Left ventricular wall stress normalization in chronic pressure-overloaded heart: a mathematical model study

It is generally accepted that the left ventricle (LV) hypertrophies (LVH) to normalize systolic wall stress (sigma(s)) in chronic pressure overload. However, LV filling pressure (P(v)) may be elevated as well, supporting the alternative hypothesis of end-diastolic wall stress (sigma(d)) normalization in LVH. We used an LV time-varying elastance model coupled to an arterial four-element lumped-parameter model to study ventricular-arterial interaction in hypertension-induced LVH. We assessed model parameters for normotensive controls and applied arterial changes as observed in hypertensive patients with LVH (resistance +40%, compliance -25%) and assumed 1) no cardiac adaptation, 2) normalization of sigma(s) by LVH, and 3) normalization of sigma(s) by LVH and increase in P(v), such that sigma(d) is normalized as well. In patients, systolic and diastolic blood pressures increase by approximately 40%, cardiac output (CO) is constant, and wall thickness increases by 30-55%. In scenarios 1 and 2, blood pressure increased by only 10% while CO dropped by 20%. In scenario 2, LV wall thickness increased by only 10%. The predictions of scenario 3 were in qualitative and quantitative agreement with in vivo human data. LVH thus contributes to the elevated blood pressure in hypertension, and cardiac adaptations include an increase in P(v), normalization of sigma(s), and preservation of CO in the presence of an impaired diastolic function.     

Conductance catheter-based assessment of arterial input impedance, arterial function, and ventricular-vascular interaction in mice

Global assessment of both cardiac and arterial function is important for a meaningful interpretation of pathophysiological changes in animal models of cardiovascular disease. We simultaneously acquired left ventricular (LV) and aortic pressure and LV volume (V(LV)) in 17 open-chest anesthetized mice (26.7 +/- 3.2g) during steady-state (BL) and caval vein occlusion (VCO) using a 1.4-Fr dual-pressure conductance catheter and in a subgroup of eight animals during aortic occlusion (AOO). Aortic flow was obtained from numerical differentiation of V(LV). AOO increased input impedance (Z(in)) for the first two harmonics, increased characteristic impedance (0.025 +/- 0.007 to 0.040 +/- 0.011 mmHg x microl(-1) x s, P < 0.05), and shifted the minimum in Z(in) from the third to the sixth harmonic. For all conditions, the Z(in) could be well represented by a four-element windkessel model. The augmentation index increased from 116.7 +/- 7.8% to 145.9 +/- 19.5% (P < 0.01) as well as estimated pulse-wave velocity (3.50 +/- 0.94 to 5.95 +/- 1.62 m/s, P < 0.05) and arterial elastance (E(a), 4.46 +/- 1.62 to 6.02 +/- 1.43 mmHg/microl, P < 0.01). AOO altered the maximal slope (E(max), 3.23 +/- 1.02 to 5.53 +/- 1.53 mmHg/microl, P < 0.05) and intercept (-19.9 +/- 8.6 to 1.62 +/- 13.51 microl, P < 0.01) of the end-systolic pressure-volume relation but not E(a)/E(max) (1.44 +/- 0.43 to 1.21 +/- 0.37, not significant). We conclude that simultaneous acquisition of Z(in) and arterial function parameters in the mouse, based solely on conductance catheter measurements, is feasible. We obtained an anticipated response of Z(in) and arterial function parameters following VCO and AOO, demonstrating the sensitivity of the measuring technique to induced physiological alterations in murine hemodynamics.     

The Collothecidae (Rotifera,Collothecacea) of Thailand,with the description of a new species and an?illustrated key to the Southeast Asian fauna

Following previous reports indicating a remarkable high diversity of sessile rotifers in Southeast Asian freshwaters, we report on an extensive study of the diversity of Collothecidae rotifers from fifteen freshwater habitats in Thailand. A total of 13 species, including two additional infraspecific variants, of Collothecidae are recorded, one of which is described as a new species of Collotheca. We further add taxonomic remarks on some of the taxa on record and illustrate the uncinate trophi of several representatives by scanning electron microscopic images. Finally, we provide illustrated identification keys to the Collothecidae recorded to date from Southeast Asia.     

Carbon (δ13C) and Nitrogen (δ15N) Stable Isotope Signatures in Bat Fur Indicate Swarming Sites Have Catchment Areas for Bats from Different Summering Areas

Migratory patterns of bats are not well understood and traditional methods to study this, like capture-mark-recapture, may not provide enough detail unless there are many records. Stable isotope profiles of many animal species have been used to make inferences about migration. Each year Myotis lucifugus and M. septentrionalis migrate from summering roosts to swarming caves and mines in the fall, but the pattern of movement between them is not well understood. In this study, fur δ¹³C and δ¹⁵N values of 305 M. lucifugus and 200 M. septentrionalis were analyzed to make inferences about migration patterns between summering areas and swarming sites in Nova Scotia, Canada. We expected that there would be greater variability in δ¹³C and δ¹⁵N among individuals at swarming sites because it was believed that these sites are used by individuals originating from many summering areas. There was extensive overlap in the standard ellipse area, corrected for small sample sizes (SEA_c), of bats at swarming sites and much less overlap in SEA_c among groups sampled at summering areas. Meaningful inference could not be made on M. septentrionalis because their low variation in SEAc may have been the result of sampling only 3 summering areas. However, for M. lucifugus, swarming sites had larger SEA_c than summering areas and predictive discriminant analysis assigned swarming bats to multiple summering areas, supporting the contention that swarming bats are mixed aggregations of bats from several summering areas. Together, these data support the contention that swarming sites have catchment areas for bats from multiple summering areas and it is likely that the catchment areas for swarming sites overlap. These data suggest that δ¹³C and δ¹⁵N profiling of bat fur offer some potential to make inferences about regional migration in bats.     

Separate effects of moisture content and water activity on the hyphal extension of Penicillium rubens on porous media

To prevent indoor fungal growth, understanding the moisture relations of fungi is a key element. Indoor moisture is quantified by the relative humidity (RH). RH controls the water activity of the indoor materials that fungi grow on, a well‐studied parameter known to limit fungal growth. RH, however, also controls the amount of water present in these materials, the moisture content. The significance of the moisture content of these materials to indoor fungal growth is currently overlooked. In the work reported here, growth experiments with the indoor fungus Penicillium rubens on gypsum substrates were performed to test whether the moisture content influences growth on porous materials. Second, we report the development of a video microscopy method that for the first time quantified hyphal growth on a porous material. It is found that a higher moisture content leads to earlier colonization and higher hyphal extension rates. This is a fundamental step in unravelling the effect of RH on indoor fungal growth. The real‐time monitoring of colonization of gypsum provides a new view of growth on indoor surfaces.     

Ultrastructural Changes Caused by Snf7 RNAi in Larval Enterocytes of Western Corn Rootworm (Diabrotica virgifera virgifera Le Conte)

The high sensitivity to oral RNA interference (RNAi) of western corn rootworm (WCR, Diabrotica virgifera virgifera Le Conte) provides a novel tool for pest control. Previous studies have shown that RNAi of DvSnf7, an essential cellular component of endosomal sorting complex required for transport (ESCRT), caused deficiencies in protein de-ubiquitination and autophagy, leading to WCR death. Here we investigated the detailed mechanism leading to larval death by analyzing the ultrastructural changes in midgut enterocytes of WCR treated with double-stranded RNA (ds-DvSnf7). The progressive phases of pathological symptoms caused by DvSnf7-RNAi in enterocytes include: 1) the appearance of irregularly shaped macroautophagic complexes consisting of relatively large lysosomes and multi-lamellar bodies, indicative of failure in autolysosome formation; 2) cell sloughing and loss of apical microvilli, and eventually, 3) massive loss of cellular contents indicating loss of membrane integrity. These data suggest that the critical functions of Snf7 in insect midgut cells demonstrated by the ultrastructural changes in DvSnf7 larval enterocytes underlies the conserved essential function of the ESCRT pathway in autophagy and membrane stability in other organisms.     

Development of a high-throughput screening assay for the discovery of small-molecule SecA inhibitors

A major pathway for bacterial preprotein translocation is provided by the Sec-dependent preprotein translocation pathway. Proteins destined for Sec-dependent translocation are synthesized as preproteins with an N-terminal signal peptide, which targets them to the SecYEG translocase channel. The driving force for the translocation reaction is provided by the peripheral membrane ATPase SecA, which couples the hydrolysis of ATP to the stepwise transport of unfolded preproteins across the bacterial membrane. Since SecA is essential, highly conserved among bacterial species, and has no close human homologues, it represents a promising target for antibacterial chemotherapy. However, high-throughput screening (HTS) campaigns to identify SecA inhibitors are hampered by the low intrinsic ATPase activity of SecA and the requirement of hydrophobic membranes for measuring the membrane or translocation ATPase activity of SecA. To address this issue, we have developed a colorimetric high-throughput screening assay in a 384-well format, employing an Escherichia coli (E. coli) SecA mutant with elevated intrinsic ATPase activity. The assay was applied for screening of a chemical library consisting of ∼27,000 compounds and proved to be highly reliable (average Z′ factor of 0.89). In conclusion, a robust HTS assay has been established that will facilitate the search for novel SecA inhibitors.     

A Prospective Study of Tobacco Smoking and Mortality in Bangladesh

Background

Limited data are available on smoking-related mortality in low-income countries, where both chronic disease burden and prevalence of smoking are increasing.

Methods

Using data on 20, 033 individuals in the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh, we prospectively evaluated the association between tobacco smoking and all-cause, cancer, and cardiovascular disease mortality during ∼7.6 years of follow-up.Cox proportional hazards models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs) for deaths from all-cause, cancer, CVD, ischemic heart disease (IHD), and stroke, in relation to status, duration, and intensity of cigarette/bidi and hookah smoking.

Results

Among men, cigarette/bidi smoking was positively associated with all-cause (HR 1.40, 95% CI 1.06 1.86) and cancer mortality (HR 2.91, 1.24 6.80), and there was a dose-response relationship between increasing intensity of cigarette/bidi consumption and increasing mortality. An elevated risk of death from ischemic heart disease (HR 1.87, 1.08 3.24) was associated with current cigarette/bidi smoking. Among women, the corresponding HRs were 1.65 (95% CI 1.16 2.36) for all-cause mortality and 2.69 (95% CI 1.20 6.01) for ischemic heart disease mortality. Similar associations were observed for hookah smoking. There was a trend towards reduced risk for the mortality outcomes with older age at onset of cigarette/bidi smoking and increasing years since quitting cigarette/bibi smoking among men. We estimated that cigarette/bidi smoking accounted for about 25.0% of deaths in men and 7.6% in women.

Conclusions

Tobacco smoking was responsible for substantial proportion of premature deaths in the Bangladeshi population, especially among men. Stringent measures of tobacco control and cessation are needed to reduce tobacco-related deaths in Bangladesh.