A Mass Spectrometry-Based Profiling of Interactomes of Viral DDB1- and Cullin Ubiquitin Ligase-Binding Proteins Reveals NF-κB Inhibitory Activity of the HIV-2-Encoded Vpx

Viruses and hosts are situated in a molecular arms race. To avoid morbidity and mortality, hosts evolved antiviral restriction factors. These restriction factors exert selection pressure on the viruses and drive viral evolution toward increasingly efficient immune antagonists. Numerous viruses exploit cellular DNA damage-binding protein 1 (DDB1)-containing Cullin RocA ubiquitin ligases (CRLs) to induce the ubiquitination and subsequent proteasomal degradation of antiviral factors expressed by their hosts. To establish a comprehensive understanding of the underlying protein interaction networks, we performed immuno-affinity precipitations for a panel of DDB1-interacting proteins derived from viruses such as mouse cytomegalovirus (MCMV, Murid herpesvirus [MuHV] 1), rat cytomegalovirus Maastricht MuHV2, rat cytomegalovirus English MuHV8, human cytomegalovirus (HCMV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV). Cellular interaction partners were identified and quantified by mass spectrometry (MS) and validated by classical biochemistry. The comparative approach enabled us to separate unspecific interactions from specific binding partners and revealed remarkable differences in the strength of interaction with DDB1. Our analysis confirmed several previously described interactions like the interaction of the MCMV-encoded interferon antagonist pM27 with STAT2. We extended known interactions to paralogous proteins like the interaction of the HBV-encoded HBx with different Spindlin proteins and documented interactions for the first time, which explain functional data like the interaction of the HIV-2-encoded Vpr with Bax. Additionally, several novel interactions were identified, such as the association of the HIV-2-encoded Vpx with the transcription factor RelA (also called p65). For the latter interaction, we documented a functional relevance in antagonizing NF-κB-driven gene expression. The mutation of the DDB1 binding interface of Vpx significantly impaired NF-κB inhibition, indicating that Vpx counteracts NF-κB signaling by a DDB1- and CRL-dependent mechanism. In summary, our findings improve the understanding of how viral pathogens hijack cellular DDB1 and CRLs to ensure efficient replication despite the expression of host restriction factors

Hypsometric

Elevation data in Kendari BayTHIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Hypsometric

Elevation data in Kendari BayTHIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Analysis of Service Performance in the Domestic and Civil Department of Bone Bolango Regency, Gorontalo Province

This study aims to analyze the performance of services in the population and civil registration offices of Bone Bolango District, and the determinants in improving service performance in the Population and Civil Registry kabupaten Bone Bolango. This type of research is qualitative research with a case study approach. Data collection is done through interviews, observation and documentation. Technical data analysis is used through the stages of data reduction, data presentation, and conclusion drawing. The results of the study show that (1) the performance of the state civil service apratur in the Population and Civil Registry Service of Bone Bolango Regency is applied in accordance with the principles of public service principles that cover 10 (ten Aspects), where only 2 (two) aspects have gone well, namely aspects ease of access, and aspects. Meanwhile 8 (eight) aspects consisting of aspects of simplicity, clarity, certainty of time, accuracy, security, responsibility, and completeness of facilities and infrastructure have not been implemented properly so that it is still needed to be addressed and improved the service process. (2) The factors that determine the improvement of the performance of human resources services are; a) Human Performance Perspective, namely the motivation and ability factors of the apparatus that are still lacking in supporting the service implementation process so that performance achievements are not optimal, b) Organizational Perspective, that is communication factors that have not been effective cause information that is not managed and utilized optimally

Analisis Persepsi Pelayanan Kapal Malam Rute Kendari - Raha Provinsi Sulawesi Tenggara

The characteristics of night ship passengers are dominated by men, the average age of passengers is 20-25 years with a percentage value of 64%, the most travel destinations are Muna Island and the dominant service users have student jobs, while the analysis results are seen in the value of 0.66- 0.8, this means that the overall CSI score for performance appraisal is 1.96 with the criteria for the value of each indicator, service users are very satisfied with the performance of night ship services on the Kendari - Raha route, Southeast Sulawesi Province. The perception of service users towards night boat services on the Kendari - Raha route as a whole with an average value of 3.5 for performance and 3.1 for satisfaction. This can be seen in the quadrant A diagram in the Cartesian diagram, which means that the service elements are very good and provided very well

Hypercoagulability and other risk factors in trauma intensive care unit patients with venous thromboembolism

Thromboelastography (TEG) on hospital admission can identify hypercoagulable trauma patients at risk for venous thromboembolism (VTE), but the value of TEGs obtained after multiple interventions, including tranexamic acid (TXA), has not been defined. We test the following hypotheses. (1) TEG on intensive care unit (ICU) admission can help stratify patients screened with Greenfield's risk assessment profile (RAP) for VTE. (2) TXA is a VTE risk factor, and its effect on fibrinolysis can be identified with TEG. Trauma patients who survived to the ICU with RAP ≥ 10 received serial venous duplex ultrasound examinations and blood samples for coagulation analysis at admission to the ICU and weekly thereafter. Six hundred seventy-eight patients were screened and 121 were enrolled; 76% blunt injury, Injury Severity Score (ISS) 27, 13% mortality. Thromboprophylaxis was administered to 90% of the patients and was started a median of 2 days after hospital admission. VTE was detected in 28% (n = 34) of the patients (27 deep vein thrombosis and 7 pulmonary emboli) and occurred a median 10 days after admission. Twenty-nine percent (n = 10) of VTE occurred within 2 days of admission. Most variables were similar between those with and without VTE, but the VTE group received more operations (3 (2) vs. 2 (2), p = 0.044), had increased ICU days (25 (34) days vs. 15 (18) days, p = 0.004), and was more likely to have abdominal injury with Abbreviated Injury Scale (AIS) score > 2 (59% vs. 39%, p = 0.050). Upon ICU admission, standard coagulation markers were within normal limits, while TEG demonstrated hypercoagulability, but neither was associated with VTE. Repeat TEG one week after admission (n = 58) remained hypercoagulable but transitioned to a different pattern with increased clot strength. TXA was associated with reduced fibrinolysis on initial TEG (p < 0.05) but was not associated with VTE. Trauma ICU patients with RAP ≥ 10 are hypercoagulable at admission to ICU and remain so during recovery. They have a ≥ 25% rate of VTE, despite thromboprophylaxis. TXA is associated with reduced fibrinolysis but does not increase VTE rates. Neither TEG nor standard coagulation markers (measured on ICU admission) stratify high-risk patients who develop VTE from those who do not. Prognostic study, level III

Vasopressor Use during Emergency Trauma Surgery

Most evidence suggests early vasopressor use is associated with death after trauma, but no previous study has focused on patients requiring emergency operative intervention (OR). We test the hypothesis that vasopressors are harmful in this population. Records from 746 patients requiring OR from July 2009 to March 2013 were retrospectively reviewed and stratified based on vasopressor use (epinephrine [EPI], phenylephrine, ephedrine, norepinephrine, dobutamine, vasopressin) or no vasopressor use. Vasopressors were administered to 225 patients (30%) during OR; 59 patients (8%) received multiple vasopressors. Patients who received vasopressors were older, more severely injured, had worse vital signs, and increased mortality rate (all P < 0.001). EPI was independently associated with mortality (odds ratio, 6.88; P = 0.001). If patients who received EPI were excluded, there was no difference in mortality between those who received vasopressors alone or in combination and those that did not (5 vs 6%, P = 0.523), although multiple markers of injury severity were worse. We conclude that vasopressor use is relatively common in the most severely injured patients requiring OR and is associated with mortality. EPI is most often used for cardiac arrest, whereas other vasopressors are used for their vasoconstrictive properties. This suggests that, except for EPI, vasopressors during OR are not independently associated with mortality

Long-term coagulation changes after resection of thoracoabdominal malignancies

The purpose of this study was to evaluate the long-term coagulation status of patients undergoing malignancy resection. A prospective observational trial was conducted with informed consent in 52 patients (age 66 ± 10 years and 60% male) with thoracoabdominal tumors (pancreas [n = 18, 35%], esophagus [n = 13, 25%], liver [n = 7, 14%], stomach [n = 6, 12%], bile duct [n = 3, 6%], retroperitoneal [n = 3, 6%], and duodenum [n = 2, 4%]) with 6- to 12-month follow-up. Coagulation was evaluated with rotational thromboelastography (ROTEM) on whole blood and with a panel of hemostatic markers on stored plasma. Maximum clot firmness (MCF) in the intrinsic, extrinsic, and fibrinogen pathways increased immediately postoperatively and then decreased by 9.2 ± 4.1 months (p < 0.05). Markers of thrombin generation (prothrombin fragment 1 + 2, fibrinolysis [D-dimer], and endothelial activation [coagulation factor VIII]) were elevated at all time points. The ROTEM pattern depended on histologic type and cancer location. All esophageal tumors were adenocarcinoma and demonstrated similar patterns to the overall population, with MCF differences over time in all 3 pathways (all p < 0.05). Regarding tumors of the pancreas or liver, there were no statistically significant differences when comparing all 3 time periods, but there were time-related differences when evaluating only primary adenocarcinomas of the liver (all p < 0.05). Three patients (6%) developed venous thromboembolism (VTE) and had decreased clot formation time, increased angle, and increased MCF (all p < 0.05). Cancer patients at risk for VTE can be identified with a point-of-care ROTEM test and may benefit from additional anticoagulation. Biomarkers reflecting different functional hemostasis activity groups (fibrinolysis, thrombin generation, and endothelial activation) confirm the ongoing prothrombotic state. The ROTEM demonstrated increased hypercoagulability postoperatively, which returned to baseline in long-term follow-up. Reversal of cancer-induced hypercoagulability occurred in some patients and varied with tumor histology and location