Treating late-onset Tay Sachs disease: Brain delivery with a dual trojan horse protein.

Tay-Sachs (TS) disease is a neurodegenerative disease resulting from mutations in the gene encoding the α-subunit (HEXA) of lysosomal β-hexosaminidase A (HexA). We report that (1) recombinant HEXA alone increased HexA activity and decreased GM2 content in human TS glial cells and peripheral mononuclear blood cells; 2) a recombinant chimeric protein composed of HEXA linked to two blood-brain barrier (BBB) entry elements, a transferrin receptor binding sequence and granulocyte-colony stimulating factor, associates with HEXB ; reaches human cultured TS cells lysosomes and mouse brain cells, especially neurons, ; lowers GM2 in cultured human TS cells; lowers whole brain GM2 concentration by approximately 40% within 6 weeks, when injected intravenously (IV) to adult TS-mutant mice mimicking the slow course of late-onset TS; and increases forelimbs grip strength. Hence, a chimeric protein equipped with dual BBB entry elements can transport a large protein such as HEXA to the brain, decrease the accumulation of GM2, and improve muscle strength, thereby providing potential treatment for late-onset TS.

Association of Early-Life Exposure to Income Inequality With Bullying in Adolescence in 40 Countries.

Importance: While the association between income inequality and interpersonal violence has been attributed to the psychosocial effects of inequality (eg, increased class anxiety, reduced social capital), longitudinal evidence for this pathway is limited by a reliance on small ecological studies and cross-sectional data. The developmental consequences of early-life inequality for subsequent involvement in violence have not been investigated.

Objective: To examine the association between income inequality during infancy and early childhood and adolescents' involvement in bullying others, experiences of being bullied, or both.

Who perpetrates violence against children? A systematic analysis of age-specific and sex-specific data.

Objective: The epidemiology of violence against children is likely to differ substantially by sex and age of the victim and the perpetrator. Thus far, investment in effective prevention strategies has been hindered by lack of clarity in the burden of childhood violence across these dimensions. We produced the first age-specific and sex-specific prevalence estimates by perpetrator type for physical, sexual and emotional violence against children globally.

Children's command of plural and possessive marking on Hebrew nouns: a comparison of obligatory versus optional inflections.

We compare learning of two inflection types - obligatory noun plurals and optional noun possessives. We tested 107 Hebrew-speaking children aged 6-7 on the same tasks at the beginning and end of first grade. Performance on both constructions improved during this short period, but plurals scored higher from the start, with improvement only in changing stems.