Arm-plane representation of shoulder compensation during pointing movements in patients with stroke

Improvements in functional motor activities are often accompanied by motor compensations to overcome persistent motor impairment in the upper limb. Kinematic analysis is used to objectively quantify movement patterns including common motor compensations such as excessive trunk displacement during reaching. However, a common motor compensation to assist reaching, shoulder abduction, is not adequately characterized by current motion analysis approaches. We apply the arm-plane representation that accounts for the co-variation between movements of the whole arm, and investigate its ability to identify and quantify compensatory arm movements in stroke subjects when making forward arm reaches. This method has not been previously applied to the analysis of motion deficits. Sixteen adults with right post-stroke hemiparesis and eight healthy age-matched controls reached in three target directions (14 trials/target; sampling rate: 100 Hz). Arm-plane movement was validated against endpoint, joint, and trunk kinematics and compared between groups. In stroke subjects, arm-plane measures were correlated with arm impairment (Fugl-Meyer Assessment) and ability (Box and Blocks) scores and were more sensitive than clinical measures to detect mild motor impairment. Arm-plane motion analysis provides new information about motor compensations involving the co-variation of shoulder and elbow movements that may help to understand the underlying motor deficits in patients with stroke.     

Optimal temperature for malaria transmission is dramatically lower than previously predicted

The ecology of mosquito vectors and malaria parasites affect the incidence, seasonal transmission and geographical range of malaria. Most malaria models to date assume constant or linear responses of mosquito and parasite life‐history traits to temperature, predicting optimal transmission at 31 °C. These models are at odds with field observations of transmission dating back nearly a century. We build a model with more realistic ecological assumptions about the thermal physiology of insects. Our model, which includes empirically derived nonlinear thermal responses, predicts optimal malaria transmission at 25 °C (6 °C lower than previous models). Moreover, the model predicts that transmission decreases dramatically at temperatures > 28 °C, altering predictions about how climate change will affect malaria. A large data set on malaria transmission risk in Africa validates both the 25 °C optimum and the decline above 28 °C. Using these more accurate nonlinear thermal‐response models will aid in understanding the effects of current and future temperature regimes on disease transmission.     

Programmed cell death occurs asymmetrically during abscission in tomato

Abscission occurs specifically in the abscission zone (AZ) tissue as a natural stage of plant development. Previously, we observed delay of tomato (Solanum lycopersicum) leaf abscission when the LX ribonuclease (LX) was inhibited. The known association between LX expression and programmed cell death (PCD) suggested involvement of PCD in abscission. In this study, hallmarks of PCD were identified in the tomato leaf and flower AZs during the late stage of abscission. These included loss of cell viability, altered nuclear morphology, DNA fragmentation, elevated levels of reactive oxygen species and enzymatic activities, and expression of PCD-associated genes. Overexpression of antiapoptotic proteins resulted in retarded abscission, indicating PCD requirement. PCD, LX, and nuclease gene expression were visualized primarily in the AZ distal tissue, demonstrating an asymmetry between the two AZ sides. Asymmetric expression was observed for genes associated with cell wall hydrolysis, leading to AZ, or associated with ethylene biosynthesis, which induces abscission. These results suggest that different abscission-related processes occur asymmetrically between the AZ proximal and distal sides. Taken together, our findings identify PCD as a key mechanism that occurs asymmetrically during normal progression of abscission and suggest an important role for LX in this PCD process.     

Heat shock protein expression in relation to reproductive cycle in land snails: Implications for survival

Land snails are subject to daily and seasonal variations in temperature and in water availability and use heat shock proteins (HSPs) as part of their survival strategy. We tested whether the reproductive cycle of land snails affects the endogenous levels of HSPs, and their involvement in the reproductive process. We examined HSP levels in the foot tissue of two Sphincterochila species, S. cariosa and S. zonata, before and after laying eggs, and analyzed the albumen gland (reproductive organ) of both species and eggs of S. cariosa for the presence and quantity of various HSPs. Our study shows reduction in the expression level of Hsp70 isoforms and Hsp90 in S. zonata foot and of Hsp74 in S. cariosa foot during the period preceding egg laying compared to the post-reproductive stage. Hsp70 isoforms and Hsp25 were highly expressed in both large albumen glands and in freshly laid eggs of S. cariosa, whereas large albumen glands of S. zonata expressed mainly Hsp70 isoforms. We conclude that a trade-off between survival and fertility is responsible for the expression level of HSPs in the foot tissue of Sphincterochila snails. Our study shows that HSPs are involved in the reproductive process. We propose that parental provision of HSPs may be part of a "be prepared" strategy of Sphincterochila snails, and that HSPs may play important roles in the survival strategy of land snails during the early life stages. Our observations also highlight the importance of the reproductive status in study of whole organisms, especially when assessing the HSP response to stress.     

AAV exploits subcellular stress associated with inflammation, endoplasmic reticulum expansion, and misfolded proteins in models of cystic fibrosis

Barriers to infection act at multiple levels to prevent viruses, bacteria, and parasites from commandeering host cells for their own purposes. An intriguing hypothesis is that if a cell experiences stress, such as that elicited by inflammation, endoplasmic reticulum (ER) expansion, or misfolded proteins, then subcellular barriers will be less effective at preventing viral infection. Here we have used models of cystic fibrosis (CF) to test whether subcellular stress increases susceptibility to adeno-associated virus (AAV) infection. In human airway epithelium cultured at an air/liquid interface, physiological conditions of subcellular stress and ER expansion were mimicked using supernatant from mucopurulent material derived from CF lungs. Using this inflammatory stimulus to recapitulate stress found in diseased airways, we demonstrated that AAV infection was significantly enhanced. Since over 90% of CF cases are associated with a misfolded variant of Cystic Fibrosis Transmembrane Conductance Regulator (ΔF508-CFTR), we then explored whether the presence of misfolded proteins could independently increase susceptibility to AAV infection. In these models, AAV was an order of magnitude more efficient at transducing cells expressing ΔF508-CFTR than in cells expressing wild-type CFTR. Rescue of misfolded ΔF508-CFTR under low temperature conditions restored viral transduction efficiency to that demonstrated in controls, suggesting effects related to protein misfolding were responsible for increasing susceptibility to infection. By testing other CFTR mutants, G551D, D572N, and 1410X, we have shown this phenomenon is common to other misfolded proteins and not related to loss of CFTR activity. The presence of misfolded proteins did not affect cell surface attachment of virus or influence expression levels from promoter transgene cassettes in plasmid transfection studies, indicating exploitation occurs at the level of virion trafficking or processing. Thus, we surmised that factors enlisted to process misfolded proteins such as ΔF508-CFTR in the secretory pathway also act to restrict viral infection. In line with this hypothesis, we found that AAV trafficked to the microtubule organizing center and localized near Golgi/ER transport proteins. Moreover, AAV infection efficiency could be modulated with siRNA-mediated knockdown of proteins involved in processing ΔF508-CFTR or sorting retrograde cargo from the Golgi and ER (calnexin, KDEL-R, β-COP, and PSMB3). In summary, our data support a model where AAV exploits a compromised secretory system and, importantly, underscore the gravity with which a stressed subcellular environment, under internal or external insults, can impact infection efficiency.     

A third of the yeast mitochondrial proteome is dual localized: a question of evolution

There are a growing number of examples of identical or almost identical proteins, which are localized to two (or more) separate compartments, a phenomenon that is termed protein dual localization, dual distribution or dual targeting. We previously divided a reference set of known yeast mitochondrial proteins into two groups, suggested to be dual localized or exclusive mitochondrial proteins. Here we examined this evaluation by screening 320 mitochondrial gene products for dual targeting, using the α-complementation assay. The analysis of the results of this experimentally independent screen supports our previous evaluation that dual localized mitochondrial proteins constitute a subgroup of mitochondrial proteins with distinctive properties. These proteins are characterized by a lower probability of mitochondrial localization (MitoProtII score), a lower net charge and are enriched for proteins with a weaker mitochondrial targeting sequence. Conversely, mRNAs of exclusive mitochondrial proteins are enriched in polysomes associated with mitochondria. Based on the discovery of more than 60 new gene products that are now assumed to be dual targeted, we have updated an annotation list of dual-targeted proteins. We currently estimate that more than a third of the mitochondrial proteome is dual targeted, and suggest that this abundant dual targeting presents an evolutionary advantage.