Background：Previous studies have shown that small molecule inhibitors of NLRP3 may be a potential treatment for Parkinson’s disease. NACHT, LRR and PYD domains-containing protein 3 (NLRP3), Heat shock protein HSP 90-beta (HSP90AB1), Caspase-1 (CASP1) and Cellular tumor antigen p53 (TP53) have significant involvement in the pathogenesis pathway of PD. Purpose：Since Parkinson’s syndrome has a serious impact on the quality of life of patients, we desire to investigate Potential Leads with artificial intelligence methods Experimental approach: Molecular docking was used to screen traditional Chinese medicine database TCM Database @Taiwan (http://tcm.cmu.edu.tw). Top TCM compounds with high affinities based on Dock Score were selected to form the drug-target interaction network in order to investigate potential candidates targeting the four proteins. Artificial intelligence model, 3D-QSAR were constructed respectively utilizing training sets of inhibitors against the four proteins with known inhibitory activities (pIC50). After that, we conducted molecular dynamics simulation of these compounds and finally identified candidate compounds. Key Results: 2007_22057, 2007_22325 and 2007_15317 which are from TCM database may show great biological activities with targets. Conclusions: The results shown that 2007_22057, 2007_22325 and 2007_15317 might be a potential medicine formula for the treatment of Parkinson’s Disease.

Background and Purpose: Oleuropein is found in olive trees and in the leaves of olive trees. It may have an important role in the treatment and possible prevention of of Alzheimer’s disease. Applied Approach: The aim of this study is to determine the chemical properties of oleuropein and determine the reactivity of this substance as well as Oleuropein’s inhibition effect on AChE.BChE. Key Results: DFT (Density functional theory), HF (Hartree-Fock) and docking methods were used to measure the chemical properties of oleuropein. The structures of the compounds were fully optimized by using the above-mentioned methods and the results were evaluated. Oleuropein is an unstable molecule and is prone to degredation possibly due to it containing a phenolic structure. Conclusion and Implications:The results of the present study indicate that it may play an important role in the treatment of Alzheimer’s disease.

It is possible to estimate the prior probability of pathogenicity for germline disease gene variants based on bioinformatic prediction of variant effect/s. However, routinely used approaches have likely led to the underestimation and underreporting of variants located outside donor and acceptor splice site motifs that affect mRNA processing. This review presents information about hereditary cancer gene germline variants, outside native splice sites, with experimentally validated splicing effects. We list 81 exonic variants that impact splicing regulatory elements in BRCA1, BRCA2, MLH1, MSH2, MSH6 and PMS2. We utilized a pre-existing large-scale BRCA1 functional dataset to map functional splicing regulatory elements, assess the relative performance of different tools to predict effects of 283 variants on such elements, and develop a generic workflow to prioritize variants that may impact splicing regulatory elements. We also describe rare examples of intronic variants that impact branchpoint sites and create pseudoexons. We discuss the challenges in predicting variant effect on branchpoint site usage and pseudoexonization, and suggest strategies to improve the bioinformatic prioritization of such variants for experimental validation. Importantly, our review highlights the importance of considering impact of variants outside donor and acceptor motifs on mRNA splicing and disease causation.

Population dynamics models combine density-dependence and environmental effects. Ignoring sampling uncertainty might lead to biased estimation of the strength of density-dependence. This is typically addressed using state-space model approaches, which integrate sampling error and population process estimates. Such models seldom include an explicit link between the sampling procedures and the true abundance, which is common in capture-recapture settings. However, many of the models proposed to estimate abundance in the presence of heterogeneity lead to incomplete likelihood functions and cannot be straightforwardly included in state-space models. We assessed the importance of estimating sampling error explicitly by taking an intermediate approach between ignoring uncertainty in abundance estimates and fully specified state-space models for density-dependence estimation based on autoregressive processes. First, we estimated individual capture probabilities based on a heterogeneity model, using a conditional multinomial likelihood, followed by a Horvitz-Thompson estimate for abundance. Second, we estimated coefficients of autoregressive models for the log abundance. Inference was performed using the methodology of integrated nested Laplace approximation (INLA). We performed an extensive simulation study to compare our approach with estimates disregarding capture history information, and using R-package VGAM, for different parameter specifications. The methods were then applied to a real dataset of gray-sided voles Myodes rufocanus from Northern Norway. We found that density-dependence estimation was improved when explicitly modelling sampling error in scenarios with low innovation variances, in which differences in coverage reached up to 8% in estimating the coefficients of the autoregressive processes. In this case, the bias also increased assuming a Poisson distribution in the observational model. For high innovation variances, the differences between methods were small and it appeared less important to model heterogeneity.

1. The reduction of plant diversity following eutrophication threatens many ecosystems worldwide. Yet, the mechanisms by which species are lost following nutrient enrichment are still not completely understood, nor are the details of when such mechanisms act during the growing season, which hampers understanding and the development of mitigation strategies. 2. Using a common garden competition experiment, we found that early-season differences in growth rates among five perennial grass species measured in monoculture predicted short-term competitive dominance in pairwise combinations and that this effect was stronger under a fertilisation treatment. 3. We also examined the role of early-season growth rate in determining the outcome of competition along an experimental nutrient gradient in an alpine meadow. Early differences in growth rate between species predicted short-term competitive dominance under both ambient and fertilized conditions and competitive exclusion under fertilized conditions. 4. The results of these two studies suggests that plant species growing faster during the early stage of the growing season gain a competitive advantage over species that initially grow more slowly, and that this advantage is magnified under fertilisation. This finding is consistent with the theory of asymmetric competition for light in which fast-growing species can intercept incident light and hence outcompete and exclude slower-growing (and hence shorter) species. We predict that the current chronic nutrient inputs into many terrestrial ecosystems worldwide will reduce plant diversity and maintain low biodiversity state by continuously favouring fast-growing species. Biodiversity management strategies should focus on controlling nutrient inputs and reducing the growth of fast-growing species early in the season.

From its origins, the concept of desertification has been controversial. The prevailing confusion between two desertification visions, one that considers it as the expansion of deserts and another that denotes its anthropogenic component, has been transferred to society. Here we illustrate misunderstandings about desertification using a very illustrative case from the Tabernas-Sorbas Basin (Almeria, Spain), where striking badlands that are often used as an image of desertification coexist with an intensive olive agriculture that is deteriorating irreversibly the only oasis in continental Europe, Los Molinos spring. The olive tree is a traditional Mediterranean dryland crop and until the 1950s only about 200 ha were irrigated. However, the profitability of the crop has caused irrigation to expand to 4,400 ha in the last two decades. The process of intensification has been reinforced giving way to super-intensive irrigation, which involves going from 210 to 1,550 trees/ha and that in a few years already occupies more than 1,500 ha. The effects on the water balance of the aquifer feeding these crops have been severe and the flow of the Los Molinos spring has gone from more than 40 L/s for the period 1970-2000 to the current 7.28 L/s. By unraveling the mechanisms of land degradation, we were able to detect its main drivers in the study area and, with them, to propose management actions to achieve a more sustainable use of resources and to combat desertification.

Snowfall, snow accumulation, and stand structure in a primitive Korean pine forest of the Xiaoxing’an Mountains, China, were assessed for 2 consecutive years. Moreover, a physical mechanism-based snow accumulation model, which can be applicable to stand-scale forests, was introduced to simulate snow accumulation in the studied region. The results showed that the mean atmospheric temperature was −17°C during the snow accumulation period. Snow density was lower during snow accumulation period but slightly higher when snow melted. Moreover, when snow accumulated, snow water equivalent was significantly higher in forest clearings than beneath dense canopies, with a maximum difference of >50%. The variability of snow water equivalent in forest clearings was relatively low, whereas that beneath dense canopies was higher. The maximum snow accumulation in the forest indicated a significant negative correlation with canopy density, tree height, effective leaf area, and slope, whereas it indicated a significant positive correlation with canopy width. However, no significant correlation was noted between the maximum snow accumulation and diameter at breast height, basal area, or canopy height. The effective leaf area index and canopy density of the primitive Korean pine forest in this region could be well explained using a power function. As snow accumulated, the presence of forest canopy significantly affected the spatial distribution of snow accumulation in the forest. When snow melted, atmospheric temperature was the main factor controlling snow melting. Canopy density, slope, and canopy width showed a significant impact on maximum snow water equivalent; this factor increased with a decrease in canopy density and slope and with an increase in canopy width. In the present study, slope was selected as one of the main factors affecting snow accumulation in the forest. Therefore, future studies on snow accumulation models should incorporate slope as a parameter to improve simulation accuracy.

Co-digestion of mixed waste activated sludge (MWAS) and fruit and vegetable waste (FVW) was studied in a two-stage (thermophilic followed by mesophilic) semi-continuous anaerobic digestion to evaluate anaerobic digester performance and stability. A mixing ratio of 75% MWAS and 25% FVW showed a 1.6-fold increase in overall methane yield and achieved 0.38 FOS/TAC ratio (volatile fatty acids to alkaline buffer capacity) compared to mixture of 50% MWAS and 50% FVW. Application of hybrid (MW-H2O2) pretreatment in the former mixing ratio increased sludge solubilisation by 33% and consequently enhanced overall methane yield by 2.17-fold. The treated digester showed increased process stability with a FOS/TAC ratio of 0.26 as a consequence of buffer capacity offered by released biopolymers during pre-treatment. The generation of superoxide radicals during digestion was studied and found to negatively correlate with sludge bioactivity. Two-stage digestion also minimizes the issue of high acidification due to co-digestion involving FVW.

Interação do observador com o sistemaPara o observador, realizar uma medição é interagir com o sistema. Como o observador também é um sistema físico, portanto, feito de partículas em interação, a interação pode mudar o estado de movimento de ambos os sistemas. No entanto, na mecânica clássica essa interação pode ser muito pequena. A medida ideal é aquela em que o observador e o sistema estão isolados um do outro e é assim que os físicos acreditavam ser a natureza da medida até o surgimento da mecânica quântica. No mundo real, é impossível medir sem interagir.Digamos que queremos coletar informações sobre uma bola de futebol. Os dados podem ter, novamente, sobre sua cor. A primeira coisa que poderíamos fazer é lançar luz sobre a bola, de modo que o sistema que interage diretamente com a bola é um feixe de luz branca. A luz em si é um sistema físico, mas não mecânico. Pode ser vista aqui como uma onda de campo eletromagnético, certamente fora do domínio da mecânica clássica. Mas este é um caso em que podemos usar a descrição clássica de partículas para discutir o assunto em questão. Para coletar a medida, no entanto, o observador deve, de alguma forma, interagir com a luz espalhada pela bola, talvez com uma câmera. A câmera também deve enviar informações para um computador, para a resposta final sobre a cor da bola. Obviamente, a câmera pode ser substituída por um olho humano e o computador pode ser substituído por um cérebro humano.A interação pode ser negligenciável, dependendo das propriedades do feixe e da bola. Normalmente, podemos ajustar a intensidade da luz para que a interação se torne fraca demais para resultar em alterações mensuráveis no estado da bola. Portanto, podemos usar essa configuração para medir a cor sem interferência sensível do processo de medição.Por outro lado, se aumentarmos a intensidade da luz, as características da bola passam a sofrer interferência da própria medição. Conseqüentemente, medir a cor de uma bola com luz muito intensa destruirá as informações que você deseja coletar em primeiro lugar. Sabemos que um feixe suficientemente forte pode incendiar uma bola.Na mecânica clássica, sempre supomos que a interação entre o observador e o sistema físico possa ser arbitrariamente negligenciável. No entanto, veremos o colapso dessa suposição se o sistema for, por exemplo, muito pequeno em comparação com a influência do aparelho de medição. Medir a cor de um elétron usando o mesmo procedimento será impossível, pois mesmo a luz mais fraca irá interagir com o elétron, alterando a própria característica que o observador deseja medir. Para sistemas quânticos, a interação do observador com o sistema é sempre esperada; portanto, o que pode ser medido é a resposta do sistema ao ato de medição.

Continuity in research group collective knowledge is critical for running a successful research program but in an undergraduate research lab, this can be particularly challenging. A wiki site dedicated to the research laboratory, a lab wiki, can bridge gaps in student-to-student knowledge transfer and contribute to longevity of a research program. A lab wiki is an organized, easily accessible, collaborative resource that can contain tutorials, group-specific directions, links to resources and guides to writing papers or proposals. The wiki language is easy for students to pick up and contributes to their participation in preserving group knowledge. This tutorial introduces the concept of a lab wiki, the advantages of it, example content and practical implementation advice.

As issues surrounding depleting fossil fuels, climate change, and various other environmental impacts are becoming more prevalent, there is a growing interest in technological shifts toward a bio-based economy. Various advanced biotechnological tools have been developed to customize cell factories for the production of a wide range of complex fine chemicals from renewable feedstock. Herein, we report development of a microbial bioprocess for high-level and potentially economical production of 5-aminolevulinic acid (5-ALA), a valuable non-proteinogenic amino acid with multiple applications in medical, agricultural, and food industries, using Escherichia coli as a cell factory. We first implemented the Shemin (i.e., C4) pathway for heterologous 5-ALA biosynthesis in E. coli. To reduce, but not to abolish, the carbon flux toward essential tetrapyrrole/porphyrin biosynthesis, we applied Clustered Regularly Interspersed Short Palindromic Repeats interference (CRISPRi) to repress hemB expression, leading to extracellular 5-ALA accumulation. We then applied metabolic engineering strategies to direct more dissimilated carbon flux toward the key precursor of succinyl-CoA for enhanced 5-ALA biosynthesis. Using these engineered E. coli strains for bioreactor cultivation, we successfully demonstrated high-level 5-ALA biosynthesis solely from glycerol (~30 g l-1) under both microaerobic and aerobic conditions, achieving up to 5.95 g l-1 (36.9% yield) and 6.93 g l-1 (50.9% yield) 5-ALA, respectively. This study represents one of the most effective bio-based production of 5-ALA from a structurally unrelated carbon to date, highlighting the importance of integrated strain engineering and bioprocessing strategies to enhance bio-based production.

Letter to the Editor, BJOG Exchange

Objective:We tried to provide an overview of philatelic materials related to Gynecology and Obstetrics. Design:Sample philatelic materials including stamps, first day covers and stamped postcards, all related to obstetrics and gynecology, from the senior author’s personal archive were grouped according to their titles and evaluated in detail. Setting:We examine how stamp designers use visual imagery to convey information to those who see, collect, and use stamps. Method:Sample philatelic materials, related to obstetrics and gynecology, were grouped according to their titles and evaluated in detail. Main outcome measures:Stamps dedicated to the Obstetrics and Gynecology are usually printed in order to (a)pay tribute to the pioneers of Obstetrics and Gynecology, (b)commemorate important Obstetrics and Gynecology Facilities&Hospitals, (c)announce solid improvements and innovations in the field or (d)memorialize important meetings. Results:The initial use of postage stamps was solely to pay the fare of a postal service. Later on it was discovered that by using stamps it was possible to distribute ideas and news among people and also to inform them about developments, inventions, achievements and historical facts. Collecting Gynecology related philatelic materials is a very specialized branch of medical philately. In general, the subjects of the stamps dedicated to Obstetrics and Gynecology are, pioneers of Obstetrics and Gynecology, important Obstetrics and Gynecology Facilities&Hospitals, solid improvements and innovations in the field and important meetings. Conclusion:Even though use of postage stamps is decreasing, they are still among the best mediums to convey messages to broad audience. Funding:None. Keywords:Commemoration, First Day Covers, Philately, Pionee

Objective We compare the adverse events in the 12 hours after double balloon catheter(DBC) or first prostaglandin(PGE) inserted and the efficacy of DBC to that of PGE in labour induction. Design Multi-centre Randomised controlled Trial (RCT), in 2 centers with 2 arms: (i)DBC (ii)prostaglandin pessary. Setting 2 tertiary hospitals, Singapore and Malaysia Population Southeast-Asian women Method This is a prospective cohort randomised controlled study. 210 women were recruited in each center and assigned randomly to cervical ripening with either DBC or prostaglandin pessary. Main outcome The adverse events in the 12 hours after DBC or first PGE inserted and the efficacy of a DBC to that of a prostaglandin in labour induction were evaluated. Results There were significantly less women with uterine hyperstimulation in the double balloon catheter group (2 vs 24, p=<0.0001) compared to the prostaglandin group. There were no women with uterine hyperstimulation and non-reassuring fetal status in the double balloon group while there were 5 women with uterine hyperstimulation and fetal distress in the prostaglandin group. Use of pain relief was significantly less in the double balloon catheter group (p=0.009). There were no significant differences in both groups in mode and time to delivery, although significant less time was needed to achieve os dilation more than 4cm in the double balloon catheter group (p=<0.0001). Conclusion DBC remains a good alternative method for inducing women in view of low adverse events and a good safety profile with low risk of hyperstimulation. Keywords: Double balloon catheter;prostaglandin;hyperstimulation;induction of labour ClinicalTrials.govIdentifier:NCT02620215.URL:https://clinicaltrials.gov/ct2/show/NCT02620215

Objective. This study aimed to determine the real-world, long-term prognostic impact and adverse effects (AEs) of bevacizumab (BEV) in Asian patients with ovarian/tubal/peritoneal cancers. Design Hospital-based observational cohort study. Setting Tertiary medical centre in Southern Taiwan. Population Women diagnosed with ovarian, tubal, peritoneal cancer. Methods. We retrospectively reviewed the medical records of consecutive patients on front-line chemotherapy with or without BEV (Cohort 1) and those who relapsed following chemotherapy and/or BEV (Cohort 2) between 2011 and 2018. Main outcome measures Patient clinicopathological characteristics, BEV dosages, clinical outcomes, survivals, and AEs were analysed. Hazard ratios for disease progression and death were analysed using a Cox model. Results. Benefits of BEV used throughout triweekly, in terms of improved progression-free survival (PFS) and overall survival (OS), were observed at a dosage of 7.5–15 mg/kg/cycle among advanced-stage Cohort 1 patients. A progression-free interval of <6 months was the strongest predictor of disease progression and death in advanced-stage patients. BEV throughout and optimal cytoreduction were independent predictors of reduced disease progression. Histology was not a prognostic predictor. BEV resulted in improved OS in Cohort 2 patients, especially in the platinum-sensitive subgroup. Most patients had a front-line BEV dosage <10 mg/kg per cycle with <10 treatment cycles. Low rates and grades of BEV-related AEs were observed. Conclusions BEV used throughout effectively extended PFS and OS in advanced-stage patients. Patients with platinum-sensitive carcinoma, treated with BEV, had a significant improvement in OS and extended PFS. Therefore, BEV can safely be added to chemotherapy for ovarian/tubal/peritoneal cancers.

To describe the method in which fallopian tube recanalization can be safely performed laparoscopically after tube ligation with two-stitch technique. Laparoscopic reversal of the unilateral tube was performed to a 38-year-old woman who underwent unilateral salpingectomy due to ectopic pregnancy. At 3 days after surgery, tubal patency was determined via hydrotubation, and the results were satisfactory. The patient was assessed via hysterosalpingography after 2 months to confirm the patency of the anastomosed fallopian tube, and no tube obstruction was noted. The two-stitch procedure can reduce surgical time and prevent the possibility of new scar formation compared to traditional four-stitch approach.

Background: PAR1 activation plays an important role in acute myocardial infarction, but the mechanism underlying the PAR1 expression under hypoxia is not clear. Method and Result: Cardiomyocytes from neonatal rats, cultured in hypoxic conditions, showed decreased PAR1 expression. The introduction of TRAP rescued the loss of PAR1 expression within 1 h of treatment. However, PAR1 expression was not affected by PAR1 activation, under normoxic condition. We detected mRNA expressions of Rab11A, Rab11B, FIP2, FIP3，and Rip11 but no Rab25, FIP1 and FIP4 in cardiomyocytes. Rab11A protein levels increased and reached the peak during the first 4h of hypoxia (4h: 179.93% ± 9.82% of control, control = normoxic group, n=5, P<0.05) and thereafter decreased; however, Rab11B protein decreased. Addition of TRAP caused 15,87 folds decrease in hypoxia-induced Rab11A expression, but 8.96 folds increase in hypoxia-decreased Rab11B expression after 4 h of hypoxia. Knockdown (with siRNA) of Rab11B, but not Rab11A, caused decreased PAR1 expression. Knockdown of Rip11 significantly inhibited the TRAP-rescued-PAR1 expression in cardiomyocytes during hypoxia. Rip11 levels decreased during hypoxia. The ratio of phosphorylated vs. non-phosphorylated Rip11 in TRAP-treated group and pervanadate-treated group showed 2 folds and 7 folds of that in vehicle group, respectively (P<0.05，n = 5). HIF-1α knockdown ( with siRNA) inhibited TRAP-rescued-PAR1 expression and Rip11 expression in hopxia cardiomyocytes. Conclusion: PAR1 activation reverses hypoxia-inhibited PAR1 expression through inhibiting Rab11A，enhancing Rab11B expression and phosphorylated HIF-1α-induced-Rip11 in cardiomyocytes during hypoxia.

BACKGROUND AND PURPOSE The use of human intestinal alkaline phosphatase (IAP) has already been validated as a novel treatment for endotoxin lipopolysaccharide (LPS)-induced inflammatory diseases, which is mediated through IAP’ s ability to detoxify LPS. However, there has been little investigation into the full extent of IAP’ s physiological function. This study investigates IAP’s non-LPS related functions and clinical applications. EXPERIMENTAL APPROACH In this study, we use freshly extracted human leukocytes to study effects of a recombinant human intestinal alkaline phosphatase (recIAP) on secretion of TNF-ɑ and IL-6 by the leukocytes in absence of LPS. Physiological substrates of alkaline phosphatase and their dephosphorylated products at neutral pH including ATP, ADP, AMP and adenosine were employed to investigate their effects on secretion of TNF-ɑ by the leukocyte. KEY RESULTS We found that recIAP inhibit TNF-α and IL-6 secretion by freshly extracted human leukocyte in the absence of LPS. recIAP dephosphorylates ATP and ADP etc at physiological pH. The dephosphorylated products by recIAP including AMP and adenosine inhibit TNF-α secretion of the freshly extracted human leukocyte. CONCLUSIONS AND IMPLICATIONS Human leukocyte migrates into inflamed tissues and secretes TNF-α and IL-6. Thus, leukocyte plays an important role in inflammatory diseases. recIAP inhibits TNF-α and IL-6 secreted by freshly extracted human leukocyte in the absence of LPS. The results in this study indicate that recIAP is a promising therapeutic candidate for diseases related to leukocyte TNF-α and IL-6 secretion.

Metalloenzyme lytic polysaccharide monooxygenase (LPMO) is a breakthrough enzyme, acting as a catalyst in the process of plant biomass conversion to biofuels. LPMOs oxidize polysaccharide in crystalline area, providing accessibility to other polysaccharide hydrolases for enhancing the saccharification process. In this review an in-silico analysis explores the active copper center and evolutionary relationship of LPMO. A radial phylogram of 168 LPMO genes from archaea to terrestrial plant infers their evolution as a paralogous enzyme catalyzing the same function in different domains. The review also emphasizes on the mechanism, electron flow, and diversity of electron-donating system for LPMO. The 3-D modeling of unexplored bacterial LPMO derived from extreme environment and its structural comparison by super positioning with well-defined TfAA10A (LPMO) of Thermobifida fusca was investigated. Result indicates the conservation in active copper center and flat surface for substrate binding from halophilic archaea to deep marine bacteria. Furthermore, annotation of different CAZymes in bacterial species with characterized LPMO and full range of glycoside hydrolase overcomes the need for consortia. The vast diversity and substrate flexibility of LPMOs along with its crucial role in pre-treatment steps of plant biomass, nano-cellulose formation, and insecticidal activity opens a wide array of biotechnological applications.

Objective: To determine whether planned cesarean section (CS) for a second delivery protects anal continence in women with obstetrical anal sphincter lesions. Design: Randomized trial. Setting: 6 maternity units in the Paris area. Sample : Women at high risk of sphincter lesions (first delivery with 3d degree laceration and/or forceps) but no symptomatic anal incontinence. Methods : Endoanal ultrasound was performed in the third trimester of the second pregnancy. Women with sphincter lesions were randomized to planned CS or vaginal delivery (VD). Main outcome measures : Anal continence at 6 months post-partum. Secondary outcomes were urinary continence, sexual morbidity, maternal and neonatal morbidities and worsening of external sphincter lesions. Results : Anal sphincter lesions were detected by ultrasound in 264/434 women enrolled (60.8%) ; 112 were randomized to planned VD and 110 to planned CS. At 6-8 weeks after delivery, there was no significant difference in anal continence between the 2 groups. At 6 months after delivery, median Vaizey scores of anal continence were 1 [IQR 0-4] in the CS group and 1 [IQR 0-3] in the VD group (p = 0.34). There were no significant differences for urinary continence, sexual functions or for other maternal and neonatal morbidities. Conclusions : In women with asymptomatic obstetrical anal sphincter lesions diagnosed by ultrasound, planning a CS had no significant impact on anal continence 6 months after the second delivery. These results do not support advising systematic CS for this indication.

Shared phylogenetic breaks across taxa, syntopic clusters of endemics, and paleogeographic reconstruction of isostatic and vegetation change over time suggest the existence of one or more ice-free glacial refugia off of North America’s North Pacific Coast. An incomplete fossil record, however, creates uncertainty over which species persisted in hypothesized refugia, obscuring interpretation of the timing, potential duration, and surrounding paleoenvironments. We use whole-genome resequencing to assess the historical biogeography of these complex northern landscapes that consist of multiple coastal archipelagos and mountain ranges. Discovery of distinct insular and continental clades within Pacific martens (M. caurina) is consistent with previous morphometric and parasitological studies and also with the Coastal Refugium Hypothesis, thereby supporting the persistence of diverse, potentially forested refugial communities along the western edges of the Alexander Archipelago. We found no evidence of admixture on islands that received translocations of American pine martens (M. americana) in the mid 1900s, but we detected introgression in two geographically distinct zones of secondary contact. Evidence of early-generational hybrids across multiple hybrid zones, each backcrossed with M. americana, is consistent with a history of genetic dilution of M. caurina through outbreeding with M. americana. Into the future, these hybrid zones will serve as iterative tests for the outcome of admixture, providing instructive natural experiments for forecasting outcomes of proactive measures such as genetic rescue by natural resource managers.

Leaf shape is a defining feature of how we recognise and classify plant species. Although there is extensive variation in leaf shape within many species, few studies have disentangled the underlying genetic architecture. We characterised the genetic architecture of leaf shape variation in Eurasian aspen (Populus tremula L.) by performing a genome wide association studies (GWAS) for physiognomy traits. To ascertain the roles of identified GWAS candidate genes within the leaf development transcriptional program, we performed gene co-expression network analyses from a developmental series, which is publicly available at http://aspleaf.plantgenie.org. We additionally used gene expression measurements across the population to analyse GWAS candidate genes in the context of a population-wide co-expression network and to identify genes that were differentially expressed between groups of individuals with contrasting leaf shapes. These data were integrated with expression GWAS (eQTL) results to define a set of candidate genes associated with leaf shape variation. Our results identified no clear adaptive link to leaf shape variation and indicate that leaf shape traits are genetically complex, likely determined by numerous small-effect variations in gene expression. Genes associated with shape variation were peripheral within the population-wide co-expression network, were not highly connected within the leaf development co-expression network and exhibited signatures of relaxed selection. As such, our results are consistent with the omnigenic model.

Most new cryptic species are described using conventional tree- and distance-based species delimitation methods (SDMs), which rely on phylogenetic arrangements and measures of genetic divergence. However, although numerous factors such as spatial population structure and gene flow are known to confound phylogenetic and species delimitation inferences, the influence of these processes on species estimation is rarely evaluated. Using large amounts of exons, introns, and ultraconserved elements obtained using the FrogCap sequence-capture protocol, we compared conventional SDMs with more robust genomic analyses that assesses spatial population structure and gene flow to characterize species boundaries in a Southeast Asian frog complex (Pulchrana picturata). Our results showed that gene flow and introgression can produce phylogenetic patterns and levels of divergence that resemble distinct species (up to 10% divergent in mitochondrial DNA). Hybrid populations were inferred as independent (singleton) clades that were highly divergent from adjacent populations (7–10%) and unusually similar (<3%) to allopatric populations. Such anomalous patterns are not uncommon in Southeast Asian amphibians, which brings into question whether the high cryptic diversity observed in other amphibian groups reflect distinct cryptic species—or, instead, highly structured and admixed metapopulation lineages. Our results also provide an alternative explanation to the conundrum of divergent (sometimes non-sister) sympatric lineages―a pattern that has been celebrated as indicative of true cryptic speciation. Based on these findings, we recommend that species delimitation of continuously distributed “cryptic” groups should not rely solely on conventional SDMs but should necessarily examine spatial population structure and gene flow to avoid taxonomic inflation.

The purpose of this study is to analyze the effects of surface defects (e.g., notches) and external environment conditions (e.g., operating temperature, the number of re-welding) on the static strength and fatigue of Al3003-O aluminum tubes used in the heat exchangers of air conditioners. In this study by the aluminum tubes to perform fatigue tests on the actual tube product and then the fatigue characteristics were evaluated using stress-life(S–N) curves. Regarding the welding conditions (maximum 600 °C and 10 s), the grain size grew and the hardness decreased as the number of re-welding increased. The effects of the operating temperatures on the fatigue life were examined at a room temperature of 25 °C and a heat exchanger operating temperature of 125 °C, resulting in the fatigue limit(57.19 MPa -> 49.02 MPa) at operating temperature was lower than room temperature. Furthermore, the fatigue limit of 29.37 MPa measured in the notched specimens (notch angle of 90 ˚, notch radius of 0.02 mm, and depth of 0.115 mm) was lower than that obtained from those without notches. The material constant (0.03) used in the Peterson equation was then computed from the fatigue notch factor (1.67 = 49.02/29.37) and the stress concentration factor (2.73) of the notched tube specimens was obtained from the structural analysis. This material constant can be used to predict a decrease in the fatigue limit over varying notch sizes in aluminum tubes (Al3003-O).