Book Review of, Russian America: An Overseas Colony of a Continental Empire, 1804–1867

Chia Yin Hsu, Assistant Professor at Portland State University with expertise in late Imperial and early Soviet Russia, reviews Russian America: An Overseas Colony of a Continental Empire, 1804–1867. By Ilya Vinkovetsky

The Untranslated Regions of Classic Swine Fever Virus RNA Trigger Apoptosis

Classical swine fever virus (CSFV) causes a broad range of disease in pigs, from acute symptoms including high fever and hemorrhages, to chronic disease or unapparent infection, depending on the virus strain. CSFV belongs to the genus Pestivirus of the family Flaviviridae. It carries a single-stranded positive-sense RNA genome. An internal ribosomal entry site (IRES) in the 5' untranslated region (UTR) drives the translation of a single open reading frame encoding a 3898 amino acid long polypeptide chain. The open reading frame is followed by a 3' UTR comprising four highly structured stem-loops. In the present study, a synthetic RNA composed of the 5' and 3' UTRs of the CSFV genome devoid of any viral coding sequence and separated by a luciferase gene cassette (designated 5'UTR-Luc-3'UTR) triggered apoptotic cell death as early as 4 h post-transfection. The apoptosis was measured by DNA laddering analysis, TUNEL assay, annexin-V binding determined by flow cytometry, and by analysis of caspase activation. Contrasting with this, only trace DNA laddering was observed in cells transfected with the individual 5' or 3' UTR RNA; even when the 5' UTR and 3' UTR were co-transfected as separate RNA molecules, DNA laddering did not reach the level induced by the chimeric 5'UTR-Luc-3'UTR RNA. Interestingly, RNA composed of the 5'UTR and of stem-loop I of the 3'UTR triggered much stronger apoptosis than the 5' or 3'UTR alone. These results indicate that the 5' and 3' UTRs act together in cis induce apoptosis. We furthered obtained evidence that the UTR-mediated apoptosis required double-stranded RNA and involved translation shutoff possibly through activation of PKR

Interoceptive awareness: MBSR training alters information processing of salience network

Mindfulness refers to a mental state of awareness of internal experience without judgment. Studies have suggested that each mindfulness practice may involve a unique mental state, but the underlying neurophysiological mechanisms remain unknown. Here we examined how distinct mindfulness practices after mindfulness-based intervention alter brain functionality. Specifically, we investigated the functional alterations of the salience network (SN) using functional magnetic resonance imaging (fMRI) among the two interoceptive mindfulness practices—breathing and body scan—associated with interoceptive awareness in fixed attention and shifted attention, respectively. Long-distance functional connectivity (FC) and regional homogeneity (ReHo) approaches were applied to measure distant and local neural information processing across various mental states. We hypothesized that mindful breathing and body scan would yield a unique information processing pattern in terms of long-range and local functional connectivity (FC). A total of 18 meditation-naïve participants were enrolled in an 8-week mindfulness-based stress reduction (MBSR) program alongside a waitlist control group (n = 14), with both groups undergoing multiple fMRI sessions during breathing, body scan and resting state for comparison. We demonstrated that two mindfulness practices affect both the long-distance FCSN and the local ReHo, only apparent after the MBSR program. Three functional distinctions between the mindfulness practices and the resting state are noted: (1) distant SN connectivity to occipital regions increased during the breathing practice (fixed attention), whereas the SN increased connection with the frontal/central gyri during the body scan (shifting attention); (2) local ReHo increased only in the parietal lobe during the body scan (shifting attention); (3) distant and local connections turned into a positive correlation only during the mindfulness practices after the MBSR training, indicating a global enhancement of the SN information processing during mindfulness practices. Though with limited sample size, the functional specificity of mindfulness practices offers a potential research direction on neuroimaging of mindfulness, awaiting further studies for verification

Chronic Kidney Disease Stage Is a Modulator on the Association between High-Sensitivity C-Reactive Protein and Coronary Vasospastic Angina

The prevalence of coronary vasospasm and also the factors associated with coronary vasospasm in CKD is still unclear. In this cross-sectional study of 859 consecutive CKD patients with angina pectoris received coronary catheterization, we evaluated the factors associated with coronary vasospasm. Patients with vasospasm were older and had higher peripheral blood white cell counts, higher peripheral blood monocyte cell counts, higher haemoglobin levels, higher hs-CRP levels, and lower levels of serum creatinine than patients without vasospasm. The results of multivariate logistic regression analysis revealed that peripheral blood monocyte count and hs-CRP level were independently associated with coronary vasospasm in patients with stage 1 CKD. Only peripheral blood monocyte count but not hs-CRP was independently associated with coronary vasospasm in patients with stages 2 and 3 of CKD. In conclusion, peripheral blood monocyte count is independently associated with coronary vasospasm in patients with stage 1–3 CKD, whereas hs-CRP is only independently associated with coronary vasospasm in patients with stage 1 CKD

Preoperative Proteinuria Is Associated with Long-Term Progression to Chronic Dialysis and Mortality after Coronary Artery Bypass Grafting Surgery

AIMS: Preoperative proteinuria is associated with post-operative acute kidney injury (AKI), but whether it is also associated with increased long-term mortality and end-stage renal disease (ESRD) is unknown. METHODS AND RESULTS: We studied 925 consecutive patients undergoing CABG. Demographic and clinical data were collected prospectively, and patients were followed for a median of 4.71 years after surgery. Proteinuria, according to dipstick tests, was defined as mild (trace to 1+) or heavy (2+ to 4+) according to the results of the dipstick test. A total of 276 (29.8%) patients had mild proteinuria before surgery and 119 (12.9%) patients had heavy proteinuria. During the follow-up, the Cox proportional hazards model demonstrated that heavy proteinuria (hazard ratio [HR], 27.17) was an independent predictor of long-term ESRD. There was a progressive increased risk for mild proteinuria ([HR], 1.88) and heavy proteinuria ([HR], 2.28) to predict all-cause mortality compared to no proteinuria. Mild ([HR], 2.57) and heavy proteinuria ([HR], 2.70) exhibited a stepwise increased ratio compared to patients without proteinuria for long-term composite catastrophic outcomes (mortality and ESRD), which were independent of the baseline GFR and postoperative acute kidney injury (AKI). CONCLUSION: Our study demonstrated that proteinuria is a powerful independent risk factor of long-term all-cause mortality and ESRD after CABG in addition to preoperative GFR and postoperative AKI. Our study demonstrated that proteinuria should be integrated into clinical risk prediction models for long-term outcomes after CABG. These results provide a high priority for future renal protective strategies and methods for post-operative CABG patients

Association of Alpha B-Crystallin Genotypes with Oral Cancer Susceptibility, Survival, and Recurrence in Taiwan

BACKGROUND: Alpha B-crystallin (CRYAB) is a protein that functions as "molecular chaperone" in preserving intracellular architecture and cell membrane. Also, CRYAB is highly antiapoptotic. Abnormal CRYAB expression is a prognostic biomarker for oral cancer, while its genomic variations and the association with carcinogenesis have never been studied. METHODOLOGY/FINDING: Therefore, we hypothesized that CRYAB single nucleotide polymorphisms may be associated with oral cancer risk. In this hospital-based study, the association of CRYAB A-1215G (rs2228387), C-802G (rs14133) and intron2 (rs2070894) polymorphisms with oral cancer in a Taiwan population was investigated. In total, 496 oral cancer patients and 992 age- and gender-matched healthy controls were genotyped and analyzed. A significantly different frequency distribution was found in CRYAB C-802G genotypes, but not in A-1215G and intron2 genotypes, between the oral cancer and control groups. The CRYAB C-802G G allele conferred an increased risk of oral cancer (P = 1.49×10(-5)). Patients carrying CG/GG at CRYAB C-802G were of lower 5-year survival and higher recurrence rate than those of CC (P<0.05). CONCLUSION/SIGNIFICANCE: Our results provide the first evidence that the G allele of CRYAB C-802G is correlated with oral cancer risk and this polymorphism may be a useful marker for oral cancer recurrence and survival prediction for clinical reference

The C-Terminus of Histone H2B Is Involved in Chromatin Compaction Specifically at Telomeres, Independently of Its Monoubiquitylation at Lysine 123

Telomeric heterochromatin assembly in budding yeast propagates through the association of Silent Information Regulator (SIR) proteins with nucleosomes, and the nucleosome array has been assumed to fold into a compacted structure. It is believed that the level of compaction and gene repression within heterochromatic regions can be modulated by histone modifications, such as acetylation of H3 lysine 56 and H4 lysine 16, and monoubiquitylation of H2B lysine 123. However, it remains unclear as to whether or not gene silencing is a direct consequence of the compaction of chromatin. Here, by investigating the role of the carboxy-terminus of histone H2B in heterochromatin formation, we identify that the disorderly compaction of chromatin induced by a mutation at H2B T122 specifically hinders telomeric heterochromatin formation. H2B T122 is positioned within the highly conserved AVTKY motif of the αC helix of H2B. Heterochromatin containing the T122E substitution in H2B remains inaccessible to ectopic dam methylase with dramatically increased mobility in sucrose gradients, indicating a compacted chromatin structure. Genetic studies indicate that this unique phenotype is independent of H2B K123 ubiquitylation and Sir4. In addition, using ChIP analysis, we demonstrate that telomere structure in the mutant is further disrupted by a defect in Sir2/Sir3 binding and the resulting invasion of euchromatic histone marks. Thus, we have revealed that the compaction of chromatin per se is not sufficient for heterochromatin formation. Instead, these results suggest that an appropriately arrayed chromatin mediated by H2B C-terminus is required for SIR binding and the subsequent formation of telomeric chromatin in yeast, thereby identifying an intrinsic property of the nucleosome that is required for the establishment of telomeric heterochromatin. This requirement is also likely to exist in higher eukaryotes, as the AVTKY motif of H2B is evolutionarily conserved

Impact of intravenous vitamin C as a monotherapy on mortality risk in critically ill patients: A meta-analysis of randomized controlled trials with trial sequential analysis

BackgroundThis meta-analysis aimed at investigating the pooled evidence regarding the effects of intravenous vitamin C (IVVC) on mortality rate in critically ill patients.MethodsDatabases including Medline, Embase, and Cochrane Library were searched from inception to October, 2022 to identify RCTs. The primary outcome was the risk of overall mortality. Subgroup analyses were performed based on IVVC dosage (i.e., cut-off value: 100 mg/kg/day or 10000 mg/day). Trial sequential analysis (TSA) was used to examine the robustness of evidence.ResultsA total of 12 trials including 1,712 patients were analyzed. Although meta-analysis demonstrated a lower risk of mortality in patients with IVVC treatment compared to those without [risk ratio (RR): 0.76, 95% CI: 0.6 to 0.97, p = 0.02, I2 = 36%, 1,711 patients), TSA suggested the need for more studies for verification. Moreover, subgroup analyses revealed a reduced mortality risk associated with a low IVVC dosage (RR = 0.72, p = 0.03, 546 patients), while no beneficial effect was noted with high IVVC dosage (RR = 0.74, p = 0.13, I2 = 60%, 1,165 patients). The durations of vasopressor [mean difference (MD): −37.75 h, 404 patients) and mechanical ventilation (MD: −47.29 h, 388 patients) use were shorter in the IVVC group than those in the controls, while there was no significant difference in other prognostic outcomes (e.g., length of stay in intensive care unit/hospital) between the two groups.ConclusionAlthough intravenous vitamin C as a monotherapy reduced pooled mortality, durations of vasopressor use and mechanical ventilation, further research is required to support our findings and to identify the optimal dosage of vitamin C in the critical care setting.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022371090