Fish species-specific TRIM gene FTRCA1 negatively regulates interferon response through attenuating IRF7 transcription

In mammals and fish, emerging evidence highlights that TRIM family members play important roles in the interferon (IFN) antiviral immune response. Fish TRIM family has undergone an unprecedented expansion leading to generation of finTRIM subfamily, which is exclusively specific to fish. Our recent results have shown that FTRCA1 (finTRIM C. auratus 1) is likely a fish species-specific finTRIM member in crucian carp C. auratus and acts as a negative modulator to downregulate fish IFN response by autophage-lysosomal degradation of protein kinase TBK1. In the present study, we found that FTRCA1 also impedes the activation of crucian carp IFN promoter by IRF7 but not by IRF3. Mechanistically, FTRCA1 attenuates IRF7 transcription levels likely due to enhanced decay of IRF7 mRNA, leading to reduced IRF7 protein levels and subsequently reduced fish IFN expression. E3 ligase activity is required for FTRCA1 to negatively regulate IRF7-mediated IFN response, because ligase-inactive mutants and the RING-deleted mutant of FTRCA1 lose the ability to block the activation of crucian carp IFN promoter by IRF7. These results together indicate that FTRCA1 is a multifaceted modulator to target different signaling factors for shaping fish IFN response in crucian carp.</p

Assessment of mild hypothermia combined with edaravone for the treatment of severe craniocerebral injury

Purpose: To study the clinical effect of combining mild hypothermia with edaravone in the treatment of severe craniocerebral injury. Methods: One hundred and twenty (120) patients with severe craniocerebral injury who were admitted to Tianjin Medical University General Hospital were assigned to control and study groups, respectively. Patients in the control group were given conventional treatment while those in the study group received combined treatment of mild hypothermia and edaravone, in addition to the conventional treatment received by control group. Clinical efficacy and prognosis were compared between the two groups. Results: The intracranial pressure (ICP) of both groups decreased after admission, but the decrease in ICP was more pronounced in the study group at various time points (p &lt; 0.05). Blood lactic acid levels decreased in both groups after admission, while brain-derived neurotrophic factor (BDNF) levels increased. Improvement in blood lactic acid and BDNF was greater in the study group than in control group (p &lt; 0.05). The treatment resulted in significant decrease in residual hematoma volume and edema range in the study group, relative to control (p &lt; 0.05). There was a decrease in National Institutes of Health Stroke Scale (NIHSS) scores, and increase in Glasgow outcome scale (GOS) scores in both groups. However, improvement in NIHSS and GOS scores in the study group was superior to those in control group (p &lt; 0.05). Conclusion: Mild hypothermia in combination with edaravone exerts a beneficial clinical effect in severe craniocerebral injury. The combined treatment rapidly reduces ICP and range of encephaledema, improves cerebral blood supply, promotes absorption of intracranial hematoma, and relieves nervous dysfunction

Forschungsdatenzentrum PIAAC: Jahresbericht 2015; Berichtszeitraum 01.01.2015-31.12.2015

We used human gastric epithelial cells (GES-1) line in an ethanol-induced cell damage model to study the protective effect of Veronicastrum axillare and its modulation to NF-κB signal pathway. The goal was to probe the molecular mechanism of V. axillare decoction in the prevention of gastric ulcer and therefore provide guidance in the clinical application of V. axillare on treating injuries from chronic nephritis, pleural effusion, gastric ulcer, and other ailments. The effects of V. axillare-loaded serums on cell viability were detected by MTT assays. Enzyme-linked immunosorbent assay (ELISA) and Real-Time PCR methods were used to analyze the protein and mRNA expression of TNF-α, NF-κB, IκBα, and IKKβ. The results showed that V. axillare-loaded serum partially reversed the damaging effects of ethanol and NF-κB activator (phorbol-12-myristate-13-acetate: PMA) and increased cell viability. The protein and mRNA expressions of TNF-α, NF-κB, IκBα, and IKKβ were significantly upregulated by ethanol and PMA while they were downregulated by V. axillare-loaded serum. In summary, V. axillare-loaded serum has significantly protective effect on GES-1 against ethanol-induced injury. The protective effect was likely linked to downregulation of TNF-α based NF-κB signal pathway

Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin

Metformin use is associated with reduced cancer mortality, but how metformin impacts cancer outcomes is controversial. Although metformin can act on cells autonomously to inhibit tumor growth, the doses of metformin that inhibit proliferation in tissue culture are much higher than what has been described in vivo. Here, we show that the environment drastically alters sensitivity to metformin and other complex I inhibitors. We find that complex I supports proliferation by regenerating nicotinamide adenine dinucleotide (NAD)+, and metformin's anti-proliferative effect is due to loss of NAD+/NADH homeostasis and inhibition of aspartate biosynthesis. However, complex I is only one of many inputs that determines the cellular NAD+/NADH ratio, and dependency on complex I is dictated by the activity of other pathways that affect NAD+ regeneration and aspartate levels. This suggests that cancer drug sensitivity and resistance are not intrinsic properties of cancer cells, and demonstrates that the environment can dictate sensitivity to therapies that impact cell metabolism. Keywords: cancer metabolism; metformin; biguanide; NAD+/NADH ratio; drug sensitivity; complex I; mitochondria; aspartateNational Institutes of Health (U.S.) (Grant P30CA1405141)National Institutes of Health (U.S.) (Grant GG006413)National Institutes of Health (U.S.) (Grant R01 CA168653)National Institutes of Health (U.S.) (Grant R01 CA201276

A Panel of Serum MicroRNAs as Specific Biomarkers for Diagnosis of Compound- and Herb-Induced Liver Injury in Rats

Drug-induced liver injury (DILI) has been a public, economic and pharmaceutical issue for many years. Enormous effort has been made for discovering and developing novel biomarkers for diagnosing and monitoring both clinical and preclinical DILI at an early stage, though progress has been relatively slow. Additionally, herb-induced liver injury is an emerging cause of liver disease because herbal medicines are increasingly being used worldwide. Recently, circulating microRNAs (miRNAs) have shown potential to serve as novel, minimally invasive biomarkers to diagnose and monitor human cancers and other diseases at early stages.In order to identify candidate miRNAs as diagnostic biomarkers for DILI, miRNA expression profiles of serum and liver tissue from two parallel liver injury Sprague-Dawley rat models induced by a compound (acetaminophen, APAP) or an herb (Dioscorea bulbifera, DB) were screened in this study. The initial screens were performed on serum using a MicroRNA TaqMan low-density qPCR array and on liver tissue using a miRCURY LNA hybridization array and were followed by a TaqMan probe-based quantitative reverse transcription-PCR (qRT-PCR) assay to validate comparison with serum biochemical parameters and histopathological examination. Two sets of dysregulated miRNA candidates in serum and liver tissue were selected in the screening phase. After qRT-PCR validation, a panel of compound- and herb- related serum miRNAs was identified.We have demonstrated that this panel of serum miRNAs provides potential biomarkers for diagnosis of DILI with high sensitivity and specificity

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good