Carpenterhaagensen2278

© 2020 Wiley Periodicals, Inc.Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM). FLNC variants are now among the more prevalent causes of genetic DCM. FLNC-associated DCM is associated with a malignant clinical course and a high risk of sudden cardiac death. The clinical spectrum of FLNC suggests different pathomechanisms related to variant types and their location in the gene. The appropriate functioning of FLNC is crucial for structural integrity and cell signaling of the sarcomere. The secondary protein structure of FLNC is critical to ensure this function. Truncating variants with subsequent haploinsufficiency are associated with DCM and cardiac arrhythmias. Interference with the dimerization and folding of the protein leads to aggregate formation detrimental for muscle function, as found in HCM and MFM. Variants associated with HCM are predominantly missense variants, which cluster in the ROD2 domain. This domain is important for binding to the sarcomere and to ensure appropriate cell signaling. We here review FLNC genotype-phenotype correlations based on available evidence. © 2020 The Authors. Santacruzamate A clinical trial Human Mutation published by Wiley Periodicals, Inc.Mutations in the human TMEM16E/ANO5 gene are causative for gnathodiaphyseal dysplasia (GDD), a rare bone malformation and fragility disorder, and for two types of muscular dystrophy (MD). Previous studies have demonstrated that TMEM16E/ANO5 is a Ca2+ -activated phospholipid scramblase and that the mutation c.1538C>T (p.Thr513Ile) causing GDD leads to a gain-of-function phenotype. Here, using established HEK293-based functional assays, we investigated the effects of MD-related and further GDD-related amino acid exchanges on TMEM16E/ANO5 function in the same expression system. These experiments also revealed that the gradual changes in HEK293 cell morphology observed upon expression of TMEM16E/ANO5GDD mutants are a consequence of aberrant protein activity. Our results collectively demonstrate that, on the level of protein function, MD mutations are associated to loss-of-function and GDD mutations to gain-of-function phenotypes, confirming conjectures made on the basis of inheritance modes. © 2020 Wiley Periodicals, Inc.Germline PTPN11 mutations cause Noonan syndrome (NS), the most common disorder among RASopathies. PTPN11 encodes SHP2, a protein tyrosine-phosphatase controlling signaling through the RAS-MAPK and PI3K-AKT pathways. Generally, NS-causing PTPN11 mutations are missense changes destabilizing the inactive conformation of the protein or enhancing its binding to signaling partners. Here, we report on two PTPN11 variants resulting in the deletion or duplication of one of three adjacent glutamine residues (Gln255 -to-Gln257 ). While p.(Gln257dup) caused a typical NS phenotype in carriers of a first family, p.(Gln257del) had incomplete penetrance in a second family. Missense mutations involving Gln256 had previously been reported in NS. This poly-glutamine stretch is located on helix B of the PTP domain, a region involved in stabilizing SHP2 in its autoinhibited state. Molecular dynamics simulations predicted that changes affecting this motif perturb the SHP2's catalytically inactive conformation and/or substrate recognition. Biochemical data showed that duplication and deletion of Gln257 variably enhance SHP2's catalytic activity, while missense changes involving Gln256 affect substrate specificity. Expression of mutants in HEK293T cells documented their activating role on MAPK signaling, uncoupling catalytic activity and modulation of intracellular signaling. These findings further document the relevance of helix B in the regulation of SHP2's function. © 2020 Wiley Periodicals, Inc.INTRODUCTION The outcome of ovarian cancer patients is highly dependent on the success of primary debulking surgery in terms of postoperative residual disease. This study critically evaluates the clinical impact of preoperative radiologic assessment of the cardiophrenic lymph node (CPLN) status in advanced ovarian cancer. MATERIAL AND METHODS Baseline CT scans of 178 stage III and IV ovarian cancer patients were retrospectively reviewed by two independent radiologists. CPLN enlargement defined at a short-axis ≥5 mm was evaluated for its prognostic value and predictive power of upper abdominal tumor involvement and the chance of complete intra-abdominal tumor resection at primary debulking surgery. Only patients without surgically removed CPLN were eligible for this study. RESULTS Enlarged CPLNs were detected in 50% of patients and correlated with radiologically suspicious (P = .028) and histologically confirmed (P = .001) paraaortic lymph node metastases. CPLNs ≥ 5 mm were associated with high CA-125 levels agy suggests extra-abdominal disease, we consistently demonstrated that patients nonetheless benefit from complete intra-abdominal tumor resection. 2020 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic.Limia islai, a new species of livebearing fish, is described from Lake Miragoane in south-western Haiti on Hispaniola. The new species has a conspicuous barred pattern consisting of several (4-12) black bars along the body, ray 4p serrae of the gonopodium in males with 10 segments and origin of dorsal fin in females slightly behind the origin of the anal fin. Although the new species colour pattern is similar to that of the humpbacked limia Limia nigrofasciata Regan 1913, L. islai sp. nov. has exclusive morphological features, such as slender body, lack of hump anterior to dorsal fin in males and presence of specific features in the gonopodial suspensory, which allow an unambiguous diagnosis from L. nigrofasciata. L. islai further differs from L. nigrofasciata in reproductive behaviour since L. islai males rely on sneak copulations and gonopodial thrusting, whereas L. nigrofasciata display an elaborate courtship behaviour. The new species is also genetically distinct in both nuclear (Rh, Myh6) and mitochondrial (12S, ND2, D-loop, Cytb) genes from other species in the genus showing reciprocal monophyly. The description of this new Limia species from Lake Miragoane confirms this lake as an important centre of endemism for the genus, with a total of eight endemic species described so far. © 2020 The Fisheries Society of the British Isles.Nine strains of five species of entomopathogenic hypocrealean fungi were tested against adults of the Asian longhorned beetle, Anoplophora glabripennis (Motschulsky). These strains have been developed as commercial biopesticide products in the United States, Brazil, South Korea, or the European Union (EU). Metarhizium anisopliae (Metschnikoff) (Hypocreales Clavicipitaceae) ESALQ E-9 and Metarhizium brunneum (Petch) F52 (formerly M. anisopliae F52) (Hypocreales Clavicipitaceae) killed 100% of treated beetles with the shortest survival times. Virulence differed among the five strains of Beauveria bassiana (Balsamo) (Hypocreales Cordycipitaceae) tested, ranging from 0 to 77.3% mortality within 28 d. Two Isaria fumosorosea (Wize, 1904) (Hypocreales Cordycipitaceae) (formerly Paecilomyces fumosoroseus) strains and the Lecanicillium muscarium (Petch) Zare & Gams (Hypocreales Cordycipitaceae) strain used in Mycotal were not pathogenic to A. glabripennis adults. Within the entomopathogenic fungi tested, the Metarhizium strains may be the most appropriate for further evaluation. © The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America.BACKGROUND Hyaline membrane disease contributes majorly to preterm mortality, particularly in the developing world. There are two animal-derived surfactants available in South Africa poractant-alfa (120 mg/1.5 ml) and beractant (100 mg/4 ml). At equivalent doses, studies have shown no difference in mortality or morbidity, although there are limited data from the developing world. Both surfactants have been available for use at Groote Schuur Hospital in Cape Town but due to policy change, poractant-alfa was no longer available from November 2014. Due to weight-based dosing charts, infants who were given poractant-alfa received 20% higher dosages of phospholipid. METHODS A before-and-after policy change non-experimental study was performed including infants from 2013 to 2015. Infants weighing less then 1500 g were recruited by identifying them from the surfactant register and further data were obtained from patient records. Data fields included infant weight, gestation, respiratory support and outcomes. RESULTS Two hundred and eight infants were included. One hundred and eight received beractant and 100 received poractant-alfa. The mean birth weight was 1031 g and gestational age 28.8 weeks. Seventy-nine percent of the infants received surfactant via the INSURE (intubation, surfactant and extubation) method. The combined outcome for death or bronchopulmonary dysplasia was 35.3% in the beractant group and 36% in the poractant-alfa group (p = 0.902). All secondary outcomes including neonatal morbidities, oxygen at 28 days or length of ventilation were not statistically significant. CONCLUSION There were no significant differences in outcomes between the two groups of infants who received different surfactants at the dosages used in our unit. This is one of the few studies of this type performed in a low- and middle-income countries. © The Author(s) [2020]. Published by Oxford University Press. All rights reserved. For permissions, please email journals.permissions@oup.com.Endometriosis is widely associated with infertility in women of childbearing age, for which there have been no effective treatments. Recent studies suggest that the dysregulation of RNAs contributes to the pathogenesis of endometriosis, so we conduct the case-control genetic analysis to characterize the expression and interaction of different subtypes of RNAs in infertile women with endometriosis. The ectopic and eutopic endometrium of patients undergoing infertility treatment were collected and subjected to high throughput sequencing, and bioinformatics analysis was conducted to construct the competing endogenous RNA (ceRNA) network. As a result, the RNA interactive network was constructed in endometriosis, and a set of mRNAs such as cyclin-dependent kinase 1 (CDK1) and proliferating cell nuclear antigen (PCNA) along with their corresponding miRNAs and lncRNAs were found to promote the growth and death of endometrial stromal cells, which was essential for the pathogenesis of endometriosis. These data suggest that RNA crosstalk is a crucial segment in the development of endometriosis, where CDK1 and PCNA may serve as emerging targets for the treatment of endometriosis-related infertility in women of childbearing age.OBJECTIVE Previous studies have provided robust evidence that cognitive impairment exists in patients with type 2 diabetes. The predictive role of S100B in a variety of neurodegenerative diseases such as Alzheimer's disease, has been shown to be closely related to cognitive function. The purpose of this study was to investigate the correlation between serum S100B levels and cognitive function in type 2 diabetes patients. RESULTS The type 2 diabetes group scored lower than the healthy control group in all domains of cognitive function except language and attention, and the former group also had lower serum levels of S100B. Besides, serum S100B levels were lower in the type 2 diabetes patients with impaired cognition than in those with normal cognition. In addition, the moderate to severe cognitive impairment group had significantly lower levels than that in mild cognitive impairment group. After adjusting for confounding factors, serum S100B levels were positively correlated with cognitive function in type 2 diabetes patients.