Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonstructural Protein σ1s Is Required for Optimal Reovirus Protein Expression

ABSTRACT Reovirus nonstructural protein σ1s is required for the establishment of viremia and hematogenous viral dissemination. However, the function of σ1s during the reovirus replication cycle is not known. In this study, we found that σ1s was required for efficient reovirus replication in simian virus 40 (SV40)-immortalized endothelial cells (SVECs), mouse embryonic fibroblasts, human umbilical vein endothelial cells (HUVECs), and T84 human colonic epithelial cells. In each of these cell lines, wild-type reovirus produced substantially higher viral titers than a σ1s-deficient mutant. The σ1s protein was not required for early events in reovirus infection, as evidenced by the fact that no difference in infectivity between the wild-type and σ1s-null viruses was observed. However, the wild-type virus produced markedly higher viral protein levels than the σ1s-deficient strain. The disparity in viral replication did not result from differences in viral transcription or protein stability. We further found that the σ1s protein was dispensable for cell killing and the induction of type I interferon responses. In the absence of σ1s, viral factory (VF) maturation was impaired but sufficient to support low levels of reovirus replication. Together, our results indicate that σ1s is not absolutely essential for viral protein production but rather potentiates reovirus protein expression to facilitate reovirus replication. Our findings suggest that σ1s enables hematogenous reovirus dissemination by promoting efficient viral protein synthesis, and thereby reovirus replication, in cells that are required for reovirus spread to the blood. IMPORTANCE Hematogenous dissemination is a critical step in the pathogenesis of many viruses. For reovirus, nonstructural protein σ1s is required for viral spread via the blood. However, the mechanism by which σ1s promotes reovirus dissemination is unknown. In this study, we identified σ1s as a viral mediator of reovirus protein expression. We found several cultured cell lines in which σ1s is required for efficient reovirus replication. In these cells, wild-type virus produced substantially higher levels of viral protein than a σ1s-deficient mutant. The σ1s protein was not required for viral mRNA transcription or viral protein stability. Since reduced levels of viral protein were synthesized in the absence of σ1s, the maturation of viral factories was impaired, and significantly fewer viral progeny were produced. Taken together, our findings indicate that σ1s is required for optimal reovirus protein production, and thereby viral replication, in cells required for hematogenous reovirus dissemination.
Comments on colorectal cancer screening.

e Editorial ”To scope or to test for colorectal cancer screening? ” was recently published in the JGLD [1] and with regard to this some speci cations and considerations are required. According to the Oxford dictionary, a screening is de ned as ”a system of checking (a person or a group) for the presence or absence of a disease” [2]. In the Editorial as in other articles the term ” colorectal cancer (CRC) screening” includes both nding the CRC and the identi cation and removal of colonic polyps. In fact, we have to deal with two distinct actions for two distinct pathologies: CRC and colon polyps. e purpose of CRC screening is to reduce the mortality caused by colon cancer, while polyp screening and their removal are part of the secondary prevention for CRC with the purpose of reducing CRC morbidity. e screening technique depends on the CRC risk. e possibilities discussed in the Editorial target the average risk group (age above 50). For the high risk group (according to the Amsterdam criteria), colonoscopy is the only accepted method which should be applied starting with the age of 40, or 10 years earlier than the age at diagnosis in familial cancer [3]. Taking into account the time necessary to nd a CRC through screening (about 4.8 years by screening 5,000 persons), the American guidelines recommend to screen only persons below the age of 75 or with a life expectancy higher than 10 years [3, 4]. e occult bleeding is another important problem. At onset, only some of the CRCs present lower digestive bleeding (less than one third), which is usually intermittent. Moreover, for a fecal occult blood test (FOBT) to be positive, the amount of blood loss should be more than 2ml/24h. Cancers located on the right colon present more important bleeding. e bleeding produced by the tumors located/situated on the transverse and le colon is not always su cient to result in a positive FOBT [5]. is is the reason why the studies conducted by using the FOBT do not show a decrease of mortality over LETTERS TO THE EDITOR
B cells are required for lupus nephritis in the polygenic, Fas-intact MRL model of systemic autoimmunity.

B cells are required for both the expression of lupus nephritis and spontaneous T cell activation/memory cell accumulation in MRL-Faslpr mice (MRL/lpr). Autoimmunity in the MRL/lpr strain is the result of Fas-deficiency and multiple background genes; however, the precise roles of background genes vs Fas-deficiency have not been fully defined. Fas-deficiency (i.e., the lpr defect) is required in B cells for optimal autoantibody expression, raising the possibility that the central role for B cells in MRL/lpr mice may not extend to MRL/+ mice and, thus, to lupus models that do not depend on Fas-deficiency ("polygenic lupus"). To address this issue, B cell-deficient, Fas-intact MRL/+ mice (JHd-MRL/) were created; and disease was evaluated in aged animals (>9 mo). The JHd-MRL/+ animals did not develop nephritis or vasculitis at a time when the B cell-intact littermates had severe disease. In addition, while activated/memory CD4+ and CD8+ T cells accumulated in B cell-intact mice, such accumulation was substantially inhibited in the absence of B cells. This effect appeared to be restricted to the MRL strain because it was not seen in B cell-deficient BALB/c mice (JHd-BALB) of similar ages. The results indicate that B cells are essential in promoting systemic autoimmunity in a Fas-independent model. Therefore, B cells have an important role in pathogenesis, generalizable to lupus models that depend on multiple genes even when Fas expression is intact. The results provide further rationale for B cell suppression as therapy for systemic lupus erythematosus.
Tetratricopeptide Repeat (TPR) Motifs of p67 phox Participate in Interaction with the Small GTPase Rac and Activation of the Phagocyte NADPH Oxidase*

The small GTPase Rac functions as a molecular switch in several important cellular events including cytoskeletal reorganization and activation of the phagocyte NADPH oxidase, the latter of which leads to production of superoxide, a precursor of microbicidal oxidants. During formation of the active oxidase complex at the membrane, the GTP-bound Rac appears to interact with the N-terminal region of p67 phox , another indispensable activator that translocates from the cytosol upon phagocyte stimulation. Here we show that the p67 phox N terminus lacks the CRIB motif, a well known Rac target, but contains four tetratricopeptide repeat (TPR) motifs with highly α-helical structure. Disruption of any of the N-terminal three TPRs, but the last one, results in defective interaction with Rac, while all the four are required for the NADPH oxidase activation. We also find that Arg-102 in the third repeat is likely involved in binding to Rac via an ionic interaction, and that replacement of this residue with Glu completely abrogates the capability of activating the oxidase both in vivo andin vitro. Thus the TPR motifs of p67 phox are packed to function as a Rac target, thereby playing a crucial role in the active oxidase complex formation.
Mucins in Lung Cancer: Diagnostic, Prognostic, and Therapeutic Implications

Aberrant expression of mucins is associated with cancer development and metastasis. An overexpression of few mucins contributes to oncogenesis by enhancing cancer cell growth and providing constitutive survival signals. This review focuses on the importance of mucins both in the normal bronchial epithelial cells and the malignant tumors of the lung and their contribution in the diagnosis and prognosis of lung cancer patients. During lung cancer progression, mucins either alone or through their interaction with many receptor tyrosine kinases mediate cell signals for growth and survival of cancer cells. Also, stage-specific expression of certain mucins, like MUC1, is associated with poor prognosis from lung cancer. Thus, mucins are emerging as attractive targets for developing novel therapeutic approaches for lung cancer. Several strategies targeting mucin expression and function are currently being investigated to control lung cancer progression.
A Herschel and CARMA view of CO and [C ii] in Hickson Compact groups

Abstract Understanding the evolution of galaxies from the starforming blue cloud to the quiescent red sequence has been revolutionized by observations taken with Herschel Space Observatory, and the onset of the era of sensitive millimeter interferometers, allowing astronomers to probe both cold dust as well as the cool interstellar medium in a large set of galaxies with unprecedented sensitivity. Recent Herschel observations of of H2-bright Hickson Compact Groups of galaxies (HCGs) has shown that [C ii] may be boosted in diffuse shocked gas. CARMA CO(1–0) observations of these [C ii]-bright HCGs has shown that these turbulent systems also can show suppression of SF. Here we present preliminary results from observations of HCGs with Herschel and CARMA, and their [C ii] and CO(1–0) properties to discuss how shocks influence galaxy transitions and star formation.
Thermo-mechanical analysis of a wafer level packaging by induction heating

In this paper, a non-linear and one-directional coupled finite element framework has been implemented to simulate induction heating process of wafer-level packaging. Based on numerical results of induction heating, thermally-caused warpages and stresses of the single-sided ceramic wafer have been evaluated. Some primary experiments have also been conducted to verify the numerical method. Using three-dimensional models, the temperature distribution, thermally-caused warpages and stress in the single-sided ceramic wafer subjected to induction heating can be clearly defined. In addition, the temperature-dependent material properties are considered in the modeling. From the finite element analysis, it is found that the induction heating is selective, that is, the temperature in the wafer is lower than that of Cu-loops during the induction heating process; the temperature variation on the Cu-loops, as well as the difference of the temperature between the Cu-loops and the wafer is related with the wafer material properties; the maximum thermal-stresses caused by the induced Joule heating occur on the middle-edge areas of the single-sided ceramic wafer. On the other hand, in order to prove the soundness of the framework established in this paper, the test results obtained by infrared radiometer are compared to that achieved from the proposed numerical analysis method. It is shown that the temperature variation and locations of initial cracks caused by thermal-stresses during the induction heating are in a good agreement with those obtained from the test.
Life Expectancy and the Older Population

In this article recent trends in old-age mortality are first reviewed. Then the effect that these developments have had on mortality projections for both the short-range and long-range future are analyzed. Next the assumptions underlying the most recent official mortality projections are detailed and evaluated. Following this, the implications of the varying mortality projections for the future size and composition of the older population are examined. Finally, the proposition is addressed that projected mortality is approaching or exceeding maximum average human life span.
Suppression of Adenylate Kinase Catalyzed Phosphotransfer Precedes and Is Associated with Glucose-induced Insulin Secretion in Intact HIT-T15 Cells*

Adenine nucleotide metabolism was characterized in intact insulin secreting HIT-T15 cells during the transition from non-stimulated (i.e. 0.2 mM glucose) to the glucose-stimulated secretory state. Metabolic dynamics were monitored by assessing rates of appearance of 18O-labeled phosphoryls of endogenous nucleotides in cells incubated in medium enriched in [18O]water. Most prominent of the metabolic alterations associated with stimulated insulin secretion was the suppression in the rate of adenylate kinase (AK)-catalyzed phosphorylation of AMP by ATP. This was manifest as a graded decrease of up to 50% in the rate of appearance of β-18O-labeled species of ADP and ATP and corresponded to the magnitude of the secretory response elicited over a range of stimulatory glucose concentrations. The only nucleotide exhibiting a significant concentration change associated with suppression of AK activity was AMP, which decreased by about 50%, irrespective of the glucose concentration. Leucine-stimulated secretion also decreased the rate of AK-catalyzed phosphotransfer. This secretory stimulus-related suppression of AK-catalyzed phosphotransfer occurs within 45 s of glucose addition, precedes insulin secretion, depends on the internalization and metabolism of glucose, and is independent of membrane depolarization and the influx of extracellular calcium. The secretory stimulus-induced decrease in AK-catalyzed phosphotransfer, therefore occurs prior to or at the time of K+ATP channel closure but it is not associated with or a consequence of events occurring subsequent to K+ATP channel closure. These results indicate that AK-catalyzed phosphotransfer may be a determinant of ATP to ADP conversion rates in the K+ATP channel microenvironment; secretory stimuli-linked decreased rates of AK-catalyzed ADP generation from ATP (and AMP) would translate into an increased probability of ATP-liganded and, therefore, closed state of the channel.
Automatic and quantitative measurement of collagen gel contraction using model-guided segmentation

Quantitative measurement of collagen gel contraction plays a critical role in the field of tissue engineering because it provides spatial–temporal assessment (e.g., changes of gel area and diameter during the contraction process) reflecting the cell behavior and tissue material properties. So far the assessment of collagen gels relies on manual segmentation, which is time-consuming and suffers from serious intra- and inter-observer variability. In this study, we propose an automatic method combining various image processing techniques to resolve these problems. The proposed method first detects the maximal feasible contraction range of circular references (e.g., culture dish) and avoids the interference of irrelevant objects in the given image. Then, a three-step color conversion strategy is applied to normalize and enhance the contrast between the gel and background. We subsequently introduce a deformable circular model which utilizes regional intensity contrast and circular shape constraint to locate the gel boundary. An adaptive weighting scheme was employed to coordinate the model behavior, so that the proposed system can overcome variations of gel boundary appearances at different contraction stages. Two measurements of collagen gels (i.e., area and diameter) can readily be obtained based on the segmentation results. Experimental results, including 120 gel images for accuracy validation, showed high agreement between the proposed method and manual segmentation with an average dice similarity coefficient larger than 0.95. The results also demonstrated obvious improvement in gel contours obtained by the proposed method over two popular, generic segmentation methods.
Relationship between rs9939609 Polymorphism of FTO Gene, Diabetes Mellitus and Tuberculosis

Tuberculosis and diabetes mellitus are the most important reasons in mortality all over the world. It’s clear that reviewing of relationship between Tuberculosis (TB) and diabetes mellitus (DM) is necessary; on the other hand it’s found that FTO gene has the positive relationship with metabolic issues. Therefore, it’s necessary pay attention to the above and dangerous sicknesses, especially in field of genetic sciences. Hence, our purpose is investigation of relationship between polymorphism rs9939609 polymorphism of FTO gene, TB and DM. With regards to the findings, it was concluded that there was considerable relationship between FTO gene rs9939609 polymorphism and DM and also it was notable development of TB among diabetic people. It can be stated that there is an indirect relationship between FTO gene rs9939609 polymorphism and TB sickness.
In and Ex Vivo MR Evaluation of Acute Myocardial Ischemia in Pigs by Determining R1 in Steady State After the Administration of the Intravascular Contrast Agent NC100150 Injection

Rationale and Objectives:To study the dose response in perfused and nonperfused myocardium by measuring relaxation rate (R1) in a steady-state situation after injection of the intravascular contrast agent NC100150 Injection in pigs and whether the dose response differs in vivo and ex vivo. Materials and Methods:The left anterior descending artery was occluded. R1 was measured using a Look-Locker sequence for 2 dose groups (2 mg Fe/kg bw, n = 4, and 5 mg Fe/kg bw, n = 5) and a control group (n = 3). Results:A significant increase in R1 was found in perfused myocardium after contrast agent injection, in contrast to nonperfused myocardium. There was a significantly larger difference in R1 between perfused and nonperfused myocardium in the 5 mg Fe/kg bw dose group compared with the other 2 groups. The difference in R1 between perfused and nonperfused myocardium was significantly higher in vivo than ex vivo. Conclusion:A nearly linear R1 dose response was found in perfused myocardium in vivo. The dose response ex vivo was less steep possibly due to larger water exchange limitations.
Journal Impact Factor: it will go away soon

Like many other investigators who participate on editorial boards of various journals, I have witnessed the emergence of the so-called ‘‘Journal Impact Factor’’ over the last 10 years. The Impact Factor (IF) is a number derived by dividing the number of citations a journal receives over a period of time by the number of papers published. It is an average indicator of how frequently papers published in a particular journal are cited (1). At board meetings, the IF dominates discussions regarding the journal’s status and well-being. Much of the time spent at such meetings evolves around strategies on how to improve the IF using any means possible. People are looking at the numerator and are trying to maximize it using conventional wisdom or tricks, including finding high-impact/highquality papers or publishing items that usually receive more citations (e.g., reviews, special issues, etc.), or by minimizing the denominator by attempting to exclude from the calculation items such as letters to the editor, brief communications, etc., even though citations received for these are included in the numerator! In general, an IF of -2 is considered poor, a value between 3 and 5 is good and anything over five is excellent; breaking the barrier of 10 indicates outstanding success. Bottles of champagne are opened when the IF breaks certain barriers (e.g., 5 or 10). Much has been written already on the IF and its limitations, and it is not my intention to repeat such discussions. In general, it is well-known that the IF of journals is dependent primarily on a few very highly cited papers, in comparison to the bulk of papers published. But who would care about IFs? Publishers are very interested because they can market their journals
The effect of primary care physician counseling on participation rate and use of sedation in colonoscopy-based colorectal cancer screening program – a randomized controlled study

Abstract Objectives. Physician recommendation is a strong predictor of colorectal cancer (CRC) screening adherence, but there are no sufficient data specific to primary colonoscopy screening programs. The primary objective was to compare the effect of primary care physician's (PCP) counseling with information leaflet about CRC screening on participation rate in opportunistic primary colonoscopy screening program. Secondary objective was to determine the impact of this counseling on a decision to choose unsedated colonoscopy. Material and methods. Six hundred consecutive subjects 50–65 years of age visiting PCP group practice for routine medical consultation were randomly assigned in a 1:1 ratio either to discuss CRC screening with PCP or to receive an information leaflet on CRC screening only. The outcome measures were the participation rate and the proportion of unsedated colonoscopies assessed on subjects' self-reports collected six months after the intervention. Multivariate logistic regression model with backward selection was used to investigate the association between independent covariates and binary endpoints. Results. Participation rate was 47.0% (141 subjects) in the counseling group and 13.7% (41 patients) in the information leaflet group. The rates of unsedated colonoscopies were 77.0% and 39.0%, respectively. In a multivariate analyses, PCP's counseling was associated with higher participation in CRC screening (adjusted odds ratio [OR] 5.33, 95% confidence intervals [95% CI] 3.55–8.00) and higher rate of unsedated colonoscopies (OR 7.75, 95% CI 2.94–20.45). Conclusion. In opportunistic primary colonoscopy screening, PCP's counseling significantly increases participation rate and decreases demand for sedation compared to recruitment with information materials only. NCT01688817.
Effect of Soy Protein Added to Casein Diet on the Development of Glomerular Injury in Spontaneous Hypercholesterolemic Male Imai Rats

Background: We have already reported an attenuating effect of a semipurified alcohol extract of soy protein (mainly consisting of isoflavones) on glomerular injury. Therefore, in the present study, we investigated whether soy protein itself has an ability to attenuate glomerular injury when added to casein diet in male Imai rats of a spontaneous focal segmental glomerulosclerosis model. Method: Male Imai rats were used and allocated into five groups. Group A of control casein diet (Ca) was fed standard diets containing 24.5% casein as a protein source. Group B of control soy protein diet (SP) was fed soy protein diet containing 24.5% protein that substituted a soy protein isolate for casein. Groups C (Ca-SP10) and D (Ca-SP20) were fed a mixture diet of casein (24.5%) and SP (10%) or SP (20%). Group E (Ca-Ca) was fed high casein diet containing the same quantity in protein content (44.5% casein) as the Ca-SP20 diet. Body weight, urinary protein, serum constituents and systolic blood pressure were investigated every 4 weeks from 12 weeks through 24 weeks of age. At 24 weeks of age, rats were studied morphologically. Results: Animals fed control SP diet showed a significantly greater body growth than animals fed the other 4 test diets. No significant differences were found in body growth among the other 4 groups except for group E, which showed a stunt at the end of the experiment. Control SP diet significantly decreased proteinuria and serum cholesterol and attenuated glomerular injury and glomerular hypertrophy as compared with control casein diet. Added SP failed to attenuate glomerular injury, but when compared with high casein diet (group E), added SP resulted in less proteinuria, less hyperlipidemia, less hypoalbuminemia, less glomerular hypertrophy and less renal histological damage despite the quantity being the same in protein content. Conclusion: The present study indicates that soy protein added to conventional casein diet did not have the ability to attenuate glomerular injury, but soy protein is not as harmful as casein as a protein source when added to casein diet in the development of glomerular injury in the rat model of spontaneous focal glomerular sclerosis.