The plasma membrane carbonic anhydrase in murine hepatocytes identified as isozyme XIV

BACKGROUND: Biochemical and histochemical studies have both previously indicated plasma membrane-associated carbonic anhydrase (CA) activity in hepatocytes which has been assumed to be CA IV. However, immunohistochemical data did not support this assignment. Recent northern blotting results indicated the presence of mRNA for the most recently discovered membrane-bound CA isozyme, CA XIV, in the liver. The present study was designed to examine whether CA XIV could contribute to the CA activity described in the hepatocytes. METHODS: Tissue samples from mouse liver were subjected to immunohistochemical staining using the antibodies raised against recombinant mouse CA XIV and CA IV. RT-PCR and western blotting were also performed for CA XIV. RESULTS: A strong immunofluorescent signal was observed in the plasma membrane of mouse hepatocytes. Although CA XIV was expressed on both the apical and basolateral surfaces, the staining was more prominent at the apical (canalicular) membrane domain. The expression of CA XIV in the liver was confirmed by RT-PCR and western blotting. CONCLUSIONS: The presence of CA XIV in the hepatocyte plasma membrane places this novel enzyme at a strategic site to control pH regulation and ion transport between the hepatocytes, sinusoids and bile canaliculi

Analysis of cardiac signals using spatial filling index and time-frequency domain

BACKGROUND: Analysis of heart rate variation (HRV) has become a popular noninvasive tool for assessing the activities of the autonomic nervous system (ANS). HRV analysis is based on the concept that fast fluctuations may specifically reflect changes of sympathetic and vagal activity. It shows that the structure generating the signal is not simply linear, but also involves nonlinear contributions. These signals are essentially non-stationary; may contain indicators of current disease, or even warnings about impending diseases. The indicators may be present at all times or may occur at random in the time scale. However, to study and pinpoint abnormalities in voluminous data collected over several hours is strenuous and time consuming. METHODS: This paper presents the spatial filling index and time-frequency analysis of heart rate variability signal for disease identification. Renyi's entropy is evaluated for the signal in the Wigner-Ville and Continuous Wavelet Transformation (CWT) domain. RESULTS: This Renyi's entropy gives lower 'p' value for scalogram than Wigner-Ville distribution and also, the contours of scalogram visually show the features of the diseases. And in the time-frequency analysis, the Renyi's entropy gives better result for scalogram than the Wigner-Ville distribution. CONCLUSION: Spatial filling index and Renyi's entropy has distinct regions for various diseases with an accuracy of more than 95%

Does left atrial volume affect exercise capacity of heart transplant recipients?

<p>Abstract</p> <p>Background</p> <p>Heart transplant (HT) recipients demonstrate limited exercise capacity compared to normal patients, very likely for multiple reasons. In this study we hypothesized that left atrial volume (LAV), which is known to predict exercise capacity in patients with various cardiac pathologies including heart failure and hypertrophic cardiomyopathy is associated with limited exercise capacity of HT recipients.</p> <p>Methods</p> <p>We analyzed 50 patients [age 57 ±2 (SEM), 12 females] who had a post-HT echocardiography and cardiopulmonary exercise test (CPX) within 9 weeks time at clinic follow up. The change in LAV (ΔLAV) was also computed as the difference in LAV from the preceding one-year to the study echocardiogram. Correlations among the measured parameters were assessed with a Pearson's correlation analysis.</p> <p>Results</p> <p>LAV (n = 50) and ΔLAV (n = 40) indexed to body surface area were 40.6 ± 11.5 ml·m^-2and 1.9 ± 8.5 ml·m^-2·year^-1, data are mean ± SD, respectively. Indexed LAV and ΔLAV were both significantly correlated with the ventilatory efficiency, assessed by the VE/VCO₂slope (r = 0.300, p = 0.038; r = 0.484, p = 0.002, respectively). LAV showed a significant correlation with peak oxygen consumption (r = -0.328, p = 0.020).</p> <p>Conclusions</p> <p>Although our study is limited by a retrospective study design and relatively small number of patients, our findings suggest that enlarged LAV and increasing change in LAV is associated with the diminished exercise capacity in HT recipients and warrants further investigation to better elucidate this relationship.</p

The state of ambient air quality in Pakistan—a review

Background and purpose: Pakistan, during the last decade, has seen an extensive escalation in population growth, urbanization, and industrialization, together with a great increase in motorization and energy use. As a result, a substantial rise has taken place in the types and number of emission sources of various air pollutants. However, due to the lack of air quality management capabilities, the country is suffering from deterioration of air quality. Evidence from various governmental organizations and international bodies has indicated that air pollution is a significant risk to the environment, quality of life, and health of the population. The Government has taken positive steps toward air quality management in the form of the Pakistan Clean Air Program and has recently established a small number of continuous monitoring stations. However, ambient air quality standards have not yet been established. This paper reviews the data being available on the criteria air pollutants: particulate matter (PM), sulfur dioxide, ozone, carbon monoxide, nitrogen dioxide, and lead. Methods: Air pollution studies in Pakistan published in both scientific journals and by the Government have been reviewed and the reported concentrations of PM, SO2, O3, CO, NO2, and Pb collated. A comparison of the levels of these air pollutants with the World Health Organization air quality guidelines was carried out. Results: Particulate matter was the most serious air pollutant in the country. NO2 has emerged as the second high-risk pollutant. The reported levels of PM, SO2, CO, NO2, and Pb were many times higher than the World Health Organization air quality guidelines. Only O3 concentrations were below the guidelines. Conclusions: The current state of air quality calls for immediate action to tackle the poor air quality. The establishment of ambient air quality standards, an extension of the continuous monitoring sites, and the development of emission control strategies are essential. © Springer-Verlag 2009

Expression of hereditary hemochromatosis C282Y HFE protein in HEK293 cells activates specific endoplasmic reticulum stress responses

<p>Abstract</p> <p>Background</p> <p>Hereditary Hemochromatosis (HH) is a genetic disease associated with iron overload, in which individuals homozygous for the mutant C282Y <it>HFE </it>associated allele are at risk for the development of a range of disorders particularly liver disease. Conformational diseases are a class of disorders associated with the expression of misfolded protein. HFE C282Y is a mutant protein that does not fold correctly and consequently is retained in the Endoplasmic Reticulum (ER). In this context, we sought to identify ER stress signals associated with mutant C282Y HFE protein expression, which may have a role in the molecular pathogenesis of HH.</p> <p>Results</p> <p>Vector constructs of Wild type HFE and Mutant C282Y HFE were made and transfected into HEK293 cell lines. We have shown that expression of C282Y HFE protein triggers both an unfolded protein response (UPR), as revealed by the increased GRP78, ATF6 and CHOP expression, and an ER overload response (EOR), as indicated by NF-κB activation. Furthermore, C282Y HFE protein induced apoptotic responses associated with activation of ER stress. Inhibition studies demonstrated that tauroursodeoxycholic acid, an endogenous bile acid, downregulates these events. Finally, we found that the co-existence of both C282Y HFE and Z alpha 1-antitrypsin protein (the protein associated with the liver disease of Z alpha 1-antitrypsin deficiency) expression on ER stress responses acted as potential disease modifiers with respect to each other.</p> <p>Conclusion</p> <p>Our novel observations suggest that both the ER overload response (EOR) and the unfolded protein response (UPR) are activated by mutant C282Y HFE protein.</p

An Indo-Pacific coral spawning database.

The discovery of multi-species synchronous spawning of scleractinian corals on the Great Barrier Reef in the 1980s stimulated an extraordinary effort to document spawning times in other parts of the globe. Unfortunately, most of these data remain unpublished which limits our understanding of regional and global reproductive patterns. The Coral Spawning Database (CSD) collates much of these disparate data into a single place. The CSD includes 6178 observations (3085 of which were unpublished) of the time or day of spawning for over 300 scleractinian species in 61 genera from 101 sites in the Indo-Pacific. The goal of the CSD is to provide open access to coral spawning data to accelerate our understanding of coral reproductive biology and to provide a baseline against which to evaluate any future changes in reproductive phenology

HIV-1 assembly in macrophages

The molecular mechanisms involved in the assembly of newly synthesized Human Immunodeficiency Virus (HIV) particles are poorly understood. Most of the work on HIV-1 assembly has been performed in T cells in which viral particle budding and assembly take place at the plasma membrane. In contrast, few studies have been performed on macrophages, the other major target of HIV-1. Infected macrophages represent a viral reservoir and probably play a key role in HIV-1 physiopathology. Indeed macrophages retain infectious particles for long periods of time, keeping them protected from anti-viral immune response or drug treatments. Here, we present an overview of what is known about HIV-1 assembly in macrophages as compared to T lymphocytes or cell lines

Retroviral matrix and lipids, the intimate interaction

Retroviruses are enveloped viruses that assemble on the inner leaflet of cellular membranes. Improving biophysical techniques has recently unveiled many molecular aspects of the interaction between the retroviral structural protein Gag and the cellular membrane lipids. This interaction is driven by the N-terminal matrix domain of the protein, which probably undergoes important structural modifications during this process, and could induce membrane lipid distribution changes as well. This review aims at describing the molecular events occurring during MA-membrane interaction, and pointing out their consequences in terms of viral assembly. The striking conservation of the matrix membrane binding mode among retroviruses indicates that this particular step is most probably a relevant target for antiviral research

Diabetes mortality and trends before 25 years of age: an analysis of the Global Burden of Disease Study 2019

Background Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods We used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990–2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. Findings In 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73·7% (68·3 to 77·4) were classified as due to type 1 diabetes. The age-standardised death rate was 0·50 (0·44 to 0·58) per 100 000 population, and 15 900 (97·5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0·13 (0·12 to 0·14) per 100 000 population in the high SDI quintile, 0·60 (0·51 to 0·70) per 100 000 population in the low-middle SDI quintile, and 0·71 (0·60 to 0·86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r2=0·62). From 1990 to 2019, age-standardised death rates decreased globally by 17·0% (−28·4 to −2·9) for all diabetes, and by 21·0% (–33·0 to −5·9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (−13·6% [–28·4 to 3·4]) and for type 1 diabetes (−13·6% [–29·3 to 8·9]). Interpretation Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations.publishedVersio