Miracle-dz/UniFAR-FTUs huggingface dataset:
Varicella-zoster virus IE63 protein represses the basal transcription machinery by disorganizing the pre-initiation complex

Abstract Using transient transfection assays, regulation properties of varicella-zoster virus (VZV)-encoded IE63 protein were analyzed on several VZV immediate early (ORF4), early (ORF28) and late (ORF67) promoters. IE63 was shown to repress the basal activity of most of the promoters tested in epithelial (Vero) and neuronal (ND7) cells to various extents. Trans-repressing activities were also observed on heterologous viral and cellular promoters. Since a construct carrying only a TATA box sequence and a series of wild-type or mutated interleukin (IL)-8 promoters was also repressed by IE63, the role of upstream regulatory elements was ruled out. Importantly, the basal activity of a TATA-less promoter was not affected by IE63. Using a series of IE63 deletion constructs, amino acids 151–213 were shown to be essential to the trans-repressing activity in Vero cells, while in ND7 cells the essential region extended to a much larger carboxy-terminal part of the protein. We also demonstrate that IE63 is capable of disrupting the transcriptional pre-initiation complex and of interacting with several general transcription factors. The central and carboxy-terminal domains of IE63 are important for these effects. Altogether, these results demonstrate that IE63 protein is a transcriptional repressor whose activity is directed towards general transcription factors.
CORRELATION BETWEEN VISUAL PROGNOSIS AND FUNDUS AUTOFLUORESCENCE AND OPTICAL COHERENCE TOMOGRAPHIC FINDINGS IN HIGHLY MYOPIC EYES WITH SUBMACULAR HEMORRHAGE AND WITHOUT CHOROIDAL NEOVASCULARIZATION

Purpose: To determine whether a significant correlation existed between the visual prognosis and fundus autofluorescence and optical coherence tomographic images in highly myopic eyes with simple macular bleeding. Methods: We reviewed the charts of 31 eyes of 28 patients with high myopia and simple bleeding. The patients were divided into those whose best-corrected visual acuity (BCVA) was 20/32 and those with BCVA <20/32 at 6 months after absorption of the hemorrhage. Results: At 6 months, 19 eyes had BCVA ≥0.7 and 12 eyes had BCVA <0.7. In the former group, the inner segment/outer segment line of photoreceptors was intact in optical coherence tomographic images at the onset but was defective in 75% of the eyes in the latter group. At 6 months, the inner segment/outer segment defect was absent in all the eyes in the former group but was observed in 67% of the latter group. A hypoautofluorescence was present at the area of the bleeding more frequently in the poor BCVA groups. Conclusion: An inner segment/outer segment defect at the onset of simple bleeding might be a useful sign to predict a limited visual recovery. The persistent hypofluorescence in fundus autofluorescence is probably caused by damage to the retinal pigment epithelium by the subretinal hemorrhage.
Regulation of bacterial cell wall growth

During growth and propagation, a bacterial cell enlarges and subsequently divides its peptidoglycan (PG) sacculus, a continuous mesh‐like layer that encases the cell membrane to confer mechanical strength and morphological robustness. The mechanism of sacculus growth, how it is regulated and how it is coordinated with other cellular processes is poorly understood. In this article, we will discuss briefly the current knowledge of how cell wall synthesis is regulated, on multiple levels, from both sides of the cytoplasmic membrane. According to the current knowledge, cytosolic scaffolding proteins connect PG synthases with cytoskeletal elements, and protein phosphorylation regulates cell wall growth in Gram‐positive species. PG‐active enzymes engage in multiple protein–protein interactions within PG synthesis multienzyme complexes, and some of the interactions modulate activities. PG synthesis is also regulated by central metabolism, and by PG maturation through the action of PG hydrolytic enzymes. Only now are we beginning to appreciate how these multiple levels of regulating PG synthesis enable the cell to propagate robustly with a defined cell shape under different and variable growth conditions.
Localized in vivo 13C-NMR of Glutamate Metabolism in the Human Brain: Initial Results at 4 Tesla

Using optimized administration of 13C-labeled glucose, the time course of the specific activity of glucose was measured directly by in vivo 13C-NMR in the human brain at 4 Tesla. Subsequent label incorporation was measured at the C2, C3 and C4 positions of both glutamate and the well-resolved C2, C3 and C4 resonances of glutamine and at the C2 and C3 positions of aspartate. GABA was clearly observed for the first time in vivo, suggesting a substantial GABA turnover in the normal human visual cortex. Likewise, lactate C3 labeled with an estimated active pool size on the order of 0.5 mM. A model of cerebral glutamate metabolism is proposed which predicts that glutamatergic action (‘neurotransmission’), pyruvate carboxylase flux, TCA cycle activity, glucose consumption and exchange across the mitochondrial membrane can be assessed simultaneously in the human brain.
Elliptical shape estimation by nonlinear least-squares method for breast cancer using UWB radar technology

Ultra wide band (UWB) microwave imaging has been proposed for detecting small malignant breast cancers and expected to detect breast cancers with safety, less-discomfort and accuracy for high resolution of UWB pulse. However, shape estimation for breast cancers has been remained as a challenge. In this paper, we propose an elliptical shape estimation method by nonlinear least-squares method in order to develop a breast cancer shape estimation using UWB radar technology. We define a regression formula of a nonlinear least-squares method for one cancer considering a two-dimensional (2D) space. We confirm that our method could estimate parameters of an elliptical shape under simple environment using 2D Finite Difference Time Domain(FDTD) calculation. We evaluate the performance of our proposed method under additive white Gaussian noise(AWGN) environment using theoretical signal sets. We could get good results of estimation of 5 elliptical parameters.
Clinical Evaluation of Functional Vision of +1.5 Diopters near Addition, Aspheric, Rotational Asymmetric Multifocal Intraocular Lens

Purpose To evaluate postoperative outcomes and visual performance in intermediate distance after implantation of a +1.5 diopters (D) addition, aspheric, rotational asymmetric multifocal intraocular lens (MIOL). Methods Patients underwent bilateral cataract surgery with implantation of an aspheric, asymmetric MIOL with +1.5 D near addition. A complete ophthalmological examination was performed preoperatively and 3 months postoperatively. The main outcome measures were monocular and binocular uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), distance corrected intermediate visual acuity (DCIVA), uncorrected near visual acuity (UNVA) and distance corrected keratometry, and manifest refraction. The Salzburg Reading Desk was used to analyze unilateral and bilateral functional vision with uncorrected and corrected reading acuity, reading distance, reading speed, and the smallest log-scaled print size that could be read effectively at near and intermediate distances. Results The study comprised 60 eyes of 30 patients (mean age, 68.30 ± 9.26 years; range, 34 to 80 years). There was significant improvement in UDVA and CDVA. Mean UIVA was 0.01 ± 0.09 logarithm of the minimum angle of resolution (logMAR) and mean DCIVA was -0.02 ± 0.11 logMAR. In Salzburg Reading Desk analysis for UIVA, the mean subjective intermediate distance was 67.58 ± 8.59 cm with mean UIVA of -0.02 ± 0.09 logMAR and mean word count of 96.38 ± 28.32 words/min. Conclusions The new aspheric, asymmetric, +1.5 D near addition MIOL offers good results for distance visual function in combination with good performance for intermediate distances and functional results for near distance.
Macrophages Are the Major Reservoir of Latent Murine Gammaherpesvirus 68 in Peritoneal Cells

ABSTRACT B cells have previously been identified as the major hematopoietic cell type harboring latent gammaherpesvirus 68 (γHV68) (N. P. Sunil-Chandra, S. Efstathiou, and A. A. Nash, J. Gen. Virol. 73:3275–3279, 1992). However, we have shown that γHV68 efficiently establishes latency in B-cell-deficient mice (K. E. Weck, M. L. Barkon, L. I. Yoo, S. H. Speck, and H. W. Virgin, J. Virol. 70:6775–6780, 1996), demonstrating that B cells are not required for γHV68 latency. To understand this dichotomy, we determined whether hematopoietic cell types, in addition to B cells, carry latent γHV68. We observed a high frequency of cells that reactivate latent γHV68 in peritoneal exudate cells (PECs) derived from both B-cell-deficient and normal C57BL/6 mice. PECs were composed primarily of macrophages in B-cell-deficient mice and of macrophages plus B cells in normal C57BL/6 mice. To determine which cells in PECs from C57BL/6 mice carry latent γHV68, we developed a limiting-dilution PCR assay to quantitate the frequency of cells carrying the γHV68 genome in fluorescence-activated cell sorter-purified cell populations. We also quantitated the contribution of individual cell populations to the total frequency of cells carrying latent γHV68. At early times after infection, the frequency of PECs that reactivated γHV68 correlated very closely with the frequency of PECs carrying the γHV68 genome, validating measurement of the frequency of viral-genome-positive cells as a measure of latency in this cell population. F4/80-positive macrophage-enriched, lymphocyte-depleted PECs harbored most of the γHV68 genome and efficiently reactivated γHV68, while CD19-positive, B-cell-enriched PECs harbored about a 10-fold lower frequency of γHV68 genome-positive cells. CD4-positive, T-cell-enriched PECs contained only a very low frequency of γHV68 genome-positive cells, consistent with previous analyses indicating that T cells are not a reservoir for γHV68 latency (N. P. Sunil-Chandra, S. Efstathiou, and A. A. Nash, J. Gen. Virol. 73:3275–3279, 1992). Since macrophages are bone marrow derived, we determined whether elicitation of a large inflammatory response in the peritoneum would recruit additional latent cells into the peritoneum. Thioglycolate inoculation increased the total number of PECs by about 20-fold but did not affect the frequency of cells that reactivate γHV68, consistent with a bone marrow reservoir for latent γHV68. These experiments demonstrate γHV68 latency in two different hematopoietic cell types, F4/80-positive macrophages and CD19-positive B cells, and argue for a bone marrow reservoir for latent γHV68.
Gender disparities in acute coronary syndrome: a closing gap in the short-term outcome

Aims The aim of the present study was to analyze gender disparities in a large cohort of acute coronary syndrome (ACS) patients from the Zurich Acute Coronary Syndrome (Z-ACS) Registry. Methods Gender disparities in ACS were examined. The primary endpoint included in-hospital death rate, and the secondary endpoint major adverse cardiac and cerebrovascular events (MACCEs) at 30-day follow-up. Furthermore, independent predictors for MACCEs and death were identified. Results In total, 2612 patients with ACS were identified. Out of these, 23% were women. The mean age was higher in women (68.6 ± 12.2; P < 0.001). Troponin-T on admission (1.33 ± 4.64 vs. 1.19 ± 3.04 &mgr;g/l; P = 0.002) and N-terminal of the prohormone brain natriuretic peptide on admission (3456.2 ± 7286.7 vs. 1665.6 ± 4800.6 ng/l; P < 0.001) were higher in women compared with men. Single-vessel disease was more common in women (44.9 vs. 39.7%; P = 0.023) and, conversely, multivessel disease was more prevalent in male patients as compared with their female counterparts (59.4 vs. 54.4%; P = 0.029). At discharge, men were more likely prescribed statins (89.4 vs. 85.2%; P = 0.004). Overall mortality and MACCEs were similar for both genders. In women, peak creatine kinase and peak C-reactive protein emerged as independent predictors for MACCEs and SBP on admission, and maximal C-reactive protein and use of glycoprotein IIb/IIIa inhibitors (GPIIb/IIIa) as strong independent predictors for in-hospital death. Conclusion The present results suggest a closing gap in short-term outcome and improvement in cardiac care between women and men. Nonetheless, differences in treatment strategies continue to exist, particularly pertaining to statin regimens at discharge, which might potentially have a powerful impact on long-term outcomes and gender disparities.
Integrins control motile strategy through a Rho–cofilin pathway

During wound healing, angiogenesis, and tumor invasion, cells often change their expression profiles of fibronectin-binding integrins. Here, we show that β1 integrins promote random migration, whereas β3 integrins promote persistent migration in the same epithelial cell background. Adhesion to fibronectin by αvβ3 supports extensive actin cytoskeletal reorganization through the actin-severing protein cofilin, resulting in a single broad lamellipod with static cell–matrix adhesions at the leading edge. Adhesion by α5β1 instead leads to the phosphorylation/inactivation of cofilin, and these cells fail to polarize their cytoskeleton but extend thin protrusions containing highly dynamic cell–matrix adhesions in multiple directions. The activity of the small GTPase RhoA is particularly high in cells adhering by α5β1, and inhibition of Rho signaling causes a switch from a β1- to a β3-associated mode of migration, whereas increased Rho activity has the opposite effect. Thus, alterations in integrin expression profiles allow cells to modulate several critical aspects of the motile machinery through Rho GTPases.
Molecular Typing of Mycobacterium bovisIsolates from Cameroon

ABSTRACT In order to gain a better understanding of the molecular epidemiology of Mycobacterium bovis isolates in Cameroon, 75 isolates of M. bovis collected in three provinces of northern Cameroon were studied by spoligotyping. For 65 of these isolates, typing was also carried out by pulsed-field gel electrophoresis (PFGE) with DraI, and 18 of the isolates were also typed by restriction fragment length polymorphism (RFLP) analysis with probe IS6110-RHS. Molecular typing of the isolates by these techniques revealed a high degree of homogeneity, with 10 spoligotypes for 75 isolates, four PFGE profiles for 65 isolates, and three RFLP types for 18 isolates. Some types were present in the three different provinces, while some were confined to one or two areas. These results suggest that geographical mapping of M. bovis strains could be helpful for the control of bovine tuberculosis at the regional level. An interesting feature of all the spoligotypes was the absence of spacer 30, suggesting a common origin for all of the Cameroon isolates tested; an evolutionary scenario for the isolates is discussed. In addition, a comparison of the three techniques showed that for M. bovis strain differentiation in Cameroon and in surrounding countries, spoligotyping would be a more discriminating and practical tool for molecular typing than the other two techniques used in this study.
Mental Health Policy Development and Implementation in Four African Countries

The purpose of the research programme introduced in this article is to provide new knowledge regarding comprehensive multisectoral approaches to breaking the negative cycle of poverty and mental ill-health. The programme undertakes an analysis of existing mental health policies in four African countries (Ghana, South Africa, Uganda, Zambia), and will carry out and evaluate interventions to assist in the development and implementation of mental health policies in those countries, over a five-year period. The four countries in which the programme is being conducted represent a variety of scenarios in mental health policy development and implementation.
Levels of oxidative damage and proinflammatory cytokines are enhanced in patients with active vitiligo

Abstract Vitiligo is an autoimmune depigmenting skin disease characterised by loss of melanocytes wherein oxidative stress is proposed to be the initial triggering factor with subsequent immune dysregulation. This study aimed to evaluate the relationship, if any, between the generation of reactive oxygen species (ROS), markers of oxidative damage and circulating cytokines in patients with active vitiligo. The generation of ROS in erythrocytes and neutrophils was significantly higher in patients with active vitiligo than healthy controls. Alongside, markers of oxidative stress-mediated damage namely lipid peroxidation, DNA damage and protein carbonylation were evaluated. Patients with active vitiligo demonstrated increased lipid and DNA damage but minimal protein damage. There was a significant decline in the free radical scavenging capacity of active vitiligo cases. A positive correlation existed between baseline levels of ROS and lipid peroxidation as also DNA damage. Patients with active vitiligo demonstrated an increase in several proinflammatory (IL-6, TNF-α, IL-1β, IFN-γ and IL-8) and some anti-inflammatory/immunoregulatory (IL-5 and IL-10) cytokines. Importantly, the levels of IFN-γ and IL-10 consistently correlated with the generation of ROS, markers of damage and their free radical scavenging capacity. Taken together, patients with active vitiligo demonstrated an enhanced generation of ROS in erythrocytes and neutrophils which mediated lipid peroxidation, DNA damage and coupled with a decline in their antioxidant capacity created a pro-oxidant milieu that favoured tissue damage and potential generation of neoantigens, accounting for disease progression.
The relationship between spotted fever group Rickettsiae and Ixodid ticks

Spotted fever group Rickettsiae are predominantly transmitted by ticks. Rickettsiae have developed many strategies to adapt to different environmental conditions, including those within their arthropod vectors and vertebrate hosts. The tick-Rickettsiae relationship has been a point of interest for many researchers, with most studies concentrating on the role of ticks as vectors. Unfortunately, less attention has been directed towards the relationship of Rickettsiae with tick cells, tissues, and organs. This review summarizes our current understanding of the mechanisms involved in the relationship between ticks and Rickettsiae and provides an update on the recent methodological improvements that have allowed for comprehensive studies at the molecular level.
Ability of Different Measures of Adiposity to Identify High Metabolic Risk in Adolescents

Introduction. This study aimed to evaluate the screening performance of different measures of adiposity: body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) for high metabolic risk in a sample of adolescents. Methods. A cross-sectional school-based study was conducted on 517 adolescents aged 15–18, from the Azorean Islands, Portugal. We measured fasting glucose, insulin, total cholesterol (TC), HDL-cholesterol, triglycerides, and systolic blood pressure. HOMA and TC/HDL-C ratio were calculated. For each of these variables, a Z-score was computed by age and sex. A metabolic risk score (MRS) was constructed by summing the Z-scores of all individual risk factors. High risk was considered when the individual had ≥1SD of this score. Receiver-operating characteristics (ROC) were used. Results. Linear regression analyses showed that, after adjusting for age and pubertal stage, all different measures of adiposity are positively and significantly associated with MRS in both sexes, with exception of WHtR for boys. BMI, WC, and WHtR performed well in detecting high MRS, indicated by areas under the curve (AUC), with slightly greater AUC for BMI than for WC and WHtR in both sexes. Conclusion. All measures of adiposity were significantly associated with metabolic risk factors in a sample of Portuguese adolescents.
Another look at the BL Lacertae flux and spectral variability: Observations by GASP-WEBT, XMM-Newton, and Swift in 2008―2009

Aims. In a previous study we suggested that the broad-band emission and variability properties of BL Lacertae can be accounted for by a double synchrotron emission component with related inverse-Compton emission from the jet, plus thermal radiation from the accretion disc. Here we investigate the matter with further data extending over a wider energy range. Methods. The GLAST-AGILE Support Program (GASP) of the Whole Earth Blazar Telescope (WEBT) monitored BL Lacertae in 2008‐2009 at radio, near-IR, and optical frequencies to follow its flux behaviour. During this period, high-energy observations were performed by XMMNewton, Swift, and Fermi. We analyse these data with particular attention to the calibration of Swift UV data, and apply a helical jet model to interpret the source broad-band variability. Results. The GASP-WEBT observations show an optical flare in 2008 February‐March, and oscillations of several tenths of mag on a few-day time scale afterwards. The radio flux is only mildly variable . The UV data from both XMM-Newton and Swift seem to confirm a UV excess that is likely caused by thermal emission from the accretion disc. The X-ray data from XMM-Newton indicate a strongly concave spectrum, as well as moderate (�4‐7%) flux variability on an hour time scale. The Swift X-ray d ata reveal fast (interday) flux changes, not correlated with those observed at lower energies. We compare the spectral energy distribution (SED) corresponding to the 2008 low-brightness state, which was characterised by a synchrotron dominance, to the 1997 outburst state, where the inverse-Compton emission was prevailing. A fit with an inhomogeneous helical jet model suggests that two synchrotron components are at work with their self inverse-Compton emission. Most likely, they represent the radiation from two distinct emitting reg ions in the jet. We show that the difference between the source SEDs in 2008 and 1997 can be explained in terms of pure geometrical variations. The outburst state occurred when the jet-emitting regions were better aligned with the line of sight, producing an increase of the Doppler beaming factor. Conclusions. Our analysis demonstrates that the jet geometry can play an extremely important role in the BL Lacertae flux and spectral v ariability. Indeed, the emitting jet is probably a bent and dynamic structure, and hence changes in the emitting regions viewing angles are likely to happen, with strong consequences on the source multiwavelength behaviour.