New type of microengine using internal combustion of hydrogen and oxygen

Microsystems become part of everyday life but their application is restricted by lack of strong and fast motors (actuators) converting energy into motion. For example, widespread internal combustion engines cannot be scaled down because combustion reactions are quenched in a small space. Here we present an actuator with the dimensions 100x100x5 um^3 that is using internal combustion of hydrogen and oxygen as part of its working cycle. Water electrolysis driven by short voltage pulses creates an extra pressure of 0.5-4 bar for a time of 100-400 us in a chamber closed by a flexible membrane. When the pulses are switched off this pressure is released even faster allowing production of mechanical work in short cycles. We provide arguments that this unexpectedly fast pressure decrease is due to spontaneous combustion of the gases in the chamber. This actuator is the first step to truly microscopic combustion engines.Comment: Paper and Supplementary Information (to appear in Scientific Reports

A Simple Method for Analyzing Exome Sequencing Data Shows Distinct Levels of Nonsynonymous Variation for Human Immune and Nervous System Genes

To measure the strength of natural selection that acts upon single nucleotide variants (SNVs) in a set of human genes, we calculate the ratio between nonsynonymous SNVs (nsSNVs) per nonsynonymous site and synonymous SNVs (sSNVs) per synonymous site. We transform this ratio with a respective factor f that corrects for the bias of synonymous sites towards transitions in the genetic code and different mutation rates for transitions and transversions. This method approximates the relative density of nsSNVs (rdnsv) in comparison with the neutral expectation as inferred from the density of sSNVs. Using SNVs from a diploid genome and 200 exomes, we apply our method to immune system genes (ISGs), nervous system genes (NSGs), randomly sampled genes (RSGs), and gene ontology annotated genes. The estimate of rdnsv in an individual exome is around 20% for NSGs and 30–40% for ISGs and RSGs. This smaller rdnsv of NSGs indicates overall stronger purifying selection. To quantify the relative shift of nsSNVs towards rare variants, we next fit a linear regression model to the estimates of rdnsv over different SNV allele frequency bins. The obtained regression models show a negative slope for NSGs, ISGs and RSGs, supporting an influence of purifying selection on the frequency spectrum of segregating nsSNVs. The y-intercept of the model predicts rdnsv for an allele frequency close to 0. This parameter can be interpreted as the proportion of nonsynonymous sites where mutations are tolerated to segregate with an allele frequency notably greater than 0 in the population, given the performed normalization of the observed nsSNV to sSNV ratio. A smaller y-intercept is displayed by NSGs, indicating more nonsynonymous sites under strong negative selection. This predicts more monogenically inherited or de-novo mutation diseases that affect the nervous system

Analysis and computer program for rupture-risk prediction of abdominal aortic aneurysms

BACKGROUND: Ruptured abdominal aortic aneurysms (AAAs) are the 13(th )leading cause of death in the United States. While AAA rupture may occur without significant warning, its risk assessment is generally based on critical values of the maximum AAA diameter (>5 cm) and AAA-growth rate (>0.5 cm/year). These criteria may be insufficient for reliable AAA-rupture risk assessment especially when predicting possible rupture of smaller AAAs. METHODS: Based on clinical evidence, eight biomechanical factors with associated weighting coefficients were determined and summed up in terms of a dimensionless, time-dependent severity parameter, SP(t). The most important factor is the maximum wall stress for which a semi-empirical correlation has been developed. RESULTS: The patient-specific SP(t) indicates the risk level of AAA rupture and provides a threshold value when surgical intervention becomes necessary. The severity parameter was validated with four clinical cases and its application is demonstrated for two AAA cases. CONCLUSION: As part of computational AAA-risk assessment and medical management, a patient-specific severity parameter 0 < SP(t) < 1.0 has been developed. The time-dependent, normalized SP(t) depends on eight biomechanical factors, to be obtained via a patient's pressure and AAA-geometry measurements. The resulting program is an easy-to-use tool which allows medical practitioners to make scientific diagnoses, which may save lives and should lead to an improved quality of life

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations

Rosiglitazone Inhibits Transforming Growth Factor-β1 Mediated Fibrogenesis in ADPKD Cyst-Lining Epithelial Cells

BACKGROUND: Interstitial fibrosis plays an important role in progressive renal dysfunction in autosomal dominant polycystic kidney disease (ADPKD). In our previous studies, we confirmed that PPAR-γ agonist, rosiglitazone could protect renal function and prolong the survival of a slowly progressive ADPKD animal model by reducing renal fibrosis. However, the mechanism remains unknown. METHODS: Primary culture epithelial cells pretreated with TGF-β1 were incubated with rosiglitazone. Extracellular matrix proteins were detected using real-time PCR and Western blotting. MAPK and Smad2 phosphorylation were measured with western blot. ERK1/2 pathway and P38 pathway were inhibited with the specific inhibitors PD98059 and SB203580. The Smad2 pathway was blocked with the siRNA. To address whether PPAR-γ agonist-mediated inhibition of TGF-β1-induced collagen type I expression was mediated through a PPAR-γ dependent mechanism, genetic and pharmaceutical approaches were used to block the activity of endogenous PPARγ. RESULTS: TGF-β1-stimulated collagen type I and fibronectin expression of ADPKD cyst-lining epithelia were inhibited by rosiglitazone in a dosage-dependent manner. Smad2, ERK1/2 and P38 pathways were activated in response to TGF-β1; however, TGF-β1 had little effect on JNK pathway. Rosiglitazone suppressed TGF-β1 induced Smad2 activation, while ERK1/2 and P38MAPK signals remained unaffected. Rosiglitazone could also attenuate TGF-β1-stimulated collagen type I and fibronectin expression in primary renal tubular epithelial cells, but had no effect on TGF-β1-induced activation of Smad2, ERK1/2 and P38 pathways. There was no crosstalk between the Smad2 and MAPK pathways in ADPKD cyst-lining epithelial cells. These inhibitory effects of rosiglitazone were reversed by the PPARγ specific antagonist GW9662 and PPARγ siRNA. CONCLUSION: ADPKD cyst-lining epithelial cells participate in TGF-β1 mediated fibrogenesis. Rosiglitazone could suppress TGF-β1-induced collagen type I and fibronectin expression in ADPKD cyst-lining epithelia through modulation of the Smad2 pathway. Our study may provide therapeutic basis for clinical applications of rosiglitazone in retarding the progression of ADPKD

Genotype V Japanese Encephalitis Virus Is Emerging

Japanese encephalitis (JE) is a global public health issue that has spread widely to more than 20 countries in Asia and has extended its geographic range to the south Pacific region including Australia. JE has become the most important cause of viral encephalitis in the world. Japanese encephalitis viruses (JEV) are divided into five genotypes, based on the nucleotide sequence of the envelope (E) gene. The Muar strain, isolated from patient in Malaya in 1952, is the sole example of genotype V JEV. Here, the XZ0934 strain of JEV was isolated from Culex tritaeniorhynchus, collected in China. The complete nucleotide and amino acid sequence of XZ0934 strain have been determined. The nucleotide divergence ranged from 20.3% to 21.4% and amino acid divergence ranged from 8.4% to 10.0% when compared with the 62 known JEV isolates that belong to genotype I–IV. It reveals low similarity between XZ0934 and genotype I–IV JEVs. Phylogenetic analysis using both complete genome and structural gene nucleotide sequences demonstrates that XZ0934 belongs to genotype V. This, in turn, suggests that genotype V JEV is emerging in JEV endemic areas. Thus, increased surveillance and diagnosis of viral encephalitis caused by genotype V JEV is an issue of great concern to nations in which JEV is endemic

Stimulation of Midbrain Dopaminergic Structures Modifies Firing Rates of Rat Lateral Habenula Neurons

Ventral tegmental area (VTA) and substantia nigra pars compacta (SNpc) are midbrain structures known to be involved in mediating reward in rodents. Lateral habenula (LHb) is considered as a negative reward source and it is reported that stimulation of the LHb rapidly induces inhibition of firing in midbrain dopamine neurons. Interestingly, the phasic fall in LHb neuronal activity may follow the excitation of dopamine neurons in response to reward-predicting stimuli. The VTA and SNpc give rise to dopaminergic projections that innervate the LHb, which is also known to be involved in processing painful stimuli. But it's unclear what physiological effects these inputs have on habenular function. In this study we distinguished the LHb pain-activated neurons of the Wistar rats and assessed their electrophysiological responsiveness to the stimulation of the VTA and SNpc with either single-pulse stimulation (300 µA, 0.5 Hz) or tetanic stimulation (80 µA, 25 Hz). Single-pulse stimulation that was delivered to either midbrain structure triggered transient inhibition of firing of ∼90% of the LHb pain-activated neurons. However, tetanic stimulation of the VTA tended to evoke an elevation in neuronal firing rate. We conclude that LHb pain-activated neurons can receive diverse reward-related signals originating from midbrain dopaminergic structures, and thus participate in the regulation of the brain reward system via both positive and negative feedback mechanisms

A Protective Mechanism against Antibiotic-Induced Ototoxicity: Role of Prestin

Hearing loss or ototoxicity is one of the major side effects associated with the use of the antibiotics, particularly aminoglycosides (AGs), which are the most commonly used antibiotics worldwide. However, the molecular and cellular events involved in the antibiotic-induced ototoxicity remains unclear. In the present study, we test the possibility that prestin, the motor protein specifically expressed in the basolateral membrane of outer hair cells (OHCs) in the cochlea with electromotility responsible for sound amplification, may be involved in the process of AG-induced apoptosis in OHCs. Our results from both mice model and cultured cell line indicate a previously unexpected role of prestin, in mediating antibiotic-induced apoptosis, the effect of which is associated with its anion-transporting capacity. The observed downregulation of prestin mRNA prior to detectable apoptosis in OHCs and hearing loss in the antibiotic-treated mice is interesting, which may serve as a protective mechanism against hearing loss induced by AGs in the early stage

Complement C1 Esterase Inhibitor Levels Linked to Infections and Contaminated Heparin-Associated Adverse Events

Activation of kinin-kallikrein and complement pathways by oversulfated-chondroitin-sulfate (OSCS) has been linked with recent heparin-associated adverse clinical events. Given the fact that the majority of patients who received contaminated heparin did not experience an adverse event, it is of particular importance to determine the circumstances that increase the risk of a clinical reaction. In this study, we demonstrated by both the addition and affinity depletion of C1inh from normal human plasma, that the level of C1inh in the plasma has a great impact on the OSCS-induced kallikrein activity and its kinetics. OSCS-induced kallikrein activity was dramatically increased after C1inh was depleted, while the addition of C1inh completely attenuated kallikrein activity. In addition, actual clinical infection can lead to increased C1inh levels. Plasma from patients with sepsis had higher average levels of functional C1inh and decreased OSCS-induced kallikrein activity. Lastly, descriptive data on adverse event reports suggest cases likely to be associated with contaminated heparin are inversely correlated with infection. Our data suggest that low C1inh levels can be a risk factor and high levels can be protective. The identification of risk factors for contact system-mediated adverse events may allow for patient screening and clinical development of prophylaxis and treatments

Prediction of protein submitochondria locations by hybridizing pseudo-amino acid composition with various physicochemical features of segmented sequence

BACKGROUND: Knowing the submitochondria localization of a mitochondria protein is an important step to understand its function. We develop a method which is based on an extended version of pseudo-amino acid composition to predict the protein localization within mitochondria. This work goes one step further than predicting protein subcellular location. We also try to predict the membrane protein type for mitochondrial inner membrane proteins. RESULTS: By using leave-one-out cross validation, the prediction accuracy is 85.5% for inner membrane, 94.5% for matrix and 51.2% for outer membrane. The overall prediction accuracy for submitochondria location prediction is 85.2%. For proteins predicted to localize at inner membrane, the accuracy is 94.6% for membrane protein type prediction. CONCLUSION: Our method is an effective method for predicting protein submitochondria location. But even with our method or the methods at subcellular level, the prediction of protein submitochondria location is still a challenging problem. The online service SubMito is now available at