The Juvenile Parkinson's Disease Mutation C212Y Impairs Mitochondrial Homeostasis in a Caenorhabditis elegans Model.

Inherited Parkinson's disease (PD) often involves missense mutations in the PRKN2 gene, encoding for Parkin protein. The PDR-1 protein is the C. elegans ortholog of human Parkin.

Twinfilin is a potent uncapper of actin capping protein and modulates actomyosin contractility in the spermatheca.

The actin cytoskeleton is dynamically remodelled by conserved regulators to control cellular and tissue mechanics. While the functions of these proteins are well studied, how they drive tissue-specific contractility remains unclear. Twinfilin, an actin uncapper and depolymerase, has not previously been linked to tissue contractility.

Genetically encoded biosensor for fluorescence lifetime imaging of PTEN dynamics in the intact brain.

The phosphatase and tensin homolog (PTEN) is a vital protein that maintains an inhibitory brake for cellular proliferation and growth. Accordingly, PTEN loss-of-function mutations are associated with a broad spectrum of human pathologies. Despite its importance, there is currently no method to directly monitor PTEN activity with cellular specificity within intact biological systems.

Chloride intracellular channel (CLIC) proteins function as fusogens.

Chloride Intracellular Channel (CLIC) family members uniquely transition between soluble and membrane-associated conformations. Despite decades of extensive functional and structural studies, CLICs' function as ion channels remains debated, rendering our understanding of their physiological role incomplete. Here, we expose the function of CLIC5 as a fusogen.

Actin-capping protein regulates actomyosin contractility to maintain germline architecture in C. elegans.

Actin dynamics play an important role in tissue morphogenesis, yet the control of actin filament growth takes place at the molecular level. A challenge in the field is to link the molecular function of actin regulators with their physiological function. Here, we report an in vivo role of the actin-capping protein CAP-1 in the Caenorhabditis elegans germline.

Inhibition of Sema-3A Promotes Cell Migration, Axonal Growth, and Retinal Ganglion Cell Survival.

Purpose: Semaphorin 3A (Sema-3A) is a secreted protein that deflects axons from inappropriate regions and induces neuronal cell death. Intravitreal application of polyclonal antibodies against Sema-3A prevents loss of retinal ganglion cells ensuing from axotomy of optic nerves. This suggested a therapeutic approach for neuroprotection via inhibition of the Sema-3A pathway.

Levodopa-responsive dystonia caused by biallelic exon inversion invisible to exome sequencing.

Biallelic pathogenic variants in (), encoding the E3 ubiquitin ligase parkin, lead to early-onset Parkinson's disease. Structural variants, including duplications or deletions, are common in due to their location within the fragile site FRA6E. These variants are readily detectable by copy number variation analysis.

Mild carotid stenosis creates gradual, progressive, lifelong brain, and eye damage: An experimental laboratory rat model.

In humans, carotid stenosis of 70% and above might be the cause of clinical symptoms such as transient ischemic attack and stroke. No clinical or animal studies have evaluated mild carotid occlusion, and few examined unilateral occlusion. Here, Westar rats underwent bilateral or unilateral carotid occlusion of 28-45%.

Germ Granules Govern Small RNA Inheritance.

In C. elegans nematodes, components of liquid-like germ granules were shown to be required for transgenerational small RNA inheritance. Surprisingly, we show here that mutants with defective germ granules can nevertheless inherit potent small RNA-based silencing responses, but some of the mutants lose this ability after many generations of homozygosity.

Sema-3A indirectly disrupts the regeneration process of goldfish optic nerve after controlled injury.

Background: Neurons of adult mammalian CNS are prevented from regenerating injured axons due to formation of a non-permissive environment. The retinal ganglion cells (RGC), which are part of the CNS, share this characteristic. In sharp contrast, the RGC of lower vertebrates, such as fish, are capable of re-growing injured optic nerve axons, and achieve, through a complex multi-factorial process, functional vision after injury.

Conditional inactivation of the NBS1 gene in the mouse central nervous system leads to neurodegeneration and disorganization of the visual system.

Nijmegen breakage syndrome (NBS) is a genomic instability disease caused by hypomorphic mutations in the NBS1 gene encoding the Nbs1 (nibrin) protein. Nbs1 is a component of the Mre11/Rad50/Nbs1 (MRN) complex that acts as a sensor of double strand breaks (DSBs) in the DNA and is critical for proper activation of the broad cellular response to DSBs. Conditional disruption of the murine ortholog of the human NBS1, Nbs1, in the CNS of mice was previously reported to cause microcephaly, severe cerebellar atrophy and ataxia.

Upregulation of Semaphorin 3A and the associated biochemical and cellular events in a rat model of retinal detachment.

Background: Retinal detachment, as a result of injury or disease, is a severe disorder that may ultimately lead to complete blindness. Despite advanced surgical repair techniques, the visual acuity of patients is often limited. We investigated some of the biochemical and morphological alterations following experimental retinal detachment in laboratory animals.

MRI evidence of white matter damage in a mouse model of Nijmegen breakage syndrome.

Nijmegen breakage syndrome (NBS) is a genomic instability disease caused by hypomorphic mutations in the NBS1 gene encoding the Nbs1 (nibrin) protein. Nbs1 is a component of the Mre11/Rad50/Nbs1 (MRN) complex that acts as a sensor of double strand breaks (DSBs) in the DNA and is critical for proper activation of the broad cellular response to DSBs. Conditional disruption of the murine ortholog of NBS1, Nbn, in the CNS of mice was previously reported to cause microcephaly, severe cerebellar atrophy and ataxia.

Examination of cellular and molecular events associated with optic nerve axotomy.

Purpose: Analyzing cellular behavior during scar formation and determining the expression of growth inhibiting molecules in the optic nerve and retina following acute optic nerve injury.

Methods: A rat model of complete transection of the optic nerve that spares the vascular supply and the neural scaffold was used. The response of the optic nerve and retinas to axotomy was studied by immunological and biochemical approaches.