JAKMIP1, a Novel Regulator of Neuronal Translation, Modulates Synaptic Function and Autistic-like Behaviors in Mouse.

Autism spectrum disorder (ASD) is a heritable, common neurodevelopmental disorder with diverse genetic causes. Several studies have implicated protein synthesis as one among several of its potential convergent mechanisms. We originally identified Janus kinase and microtubule-interacting protein 1 (JAKMIP1) as differentially expressed in patients with distinct syndromic forms of ASD, fragile X syndrome, and 15q duplication syndrome. Here, we provide multiple lines of evidence that JAKMIP1 is a component of polyribosomes and an RNP translational regulatory complex that includes fragile X mental retardation protein, DEAD box helicase 5, and the poly(A) binding protein cytoplasmic 1. JAKMIP1 loss dysregulates neuronal translation during synaptic development, affecting glutamatergic NMDAR signaling, and results in social deficits, stereotyped activity, abnormal postnatal vocalizations, and other autistic-like behaviors in the mouse. These findings define an important and novel role for JAKMIP1 in neural development and further highlight pathways regulating mRNA translation during synaptogenesis in the genesis of neurodevelopmental disorders

Cardiac arrest and cardiopulmonary resuscitation outcome reports : update of the Utstein resuscitation registry template for in-hospital cardiac arrest : a consensus report from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian and New Zealand Council on Resuscitation, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa, Resuscitation Council of Asia)

Utstein-style reporting templates provide a structured framework with which to compare systems of care for cardiac arrest. The 2004 Utstein reporting template encompassed both out-of-hospital and in-hospital cardiac arrest. A 2015 update of the Utstein template focused on out-of-hospital cardiac arrest, which makes this update of the in-hospital template timely. Representatives of the International Liaison Committee on Resuscitation developed an updated in-hospital Utstein reporting template iteratively by meeting face-to-face, by teleconference, and by online surveys between 2013 and 2018. Data elements were grouped by hospital factors, patient variables, pre-event factors, cardiac arrest and postresuscitation processes, and outcomes. Elements were classified as core or supplemental by use of a modified Delphi process. Variables were described as core if they were considered essential. Core variables should enable reasonable comparisons between systems and are considered essential for quality improvement programs. Together with core variables, supplementary variables are considered useful for research

Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel

Importance: Compared with non-Hispanic White individuals, African American individuals from the same community are approximately twice as likely to develop Alzheimer disease. Despite this disparity, the largest Alzheimer disease genome-wide association studies to date have been conducted in non-Hispanic White individuals. In the largest association analyses of Alzheimer disease in African American individuals, ABCA7, TREM2, and an intergenic locus at 5q35 were previously implicated. Objective: To identify additional risk loci in African American individuals by increasing the sample size and using the African Genome Resource panel. Design, setting, and participants: This genome-wide association meta-analysis used case-control and family-based data sets from the Alzheimer Disease Genetics Consortium. There were multiple recruitment sites throughout the United States that included individuals with Alzheimer disease and controls of African American ancestry. Analysis began October 2018 and ended September 2019. Main outcomes and measures: Diagnosis of Alzheimer disease. Results: A total of 2784 individuals with Alzheimer disease (1944 female [69.8%]) and 5222 controls (3743 female [71.7%]) were analyzed (mean [SD] age at last evaluation, 74.2 [13.6] years). Associations with 4 novel common loci centered near the intracellular glycoprotein trafficking gene EDEM1 (3p26; P = 8.9 × 10-7), near the immune response gene ALCAM (3q13; P = 9.3 × 10-7), within GPC6 (13q31; P = 4.1 × 10-7), a gene critical for recruitment of glutamatergic receptors to the neuronal membrane, and within VRK3 (19q13.33; P = 3.5 × 10-7), a gene involved in glutamate neurotoxicity, were identified. In addition, several loci associated with rare variants, including a genome-wide significant intergenic locus near IGF1R at 15q26 (P = 1.7 × 10-9) and 6 additional loci with suggestive significance (P ≤ 5 × 10-7) such as API5 at 11p12 (P = 8.8 × 10-8) and RBFOX1 at 16p13 (P = 5.4 × 10-7) were identified. Gene expression data from brain tissue demonstrate association of ALCAM, ARAP1, GPC6, and RBFOX1 with brain β-amyloid load. Of 25 known loci associated with Alzheimer disease in non-Hispanic White individuals, only APOE, ABCA7, TREM2, BIN1, CD2AP, FERMT2, and WWOX were implicated at a nominal significance level or stronger in African American individuals. Pathway analyses strongly support the notion that immunity, lipid processing, and intracellular trafficking pathways underlying Alzheimer disease in African American individuals overlap with those observed in non-Hispanic White individuals. A new pathway emerging from these analyses is the kidney system, suggesting a novel mechanism for Alzheimer disease that needs further exploration. Conclusions and relevance: While the major pathways involved in Alzheimer disease etiology in African American individuals are similar to those in non-Hispanic White individuals, the disease-associated loci within these pathways differ

Os Contornos e o Entorno da Nova Sociologia da Moral

Neste ensaio vou expor brevemente como vejo o desenvolvimento do campo da Sociologia da Moral, com foco em seu potencial fundamentalmente interdisciplinar, destacando os estudos e tradições que merecem ser incorporados à sociologia. A moral, como tema de investigação da ciência social, perpassa os campos da psicologia (social e do desenvolvimento), sociologia, antropologia, neurociências e economia. Aqueles entre nós implicados no seu desenvolvimento afirmam que ela serve de fundamento para toda a organização e interação social. Assumo, implicitamente, a posição do filósofo Charles Taylor e do sociólogo Christian Smith de que os seres humanos vivem envolvidos em teias de significados, pelas quais são moldados, conforme versões de "certo" e de "bem". Os seres humanos são fundamentalmente morais, não no sentido de serem convencionalmente altruístas ou de se preocuparem com os outros, mas de que as pessoas humanas, por serem seres sociais habitando um espaço social, devem assumir posições sobre temas relevantes nessas sociedades e grupos. As pessoas, de um modo geral, nesse meu paradigma, ancoram seus sentidos de si em posicionamentos morais, padrões que oferecem um solo a partir do qual dão sentido ao mundo através de lentes morais. Uma sociologia da moral compreende a formação dessas crenças, sua relativa imutabilidade ou as circunstâncias pelas quais elas mudam, sua influência sobre a ação e sua reconstrução retrospectiva diante de efeitos desajustados ou de pressões sociais