Range-wide life-history diversity and climate exposure in Chinook salmon

Climate change risk for migratory species is intertwined with their life-history diversity. Here I quantify climate risk, exposure, and phenological adaptive capacity in Chinook salmon during their spawning migrations for populations from across their North American range. First, I assessed how migration timing varies with watershed characteristics. Populations with longer migration distances and from higher elevations entered freshwater earlier. Second, I quantified climate exposure and risk by linking migration timing data to recent (1990s) and future (2040s) water temperatures. Nearly a quarter of populations will be exposed to future temperatures above thermally stressful thresholds. Third, I assessed the rate and direction of phenological shifts that would enable Chinook to adapt to climate warming. Spring populations would need to shift earlier, while fall populations would need to shift later. Broadly, my thesis highlights that climate exposure, risk and adaptive capacity are structured by phenology and latitude in a diverse migratory species

Regulation of type IV pili formation and function by the small GTPase MglA in Myxococcus xanthus

Myxococcus xanthus cells are rod-shaped and move in the direction of their long axis, using two distinct motility systems. Adventurous gliding (A-) depends on the Agl/Glt motility complexes that assemble at the leading pole, adhere to the substratum, and disassemble at the lagging pole. Social (S-) motility depends on type IV pili (T4P) that localize at the leading cell pole. T4P are anchored in the cell envelope and pull cells forward through cycles of extension, surface adhesion and retraction powered by the T4P machine. This machine includes 10 proteins spanning the outer membrane, periplasm, inner membrane and cytoplasm. Most of the proteins in the machine form stationary complexes at the two poles while the two ATPases PilB and PilT localize mostly at the leading and lagging pole, respectively. M. xanthus cells occasionally stop and resume movement in the opposite direction. These reversals are regulated by the Frz chemosensory system. During reversals the old lagging pole becomes the new leading and vice versa, the two motility systems invert polarity and after a reversal, T4P are formed at the new leading pole. Thus, T4P can assemble at both poles but at any point in time, T4P only assemble at one pole. The mechanism(s) underlying unipolar T4P formation during cell movement remains unknown. The small GTPase MglA is essential for motility in M. xanthus. MglA cycles between the active MglA-GTP state, which is essential for motility, and the inactive MglA-GDP state. MglA is activated by the RomR/RomX complex, which has guanine nucleotide exchange factor (GEF) activity, and is inhibited by MglB, which is a GTPase activating protein (GAP). MglA-GTP mostly localizes to the leading pole while MglB as well as RomR/RomX localize in bipolar, asymmetric pattern with the large cluster at the lagging pole. RomR/RomX recruits MglA-GTP to the leading pole while MglB excludes MglA-GTP from the lagging pole by converting MglA-GTP to MglAGDP. Among these four proteins, only MglA is essential for T4P-dependent motility. However, the precise function of MglA for the T4P-dependent motility remains unclear. Here, we demonstrate that MglA-GTP stimulates T4P formation and function while MglB ensures T4P unipolarity by excluding MglA-GTP from the lagging pole. Moreover, we identify the TPR domain-containing protein SgmX and show that it is important for T4P formation. Epistasis analyses support that MglA-GTP and SgmX act in the same genetic pathway and that SgmX acts downstream of MglA-GTP. In vitro analyses support that SgmX interacts directly with MglA-GTP. Additionally, SgmX stimulates polar accumulation of the PilB extension ATPase. Based on these findings, we propose a model in which MglA-GTP stimulates T4P assembly via direct interaction with SgmX, which in turn interacts with PilB to stimulate T4P extension

Situation-bound utterances as cultural scripts in spoken discourse

AbstractThis paper provides insight into the pervasive use of situation-bound utterances and their pragmatic functions in spoken discourse. It is corroborated that situation-bound utterances are socially and culturally charged communication routines used by the native speakers in actual speech. The paper analyzes the cultural content of situation-bound utterances and their role in non-native communication. We attempt to show that situation-bound utterances as cultural scripts pertain to cognitive mechanisms of spoken discourse and culture. The study shows that analysis of SBUs as cultural scripts might be used as a learning strategy in foreign language acquisition

Systematic cross-validation of 454 sequencing and pyrosequencing for the exact quantification of DNA methylation patterns with single CpG resolution

<p>Abstract</p> <p>Background</p> <p>New high-throughput sequencing technologies promise a very sensitive and high-resolution analysis of DNA methylation patterns in quantitative terms. However, a detailed and comprehensive comparison with existing validated DNA methylation analysis methods is not yet available. Therefore, a systematic cross-validation of 454 sequencing and conventional pyrosequencing, both of which offer exact quantification of methylation levels with a single CpG dinucleotide resolution, was performed.</p> <p>Results</p> <p>To this end the methylation patterns of 12 loci (<it>GSTπ1, p16</it>^{<it>INK4a</it>}<it>, RASSF1A, SOCS1, MAL, hsa-mir-1-1, hsa-mir-9-3, hsa-mir-34a, hsa-mir-596, hsa-mir-663, MINT31</it>, and <it>LINE-1</it>) were analyzed in ten primary hepatocellular carcinoma specimens. After applying stringent quality control criteria, 35749 sequences entered further analysis. The methylation level of individual CpG dinucleotides obtained by 454 sequencing was systematically compared with the corresponding values obtained by conventional pyrosequencing. Statistical analyses revealed an excellent concordance of methylation levels for all individual CpG dinucleotides under study (r²= 0.927).</p> <p>Conclusions</p> <p>Our results confirm that 454 sequencing of bisulfite treated genomic DNA provides reliable high quality quantitative methylation data and identify <it>MAL, hsa-mir-9-3, hsa-mir-596, and hsa-mir-663 </it>as new targets of aberrant DNA methylation in human hepatocelluar carcinoma. In addition, the single molecule resolution of 454 sequencing provides unprecedented information about the details of DNA methylation pattern heterogeneity in clinical samples.</p

Pharmacological evaluation of the efficacy of metabolic drugs for acute biliary pancreatitis

Rate of acute pancreatitis is up to 40 cases per year per 100,000 adults, while about 10-15% of patients have severe forms of this disease, among which the mortality rate reaches 80%. Aim: to experimentally evaluate the pharmacological efficacy of the combined use of drugs (immunomodulators, antioxidants and membrane protectors) in acute biliary pancreatitis with a high degree of severity. A laboratory rat population was used for the study. 210 animals were divided into 3 groups. Group 1 did not receive any drugs, group 2 received a combination of ferrovir, mexidol and phosphogliv, and group 3 received a combination of polyoxidonium and Essentiale N. Before and after the administration of drugs combination, the indicators of the immunological status and parameters of the oxidative system were evaluated. Combination of ferrovir, mexidol and phosphogliv with mild pancreatitis corrects 12.0% and normalizes 75% of the studied laboratory immune and oxidative indices, respectively. With a moderate degree of pancreatitis, these indicators were 19.2% and 45%, and with a severe degree, corresponding to the control values. For group 3, drug combination leads to normal laboratory values of immune and oxidative status in mild pancreatitis, with moderate severity it normalizes 27% and correlates in 73% of cases, and with severe severe it correlates with all studied results. As established experimentally, mild forms of biliary pancreatitis are completely corrected with different drug combinations. With moderate and severe severity, there are immunometabolic disorders recorded. The combination proposed in this case is neither sufficiently effective nor ineffective. This study has convincingly proved the relevance of drug treatment of mild biliary pancreatitis with drug combination on the example of laboratory animals. At the same time, drug treatment is ineffective for moderate and severe pancreatitis. The study requires the continuation and testing of the resulting drug combination for mild biliary pancreatitis

Pilot studies of the unique highland palsa mire in Western Sayan (Tuva Republic, Russian Federation)

In contrast to the well-studied West Siberian sector of frozen bogs in the Russian Arctic, the frozen mound bogs (so-called “palsas”) on the highlands of Southern Siberia have not yet been studied, but they are suspected to be even more sensitive to ongoing climate change. This article provides the pilot study on palsa mire Kara-Sug in the highland areas of Western Sayan mountain system, Tuva Republic. The study focuses on the current state of palsa mire and surrounding landscapes, providing wide range of ecological characteristics while describing ongoing transformations of natural landscapes under a changing climate. The study used a variety of field and laboratory methods: the integrated landscape-ecological approach, the study of peat deposits, geobotanical analysis, and modern analysis of the chemical composition of water, peat, and soils. The study shows that highland palsa mires are distinguished by their compactness and high variety of cryogenic landforms leading to high floristic and ecosystem diversity compared with lowland palsa mires. This information brings new insights and contributes to a better understanding of extrazonal highland palsa mires, which remain a “white spot” in the global environmental sciences

Adherence to Prescribed E-Diary Recording by Patients With Seasonal Allergic Rhinitis: Observational Study

Background: Complete diagnosis and therapy of seasonal allergic rhinoconjunctivitis require evidence that exposure to the sensitizing pollen triggers allergic symptoms. Electronic clinical diaries, by recording disease severity scores and pollen exposure, can demonstrate this association. However, patients who spontaneously download an e-diary app show very low adherence to their recording. Objective: The objective of our study was to assess adherence of patients with seasonal allergic rhinitis to symptom recording via e-diary explicitly prescribed by an allergist within a blended care approach. Methods: The @IT-2020 project is investigating the diagnostic synergy of mobile health and molecular allergology in patients with seasonal allergic rhinitis. In the pilot phase of the study, we recruited Italian children (Rome, Italy) and adults (Pordenone, Italy) with seasonal allergic rhinitis and instructed them to record their symptoms, medication intake, and general conditions daily through a mobile app (Allergy.Monitor) during the relevant pollen season. Results: Overall, we recruited 101 Italian children (Rome) and 93 adults (Pordenone) with seasonal allergic rhinitis. Adherence to device use slowly declined during monitoring in 3 phases: phase A: first week, ≥1267/1358, 90%; phase B: second to sixth week, 4992/5884, 80% to 90%; and phase C: seventh week onward, 2063/2606, 70% to 80%. At the individual level, the adherence assessed in the second and third weeks of recording predicted with enough confidence (Rome: Spearman ρ=0.75; P<.001; Pordenone: ρ=0.81; P<.001) the overall patient adherence to recording and was inversely related to postponed reporting (ρ=-0.55; P<.001; in both centers). Recording adherence was significantly higher during the peak grass pollen season in Rome, but not in Pordenone. Conclusions: Adherence to daily recording in an e-diary, prescribed and motivated by an allergist in a blended care setting, was very high. This observation supports the use of e-diaries in addition to face-to-face visits for diagnosis and treatment of seasonal allergic rhinitis and deserves further investigation in real-life contexts

3-Deazaadenosine alleviates senescence to promote cellular fitness and cell therapy efficiency in mice

International audienc

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts