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Technologies that can safely edit genes in the brains of adult animals may revolutionize the treatment of neurological diseases and the understanding of brain function. Here, we demonstrate that intracranial injection of CRISPR–Gold, a nonviral delivery vehicle for the CRISPR–Cas9 ribonucleoprotein, can edit genes in the brains of adult mice in multiple mouse models. CRISPR–Gold can deliver both Cas9 and Cpf1 ribonucleoproteins, and can edit all of the major cell types in the brain, including neurons, astrocytes and microglia, with undetectable levels of toxicity at the doses used. We also show that CRISPR–Gold designed to target the metabotropic glutamate receptor 5 (mGluR5) gene can efficiently reduce local mGluR5 levels in the striatum after an intracranial injection. The effect can also rescue mice from the exaggerated repetitive behaviours caused by fragile X syndrome, a common single-gene form of autism spectrum disorders. CRISPR–Gold may significantly accelerate the development of brain-targeted therapeutics and enable the rapid development of focal brain-knockout animal models.

Background This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data. Methods This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated. Results In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes. Conclusion The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

Summary How transmitter receptors modulate neuronal signaling by regulating voltage-gated ion channel expression remains an open question. Here we report dendritic localization of mRNA of Kv4.2 voltage-gated potassium channel, which regulates synaptic plasticity, and its local translational regulation by fragile X mental retardation protein (FMRP) linked to fragile X syndrome (FXS), the most common heritable mental retardation. FMRP suppression of Kv4.2 is revealed by elevation of Kv4.2 in neurons from fmr1 knockout (KO) mice, and in neurons expressing Kv4.2-3′UTR that binds FMRP. Moreover, treating hippocampal slices from fmr1 KO mice with Kv4 channel blocker restores long-term potentiation (LTP) induced by moderate stimuli. Surprisingly, recovery of Kv4.2 after N-methyl-D-aspartate receptor (NMDAR)-induced degradation also requires FMRP, likely due to NMDAR-induced FMRP dephosphorylation, which turns off FMRP suppression of Kv4.2. Our study of FMRP regulation of Kv4.2 reveals a novel aspect of NMDAR signaling and a new FMRP target of potential relevance to FXS.

Summary A major gap in our understanding of sensation is how a single sensory neuron can differentially respond to a multitude of different stimuli (polymodality), such as propio- or noci- sensation. The prevailing hypothesis is that different stimuli are transduced through ion channels with diverse properties and subunit composition. In a screen for ion channel genes expressed in polymodal nociceptive neurons we identified Ppk26, a member of the trimeric Degenerin/Epithelial Sodium (DEG/ENaC) channel family as being necessary for proper locomotion behavior in Drosophila larvae in a mutually dependent fashion with co-expressed Ppk1, another member of the same family. Mutants lacking Ppk1 and Ppk26 were defective in mechanical but not thermal nociception behavior. Mutants of Piezo, a channel involved in mechanical nociception in the same neurons, did not show a defect in locomotion, suggesting distinct molecular machinery for mediating locomotor feedback and mechanical nociception.

The cross section of the reaction 112 Sn(α, γ ) 116 Te has been measured in the energy range of astrophysical interest for the p-process. Highly enriched self-supporting 112 Sn foils were bombarded with α beams in the effective center of mass energy range from 7.59 to 11.42 MeV at the Notre Dame FN Tandem Van de Graaff accelerator. The characteristic activity of 116 Te was counted with a pair of large volume Ge clover detectors in close geometry to maximize the detection efficiency. The cross section of the concurrent (α, p) reaction has also been measured. The results are compared with statistical model predictions for different global α-nucleus potentials.

Rapamycin, a specific inhibitor for mTOR complex 1, is an FDA-approved immunosuppressant for organ transplant. Recent developments have raised the prospect of using rapamycin to treat cancer or diabetes and to delay aging. It is therefore important to assess how rapamycin treatment affects glucose homeostasis. Here, we show that the same rapamycin treatment reported to extend mouse life span significantly impaired glucose homeostasis of aged mice. Moreover, rapamycin treatment of lean C57B/L6 mice reduced glucose-stimulated insulin secretion in vivo and ex vivo as well as the insulin content and beta cell mass of pancreatic islets. Confounding the diminished capacity for insulin release, rapamycin decreased insulin sensitivity. The multitude of rapamycin effects thus all lead to glucose intolerance. As our findings reveal that chronic rapamycin treatment could be diabetogenic, monitoring glucose homeostasis is crucial when using rapamycin as a therapeutic as well as experimental reagent.

The aim of this study was to investigate the prevalence and correlates of depressive symptoms in the largest number of Korean individuals examined to date. We analyzed cross-sectional data collected from 229,595 Korean adults aged 19 yr and above who participated in a Korean Community Health Survey conducted in 2009. The Center for Epidemiologic Studies Depression Scale (CES-D) was used as the measurement tool for depressive symptoms (CES-D score over 16) and definite depression (CES-D score over 25). Multivariate logistic regression analysis was performed to identify associations between sociodemographic factors and depressive symptoms. The percentages of depressive symptoms and definite depression in the total study population were 11% (7.8% for men, 14.0% for women) and 3.7%, (2.4% for men, 5.0% for women), respectively. Female gender, older age, disrupted marital status, low education and income level, multigenerational household composition and metropolitan residence were associated with greater risk of depressive symptoms. The present study provides a valid prevalence and correlates of depressive symptoms, using the largest representative sample of the Korean general population to date. Various sociodemographic factors contribute to the prevalence and effects of depressive symptoms in Korea.