Rare missense variants of the leukocyte common antigen related receptor (LAR) display reduced activity in transcellular adhesion and synapse formation.

The leukocyte common antigen related receptor (LAR) is a member of the LAR receptor protein tyrosine phosphatase (RPTP) family of synaptic adhesion molecules that contribute to the proper alignment and specialization of synaptic connections in the mammalian brain. LAR-RPTP members have been genetically associated with neuropsychiatric disorders, but the molecular consequences of genetic perturbations of LAR remain unstudied. Using exome sequencing data from psychiatric patients and controls, we identify rare missense variants of LAR that render the extracellular domain (ECD) unstable and susceptible to proteolytic cleavage.

Model-based estimation of thyroid cancer incidence from ultrasound examinations in the Fukushima Health Management Survey: estimated results considering the non-examinees in the first, second and third rounds of the cohort study.

Background: In October 2011, the Fukushima prefectural government started a thyroid ultrasound examination (TUE) as part of the Fukushima Health Management Survey following the Fukushima Daiichi Nuclear Power Plant accident. The proportion of examinees is an important factor when interpreting the results.

Objectives: To construct models that assess the relationship between the proportion of non-examinees and the characteristics of eligible participants in the first-round to third-round TUEs.

Changes in peripheral blood test results among adults in the six years following the Great East Japan Earthquake: the Fukushima Health Management Survey.

The Fukushima Health Management Survey, conducted by Fukushima Prefecture since the 2011 Great East Japan Earthquake (GEJE), has not identified any health effects from radiation exposure.　Complete blood counts (CBC), which are sensitive to radiation exposure, have not shown lymphocytopenia, neutropenia, anemia, or thrombocytopenia, but the white blood cell fractions have not yet been analyzed since 2011.　We classified 25,885 residents (11,383 male, 14,502 female;age range, 16-84 years) in evacuation areas with external exposure dose estimates based on behavioral surveys conducted 4 months after the GEJE into two groups (0-1 [≥0 and <1] and ≥1 mSv) and analyzed changes in CBC and leukocyte fractions from fiscal year (FY) 2011 to FY2017 and their influencing factors.

Rare missense variants of the leukocyte common antigen related receptor (LAR) display reduced activity in transcellular adhesion and synapse formation.

The leukocyte common antigen related receptor (LAR) is a member of the LAR receptor protein tyrosine phosphatase (RPTP) family of synaptic adhesion molecules that contribute to the proper alignment and specialization of synaptic connections in the mammalian brain. LAR-RPTP members have been genetically associated with neuropsychiatric disorders, but the molecular consequences of genetic perturbations of LAR remain unstudied. Using exome sequencing data from psychiatric patients and controls, we identify rare missense variants of LAR that render the extracellular domain (ECD) unstable and susceptible to proteolytic cleavage.

Screening of 1-Month-Old Infants With Prolonged QT Interval and Its Cutoff Value.

Background: The prevalence of congenital long QT syndrome (LQTS) (1 : 2,000) is based on genetic testing and ECG data, but the prevalence of electrocardiographically determined prolonged corrected QT interval (pQTc) in infants is unclear.

Methods And Results: Subjects were 10,282 1-month-old infants who participated in 2 prospective ECG screening studies performed in 2010-2011 and 2014-2016. Infants with a QTc ≥0.

The TrkC-PTPσ complex governs synapse maturation and anxiogenic avoidance via synaptic protein phosphorylation.

The precise organization of pre- and postsynaptic terminals is crucial for normal synaptic function in the brain. In addition to its canonical role as a neurotrophin-3 receptor tyrosine kinase, postsynaptic TrkC promotes excitatory synapse organization through interaction with presynaptic receptor-type tyrosine phosphatase PTPσ. To isolate the synaptic organizer function of TrkC from its role as a neurotrophin-3 receptor, we generated mice carrying TrkC point mutations that selectively abolish PTPσ binding.

Molecular mechanism of contactin 2 homophilic interaction.

Contactin 2 (CNTN2) is a cell adhesion molecule involved in axon guidance, neuronal migration, and fasciculation. The ectodomains of CNTN1-CNTN6 are composed of six Ig domains (Ig1-Ig6) and four FN domains. Here, we show that CNTN2 forms transient homophilic interactions (K ∼200 nM).

An Alternative Approach to Determining Metabolic Syndrome Component Cutoffs in Children and Adolescents Using Segmental Regression Analysis.

The prevalence of metabolic syndrome is increasing in children and adolescents. Although some diagnostic criteria for metabolic syndrome exist, further research is needed to determine appropriate age-, sex-, and race-specific cutoffs for each component. Health examinations were conducted in 1,679 children aged 6-15 years in 9 regions of Japan.

Structural and functional characterization of the IgSF21-neurexin2α complex and its related signaling pathways in the regulation of inhibitory synapse organization.

The prevailing model behind synapse development and specificity is that a multitude of adhesion molecules engage in transsynaptic interactions to induce pre- and postsynaptic assembly. How these extracellular interactions translate into intracellular signal transduction for synaptic assembly remains unclear. Here, we focus on a synapse organizing complex formed by immunoglobulin superfamily member 21 (IgSF21) and neurexin2α (Nrxn2α) that regulates GABAergic synapse development in the mouse brain.

Effects of Overweight on Risk of Thyroid Nodules in Children and Adolescents: The Fukushima Health Management Survey.

Context: Examining how overweight/obesity impacts thyroid nodule development in children and adolescents by sex and age allows speculation on the mechanism.

Objective: We examined whether overweight/obesity in children and adolescents is associated with thyroid nodule development by sex and age.

Methods: Approximately 300 000 participants who underwent thyroid ultrasonography in the Fukushima Health Management Survey after a nuclear accident were enrolled.

Workplace factors associated with willingness to undergo human immunodeficiency virus testing during workplace health checkups.

Background: To examine workplace factors associated with willingness to undergo human immunodeficiency virus (HIV) testing during workplace health checkups.

Methods: This cross-sectional study used an Internet-based self-administered questionnaire to obtain data from a pool of 24,287 Japanese workers. Binary and multiple logistic regression analyses evaluated the association between workplace factors and HIV testing.

α-Synuclein Preformed Fibrils Bind to β-Neurexins and Impair β-Neurexin-Mediated Presynaptic Organization.

Synucleinopathies form a group of neurodegenerative diseases defined by the misfolding and aggregation of α-synuclein (α-syn). Abnormal accumulation and spreading of α-syn aggregates lead to synapse dysfunction and neuronal cell death. Yet, little is known about the synaptic mechanisms underlying the α-syn pathology.

Designer molecules of the synaptic organizer MDGA1 reveal 3D conformational control of biological function.

MDGAs (MAM domain-containing glycosylphosphatidylinositol anchors) are synaptic cell surface molecules that regulate the formation of trans-synaptic bridges between neurexins (NRXNs) and neuroligins (NLGNs), which promote synaptic development. Mutations in MDGAs are implicated in various neuropsychiatric diseases. MDGAs bind NLGNs in cis on the postsynaptic membrane and physically block NLGNs from binding to NRXNs.

Delayed Diagnosis and Prognostic Impact of Breast Cancer During the COVID-19 Pandemic.

Background: Breast screening services were suspended for several months owing to the coronavirus disease 2019 (COVID-19) pandemic. We estimated the potential impact on breast cancer mortality using long-term global observations. However, the magnitude of the impact may vary across countries; therefore, we conducted an analysis and modeling study of this impact in Japan.