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Novel Truncating Variants in PODXL Represent a New Entity to Be Explored Among Podocytopathies.

BACKGROUND/OBJECTIVES: Podocalyxin is a sialoprotein mainly expressed in the kidney cortex and lung tissue, which has been described as a component of the podocyte glycocalyx. This protein promotes the reorganization of the podocyte cytoskeleton, as well as the morphogenesis and differentiation of nascent podocytes, actively participating in glomerular filtration. Previous research has suggested that PODXL haploinsufficiency leads to podocytopathy with development of focal segmental glomerulosclerosis, a disorder that has been demonstrated in Podxl-deficient animal models and proposed as a pri…

Exploring the oncogenic roles of T-box transcription factor TBX2 and its potential as a therapeutic target.

During embryonic development, the T-box transcription factor TBX2 regulates key processes such as cell fate decisions, migration and tissue morphogenesis, and mutations that lead to reduced TBX2 levels result in developmental abnormalities including congenital heart and skeletal defects. TBX2, on the other hand, is overexpressed in a plethora of cancers where it functions as a powerful oncogene contributing to processes ranging from the bypass of senescence and cell death pathways to the promotion of cell proliferation, and epithelial-to-mesenchymal transition to drive invasion and metastasis.…

Inhibiting 5-HT2C receptor in the hippocampus rescues EphB2-dependent memory impairment in mice.

EphB2 is a tyrosine kinase receptor that regulates key neuronal functions such as synaptic transmission and morphogenesis. EphB2 dysfunction is associated with neurological disorders and dementia. In Alzheimer's disease, EphB2 depletion leads to memory deficits in mouse models, and its level is reduced in patients. EphB2 expression also declines with aging. Moreover, EphB2 dysfunction has been linked to autism. Here, we show that long-term memory (LTM) of auditory fear conditioning is impaired in EphB2lacZ/lacZ male mice that lack EphB2 forward signaling. However, LTM was significantly increas…

Cdc42 is crucial for mural cell migration, proliferation and patterning of the retinal vasculature.

AIMS: Mural cells constitute the outer lining of blood vessels and are essential for vascular development and function. Mural cell loss or m … ed for mural cell migration and proliferation and suggest that mural cells are essential for normal morphogenesis and patterning of the developing retinal vasculature.

Repurposing of quinine as an antifungal antibiotic: Identification of molecular targets in Candida albicans.

Quinine, a component of the bark of the cinchona tree, is commonly used to treat malaria. The present study focused on the identification of anti-Candida albicans activity of quinine and its mechanism of action. Quinine showed planktonic growth inhibitory activity at 0.5 mg/mL and fungicidal activity at 4 mg/mL concentration. Time-dependent killing of C. albicans cells was seen after the treatment of quinine at 4 mg/mL concentration. The MIC50 of quinine against yeast to hyphal morphogenesis, adhesion and biofilm formation of C. albicans were observed at 0.25 mg/mL, 1 mg/mL and 0.031 mg/mL, re…

Embryotoxicity analysis of anti-arrhythmia drugs amiodarone, dronedarone, and their metabolites using 3D gastruloid models.

Amiodarone and dronedarone are anti-arrhythmic drugs that are structurally related but differ in iodine content. Although contraindicated during pregnancy due to suspected embryotoxicity based on animal studies, their mechanisms of action and relevance to human development remain unclear. Here, we used gastruloids - 3D aggregates of mouse or human pluripotent stem cells that recapitulate axial elongation morphogenesis of early embryos - to investigate their developmental effects. In mouse gastruloids, both drugs and their major metabolites impaired growth and elongation at 1.5 - 3.0 µM. They a…

Specific sperm morphological abnormalities and their functional implications in a cohort of Turkish men from a single-center clinical population.

The role of sperm morphology in male fertilization potential remains unclear. This study aimed to evaluate the incidence of specific sperm m … disorders and suggest that specific defects may arise from disruptions in different stages of sperm morphogenesis.

Changes in the position of skeletal elements of the ankle and foot during late embryonic and fetal periods.

The morphology of the ankle joint and foot during early development exhibits distinct differences from that observed in adults, with physiol … e positions, indicating that the concept of "differential growth" may apply to ankle-joint and foot morphogenesis. Findings of the present study are expected to enhance understanding of the pathogenesis and mechanisms underlying clubfoot and facilitate fetal diagnosis via morphological assessments.

CCDC39 Mutation-Related Primary Ciliary Dyskinesia with Congenitally Corrected Transposition of the Great Arteries: A Case Report.

BACKGROUND Primary ciliary dyskinesia (PCD) is an uncommon autosomal recessive disease resulting from dysfunction of motile cilia that cause … ic spectrum of CCDC39 mutations. This report emphasizes the pivotal role of motile cilia in cardiac morphogenesis and underscores the importance of considering PCD in neonates with laterality anomalies and complex congenital heart defects. Early genetic testing and a multidisciplinary approach are critical to timely diagnosis and management.

Charting the future: current and future directions in translational research for individuals with Down syndrome.

The most common genetic cause of intellectual and developmental disability is trisomy of human chromosome 21 (trisomy 21) or Down syndrome. Relative to the general population, individuals with Down syndrome heterogeneously experience atypical morphogenesis, a distinct neurocognitive profile, and a unique spectrum of diverse medical conditions that impact every major organ system. How trisomy 21 results in the highly variable manifestations of Down syndrome remains largely unknown and an active area of heavy investigation with therapeutic implications. For example, common inflammatory and metab…

AOP 460: Antagonism of Smoothened receptor leading to orofacial clefting.

Sonic hedgehog (SHH) is a major intercellular signaling pathway involved in the orchestration of embryogenesis, including orofacial morphogenesis. The SHH pathway is sensitive to disruption, including both genetic predisposition and chemical-induced disruption at multiple molecular targets including antagonism of the SHH signal transducer smoothened (SMO). Here we report the adverse outcome pathway (AOP) 460 describing the linkage between antagonism of the SMO receptor, a key intermediate in hedgehog signaling, and orofacial clefts (OFCs). Multiple antago­nists of SMO have been identified, inc…

Cell expansion for notochord mechanics and endochondral bone lengthening in zebrafish depends on the 5'-inositol phosphatase Inppl1a.

Cell size is a key contributor to tissue morphogenesis. As a notable example, growth plate hypertrophic chondrocytes use cellular biogenesis and disproportionate fluid uptake to expand 10 to 20 times in size to drive lengthening of endochondral bone. Similarly, notochord vacuolated cells expand to one of the largest cell types in the developing embryo to drive axial extension. In zebrafish, the notochord vacuolated cells undergo vacuole fusion to form a single large, fluid-filled vacuole that fills the cytoplasmic space and contributes to vacuolated cell expansion. When this process goes awry,…

Skeletal progenitor LRP1 deficiency causes severe and persistent skeletal defects with Wnt pathway dysregulation.

Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor whose dysfunction is linked to development … and joints by regulating Wnt signalling, providing novel insights into the fundamental processes of morphogenesis and the emergence of skeletal pathologies.

Tracking control of air flow based on a fractional-order model of the lung impedance.

A fractional order output feedback controller for a lung ventilator is designed. This is based on a state-of-the-art electrical analogue model of the human respiratory system in the form of a network of resistors and fractional capacitors. The electrical input impedance of the adopted analogue can be suitably tuned to fit experimental ventilation impedance data. Furthermore, it can explicitly account for the different physiological fractal type characteristics associated with lung formation such as branching morphogenesis associated to the treelike tubular network and alveolar differentiation …

Spatiotemporal cellular map of the developing human reproductive tract.

The human reproductive tract is essential for species perpetuation and overall health. Its development involves complex processes of sex specification, tissue patterning and morphogenesis, the disruption of which can cause lifelong issues, including infertility1-5. Here we present an extensive single-cell and spatial multi-omic atlas of the human reproductive tract during prenatal development to provide insights beyond those that are possible with smaller-scale, organ-focused studies. We describe potential regulators of sexual dimorphism in reproductive organs and pinpoint previously unknown g…

Comprehensive multi-omics analysis uncovers potential risks of aged sperm on offspring development after short-term storage.

BACKGROUND: Recent studies have demonstrated that prolonged sperm storage adversely affects offspring through epigenetics, yet its broader e … evealed storage-induced alterations of genes associated with nervous system development, myocardial morphogenesis and cellular responses to stimuli. Proteomic analyses showed that in addition to visual perception and nervous system function, pathways of the immunity system were also enriched. Results provide strong evidence of the epigenetic inheritance of the …

Диметилфумарат является ингибитором патологического ангиогенеза.

Велосипедный эндотелиальный фактор роста (VEGF), проангиогенная молекула, поддерживает рост кровеносных сосудов во время заживления ран, но также стимулирует патологическую неоваскуляризацию при ослепляющих заболеваниях глаз, таких, как неоваскулярная дегенерация, связанная с неокулярным возрастом (nAMD). Диметилфумарат (ДМФу), одобренный УЛХ лекарство от множественных склерозов, продемонстрировал многообещающие антивоспалительные свойства в эпителии сетчатки, которая является важнейшей структурой, нарушенной в NAMD. Здесь мы расширяем терапевтический потенциал DMFu, выявляя антиангиогенные сп

Совпадение в аннотации оригинала
Vascular endothelial growth factor (VEGF), a pro-angiogenic molecule, supports blood vessel growth during wound healing but also drives path … ene set enrichment analyses confirmed downregulation of pathways involved in branching blood vessel morphogenesis but also revealed novel transcriptional mechanisms of action, including control of microtubule transport and ATP synthesis coupled electron transport. DMFu induced a decrease in maximal mitochondrial respiration, an increase in glycolysis and glycol …

From Gene to Protein: Unraveling the Reproductive Blueprint of Male Grey Squirrels via Nerve Growth Factor (NGF) and Cognate Receptors.

The grey squirrel, an invasive species, threatens the Eurasian red squirrel's conservation, particularly in Umbria, Italy. Understanding its reproductive biology is essential to limiting its reproductive success. This study investigates the NGF system and its receptors (NTRK1 and p75NTR) in the testes of male grey squirrels, following prior research on female reproductive biology. NGF plays a role in testicular morphogenesis and spermiogenesis in animals and humans. As part of the LIFE Project U-SAVEREDS, eighteen squirrels were captured and classified into three morphotypes (immature, puberta…

The disturbance of intestinal microbiome caused by the novel duck reovirus infection in Cherry Valley ducklings can induce intestinal damage.

Novel duck reovirus disease is an infectious disease mainly caused by novel duck reovirus (NDRV), which is characterized by spleen necrosis and persistent diarrhea in ducks. However, the pathogenic mechanism of NDRV infection in Cherry Valley ducks remains unclear. To investigate the distribution of NDRV in the intestines of Cherry Valley ducks, intestinal morphogenesis, intestinal permeability, inflammatory cytokines, and the expression of tight junction proteins (TJPs), we introduced NDRV via intramuscular infection. The diversity and composition of ileum flora and content of short-chain fat…

Microneedle Patch for Transdermal Sequential Delivery of KGF-2 and aFGF to Enhance Burn Wound Therapy.

Severe burn wounds usually destroy key cells' functions of the skin resulting in delayed re-epithelization and wound regeneration. Promoting key cells' activities is crucial for burn wound repair. It is well known that keratinocyte growth factor-2 (KGF-2) participates in the proliferation and morphogenesis of epithelial cells while acidic fibroblast growth factor (aFGF) is a key mediator for fibroblast and endothelial cell growth and differentiation. However, thick eschar and the harsh environment of a burn wound often decrease the delivery efficiency of fibroblast growth factor (FGF) to the w…