The relationship between childhood gender nonconformity, aversive childhood experiences, and mental health in heterosexual and non-heterosexual cisgender men: The buffering effect of sense of coherence

Childhood gender nonconformity (CGNC) seems to be associated with more mental health problems in adulthood. Previous research has suggested that this link might be mediated via the increased risk for aversive childhood experiences (ACEs) as a negative social reaction to CGNC. However, no study yet examined the role of resilience factors in this relationship. The present study aims to address this gap by examining the potential buffering effect of sense of coherence (SOC). In a German sample of 371 cisgender men, we used mediation models to investigate the relationship between CGNC, ACEs, and mental health problems in adulthood, that is, depressive symptoms, loneliness, and suicidal behavior. We then employed moderated mediation models to examine the buffering effect of SOC on the association ACEs and mental health problems. The results showed that higher levels of CGNC were associated with more severe adult mental health problems, with this link being partially mediated by higher levels of ACEs. For depressive symptoms and suicidal behavior in the last 12 months, we found evidence of a buffering effect of SOC. Higher levels of SOC were associated with a weaker association between ACEs and mental health problems. In contrast, this effect was absent for loneliness and lifetime suicidal behavior. Our study provides evidence that ACEs partly account for the relationship between CGNC and mental health in adulthood. Moreover, we found support for SOC having a buffering effect on this link. Future studies need to examine whether SOC might be an important target for resilience training in those experiencing CGNC. However, sustainable interventions may rather address the negative social reactions to CGNC

A missense mutation in Ehd1 associated with defective spermatogenesis and male infertility

Normal function of the C-terminal Eps15 homology domain-containing protein 1 (EHD1) has previously been associated with endocytic vesicle trafficking, shaping of intracellular membranes, and ciliogenesis. We recently identified an autosomal recessive missense mutation c.1192C>T (p.R398W) of EHD1 in patients who had low molecular weight proteinuria (0.7–2.1 g/d) and high-frequency hearing loss. It was already known from Ehd1 knockout mice that inactivation of Ehd1 can lead to male infertility. However, the exact role of the EHD1 protein and its p.R398W mutant during spermatogenesis remained still unclear. Here, we report the testicular phenotype of a knockin mouse model carrying the p.R398W mutation in the EHD1 protein. Male homozygous knockin mice were infertile, whereas the mutation had no effect on female fertility. Testes and epididymes were significantly reduced in size and weight. The testicular epithelium appeared profoundly damaged and had a disorganized architecture. The composition of developing cell types was altered. Malformed acrosomes covered underdeveloped and misshaped sperm heads. In the sperm tail, midpieces were largely missing indicating disturbed assembly of the sperm tail. Defective structures, i.e., nuclei, acrosomes, and sperm tail midpieces, were observed in large vacuoles scattered throughout the epithelium. Interestingly, cilia formation itself did not appear to be affected, as the axoneme and other parts of the sperm tails except the midpieces appeared to be intact. In wildtype mice, EHD1 co-localized with acrosomal granules on round spermatids, suggesting a role of the EHD1 protein during acrosomal development. Wildtype EHD1 also co-localized with the VPS35 component of the retromer complex, whereas the p.R398W mutant did not. The testicular pathologies appeared very early during the first spermatogenic wave in young mice (starting at 14 dpp) and tubular destruction worsened with age. Taken together, EHD1 plays an important and probably multifaceted role in spermatogenesis in mice. Therefore, EHD1 may also be a hitherto underestimated infertility gene in humans

The design of avalanche protection dams : Recent practical and theoretical developments

This book discusses the design of dams and other protective measures in the run-out zones of wet- and dry-snow avalanches. It summarises recent theoretical developments and the results of field and laboratory studies, combining them with traditional design guidelines and principles to formulate design recommendations. Not discussed are hazard zoning, land use planning, evacuations, supporting structures in starting zones, snow fences in catchment areas, and other safety measures outside the run-out zone. Reinforcement of individual buildings also falls outside the scope of the book, as do protective measures against landslides and slushflows.European Comissio

Quantification of FAM20A in human milk and identification of calcium metabolism proteins

BACKGROUND: FAM20A, a recently discovered protein, is thought to have a fundamental role in inhibiting ectopic calcification. Several studies have demonstrated that variants of FAM20A are causative for the rare autosomal recessive disorder, enamel-renal syndrome (ERS). ERS is characterized by defective mineralization of dental enamel and nephrocalcinosis suggesting that FAM20A is an extracellular matrix protein, dysfunction of which causes calcification of the secretory epithelial tissues. FAM20A is a low-abundant protein that is difficult to detect in biofluids such as blood, saliva, and urine. Thus, we speculated the abundance of FAM20A to be high in human milk, since the secretory epithelium of lactating mammary tissue is involved in the secretion of highly concentrated calcium. Therefore, the primary aim of this research is to describe the processes/methodology taken to quantify FAM20A in human milk and identify other proteins involved in calcium metabolism. METHOD: This study used mass spectrometry-driven quantitative proteomics: (1) to quantify FAM20A in human milk of three women and (2) to identify proteins associated with calcium regulation by bioinformatic analyses on whole and milk fat globule membrane fractions. RESULTS: Shotgun MS/MS driven proteomics identified FAM20A in whole milk, and subsequent analysis using targeted proteomics also successfully quantified FAM20A in all samples. Combination of sample preparation, fractionation, and LC-MS/MS proteomics analysis generated 136 proteins previously undiscovered in human milk; 21 of these appear to be associated with calcium metabolism. CONCLUSION: Using mass spectrometry-driven proteomics, we successfully quantified FAM20A from transitional to mature milk and obtained a list of proteins involved in calcium metabolism. Furthermore, we show the value of using a combination of both shotgun and targeted driven proteomics for the identification of this low abundant protein in human milk

Anomalies and WZW-term of two-flavour QCD

The U(2)_R x U(2)_L symmetry of QCD with two massless flavours is subject to anomalies which affect correlation functions involving the singlet currents A^0_\mu or V^0_\mu. These are relevant for pion-photon interactions, because - for two flavours - the electromagnetic current contains a singlet piece. We give the effective Lagrangian required for the corresponding low energy analysis to next-to-leading order, without invoking an expansion in the mass of the strange quark. In particular, the Wess-Zumino-Witten term that accounts for the two-flavour anomalies within the effective theory is written down in closed form.Comment: 17 pages, 1 figur

Mir-132/212 is required for maturation of binocular matching of orientation preference and depth perception

MicroRNAs (miRNAs) are known to mediate post-transcriptional gene regulation, but their role in postnatal brain development is still poorly explored. We show that the expression of many miRNAs is dramatically regulated during functional maturation of the mouse visual cortex with miR-132/212 family being one of the top upregulated miRNAs. Age-downregulated transcripts are significantly enriched in miR-132/miR-212 putative targets and in genes upregulated in miR-132/212 null mice. At a functional level, miR-132/212 deletion affects development of receptive fields of cortical neurons determining a specific impairment of binocular matching of orientation preference, but leaving orientation and direction selectivity unaltered. This deficit is associated with reduced depth perception in the visual cliff test. Deletion of miR-132/212 from forebrain excitatory neurons replicates the binocular matching deficits. Thus, miR-132/212 family shapes the age-dependent transcriptome of the visual cortex during a specific developmental window resulting in maturation of binocular cortical cells and depth perception

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

Recent Developments in Chiral Perturbation Theory

I review recent developments in chiral perturbation theory (CHPT) which is the effective field theory of the standard model below the chiral symmetry breaking scale. The effective chiral Lagrangian formulated in terms of the pseudoscalar Goldstone bosons ($\pi, \, K, \, \eta$) is briefly discussed. It is shown how one can gain insight into the ratios of the light quark masses and to what extent these statements are model--independent. A few selected topics concerning the dynamics and interactions of the Goldstone bosons are considered. These are $\pi \pi$ and $\pi K$ scattering, some non--leptonic kaon decays and the problem of strong pionic final state interactions. CHPT also allows to make precise statements about the temperature dependence of QCD Green functions and the finite size effects related to the propagation of the (almost) massless pseudoscalar mesons. A central topic is the inclusion of matter fields, baryon CHPT. The relativistic and the heavy fermion formulation of coupling the baryons to the Goldstone fields are discussed. As applications, photo--nucleon processes, the $\pi N$ $\Sigma$--term and non--leptonic hyperon decays are presented. Implications of the spontaneously broken chiral symmetry on the nuclear forces and meson exchange currents are also described. Finally, the use of effective field theory methods in the strongly coupled Higgs sector and in the calculation of oblique electroweak corrections is touched upon.Comment: TeX, 110 pages, 15 figures available upon request, BUTP-93/0