Miracle-dz/UniFAR-FTUs huggingface dataset:
Secretory protein trafficking in Giardia intestinalis

Early diverged extant organisms, which may serve as convenient laboratory models to look for and study evolutionary ancient features of eukaryotic cell biology, are rare. The diplomonad Giardia intestinalis, a protozoan parasite known to cause diarrhoeal disease, has become an increasingly popular object of basic research in cell biology, not least because of a genome sequencing project nearing completion. Commensurate with its phylogenetic status, the Giardia trophozoite has a very basic secretory system and even lacks hallmark structures such as a morphologically identifiable Golgi apparatus. The cell's capacity for protein sorting is nevertheless unimpeded, exemplified by its ability to cope with massive amounts of newly synthesized cyst wall proteins and glycans, which are sorted to dedicated Golgi‐like compartments termed encystation‐specific vesicles (ESVs) generated from endoplasmic reticulum (ER)‐derived transport intermediates. This soluble bulk cargo is kept strictly separate from constitutively transported variant surface proteins during export, a function that is dependent on the stage‐specific recognition of trafficking signals. Encysting Giardia therefore provide a unique system for the study of unconventional, Golgi‐independent protein trafficking mechanisms in the broader context of eukaryotic endomembrane organization and evolution.
Purification and Characterization of a Membrane-bound Nonlysosomal Ceramidase from Rat Brain*

We have purified a membrane bound ceramidase 22,300-fold to apparent homogeneity. The purification scheme included Triton X-100 extraction of membranes followed by Q-Sepharose, blue Sepharose, phenyl-Sepharose, and MonoS column chromatography. The purified enzyme showed an apparent molecular mass of 90 kDa as estimated by SDS-polyacrylamide gel electrophoresis under reducing conditions and 95 kDa by chromatography on Superose 12. Using C16-ceramide as substrate, the enzyme showed a broad pH optimum in the neutral to alkaline range. A mixed micelle assay was developed, and using Triton X-100/ceramide mixed micelles, the enzyme exhibited classical Michaelis-Menten kinetics, with aK m of 1.29 mol % and aV max of 4.4 μmol/min/mg. When dihydroceramide was used as substrate, these values were 3.84 mol % and 1.2 μmol/min/mg, respectively, indicating that the enzyme hydrolyzes ceramides preferentially. The activity of the purified ceramidase did not require cations, and it was inhibited by reducing agents. Phosphatidylcholine and sphingomyelin were without effect on the enzyme activity, whereas phosphatidic acid and phosphatidylserine stimulated the activity 3-fold. Sphingosine acted as a competitive inhibitor with an IC50 of 5–10 μm. These results indicate that the purified enzyme is a novel ceramidase.
The technological impact on well-being through listening to music : A theoretical exploration of the impact of technology on the circumstances under which listening to music can induce emotions and with that influence well-being.

Listening to music is an everyday activity that has been reported to be able to evoke genuine emotional responses in music listeners and to improve the well-being of music listeners. However, this relatedness between music, emotions and well-being is much more controversial than it seems at first sight. In this thesis I present a critical and holistic theoretical exploration in the fields of philosophy, psychology and STS about the possible benefits of emotions while listening to music for the well-being of music listeners and the impact of music-listening technologies on these benefits. I demonstrate that mainly the dominance over the musical event, the circumstances while listening to music, determines this influence of music listening on well-being. Music-listening technologies have provided music listeners in a very high degree of dominance. This has both a positive and a negative influence on well-being. This focus on the dominance over a musical event is of paramount importance in studies about the influences of listening to music. Future interdisciplinary studies should take this role into account in order to explore how music can have a positive impact on our society and how music-listening technologies can be designed specifically to improve our well-being.
Proposal for an Extension of Traditional Named Entities: From Guidelines to Evaluation, an Overview

Within the framework of the construction of a fact database, we defined guidelines to extract named entities, using a taxonomy based on an extension of the usual named entities definition. We thus defined new types of entities with broader coverage including substantive-based expressions. These extended named entities are hierarchical (with types and components) and compositional (with recursive type inclusion and metonymy annotation). Human annotators used these guidelines to annotate a 1.3M word broadcast news corpus in French. This article presents the definition and novelty of extended named entity annotation guidelines, the human annotation of a global corpus and of a mini reference corpus, and the evaluation of annotations through the computation of inter-annotator agreements. Finally, we discuss our approach and the computed results, and outline further work.
Tracking episomal HIV DNA: implications for viral persistence and eradication of HIV

Purpose of reviewIn this review, methods with which investigators detect and monitor HIV persistence will be described. In particular, we will focus on the work that provides evidence that low-level virus replication persists despite the suppressive effects of therapy and the approaches that can be employed to measure and characterize the ongoing virus replication in apparently aviremic individuals. Recent findingsWith the effectiveness of antiretroviral therapy, there is a need for assays to probe the nature of reservoirs that are maintained despite therapy and to assess the impact of intensification on their stability. Detection and quantitation of surrogate markers for ongoing replication (two long terminal repeat circles) have recently been used to monitor the effects of therapy intensification, source of viral rebound, and characterization of viral variants that contribute to treatment failure. SummaryWith successful antiviral therapy, increasingly more attention has turned to the ultimate goal of virus eradication. In order to assess the effectiveness of new therapies and eradication strategies, an assay that can be broadly applied is needed. Amplification of unintegrated DNA is an approach that should be considered to study the effects of therapy intensification and protocols designed to eliminate the reservoirs that persist in HIV-infected individuals.
A school-based intervention for diabetes risk reduction.

BACKGROUND We examined the effects of a multicomponent, school-based program addressing risk factors for diabetes among children whose race or ethnic group and socioeconomic status placed them at high risk for obesity and type 2 diabetes. METHODS Using a cluster design, we randomly assigned 42 schools to either a multicomponent school-based intervention (21 schools) or assessment only (control, 21 schools). A total of 4603 students participated (mean [+/- SD] age, 11.3 [+/- 0.6 years; 54.2% Hispanic and 18.0% black; 52.7% girls). At the beginning of 6th grade and the end of 8th grade, students underwent measurements of body-mass index (BMI), waist circumference, and fasting glucose and insulin levels. RESULTS There was a decrease in the primary outcome--the combined prevalence of overweight and obesity--in both the intervention and control schools, with no significant difference between the school groups. The intervention schools had greater reductions in the secondary outcomes of BMI z score, percentage of students with waist circumference at or above the 90th percentile, fasting insulin levels (P=0.04 for all comparisons), and prevalence of obesity (P=0.05). Similar findings were observed among students who were at or above the 85th percentile for BMI at baseline. Less than 3% of the students who were screened had an adverse event; the proportions were nearly equivalent in the intervention and control schools. CONCLUSIONS Our comprehensive school-based program did not result in greater decreases in the combined prevalence of overweight and obesity than those that occurred in control schools. However, the intervention did result in significantly greater reductions in various indexes of adiposity. These changes may reduce the risk of childhood-onset type 2 diabetes. (Funded by the National Institutes of Health and the American Diabetes Association; ClinicalTrials.gov number, NCT00458029.)
Llama Antibody Fragments Recognizing Various Epitopes of the CD4bs Neutralize a Broad Range of HIV-1 Subtypes A, B and C

Many of the neutralising antibodies, isolated to date, display limited activities against the globally most prevalent HIV-1 subtypes A and C. Therefore, those subtypes are considered to be an important target for antibody-based therapy. Variable domains of llama heavy chain antibodies (VHH) have some superior properties compared with classical antibodies. Therefore we describe the application of trimeric forms of envelope proteins (Env), derived from HIV-1 of subtype A and B/C, for a prolonged immunization of two llamas. A panel of VHH, which interfere with CD4 binding to HIV-1 Env were selected with use of panning. The results of binding and competition assays to various Env, including a variant with a stabilized CD4-binding state (gp120Ds2), cross-competition experiments, maturation analysis and neutralisation assays, enabled us to classify the selected VHH into three groups. The VHH of group I were efficient mainly against viruses of subtype A, C and B′/C. The VHH of group II resemble the broadly neutralising antibody (bnmAb) b12, neutralizing mainly subtype B and C viruses, however some had a broader neutralisation profile. A representative of the third group, 2E7, had an even higher neutralization breadth, neutralizing 21 out of the 26 tested strains belonging to the A, A/G, B, B/C and C subtypes. To evaluate the contribution of certain amino acids to the potency of the VHH a small set of the mutants were constructed. Surprisingly this yielded one mutant with slightly improved neutralisation potency against 92UG37.A9 (subtype A) and 96ZM651.02 (subtype C). These findings and the well-known stability of VHH indicate the potential application of these VHH as anti-HIV-1 microbicides.
Effects of Local Disturbance of Tropical Forests on Frugivores and Seed Removal of a Small‐Seeded Afrotropical Tree

Abstract: Small‐scale, local disturbance of tropical forests, for example from selective logging, is widespread, but its effects on biodiversity and ecosystem function have rarely been studied. In 3 East African tropical rainforests, we investigated the effect of different levels of local forest disturbance on the frugivore community and on tree visitation and fruit removal rates of the small‐seeded tree Celtis durandii. We quantified birds and primates in little and heavily disturbed sites, distinguishing between forest specialists, forest generalists, and forest visitors. We quantified frugivorous tree visitors and seed removal rates of C. durandii trees in the same sites. Forest disturbance reduced the species richness and density of the frugivore community and of forest specialists. Frugivorous species and individuals visiting the study trees were reduced significantly, which led to a marginally significant decline in fruit removal by all frugivores and a significant reduction in removal by forest specialists. Reduction in fruit removal by forest specialists was not compensated for by increases in removal by forest generalists or visitors. Results did not differ among the 3 rainforests, which suggests they were consistent at a regional scale. So local forest disturbance led to a loss of frugivores and their seed removal services. This suggests that large‐seeded tree species and trees with small fruits are losing seed dispersers. Thus, local forest disturbance appears to have a more general negative impact on frugivores and their seed dispersal services than anticipated previously.
Distributed Statistical Estimation and Rates of Convergence in Normal Approximation

This paper presents a class of new algorithms for distributed statistical estimation that exploit divide-and-conquer approach. We show that one of the key benefits of the divide-and-conquer strategy is robustness, an important characteristic for large distributed systems. We establish connections between performance of these distributed algorithms and the rates of convergence in normal approximation, and prove non-asymptotic deviations guarantees, as well as limit theorems, for the resulting estimators. Our techniques are illustrated through several examples: in particular, we obtain new results for the median-of-means estimator, as well as provide performance guarantees for distributed maximum likelihood estimation.
Global proteomic analysis of advanced glycation end products in the Arabidopsis proteome provides evidence for age-related glycation hot spots

Glycation is a post-translational modification resulting from the interaction of protein amino and guanidino groups with carbonyl compounds. Initially, amino groups react with reducing carbohydrates, yielding Amadori and Heyns compounds. Their further degradation results in formation of advanced glycation end products (AGEs), also originating from α-dicarbonyl products of monosaccharide autoxidation and primary metabolism. In mammals, AGEs are continuously formed during the life of the organism, accumulate in tissues, are well-known markers of aging, and impact age-related tissue stiffening and atherosclerotic changes. However, the role of AGEs in age-related molecular alterations in plants is still unknown. To fill this gap, we present here a comprehensive study of the age-related changes in the Arabidopsis thaliana glycated proteome, including the proteins affected and specific glycation sites therein. We also consider the qualitative and quantitative changes in glycation patterns in terms of the general metabolic background, pathways of AGE formation, and the status of plant anti-oxidative/anti-glycative defense. Although the patterns of glycated proteins were only minimally influenced by plant age, the abundance of 96 AGE sites in 71 proteins was significantly affected in an age-dependent manner and clearly indicated the existence of age-related glycation hot spots in the plant proteome. Homology modeling revealed glutamyl and aspartyl residues in close proximity (less than 5 Å) to these sites in three aging-specific and eight differentially glycated proteins, four of which were modified in catalytic domains. Thus, the sites of glycation hot spots might be defined by protein structure that indicates, at least partly, site-specific character of glycation.
Relationships between astrogliosis and 1H MR spectroscopic measures of brain choline/creatine and myo-inositol/creatine in a primate model.

BACKGROUND AND PURPOSE In vivo 1H MR spectroscopy demonstrates elevated choline (Cho)/creatine (Cr) and myo-inositol (MI)/Cr in many neurologic diseases that has been ascribed to gliosis. We tested the hypotheses that in vivo Cho/Cr and/or MI/Cr levels are correlated with glial fibrillary acidic protein (GFAP) immunostains and that the changes are water-soluble metabolites. METHODS We performed postmortem 1H MR spectroscopy and GFAP immunohistochemistry in brains from seven rhesus macaques acutely infected with simian immunodeficiency virus (SIV) and in four controls and compared the findings with previous in vivo MR spectroscopic results. Changes in neuropathologic and MR spectroscopic markers after infection and relationships among plasma viral load, GFAP immunostaining results, and ex vivo and in vivo MR spectroscopic measures were statistically evaluated. RESULTS On GFAP immunostaining and in vivo MR spectroscopy, GFAP, Cho/Cr and MI/Cr were highest near the time of peak plasma viral load at 11 days postinfection (dpi). Immunostains returned to baseline by 14 dpi, whereas Cho/Cr and MI/Cr had different time courses, with the former dropping below baseline and the latter remaining elevated. Viral load and immunostains were significantly correlated. No correlation was found between ex vivo Cho/Cr or MI/Cr and viral load or between metabolite ratios from in vivo and ex vivo MR spectroscopy. CONCLUSION In acute SIV infection, plasma viral load was significantly correlated with brain GFAP immunostains and in vivo 1H MR spectroscopic Cho/Cr. In vivo changes in Cho/Cr and MI/Cr were principally due to contributions other than those of low-molecular-weight water-soluble metabolites.
Q Methodology in Assessment and Research

The purpose of this seminar is to introduce statistical and methodological principles associated with the use of Q method in the study of subjectivity—with primary emphasis on its applicability to problems of public policy—and to locate Q methodology within the framework of contemporary science. Q methodology evolved from factor-analytic theory in the 1930s, and since that time has been applied in the systematic study of a wide range of subject matters in psychology, political science, communication, the health sciences, education, and the behavioral and human sciences more generally, and increasingly in the policy field. Attention will focus initially on historical and methodological developments, with special emphasis on factor-analytic and epistemological foundations, and on the fundamental importance of subjectivity in all human action. Subsequently, the seminar will move to applications in substantive areas of particular interest to participants. Time and other resources permitting, actual studies will be undertaken, individually or collectively.
Conservatism vs. conservationism: differential influences of social identities on beliefs about fracking

ABSTRACT Although recent expansions in hydraulic fracking operations across the United States have led to greater news coverage and attention from the public, overall understanding remains fairly low. For some, relevant social identities, including environmental or political, may provide a short cut to becoming informed about fracking, or to determining what they believe about it and how that influences their positions on fracking policies. Social identity influence frameworks provide an approach to understanding the relationships between belief and identity, which this study investigates through its affiliational and attitudinal components. National survey data are used to model pathways from environmental and political identities to beliefs about risks associated with fracking. Environmental attitudes significantly predicted belief that fracking has health risks, and mediated a relationship from environmental group affiliation, but environmental information was not significant. Ideology had direct and indirect effects, through partisan media use, while partisanship had direct effects on beliefs about environmental risks.
A TLR4-interacting peptide inhibits lipopolysaccharide-stimulated inflammatory responses, migration and invasion of colon cancer SW480 cells

Inflammation is a major risk factor for carcinogenesis in patients affected by chronic colitis, yet the molecular mechanisms underlying the progression from chronic inflammation to cancer are not completely understood. Activation of the Toll-like receptor 4 (TLR4)-NFκB signaling axis is associated with inflammation. Thus, we hypothesized that inhibition of TLR4-NFκB signaling might help in limiting inflammatory responses and inflammation-induced oncogenesis. In this work, we studied the effects of a TLR4-interacting surfactant protein A-derived (SPA4) peptide on lipopolysaccharide (LPS)-induced TLR4-NFκB signaling and cancer progression. We first characterized this peptide for its ability to bind the TLR4 ligand-LPS and for physico-chemical characteristics. Inflammation was induced by challenging the colon cancer SW480 cells with Escherichia coli LPS. Cells were then treated with varying amounts of the SPA4 peptide. Changes in the expression of TLR4, interleukin (IL)-1β and IL-6, in intracellular NFκB-related signal transducers (IKBα, p65, phosphorylated IKBα, phosphorylated p65, RelB, COX-2) as well as in the transcriptional activity of NFκB were studied by immunocytochemistry, immunoblotting and NFκB reporter assay, respectively. Simultaneously, the effects on LPS-induced cell migration and invasion were determined. We found that the SPA4 peptide does not bind to LPS. Rather, its binding to TLR4 inhibits the LPS-induced phosphorylation of p65, production of IL-1β and IL-6, activity of NFκB, migration and invasion of SW480 cells. In conclusion, our results suggest that the inhibition of TLR4-NFκB signaling by a TLR4-binding peptide may help for the treatment of chronic inflammation and prevention of inflammation-induced cancer in patients with colitis.
A Test of the Behavioral Perspective Model in the Context of an E-Mail Marketing Experiment

An e-mail marketing experiment based on the behavioral perspective model was conducted to investigate consumer choice. Conversion e-mails were sent to two groups from the same marketing database of registered consumers interested in children’s books. The experiment was based on A-B-A-C-A and A-C-A-B-A withdrawal designs and consisted of sending B = utilitarian (economic/functional) and C = informational (social) advertising stimuli with a clear call for action. Key measurements consisted of individuals receiving the e-mail, opening it, clicking on a link, and buying the target books. Aggregated results showed that the informational stimuli were more successful in inducing consumers to open the e-mails whereas the utilitarian stimuli were beneficial in increasing buying behavior. Data for individual consumer behavior indicate possible stimulus control in the case of particular consumers and potentials for functional analysis. The results show different appropriateness of stimuli for shaping consumer responses online and possibilities for translational work in behavior analysis.
Enhancement of Immunoglobulin G2a and Cytotoxic T-Lymphocyte Responses by a Booster Immunization with Recombinant Hepatitis C Virus E2 Protein in E2 DNA-Primed Mice

ABSTRACT The induction of strong cytotoxic T-lymphocyte (CTL) and humoral responses appear to be essential for the elimination of persistently infecting viruses, such as hepatitis C virus (HCV). Here, we tested several vaccine regimens and demonstrate that a combined vaccine regimen, consisting of HCV E2 DNA priming and boosting with recombinant E2 protein, induces the strongest immune responses to HCV E2 protein. This combined vaccine regimen augments E2-specific immunoglobulin G2a (IgG2a) and CD8+ CTL responses to a greater extent than immunizations with recombinant E2 protein and E2 DNA alone, respectively. In addition, the data showed that a protein boost following one DNA priming was also effective, but much less so than those following two DNA primings. These data indicate that sufficient DNA priming is essential for the enhancement of DNA encoded antigen-specific immunity by a booster immunization with recombinant E2 protein. Furthermore, the enhanced CD8+ CTL and IgG2a responses induced by our combined vaccine regimens are closely associated with the protection of BALB/c mice from challenge with modified CT26 tumor cells expressing HCV E2 protein. Together, our results provide important implications for vaccine development for many pathogens, including HCV, which require strong antibody and CTL responses.