A novel constitutive model for passive right ventricular myocardium: evidence for myofiber–collagen fiber mechanical coupling

The function of right ventricle (RV) is recognized to play a key role in the development of many cardiopulmonary disorders, such as pulmonary arterial hypertension (PAH). Given the strong link between tissue structure and mechanical behavior, there remains a need for a myocardial constitutive model that accurately accounts for right ventricular myocardium architecture. Moreover, most available myocardial constitutive models approach myocardium at the length scale of mean fiber orientation and do not explicitly account for different fibrous constituents and possible interactions among them. In the present work, we developed a fiber-level constitutive model for the passive mechanical behavior of the right ventricular free wall (RVFW). The model explicitly separates the mechanical contributions of myofiber and collagen fiber ensembles, and accounts for the mechanical interactions between them. To obtain model parameters for the healthy passive RVFW, the model was informed by transmural orientation distribution measurements of myo- and collagen fibers and was fit to the mechanical testing data, where both sets of data were obtained from recent experimental studies on non-contractile, but viable, murine RVFW specimens. Results supported the hypothesis that in the low-strain regime, the behavior of the RVFW is governed by myofiber response alone, which does not demonstrate any coupling between different myofiber ensembles. At higher strains, the collagen fibers and their interactions with myofibers begin to gradually contribute and dominate the behavior as recruitment proceeds. Due to the use of viable myocardial tissue, the contribution of myofibers was significant at all strains with the predicted tensile modulus of \(\sim \)32 kPa. This was in contrast to earlier reports (Horowitz et al. 1988) where the contribution of myofibers was found to be insignificant. Also, we found that the interaction between myo- and collagen fibers was greatest under equibiaxial strain, with its contribution to the total stress not exceeding 20 %. The present model can be applied to organ-level computational models of right ventricular dysfunction for efficient diagnosis and evaluation of pulmonary hypertension disorder.     

Serological evidence of typhus group rickettsia in a homeless population in Houston, Texas

We tested sera from 176 homeless people in Houston for antibodies against typhus group rickettsiae (TGR). Sera from 19 homeless people were reactive to TGR antigens by ELISA and IFA. Two people had antibodies against Rickettsia prowazekii (epidemic typhus) and the remaining 17 had antibodies against Rickettsia typhi (murine typhus).     

Variations in stress sensitivity and genomic expression in diverse S. cerevisiae isolates

Interactions between an organism and its environment can significantly influence phenotypic evolution. A first step toward understanding this process is to characterize phenotypic diversity within and between populations. We explored the phenotypic variation in stress sensitivity and genomic expression in a large panel of Saccharomyces strains collected from diverse environments. We measured the sensitivity of 52 strains to 14 environmental conditions, compared genomic expression in 18 strains, and identified gene copy-number variations in six of these isolates. Our results demonstrate a large degree of phenotypic variation in stress sensitivity and gene expression. Analysis of these datasets reveals relationships between strains from similar niches, suggests common and unique features of yeast habitats, and implicates genes whose variable expression is linked to stress resistance. Using a simple metric to suggest cases of selection, we found that strains collected from oak exudates are phenotypically more similar than expected based on their genetic diversity, while sake and vineyard isolates display more diverse phenotypes than expected under a neutral model. We also show that the laboratory strain S288c is phenotypically distinct from all of the other strains studied here, in terms of stress sensitivity, gene expression, Ty copy number, mitochondrial content, and gene-dosage control. These results highlight the value of understanding the genetic basis of phenotypic variation and raise caution about using laboratory strains for comparative genomics.     

A biochemical and genetic study of Leishmania donovani pyruvate kinase

Here we present a biochemical and molecular biology study of the enzyme pyruvate kinase (PYK) from the parasitic protozoa Leishmania donovani. The PYK gene was cloned, mutagenised and over expressed and its kinetic parameters determined. Like in other kinetoplastids, L. donovani PYK is allosterically stimulated by the effector fructose 2,6 biphosphate and not by fructose 1,6 biphosphate. When the putative effector binding site of L. donovani PYK was mutagenised, we obtained two mutants with extreme kinetic behavior: Lys453Leu, which retained a sigmoidal kinetics and was little affected by the effector; and His480Gln, which deployed a hyperbolic kinetics that was not changed by the addition of the effector. Molecular Dynamics (MD) studies revealed that the mutations not only altered the effector binding site of L. donovani PYK but also changed the folding of its domain C.     

Ranking predicted protein structures with support vector regression

Protein structure prediction is an important problem of both intellectual and practical interest. Most protein structure prediction approaches generate multiple candidate models first, and then use a scoring function to select the best model among these candidates. In this work, we develop a scoring function using support vector regression (SVR). Both consensus-based features and features from individual structures are extracted from a training data set containing native protein structures and predicted structural models submitted to CASP5 and CASP6. The SVR learns a scoring function that is a linear combination of these features. We test this scoring function on two data sets. First, when used to rank server models submitted to CASP7, the SVR score selects predictions that are comparable to the best performing server in CASP7, Zhang-Server, and significantly better than all the other servers. Even if the SVR score is not allowed to select Zhang-Server models, the SVR score still selects predictions that are significantly better than all the other servers. In addition, the SVR is able to select significantly better models and yield significantly better Pearson correlation coefficients than the two best Quality Assessment groups in CASP7, QA556 (LEE), and QA634 (Pcons). Second, this work aims to improve the ability of the Robetta server to select best models, and hence we evaluate the performance of the SVR score on ranking the Robetta server template-based models for the CASP7 targets. The SVR selects significantly better models than the Robetta K*Sync consensus alignment score.     

Do energetic demands constrain incubation scheduling in a biparental species?

The high energetic demands of incubation in birds may be animportant ecological factor limiting the evolution of life-historytraits, such as clutch size. In biparental species, however,the demands of incubation may not be a major constraint becausethere may always be sufficient feeding time available for theoff-duty bird to regain energy used during an incubation bout.We investigated whether the energetic demands of incubationconstrain optimum incubation bout length in a biparental incubatorby decreasing the energetic demands of incubation. We put aninsulated cup around the lining of semipalmated sandpiper nestsso that the rate of cooling of eggs was reduced by 21%. Semipalmatedsandpipers responded by increasing their mean incubation boutlength of around 11.1 h by about 10%. Bout lengths in unmanipulatednatural nests became longer as hatch approached (incubationstage), and this was independent of weather. Bout lengths mayhave decreased with increasing rainfall and were independentof time of day. The results suggest that bout length in semipalmatedsandpipers is constrained by their cumulative energetic expenditureduring an incubation bout, and this is determined partly bythe high costs of steady-state incubation. The results alsosuggest that the incubating bird determines the bout lengthrather than the returning bird. Semipalmated sandpipersmay havemaximized incubation bout length to minimize changeovers duringincubation because these probably increasepredation risk. Selectionto minimize the frequency of changeover may then be a factorcontributing to the evolution ofbiparental care and life-historytraits in semipalmated sandpipers.     

Mutant Telomeric Repeats in Yeast Can Disrupt the Negative Regulation of Recombination-Mediated Telomere Maintenance and Create an Alternative Lengthening of Telomeres-Like Phenotype

Some human cancers maintain telomeres using alternative lengthening of telomeres (ALT), a process thought to be due to recombination. In Kluyveromyces lactis mutants lacking telomerase, recombinational telomere elongation (RTE) is induced at short telomeres but is suppressed once telomeres are moderately elongated by RTE. Recent work has shown that certain telomere capping defects can trigger a different type of RTE that results in much more extensive telomere elongation that is reminiscent of human ALT cells. In this study, we generated telomeres composed of either of two types of mutant telomeric repeats, Acc and SnaB, that each alter the binding site for the telomeric protein Rap1. We show here that arrays of both types of mutant repeats present basally on a telomere were defective in negatively regulating telomere length in the presence of telomerase. Similarly, when each type of mutant repeat was spread to all chromosome ends in cells lacking telomerase, they led to the formation of telomeres produced by RTE that were much longer than those seen in cells with only wild-type telomeric repeats. The Acc repeats produced the more severe defect in both types of telomere maintenance, consistent with their more severe Rap1 binding defect. Curiously, although telomerase deletion mutants with telomeres composed of Acc repeats invariably showed extreme telomere elongation, they often also initially showed persistent very short telomeres with few or no Acc repeats. We suggest that these result from futile cycles of recombinational elongation and truncation of the Acc repeats from the telomeres. The presence of extensive 3′ overhangs at mutant telomeres suggests that Rap1 may normally be involved in controlling 5′ end degradation.     

Diurnal foraging routines in a tropical bird,the rock finch Lagonosticta sanguinodorsalis: how important is predation risk?

An animal's foraging decisions are the outcome of the relative importance of the risk of starvation and predation. Fat deposition insures against periods of food shortage but it also carries a cost in terms of mass dependent predation risk due to reduced escape probability and extended exposure time. Accordingly, birds have been observed to show a unimodal foraging pattern with foraging concentrated at the end of the day under conditions of predictable food resources and high predation risk. We tested this hypothesis in a tropical granivorous finch, the rock firefinch Lagonosticta sanguinodorsalis , in an outdoor aviary experiment during which food was provided ad lib and the risk of predation was varied by providing food either adjacent to, or 5 m away from cover. Rock firefinches showed a bimodal foraging pattern regardless of the risk of predation at which they fed. The results suggest that predation is relatively unimportant in shaping their daily feeding pattern despite mass gain during the day being similar to temperate birds. Foraging patterns closely follow diurnal temperature variation and this is suggested to be the main determinant of the observed bimodal pattern.     

Climate change, conservation and management: an assessment of the peer-reviewed scientific journal literature

Recent reviews of the conservation literature indicate that significant biases exist in the published literature regarding the regions, ecosystems and species that have been examined by researchers. Despite the global threat of climatic change, similar biases may be occurring within the sub-discipline of climate-change ecology. Here we hope to foster critical thought and discussion by considering the directions taken by conservation researchers when addressing climate change. To form a quantitative basis for our perspective, we assessed 248 papers from the climate change literature that considered the conservation management of biodiversity and ecosystems. We found that roughly half of the studies considered climate change in isolation from other threatening processes. We also found that the majority of surveyed scientific publications were conducted in the temperate forests of Europe and North America. Regions such as Latin America that are rich in biodiversity but may have low adaptive capacity to climate change were not well represented. We caution that such biases in research effort may be distracting our attention away from vulnerable regions, ecosystems and species. Specifically we suggest that the under-representation of research from regions low in adaptive capacity and rich in biodiversity requires international collaboration by those experienced in climate-change research, with researchers from less wealthy nations who are familiar with local issues, ecosystems and species. Furthermore, we caution that the propensity of ecologists to work in essentially unmodified ecosystems may fundamentally hamper our ability to make useful recommendations in a world that is experiencing significant global change.