Miracle-dz/UniFAR-FTUs huggingface dataset:
Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru

Background. Nearly half of the world’s population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010-2011, 15 years after the first outbreak of DENV-2 in the region. Methodology/Principal Findings. We estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010-2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0% -- 65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1 – 17.7). Conclusions/Significance. Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics. Author Summary Homotypic immunity against DENV infection has been assumed to be complete and lifelong, and to our knowledge, instances of homologous DENV re-infection have not been rigorously documented. However, few long-term studies have been conducted in such a way that homologous re-infection could be observed, if it did in fact occur. Our study provides evidence that homologous re-infection may occur in certain circumstances. We draw from data collected during a 2010-2011 DENV-2 epidemic in northeastern Peru, 15 years after the initial DENV-2 outbreak in the region. This finding has significant implications for our understanding of dengue epidemiology and for dengue vaccine formulation, which may need to consider multiple genotypes of each serotype. Data from other long-term dengue epidemiology studies should be analyzed to determine of homologous re-infection is a more widespread phenomenon.
Biodiversité des eaux souterraines dans un gradient de temps de résidence et d'influence anthropique : approches métagénomique et géochimique couplées

Les aquiferes de socle fractures tres repandus en Bretagne, constituent des formations geologiques heterogenes renfermant des ressources en eau. Ces structures sont souvent constituees d'une zone alteree et d'une zone fracturee. La zone alteree est peu epaisse et proche de la surface, elle est constituee de roches alterees envahies par l'eau souterraine qui y circule rapidement des hauts topographiques du bassin versant vers l'exutoire. L'eau y presente des temps de residence courts ( 40 ans). Dans cette zone, l'eau est plus mineralisee et souvent riche en fer en Bretagne. Ces differentes circulations d'eau, induisent des conditions chimiques contrastees dans les zones alteree et fracturee, mais leur effet sur l'ecosysteme microbien des eaux souterraines n'a jamais ete explore. Cette etude montre que les circulations hydrologiques influencent a l'echelle regionale et locale la structuration des communautes microbiennes au sein des eaux souterraines d'aquiferes de socle. La position d'une eau souterraine le long des voies de circulations des eaux souterraines dites « boucles hydrologiques » controle directement la structure des communautes microbiennes via le controle de la succession des donneurs et accepteurs d'electrons disponibles. Les communautes microbiennes analysees montrent une predominance de Nitrobacter. Dans l'eau souterraine recente ( 40 ans) et isolee donc dans la zone fracturee, ce sont en grande majorite des Gallionellaceae, microorganismes microaerophiles specialises dans l'oxydation du fer(II). La predominance des Gallionellaceae dans la zone fracturee suggere un ecosysteme profond base sur l'oxydation du fer(II). Cependant, ce processus suppose une arrivee minimale d'oxygene dans la partie profonde, via par exemple un melange avec une masse d'eau recente oxygenee. La proportion de Gallionellaceae dans les differentes eaux analysees montre une correlation positive avec le degre de melange des eaux anciennes avec des eaux recentes, jusqu'a une limite de 20% d'eau recente. Le suivi temporel de la dynamique des communautes d'un aquifere avant et au debut de la recharge a montre dans la zone alteree des conditions chimiques tres fluctuantes et une communaute microbienne tres changeante mais toujours constituee de nombreux potentiels denitrifiants. Dans la zone fracturee, la communaute dominee par les Gallionellaceae est relativement stable, malgre des changements chimiques ponctuels substantiels et un degre de melange transitoire important (jusqu'a 60% d'eau recente) au debut de la recharge. Les Gallionellaceae semblent donc capables de resister a des changements ponctuels et importants des conditions chimiques. Les eaux souterraines de la partie profonde des aquiferes, bien qu'isolees, restent relativement connectees a la surface ce qui permet probablement le maintien de l'ecosysteme microbien profond.
Comparison of Decellularization Protocols for Preparing a Decellularized Porcine Annulus Fibrosus Scaffold

Tissue-specific extracellular matrix plays an important role in promoting tissue regeneration and repair. We hypothesized that decellularized annular fibrosus matrix may be an appropriate scaffold for annular fibrosus tissue engineering. We aimed to determine the optimal decellularization method suitable for annular fibrosus. Annular fibrosus tissue was treated with 3 different protocols with Triton X-100, sodium dodecyl sulfate (SDS) and trypsin. After the decellularization process, we examined cell removal and preservation of the matrix components, microstructure and mechanical function with the treatments to determine which method is more efficient. All 3 protocols achieved decellularization; however, SDS or trypsin disturbed the structure of the annular fibrosus. All protocols maintained collagen content, but glycosaminoglycan content was lost to different degrees, with the highest content with TritonX-100 treatment. Furthermore, SDS decreased the tensile mechanical property of annular fibrosus as compared with the other 2 protocols. MTT assay revealed that the decellularized annular fibrosus was not cytotoxic. Annular fibrosus cells seeded into the scaffold showed good viability. The Triton X-100–treated annular fibrosus retained major extracellular matrix components after thorough cell removal and preserved the concentric lamellar structure and tensile mechanical properties. As well, it possessed favorable biocompatibility, so it may be a suitable candidate as a scaffold for annular fibrosus tissue engineering.
A large scale model of the cerebellar cortex using PGENESIS 1

In an investigation into the transformation of mossy ber input to Purkinje cell output in the cerebellar cortex, we have developed a network model including a sophisticated compartmental model of the Purkinje cell. Analysis and simulations demonstrated the need to include a large number of parallel bers (244,000) to obtain realistic Purkinje cell ring patterns for random mossy ber input. Using smaller numbers of parallel ber inputs resulted in unrealistic Purkinje cell spiking characterized by spontaneous dendritic calcium spikes. Because the scale required is beyond workstation capabilites, we used a 128-processor Cray T3E running PGENESIS. This size network could produce realistic spiking patterns provided the stellate cell inhibition was tuned carefully.
Exhaustible resource consumption and lessons for greenhouse gas limitationsa three-country, three-period model of iterative decision-making

4 Introduction. 5 CHAPTER 1: Literature Review. 10 CHAPTER 2: Model Overview and the Baseline Simulation. 23 CHAPTER 3: More Simulations. 29 Conclusion. 42 Postscript. 47 Reference. 49 APPENDIX 1: Figures and Tables I. Figures. 52 II. Tables. 67 APPENDIX 2: Technical Summary I. Technical Details for Chapter 2. 77 II. Technical Details for Chapter 3. 84
BRG1 expression is increased in thoracic aortic aneurysms and regulates proliferation and apoptosis of vascular smooth muscle cells through the long non-coding RNA HIF1A-AS1 in vitro.

OBJECTIVES Brahma-related gene 1 (BRG1) and long non-coding RNAs (lncRNAs) play important roles in cellular processes. However, little is known regarding their roles in thoracic aortic aneurysms. We investigated BRG1 expression in thoracic aortic aneurysms and the roles of BRG1 and the lncRNA HIF 1 alpha-antisense RNA 1 in regulating the proliferation and apoptosis of aortic smooth muscle cells in vitro. METHODS BRG1 mRNA and protein expression in human aortic media specimens were examined by quantitative real-time polymerase chain reaction, immunohistochemical staining and western blot. BRG1 expression was up-regulated by lentiviral vectors. Vascular smooth muscle cell proliferation and apoptosis were studied using Cell Counting Kit-8 and terminal deoxynucleotidyl transferase dUTP nick-end labelling assays. We performed western blots to detect Caspase3 and Bcl2 protein expression. LncRNAs regulated by BRG1 were identified through microarray in BRG1 gain- and loss-of-function vascular smooth muscle cells. Finally, the expression of HIF 1 alpha-antisense RNA 1 was reduced by siRNA and cell proliferation and apoptosis was studied using Cell Counting Kit-8 assays, caspase-3 activity assays and western blot. RESULTS BRG1 expression in the aortic media was significantly higher in thoracic aortic aneurysms than in normal controls. Overexpression of BRG1 in human aortic smooth muscle cells promoted apoptosis and reduced proliferation. The expression of HIF 1 alpha-antisense RNA 1 was significantly down- and up-regulated in BRG1 knock-down and overexpressing vascular smooth muscle cells, respectively. We further demonstrated that suppression of HIF 1 alpha-antisense RNA 1 by siRNA in vascular smooth muscle cells reduced apoptosis and promoted proliferation. CONCLUSIONS BRG1 is overexpressed in the aortic media of thoracic aortic aneurysms and the interaction between BRG1 and HIF 1 alpha-antisense RNA 1 plays a key role in the proliferation and apoptosis of vascular smooth muscle cells in vitro, which may contribute to the pathogenesis of thoracic aortic aneurysms.
Foxp2 Regulates Gene Networks Implicated in Neurite Outgrowth in the Developing Brain

Forkhead-box protein P2 is a transcription factor that has been associated with intriguing aspects of cognitive function in humans, non-human mammals, and song-learning birds. Heterozygous mutations of the human FOXP2 gene cause a monogenic speech and language disorder. Reduced functional dosage of the mouse version (Foxp2) causes deficient cortico-striatal synaptic plasticity and impairs motor-skill learning. Moreover, the songbird orthologue appears critically important for vocal learning. Across diverse vertebrate species, this well-conserved transcription factor is highly expressed in the developing and adult central nervous system. Very little is known about the mechanisms regulated by Foxp2 during brain development. We used an integrated functional genomics strategy to robustly define Foxp2-dependent pathways, both direct and indirect targets, in the embryonic brain. Specifically, we performed genome-wide in vivo ChIP–chip screens for Foxp2-binding and thereby identified a set of 264 high-confidence neural targets under strict, empirically derived significance thresholds. The findings, coupled to expression profiling and in situ hybridization of brain tissue from wild-type and mutant mouse embryos, strongly highlighted gene networks linked to neurite development. We followed up our genomics data with functional experiments, showing that Foxp2 impacts on neurite outgrowth in primary neurons and in neuronal cell models. Our data indicate that Foxp2 modulates neuronal network formation, by directly and indirectly regulating mRNAs involved in the development and plasticity of neuronal connections.
Intercomparison of snow water equivalent observations in the Northern Great Plains

In the Northern Great Plains, melting snow is a primary driver of spring flooding, but limited knowledge of the magnitude and spatial distribution of snow water equivalent (SWE) hampers flood forecasting. Passive microwave remote sensing has the potential to enhance operational river flow forecasting but is not routinely incorporated in operational flood forecasting. We compare satellite passive microwave estimates from the Advanced Microwave Scanning Radiometer for the Earth Observing System (AMSR‐E) to the National Oceanic and Atmospheric Administration Office of Water Prediction (OWP) airborne gamma radiation snow survey and U.S. Army Corps of Engineers (USACE) ground snow survey SWE estimates in the Northern Great Plains from 2002 to 2011. AMSR‐E SWE estimates compare favourably with USACE SWE measurements in the low relief, low vegetation study area (mean difference = −3.8 mm, root mean squared difference [RMSD] = 34.7 mm), but less so with OWP airborne gamma SWE estimates (mean difference = −9.5 mm, RMSD = 42.7 mm). An error simulation suggests that up to half of the error in the former comparison is potentially due to subpixel scale SWE variability, limiting the maximum achievable RMSD between ground and satellite SWE to approximately 26–33 mm in the Northern Great Plains. The OWP gamma versus AMSR‐E SWE comparison yields larger error than the point‐scale USACE versus AMSR‐E comparison, despite a larger measurement footprint (5–7 km2 vs. a few square centimetres, respectively), suggesting that there are unshared errors between the USACE and OWP gamma SWE data.
Joint Learning from Earth Observation and OpenStreetMap Data to Get Faster Better Semantic Maps

In this work, we investigate the use of OpenStreetMap data for semantic labeling of Earth Observation images. Deep neural networks have been used in the past for remote sensing data classification from various sensors, including multispectral, hyperspectral, SAR and LiDAR data. While OpenStreetMap has already been used as ground truth data for training such networks, this abundant data source remains rarely exploited as an input information layer. In this paper, we study different use cases and deep network architectures to leverage OpenStreetMap data for semantic labeling of aerial and satellite images. Especially, we look into fusion based architectures and coarseto- fine segmentation to include the OpenStreetMap layer into multispectral-based deep fully convolutional networks. We illustrate how these methods can be successfully used on two public datasets: ISPRS Potsdam and DFC2017. We show that OpenStreetMap data can efficiently be integrated into the vision-based deep learning models and that it significantly improves both the accuracy performance and the convergence speed of the networks.
Age at First Birth and Fathers' Subsequent Health: Evidence From Sibling and Twin Models

Using a sample of 540 siblings and twins from the National Survey of Midlife Development in the United States, this study examines the relationship between the age at which men become biological fathers and their subsequent health. The analysis includes both between-family models that treat brothers as independent observations and within-family models that account for unobserved genetic and early-life environmental endowments shared by brothers within families. Findings indicate that age at first birth has a positive, linear effect on men's health, and this relationship is not explained by the confounding influences of unobserved early-life characteristics. However, the effect of age at first birth on fathers' health is explained by men's socioeconomic and family statuses. Whereas most research linking birth timing to specific diseases focuses narrowly on biological mechanisms among mothers, this study demonstrates the importance of reproductive decisions for men's health and well-being.
Inverse Relationship Between Cerebrovascular Lesions and Severity of Lewy Body Pathology in Patients With Lewy Body Diseases

Cerebrovascular pathology is a major cause of stroke and mortality. Studies on prevalence of cerebrovascular pathologies in dementia with Lewy bodies (DLBs) and Parkinson disease (PD) patients are scarce and contradictory. We aimed to determine the prevalence and severity of cerebrovascular pathologies in DLB and PD and to analyze their relationship to LB pathology. The prevalence and severity of atherosclerosis in the circle of Willis, cerebral amyloid angiopathy, cerebral infarcts, hemorrhages, small-vessel disease, white matter lesions, including the Consortium to Establish a Registry for Alzheimer Disease (CERAD) protocol as well as Braak neurofibrillary tangle stages for AD pathology were analyzed in autopsy-verified DLB (n = 13), PD (n = 102), and control subjects (n = 53). In all patient groups, the extent of LB pathology was inversely correlated to the severity of most vascular pathologies (atherosclerosis, infarcts, and small-vessel disease; all p < 0.05). By contrast, cerebral amyloid angiopathy, CERAD, and Braak neurofibrillary tangle stages were positively correlated with LB pathology (p < 0.05). Whereas the overall prevalence and severity of small-vessel disease, infarcts, hemorrhages, and white matter lesions were comparable among both disease groups, the extents of atherosclerosis, cerebral amyloid angiopathy, CERAD, and Braak neurofibrillary tangle stages were significantly higher in DLB than in those of PD patients (p < 0.05). Microinfarcts were statistically more prevalent in each patient group than in controls, whereas gross infarcts predominated in controls (p < 0.05 each). In conclusion, DLB and PD patients with advanced LB pathology were less likely to show severe cerebrovascular disease or history of stroke.
Proteinuria is common among HIV patients: what are we missing?

OBJECTIVES: HIV-related renal diseases are the leading causes of chronic kidney diseases worldwide. The present study aimed to investigate the prevalence of pathological proteinuria and its risk factors among HIV patients. METHODS: A review of the medical records of 666 HIV-infected individuals aged 18 years or older in an urban HIV/AIDS clinic based in Porto Alegre in southern Brazil. Overt proteinuria was defined as a protein-to-creatinine ratio greater than 150 mg/g according to Kidney Disease: Improving Global Outcomes. RESULTS: The prevalence of pathological proteinuria in the present study cohort was 20%. Characteristics associated with pathological proteinuria after univariate analysis included alcohol abuse, hepatitis C virus coinfection, the occurrence of diabetes and therapy including tenofovir. Adjusted residuals analysis indicated an association between pathological proteinuria and both a CD4 lymphocyte count below 200 cells/mm3 and a viral load higher than 1000 copies/mL. Additionally, an absence of pathological proteinuria was associated with a CD4 lymphocyte count higher than 500 cells/mm3. After adjustment for variables with p<0.2 in the univariate analysis using a Poisson regression model, tenofovir-containing regimens and a CD4 lymphocyte count below 200 cells/mm3 were significantly associated with pathological proteinuria. CONCLUSION: The risk of chronic kidney diseases in this large contemporary cohort of HIV-infected individuals appeared to be attributable to a combination of HIV-related risk factors. In addition to the traditional risk factors cited in the literature, both regimens containing tenofovir and HIV disease severity seem to be associated with chronic kidney diseases in patients with HIV. Assessment of proteinuria constitutes a novel method for chronic kidney disease staging in HIV-infected individuals and may be effectively used to stratify the risk of progression to end-stage renal disease.
A Single Binding Motif is Required for SPAK Activation of the Na-K-2Cl Cotransporter

Background: SPAK (Ste20p-related proline alanine-rich kinase) phosphorylates and activates NKCC1 (Na-K-2Cl cotransporter) in the presence of another serine/threonine kinase WNK4 (With No lysine (K)). However, whether or not the docking of SPAK to NKCC1 is a requirement for cotransporter activation has not been fully resolved. Methods: We mutated both SPAK binding motifs in the amino-terminal tail of NKCC1 and tested the interaction between SPAK and NKCC1 using a semi in vivo yeast two-hybrid assay, 32P-ATP in vitro phosphorylation assays, and 86Rb+ uptake (a K+ congener) assays in heterologously expressed Xenopus laevis oocytes. We also used site-directed mutagenesis to identify the principle phospho-regulatory threonine residues in the amino-terminal tail of NKCC1. Results: A single SPAK binding motif is necessary for isotonic NKCC1 activation. Mutation of the phenylalanine (F) residue within the motif abrogates binding and function. Phosphorylation of the cotransporter is markedly reduced in the absence of SPAK docking to NKCC1. Truncations of internal regions of the amino-terminus of NKCC1 do not disrupt protein structure enough to affect cotransporter function. Threonine residues (T206 and T211) are both identified as phospho-regulatory sites of NKCC1 function. Conclusion: We demonstrate that physical docking of SPAK to NKCC1 is necessary for cotransporter activity under both baseline and hyperosmotic conditions. We identify T206 and T211 as major phospho-acceptor sites involved in cotransporter function, with T206 common to two separate regulatory pathways: one involving SPAK, the other involving a still unknown kinase that is responsive to forskolin/PKA stimulation.
Send Orders of Reprints at Reprints@benthamscience.org the Important Role of Osteoblasts and Citrate Production in Bone Formation: " Osteoblast Citration " as a New Concept for an Old Relationship

It has been known for about seventy years that bone, in all vertebrates, contains uniquely high citrate levels. However, the role of citrate, its source, its regulation, and its implication in normal bone formation and in bone disorders have remained largely unknown. For the past thirty-five years, the relationship of citrate in bone has been a neglected area of attention and research. It has recently been discovered that citrate is critical for the structure of the apatite nanocrystal, and is required to impart the important properties of bone such as its stability, strength, and resistance to fracture. This brings to focus the need for a renewed interest and research into the relationships of citrate in bone formation. A most fundamental question that must be resolved is " What is the source of citrate in bone? ". This presentation provides a historical review of the early research to the present status of citrate implications in bone. This leads to a new concept of the role of osteoblasts as specialized citrate producing cells that provide the source of citrate in bone formation; i.e. the " osteoblast citration " process. This also brings into focus a new insight into the role of zinc in bone in relation to osteoblast citrate production. The genetic/hormonal/metabolic relationships of " net citrate production " are described. The intent of this presentation is to provide the background for a new perspective of the important implications of osteoblasts and citrate in bone formation; which, hopefully, will stimulate a renewed interest and essential research.