Fossils from the Middle Jurassic of China shed light on morphology of Choristopsychidae (Insecta, Mecoptera)

Choristopsychidae, established by Martynov in 1937 with a single isolated forewing, is a little known extinct family in Mecoptera. Since then, no new members of this enigmatic family have been described. Based on 23 well-preserved specimens with complete body and wings from the Middle Jurassic of northeastern China, we report one new genus and three new species of Choristopsychidae, two new species of the genus Choristopsyche Martynov, 1937: C. perfecta sp. n. and C. asticta sp. n.; one new species of Paristopsyche gen. n.: P. angelineae sp. n.; and re-describe C. tenuinervis Martynov, 1937. In addition, we emend the diagnoses of Choristopsychidae and Choristopsyche. Analyzing the forewing length/width ratios of representative species in Mecoptera, we confirm that choristopsychids have the lowest ratio of forewing length/width, meaning broadest forewings. These findings, the first fossil choristopsychids with wellpreserved body structure and the first record of Choristopsychidae in China, shed light on the morphology of these taxa and broaden their distribution from Tajikistan to China, while increasing the diversity of Mesozoic Mecoptera in China.Fil: Qiao, Xiao. Capital Normal University; ChinaFil: Shih, Chung Kun. Capital Normal University; ChinaFil: Petrulevicius, Julian Fernando. Universidad Nacional de la Plata. Facultad de Cs.naturales y Museo. Div.paleozoologia Invertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ren, Dong. Capital Normal University; Chin

Fossils from the Middle Jurassic of China shed light on morphology of Choristopsychidae (Insecta, Mecoptera)

Choristopsychidae, established by Martynov in 1937 with a single isolated forewing, is a little known extinct family in Mecoptera. Since then, no new members of this enigmatic family have been described. Based on 23 well-preserved specimens with complete body and wings from the Middle Jurassic of northeastern China, we report one new genus and three new species of Choristopsychidae, two new species of the genus Choristopsyche Martynov, 1937: C. perfecta sp. n. and C. asticta sp. n.; one new species of Paristopsyche gen. n.: P. angelineae sp. n.; and re-describe C. tenuinervis Martynov, 1937. In addition, we emend the diagnoses of Choristopsychidae and Choristopsyche. Analyzing the forewing length/width ratios of representative species in Mecoptera, we confirm that choristopsychids have the lowest ratio of forewing length/width, meaning broadest forewings. These findings, the first fossil choristopsychids with wellpreserved body structure and the first record of Choristopsychidae in China, shed light on the morphology of these taxa and broaden their distribution from Tajikistan to China, while increasing the diversity of Mesozoic Mecoptera in China.Facultad de Ciencias Naturales y Muse

Fossils from the Middle Jurassic of China shed light on morphology of Choristopsychidae (Insecta, Mecoptera)

Choristopsychidae, established by Martynov in 1937 with a single isolated forewing, is a little known extinct family in Mecoptera. Since then, no new members of this enigmatic family have been described. Based on 23 well-preserved specimens with complete body and wings from the Middle Jurassic of northeastern China, we report one new genus and three new species of Choristopsychidae, two new species of the genus Choristopsyche Martynov, 1937: C. perfecta sp. n. and C. asticta sp. n.; one new species of Paristopsyche gen. n.: P. angelineae sp. n.; and re-describe C. tenuinervis Martynov, 1937. In addition, we emend the diagnoses of Choristopsychidae and Choristopsyche. Analyzing the forewing length/width ratios of representative species in Mecoptera, we confirm that choristopsychids have the lowest ratio of forewing length/width, meaning broadest forewings. These findings, the first fossil choristopsychids with wellpreserved body structure and the first record of Choristopsychidae in China, shed light on the morphology of these taxa and broaden their distribution from Tajikistan to China, while increasing the diversity of Mesozoic Mecoptera in China.Facultad de Ciencias Naturales y Muse

Cell volume restriction by mercury chloride reduces M1-like inflammatory response of bone marrow-derived macrophages

Dysregulation of macrophages in the pro-inflammatory (M1) and anti-inflammatory (M2) sub-phenotypes is a crucial element in several inflammation-related diseases and injuries. We investigated the role of aquaporin (AQP) in macrophage polarization using AQP pan-inhibitor mercury chloride (HgCl2). Lipopolysaccharides (LPSs) induced the expression of AQP-1 and AQP-9 which increased the cell size of bone marrow-derived macrophages. The inhibition of AQPs by HgCl2 abolished cell size changes and significantly suppressed M1 polarization. HgCl2 significantly reduced the activation of the nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways and inhibited the production of IL-1β. HgCl2 attenuated LPS-induced activation of mitochondria and reactive oxygen species production and autophagy was promoted by HgCl2. The increase in the light chain three II/light chain three I ratio and the reduction in PTEN-induced kinase one expression suggests the recycling of damaged mitochondria and the restoration of mitochondrial activity by HgCl2. In summary, the present study demonstrates a possible mechanism of the AQP inhibitor HgCl2 in macrophage M1 polarization through the restriction of cell volume change, suppression of the p38 MAPK/NFκB pathway, and promotion of autophagy

The dimer interface of the SARS coronavirus nucleocapsid protein adapts a porcine respiratory and reproductive syndrome virus-like structure

AbstractWe have employed NMR to investigate the structure of SARS coronavirus nucleocapsid protein dimer. We found that the secondary structure of the dimerization domain consists of five α helices and a β-hairpin. The dimer interface consists of a continuous four-stranded β-sheet superposed by two long α helices, reminiscent of that found in the nucleocapsid protein of porcine respiratory and reproductive syndrome virus. Extensive hydrogen bond formation between the two hairpins and hydrophobic interactions between the β-sheet and the α helices render the interface highly stable. Sequence alignment suggests that other coronavirus may share the same structural topology

Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV)

BACKGROUND: Severe acute respiratory syndrome (SARS), a recent epidemic human disease, is caused by a novel coronavirus (SARS-CoV). First reported in Asia, SARS quickly spread worldwide through international travelling. As of July 2003, the World Health Organization reported a total of 8,437 people afflicted with SARS with a 9.6% mortality rate. Although immunopathological damages may account for the severity of respiratory distress, little is known about how the genome-wide gene expression of the host changes under the attack of SARS-CoV. RESULTS: Based on changes in gene expression of peripheral blood, we identified 52 signature genes that accurately discriminated acute SARS patients from non-SARS controls. While a general suppression of gene expression predominated in SARS-infected blood, several genes including those involved in innate immunity, such as defensins and eosinophil-derived neurotoxin, were upregulated. Instead of employing clustering methods, we ranked the severity of recovering SARS patients by generalized associate plots (GAP) according to the expression profiles of 52 signature genes. Through this method, we discovered a smooth transition pattern of severity from normal controls to acute SARS patients. The rank of SARS severity was significantly correlated with the recovery period (in days) and with the clinical pulmonary infection score. CONCLUSION: The use of the GAP approach has proved useful in analyzing the complexity and continuity of biological systems. The severity rank derived from the global expression profile of significantly regulated genes in patients may be useful for further elucidating the pathophysiology of their disease

Effects of Combinatorial Treatment with Pituitary Adenylate Cyclase Activating Peptide and Human Mesenchymal Stem Cells on Spinal Cord Tissue Repair

The aim of this study is to understand if human mesenchymal stem cells (hMSCs) and neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) have synergistic protective effect that promotes functional recovery in rats with severe spinal cord injury (SCI). To evaluate the effect of delayed combinatorial therapy of PACAP and hMSCs on spinal cord tissue repair, we used the immortalized hMSCs that retain their potential of neuronal differentiation under the stimulation of neurogenic factors and possess the properties for the production of several growth factors beneficial for neural cell survival. The results indicated that delayed treatment with PACAP and hMSCs at day 7 post SCI increased the remaining neuronal fibers in the injured spinal cord, leading to better locomotor functional recovery in SCI rats when compared to treatment only with PACAP or hMSCs. Western blotting also showed that the levels of antioxidant enzymes, Mn-superoxide dismutase (MnSOD) and peroxiredoxin-1/6 (Prx-1 and Prx-6), were increased at the lesion center 1 week after the delayed treatment with the combinatorial therapy when compared to that observed in the vehicle-treated control. Furthermore, in vitro studies showed that co-culture with hMSCs in the presence of PACAP not only increased a subpopulation of microglia expressing galectin-3, but also enhanced the ability of astrocytes to uptake extracellular glutamate. In summary, our in vivo and in vitro studies reveal that delayed transplantation of hMSCs combined with PACAP provides trophic molecules to promote neuronal cell survival, which also foster beneficial microenvironment for endogenous glia to increase their neuroprotective effect on the repair of injured spinal cord tissue

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie