Clinical and translational implications of the caveolin gene family: lessons from mouse models and human genetic disorders.

Here we review the clinical and translational implications of the caveolin gene family for understanding the pathogenesis of human diseases, including breast and prostate cancers, pulmonary hypertension, cardiomyopathy, diabetes, and muscular dystrophy. Detailed phenotypic analysis of caveolin knockout mice has served to highlight the crucial role of a caveolin deficiency in the pathogenesis of many human disease processes. Mutations in the human caveolin genes are associated with a number of established genetic disorders (such as breast cancer, lipodystrophy, muscular dystrophy, and cardiomyopathy), making the caveolins important and novel targets for drug development. The implementation of new strategies for caveolin replacement therapy-including caveolin mimetic peptides-is ongoing

Ice core evidence for a recent increase in snow accumulation in coastal Dronning Maud Land, East Antarctica

Abstract. Ice cores provide temporal records of snow accumulation, a crucial component of Antarctic mass balance. Coastal areas are particularly under-represented in such records, despite their relatively high and sensitive accumulation rates. Here we present records from a 120 m ice core drilled on Derwael Ice Rise, coastal Dronning Maud Land (DML), East Antarctica in 2012. We date the ice core bottom back to 1745 ± 2 AD. δ18O and δD stratigraphy is supplemented by discontinuous major ion profiles, and verified independently by electrical conductivity measurements (ECM) to detect volcanic horizons. The resulting annual layer history is combined with the core density profile to calculate accumulation history, corrected for the influence of ice deformation. The mean long-term accumulation is 0.425 ± 0.035 m water equivalent (w.e.) a−1 (average corrected value). Reconstructed annual accumulation rates show an increase from 1955 onward to a mean value of 0.61 ± 0.02 m w.e. a−1 between 1955 and 2012. This trend is compared to other reported accumulation data in Antarctica, generally showing a high spatial variability. Output of the fully coupled Community Earth System Model demonstrates that sea ice and atmospheric patterns largely explain the accumulation variability. This is the first and longest record from a coastal ice core in East Antarctica showing a steady increase during the 20th and 21st centuries, thereby supporting modelling predictions. </jats:p

Effects of climate extremes on the terrestrial carbon cycle : concepts, processes and potential future impacts

This article is protected by copyright. All rights reserved. Acknowledgements This work emerged from the CARBO-Extreme project, funded by the European Community’s 7th framework programme under grant agreement (FP7-ENV-2008-1-226701). We are grateful to the Reviewers and the Subject Editor for helpful guidance. We thank to Silvana Schott for graphic support. Mirco Miglivacca provided helpful comments on the manuscript. Michael Bahn acknowledges support from the Austrian Science Fund (FWF; P22214-B17). Sara Vicca is a postdoctoral research associate of the Fund for Scientific Research – Flanders. Wolfgang Cramer contributes to the Labex OT-Med (n° ANR-11- LABX-0061) funded by the French government through the A*MIDEX project (n° ANR-11-IDEX-0001-02). Flurin Babst acknowledges support from the Swiss National Science Foundation (P300P2_154543).Peer reviewedPublisher PD

Ice core evidence for a 20th century increase in surface mass balance in coastal Dronning Maud Land, East Antarctica

Ice cores provide temporal records of surface mass balance (SMB). Coastal areas of Antarctica have relatively high and variable SMB, but are under-represented in records spanning more than 100 years. Here we present SMB reconstruction from a 120m-long ice core drilled in 2012 on the Derwael Ice Rise, coastal Dronning Maud Land, East Antarctica. Water stable isotope (δ18O and δD) stratigraphy is supplemented by discontinuous major ion profiles and continuous electrical conductivity measurements. The base of the ice core is dated to AD1759±16, providing a climate proxy for the past 1/4&250 years. The core's annual layer thickness history is combined with its gravimetric density profile to reconstruct the site's SMB history, corrected for the influence of ice deformation. The mean SMB for the core's entire history is 0.47±0.02m water equivalent (w.e.)a'1. The time series of reconstructed annual SMB shows high variability, but a general increase beginning in the 20th century. This increase is particularly marked during the last 50 years (1962&ndash;2011), which yields mean SMB of 0.61±0.01mw.e.a'1. This trend is compared with other reported SMB data in Antarctica, generally showing a high spatial variability. Output of the fully coupled Community Earth System Model (CESM) suggests that, although atmospheric circulation is the main factor influencing SMB, variability in sea surface temperatures and sea ice cover in the precipitation source region also explain part of the variability in SMB. Local snow redistribution can also influence interannual variability but is unlikely to influence long-term trends significantly. This is the first record from a coastal ice core in East Antarctica to show an increase in SMB beginning in the early 20th century and particularly marked during the last 50 years.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Detecting K-complexes for sleep stage identification using nonsmooth optimisation

The process of sleep stage identification is a labour-intensive task that involves the specialized interpretation of the polysomnographic signals captured from a patient&rsquo;s overnight sleep session. Automating this task has proven to be challenging for data mining algorithms because of noise, complexity and the extreme size of data. In this paper we apply nonsmooth optimization to extract key features that lead to better accuracy. We develop a specific procedure for identifying K-complexes, a special type of brain wave crucial for distinguishing sleep stages. The procedure contains two steps. We first extract &ldquo;easily classified&rdquo; K-complexes, and then apply nonsmooth optimization methods to extract features from the remaining data and refine the results from the first step. Numerical experiments show that this procedure is efficient for detecting K-complexes. It is also found that most classification methods perform significantly better on the extracted features

Імунологічні аспекти діагностики та лікування постгістеректомічного синдрому

В статье представлены данные клинико-иммунологического, вегетологического, психологического статуса 80 женщин, страдающих постгистерэктомическими расстройствами с целью поиска оптимальных подходов к терапии. Установлено, что постгистерэктомический синдром сопровождается различными изменениями нейровегетативной регуляции, коррелирующими с гормонально-иммунологическими нарушениями. Стабильные положительные клинико-иммунологические сдвиги у пациенток с постгистерэктомическим синдромом показали высокую эффективность включения иммунокорригирующих препаратов для оптимизации терапевтических мероприятий в борьбе с указанной патологией.Basing on clinical, immunological, vegetologycal investigations in 80 women with posthysterectomy disorders with the purpose of search of optimum pathogenetic approaches to therapy. It has been found that a posthysterectomy syndrome is accompanied by the different changes neyrovegetatic regulationand also psychoemotional disorders. New important hormonal and immunological aspects of pathogenesis were determinated. Stable positive clinical and immunological changes at patients with a postgysterektomy syndrome showed high effect of including of immunological correction for the complex of treatment of patients with this pathology

Secondary structure of human apolipoprotein A-I(1–186) in lipid-mimetic solution

AbstractThe solution structure of an apoA-I deletion mutant, apoA-I(1–186) was determined by the chemical shift index (CSI) method and the torsion angle likelihood obtained from shift and sequence similarity (TALOS) method, using heteronuclear multidimensional NMR spectra of [u-13C, u-15N, u-50% 2H]apoA-I(1–186) in the presence of sodium dodecyl sulfate (SDS). The backbone resonances were assigned from a combination of triple-resonance data (HNCO, HNCA, HN(CO)CA, HN(CA)CO and HN(COCA)HA), and intraresidue and sequential NOEs (three-dimensional (3D) and four-dimensional (4D) 13C- and 15N-edited NOESY). Analysis of the NOEs, Hα, Cα and C′ chemical shifts shows that apoA-I(1–186) in lipid-mimetic solution is composed of α-helices (which include the residues 8–32, 45–64, 67–77, 83–87, 90–97, 100–140, 146–162, and 166–181), interrupted by short irregular segments. There is one relatively long, irregular and mostly flexible region (residues 33–44), that separates the N-terminal domain (residues 1–32) from the main body of protein. In addition, we report, for the first time, the structure of the N-terminal domain of apoA-I in a lipid-mimetic environment. Its structure (α-helix 8–32 and flexible linker 33–44) would suggest that this domain is structurally, and possibly functionally, separated from the other part of the molecule

Transcriptional evidence for the "Reverse Warburg Effect" in human breast cancer tumor stroma and metastasis: Similarities with oxidative stress, inflammation, Alzheimer's disease, and "Neuron-Glia Metabolic Coupling"

Caveolin-1 (-/-) null stromal cells are a novel genetic model for cancer-associated fibroblasts and myofibroblasts. Here, we used an unbiased informatics analysis of transcriptional gene profiling to show that Cav-1 (-/-) bone-marrow derived stromal cells bear a striking resemblance to the activated tumor stroma of human breast cancers. More specifically, the transcriptional profiles of Cav-1 (-/-) stromal cells were most closely related to the primary tumor stroma of breast cancer patients that had undergone lymph-node (LN) metastasis. This is consistent with previous morphological data demonstrating that a loss of stromal Cav-1 protein (by immuno-histochemical staining in the fibroblast compartment) is significantly associated with increased LN-metastasis. We also provide evidence that the tumor stroma of human breast cancers shows a transcriptional shift towards oxidative stress, DNA damage/repair, inflammation, hypoxia, and aerobic glycolysis, consistent with the "Reverse Warburg Effect". Finally, the tumor stroma of "metastasis-prone" breast cancer patients was most closely related to the transcriptional profiles derived from the brains of patients with Alzheimer's disease. This suggests that certain fundamental biological processes are common to both an activated tumor stroma and neuro-degenerative stress. These processes may include oxidative stress, NO over-production (peroxynitrite formation), inflammation, hypoxia, and mitochondrial dysfunction, which are thought to occur in Alzheimer's disease pathology. Thus, a loss of Cav-1 expression in cancer-associated myofibroblasts may be a protein biomarker for oxidative stress, aerobic glycolysis, and inflammation, driving the "Reverse Warburg Effect" in the tumor micro-environment and cancer cell metastasis

The 20-minute whole blood clotting test (20WBCT) for snakebite coagulopathy—A systematic review and meta-analysis of diagnostic test accuracy

Background The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming. Methods and findings Databases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953). The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen <100 mg/dL was 0.72 (CI 0.58 to 0.83), the specificity was 0.94 (CI 0.88 to 0.98) and the SROC AUC was 0.93 (0.91 to 0.95). Both analyses that used INR and fibrinogen as the reference test displayed considerable heterogeneity. Conclusions In the absence of laboratory clotting assays, the 20WBCT remains a highly specific and fairly sensitive bedside test at detecting coagulopathy following snakebite. However, clinicians should be aware of the importance of operator training, standardized equipment and the lower sensitivity of the 20WBCT at detecting mild coagulopathy and resolution of coagulopathy following antivenom

Water vapour in the atmosphere of a transiting extrasolar planet

Copyright © 2007 Nature Publishing GroupWater is predicted to be among the most abundant (if not the most abundant) molecular species after hydrogen in the atmospheres of close-in extrasolar giant planets ('hot Jupiters'). Several attempts have been made to detect water on such planets, but have either failed to find compelling evidence for it or led to claims that should be taken with caution. Here we report an analysis of recent observations of the hot Jupiter HD 189733b (ref. 6) taken during the transit, when the planet passed in front of its parent star. We find that absorption by water vapour is the most likely cause of the wavelength-dependent variations in the effective radius of the planet at the infrared wavelengths 3.6 mum, 5.8 mum (both ref. 7) and 8 mum (ref. 8). The larger effective radius observed at visible wavelengths may arise from either stellar variability or the presence of clouds/hazes. We explain the report of a non-detection of water on HD 189733b (ref. 4) as being a consequence of the nearly isothermal vertical profile of the planet's atmosphere