Huntingtin interactome reveals huntingtin role in regulation of double strand break DNA damage response (DSB/DDR), chromatin remodeling and RNA processing pathways.

Huntington's Disease (HD), a progressive neurodegenerative disorder with no disease-modifying therapies, is caused by a CAG repeat expansion in the HD gene encoding polyglutamine-expanded huntingtin (HTT) protein. Mechanisms of HD cellular pathogenesis and cellular functions of the normal and mutant HTT proteins are still not completely understood. HTT protein has numerous interaction partners, and it likely provides a scaffold for assembly of multiprotein complexes many of which may be altered in HD.

Mortality in Haemophilia Patients in India: A National Cohort Study.

Introduction: Mortality and morbidity in persons with haemophilia (PWH) have decreased due to improved diagnosis and treatment along with comprehensive population outreach efforts, but the impact is not uniform in different countries.

Aim: The study aims to assess all-cause and intracranial haemorrhage (ICH)-specific mortality of PWH in India.

Methods: This is a retrospective, observational, multi-centric cohort study of 1020 haemophilia patients from three centres in India.

Transfection Potency of Lipid Nanoparticles Containing mRNA Depends on Relative Loading Levels.

When formulating mRNA into lipid nanoparticles (LNP), various copy numbers of mRNA are encapsulated, leading to a distribution of mRNA loading levels within the LNPs. It is unclear whether the mRNA loading level affects the functional delivery of the message. Here we show that depending on the mRNA loading level, LNPs exhibit distinct mass densities and can be fractionated via ultracentrifugation.

The Health Benefits of Extended Union Membership among Women: A Family Status Perspective.

Workers in labor unions have better access to high quality health insurance plans, better pensions, and higher wages leading to increased lifetime earnings likely leading to better health. Additionally, much of the gendered hiring, promotion, and wage discrimination faced by women in the workplace is dependent on social characteristics (marital status and/or their status as a mother). While many of the benefits associated with union membership can potentially buffer the gendered workplace inequalities that lead to poorer health outcomes, unions have been largely ignored in health disparities literature.

In vivo self-assembled siRNAs within small extracellular vesicles attenuate LRRK2-induced neurodegeneration in Parkinson's disease models.

Rationale: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene play an important role in Parkinson's disease (PD) pathogenesis, and downregulation of LRRK2 has become a promising therapy for PD. Here, we developed a synthetic biology strategy for the self-assembly and delivery of small interfering RNAs (siRNAs) of LRRK2 into the substantia nigra via small extracellular vesicles (sEVs) using a genetic circuit (in the form of naked DNA plasmid) to attenuate PD-like phenotypes in mouse model.

Methods: We generated the genetic circuit encoding both a neuron-targeting rabies virus glycoprotein (RVG) tag and a LRRK2 siRNA under the control of a cytomegalovirus (CMV) promoter, and assessed its therapeutic effects using LRRK2 mouse models of PD.