Expression of the neuroprotective slow Wallerian degeneration (WldS) gene in non-neuronal tissues

<p>Abstract</p> <p>Background</p> <p>The slow Wallerian Degeneration (<it>Wld</it>^<it>S</it>) gene specifically protects axonal and synaptic compartments of neurons from a wide variety of degeneration-inducing stimuli, including; traumatic injury, Parkinson's disease, demyelinating neuropathies, some forms of motor neuron disease and global cerebral ischemia. The <it>Wld</it>^{<it>S </it>}gene encodes a novel Ube4b-Nmnat1 chimeric protein (Wld^Sprotein) that is responsible for conferring the neuroprotective phenotype. How the chimeric Wld^Sprotein confers neuroprotection remains controversial, but several studies have shown that expression in neurons <it>in vivo </it>and <it>in vitro </it>modifies key cellular pathways, including; NAD biosynthesis, ubiquitination, the mitochondrial proteome, cell cycle status and cell stress. Whether similar changes are induced in non-neuronal tissue and organs at a basal level <it>in vivo </it>remains to be determined. This may be of particular importance for the development and application of neuroprotective therapeutic strategies based around <it>Wld</it>^<it>S</it>-mediated pathways designed for use in human patients.</p> <p>Results</p> <p>We have undertaken a detailed analysis of non-neuronal <it>Wld</it>^{<it>S </it>}expression in <it>Wld</it>^{<it>S </it>}mice, alongside gravimetric and histological analyses, to examine the influence of <it>Wld</it>^{<it>S </it>}expression in non-neuronal tissues. We show that expression of <it>Wld</it>^{<it>S </it>}RNA and protein are not restricted to neuronal tissue, but that the relative RNA and protein expression levels rarely correlate in these non-neuronal tissues. We show that <it>Wld</it>^{<it>S </it>}mice have normal body weight and growth characteristics as well as gravimetrically and histologically normal organs, regardless of Wld^Sprotein levels. Finally, we demonstrate that previously reported <it>Wld</it>^<it>S</it>-induced changes in cell cycle and cell stress status are neuronal-specific, not recapitulated in non-neuronal tissues at a basal level.</p> <p>Conclusions</p> <p>We conclude that expression of Wld^Sprotein has no adverse effects on non-neuronal tissue at a basal level <it>in vivo</it>, supporting the possibility of its safe use in future therapeutic strategies targeting axonal and/or synaptic compartments in patients with neurodegenerative disease. Future experiments determining whether Wld^Sprotein can modify responses to injury in non-neuronal tissue are now required.</p

What Therapists Learn from Psychotherapy Clients: Effects on Personal and Professional Lives

While considerable research has examined how clients learn from psychotherapists, there is only sparse literature on what therapists learn from their therapy clients. In a qualitative, exploratory study, nine researchers interviewed 61 psychologists from across North America in order to see what psychotherapists may have learned and how they have been affected by their clients both personally and professionally. Participants responded to nine open-ended questions on learning about life-lessons, relationships, ethical decision-making, coping, courage, wisdom, psychopathology, personality, cultural differences, lifespan development and more. Participants’ richly elaborated responses were coded thematically and narrative data illustrates the most frequent themes. Therapists reported learning a great deal across each of the questions, consistently expressing respect for their clients\u27 resilience, courage and moral sensibilities

State-wide random seroprevalence survey of SARS-CoV-2 past infection in a southern US State, 2020.

The purpose of this cross-sectional study was to estimate the proportion of Arkansas residents who were infected with the SARS-CoV-2 virus between May and December 2020 and to assess the determinants of infection. To estimate seroprevalence, a state-wide population-based random-digit dial sample of non-institutionalized adults in Arkansas was surveyed. Exposures were age, sex, race/ethnicity, education, occupation, contact with infected persons, comorbidities, height, and weight. The outcome was past COVID-19 infection measured by serum antibody test. We found a prevalence of 15.1% (95% CI: 11.1%, 20.2%) by December 2020. Seropositivity was significantly elevated among participants who were non-Hispanic Black, Hispanic (prevalence ratio [PRs]:1.4 [95% CI: 0.8, 2.4] and 2.3 [95% CI: 1.3, 4.0], respectively), worked in high-demand essential services (PR: 2.5 [95% CI: 1.5, 4.1]), did not have a college degree (PR: 1.6 [95% CI: 1.0, 2.4]), had an infected household or extra-household contact (PRs: 4.7 [95% CI: 2.1, 10.1] and 2.6 [95% CI: 1.2, 5.7], respectively), and were contacted in November or December (PR: 3.6 [95% CI: 1.9, 6.9]). Our results indicate that by December 2020, one out six persons in Arkansas had a past SARS-CoV-2 infection

JARID2 haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome

Purpose: JARID2, located on chromosome 6p22.3, is a regulator of histone methyltransferase complexes that is expressed in human neurons. So far, 13 individuals sharing clinical features including intellectual disability (ID) were reported with de novo heterozygous deletions in 6p22–p24 encompassing the full length JARID2 gene (OMIM 601594). However, all published individuals to date have a deletion of at least one other adjoining gene, making it difficult to determine if JARID2 is the critical gene responsible for the shared features. We aim to confirm JARID2 as a human disease gene and further elucidate the associated clinical phenotype. Methods: Chromosome microarray analysis, exome sequencing, and an online matching platform (GeneMatcher) were used to identify individuals with single-nucleotide variants or deletions involving JARID2. Results: We report 16 individuals in 15 families with a deletion or single-nucleotide variant in JARID2. Several of these variants are likely to result in haploinsufficiency due to nonsense-mediated messenger RNA (mRNA) decay. All individuals have developmental delay and/or ID and share some overlapping clinical characteristics such as facial features with those who have larger deletions involving JARID2. Conclusion: We report that JARID2 haploinsufficiency leads to a clinically distinct neurodevelopmental syndrome, thus establishing gene–disease validity for the purpose of diagnostic reporting

JARID2 haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome

Purpose: JARID2, located on chromosome 6p22.3, is a regulator of histone methyltransferase complexes that is expressed in human neurons. So far, 13 individuals sharing clinical features including intellectual disability (ID) were reported with de novo heterozygous deletions in 6p22–p24 encompassing the full length JARID2 gene (OMIM 601594). However, all published individuals to date have a deletion of at least one other adjoining gene, making it difficult to determine if JARID2 is the critical gene responsible for the shared features. We aim to confirm JARID2 as a human disease gene and further elucidate the associated clinical phenotype. Methods: Chromosome microarray analysis, exome sequencing, and an online matching platform (GeneMatcher) were used to identify individuals with single-nucleotide variants or deletions involving JARID2. Results: We report 16 individuals in 15 families with a deletion or single-nucleotide variant in JARID2. Several of these variants are likely to result in haploinsufficiency due to nonsense-mediated messenger RNA (mRNA) decay. All individuals have developmental delay and/or ID and share some overlapping clinical characteristics such as facial features with those who have larger deletions involving JARID2. Conclusion: We report that JARID2 haploinsufficiency leads to a clinically distinct neurodevelopmental syndrome, thus establishing gene–disease validity for the purpose of diagnostic reporting