Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteolysis-Independent Downregulation of DELLA Repression in Arabidopsis by the Gibberellin Receptor GIBBERELLIN INSENSITIVE DWARF1[W]

This article presents evidence that DELLA repression of gibberellin (GA) signaling is relieved both by proteolysis-dependent and -independent pathways in Arabidopsis thaliana. DELLA proteins are negative regulators of GA responses, including seed germination, stem elongation, and fertility. GA stimulates GA responses by causing DELLA repressor degradation via the ubiquitin-proteasome pathway. DELLA degradation requires GA biosynthesis, three functionally redundant GA receptors GIBBERELLIN INSENSITIVE DWARF1 (GID1a, b, and c), and the SLEEPY1 (SLY1) F-box subunit of an SCF E3 ubiquitin ligase. The sly1 mutants accumulate more DELLA proteins but display less severe dwarf and germination phenotypes than the GA biosynthesis mutant ga1-3 or the gid1abc triple mutant. Interestingly, GID1 overexpression rescued the sly1 dwarf and infertility phenotypes without decreasing the accumulation of the DELLA protein REPRESSOR OF ga1-3. GID1 rescue of sly1 mutants was dependent on the level of GID1 protein, GA, and the presence of a functional DELLA motif. Since DELLA shows increasing interaction with GID1 with increasing GA levels, it appears that GA-bound GID1 can block DELLA repressor activity by direct protein–protein interaction with the DELLA domain. Thus, a SLY1-independent mechanism for GA signaling may function without DELLA degradation.
Effects of long‐term ethanol consumption and Aldh1b1 depletion on intestinal tumourigenesis in mice

Ethanol and its metabolite acetaldehyde have been classified as carcinogens for the upper aerodigestive tract, liver, breast, and colorectum. Whereas mechanisms related to oxidative stress and Cyp2e1 induction seem to prevail in the liver, and acetaldehyde has been proposed to play a crucial role in the upper aerodigestive tract, pathological mechanisms in the colorectum have not yet been clarified. Moreover, all evidence for a pro‐carcinogenic role of ethanol in colorectal cancer is derived from correlations observed in epidemiological studies or from rodent studies with additional carcinogen application or tumour suppressor gene inactivation. In the current study, wild‐type mice and mice with depletion of aldehyde dehydrogenase 1b1 (Aldh1b1), an enzyme which has been proposed to play an important role in acetaldehyde detoxification in the intestines, received ethanol in drinking water for 1 year. Long‐term ethanol consumption led to intestinal tumour development in wild‐type and Aldh1b1‐depleted mice, but no intestinal tumours were observed in water‐treated controls. Moreover, a significant increase in DNA damage was detected in the large intestinal epithelium of ethanol‐treated mice of both genotypes compared with the respective water‐treated groups, along with increased proliferation of the small and large intestinal epithelium. Aldh1b1 depletion led to increased plasma acetaldehyde levels in ethanol‐treated mice, to a significant aggravation of ethanol‐induced intestinal hyperproliferation, and to more advanced features of intestinal tumours, but it did not affect intestinal tumour incidence. These data indicate that ethanol consumption can initiate intestinal tumourigenesis without any additional carcinogen treatment or tumour suppressor gene inactivation, and we provide evidence for a role of Aldh1b1 in protection of the intestines from ethanol‐induced damage, as well as for both carcinogenic and tumour‐promoting functions of acetaldehyde, including increased progression of ethanol‐induced tumours. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Resistance Profile of a Hepatitis C Virus RNA-Dependent RNA Polymerase Benzothiadiazine Inhibitor

ABSTRACT Recently, a benzo-1,2,4-thiadiazine antiviral agent (C21H21N3O4S; compound 4) was shown to be a potent, highly specific inhibitor of the primary catalytic enzyme of the hepatitis C virus (HCV) replicase complex. In this study, we selected for resistance to confirm the mechanism of action for compound 4 in HCV replicon cells. As expected, spontaneous mutations or fluidity in the HCV polymerase (NS5B) coding sequence occurred upon routine passage of the HCV replicon cells in the absence of compound 4. After 1 month of culture in the presence of 10 μM compound 4, or 20 times the 50% inhibitory concentration of the replicon, replicon cells were almost 20-fold less susceptible to compound 4. Twenty-one NS5B cDNA clones were generated from the resistant replicon cells. Five mutations in the 21 NS5B clones were present at frequencies higher than that of control replicon cells, and no clone contained more than a single mutation within the polymerase gene. RNA-dependent RNA polymerase studies using purified recombinant NS5B containing these single point mutations allowed the identification of residue 414 as sufficient for biochemical resistance to compound 4. Further, the contribution of this residue to confer cell-based resistance to compound 4 was validated using a stable recombinant mutant replicon cell line which harbors a methionine-to-threonine change at residue 414. The potential for additional mutations in other nonstructural genes of HCV to contribute to the resistance profile of compound 4 is discussed.
Exposure measurement error in time-series studies of air pollution: concepts and consequences.

Misclassification of exposure is a well-recognized inherent limitation of epidemiologic studies of disease and the environment. For many agents of interest, exposures take place over time and in multiple locations; accurately estimating the relevant exposures for an individual participant in epidemiologic studies is often daunting, particularly within the limits set by feasibility, participant burden, and cost. Researchers have taken steps to deal with the consequences of measurement error by limiting the degree of error through a study's design, estimating the degree of error using a nested validation study, and by adjusting for measurement error in statistical analyses. In this paper, we address measurement error in observational studies of air pollution and health. Because measurement error may have substantial implications for interpreting epidemiologic studies on air pollution, particularly the time-series analyses, we developed a systematic conceptual formulation of the problem of measurement error in epidemiologic studies of air pollution and then considered the consequences within this formulation. When possible, we used available relevant data to make simple estimates of measurement error effects. This paper provides an overview of measurement errors in linear regression, distinguishing two extremes of a continuum-Berkson from classical type errors, and the univariate from the multivariate predictor case. We then propose one conceptual framework for the evaluation of measurement errors in the log-linear regression used for time-series studies of particulate air pollution and mortality and identify three main components of error. We present new simple analyses of data on exposures of particulate matter < 10 microm in aerodynamic diameter from the Particle Total Exposure Assessment Methodology Study. Finally, we summarize open questions regarding measurement error and suggest the kind of additional data necessary to address them. ImagesFigure 1Figure 2Figure 3
Influence of melatonin therapy and orchiectomy on T cell subsets in male Wistar rats infected with Trypanosoma cruzi

Abstract: Gonadal steroids exert an important influence on the host immune response during infection. Changes resulting from the absence or replacement of gonadal hormones may represent a distinct evolution of a particular parasite. Taking into account the greater susceptibility of males to parasites, the magnitude of the immune response seems to depend on the interaction of many hormones that will act synergistically with other immune cells. The aims of this research were to evaluate the effects of the luck of male sex hormones due to orchiectomy, and the influence of oral administration of melatonin on the immune response of male Wistar rats infected with the Y strain of Trypanosoma cruzi. The percentage of CD3+ CD4+ and CD3+ CD8+ lymphocyte T cell subsets were evaluated using flow cytometry and the measurement of IL‐2 and IL‐12. For all parameters examined, a synergistic action of melatonin and orchiectomy on the host’s immune response was observed, promoting an effective response against the parasite during the acute phase of infection. These results offer insight into other possibilities for possibly controlling T. cruzi proliferation through melatonin therapy and also the stimulatory effects on host’s immune response triggered by the absence of male gonadal steroids during the acute phase of infection.
Medicine

Rapid Method of Demonstrating Tubercle Bacilli in Sputa. Reagents. (1) A saturated alcoholic solution of fuchsin. (2) A five per cent, solution of carbolic acid in distilled water. (3) A twenty-five per cent, solution of nitric acid for decolorising. Method. On a cover-glass with sputum first drop the carbolic acid solution and then the fuchsin solution, in the proportion of 1 part of the latter to 3 parts of the former, i.e., until the fuchsin precipitate clears up. Hold the coverglass over a flame; but do not let the stain dry on the glass. Wash the glass in running water, and then immerse in the decolorising nitric acid solution for 20 or 30 seconds, until all color is lost. Wash the glass again in running water, and then dry it with blotting paper and heat. Put a drop of glycerine, balsam, or water on the
Capacity of Physiotherapy Workforce Production in Thailand: Public-Private Mix, Secular Trend and Geographic Distribution.

BACKGROUND AND PURPOSE In Thailand, the shortage of physiotherapists has been an increasing concern because of increased health burden from demographic and epidemiologic changes. This study aims to analyse the current situation of the physiotherapy workforce production system, secular trend, geographical distribution and comparison of public and private physiotherapy training institutes. METHODS Longitudinal data related to production capacity of the physiotherapy institutes were applied. Data from 2008 to 2012 were obtained from all 16 physiotherapy institutes in Thailand. Data during 2000-2007 were also retrieved from annual reports from the Ministry of Education. Descriptive statistics were initially used. Comparison was made between public and private physiotherapy institutes in terms of the number of students admitted and graduated, number of teachers, annual tuition fee, student-teacher ratio and dropout rate within 1 year. Predictive factors for graduation within 4 years were determined using logistic regression. RESULTS In Thailand, there was an average of 800 physiotherapy graduates per year. New private institutes have been recently established and have steadily increased student admission rates. However, this has resulted in a high student-teacher ratio (median 7.1, inter-quartile range (IQR) 5.9-10.0). The first-year dropout rate in 2012 was 29.1%. Geographically, the majority of the institutes are clustered in the central region. Multivariate analysis revealed significantly lower probability of graduation within 4 years among students admitted to the private institutes and those in non-north-east region. CONCLUSION The production capacity of the physiotherapy workforce is below an estimated need. Private physiotherapy institutes need more support to improve the situation of staff shortages and student graduation rates. The non-central regions should be encouraged to produce more physiotherapists. Copyright © 2015 John Wiley & Sons, Ltd.
Small RNAs in the control of RpoS, CsgD, and biofilm architecture of Escherichia coli

Amyloid curli fibers and cellulose are extracellular matrix components produced in the stationary phase top layer of E. coli macrocolonies, which confer physical protection, strong cohesion, elasticity, and wrinkled morphology to these biofilms. Curli and cellulose synthesis is controlled by a three-level transcription factor (TF) cascade with the RpoS sigma subunit of RNA polymerase at the top, the MerR-like TF MlrA, and the biofilm regulator CsgD, with two c-di-GMP control modules acting as key switching devices. Additional signal input and fine-tuning is provided by an entire series of small RNAs—ArcZ, DsrA, RprA, McaS, OmrA/OmrB, GcvB, and RydC—that differentially control all three TF modules by direct mRNA interaction. This review not only summarizes the mechanisms of action of these sRNAs, but also addresses the question of how these sRNAs and the regulators they target contribute to building the intriguing three-dimensional microarchitecture and macromorphology of these biofilms.
Prospects for Developing Odour Baits To Control Glossina fuscipes spp., the Major Vector of Human African Trypanosomiasis

We are attempting to develop cost-effective control methods for the important vector of sleeping sickness, Glossina fuscipes spp. Responses of the tsetse flies Glossina fuscipes fuscipes (in Kenya) and G. f. quanzensis (in Democratic Republic of Congo) to natural host odours are reported. Arrangements of electric nets were used to assess the effect of cattle-, human- and pig-odour on (1) the numbers of tsetse attracted to the odour source and (2) the proportion of flies that landed on a black target (1×1 m). In addition responses to monitor lizard (Varanus niloticus) were assessed in Kenya. The effects of all four odours on the proportion of tsetse that entered a biconical trap were also determined. Sources of natural host odour were produced by placing live hosts in a tent or metal hut (volumes≈16 m3) from which the air was exhausted at ∼2000 L/min. Odours from cattle, pigs and humans had no significant effect on attraction of G. f. fuscipes but lizard odour doubled the catch (P<0.05). Similarly, mammalian odours had no significant effect on landing or trap entry whereas lizard odour increased these responses significantly: landing responses increased significantly by 22% for males and 10% for females; the increase in trap efficiency was relatively slight (5–10%) and not always significant. For G. f. quanzensis, only pig odour had a consistent effect, doubling the catch of females attracted to the source and increasing the landing response for females by ∼15%. Dispensing CO2 at doses equivalent to natural hosts suggested that the response of G. f. fuscipes to lizard odour was not due to CO2. For G. f. quanzensis, pig odour and CO2 attracted similar numbers of tsetse, but CO2 had no material effect on the landing response. The results suggest that identifying kairomones present in lizard odour for G. f. fuscipes and pig odour for G. f. quanzensis may improve the performance of targets for controlling these species.
Capsular Polysaccharide Phase Variation in Vibrio vulnificus

ABSTRACT Commonly found in raw oysters, Vibrio vulnificus poses a serious health threat to immunocompromised individuals and those with serum iron overload, with a fatality rate of approximately 50%. An essential virulence factor is its capsular polysaccharide (CPS), which is responsible for a significant increase in virulence compared to nonencapsulated strains. However, this bacterium is known to vary the amount of CPS expressed on the cell surface, converting from an opaque (Op) colony phenotype to a translucent (Tr) colony phenotype. In this study, the consistency of CPS conversion was determined for four strains of V. vulnificus. Environmental conditions including variations in aeration, temperature, incubation time, oxidative stress, and media (heart infusion or modified maintenance medium agar) were investigated to determine their influence on CPS conversion. All conditions, with the exception of variations in media and oxidative stress, significantly affected the conversion of the population, with high ranges of CPS expression found even within cells from a single colony. The global quorum-sensing regulators RpoS and AI-2 were also examined. While RpoS was found to significantly mediate phenotypic conversion, quorum sensing was not. Finally, 12 strains that comprise the recently found clinical (C) and environmental (E) genotypes of V. vulnificus were examined to determine their rates of population conversion. C-genotype strains, which are most often associated with infection, had a significantly lower rate of population conversion from Op to Tr phenotypes than did E-genotype strains (ca. 38% versus ca. 14%, respectively). Biofilm capabilities of these strains, however, were not correlated with increased population conversion.
Role of endothelial‐to‐mesenchymal transition induced by TGF‐β1 in transplant kidney interstitial fibrosis

Chronic allograft dysfunction (CAD) induced by kidney interstitial fibrosis is the main cause of allograft failure in kidney transplantation. Endothelial‐to‐mesenchymal transition (EndMT) may play an important role in kidney fibrosis. We, therefore, undertook this study to characterize the functions and potential mechanism of EndMT in transplant kidney interstitial fibrosis. Proteins and mRNAs associated with EndMT were examined in human umbilical vein endothelial cells (HUVECs) treated with transforming growth factor‐beta1 (TGF‐β1) at different doses or at different intervals with western blotting, qRT‐PCR and ELISA assays. Cell motility and migration were evaluated with motility and migration assays. The mechanism of EndMT induced by TGF‐β1 was determined by western blotting analysis of factors involved in various canonical and non‐canonical pathways. In addition, human kidney tissues from control and CAD group were also examined for these proteins by HE, Masson's trichrome, immunohistochemical, indirect immunofluorescence double staining and western blotting assays. TGF‐β1 significantly promoted the development of EndMT in a time‐dependent and dose‐dependent manner and promoted the motility and migration ability of HUVECs. The TGF‐β/Smad and Akt/mTOR/p70S6K signalling pathways were found to be associated with the pathogenesis of EndMT induced by TGF‐β1, which was also proven in vivo by the analysis of specimens from the control and CAD groups. EndMT may promote transplant kidney interstitial fibrosis by targetting the TGF‐β/Smad and Akt/mTOR/p70S6K signalling pathways, and hence, result in the development of CAD in kidney transplant recipients.
Complexity and Continuity of Treatments Among Privately Insured Youth Diagnosed with Bipolar Disorder

Objectives: To examine longitudinal patterns of complexity, continuity, and initiation of treatment for youth diagnosed with bipolar disorder. Additionally, we explore bipolar diagnosis stability and its relationship to observed treatment patterns. Methods: A cohort of 426 privately insured youth (ages 6–18) diagnosed with bipolar disorder was identified from the 2000–2001 Thomson/Medstat-MarketScan® database. Medication complexity was defined as number of different psychotropic medication classes dispensed during a 6-month period following a new treatment episode of bipolar disorder. Treatment continuity was examined over a 6-month follow-up period, specifically focusing on mood stabilizing medications and antidepressant monotherapy. Predictors of complexity and continuity were investigated. Results: Fifty-five percent of youth received more than one and 25% received three or more different types of psychotropic medication classes during follow-up. This was contrasted with several youth having no prescription fills (21%) and 31% discontinuing mood stabilizing medication. Youth with a stable bipolar diagnosis were more likely to have continuity of mood stabilizing prescriptions (OR: 4.05), but also greater psychotropic medication complexity. Age, health status/comorbidity, and being in a managed care plan were also related to complexity and continuity of psychotropic medication class regimens. Conclusions: More evidence is needed on the causal patterns leading to increased psychotropic medication complexity and continuity and how diagnosis of bipolar disorder may drive treatment patterns.
SOS Response Activation and Competence Development Are Antagonistic Mechanisms in Streptococcus thermophilus

ABSTRACT Streptococcus includes species that either contain or lack the LexA-like repressor (HdiR) of the classical SOS response. In Streptococcus pneumoniae, a species which belongs to the latter group, SOS response inducers (e.g., mitomycin C [Mc] and fluoroquinolones) were shown to induce natural transformation, leading to the hypothesis that DNA damage-induced competence could contribute to genomic plasticity and stress resistance. Using reporter strains and microarray experiments, we investigated the impact of the SOS response inducers mitomycin C and norfloxacin and the role of HdiR on competence development in Streptococcus thermophilus. We show that both the addition of SOS response inducers and HdiR inactivation have a dual effect, i.e., induction of the expression of SOS genes and reduction of transformability. Reduction of transformability results from two different mechanisms, since HdiR inactivation has no major effect on the expression of competence (com) genes, while mitomycin C downregulates the expression of early and late com genes in a dose-dependent manner. The downregulation of com genes by mitomycin C was shown to take place at the level of the activation of the ComRS signaling system by an unknown mechanism. Conversely, we show that a ComX-deficient strain is more resistant to mitomycin C and norfloxacin in a viability plate assay, which indicates that competence development negatively affects the resistance of S. thermophilus to DNA-damaging agents. Altogether, our results strongly suggest that SOS response activation and competence development are antagonistic processes in S. thermophilus.
Evidence for Large Decadal Variability in the Tropical Mean Radiative Energy Budget

It is widely assumed that variations in Earth's radiative energy budget at large time and space scales are small. We present new evidence from a compilation of over two decades of accurate satellite data that the top-of-atmosphere (TOA) tropical radiative energy budget is much more dynamic and variable than previously thought. Results indicate that the radiation budget changes are caused by changes in tropical mean cloudiness. The results of several current climate model simulations fail to predict this large observed variation in tropical energy budget. The missing variability in the models highlights the critical need to improve cloud modeling in the tropics so that prediction of tropical climate on interannual and decadal time scales can be improved.