Interaction of the sorting nexin 25 homologue Snazarus with Rab11 balances endocytic and secretory transport and maintains the ultrafiltration diaphragm in nephrocytes.

Proper balance of exocytosis and endocytosis is important for the maintenance of plasma membrane lipid and protein homeostasis. This is especially critical in human podocytes and the podocyte-like Drosophila nephrocytes that both use a delicate diaphragm system with evolutionarily conserved components for ultrafiltration. Here, we show that the sorting nexin 25 homologue Snazarus (Snz) binds to Rab11 and localizes to Rab11-positive recycling endosomes in Drosophila nephrocytes, unlike in fat cells where it is present in plasma membrane/lipid droplet/endoplasmic reticulum contact sites. Loss of Snz leads to redistribution of Rab11 vesicles from the cell periphery and increases endocytic activity in nephrocytes. These changes are accompanied by defects in diaphragm protein distribution that resemble those seen in Rab11 gain-of-function cells. Of note, co-overexpression of Snz rescues diaphragm defects in Rab11 overexpressing cells, whereas snz knockdown in Rab11 overexpressing nephrocytes or simultaneous knockdown of snz and tbc1d8b encoding a Rab11 GTPase-activating protein (GAP) leads to massive expansion of the lacunar system that contains mislocalized diaphragm components: Sns and Pyd/ZO-1. We find that loss of Snz enhances while its overexpression impairs secretion, which, together with genetic epistasis analyses, suggest that Snz counteracts Rab11 to maintain the diaphragm via setting the proper balance of exocytosis and endocytosis.

Isolation and characterization of novel plekhm1 and def8 mutant alleles in Drosophila.

Lysosomal degradation of cytoplasmic components by autophagy ensures the continuous turnover of proteins and organelles and aids cellular survival during nutrient deprivation and other stress conditions. Lysosomal targeting of cytoplasmic proteins and organelles requires the concerted action of several proteins and multisubunit complexes. The core components of this machinery are conserved from yeast to humans and many of them are well-characterized; however, novel molecular players have been recently discovered and are waiting for detailed analysis. The osteopetrosis-linked PLEKHM1 protein is a lysosomal adaptor involved in autophagosome and endosome to lysosome fusion events and its role in lysosomal positioning in osteoclasts was reported together with its proposed binding partner, the relatively uncharacterized DEF8 protein. Here, we report the generation and subsequent analysis of novel mutant alleles of Drosophila plekhm1 and def8. Interestingly, the CRISPR-generated null mutations of these genes do not have any obvious effects on autophagy in Drosophila tissues, even though RNAi knockdown of these genes seems to perturb autophagy. Although these results are quite surprising and raise the possibility of compensatory changes in the case of null mutants, the new alleles will be valuable tools in future studies to understand the cellular functions of Drosophila Plekhm1 and Def8 proteins.

Quality of life and related constructs in a group of infertile Hungarian women: a validation study of the FertiQoL.

Quality-of-life measurement is a basic prerequisite for psychologically sensitive fertility care and the FertiQoL is a psychometrically sound outcome measure in this field. The aim of the present research was to investigate the reliability and validity of the Hungarian Core FertiQoL. Two independent samples of infertile women were merged (n = 320). While the model fit of the four-factor Confirmatory Factor Analysis was under the level of acceptability (χ2(246) = 626.36, p < 0.001, RMSEA = 0.070 [CI90 = 0.063-0.076], CFI = 0.878, SRMR = 0.071), the four-factor Exploratory Structural Equation Model showed much improved model fit (χ2(186) = 395.63, p < 0.001, RMSEA = 0.059 [CI90 = 0.051-0.067], CFI = 0.933, SRMR = 0.035). Good internal consistency (Cronbach's Alphas 0.77-0.92) and construct reliability (0.75-0.95) were found for both factor structures. Depression correlated negatively with fertility-specific quality of life. Almost a quarter of the sample suffered from moderate-to-severe depression. Multivariate analysis of variance indicated that Beck Depression Inventory categories (mild, moderate etc.) co-occurred with significantly distinct FertiQoL score ranges, leading to a possible, clinically meaningful threshold on the Core FertiQoL. Pearson coefficients showed secondary infertility, rural residency and pre-treatment status to be associated with better fertility quality of life.

Anxiety and depression among infertile women: a cross-sectional survey from Hungary.

BACKGROUND: Infertility is often associated with a chronic state of stress which may manifest itself in anxiety-related and depressive symptoms. The aim of our study is to assess the psychological state of women with and without fertility problems, and to investigate the background factors of anxiety-related and depressive symptoms in women struggling with infertility. METHODS: Our study was conducted with the participation of 225 (134 primary infertile and 91 fertile) women, recruited in a clinical setting and online. We used the following questionnaires: Spielberger Trait Anxiety Inventory (STAI-T), Shortened Beck Depression Inventory (BDI) and Fertility Problem Inventory (FPI). We also interviewed our subjects on the presence of other sources of stress (the quality of the relationship with their mother, financial and illness-related stress), and we described sociodemographic and fertility-specific characteristics. We tested our hypotheses using independent-samples t-tests (M ± SD) and multiple linear regression modelling (ß). RESULTS: Infertile women were younger (33.30 ± 4.85 vs. 35.74 ± 5.73, p = .001), but had significantly worse psychological well-being (BDI = 14.94 ± 12.90 vs. 8.95 ± 10.49, p < .0001; STAI-T = 48.76 ± 10.96 vs. 41.18 ± 11.26, p < .0001) than fertile subjects. Depressive symptoms and anxiety in infertile women were associated with age, social concern, sexual concern and maternal relationship stress. Trait anxiety was also associated with financial stress. Our model was able to account for 58% of the variance of depressive symptoms and 62% of the variance of trait anxiety. CONCLUSIONS: Depressive and anxiety-related symptoms of infertile women are more prominent than those of fertile females. The measurement of these indicators and the mitigation of underlying distress by adequate psychosocial interventions should be encouraged.

[Relationships between psychological well-being, lifestyle factors and fertility]. / A pszichés jóllét, az életmód és a termékenység összefüggései.

INTRODUCTION: 10 to 15% of the Hungarian fertile age population struggles with reproductivity problems. Previous researches have shown that psychological well-being and lifestyle factors play a pivotal role in overall health status, which is closely related to fertility. AIM: The aim of the study was to examine fertility-related psychological and lifestyle factors in a Hungarian sample. METHOD: 194 women (115 infertile and 79 fertile) took part in the study. Standardized, validated questionnaires were used for the assessment of psychological factors and self-administered questions were used for exploring lifestyle factors. RESULTS: The results show that infertile women are younger (33.98±4.89 vs. 36.43±5.81 years, p<0.005) and their psychological status is significantly worse compared to their fertile counterparts. The number of their depressive (BDI 14.00±12.21 vs. 7.79±9.17, p<0.005) and anxiety symptoms is higher (STAI-T 48.53±10.56 vs. 40.25±10.65, p<0.005) compared to fertile women. Findings related to lifestyle factors show that lower level of fluid consumption (1.71±0.67 vs. 1.95±0.68, p<0.05) and diet (31.30% vs. 18.42%, p<0.05) is significantly related to infertility. In this sample higher level of fluid consumption was associated with the fertile group (OR = 1.65, CI = 2.58-1.06), independently of body mass index and age. CONCLUSIONS: The results confirm the findings of international researches showing that women struggling with infertility are in worse psychological condition than their fertile counterparts. The authors conclude that the findings demand further investigations and follow-up studies in order to more specifically determine the relationship between fluid consumption and fertility.