Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of type I and type III interferons by a secreted glycoprotein from Yaba-like disease virus

Type I (IFN-α/β) and type III (IFN-λs) IFNs are important components of the host antiviral response. Although type III IFNs possess intrinsic antiviral activity similar to that of type I IFNs, they signal through a specific unique receptor complex, and their functional importance for antiviral resistance is largely uncharacterized. Here, we report the first virus defense mechanism that directly targets type III IFNs. Y136 from Yaba-like disease virus, a yatapoxvirus, is a secreted glycoprotein related to protein B18 from Vaccinia virus, a known type I IFN-binding protein and a member of the Ig superfamily. Surprisingly, whereas B18 inhibits only type I IFNs, Y136 inhibits both type I and type III IFNs. Y136 inhibits IFN-induced signaling and suppresses IFN-mediated biological activities including up-regulation of MHC class I antigen expression and induction of the antiviral state. These data demonstrate that poxviruses have developed unique strategies to counteract IFN-mediated antiviral protection and highlight the importance of type III IFNs in antiviral defense. These results suggest that type III IFNs may be an effective treatment for some poxviral infections.
In vitro modulation of microglia motility by glioma cells is mediated by hepatocyte growth factor/scatter factor.

OBJECTIVE Considered as immune effector cells of the central nervous system, microglia represent a major component of the inflammatory cells found in malignant gliomas. Although their role in brain tumor biology is unclear, accumulation of microglia in malignant brain tumors may be mediated through active secretion of cytokines by glioma cells. Because hepatocyte growth factor/scatter factor (HGF/SF) has been shown to modulate glioma motility through an autocrine mechanism, and because microglia have been reported to express the HGF/SF receptor Met, we hypothesized that microglia recruitment by gliomas may also occur through the secretion of HGF/SF. METHODS The effect of glioma cells in augmenting BV-2 murine microglia motility was studied by using an in vitro Boyden chamber migration assay. To determine the chemokines involved in microglia migration, neutralizing monoclonal antibodies against monocyte chemotactic protein-1 and HGF/SF were tested. Immunoblotting was used to check for the expression of HGF/SF by glioma cells, and the expression of Met by BV-2 cells was examined by flow cytometry. RESULTS BV-2 migration was noted within 7 hours of incubation with both human (U251 MG and U373 MG) and murine (GL261) glioma cell lines. This migration corresponded to HGF/SF secretion by glioma cells and was completely inhibited by neutralizing monoclonal antibody against HGF/SF, but not monocyte chemotactic protein-1. Exposure of BV-2 cells to recombinant HGF/SF, but not monocyte chemotactic protein-1, resulted in their migration and down-regulation of Met in a dose-dependent fashion. CONCLUSION HGF/SF, which plays a role in glioma motility and mitogenesis, may also act as a chemokine for microglia and may be responsible for the microglia infiltration in malignant gliomas. This active recruitment of microglia may play an important role in glioma biology.
New evidence for Late Pleistocene human exploitation of Jefferson's Ground Sloth (Megalonyx jeffersonii) from northern Ohio, USA

Abstract The nature and extent of early human exploitation of late Pleistocene mega-mammals of North America have been vigorously debated; however, direct evidence of predation has been established for a small number of taxa. Until now, evidence of butchering and human utilization of ground sloths has been limited to South America. Osteological and taphonomic analyses of one curated collection of Jefferson's Ground Sloth (Megalonyx jeffersonii) from northern Ohio, USA, have identified possible butchering marks on one femur. Historical research determined that the skeletal remains were originally recovered from a bog prior to 1915. Metric assessment of the ten skeletal elements identified this sloth as one of the largest individuals on record. SEM analysis of the left femur documented forty-one stone-tool marks, and their pattern and location indicate the filleting of leg muscles. XAD-purified bone collagen from the femur returned an AMS 14C radiocarbon age of 11,740±35 bp (13,738 to 13,435 cal. bp), which is as much as 700 years older than the calculated maximum age for Clovis. Although diminished somewhat by the lack of primary provenience data, these results offer significant evidence for late Pleistocene human exploitation of this North American taxon.
Finding clusters in VLSI circuits

Circuit partitioning plays a fundamental role in hierarchical layout systems. Identifying the strongly connected subcircuits, the clusters, of the logic can significantly reduce the delay of the circuit and the total interconnection length. Finding such a cluster partition however, is NP-complete. The authors propose a fast heuristic algorithm based on a simple, local criterion. They are able to prove that for highly structured circuits the clusters found by this algorithm correspond with high probability to the 'natural' clusters. An application to large scale real world circuits shows that by this method the number of nets cut is reduced by up to 46% compared to the standard mincut approach. <<ETX>>
Sequential action of two hsp70 complexes during protein import into mitochondria

The mitochondrial chaperone mhsp70 mediates protein transport across the inner membrane and protein folding in the matrix. These two reactions are effected by two different mhsp70 complexes. The ADP conformation of mhsp70 favors formation of a complex on the inner membrane; this ‘import complex’ contains mhsp70, its membrane anchor Tim44 and the nucleotide exchange factor mGrpE. The ATP conformation of mhsp70 favors formation of a complex in the matrix; this ‘folding complex’ contains mhsp70, the mitochondrial DnaJ homolog Mdj1 and mGrpE. A precursor protein entering the matrix interacts first with the import complex and then with the folding complex. A chaperone can thus function as part of two different complexes within the same organelle.
Ventilator-induced lung injury: the role of gene activation

Purpose of reviewVentilator-induced lung injury (VILI) is a ubiquitous iatrogenic clinical problem in critical care. Aside from avoiding large tidal volumes, little progress has been made in identifying effective clinical strategies to minimize this injury. With recent rapid development in bioinformatics and high-throughput molecular technology, the genetic basis of lung injury has been intensively investigated. This review will describe recent insights and potential therapies developed in the field. Recent findingsMuch progress has been made in delineating the possible genes and gene products involved in VILI through various mechanisms such as early induced genes, capillary leak, apoptosis, fibrin deposition, inflammatory cytokines, oxidative stress, disrupted angiogenesis, and neutrophil infiltration. Some studies have translated bench findings to the bedside in an attempt to identify clinically important genetic susceptibility, which could aid in the identification of at-risk individuals who might benefit from careful titration of mechanical ventilation. Genetic insights also provide candidate pharmaceutical approaches that may ameliorate VILI in the future. SummaryMuch relevant information exists for investigators and clinicians interested in VILI. Future research will interlink evolving data to provide a more integrated picture of the molecular mechanisms involved in VILI enabling translation of the most promising candidate therapies.
Beam-forming network characteristics of spatial optical signal processing array antenna for multibeam reception

We have experimentally investigated the basic characteristics of a beam-forming network in a spatial optical signal processing array antenna for multibeam reception. In this experiment, two RF signals, which were simulated multibeam antenna receiving signals from different directions, were separated according to the signal arrival direction in the optical domain. The obtained results generally agreed with calculated values.
Glutathione S-transferase isoenzymes in rat brain neurons and glia

The glutathione S-transferases (GSTs) constitute a family of cytosolic isoenzymes and a structurally unrelated microsomal enzyme that is involved in the detoxication of electrophilic xenobiotics. These enzymes also participate in the intracellular binding and transport of a broad range of lipophilic compounds including bilirubin, and hormones such as the glucocorticoids and thyroid hormones. The present investigation demonstrates that GSTs are present in neurons of the brainstem, forebrain, and cerebellum. An isoenzyme-specific distribution of GSTs was found in cytoplasm, nuclei, and nucleoli. The regional and cellular distribution of cytosolic GSTs in the brain was studied by immunohistochemistry, spectrophotometric enzyme assay, and reverse-phase HPLC. Polyclonal antibody against microsomal GST was strongly reactive with Purkinje cells throughout the cerebellar cortex, and with neurons in the brainstem and hippocampus. Nuclei of Purkinje cells and of neurons in the brainstem, hippocampus, and cerebral cortex were immunopositive for alpha-class GST 1–1 (YaYa), whereas alpha-class GST 2–2 (YcYc) antibody was consistently immunoreactive with the nucleolus, but not with the nucleus or soma. All alpha-class GST antibodies studied were reactive, to various degrees, with astrocytes and choroid plexus; however, ependymal cells of the subventricular zones were immunonegative. alpha-class GST 8–8 (YkYk) immunoreactivity was specifically localized to endothelial cells and/or astrocytic end feet associated with blood vessels. Reverse-phase HPLC indicated that there were also substantial regional differences in the pattern of alpha-, mu-, and pi-class GST subunit expression. For example, the thalamus/hypothalamus had the highest GST activity and greatest concentration of total GST protein and mu-class GST subunit 6 (Yb3), whereas the brainstem had the greatest concentration of pi-class GST subunit (Yp). This regional variation in GST expression may be reflective of regional differences in cell populations. In cerebellar cortex, the concentration of mu-class GST subunit 4 (Yb2) was greatest in the flocculus and lowest in the vermis. This is of clinical interest because the pattern of expression of mu-class GST subunit 4 (Yb2) in the cerebellum coincides with the known regional susceptibility of this structure to degeneration after exposure to toxic or metabolic insults. The vermis is most susceptible to these insults, whereas the lateral lobes and flocculus are most resistant. (ABSTRACT TRUNCATED AT 400 WORDS)
The Effects of Diet, Sulfonylurea, and Repaglinide Therapy on Clinical and Metabolic Parameters in Type 2 Diabetic Patients During Ramadan

Background and Aim: Diabetes and its treatment can cause problems for the Muslim population. The aim of this study was to evaluate the effect of different therapy models on clinical and metabolic status in type 2 diabetic patients during Ramadan. Material and Methods: Fifty‐two type 2 diabetic patients were included to this study. Twelve of patients were on diabetic diet only before and during Ramadan (Group 1). Forty of patients had had sulfonylurea (Glimepiride 23 patients, gliclazide 17 patients) before Ramadan. Thirteen of these patients were on a single dose sulfonylurea (Glimepiride 8 patients, gliclazide 5 patients) (Group 2) and 27 were on Repaglinide 2 × 2 mg (Group 3) during Ramadan. β‐Hydroxybutyric acid, glucose, fructosamine, HbA1c, lipid levels and body weight were measured before and after Ramadan. Results: Body weight, fasting plasma glucose, fructosamine, HbA1c, total cholesterol were not changed in groups during the study. Triglyceride level decreased after Ramadan in groups 2 (p = 0.002) and 3 (p = 0.024). HDL‐cholesterol level increased in group 3 (p = 0.022). Fasting capillary β‐hydroxybutyric acid level increased in group 1 (p = 0.034) and didn't change in groups 2 and 3 during the Ramadan. Only one hypoglycemic event occurred at day 6 of Ramadan in patients in group 2 (the patient was on 3 mg glimepiride). Conclusion: Our results conclude that Ramadan fasting affects metabolic parameters in type 2 diabetes and hypoglycemia should be kept in mind especially in patients using sulfonylurea treatment. Ramadan fasting is not advised for type 2 diabetics while taking medical therapy. If the patient wants Ramadan fasting, these patients using Repaglinide can reduce the frequency of hypoglycemia.
Treatment outcomes and clinicopathologic characteristics of triple‐negative breast cancer patients who received platinum‐containing chemotherapy

The aim of this study was to evaluate the role of platinum‐containing chemotherapy for metastatic triple‐negative breast cancer (TNBC) patients in terms of the response rate (RR) and progression‐free survival. A second aim was to characterize the clinical behavior at the time of relapse of TNBC. We retrospectively analyzed the clinical outcomes of patients with metastatic breast cancer who received taxane–platinum chemotherapy as the first‐ or second‐line treatment, focusing on the TN phenotype. In total, 257 patients with metastatic breast cancer received platinum‐containing chemotherapy at Samsung Medical Center from 1999 to 2006. Of these patients, 106 patients with available data on estrogen (ER), progesterone (PgR) and human epidermal growth factor receptor‐2 (HER2) receptor status received taxane–platinum regimen as the first‐ or second‐line treatment. The overall RR of patients with TNBC was 39%. This rate did not differ significantly from those of patients with other phenotypes. The time to death after chemotherapy (19 vs. 50 months, p = 0.037) and overall survival (OS) (21 vs. 56 months, p = 0.030) differed significantly between patients with TNBC and non‐TNBC. TNBC showed a unique locoregional infiltration pattern at relapse, which might reflect its aggressive clinical behavior. Despite the similar response to platinum‐containing chemotherapy, patients with TNBC had a shorter OS than patients with non‐TNBC. The implication of TN phenotype as poor prognostic factor is uncertain, because it needs to be defined whether poor outcome is related to the rapid growing characteristics of tumor itself or the resistance to drug therapy. Further prospective studies are warranted. © 2008 Wiley‐Liss, Inc.
Pulmonary Specific Ancillary Treatment for Pediatric Acute Respiratory Distress Syndrome: Proceedings From the Pediatric Acute Lung Injury Consensus Conference

Objective: To provide an overview of the current literature on pulmonary-specific therapeutic approaches to pediatric acute respiratory distress syndrome to determine recommendations for clinical practice and/or future research. Data Sources: PubMed, EMBASE, CINAHL, SCOPUS, and the Cochrane Library were searched from inception until January 2013 using the following keywords in various combinations: ARDS, treatment, nitric oxide, heliox, steroids, surfactant, etanercept, prostaglandin therapy, inhaled beta adrenergic receptor agonists, N-acetylcysteine, ipratroprium bromide, dornase, plasminogen activators, fibrinolytics or other anticoagulants, and children. No language restrictions were applied. References from identified articles were searched for additional publications. Study Selection: All clinical studies pertaining to pulmonary-specific therapeutic approaches to pediatric acute respiratory distress syndrome were reviewed. If clinical pediatric data were sparse or unavailable, the findings from studies of adult acute respiratory distress syndrome and animal models that might be relevant to pediatric acute respiratory distress syndrome were examined. Data Extraction: All relevant studies were reviewed and pertinent data abstracted. Data Synthesis: Over the course of three international meetings, the pertinent findings of the literature review were discussed by a panel of 24 experts in the field representing 21 academic institutions and 8 countries. Recommendations developed and the supporting literature were distributed to all panel members without a conflict of interest and were scored by using the Research ANd Development/University of California, Los Angeles Appropriateness method. The modified Delphi approach was used as the methodology to achieve consensus among the panel. Conclusions: Overall, the routine use of surfactant, inhaled nitric oxide, glucocorticoids, prone positioning, endotracheal suctioning, and chest physiotherapy cannot be recommended. Inhaled nitric oxide should only be used for patients with documented pulmonary hypertension and/or right ventricular failure. Prone positioning may be considered in patients with severe pediatric acute respiratory distress syndrome. Future studies are definitely warranted to establish the role, if any, of these ancillary treatment modalities in pediatric acute respiratory distress syndrome.
Big Ding 鼎 and China Power: Divine Authority and Legitimacy

Paleographic, art historical, metallurgical, and archaeological data are used to identify the monumental bronze tetrapod ding vessel as a preeminent symbol of state authority and divine power during the Shang era of ca. 1640–1046 b.c.e . Paleographic data based on oracle bone terms and inscriptions includes reference to ding as a verb of ancestral sacrifice, and the ding vessel in the specialized compound, yiding, referring to the ritually and metamorphically empowered ding vessel. Art historical data accounts for differences in form and style between ding tetrapod and tripod types. Metallurgical data derives primarily from a unique source of high radiogenic lead in southern China exploited during the early Shang period. Archaeological data derives from excavated Shang tetrapod ding in royal burial or cache burials.
Effect of intrauterine growth restriction on blood pressure, glucose tolerance and sympathetic nervous system activity in the rat at 3-4 months of age.

OBJECTIVE Epidemiological studies suggest that intrauterine growth restriction (IUGR) due to maternal undernutrition during pregnancy represents a major risk factor for hypertension and diabetes in adult age. However, placental insufficiency, rather than maternal malnutrition, is the main cause of IUGR in the Western world. We therefore studied the relationship between birth weight and adult blood pressure and glucose tolerance in an established animal model of placental insufficiency. DESIGN IUGR was induced by uterine artery ligation in pregnant rats and the offspring were studied at 3-4 months of age. METHODS In one subgroup of animals (n = 41, birth weight range 3.2-6.6 g) blood pressure was recorded over 72 h using telemetry and hypothalamic tissue levels of noradrenaline was measured. In another subgroup (n = 30, birth weight range 3.0-6.8 g) the activity of the sympathetic nervous system (SNS) was assessed by noradrenaline isotope dilution techniques and glucose tolerance determined by an intravenous glucose load. RESULTS Adult blood pressure was independent of birth weight Haemodynamic responses of IUGR rats to moderate sound stress was unaltered. In male rats neither SNS activity, hypothalamic noradrenaline concentrations nor glucose tolerance was associated with birth weight In contrast, IUGR in female rats was associated with increased SNS activity, elevated fasting blood glucose as well as lower insulin and higher glucose levels in response to a glucose load. CONCLUSION IUGR is not linked to an elevated blood pressure at 3-4 months of age in this model. However, in female rats, IUGR is associated with increased SNS activity and impaired glucose tolerance in adult life.
Sipatrigine and oligodendrocyte and axonal pathology following transient focal cerebral ischaemia in the rat

The ability of Sipatrigine (BW619c89), a sodium and calcium channel blocker to protect neuronal perikarya, axons and oligodendrocytes from ischaemia has been evaluated in the rat. Sipatrigine (30 mg/kg) was administered 15 min prior to transient (2 h) occlusion of the middle cerebral artery with animals being sacrificed 24 h after induction of ischaemia. Sipatrigine significantly reduced the volumes of neuronal perikarya damage (by 35%) and oligodendrocyte damage (by 54%). Sipatrigine minimally altered axonal damage (median scores: vehicle ∼30, Sipatrigine ∼26). The present report provides evidence that neuronal perikarya, axons and oligodendrocytes may be differentially protected by pharmacological intervention in focal cerebral ischaemia.
Host SAMHD1 Protein Promotes HIV-1 Recombination in Macrophages*

Background: Delaying DNA synthesis kinetics of HIV-1 reverse transcriptase by lowering dNTP concentrations elevates biochemical RNA template switch. Results: Degradation of SAMHD1 by Vpx, which increases dNTP levels, reduces HIV-1 template switching in macrophages, but not in CD4+ T cells. Conclusion: Altering cellular dNTP levels directly affects in vivo HIV-1 template switching. Significance: Cellular dNTP abundance controlled by SAMHD1 contributes to HIV-1 template switching in macrophages. Template switching can occur during the reverse transcription of HIV-1. Deoxynucleotide triphosphate (dNTP) concentrations have been biochemically shown to impact HIV-1 reverse transcriptase (RT)-mediated strand transfer. Lowering the dNTP concentrations promotes RT pausing and RNA template degradation by RNase H activity of the RT, subsequently leading to strand transfer. Terminally differentiated/nondividing macrophages, which serve as a key HIV-1 reservoir, contain extremely low dNTP concentrations (20–50 nm), which results from the cellular dNTP hydrolyzing sterile α motif and histidine aspartic domain containing protein 1 (SAMHD1) protein, when compared with activated CD4+ T cells (2–5 μm). In this study, we first observed that HIV-1 template switching efficiency was nearly doubled in human primary macrophages when compared with activated CD4+ T cells. Second, SAMHD1 degradation by viral protein X (Vpx), which elevates cellular dNTP concentrations, decreased HIV-1 template switching efficiency in macrophages to the levels comparable with CD4+ T cells. Third, differentiated SAMHD1 shRNA THP-1 cells have a 2-fold increase in HIV-1 template switching efficiency. Fourth, SAMHD1 degradation by Vpx did not alter HIV-1 template switching efficiency in activated CD4+ T cells. Finally, the HIV-1 V148I RT mutant that is defective in dNTP binding and has DNA synthesis delay promoted RT stand transfer when compared with wild type RT, particularly at low dNTP concentrations. Here, we report that SAMHD1 regulation of the dNTP concentrations influences HIV-1 template switching efficiency, particularly in macrophages.
Malaguarnera : IR and cancer Studies linking insulin resistance , circulating insulin , and cancer

The widespread epidemic of obesity and type 2 diabetes has raised concern for the impact of these disorders as risk factors for cancer and has renewed the interest for studies regarding the involvement of hyperinsulinemia and insulin receptor (IR) in cancer progression. Overexpression of IR in cancer cells may explain their increased sensitivity to hyperinsulinemia. Moreover, IR isoform A (IR-A) together with autocrine production of its ligand IGF2 is emerging as an important mechanism of normal and cancer stem cell expansion and is a feature of several malignancies. De novo activation of the IR-A/IGF2 autocrine loop also represents a mechanism of resistance to anticancer therapies. Increasing knowledge of the IR role in cancer has important implications for cancer prevention, which should include control of insulin resistance and hyperinsulinemia in the population and meticulous evaluation of new antidiabetic drugs for their metabolic:mitogenic ratio. We are now aware that several anticancer treatments may induce or worsen insulin resistance that may limit therapy efficacy. Future anticancer therapies need to target the IR-A pathway in order to inhibit the tumor promoting effect of IR without impairing the metabolic effect of insulin. Endocrine-Related Cancer (2011) 18 R125–R147