Self-assembly properties of a model RING domain.

RING domains act in a variety of essential cellular processes but have no general function ascribed to them. Here, we observe that purified arenaviral protein Z, constituted almost entirely by its RING domain, self-assembles in vitro into spherical structures that resemble functional bodies formed by Z in infected cells. By using a variety of biophysical methods we provide a thermodynamic and kinetic framework for the RING-dependent self-assembly of Z. Assembly appears coupled to substantial conformational reorganization and changes in zinc coordination of site II of the RING. Thus, the rate-limiting nature of conformational reorganization observed in the folding of monomeric proteins can also apply to the assembly of macromolecular scaffolds. These studies describe a unique mechanism of nonfibrillar homogeneous self-assembly and suggest a general function of RINGs in the formation of macromolecular scaffolds that are positioned to integrate biochemical processes in cells.     

Competition between T cells maintains clonal dominance during memory inflation induced by MCMV

Both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) establish persistent infections that induce the accumulation of virus‐specific T cells over time in a process called memory inflation. It has been proposed that T cells expressing T‐cell receptors (TCRs) with high affinity for HCMV‐derived peptides are preferentially selected after acute HCMV infection. To test this in the murine model, small numbers of OT‐I transgenic T cells, which express a TCR with high affinity for the SIINFEKL peptide, were transferred into congenic mice and recipients were challenged with recombinant MCMV expressing SIINFEKL. OT‐I T cells were selectively enriched during the first 3 weeks of infection. Similarly, in the absence of OT‐I T cells, the functional avidity of SIINFEKL‐specific T cells increased from early to late times postinfection. However, even when exceedingly small numbers of OT‐I T cells were transferred, their inflation limited the inflation of host‐derived T cells specific for SIINFEKL. Importantly, subtle minor histocompatibility differences led to late rejection of the transferred OT‐I T cells in some mice, which allowed host‐derived T cells to inflate substantially. Thus, T cells with a high functional avidity are selected shortly after MCMV infection and continuously sustain their clonal dominance in a competitive manner.     

Risk Factors for Campylobacteriosis in Two Washington State Counties with High Numbers of Dairy Farms

Campylobacteriosis is a frequently reported, food-borne, human bacterial disease that can be associated with ruminant reservoirs, although public health messages primarily focus on poultry. In Washington State, the two counties with the highest concentrations of dairy cattle also report the highest incidences of campylobacteriosis. Conditional logistic regression analysis of case-control data from both counties found living or working on a dairy farm (odds ratio [OR], 6.7 [95% confidence interval [CI], 1.7 to 26.4]) and Hispanic ethnicity (OR, 6.4 [95% CI, 3.1 to 13.1]) to have the strongest significant positive associations with campylobacteriosis. When the analysis was restricted to residents of one county, Hispanic ethnicity (OR, 9.3 [95% CI, 3.9 to 22.2]), contact with cattle (OR, 5.0 [95% CI, 1.3 to 19.5]), and pet ownership (OR, 2.6 [95% CI, 1.1 to 6.3]) were found to be independent risk factors for disease. Campylobacter jejuni isolates from human (n = 65), bovine (n = 28), and retail poultry (n = 27) sources from the same counties were compared using multilocus sequence typing. These results indicated that sequence types commonly found in human isolates were also commonly found in bovine isolates. These findings suggest that, in areas with high concentrations of dairy cattle, exposure to dairy cattle may be more important than food-borne exposure to poultry products as a risk for campylobacteriosis.     

FBXO28 causes developmental and epileptic encephalopathy with profound intellectual disability

Chromosome 1q41‐q42 deletion syndrome is a rare cause of intellectual disability, seizures, dysmorphology, and multiple anomalies. Two genes in the 1q41‐q42 microdeletion, WDR26 and FBXO28, have been implicated in monogenic disease. Patients with WDR26 encephalopathy overlap clinically with those with 1q41‐q42 deletion syndrome, whereas only one patient with FBXO28 encephalopathy has been described. Seizures are a prominent feature of 1q41‐q42 deletion syndrome; therefore, we hypothesized that pathogenic FBXO28 variants cause developmental and epileptic encephalopathies (DEEs). We describe nine new patients with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and analyze all 10 known cases to delineate the phenotypic spectrum. All patients had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features, albeit different to those typically seen in 1q41‐q42 deletion syndrome and WDR26 encephalopathy. We distinguish FBXO28 encephalopathy from both of these disorders with more severe intellectual impairment, drug‐resistant epilepsy, and hyperkinetic movement disorders.     

Developing a Sound Body: Open Trial Results of a Group Healthy Lifestyle Intervention for Young Adults with Psychosis

Community Mental Health Journal - The mortality disparity for persons with schizophrenia spectrum disorders (SSDs) due to cardiovascular disease is a devastating problem. Many risk factors are...     

Interaction of Blood Manganese Concentrations with GSTT1 in Relation to Autism Spectrum Disorder in Jamaican Children

Journal of Autism and Developmental Disorders - Using data from 266 age- and sex-matched pairs of Jamaican children with autism spectrum disorder (ASD) and typically developing (TD) controls...     

Correction to: “Best Things”: Parents Describe Their Children with Autism Spectrum Disorder Over Time

Journal of Autism and Developmental Disorders -