Activation of Hippo Pathway Damages Slit Diaphragm by Deprivation of Ajuba Proteins.

Significance Statement: Nuclear exclusion of the cotranscription factor YAP, which is a consequence of activation of the Hippo signaling pathway, leads to FSGS and podocyte apoptosis. Ajuba proteins play an important role in the glomerular filtration barrier by keeping the Hippo pathway inactive. In nephrocytes from Drosophila melanogaster , a well-established model system for podocyte research, Ajuba proteins ensure slit diaphragm (SD) formation and function.

Linking human Dead end 1 (DND1) variants to male infertility employing zebrafish embryos.

Study Question: Is the vertebrate protein Dead end (DND1) a causative factor for human infertility and can novel in vivo assays in zebrafish help in evaluating this?

Summary Answer: Combining patient genetic data with functional in vivo assays in zebrafish reveals a possible role for DND1 in human male fertility.

What Is Known Already: About 7% of the male population is affected by infertility but linking specific gene variants to the disease is challenging. The function of the DND1 protein was shown to be critical for germ cell development in several model organisms but a reliable and cost-effective method for evaluating the activity of the protein in the context of human male infertility is still missing.

Functional assessment of DMRT1 variants and their pathogenicity for isolated male infertility.

Objective: To study the impact of Doublesex and mab-3-related transcription factor 1 (DMRT1) gene variants on the encoded protein's function and the variants' pathogenic relevance for isolated male infertility caused by azoospermia.

Design: This study established a novel luciferase assay for DMRT1 missense variants using 2 different target promotors and validated the assay by analyzing previously published variants associated with differences in sex development.

Setting: University genetics research institute and tertiary referral center for couples' infertility.

Genetic Architecture of Azoospermia-Time to Advance the Standard of Care.

Background: Crypto- and azoospermia (very few/no sperm in the semen) are main contributors to male factor infertility. Genetic causes for spermatogenic failure (SPGF) include Klinefelter syndrome and Y-chromosomal azoospermia factor microdeletions, and CFTR mutations for obstructive azoospermia (OA). However, the majority of cases remain unexplained because monogenic causes are not analysed.

Deficiency Causes Germ Cell Loss During Mouse Embryogenesis and Is Associated With Human Male Infertility.

Mutations affecting the germline can result in infertility or the generation of germ cell tumors (GCT), highlighting the need to identify and characterize the genes controlling germ cell development. The RNA-binding protein and E3 ubiquitin ligase TRIM71 is essential for embryogenesis, and its expression has been reported in GCT and adult mouse testes. To investigate the role of TRIM71 in mammalian germ cell embryonic development, we generated a germline-specific conditional knockout mouse (cKO) using the early primordial germ cell (PGC) marker as a Cre-recombinase driver.

Assessment of the Quorum Sensing Inhibition Activity of a Non-Toxic Chitosan in an -Acyl Homoserine Lactone (AHL)-Based Biosensor.

New approaches to deal with drug-resistant pathogenic bacteria are urgent. We studied the antibacterial effect of chitosans against an quorum sensing biosensor reporter strain and selected a non-toxic chitosan to evaluate its quorum sensing (QS) inhibition activity and its effect on bacterial aggregation. To this end, chitosans of varying degree of acetylation (DA) (12 to 69%) and molecular weight () (29 to 288 kDa) were studied.