Knockdown of EIF2AK2-OAS1 axis reduces ATP production inducing AMPK phosphorylation to inhibit the malignant behavior of gastric cancer cells.

Energy metabolism has always been a hot topic in cancer progression and targeted therapy, and exploring the role of genes in energy metabolic pathways in cancer cells has become key to address this issue. Eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) plays regulatory roles in cancer and disorders of energy metabolism. Indeed, the role of EIF2AK2 in energy metabolism has been underestimated. The aim of this study is to reveal the expression specificity of EIF2AK2 in gastric cancer (GC) progression and metastasis, and to demonstrate the role of EIF2AK2 in energy metabolism, cytoskeleton, proliferation, death and metastasis pathways in GC cells. Mechanistically, EIF2AK2 overexpression promoted cytoskeleton remodeling and ATP production, mediated cell proliferation and metastasis, upregulated OAS1 expression, decreases p-AMPK expression and inhibited apoptosis in GC cells. Conversely, knockdown of EIF2AK2 resulted in the opposite effect. However, overexpression of OAS1 mediated the upregulation of mitochondrial membrane potential and promoted ATP production and NAD+/NADH ratio, but knockdown of OAS1 inhibited the above effects. In addition, knockdown of OAS1 had no effect on EIF2AK2 expression, but inhibited AMPK and upregulated p-AMPK expression. In conclusion, our study identified EIF2AK2 and OAS1 as previously undescribed regulators of energy metabolism in GC cells. We hypothesized that EIF2AK2-OAS1 axis may regulate energy metabolism and inhibit cellular malignant behavior in cancer cells by affecting ATP production to induce AMPK phosphorylation, suggesting EIF2AK2 as a potential therapeutic target for cancer cell progression.

Knock-down of IGFBP2 ameliorates lung fibrosis and inflammation in rats with severe pneumonia through STAT3 pathway.

OBJECTIVE: To observe the mechanism of IGFBP2 knock-down in improving lung fibrosis and inflammation through STAT3 pathway in rats with severe pneumonia. MATERIALS AND METHODS: First, SP rat model was established. Then rats were divided into the Control group, the SP group, the SP + Lv-vector shRNA group, the SP + Lv-IGFBP2 shRNA group, the SP + Lv-vector group, and the SP + Lv-IGFBP2 group. The mRNA and protein levels of IGFBP2, NOS, CD206 and Arg 1 were detected by RT-qPCR and Western blot. IHC was used to check the positive expression of IGFBP2 and MCP1. A fully automated blood gas analyzer was used to detected PaCO2, CO2 content, PaO2 and SaO2. HE and Masson staining were performed to observe the lung tissue injury and collagen deposition of rats in each group. ELISA assays were used to calculate the levels of inflammatory factors IL-1ß, IL-6, TNF-α, IL-4, and IL-10. Flow cytometry was conducted to acquire the ratio of M1-type AMs and M2-type AMs. RESULTS: Compared with the Control group, IGFBP2, iNOS, CD206, and Arg1 mRNA and protein expression levels, IGFBP2 and MCP1 positive expressions, PaCO2, p-STAT3/STAT3, p-JAK2/JAK2, IL-1ß, IL-6, and TNF-α levels, the number of AMs and neutrophils, the proportion of M1 type AMs and the expressions of α-SMA, Collagen-I, Collagen III, and Fibronectin were significantly increased in SP rats (p < 0.05), while PaCO2, CO2, and SaO2, IL-4 and IL-10 levels, and the proportion of M2 type AMs decreased (p < 0.05). However, the knockdown of IGFBP2 reversed the above index trends. CONCLUSION: Knock-down of IGFBP2 ameliorated lung injury in SP rats, inhibited inflammation and pulmonary fibrosis, and promoted M2-type transformation of AMs by activating the STAT3 pathway.

Factors Associated with First-Time HIV Testing Among MSM via Secondary Distribution of HIV Self-test Kits in Zhuhai, China.

HIV self-testing (HIVST) is an effective method to expand HIV testing coverage worldwide. We analyze the results of HIVST and sexual behaviors of first-time testers among Men who have sex with men (MSM) who participated in a secondary distribution of HIVST kits. A total of 589 participants were recruited, including 173 first-time testers and 416 non-first-time testers. The first-time testers were mainly of Han ethnicity (aOR 1.88, 95% CI 1.10, 3.24), more likely to be HIV positive (aOR 7.18, 95% CI 2.37, 21.72), and had higher income (aOR 2.01, 95% CI 1.10, 3.69). Both groups were less likely to have anal sex with male partners (χ2: 146.24, P < 0.01), (χ2: 582.72, P < 0.01) or have sex with female partners (χ2: 19.01, P < 0.01), (χ2: 35.74, P < 0.01) after HIVST. We should expand HIVST among MSM and other key populations to identify first-time testers.

An overlooked subset of Cx3cr1wt/wt microglia in the Cx3cr1CreER-Eyfp/wt mouse has a repopulation advantage over Cx3cr1CreER-Eyfp/wt microglia following microglial depletion.

BACKGROUND: Fluorescent reporter labeling and promoter-driven Cre-recombinant technologies have facilitated cellular investigations of physiological and pathological processes, including the widespread use of the Cx3cr1CreER-Eyfp/wt mouse strain for studies of microglia. METHODS: Immunohistochemistry, Flow Cytometry, RNA sequencing and whole-genome sequencing were used to identify the subpopulation of microglia in Cx3cr1CreER-Eyfp/wt mouse brains. Genetically mediated microglia depletion using Cx3cr1CreER-Eyfp/wtRosa26DTA/wt mice and CSF1 receptor inhibitor PLX3397 were used to deplete microglia. Primary microglia proliferation and migration assay were used for in vitro studies. RESULTS: We unexpectedly identified a subpopulation of microglia devoid of genetic modification, exhibiting higher Cx3cr1 and CX3CR1 expression than Cx3cr1CreER-Eyfp/wtCre+Eyfp+ microglia in Cx3cr1CreER-Eyfp/wt mouse brains, thus termed Cx3cr1highCre-Eyfp- microglia. This subpopulation constituted less than 1% of all microglia under homeostatic conditions, but after Cre-driven DTA-mediated microglial depletion, Cx3cr1highCre-Eyfp- microglia escaped depletion and proliferated extensively, eventually occupying one-third of the total microglial pool. We further demonstrated that the Cx3cr1highCre-Eyfp- microglia had lost their genetic heterozygosity and become homozygous for wild-type Cx3cr1. Therefore, Cx3cr1highCre-Eyfp- microglia are Cx3cr1wt/wtCre-Eyfp-. Finally, we demonstrated that CX3CL1-CX3CR1 signaling regulates microglial repopulation both in vivo and in vitro. CONCLUSIONS: Our results raise a cautionary note regarding the use of Cx3cr1CreER-Eyfp/wt mouse strains, particularly when interpreting the results of fate mapping, and microglial depletion and repopulation studies.

Concentrations, leachability, and health risks of mercury in green tea from major production areas in China.

Green tea has many health benefits and is the most consumed type in China. However, the heavy metals and contaminants in tea can also pose a great risk to human health. In this study, mercury (Hg) concentration in green tea collected from 11 provinces in China was examined. The leaching characteristics of Hg during brewing and the associated exposure to drinkers were also evaluated. Results indicated a low potential of Hg accumulation in green tea. The Hg content of green tea from Wanshan District, Guizhou Province-which has the largest Hg mine in China and is severely contaminated by Hg-could be limited by controlling the harvest time of tea leaves. The average Hg content of green tea from 43 tea production sites in China was only 6.3 ± 6.4 µg/kg dry weight. The brewing experiments of green tea showed that the leaching ratio of Hg was 22.61 ± 7.58% for 40 min of a single brew, and increased to 32.83 ± 12.37% after four rounds (3 min/ round) of brewing. The leaching of Hg from tea leaves was significantly affected by leaching time, temperature, and solid-liquid ratio but not by water hardness. The risk of Hg exposure from green tea intake was found to be very low, with an average hazard quotient (HQ) value of only 1.82 ± 1.85% for a single brew in 40 min and 2.64 ± 2.68% after four rounds of brewing. However, in some highly contaminated areas, with HQ values as high as 43.12 ± 2.41%, green tea intake may still pose a high risk of Hg exposure, and this risk should not be ignored.

Myoelectric characteristics of tensor palatini and collapsibility of upper airway in OSA patients with different phenotypes under DISE.

OBJECTIVE: This study aims to evaluate the combination of myoelectric characteristics of tensor palatini muscle (TP) and collapsibility of upper airway in obstructive sleep apnea (OSA) patients with different external phenotypes of collapse pattern at velum level under drug-induced sleep endoscopy (DISE). STUDY DESIGN: Case series with planned data collection. SETTING: Operation room. SUBJECTS AND METHODS: 36 mainly collapse pattern at velum level OSA subjects underwent DISE with synchronous tensor palatini electromyograms (TP EMG), and polysomnography (ALICE 6). According to the phenotype of collapse pattern at velum level in DISE, the subjects were divided into group 1 (concentric collapse), group 2 (anteroposterior collapse), and group 3 (lateral collapse). Each group consisted of 13, 14, and 9 subjects, respectively, and was observed the electromyographic indexes at awake, sleep onset, during apnea and the third respiratory cycle after apnea. The active and passive upper airway critical closing pressure (Pcrit) of each group were measured at the same time, and the difference of neuromuscular response between different groups was evaluated. RESULTS: In tonic TPEMG, group 1 showed the highest value during awake and sleep onset, while group 2 was the highest during apnea and after apnea. In peak TPEMG, group 1 showed the highest value during awake. Group 2 showed the highest value during other states. In passive Pcrit and D value (difference between passive Pcrit and active Pcrit), group 2 was the highest, while group 1 was the highest in active Pcrit. Difference was statistically significant. CONCLUSIONS: Under different states of awake, sleep onset, apnea and after apnea, the response force of tensor palatini muscle of OSA subjects with different phenotypes under DISE was different. Group 1 showed the highest EMG values only when awake and sleep onset, and it was most prone to collapse. Group 2 had the highest anatomical load (passive Pcrit) and the highest neuromuscular compensatory effect (D value).

Machine learning for cell classification and neighborhood analysis in glioma tissue.

Multiplexed and spatially resolved single-cell analyses that intend to study tissue heterogeneity and cell organization invariably face as a first step the challenge of cell classification. Accuracy and reproducibility are important for the downstream process of counting cells, quantifying cell-cell interactions, and extracting information on disease-specific localized cell niches. Novel staining techniques make it possible to visualize and quantify large numbers of cell-specific molecular markers in parallel. However, due to variations in sample handling and artifacts from staining and scanning, cells of the same type may present different marker profiles both within and across samples. We address multiplexed immunofluorescence data from tissue microarrays of low-grade gliomas and present a methodology using two different machine learning architectures and features insensitive to illumination to perform cell classification. The fully automated cell classification provides a measure of confidence for the decision and requires a comparably small annotated data set for training, which can be created using freely available tools. Using the proposed method, we reached an accuracy of 83.1% on cell classification without the need for standardization of samples. Using our confidence measure, cells with low-confidence classifications could be excluded, pushing the classification accuracy to 94.5%. Next, we used the cell classification results to search for cell niches with an unsupervised learning approach based on graph neural networks. We show that the approach can re-detect specialized tissue niches in previously published data, and that our proposed cell classification leads to niche definitions that may be relevant for sub-groups of glioma, if applied to larger data sets.

lncRNA AABR07005593.1 potentiates PM2.5-induced interleukin-6 expression by targeting MCCC1.

BACKGROUND: Fine particle pollution, specifically pollution by fine particulate matter (PM2.5), remains a significant concern in developing countries and plays an important role in the development and progression of respiratory diseases. Increasing evidences have demonstrated that long non-coding RNAs (lncRNAs) may act as vital molecules by binding to specific RNA-binding protein (RBP); however, their relationship with PM2.5 pollution is largely unexplored. OBJECTIVE: We investigated the association between lncRNA and respiratory system inflammation caused by PM2.5. METHODS: PM2.5 components were detected by gas chromatography-mass spectrometry (GC-MS), inductively coupled plasma-mass spectrometry (ICP-MS), and ionic chromatography. We established an inflammation model of PM2.5-induced toxicity in vivo (male and female SD rats, 0, 25, 50 and 100 mg/k PM2.5, 1, 7 and 14 days, single non-invasive tracheal instillation) and in vitro (rat alveolar macrophage cell line (NR8383), 0, 50, 100, 200, 400 µM PM2.5 for 24, 48, and 72 h). lncRNA high-throughput sequencing (lncRNA-seq) was used to investigate lncRNA profiles in PM2.5-treated NR8383 cells, and RNA interference (RNAi) was applied to explore the function of the target lncRNA. The mechanisms associated with specific lncRNAs were explored using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS) and western blot. RESULTS: PM2.5-treated NR8383 cells and SD rats exhibited respiratory inflammation. lncRNA AABR07005593.1 was a pro-inflammatory factor that regulated IL-6 levels. Mechanistically, ChIRP-MS and western blot analyses revealed that highly expressed lncRNA AABR07005593.1 interacted with MCCC1 to involve in the activation of NF-κB pathway, and ultimately promoted the expression of IL-6. CONCLUSION: This study demonstrated that PM2.5 induced inflammation in vivo and in vitro. Furthermore, lncRNA AABR07005593.1 bound to MCCC1 to potentiated IL-6 expression. Therefore, lncRNA AABR07005593.1 may act as a potential biomarker for PM2.5 inflammation.

Predicting outcome of velopharyngeal surgery in drug-induced sleep endoscopy by traction velum.

BACKGROUND: Outcomes of surgical management of obstructive sleep apnea-hypopnea syndrome (OSAHS) can be difficult to predict preoperatively. AIMS/OBJECTIVES: To study the effect of applying traction to the velum during drug-induced sleep endoscopy (DISE) in OSAHS patients, and to describe the use of traction velum in predicting surgical success. MATERIALS AND METHODS: 41 adult surgical patients with OSA (Friedman tongue position II and III) were evaluated by DISE. All patients subsequently underwent velopharyngeal surgery in the form of uvulopalatopharyngoplasty with tonsillectomy plus barbed reposition pharyngoplasty. RESULTS: Surgical responders (n = 26, 63.4%) and nonresponders (n = 15, 36.6%) demonstrated no significant differences with regard to preoperative AHI, age, sex, body mass index, and mean/lowest O2 saturation. Responders had a marked decrease in desaturation events (2.96 vs 0.03, p < 0.001) and percentage change in number of desaturation events before/after traction velum (56.7 vs 4.5, p < 0.001). Regression analysis revealed that reduction in mean desaturation events, with traction velum, by a percentage > 26.8% (odds ratio [OR] 1.046; 95% confidence interval [CI] 1.018-1.075; p = 0.001) was the only independent predictor of surgery success. CONCLUSIONS AND SIGNIFICANCE: OSAHS patients' velopharyngeal surgical outcome can be predicted by measuring the percentage change in the number of oxygen desaturation events before and after traction velum in DISE.

Okra-Like Fe7 S8 /C@ZnS/N-C@C with Core-Double-Shelled Structures as Robust and High-Rate Sodium Anode.

Core-multishelled structures with controlled chemical composition have attracted great interest due to their fascinating electrochemical performance. Herein, a metal-organic framework (MOF)-on-MOF self-templated strategy is used to fabricate okra-like bimetal sulfide (Fe7 S8 /C@ZnS/N-C@C) with core-double-shelled structure, in which Fe7 S8 /C is distributed in the cores, and ZnS is embedded in one of the layers. The MOF-on-MOF precursor with an MIL-53 core, a ZIF-8 shell, and a resorcinol-formaldehyde (RF) layer (MIL-53@ZIF-8@RF) is prepared through a layer-by-layer assembly method. After calcination with sulfur powder, the resultant structure has a hierarchical carbon matrix, abundant internal interface, and tiered active material distribution. It provides fast sodium-ion reaction kinetics, a superior pseudocapacitance contribution, good resistance of volume changes, and stepwise sodiation/desodiation reaction mechanism. As an anode material for sodium-ion batteries, the electrochemical performance of Fe7 S8 /C@ZnS/N-C@C is superior to that of Fe7 S8 /C@ZnS/N-C, Fe7 S8 /C, or ZnS/N-C. It delivers a high and stable capacity of 364.7 mAh g-1 at current density of 5.0 A g-1 with 10 000 cycles, and registers only 0.00135% capacity decay per cycle. This MOF-on-MOF self-templated strategy may provide a method to construct core-multishelled structures with controlled component distributions for the energy conversion and storage.

The use of visceral adiposity variables in the prediction of obstructive sleep apnea: evidence from a large cross-sectional study.

PURPOSE: The purposes of this study were to evaluate the ability of visceral adiposity variables [the lipid accumulation product (LAP), the visceral adiposity index (VAI), and the triglyceride-glucose index (TyG)] in predicting obstructive sleep apnea hypopnea syndrome (OSAHS) and to determine the effect of sex on the prediction. METHODS: A total of 5539 subjects admitted to the sleep center for suspected OSAHS were consecutively recruited from 2007 to 2016. Anthropometric measurements, biological indicators, Epworth sleepiness scale score, and polysomnographic variables were collected. Prediction models for diagnosing OSAHS were established in the test group by logistic regression and verified in the validation group by receiver operating characteristic (ROC) curves. RESULTS: A total of 4703 patients were included in total. LAP and TyG were of moderate diagnostic accuracy for OSAHS, with the diagnostic efficiency differing between men and women. A prediction model was developed that combined visceral adiposity indicators with waist circumstance and the lowest SpO2. The sensitivity of those indicators were both 84% in men and women, respectively, and their specificity were both 90%. In addition, the model was confirmed in the validation group with a sensitivity and specificity of 83% and 85% in men and 85% and 84% in women. CONCLUSIONS: LAP and TyG were of moderate efficiency in screening for OSAHS. The prediction model provides a simple and practical screening tool for OSAHS.

PM2.5-inducible long non-coding RNA (NONHSAT247851.1) is a positive regulator of inflammation through its interaction with raf-1 in HUVECs.

Several studies have demonstrated that PM2.5 inhalation is associated with an increased risk of cerebrovascular disease (CVD), in which inflammation plays an important role. The mechanisms of this disease are not fully understood to date. Long non-coding RNAs (lncRNAs) are involved in many pathophysiological processes, such as immune responses; however, their functions associated with inflammation are largely unexplored. High-throughput sequencing assay and obtained numerous lncRNAs that altered the expression in response to PM2.5 treatment in HUVECs. NONHSAT247851.1 was also identified, which was significantly up-regulated to control the expression of immune response genes. Mechanistically, the results indicated that NONHSAT247851.1 knockdown reduced the expression of IL1ß. In study, we investigated NONHSAT247851.1 as a promoter in regulating immune response genes via binding with raf-1 to regulate the phosphorylation level of p65 protein in HUVECs. The data collected suggests that NONHSAT247851.1 regulates inflammation via interaction with raf-1 to control the inflammatory expression in PM2.5 exposure.

Optimum feeding frequency of juvenile largemouth bass (Micropterus salmoides) reared in in-pond raceway recirculating culture system.

This study was conducted to determine the effects of feeding frequency on the growth, serum biochemical parameters, antioxidant status and hepatic growth hormone (GH), insulin-like growth factor I (IGF-I), lipoprotein lipase (LPL) and hepatic lipase (HL) gene expression levels of juvenile largemouth bass (Micropterus salmoides) reared in an in-pond raceway recirculating culture system (IPRS). Fish (initial body weight 5.0 ± 0.4 g) were hand-fed with a commercial diet under one of three different feeding frequency treatments (2, 3 or 4 meals/day) for 120 days. The results indicated that no significant differences were observed in the final body weight, weight gain and specific growth rate of fish fed different feeding frequencies on 30 days and 60 days (P > 0.05). Fish fed 2 times/day had higher growth than that fed 4 times/day on 90 days but had higher growth than those fed 3 and 4 times/day on 120 days. No significant differences were found in serum alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) activities, total protein (TP), lysozyme and triglyceride (TG) content, hepatic total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX) activities and malondialdehyde (MDA) content among fish fed different feeding frequency (P > 0.05). Serum glucose (Glu) content and catalase (CAT) activity decreased, while total cholesterol (TC) content increased with increasing feeding frequency. Fish fed 2 times/day had higher hepatic total superoxide dismutase (T-SOD) than that fed 4 times/day on 60 days, 90 days and 120 days (P < 0.05). Fish fed 2 times/day had higher IGF-1 gene mRNA expression on 30 days, 60 days and 120 days (P < 0.05), while no significant difference on 90 days. No significant difference was found in GH gene mRNA expression on 30 days and 60 days, while fish fed 4 times/day had lower values than that fed 2 times/day on 90 days and 120 days (P < 0.05). Fish fed 2 times/day had significantly higher LPL mRNA expression level than that fed 4 times/day on 60 days and 90 days and had significantly higher HL mRNA expression level on 60 days, 90 days and 120 days (P < 0.05). Based on growth, physiology, hepatic gene expression levels, labour costs and intensity, the optimal feeding frequency of largemouth bass (average body weight 5.0 ± 0.4 g) reared in IPRS is 2 times/day. These data are very necessary for the optimizing of culture conditions and feeding management strategy in IPRS culture operations.

Atmospheric Initial Nucleation Containing Carboxylic Acids.

The possible involvement of chemical components in atmospheric new particle formation has received increased attention in recent years. However, the deep understanding of the clusters formed between atmospheric gas-phase organic acids is incomplete. In this work, the chemical and physical properties of the cluster formed between three organic acids [glyoxylic acid (GA), oxalic acid (OA), and pyruvic acid (PA)] with common atmospheric nucleation precursors [methyl hydrogen sulfate (MHS), methanesulfonic acid (MSA), and hydroxymethanesulfonic acid (HMSA)] have been investigated with density functional theory and ab initio coupled-cluster singles and doubles with perturbative triples (CCSD(T)) theory. Six- to nine-membered cyclic ring structures are mainly arranged via two classes of intermolecular hydrogen bonds: SO-H···O and CO-H···O. The GA/OA/PA-MHS/MSA/HMSA complexes with the nine- and eight-membered cyclic ring structures are thermodynamically more stable than the others. Large red shifts of the OH-stretching vibrational frequencies of both SO-H···O (354-794 cm-1) and CO-H···O (320-481 cm-1) are obtained with regard to the isolated gas monomers. Atoms in molecules topological analysis reveals that the Laplacian of the charge density of the bimolecular interactions in the GA/OA/PA-MHS/MSA/HMSA complexes is higher than the upper value of the hydrogen bond criteria. The thermodynamic data, dipole moments, and atmospheric mixing ratios indicate that the MHS- and MSA-containing complexes possibly take part in atmospheric new particle formation. Additionally, the environmental factors, such as temperature and pressure, are also important in atmospheric particle nucleation, and the gas-mixing ratios of the clusters at 12 km are much enhanced by 18-44 times with respect to the ones at the ground level. This study suggests that small cluster calculations may be helpful in simulating atmospheric new particle formation.

Gene Selection and Evolutionary Modeling Affect Phylogenomic Inference of Neuropterida Based on Transcriptome Data.

Neuropterida is a super order of Holometabola that consists of the orders Megaloptera (dobsonflies, fishflies, and alderflies), Neuroptera (lacewings) and Raphidioptera (snakeflies). Several proposed higher-level relationships within Neuropterida, such as the relationships between the orders or between the families, have been extensively debated. To further understand the evolutionary history of Neuropterida, we conducted phylogenomic analyses of all 13 published transcriptomes of the neuropterid species, as well as of a new transcriptome of the fishfly species Ctenochauliodes similis of Liu and Yang, 2006 (Megaloptera: Corydalidae: Chauliodinae) that we sequenced. Our phylogenomic data matrix contained 1392 ortholog genes from 22 holometabolan species representing six families from Neuroptera, two families from Raphidioptera, and two families from Megaloptera as the ingroup taxa, and nine orders of Holometabola as outgroups. Phylogenetic reconstruction was performed using both concatenation and coalescent-based approaches under a site-homogeneous model as well as under a site-heterogeneous model. Surprisingly, analyses using the site-homogeneous model strongly supported a paraphyletic Neuroptera, with Coniopterygidae assigned as the sister group of all other Neuropterida. In contrast, analyses using the site-heterogeneous model recovered Neuroptera as monophyletic. The monophyly of Neuroptera was also recovered in concatenation and coalescent-based analyses using genes with stronger phylogenetic signals [i.e., higher average bootstrap support (ABS) values and higher relative tree certainty including all conflicting bipartitions (RTCA) values] under the site-homogeneous model. The present study illustrated how both data selection and model selection influence phylogenomic analyses of large-scale data matrices comprehensively.

Mitochondrial Genomes Provide Insights into the Phylogeny of Culicomorpha (Insecta: Diptera).

Culicomorpha is a monophyletic group containing most bloodsucking lower dipterans, including many important vectors of pathogens. However, the higher-level phylogenetic relationships within Culicomorpha are largely unresolved, with multiple competing hypotheses based on molecular sequence data. Here we sequenced four nearly complete mitochondrial (mt) genomes representing four culicomorph families, and combined these new data with published mt genomes to reconstruct the phylogenetic relationships of all eight extant culicomorph families. We estimated phylogenies using four datasets and three methods. We also used four-cluster likelihood mapping to study potential incongruent topologies supported by the different datasets and phylogenetic questions generated by the previous studies. The results showed that a clade containing Ceratopogonidae, Thaumaleidae and Simuliidae was the sister group to all other Culicomorpha; in another clade, the Dixidae was basal to the remaining four families; Chaoboridae, Corethrellidae and Culicidae formed a monophyletic group and the Chironomidae was the sister group to this clade; Culicidae and Corethrellidae were sister groups in all trees. Our study provides novel mt genome data in Culicomorpha for three new family representatives, and the resulting mt phylogenomic analysis helps to resolve the phylogeny and taxonomy of Culicomorpha.

Phosphotyrosine signalling and the origin of animal multicellularity.

The evolution of multicellular animals (i.e. metazoans) from a unicellular ancestor is one of the most important yet least understood evolutionary transitions. Historically, given its indispensable functions in intercellular communication and exclusive presence in metazoans, phosphotyrosine (pTyr) signalling was considered a metazoan-specific evolutionary innovation that might have contributed to the origin of metazoan multicellularity. However, recent studies have led to a new understanding of pTyr signalling evolution and its role in the metazoan origin. Sequence analyses have unravelled a much earlier emergence of pTyr signalling in eukaryotic evolution. Even so, several distinct properties of holozoan pTyr signalling may have paved the way for a hypothesized functional transition of pTyr signalling at the multicellular origin, from environmental sensing to intercellular communication, and for it to evolve as a powerful intercellular signalling system for multicellularity. Biochemical analyses of premetazoan pTyr signalling components have further revealed the premetazoan origin of many key features of metazoan pTyr signalling, and the metazoan establishment of others, including the Csk-mediated negative regulation of the activity of Src, a conserved tyrosine kinase in the Holozoa. Finally, potential future directions are discussed, with a stress on the biological functions of premetazoan pTyr signalling via newly developed gene manipulation tools in non-animal holozoans.

Mitochondrial phylogenomics illuminates the evolutionary history of Neuropterida.

Neuroptera (lacewings) and allied orders Megaloptera (dobsonflies, alderflies) and Raphidioptera (snakeflies) are predatory insects and together make up the clade Neuropterida. The higher-level relationships within Neuropterida have historically been widely disputed with multiple competing hypotheses. Moreover, the evolution of important biological innovations among various Neuropterida families, such as the origin, timing and direction of transitions between aquatic and terrestrial habitats of larvae, remains poorly understood. To investigate the origin and diversification of lacewings and their allies, we undertook phylogenetic analyses of mitochondrial genomes of all families of Neuropterida using Bayesian inference, maximum likelihood and maximum parsimony methods. We present a robust, fully resolved phylogeny and divergence time estimation for Neuropterida with strong statistical support for almost all nodes. Mitochondrial sequence data are typified by significant compositional heterogeneity across lineages, and parsimony and models assuming homogeneous rates did not recover Neuroptera as monophyletic. Only a model accounting for compositional heterogeneity (i.e. CAT-GTR) recovered all orders of Neuropterida as monophyletic. Significant findings of the mitogenomic phylogeny include recovering Raphidioptera as sister to Megaloptera plus Neuroptera. The sister family of all other lacewings are the dusty-wings (Coniopterygidae), rather than Nevrorthidae. Nevrorthidae are instead returned to their traditional position as the sister group of the spongilla-flies (Sisyridae) and closely related to Osmylidae. Our divergence time analysis indicates that the Mesozoic was indeed a 'golden age' for lacewings, with most families of Neuropterida diverging during the Triassic and Jurassic and all extant families present by the Early Cretaceous. Based on ancestral character state reconstructions of larval habitat we evaluate competing hypotheses regarding the life style of early neuropteridan larvae as either aquatic or terrestrial.

Patients with Obstructive Sleep Apnea Display Decreased Flow-Mediated Dilatation: Evidence from a Meta-Analysis.

BACKGROUND Endothelial dysfunction, which can be measured by flow-mediated dilatation (FMD), is an early clinical marker of atherosclerosis, which is considered to be the main cause of the observed cardiovascular complications in obstructive sleep apnea (OSA) patients. The association between OSA and endothelial dysfunction has been reported in a number of studies; however, the findings are not entirely consistent. Our aim was to meta-analytically synthesize the existing evidence to explore the association between OSA and endothelial dysfunction. MATERIAL AND METHODS Data from PubMed, EMBASE, the Cochrane library, and Google Scholar for all trials that investigated the relationship between endothelial dysfunction and OSA were systematically reviewed. The minimum inclusion criteria for the studies were reporting of the Apnea-Hypopnea Index (AHI) and FMD measurements (as an indicator of endothelial dysfunction) for both OSA and control groups. Data from case-control studies that met the inclusion criteria were extracted. RESULTS Twenty-eight studies comprising a total of 1496 OSA patients and 1135 controls were included in the meta-analysis. A random-effects model was used. The weighted mean difference in the FMD measurements was -3.07 and the 95% confidence interval was -3.71 to -2.43 (P<0.01). Meta-regression analysis showed that age, sex, body mass index (BMI), blood pressure, glucose, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol did not explain the heterogeneity. CONCLUSIONS This meta-analysis showed that patients with OSA have decreased FMD, which may contribute to the development of atherosclerosis.