Miracle-dz/UniFAR-FTUs huggingface dataset:
Dramatic Rise in Plasma Viremia after CD8+ T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques

To determine the role of CD8+ T cells in controlling simian immunodeficiency virus (SIV) replication in vivo, we examined the effect of depleting this cell population using an anti-CD8 monoclonal antibody, OKT8F. There was on average a 99.9% reduction of CD8 cells in peripheral blood in six infected Macaca mulatta treated with OKT8F. The apparent CD8 depletion started 1 h after antibody administration, and low CD8 levels were maintained until day 8. An increase in plasma viremia of one to three orders of magnitude was observed in five of the six macaques. The injection of a control antibody to an infected macaque did not induce a sustained viral load increase, nor did it significantly reduce the number of CD8+ T cells. These results demonstrate that CD8 cells play a crucial role in suppressing SIV replication in vivo.
Muscle-wide secretion of a miniaturized form of neural agrin rescues focal neuromuscular innervation in agrin mutant mice

Agrin and its receptor MuSK are required for the formation of the postsynaptic apparatus at the neuromuscular junction (NMJ). In the current model the local deposition of agrin by the nerve and the resulting local activation of MuSK are responsible for creating and maintaining the postsynaptic apparatus including clusters of acetylcholine receptors (AChRs). Concomitantly, the release of acetylcholine (ACh) and the resulting depolarization disperses those postsynaptic structures that are not apposed by the nerve and thus not stabilized by agrin-MuSK signaling. Here we show that a miniaturized form of agrin, consisting of the laminin-binding and MuSK-activating domains, is sufficient to fully restore NMJs in agrin mutant mice when expressed by developing muscle. Although miniagrin is expressed uniformly throughout muscle fibers and induces ectopic AChR clusters, the size and the number of those AChR clusters contacted by the motor nerve increase during development. We provide experimental evidence that this is due to ACh, because the AChR agonist carbachol stabilizes AChR clusters in organotypic cultures of embryonic diaphragms. In summary, our results show that agrin function in NMJ development requires only two small domains, and that this function does not depend on the local deposition of agrin at synapses. Finally, they suggest a novel local function of ACh in stabilizing postsynaptic structures.
An Optimal Any-Angle Pathfinding Algorithm

Any-angle pathfinding is a common problem from robotics and computer games: it requires finding a Euclidean shortest path between a pair of points in a grid map. Prior research has focused on approximate online solutions. A number of exact methods exist but they all require supra-linear space and preprocessing time. In this paper we describe Anya: a new optimal any-angle pathfinding algorithm which searches over sets of states represented as intervals. Each interval is identified online. From each we select a representative point to derive a corresponding f-value for the set. Anya always returns an optimal path. Moreover it does so entirely online, without any preprocessing or memory overheads. This result answers an open question from the areas of Artificial Intelligence and Game Development: is there an any-angle pathfinding algorithm which is online and optimal? The answer is yes.
Asymmetric PTEN Distribution Regulated by Spatial Heterogeneity in Membrane-Binding State Transitions

The molecular mechanisms that underlie asymmetric PTEN distribution at the posterior of polarized motile cells and regulate anterior pseudopod formation were addressed by novel single-molecule tracking analysis. Heterogeneity in the lateral mobility of PTEN on a membrane indicated the existence of three membrane-binding states with different diffusion coefficients and membrane-binding lifetimes. The stochastic state transition kinetics of PTEN among these three states were suggested to be regulated spatially along the cell polarity such that only the stable binding state is selectively suppressed at the anterior membrane to cause local PTEN depletion. By incorporating experimentally observed kinetic parameters into a simple mathematical model, the asymmetric PTEN distribution can be explained quantitatively to illustrate the regulatory mechanisms for cellular asymmetry based on an essential causal link between individual stochastic reactions and stable localizations of the ensemble.
A Single Vector Platform for High-Level Gene Transduction of Central Neurons: Adeno-Associated Virus Vector Equipped with the Tet-Off System

Visualization of neurons is indispensable for the investigation of neuronal circuits in the central nervous system. Virus vectors have been widely used for labeling particular subsets of neurons, and the adeno-associated virus (AAV) vector has gained popularity as a tool for gene transfer. Here, we developed a single AAV vector Tet-Off platform, AAV-SynTetOff, to improve the gene-transduction efficiency, specifically in neurons. The platform is composed of regulator and response elements in a single AAV genome. After infection of Neuro-2a cells with the AAV-SynTetOff vector, the transduction efficiency of green fluorescent protein (GFP) was increased by approximately 2- and 15-fold relative to the conventional AAV vector with the human cytomegalovirus (CMV) or human synapsin I (SYN) promoter, respectively. We then injected the AAV vectors into the mouse neostriatum. GFP expression in the neostriatal neurons infected with the AAV-SynTetOff vector was approximately 40-times higher than that with the CMV or SYN promoter. By adding a membrane-targeting signal to GFP, the axon fibers of neostriatal neurons were clearly visualized. In contrast, by attaching somatodendritic membrane-targeting signals to GFP, axon fiber labeling was mostly suppressed. Furthermore, we prepared the AAV-SynTetOff vector, which simultaneously expressed somatodendritic membrane-targeted GFP and membrane-targeted red fluorescent protein (RFP). After injection of the vector into the neostriatum, the cell bodies and dendrites of neostriatal neurons were labeled with both GFP and RFP, whereas the axons in the projection sites were labeled only with RFP. Finally, we applied this vector to vasoactive intestinal polypeptide-positive (VIP+) neocortical neurons, one of the subclasses of inhibitory neurons in the neocortex, in layer 2/3 of the mouse primary somatosensory cortex. The results revealed the differential distribution of the somatodendritic and axonal structures at the population level. The AAV-SynTetOff vector developed in the present study exhibits strong fluorescence labeling and has promising applications in neuronal imaging.
Characterization of Atmospheric Particulate Matter at E-Waste Landfill Site in Agbogbloshie, Accra

1 1 Chapter 1: General Introduction 3 1.1 What is the current situation of air pollution in Ghana? 6 1.2 Problem statement . 7 1.3 Current situation at Agbogloshie . 8 1.4 Objectives . 11 1.5 Scope of the project . 12 vii University of Ghana http://ugspace.ug. edu.gh
An Improved microRNA Annotation of the Canine Genome

The domestic dog, Canis familiaris, is a valuable model for studying human diseases. The publication of the latest Canine genome build and annotation, CanFam3.1 provides an opportunity to enhance our understanding of gene regulation across tissues in the dog model system. In this study, we used the latest dog genome assembly and small RNA sequencing data from 9 different dog tissues to predict novel miRNAs in the dog genome, as well as to annotate conserved miRNAs from the miRBase database that were missing from the current dog annotation. We used both miRCat and miRDeep2 algorithms to computationally predict miRNA loci. The resulting, putative hairpin sequences were analysed in order to discard false positives, based on predicted secondary structures and patterns of small RNA read alignments. Results were further divided into high and low confidence miRNAs, using the same criteria. We generated tissue specific expression profiles for the resulting set of 811 loci: 720 conserved miRNAs, (207 of which had not been previously annotated in the dog genome) and 91 novel miRNA loci. Comparative analyses revealed 8 putative homologues of some novel miRNA in ferret, and one in microbat. All miRNAs were also classified into the genic and intergenic categories, based on the Ensembl RefSeq gene annotation for CanFam3.1. This additionally allowed us to identify four previously undescribed MiRtrons among our total set of miRNAs. We additionally annotated piRNAs, using proTRAC on the same input data. We thus identified 263 putative clusters, most of which (211 clusters) were found to be expressed in testis. Our results represent an important improvement of the dog genome annotation, paving the way to further research on the evolution of gene regulation, as well as on the contribution of post-transcriptional regulation to pathological conditions.
Experiencing Oneself vs Another Person as Being the Cause of an Action: The Neural Correlates of the Experience of Agency

The present study is aimed at identifying the neural correlates of two kinds of attribution: experiencing oneself as the cause of an action (the sense of agency) or experiencing another person as being the cause of that action. The experimental conditions were chosen so that they differed only in their requirement to attribute an action to another person or to oneself. The same motor task and the same visual stimuli were used in the experimental conditions. Subjects used a joystick to drive a circle along a T-shaped path. They were told that the circle would be driven either by themselves or by the experimenter. In the former case subjects were requested to drive the circle, to be aware that they drove the circle, and thus to mentally attribute the action seen on the screen to themselves. In the latter case they were also requested to perform the task, but they were aware that action seen on the screen was driven by the experimenter. In accord with previous studies, the results showed that being aware of causing an action was associated with activation in the anterior insula, whereas being aware of not causing the action and attributing it to another person was associated with activation in the inferior parietal cortex. These two regions are involved in the perception of complex representations of the self and of its interactions with the external world. We suggest that the anterior insula is concerned with the integration of all the concordant multimodal sensory signals associated with voluntary movements. The inferior parietal cortex, in contrast, represents movements in an allocentric coding system that can be applied to the actions of others as well as the self.
Clinical Presentation as a Guide to Early Prognosis in Vertebrobasilar Stroke

This study attempts to assess the feasibility and heuristic value of a classification scheme for vertebrobasilar stroke. Method Fifty-seven consecutive patients with vertebrobasilar stroke were classified on the basis of clinical features and computed tomographic abnormalities into single-sector (n=19), multisector (n=11), and top-of-the-basilar (n=27) groups; a sector was denned as that portion of the brain stem supplied by a single penetrating (median) or branch (paramedian or lateral) artery. Results Thirty-day and 3-year survival rates were 100% and 71%, respectively, in the single-sector group, and 96% and 73%, respectively, in the top-of-the-basilar group. Thirty-day and 3-year stroke recurrence free survival rates were 89% and 76%, respectively, in the single-sector group, and 96% and 88%, respectively, in the top-of-the-basilar group. Seven of the 11 patients in the multisector group died within 2 months of ictus, three having experienced recurrence. Conclusions These data, in part supported by prior studies, demonstrate the feasibility and heuristic value of the classification scheme and suggest that single-sector and top-of-the-basilar stroke patients have a relatively benign early prognosis and modest long-term stroke rates.
Hoxa9 and Meis1 Are Key Targets for MLL-ENL-Mediated Cellular Immortalization

ABSTRACT MLL fusion proteins are oncogenic transcription factors that are associated with aggressive lymphoid and myeloid leukemias. We constructed an inducible MLL fusion, MLL-ENL-ERtm, that rendered the transcriptional and transforming properties of MLL-ENL strictly dependent on the presence of 4-hydroxy-tamoxifen. MLL-ENL-ERtm-immortalized hematopoietic cells required 4-hydroxy-tamoxifen for continuous growth and differentiated terminally upon tamoxifen withdrawal. Microarray analysis performed on these conditionally transformed cells revealed Hoxa9 and Hoxa7 as well as the Hox coregulators Meis1 and Pbx3 among the targets upregulated by MLL-ENL-ERtm. Overexpression of the Hox repressor Bmi-1 inhibited the growth-transforming activity of MLL-ENL. Moreover, the enforced expression of Hoxa9 in combination with Meis1 was sufficient to substitute for MLL-ENL-ERtm function and to maintain a state of continuous proliferation and differentiation arrest. These results suggest that MLL fusion proteins impose a reversible block on myeloid differentiation through aberrant activation of a limited set of homeobox genes and Hox coregulators that are consistently expressed in MLL-associated leukemias.
A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel

Opening of BK-type Ca2+ activated K+ channels protects the heart against ischemia-reperfusion (IR) injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse perfused heart model of IR injury. As anticipated, deletion of the Slo1 gene blocked this protection. However, in an isolated cardiomyocyte model of IR injury, protection by NS1619 and NS11021 was insensitive to Slo1 deletion. These data suggest that protection in intact hearts occurs by a non-cardiomyocyte autonomous, SLO1-dependent, mechanism. In this regard, an in-situ assay of intrinsic cardiac neuronal function (tachycardic response to nicotine) revealed that NS1619 preserved cardiac neurons following IR injury. Furthermore, blockade of synaptic transmission by hexamethonium suppressed cardioprotection by NS1619 in intact hearts. These results suggest that opening SLO1 protects the heart during IR injury, via a mechanism that involves intrinsic cardiac neurons. Cardiac neuronal ion channels may be useful therapeutic targets for eliciting cardioprotection.
Population land use and the environment in developing countries: what can we learn from cross-national data?

Environmental degradation is the key word for the 1990s. This review of the ways in which population change can influence land use patterns was an initial attempt to advance the limited knowledge base on environmental issues. Cross country and world regional data were used to exemplify the linkages between land use and environmental change for rural areas of developing countries. Data quality was best for demographic measures less so for land use data and much weaker for environmental data; quality even for demographic data still varied by country. Land use data may be dated and based on limited agricultural census. Desertification and soil erosion figures were non existent and deforestation figures were variable by source. Population data included rural population growth from the 1960s to the 1980s and population density. Land use variables included total land area devoted to agricultural uses in 1965 and 1985 median changes land per agricultural worker the 1987 per capital Gross National Product and the average kilograms of fertilizer used per hectare of cropland for 1975-77 and 1985-87 (agricultural intensification). World Resources Institute data were used for the average annual loss of closed canopy and open canopy forests. Other variables included land and labor productivity and ungraphed variables: the Gini coefficients for land distribution and income equality the population-supporting capacity of land equality pesticide and tractor usage food production and total fertility rates. Analytical problems other than poor data quality and missing data also exist for determining how to measure some concepts and what measures of what variables should be compared with what measures of other variables. Shortcomings were identified as unavailability of the change in rural population density data lack of specification of quality of land or whether land is in use or fallow lack of specification of excessive fertilizer use or type of fertilizer lack of data on losses in irrigation by cause and inadequate and missing environmental data. Results of simple correlations for example indicated a positive relationship between population growth and land use but it was weaker than expected and conditional. If Brazil is included there is weak inverse correlation between rural population growth and loss of forests but it is positive and insignificant if Brazil and countries reporting zero closed forest loss are excluded.
Mean Field Games: Numerical Methods

Mean field type models describing the limiting behavior, as the number of players tends to $+\infty$, of stochastic differential game problems, have been recently introduced by J.-M. Lasry and P.-L. Lions [C. R. Math. Acad. Sci. Paris, 343 (2006), pp. 619-625; C. R. Math. Acad. Sci. Paris, 343 (2006), pp. 679-684; Jpn. J. Math., 2 (2007), pp. 229-260]. Numerical methods for the approximation of the stationary and evolutive versions of such models are proposed here. In particular, existence and uniqueness properties as well as bounds for the solutions of the discrete schemes are investigated. Numerical experiments are carried out.
The integration of parallel and serial processing mechanisms in visual search: evidence from eye movement recording

We examined timing and scanning paths of eye movements during a visual search task, in which subjects had to detect, as quickly as possible, the presence or absence of a target among distractors [Q‐like element among O stimuli (QvsO) and vice‐versa (OvsQ)]. According to an influential theory [Treisman, A. & Gelade, G. (1980) Cognitive Psychol, 12, 97–136; Treisman, A. & Sato, S. (1990) J. Exp. Psychol. Hum. Percept. Perform. , 16, 459–478], only tasks yielding nonflat search functions (OvsQ) involve focal attention. Alternative models propose that all kinds of visual search are resolved by a biased competitive process, working in parallel across the visual field. Data show that QvsO and OvsQ tasks are characterized by quantitative rather than by qualitative differences in search strategy. No differences between the two tasks were found regarding either the percentage of saccades foveating single stimulus items or the timing of the button response with respect to the onset of the last foveation saccade within a trial. Furthermore, the number of saccades made during search predicted very accurately the time required to accomplish the task and fixation times were independent of the number of stimulus items. On the basis of our results there is no reason to postulate the occurrence of shifts of visuospatial attention, other than those associated with the executions of saccadic eye movements, which are driven by a parallel feature analysis of the visual scene, in both types of search tasks. A time‐limited competitive model for attentive target identification, in which both parallel (competitive) and serial (attentive) processing mechanisms are integrated, can account for these findings, providing a unified conceptual framework for all kinds of visual search.
Conformational Changes in the Capsid of a Calicivirus upon Interaction with Its Functional Receptor

ABSTRACT Nonenveloped viral capsids are metastable structures that undergo conformational changes during virus entry that lead to interactions of the capsid or capsid fragments with the cell membrane. For members of the Caliciviridae, neither the nature of these structural changes in the capsid nor the factor(s) responsible for inducing these changes is known. Feline junctional adhesion molecule A (fJAM-A) mediates the attachment and infectious viral entry of feline calicivirus (FCV). Here, we show that the infectivity of some FCV isolates is neutralized following incubation with the soluble receptor at 37°C. We used this property to select mutants resistant to preincubation with the soluble receptor. We isolated and sequenced 24 soluble receptor-resistant (srr) mutants and characterized the growth properties and receptor-binding activities of eight mutants. The location of the mutations within the capsid structure of FCV was mapped using a new 3.6-Å structure of native FCV. The srr mutations mapped to the surface of the P2 domain were buried at the protruding domain dimer interface or were present in inaccessible regions of the capsid protein. Coupled with data showing that both the parental FCV and the srr mutants underwent increases in hydrophobicity upon incubation with the soluble receptor at 37°C, these findings indicate that FCV likely undergoes conformational change upon interaction with its receptor. Changes in FCV capsid conformation following its interaction with fJAM-A may be important for subsequent interactions of the capsid with cellular membranes, membrane penetration, and genome delivery.
Degradation of  T Cell Receptor (TCR)–CD3-ζ Complexes after Antigenic Stimulation

T cell activation by specific antigen results in a rapid and long-lasting downregulation of triggered T cell receptors (TCRs). In this work, we investigated the fate of downregulated TCR– CD3-ζ complexes. T cells stimulated by peptide-pulsed antigen-presenting cells (APCs) undergo an antigen dose-dependent decrease of the total cellular content of TCR-β, CD3-ε, and ζ chains, as detected by FACS® analysis on fixed and permeabilized T–APC conjugates and by Western blot analysis on cell lysates. The time course of CD3-ζ chain consumption overlaps with that of TCR downregulation, indicating that internalized TCR–CD3 complexes are promptly degraded. Inhibitors of lysosomal function (bafilomycin A1, folimycin) markedly reduced ζ chain degradation, leading to the accumulation of ζ chain in large Lamp1+ vesicles. These results indicate that in T cell–APC conjugates, triggered TCRs are rapidly removed from the cell surface and are degraded in the lysosomal compartment.
Diversity of Dicotyledenous-Infecting Geminiviruses and Their Associated DNA Molecules in Southern Africa, Including the South-West Indian Ocean Islands

The family Geminiviridae comprises a group of plant-infecting circular ssDNA viruses that severely constrain agricultural production throughout the temperate regions of the world, and are a particularly serious threat to food security in sub-Saharan Africa. While geminiviruses exhibit considerable diversity in terms of their nucleotide sequences, genome structures, host ranges and insect vectors, the best characterised and economically most important of these viruses are those in the genus Begomovirus. Whereas begomoviruses are generally considered to be either monopartite (one ssDNA component) or bipartite (two circular ssDNA components called DNA-A and DNA-B), many apparently monopartite begomoviruses are associated with additional subviral ssDNA satellite components, called alpha- (DNA-αs) or betasatellites (DNA-βs). Additionally, subgenomic molecules, also known as defective interfering (DIs) DNAs that are usually derived from the parent helper virus through deletions of parts of its genome, are also associated with bipartite and monopartite begomoviruses. The past three decades have witnessed the emergence and diversification of various new begomoviral species and associated DI DNAs, in southern Africa, East Africa, and proximal Indian Ocean islands, which today threaten important vegetable and commercial crops such as, tobacco, cassava, tomato, sweet potato, and beans. This review aims to describe what is known about these viruses and their impacts on sustainable production in this sensitive region of the world.