Miracle-dz/UniFAR-FTUs huggingface dataset:
Nutrient Metabolism Polymeric Proanthocyanidins Are Catabolized by Human Colonic Microflora into Low-Molecular-Weight Phenolic Acids 1

Polymeric proanthocyanidins are common constituents of many foods and beverages. Their fate in the human body remains largely unknown. Their metabolism by human colonic microflora incubated in vitro in anoxic conditions has been investigated using nonlabeled and C-labeled purified proanthocyanidin polymers. Polymers were almost totally degraded after 48 h of incubation. Phenylacetic, phenylpropionic and phenylvaleric acids, monohydroxylated mainly in the meta or para position, were identified as metabolites by gas chromatography coupled to mass spectrometry (GC-MS). Yields were similar to those previously reported for flavonoid monomers. These results provide the first evidence of degradation of dietary phenolic polymers into low-molecularweight aromatic compounds. To understand the nutritional properties of proanthocyanidins, it is therefore essential to consider the biological properties of these metabolites. J. Nutr. 130: 2733–2738, 2000.
Validation of the Dutch and the French version of the Tinnitus Questionnaire.

OBJECTIVES To validate the Dutch and the French version of the Tinnitus Questionnaire and characterise the subscales. The original Tinnitus Questionnaire has already proven to be a usable measurement tool to discriminate complaining from non-complaining tinnitus patients and it provides differentiation into 5 dimensions. METHODS The English version of the TQ was used. The Dutch and the French version were obtained by the process of translation and back-translation. The TQ was assessed in 167 patients whose mother tongue was Dutch and who presented at the ENT department of the Antwerp University Hospital. Internal consistency was evaluated using Cronbach's alpha coefficient. Factor analysis with Varimax oblique rotation was compared to the results from previous psychometric analysis of the original TQ. RESULTS The internal consistency of the Dutch version of the TQ proved to be very high, with a Cronbach's alpha value of 0.95. Independent factor analysis identified the five subscales in accordance with the Hiller and Goebel's findings: emotional and cognitive distress, intrusiveness, auditory perceptual difficulties, sleep disturbances and somatic complaints. CONCLUSION The Dutch and the French translation of the TQ are included here. The psychometric characters of the Dutch questionnaire are similar to the original English questionnaire. This questionnaire provides appropriate disease-specific health-related quality-of-life outcome measures in tinnitus patients. In addition to the TQ, we advise the incorporation of three equal-appearing interval scales in all tinnitus anamnesis and follow-up.
The Nodulation of Alfalfa by the Acid-Tolerant Rhizobium sp. Strain LPU83 Does Not Require Sulfated Forms of Lipochitooligosaccharide Nodulation Signals

ABSTRACT The induction of root nodules by the majority of rhizobia has a strict requirement for the secretion of symbiosis-specific lipochitooligosaccharides (nodulation factors [NFs]). The nature of the chemical substitution on the NFs depends on the particular rhizobium and contributes to the host specificity imparted by the NFs. We present here a description of the genetic organization of the nod gene cluster and the characterization of the chemical structure of the NFs associated with the broad-host-range Rhizobium sp. strain LPU83, a bacterium capable of nodulating at least alfalfa, bean, and Leucena leucocephala. The nod gene cluster was located on the plasmid pLPU83b. The organization of the cluster showed synteny with those of the alfalfa-nodulating rhizobia, Sinorhizobium meliloti and Sinorhizobium medicae. Interestingly, the strongest sequence similarity observed was between the partial nod sequences of Rhizobium mongolense USDA 1844 and the corresponding LPU83 nod genes sequences. The phylogenetic analysis of the intergenic region nodEG positions strain LPU83 and the type strain R. mongolense 1844 in the same branch, which indicates that Rhizobium sp. strain LPU83 might represent an early alfalfa-nodulating genotype. The NF chemical structures obtained for the wild-type strain consist of a trimeric, tetrameric, and pentameric chitin backbone that shares some substitutions with both alfalfa- and bean-nodulating rhizobia. Remarkably, while in strain LPU83 most of the NFs were sulfated in their reducing terminal residue, none of the NFs isolated from the nodH mutant LPU83-H were sulfated. The evidence obtained supports the notion that the sulfate decoration of NFs in LPU83 is not necessary for alfalfa nodulation.
Transgenic Mouse Model Expressing the Caspase 6 Fragment of Mutant Huntingtin

Huntington's disease (HD) is caused by a polyglutamine expansion in the Huntingtin (Htt) protein. Proteolytic cleavage of Htt into toxic N-terminal fragments is believed to be a key aspect of pathogenesis. The best characterized putative cleavage event is at amino acid 586, hypothesized to be mediated by caspase 6. A corollary of the caspase 6 cleavage hypothesis is that the caspase 6 fragment should be a toxic fragment. To test this hypothesis, and further characterize the role of this fragment, we have generated transgenic mice expressing the N-terminal 586 aa of Htt with a polyglutamine repeat length of 82 (N586–82Q), under the control of the prion promoter. N586–82Q mice show a clear progressive rotarod deficit by 4 months of age, and are hyperactive starting at 5 months, later changing to hypoactivity before early mortality. MRI studies reveal widespread brain atrophy, and histologic studies demonstrate an abundance of Htt aggregates, mostly cytoplasmic, which are predominantly composed of the N586–82Q polypeptide. Smaller soluble N-terminal fragments appear to accumulate over time, peaking at 4 months, and are predominantly found in the nuclear fraction. This model appears to have a phenotype more severe than current full-length Htt models, but less severe than HD mouse models expressing shorter Htt fragments. These studies suggest that the caspase 6 fragment may be a transient intermediate, that fragment size is a factor contributing to the rate of disease progression, and that short soluble nuclear fragments may be most relevant to pathogenesis.
Conkunitzin-S1 Is the First Member of a New Kunitz-type Neurotoxin Family

Conkunitzin-S1 (Conk-S1) is a 60-residue neurotoxin from the venom of the cone snail Conus striatus that interacts with voltage-gated potassium channels. Conk-S1 shares sequence homology with Kunitz-type proteins but contains only two out of the three highly conserved cysteine bridges, which are typically found in these small, basic protein modules. In this study the three-dimensional structure of Conk-S1 has been solved by multidimensional NMR spectroscopy. The solution structure of recombinant Conk-S1 shows that a Kunitz fold is present, even though one of the highly conserved disulfide cross-links is missing. Introduction of a third, homologous disulfide bond into Conk-S1 results in a functional toxin with similar affinity for Shaker potassium channels. The affinity of Conk-S1 can be enhanced by a pore mutation within the Shaker channel pore indicating an interaction of Conk-S1 with the vestibule of potassium channels.
Interactions between a herpes simplex virus regulatory protein and cellular mRNA processing pathways.

The herpes simplex virus type 1 (HSV-1) immediate-early regulatory protein ICP27 performs essential functions during viral lytic infection. Studies with viral mutants have demonstrated that ICP27 affects the shutoff of host protein synthesis, HSV-1 DNA replication, and the expression of viral early and late genes. Mounting evidence has been presented to demonstrate that ICP27 functions predominantly at the posttranscriptional level by affecting mRNA processing. That is, ICP27 alters poly(A) site usage, impairs host cell splicing, and facilitates the export of viral intronless mRNAs. These diverse effects occur by the interaction of ICP27 with viral and host proteins and by binding RNA. To define the precise mechanisms by which ICP27 affects RNA processing pathways, it is necessary to identify all of the molecular interactions of ICP27 in vivo and to determine the functional significance of these interactions. In vivo approaches will be emphasized here. Protein-protein interactions have been analyzed by coimmunoprecipitation studies, followed by immunoblotting to confirm the identity of coprecipitating proteins. Indirect immunofluorescence staining has been performed on cells treated with RNA polymerase II inhibitors to determine the intracellular distribution of ICP27 related to its RNA export function. Finally, in vivo UV irradiation has been used to covalently cross-link ICP27 to mRNAs in direct contact. This was followed with procedures to isolate and analyze the protein-RNA complexes. These studies have revealed several splicing complex proteins with which ICP27 interacts and have identified a number of intronless RNA transcripts to which ICP27 binds in the nucleus and cytoplasm in its role in RNA transport.
Building Community Capacity: Sustaining the Effects of Multiple, Two-Year Community-based Participatory Research Projects

Background: The time-limited nature of health and public health research fellowships poses a challenge to trainees’ and community partners’ efforts to sustain effective, collaborative, community-based participatory research (CBPR) relationships.Objectives: This paper presents CBPR case studies of partnerships between health services research trainees and community organization leaders in a medium-sized city to describe how participation in the partnership altered community partners’ understanding and willingness to conduct research and to engage with research-derived data.Methods: Trainees and faculty used participatory methods with community leaders to identify research questions, and conduct and disseminate research. Throughout the process, trainees and faculty included research capacity building of community partners as a targeted outcome. Community partners were asked to reflect retrospectively on community research capacity building in the context of CBPR projects. Reflections were discussed and categorized by the authorship team, who grouped observations into topics that may serve as a foundation for development of future prospective analyses.Results: Important ideas shared include that trainee participation in CBPR may have an enduring impact on the community by increasing the capacity of community partners and agencies to engage in research beyond that which they are conducting with the current trainee.Conclusion: We posit that CBPR with research trainees may have an additive effect on community research capacity when it is conducted in collaboration with community leaders and focuses on a single region. More research is needed to characterize this potential outcome.
Expression of urokinase plasminogen activator receptor in resting and activated bovine neutrophils

Changes in urokinase-plasminogen activator (u-PA) and u-PA receptor (u-PAR) expression at the protein and mRNA level in resting neutrophils and in neutrophils activated by phorbol myristate acetate (PMA) were examined. Low amounts of u-PA were found intracellularly or membrane-bound in resting neutrophils. However, incubation of resting neutrophils with purified exogenous u-PA (10 IU/ml) revealed extensive binding of u-PA to cell membranes. Excess amino-terminal fragment of the u-PA molecule, a proteolytically inactive fragment of u-PA (amino acids 1–135) blocked binding of exogenous u-PA to the cell membrane. These results, collectively, indicate that the binding of u-PA is specific and that resting neutrophils have unoccupied u-PA receptors on their cell membrane. Addition of PMA led to an increase (P<0.01) in total cell-associated, membrane-bound u-PA activity and u-PA mRNA expression by bovine neutrophils. In contrast, PMA increased u-PAR mRNA levels but this was accompanied by a decrease (2.5-fold; P<0.01) in free, unoccupied u-PA binding sites. No significant effects on total cell-associated or membrane-bound u-PA were found when neutrophils were treated with 4-phorbol 12,13 didecanoate, a phorbol ester that does not activate protein kinase C (PKC). Furthermore, addition of 1-(5-isoquinolinesylphonyl)-2-methylpiperazine dihydrochloride (H-7), a potent PKC inhibitor, blocked the effect of PMA on total cell-associated u-PA activity. Thus, PKC plays a role in the modulation of u-PA and u-PAR by PMA in bovine neutrophils.
Relationship between the Antifungal Susceptibility Profile and the Production of Virulence-Related Hydrolytic Enzymes in Brazilian Clinical Strains of Candida glabrata

Candida glabrata is a facultative intracellular opportunistic fungal pathogen in human infections. Several virulence-associated attributes are involved in its pathogenesis, host-pathogen interactions, modulation of host immune defenses, and regulation of antifungal drug resistance. This study evaluated the in vitro antifungal susceptibility profile to five antifungal agents, the production of seven hydrolytic enzymes related to virulence, and the relationship between these phenotypes in 91 clinical strains of C. glabrata. All C. glabrata strains were susceptible to flucytosine. However, some of these strains showed resistance to amphotericin B (9.9%), fluconazole (15.4%), itraconazole (5.5%), or micafungin (15.4%). Overall, C. glabrata strains were good producers of catalase, aspartic protease, esterase, phytase, and hemolysin. However, caseinase and phospholipase in vitro activities were not detected. Statistically significant correlations were identified between micafungin minimum inhibitory concentration (MIC) and esterase production, between fluconazole and micafungin MIC and hemolytic activity, and between amphotericin B MIC and phytase production. These results contribute to clarify some of the C. glabrata mechanisms of pathogenicity. Moreover, the association between some virulence attributes and the regulation of antifungal resistance encourage the development of new therapeutic strategies involving virulence mechanisms as potential targets for effective antifungal drug development for the treatment of C. glabrata infections.
The role of genotoxicity in asbestos-induced mesothelioma: an explanation for the differences in carcinogenic potential among fiber types

Abstract The mechanism(s) underlying asbestos toxicity associated with the pathogenesis of mesothelioma has been a challenge to unravel for more than 60 years. A significant amount of research has focused on the characteristics of different fiber types and their potential to induce mesothelioma. These mechanistic studies of fiber toxicity have proceeded along two lines: those demonstrating biochemical mechanisms by which fibers induce disease and those investigating human susceptibility. Most recent studies focused on in vitro genotoxic effects induced by asbestos as the mechanism responsible for asbestos-induced disease. Although asbestos exerts a genotoxic effect at certain concentrations in vitro, a positive response in these tests does not indicate that the chemical is likely to produce an increased risk of carcinogenesis in exposed human populations. Thus far, findings from studies on the effects of fiber type in mesothelial cells are seriously flawed by a lack of a dose response relationship. The common limitation of these in vitro experiments is the lack of attention paid to the complexities of the human anatomy, biochemistry and physiology, which make the observed effects in these experimental systems difficult to extrapolate to persons in the workplace. Mechanistic differences between carcinogenic and genotoxic processes indicate why tests for genotoxicity do not provide much insight regarding the ability to predict carcinogenic potential in workers exposed to asbestos doses in the post-Occupational Safety and Health Administration era. This review discusses the existing literature on asbestos-induced genotoxicity and explains why these studies may or may not likely help characterize the dose-response curve at low dose.
Analyzing direct and indirect effects of treatment using dynamic path analysis applied to data from the Swiss HIV Cohort Study

When applying survival analysis, such as Cox regression, to data from major clinical trials or other studies, often only baseline covariates are used. This is typically the case even if updated covariates are available throughout the observation period, which leaves large amounts of information unused. The main reason for this is that such time‐dependent covariates often are internal to the disease process, as they are influenced by treatment, and therefore lead to confounded estimates of the treatment effect. There are, however, methods to exploit such covariate information in a useful way. We study the method of dynamic path analysis applied to data from the Swiss HIV Cohort Study. To adjust for time‐dependent confounding between treatment and the outcome ‘AIDS or death’, we carried out the analysis on a sequence of mimicked randomized trials constructed from the original cohort data. To analyze these trials together, regular dynamic path analysis is extended to a composite analysis of weighted dynamic path models. Results using a simple path model, with one indirect effect mediated through current HIV‐1 RNA level, show that most or all of the total effect go through HIV‐1 RNA for the first 4 years. A similar model, but with CD4 level as mediating variable, shows a weaker indirect effect, but the results are in the same direction. There are many reasons to be cautious when drawing conclusions from estimates of direct and indirect effects. Dynamic path analysis is however a useful tool to explore underlying processes, which are ignored in regular analyses. Copyright © 2011 John Wiley & Sons, Ltd.
Resistance to antiretroviral drugs in newly diagnosed, young treatment‐naïve HIV‐positive pregnant women in the province of KwaZulu‐Natal, South Africa

In 2004, KwaZulu‐Natal initiated one of the world's largest HIV/AIDS treatment programs. Studies in South Africa have shown that patients on antiretroviral therapy (ART) develop rapidly and transmit drug resistant mutations. Since resistance testing is not widely available in Kwazulu‐Natal, the Department of Health conducted the first HIV drug resistance (HIVDR) threshold survey in 2005, which did not identify any mutations associated with HIVDR. The objective of this study was to conduct a follow‐up threshold survey to update the information on HIVDR. This study was conducted in 2009 in five antenatal care sites in Kwazulu‐Natal using the HIVDR threshold survey method developed by WHO. Two hundred and thirteen newly‐diagnosed HIV positive, drug‐naïve primigravidae, less than 22 years of age were included in the survey. Of the 82 HIV positive specimens, 17 had insufficient volume for genotyping and, of the remaining 65, 47 were genotyped sequentially. Drug resistance was identified by sequencing the HIV‐1 pol gene, using the ViroSeq® HIV‐1 genotyping system v2.0. Of the 47 samples that were genotyped, only one presented with a K103N mutation, which equates to a prevalence of transmitted HIVDR of <5%. The low prevalence of transmitted HIVDR is in keeping with statistical models of the early stages of ART rollout. As ART coverage is increasing continuously, there is a need to ensure that vigilance of HIVDR continues so that the emergence and spread of HIVDR is minimized. This survey should be repeated in 2011, in accordance with WHO guidelines. J. Med. Virol. 83:1508–1513, 2011. © 2011 Wiley‐Liss, Inc.
The secreted hemolysins of Proteus mirabilis, Proteus vulgaris, and Morganella morganii are genetically related to each other and to the alpha-hemolysin of Escherichia coli

Secreted hemolysins were extremely common among clinical isolates of Proteus mirabilis, Proteus vulgaris, and Morganella morganii, and hemolytic activity was either cell associated or cell free. Southern hybridization of total DNA from hemolytic isolates to cloned regions of the Escherichia coli alpha-hemolysin (hly) determinant showed clear but incomplete homology between genes encoding production of hemolysins in the four species. One of the two E. coli secretion genes, hlyD, hybridized only with DNA from P. vulgaris and M. morganii, which produced cell-free hemolysis, but not with that from P. mirabilis, which showed only cell-associated activity. Molecular cloning of the genetic determinants of cell-free hemolytic activity from P. vulgaris and M. morganii chromosomal DNA allowed their functional analysis via inactivation with the transposons Tn1000 and Tn5. Both hemolysin determinants were about 7.5 kilobase pairs and comprised contiguous regions directing regulation, synthesis, and specific secretion out of the cell. Transposon mutations which eliminated secretion of the Proteus and Morganella hemolysins could be complemented specifically by the E. coli hemolysin secretion genes hlyB or hlyD. Alignment of the physically and functionally defined hly determinants from P. vulgaris and M. morganii with that of the E. coli alpha-hemolysin confirmed a close genetic relationship but also indicated extensive evolutionary divergence.