University of Massachusetts Medical School

About: University of Massachusetts Medical School is a education organization based out in Worcester, Massachusetts, United States. It is known for research contribution in the topics: Population & Health care. The organization has 16161 authors who have published 31822 publications receiving 1909739 citations. The organization is also known as: UMass Medical School.

Degradation of cell proteins and the generation of MHC class I-presented peptides.

Abstract: Major histocompatibility complex (MHC) class I molecules display on the cell surface 8- to 10-residue peptides derived from the spectrum of proteins expressed in the cells. By screening for non-self MHC-bound peptides, the immune system identifies and then can eliminate cells that are producing viral or mutant proteins. These antigenic peptides are generated as side products in the continual turnover of intracellular proteins, which occurs primarily by the ubiquitin-proteasome pathway. Most of the oligopeptides generated by the proteasome are further degraded by distinct endopeptidases and aminopeptidases into amino acids, which are used for new protein synthesis or energy production. However, a fraction of these peptides escape complete destruction and after transport into the endoplasmic reticulum are bound by MHC class I molecules and delivered to the cell surface. Herein we review recent discoveries about the proteolytic systems that degrade cell proteins, how the ubiquitin-proteasome pathway generates the peptides presented on MHC-class I molecules, and how this process is stimulated by immune modifiers to enhance antigen presentation.

Young Adult Outcome of Hyperactive Children: Adaptive Functioning in Major Life Activities

Abstract: Objective The authors report the adaptive functioning of hyperactive and control children in southeastern Wisconsin (Milwaukee) followed to young adulthood. Method Interviews with participants concerning major life activities were collected between 1992 and 1996 and used along with employer ratings and high school records at the young adult follow-up (mean = 20 years, range 19-25) for this large sample of hyperactive (H; n = 149) and community control (CC; n = 72) children initially seen in 1978-1980 and studied for at least 13 years. Age, duration of follow-up, and IQ were statistically controlled as needed. Results The H group had significantly lower educational performance and attainment, with 32% failing to complete high school. H group members had been fired from more jobs and manifested greater employer-rated attention-deficit/hyperactivity disorder and oppositional defiant disorder symptoms and lower job performance than the CC group. Socially, the H group had fewer close friends, more trouble keeping friends, and more social problems as rated by parents. Far more H than CC group members had become parents (38% versus 4%) and had been treated for sexually transmitted disease (16% versus 4%). Severity of lifetime conduct disorder was predictive of several of the most salient outcomes (failure to graduate, earlier sexual intercourse, early parenthood) whereas attention-deficit/hyperactivity disorder and oppositional defiant disorder at work were predictive of job performance and risk of being fired. Conclusions These findings corroborate prior research and go further in identifying sexual activity and early parenthood as additional problematic domains of adaptive functioning at adulthood.

An investigation of language impairment in autism: Implications for genetic subgroups

Abstract: Autism involves primary impairments in both language and communication, yet in recent years the main focus of research has been on the communicative deficits that define the population. The study reported in this paper investigated language functioning in a group of 89 children diagnosed with autism using the ADI-R, and meeting DSM-IV criteria. The children, who were between 4- and 14- years-old were administered a battery of standardized language tests tapping phonological, lexical, and higher-order language abilities. The main findings were that among the children with autism there was significant heterogeneity in their language skills, although across all the children, articulation skills were spared. Different subgroups of children with autism were identified on the basis on their performance on the language measures. Some children with autism have normal language skills; for other children, their language skills are significantly below age expectations. The profile of performance across the standardized measures for the language-impaired children with autism was similar to the profile that defines the disorder specific language impairment (or SLI). The implications of this language impaired subgroup in autism for understanding the genetics and definition of both autism and SLI are discussed.

Family income, parental education and brain structure in children and adolescents

Abstract: Socioeconomic disparities are associated with differences in cognitive development. The extent to which this translates to disparities in brain structure is unclear. We investigated relationships between socioeconomic factors and brain morphometry, independently of genetic ancestry, among a cohort of 1,099 typically developing individuals between 3 and 20 years of age. Income was logarithmically associated with brain surface area. Among children from lower income families, small differences in income were associated with relatively large differences in surface area, whereas, among children from higher income families, similar income increments were associated with smaller differences in surface area. These relationships were most prominent in regions supporting language, reading, executive functions and spatial skills; surface area mediated socioeconomic differences in certain neurocognitive abilities. These data imply that income relates most strongly to brain structure among the most disadvantaged children.

Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals

Abstract: Several recent studies link parental environments to phenotypes in subsequent generations. In this work, we investigate the mechanism by which paternal diet affects offspring metabolism. Protein restriction in mice affects small RNA (sRNA) levels in mature sperm, with decreased let-7 levels and increased amounts of 5′ fragments of glycine transfer RNAs (tRNAs). In testicular sperm, tRNA fragments are scarce but increase in abundance as sperm mature in the epididymis. Epididymosomes (vesicles that fuse with sperm during epididymal transit) carry RNA payloads matching those of mature sperm and can deliver RNAs to immature sperm in vitro. Functionally, tRNA-glycine-GCC fragments repress genes associated with the endogenous retroelement MERVL, in both embryonic stem cells and embryos. Our results shed light on sRNA biogenesis and its dietary regulation during posttesticular sperm maturation, and they also link tRNA fragments to regulation of endogenous retroelements active in the preimplantation embryo.