non-specific DNA; features that are shared with other RDFs. By analysing Apl’s repression of pR and pL, and the effect of operator mutants in vivo with a simple mathematical model, we were able to extract estimates of binding energies for single specific and non-specific sites and for Apl cooperativity, revealing that Apl monomers bind to DNA with low sequence specificity but with strong cooperativity between immediate neighbours. This model fit was then independently validated with in vitro data. The model we employed here is a simple but powerful tool that enabled better understanding of the balance between binding affinity and cooperativity required for RDF function. A modelling approach such as this is broadly applicable to other systems.
Checklist and practical identification key for the cichlid fishes (Cichliformes: Cichlidae) of the La Plata drainage in Bolivia, including three new geographical records
Authors: Hablützel Pascal I. , Huanto Robert B. 
Published: September 2019

AbstractIn comparison with the Bolivian Amazon, the ichthyofauna of the La Plata drainage of Bolivia received relatively little attention historically. Until now, 14 species of cichlid fish have been registered from this area. After an exhaustive review of museum collections (Museo de Historia Natural Noel Kempff Mercado y Colección Boliviana de Fauna), we can report three additional species:Astronotus crassipinnis(Heckel, 1840),Mesonauta festivus(Heckel, 1840) andSatanoperca pappaterra(Heckel, 1840). Four other species, which have been listed in previous publications, can be confirmed for the La Plata drainage of Bolivia based on the examination of voucher specimens:Aequidens plagiozonatusKullander, 1984,Apistogramma commbrae(Regan, 1906),A. trifasciata(Eigenmann & Kennedy, 1903) andCrenicichla vittataHeckel, 1840. As such, 16 of the 17 species can be referenced with voucher specimens in museum collections. We also provide an identification key for the cichlid fish species of the study area.
Systemic muscle wasting and coordinated tumour response drive tumourigenesis
Authors: Newton Holly , Wang Yi-Fang , Camplese Laura , Brown André E.X. , Hirabayashi Susumu 
Published: September 2019

SUMMARYCancer cells demand excess nutrients to support their proliferation, but how tumours exploit extracellular amino acids during systemic metabolic pertubations remain incompletely understood. Here we use a Drosophila model of obesity-enhanced tumourigenesis to uncover a systemic host-tumour nutrient circuit that supports tumour growth. We demonstrate coordinate induction of systemic cachexia-like muscle wasting with tumour-autonomous SLC36-family amino acid transporter expression as a proline-scavenging programme to drive tumourigenesis. This coordinated induction of cachexia and SLC36-transporters pertains to human kidney cancer and associates with significantly worse survival outcomes. We identify Indole-3-propionic acid as an optimal amino acid derivative to rationally target the proline-dependency of tumour growth. Combining insights from whole-animal Drosophila models and human cancer database analysis provides a powerful approach towards the identification and therapeutic exploitation of the amino acid vulnerabilities of tumourigenesis in the context of perturbed systemic metabolic network.
Maternal hypothyroidism in mice influences glucose metabolism in adult offspring
Authors: Kemkem Yasmine , Nasteska Daniela , De Bray Anne , Bargi-Souza Paula , Peliciari-Garcia Rodrigo A. , Guillou Anne , Mollard Patrice , Hodson David J. , Schaeffer Marie 
Published: September 2019

ABSTRACTDuring pregnancy, maternal metabolic diseases and hormonal imbalance may alter fetal beta cell development and/or proliferation, thus leading to an increased risk for developing type 2 diabetes in adulthood. Although thyroid hormones play an important role in fetal endocrine pancreas development, the impact of maternal hypothyroidism on glucose homeostasis in adult offsprings remains poorly understood. Here, we show that when fed normal chow, adult mice born to hypothyroid mothers were more glucose-tolerant due to beta cell hyperproliferation and increased insulin sensitivity. However, following high fat feeding, these offsprings became profoundly hyperinsulinemic, insulin-resistant and glucose-intolerant compared to controls from euthyroid mothers. Suggesting presence of epigenetic changes, altered glucose metabolism was maintained in a second generation of animals. As such, gestational hypothyroidism induces long-term and persistent alterations in endocrine pancreas function, which may have important implications for type 2 diabetes prevention in affected individuals.SIGNIFICANCEDiabetes and hypothyroidism are two major public health issues, affecting ∼ 9 and 2 % of the population worldwide, respectively. As master metabolic gatekeepers, the thyroid hormones play an essential role in metabolism and fetal development. However, gestation increases demand on the thyroid axis in the mother, leading to hypothyroidism in 0.5 % of pregnancies. Maternal hypothyroidism is associated with deficits in fetal growth that may lead to long-term alterations in metabolism in the offspring. We therefore sought to investigate the effects of gestational hypothyroidism on glucose metabolism in adult offspring and their descendants, and how this may predispose to diabetes development.
Dissecting the structural and functional roles of a vicinal iron-binding site in encapsulated ferritins
Authors: Piergentili Cecilia , Ross Jennifer , He Didi , Gallagher Kelly J. , Stanley Will A. , Adam Laurène , Mackay C. Logan , Waldron Kevin J. , Clarke David J. , Marles-Wright Jon 
Published: September 2019

AbstractEncapsulated ferritins belong to the universally distributed ferritin superfamily, which function as iron detoxification and storage systems. Encapsulated ferritins have a distinct annular structure and must associate with an encapsulin nanocage to form a competent iron store that is capable of holding significantly more iron than classical ferritins. The catalytic mechanism of iron oxidation in the ferritin family is still an open question, due to differences in organization of the ferroxidase catalytic site and secondary metal binding sites vicinal to this. We have previously identified a metal binding site on the inner surface of theRhodospirillum rubrumencapsulated ferritin at the interface between the two-helix subunits and proximal to the ferroxidase center. Here we present a comprehensive structural and functional study to investigate the functional relevance of this proposed iron entry site by means of enzymatic assays, mass-spectrometry, and X-ray crystallography. We show that catalysis occurs in the ferroxidase center and suggest a dual role for the secondary site, which both serves to attract metal ions to the ferroxidase center and acts as a flow-restricting valve to limit the activity of the ferroxidase center. Moreover, confinement of encapsulated ferritins within the encapsulin nanocage, while enhancing the ability of the encapsulated ferritin to undergo catalysis, does not influence the function of the secondary site.
Monodelphis domesticaas a fetal intra-cerebral inoculation model for Zika virus pathogenesis
Authors: Thomas John M. , Garcia Juan , Terry Matthew , Lozano Ileana , Mahaney Susan M. , Quintanilla Oscar , Carlo-Silva Dionn , Morales Marisol , VandeBerg John L. 
Published: September 2019

ABSTRACTMonodelphis domestica, also known as the laboratory opossum, is a marsupial native to South America. At birth, these animals are developmentally equivalent to human embryos at approximately 5 weeks of gestation which, when coupled with other characteristics including the size of the animals, the development of a robust immune system during juvenile development, and the relative ease of experimental manipulation, have madeM. domesticaa valuable model in many areas of biomedical research. However, their suitability as models for infectious diseases, especially diseases caused by viruses such as Zika virus (ZIKV), is currently unknown. Here, we describe the replicative effects of ZIKV using a fetal intra-cerebral model of inoculation. Using immunohistochemistry and in situ hybridization, we found that opossum embryos and fetuses are susceptible to infection by ZIKV administered intra-cerebrally, that the infection persists long term, and that the infection and viral replication consistently results in neural pathology and may occasionally result in global growth restriction. These results demonstrate the utility ofM. domesticaas a new animal model for investigating ZIKV infectionin vivo.This new model will facilitate further inquiry into viral pathogenesis, particularly for those viruses that are neurotropic, that may require a host with the ability to support sustained viral infection, and/or that may require intra-cerebral inoculations of large numbers of embryos or fetuses.AUTHOR SUMMARYHere we show that the laboratory opossum (Monodelphis domestica) is a valuable new model for studying Zika virus pathogenesis. Newborns are at the developmental stage of 5-week human embryos. Zika virus inoculated on a single occasion into the brains of pups at the human developmental stages of 8-20 weeks post conception replicated in neuronal cells and persisted as a chronic infection until the experimental endpoint at 74-days post infection. In addition, we observed global growth restriction in one of 16 inoculated animals; global growth restriction has been observed in humans and other animal models infected with Zika virus. The results illustrate great potential for this new animal model for high throughput research on the neurological effects of Zika virus infection of embryos and fetuses.