Stochastic dynamics of remote knock-on permeation in biological ion channels

Brownian dynamics simulations provide evidence for a remote knock-on mechanism facilitating the permeation of a biological ion channel by an ion that is initially trapped at the selectivity filter (SF). Unlike the case of conventional direct knock-on, the second ion that instigates permeation does not need to enter the channel. Nor does it necessarily take the place of the permeating ion at the SF, and it can even be of a different ionic species. The study is based on the simultaneous, self-consistent, solution of the coupled Poisson and Langevin equations for a simple generic model, taking account of all the charges present. The new permeation mechanism involves electrostatic amplification attributable to the permittivity mismatch between water and protein: the arrival of the instigating ion at the channel entrance reduces the exit barrier for the ion trapped at the SF, facilitating escape

The mitochondrial protease HtrA2 restricts the NLRP3 and AIM2 inflammasomes.

Activation of the inflammasome pathway is crucial for effective intracellular host defense. The mitochondrial network plays an important role in inflammasome regulation but the mechanisms linking mitochondrial homeostasis to attenuation of inflammasome activation are not fully understood. Here, we report that the Parkinson\u27s disease-associated mitochondrial serine protease HtrA2 restricts the activation of ASC-dependent NLRP3 and AIM2 inflammasomes, in a protease activity-dependent manner. Consistently, disruption of the protease activity of HtrA2 results in exacerbated NLRP3 and AIM2 inflammasome responses in macrophages ex vivo and systemically in vivo. Mechanistically, we show that the HtrA2 protease activity regulates autophagy and controls the magnitude and duration of inflammasome signaling by preventing prolonged accumulation of the inflammasome adaptor ASC. Our findings identify HtrA2 as a non-redundant mitochondrial quality control effector that keeps NLRP3 and AIM2 inflammasomes in check

Making sense of methods – a conversation about qualitative research in library and information studies

Currently there is an embarrassment of riches with regards to the range of research methods appropriate for library and information studies [LIS]; including qualitative and quantitative methods as well as ‘mixed methods’. All of this provides a rich body of resources for researchers, but this abundance also has a downside since it can also result in confusion and perplexity amongst researchers as they plan their investigative studies. Contributions such as this special issue are welcome opportunities to resolve and ameliorate this situation, and so in our contribution we seek to address some of these issues in the form of an interchange between two researchers with interests that include, but are not limited to, research in LIS. Between us we have a wide range of publications, as well as 80 plus PhD completions, many of which fall under the heading of LIS – broadly conceived. In particular we would claim specific expertise in Grounded Theory [Bryant] and Action Research [Abbott-Halpin]. Our aim is to seek clarification of some of the key methodological issues; although we realize that this is unlikely to provide any definitive outcome, it may assist those seeking guidance on these matters

Reducing Delirium in Patients with COVID-19

The purpose of our critically appraised topic is to synthesize the best current evidence regarding interventions that would be effective in reducing delirium in patients with COVID-19 in the acute care setting. The final portfolio contains a total of five research articles. Study designs include three randomized controlled trials, one non randomized controlled trial, and one quasi-experimental quantitative design. All studies relate directly to interventions within the OT scope of practice and were implemented in the acute care setting. Due to limited research on the novel coronavirus, these findings apply to critically ill patients but are not specific to patients with COVID-19. Early and intensive OT intervention in combination with multicomponent intervention strategies were found to significantly decrease delirium. Promising evidence can be used to draft new practice guidelines for decreasing delirium in critically ill patients within the acute care setting. In addition, modified implementation of slow tempo music and family participation/visitation interventions are recommended for patients with COVID-19. Due to the minimal time for therapy interventions within the acute care setting, implementation of these interventions as frequently as possible is recommended

Epistasis not needed to explain low dN/dS

An important question in molecular evolution is whether an amino acid that occurs at a given position makes an independent contribution to fitness, or whether its effect depends on the state of other loci in the organism's genome, a phenomenon known as epistasis. In a recent letter to Nature, Breen et al. (2012) argued that epistasis must be "pervasive throughout protein evolution" because the observed ratio between the per-site rates of non-synonymous and synonymous substitutions (dN/dS) is much lower than would be expected in the absence of epistasis. However, when calculating the expected dN/dS ratio in the absence of epistasis, Breen et al. assumed that all amino acids observed in a protein alignment at any particular position have equal fitness. Here, we relax this unrealistic assumption and show that any dN/dS value can in principle be achieved at a site, without epistasis. Furthermore, for all nuclear and chloroplast genes in the Breen et al. dataset, we show that the observed dN/dS values and the observed patterns of amino acid diversity at each site are jointly consistent with a non-epistatic model of protein evolution.Comment: This manuscript is in response to "Epistasis as the primary factor in molecular evolution" by Breen et al. Nature 490, 535-538 (2012

Exploring the Performance of Methods to Deal Multicollinearity: Simulation and Real Data in Radiation Epidemiology Area

The issue of multicollinearity has long been acknowledged in statistical modelling; however, it is often untreated in the most of published papers. Indeed, the use of methods for multicollinearity correction is still scarce. One important reason is that despite many proposed methods, little is known about their strength or performance. We compare the statistical properties and performance of four main techniques to correct multicollinearity, i.e., Ridge Regression (R-R), Principal Components Regression (PC-R), Partial Least Squares Regression (PLS-R), and Lasso Regression (L-R), in both a simulation study and two real data examples used for modelling volumes of heart and Thyroid as a function of clinical and anthropometric parameters. We find that when the statistical approaches were used to address different levels of collinearity, we observed that R-R, PC-R and PLS-R appeared to have a somewhat similar behavior, with a slight advantage for the PLS-R. Indeed, in all implemented cases, the PLS-R always provided the smallest value of root mean square error (RMSE). When the degree of collinearity was moderate, low or very low, the L-R method had also somewhat similar performance to other methods. Furthermore, correction methods allowed us to provide stable and trustworthy parameter estimates for predictors in the modelling of heart and Thyroid volumes. Therefore, this work will contribute to highlighting performances of methods used only for situations ranging from low to very high multicollinearity

Impact of Climate Change on Priority Plant Species Conservation in The Forests Under ONAB (the National Wood Office of Benin) Management

The sustainable conservation of forest resources in a context of climate change and population growth would be compromised in their current form of exploitation by rural communities. The objective of this study is to assess the impact of climate change on the dynamics of habitats favorable to species of conservation priority in the forests under ONAB management as these species are heavily used by the populations living along the shores of these forests. The study will consist of: Khaya senegalensis, Afzelia africana, Khaya grandifoliola, Pterocarpus erinaceus, Anogeissus leiocarpa, Milicia excelsa, Albizia zygia, Vitex doniana, Antidesma laciniatum and Bombax costatum. Techniques based on the principle of maximum entropy (Maxent) combined with GIS were used to project the favorable habitats of these ten species under current and future climatic conditions (Horizon 2050). Species occurrence data were collected and combined with bioclimatic data derived from the Worldclim database and the edaphic (soil) variable. Two climate models were used for future projections (CNRM-CM5, HadGEM-ES models) under the IPCC A2 scenario, and the partial ROC approach was used for the evaluation of the predictions of ecological niche models. Variables such as cec2 (cation exchange capacity, horizon 5-15cm), bio17 (precipitation of the driest quarter), bio12 (annual precipitation), bio3 (isothermality), bio6 (minimum temperature of the coldest month) and bio7 (annual thermal amplitude) were found to be the most relevant respectively for the distribution of Khaya grandifoliola, Albizia zygia, Anogeissus leiocarpa, Antidesma laciniatum, Afzelia africana and Khaya senegalensis. Under current conditions, only 7% of the Beninese territory would be very favorable to the conservation of Khaya senegalensis and the CNRM-CM5 model predicts an increase of 27.5% and 13.2% respectively of these very favorable and moderately favorable areas by 2050 through conversion of unfavorable areas (7.4%). On the other hand, this model predicts an opposite trend at the level of Afzelia africana where it predicts a decrease of 8.1% and 1.8% respectively of the very favorable and moderately favorable areas and an increase of 5.1% of the unfavorable areas. Ecological niche modeling has basically revealed the conversion of some currently unfavorable habitats into very favorable habitats for conservation (this is the case of Khaya grandifoliola, Khaya senegalensis and Vitex doniana) and the extension of some habitats unfavorable to conservation (Anogeissus leiocarpa, Bombax costatum, and Pterocarpus erinaceus) by 2050. This study provides scientific support for planning and is a decision support tool for the conservation of these species at the socio-economic level

Brain-Derived Neurotrophic Factor Val66Met and Blood Glucose: A Synergistic Effect on Memory

Age-related declines in episodic memory performance are frequently reported, but their mechanisms remain poorly understood. Although several genetic variants and vascular risk factors have been linked to mnemonic performance in general and age differences therein, it is unknown whether and how they modify age-related memory declines. To address that question, we investigated the effect of Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism that affects secretion of BDNF, and fasting blood glucose level (a vascular risk factor) on episodic memory in a sample of healthy volunteers (age 19–77). We found that advanced age and high-normal blood glucose levels were associated with reduced recognition memory for name-face associations and poorer prose recall. However, elevated blood glucose predicted lower memory scores only in carriers of the BDNF 66Met allele. The effect on associative memory was stronger than on free recall. These findings indicate that even low-level vascular risk can produce negative cognitive effects in genetically susceptible individuals. Alleviation of treatable vascular risks in such persons may have a positive effect on age-related cognitive declines

Caesarean section at Koudougou regional hospital centre: indications and prognosis

Background: Objective was to study the indications and the prognosis of cesarean section in the obstetrics and gynecology department of CHR Koudougou from August 1st to October 16th 2018.Methods: This was a cross-sectional study for descriptive purposes with prospective collection of data over the month and monitoring of parturients up to the 42nd day post caesarean section. The study covered the period from August 1 to October 16, 2018. Gestures received in the work room and those hospitalized for a scheduled cesarean were involved in this study.Results: This study involved 316 deliveries. The caesarean section rate was 34.8% (n=110). The average age was 26.75 years with extremes of 12 and 42 years. Term pregnancies represented 90.9%. History of cesarean section was observed in 47, 3%. The main groups contributing to the caesarean section rate represent: Groups 5 (9.5%), Group 1 (9.2%), Group 3 (5.1%), the scar uterus (17.3%) and suffering fetal (14.6%). The reported complications were 15.5% including 3.6% parietal suppuration and 0.8% stillbirth.Conclusions: The caesarean section occupies an important place in the maternity service of the RHC of Koudougou. Robson's group 5 was the largest contributor to the overall cesarean rate in our study. Measures should be taken in this group so that the uterine scar does not become an absolute indication for cesarean