Miracle-dz/UniFAR-FTUs huggingface dataset:
Possible Involvement of the Double-Stranded RNA-Binding Core Protein ςA in the Resistance of Avian Reovirus to Interferon

ABSTRACT Treatment of primary cultures of chicken embryo fibroblasts with a recombinant chicken alpha/beta interferon (rcIFN) induces an antiviral state that causes a strong inhibition of vaccinia virus and vesicular stomatitis virus replication but has no effect on avian reovirus S1133 replication. The fact that avian reovirus polypeptides are synthesized normally in rcIFN-treated cells prompted us to investigate whether this virus expresses factors that interfere with the activation and/or the activity of the IFN-induced, double-stranded RNA (dsRNA)-dependent enzymes. Our results demonstrate that extracts of avian-reovirus-infected cells, but not those of uninfected cells, are able to relieve the translation-inhibitory activity of dsRNA in reticulocyte lysates, by blocking the activation of the dsRNA-dependent enzymes. In addition, our results show that protein ςA, an S1133 core polypeptide, binds to dsRNA in an irreversible manner and that clearing this protein from extracts of infected cells abolishes their protranslational capacity. Taken together, our results raise the interesting possibility that protein ςA antagonizes the IFN-induced cellular response against avian reovirus by blocking the intracellular activation of enzyme pathways dependent on dsRNA, as has been suggested for several other viral dsRNA-binding proteins.
TPD1 of Saccharomyces cerevisiae encodes a protein phosphatase 2C-like activity implicated in tRNA splicing and cell separation

The Saccharomyces cerevisiae TPD1 gene has been implicated in tRNA splicing because a tpd1-1 mutant strain accumulates unspliced precursor tRNAs at high temperatures (W. H. van Zyl, N. Wills, and J. R. Broach, Genetics 123:55-68, 1989). The wild-type TPD1 gene was cloned by complementation of the tpd1-1 mutation and shown to encode a protein with substantial homology to protein phosphatase 2C (PP2C) of higher eukaryotes. Expression of Tpd1p in Escherichia coli results in PP2C-like activity. Strains deleted for the TPD1 gene exhibit multiple phenotypes: temperature-sensitive growth, accumulation of unspliced precursor tRNAs, sporulation defects, and failure of cell separation during mitotic growth. On the basis of the presence of these observable phenotypes and the fact that Tpd1p accounts for a small percentage of the observed PP2C activity, we argue that Tpd1p is a unique member of the PP2C family.
Effects of Diving and Swimming Behavior on Body Temperatures of Pacific Leatherback Turtles in Tropical Seas

Mathematical models and recordings of cloacal temperature suggest that leatherback turtles (Dermochelys coriacea) maintain core body temperature higher than ambient water temperature (TW) while freely swimming at sea. We investigated the thermoregulatory capabilities of free‐ranging leatherbacks and, specifically, the effect that changes in diving patterns and ambient temperatures have on leatherback body temperatures (TB). Data loggers were used to record subcarapace and gastrointestinal tract temperatures (TSC and TGT, respectively), TW, swim speed, dive depth, and dive times of female leatherback turtles during internesting intervals off the coast of Guanacaste, Costa Rica. Mean TSC (28.7°–29.0°C) was significantly higher than mean TW (25.0°–27.5°C). There was a significant positive relationship between TSC and TW and a significant negative correlation between TSC and dive depth and TGT and dive depth. Rapid fluctuations in TGT occurred during the first several days of the internesting interval, which suggests that turtles were ingesting prey or water during this time. Turtles spent 79%–91% of the time at sea swimming at speeds greater than 0.2 m s−1, and the average swim speed was 0.7 ± 0.2 m s−1. Results from this study show that alterations in diving behavior and TW affect TB of leatherback turtles in the tropics. Body temperatures of free‐ranging leatherback turtles correspond well with values for TB predicted by mathematical models for tropical conditions.
PTEN as a Molecular Marker to Distinguish Metastatic From Primary Synchronous Endometrioid Carcinomas of the Ovary and Uterus

The distinction between two primary carcinomas on the one hand and a metastatic disease on the other hand in patients suffering from synchronous endometrioid carcinomas of the uterus and ovary is difficult. Exclusive histopathologic analysis appears to be insufficient and sometimes misleading. The tumor suppressor PTEN was found to be important in early neoplastic transformation in endometrioid carcinomas of the uterus. In this study, we screened synchronous endometrioid carcinomas of the uterus and ovary of 10 patients for loss of heterozygosity using seven different microsatellite markers at 10q23.3 and for mutations in the entire coding region of PTEN. Point mutations or microdeletions/insertions were found in six patients. Allelic loss at 10q23.3 was detected in eight patients. Based on conventional histology, a metastatic disease was diagnosed in seven patients and a concomitant uterine and ovarian carcinoma in three patients. After molecular analysis, the histopathologic diagnosis of three patients had to be revised. Histopathology represents the standard method to process tumor specimens from these patients. Nevertheless, mutation screen for PTEN and LOH analysis at 10q23.3 provide helpful genetic tools to establish a correct final diagnosis, which is important in view of prognosis and therapeutic implications.
ESR identification of free radicals formed from the oxidation of catechol estrogens by Cu2+.

Catechol estrogens are genotoxic, indirectly through redox cycling mechanisms leading to oxidative DNA damage and directly by formation of quinone-DNA adducts. Previously, we demonstrated that Cu2+ can oxidize estradiol (E2) catechols, establishing a copper redox cycle leading to the formation of DNA strand breaks. The goal of this study was to use electron spin resonance techniques to identify the free radical intermediates formed. The 2- and 4-OH catechols of E2 and ethinyl estradiol (EE) were oxidized to semiquinone intermediates, stabilized by Mg2+, when incubated with Cu2+. The 4-OH-EE semiquinone decayed more slowly than the 2-OH-EE semiquinone. Using the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone, 4-OH-E2 plus Cu2+ generated hydroxyl radicals at a greater rate than 2-OH-E2 plus Cu2+. Formation of hydroxyl and methyl radical adducts was detected, using 5,5-dimethyl-1-pyrroline-N-oxide as the spin trap, when 2-OH-E2 was incubated with Cu2+ and 1% dimethyl sulfoxide. This was inhibited by the Cu1+ chelator bathocuproinedisulfonic acid and catalase. These data demonstrate that the oxidation of estrogen catechols by Cu2+ leads to a Cu-dependent mechanism of hydroxyl radical production via a hydrogen peroxide intermediate and suggest a mechanism for estrogen-associated site-specific DNA damage and mutagenesis.
Differential Binding of Pyruvate Dehydrogenase Complex-E2 Epitopes by DRB1*08:01 and DRB1*11:01 Is Predicted by Their Structural Motifs and Correlates with Disease Risk

DRB1*08:01 (DR0801) and DRB1*11:01 (DR1101) are highly homologous alleles that have opposing effects on susceptibility to primary biliary cirrhosis (PBC). DR0801 confers risk and shares a key feature with other HLA class II alleles that predispose to autoimmunity: a nonaspartic acid at beta57. DR1101 is associated with protection from PBC, and its sequence includes an aspartic acid at beta57. To elucidate a mechanism for the opposing effects of these HLA alleles on PBC susceptibility, we compared the features of epitopes presented by DR0801 and DR1101. First, we identified DR0801- and DR1101-restricted epitopes within multiple viral Ags, observing both shared and distinct epitopes. Because DR0801 is not well characterized, we deduced its motif by measuring binding affinities for a library of peptides, confirming its key features through structural modeling. DR0801 was distinct from DR1101 in its ability to accommodate charged residues within all but one of its binding pockets. In particular, DR0801 strongly preferred acidic residues in pocket 9. These findings were used to identify potentially antigenic sequences within PDC-E2 (an important hepatic autoantigen) that contain a DR0801 motif. Four peptides bound to DR0801 with reasonable affinity, but only one of these bound to DR1101. Three peptides, PDC-E2145–159, PDC-E2249–263, and PDC-E2629–643, elicited high-affinity T cell responses in DR0801 subjects, implicating these as likely autoreactive specificities. Therefore, the unique molecular features of DR0801 may lead to the selection of a distinct T cell repertoire that contributes to breakdown of self-tolerance in primary biliary cirrhosis, whereas those of DR1101 promote tolerance.
[The study of gene mutations in unknown refractory viral infection and primary hemophagocytic lymphohistiocytosis].

OBJECTIVE To study the type and corresponding clinical characteristics of primary hemophagocytic lymphohistiocytosis (HLH) associated immune gene mutations in the refractory virus infection or HLH of unknown causes. METHODS From December 2009 to July 2010, the patients with refractory virus infection or HLH of unknown causes were screened for the primary HLH associated immune genes mutations by DNA sequence analysis, including PRF1, UNC13D, STX11, STXBP2, SH2D1A and XIAP. The clinical characteristics and outcomes were followed up. RESULTS Totally 25 patients with refractory virus infection or HLH of unknown causes were investigated for the 6 genes and 13 cases were found carrying gene mutations, composing of 6 of PRF1 mutation, 3 of UNC13D, and each one of STX11, XIAP, SH2D1A and STXBP2, respectively. Among the 13 cases with gene mutations, 5 suffered from Epstein-Barr virus associated HLH (EBV-HLH), 1 human herpes virus 7 associated HLH (HHV7-HLH), 1 HLH without causes, 4 chronic activated EB virus infection (CAEBV) with 1 progressing to Hodgkin's lymphoma carrying abnormal chromosome of t(15;17) (q22;q25) and hyperdiploid, 2 EBV associated lymphoma. Among the other 12 patients without gene mutation, 4 suffered from EBV-HLH with 1 progressing to peripheral T lymphoma, 8 suffered from CAEBV. CONCLUSIONS Primary HLH associated immune gene mutations are critical causes of refractory virus infection of unknown causes, most patients manifest as HLH, some cases appear in CAEBV and EBV associated lymphoma. DNA sequence analysis is helpful to early diagnosis and correct decision-making for treatment.
Risk factors for and trends in gonorrhea incidence among persons infected with HIV in the United States

ObjectiveTo determine the risk factors for and trends in gonorrhea infections among HIV-infected persons. Design Longitudinal review of medical records of HIV-infected patients. Methods We analyzed data about HIV-infected patients obtained from 1991 to 1998 in over 100 facilities participating in the Adult/Adolescent Spectrum of HIV Disease Project. Results The overall incidence of gonorrhea was 9.5 cases per 1000 person–years. Factors associated with higher gonorrhea incidence (P < 0.01) included younger age, male–male sex, black race, HIV infection without AIDS (namely AIDS-defining opportunistic illness or CD4 cell count < 200 × 106 cells/l), and recent recreational use of injection or non-injection drugs. There was an increase in the trend among men who have sex with men (P < 0.01) and a decrease in the trend among patients with heterosexual contact as their HIV exposure risk (P < 0.01). Among injection drug users there was no significant trend from 1991 to 1996, but there was an increase in gonorrhea incidence from 6.6 cases/1000 person–years in 1997 to 16.3 cases/1000 person–years in 1998. Conclusions Following HIV diagnosis, some individuals continue to practice risky sexual behaviors which result in gonorrhea and may transmit HIV. The increase in the trend in gonorrhea incidence among HIV-infected men who have sex with men is of particular concern because it suggests an increase in risky sexual behaviors. These findings indicate a need for effective HIV prevention strategies that involve reducing risky sexual behaviors in HIV-infected persons.
Introductory Remarks: Bacterial Endosymbionts or Pathogens of Free-Living Amebae1

Abstract Free-living amebae are ubiquitous in the environment and can be isolated from a variety of habitats including water, soil, air, hospital water systems, dental units, contact lens cases, and cooling towers. The interaction of amebae with other microorganisms in their environment is varied. Bacteria are a major food source for free-living amebae. However, some bacteria have established a stable symbiotic relationship with amebae. Recent reports indicate an association of amebae with intracellular bacterial pathogens. Such amebae may serve as reservoirs for maintaining and dispersing pathogenic bacteria in the environment or as vectors of bacterial disease in humans.
Hazelnut allergy: from pollen-associated mild allergy to severe anaphylactic reactions

Purpose of reviewHazelnut allergy can vary between mild oral symptoms and potentially dangerous anaphylaxis. There is a need to predict which subjects are at risk for severe reactions. In this study, possibilities for ‘component-resolved diagnosis’, based on sensitization to different allergens in hazelnut, are discussed. Recent findingsOne type of hazelnut allergy can be associated with sensitization to homologues of pollen allergens, predominantly birch, in hazelnut: Cor a 1 (Bet v 1) and Cor a 2 (profilin). These allergens account for relatively mild symptoms. However, subjects can also be sensitized to several other allergens in hazelnut that are related to more severe symptoms. These allergens are homologues of allergens in other nuts and peanut: Cor a 8 (lipid transfer protein) and Cor a 9 (11S globulin) and perhaps Cor a 11 (7S globulin). The clinical relevance of these and other potential hazelnut allergens has to be further defined. The diagnosis of hazelnut has to be confirmed by oral double-blind placebo-controlled food challenge. SummarySensitization to hazelnut can either be associated with mild oral symptoms, depending on sensitization to pollen, or with more serious allergic symptoms, related to sensitization to homologues of nut and peanut allergens.
Suicide in the World

Introduction: Over the past 20 years the WHO has considerably improved world mortality data. There are still shortcomings but more countries now report data and world-wide estimates are regularly made. Methods: Data about mortality have been retrieved from the WHO world database. Worldwide injury mortality estimates for 2008 as well as trends of the suicide rate from 1950 to 2009 were analysed. Results: Suicides in the world amount to 782 thousand in 2008 according to the WHO estimate, which is 1.4% of total mortality and 15% of injury mortality. The suicide rate for the world as a whole is estimated at 11.6 per 100,000 inhabitants. The male–female rate ratio of suicide is estimated to be highest in the European Region (4.0) and the lowest in the Eastern Mediterranean region (1.1). Among males the highest suicide rate in the 15–29 age group is in the SE Asian region, in the 45–59 age group in European males and for ages above 60 in the Western Pacific region. Females from SE Asia have a remarkably high suicide rate among 15–29-year-olds and from age 45 in the Western Pacific region. The leading country is currently Lithuania, with a suicide rate of 34.1 per 100,000 inhabitants. Also among males the suicide rate is the highest in Lithuania at 61.2. Among females South Korea with 22.1 is at the top of world suicide rates. Conclusions: During the past six decades, according to the WHO Japan, Hungary, and Lithuania have topped the list of world countries by suicide rate, but if the current trends continue South Korea will overtake all others in a few years. The heart of the problem of suicide mortality has shifted from Western Europe to Eastern Europe and now seems to be shifting to Asia. China and India are the biggest contributors to the absolute number of suicides in the world.
Critical windows in development of the rodent immune system

The immune system of rodents, like that in humans, develops from a population of pluripotential hematopoietic stem cells (HSC) that are generated early in gestation from uncommitted mesenchymal stem cells in the intra-embryonic splanchnoplure surrounding the heart. This early population of HSC gives rise to all circulating blood cell lineages, including cells of the innate and acquired immune system. To access the impact of chemical exposure on the developing immune system and establish developmental windows of potential vulnerability to these exposures, it is essential to first consider the anatomical development of hematopoietic and lymphopoietic tissues and the sequence of appearance of cells that give rise to the immune system. This is particularly true in embryonic development because, after they initially appear in intra-embryonic mesenchyme early in gestation, HSC migrate through an orderly series of tissues before establishing residence in the bone marrow and thymus. The effect of exposure to chemical insults in utero, then, may differ depending on the specific timing of exposure and anatomical location of hematopoiesis. Mechanisms and consequences of developmental immunotoxicity in experimental animals will need to be considered in that context. This review presents an overview of developmental hematopoiesis and a working hypothesis of critical developmental windows of vulnerability of this developmental system to toxic insult by chemical exposure.
Differential Requirements for Tcf1 Long Isoforms in CD8+ and CD4+ T Cell Responses to Acute Viral Infection

In response to acute viral infection, activated naive T cells give rise to effector T cells that clear the pathogen and memory T cells that persist long-term and provide heightened protection. T cell factor 1 (Tcf1) is essential for several of these differentiation processes. Tcf1 is expressed in multiple isoforms, with all isoforms sharing the same HDAC and DNA-binding domains and the long isoforms containing a unique N-terminal β-catenin–interacting domain. In this study, we specifically ablated Tcf1 long isoforms in mice, while retaining expression of Tcf1 short isoforms. During CD8+ T cell responses, Tcf1 long isoforms were dispensable for generating cytotoxic CD8+ effector T cells and maintaining memory CD8+ T cell pool size, but they contributed to optimal maturation of central memory CD8+ T cells and their optimal secondary expansion in a recall response. In contrast, Tcf1 long isoforms were required for differentiation of T follicular helper (TFH) cells, but not TH1 effectors, elicited by viral infection. Although Tcf1 short isoforms adequately supported Bcl6 and ICOS expression in TFH cells, Tcf1 long isoforms remained important for suppressing the expression of Blimp1 and TH1-associated genes and for positively regulating Id3 to restrain germinal center TFH cell differentiation. Furthermore, formation of memory TH1 and memory TFH cells strongly depended on Tcf1 long isoforms. These data reveal that Tcf1 long and short isoforms have distinct, yet complementary, functions and may represent an evolutionarily conserved means to ensure proper programming of CD8+ and CD4+ T cell responses to viral infection.
Good Work for dentists - a qualitative analysis.

OBJECTIVE This study explores dentists' perceptions of Good Work in the meaning of positive and rewarding aspects in their work in contrast to a traditional problem-centred focus on work life. METHODS Nine informants were selected among Danish and Swedish general dental practitioners to obtain variation as to country of origin, gender, age and clinical work experience. Semi-structured, in-depth interviews were audio-recorded and transcribed verbatim in the original language. Statements concerning positive aspects of work were used for systematic text condensation according to the principles of Giorgi's phenomenological analysis, as modified by Malterud, generalizing descriptions reflecting aspects of Good Work. Selection of participants continued until saturation of the emerging categories was achieved. RESULTS The core of Good Work emanates from the clinical encounter: from the relation with the patient and from the opportunity to carry out high quality odontological handicraft. Social relations at the workplace, as well as organizational values and conditions were perceived as influencing the opportunities to achieve the rewarding aspects from the clinical encounter. CONCLUSIONS The results implicate a need for developing a work-environmental model with intrinsic as well as extrinsic rewards when dealing with human service organizations. At policy level it is necessary to address the professional culture.
p16INK4A and p15INK4B Gene Alteration Associated with Oxidative Stress in Renal Cell Carcinomas After the Chernobyl Accident (Pilot Study)

Our study was undertaken to better understand the role of G1/S transition abnormalities in the malignant progression of renal cell carcinomas (RCCs), exposed to long-term low doses of ionizing radiation (IR), from patients living in radiocontaminated areas of the Ukraine after the Chernobyl accident. We studied p16INK4A and p15INK4B gene alteration in association with oxidative stress markers, including inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). We analyzed 88 samples collected from 22 patients with RCCs and with different exposure to IR. Homozygous deletion of the p16INK4A and p15INK4B genes, as well as hypermethylation of the 5CpG island in the promoter region of the same genes, were analyzed by differential PCR and Methylation-Specific PCR respectively, in association with histopathology and immunohistochemical analysis of p16INK4A and p15INK4B proteins. COX2 and iNOS expression in the same tumors were likewise analyzed. Aberrant hypermethylation was observed in 7 (32%) and 5 (23%) cases accompanied, by immunohistochemical loss of expression for p16INK4A and p15INK4B genes respectively, in both high stage and grade tumors from patients living in radiocontaminated areas, this being especially outstanding for the p16INK4A gene. An association with COX2 and less iNOS overexpression in the same tumors was observed. Our data suggest that inactivation of p16INK4A gene, but not p15INK4B, induced by increased oxidative stress generated by persistent chronic exposure to IR, could be one of the major pathways responsible for RCCs malignant progression.
Down-regulation of miR-503 expression predicate advanced mythological features and poor prognosis in patients with NSCLC.

OBJECTIVE We aimed to explore what impact miR-503 has on the prognosis of patients with non-small cell lung cancer (NSCLC). METHODS Cancer and matched non-malignant lung tissue specimens were collected from 109 patients who underwent surgery in Tanisha Hospital from Jun 2006 to July 2013. Overall survival (OS) curves were analyzed using the Lapland-Meier method, and the differences were examined using log-rank tests. Cox proportional- hazards regression analysis was applied in order to estimate univariate and multivariate hazard ratios for OS. RESULTS The relative expression of miR-503 in NSCLC tissues (0.366±0.130) was significantly lower than that in matched noncancerous lung tissues (1.667±1.047, P<0.01). Statistically significant association was observed between miR-503 expression and lymphatic invasion (P=0.005), distant metastasis (P=0.002), TNM stage (P=0.008), and tumor grade (P=0.043). Lapland Meier analysis clearly illustrated that the patients with the lower expression of miR-503 had a worse outcome compared to patients with higher miR-503 expression (P=0.004). Furthermore, multivariate analysis revealed that miR-503 expression level was an independent prognostic factor for overall survival (HR=3.992, 95% CI: 2.276-9.872; P=0.018) in NSCLC. CONCLUSION In patients with NSCLC, low miR-503 expression is an independent prognostic factor.