Divergent projections of the prelimbic cortex mediate autism- and anxiety-like behaviors.

The comorbidity of autism spectrum disorder and anxiety is common, but the underlying circuitry is poorly understood. Here, Tmem74-/- mice showed autism- and anxiety-like behaviors along with increased excitability of pyramidal neurons (PNs) in the prelimbic cortex (PL), which were reversed by Tmem74 re-expression and chemogenetic inhibition in PNs of the PL. To determine the underlying circuitry, we performed conditional deletion of Tmem74 in the PNs of PL of mice, and we found that alterations in the PL projections to fast-spiking interneurons (FSIs) in the dorsal striatum (dSTR) (PLPNs-dSTRFSIs) mediated the hyperexcitability of FSIs and autism-like behaviors and that alterations in the PL projections to the PNs of the basolateral amygdaloid nucleus (BLA) (PLPNs-BLAPNs) mediated the hyperexcitability of PNs and anxiety-like behaviors. However, the two populations of PNs in the PL had different spatial locations, optogenetic manipulations revealed that alterations in the activity in the PL-dSTR or PL-BLA circuits led to autism- or anxiety-like behaviors, respectively. Collectively, these findings highlight that the hyperactivity of the two populations of PNs in the PL mediates autism and anxiety comorbidity through the PL-dSTR and PL-BLA circuits, which may lead to the development of new therapeutics for the autism and anxiety comorbidity.

Massilia aquatica sp. nov., Isolated from a Subtropical Stream in China.

A Gram-stain-negative, catalase- and oxidase-positive, rod-shaped and motile strain FT127WT was isolated from a subtropical stream in China. Comparison based on 16S rRNA gene sequences showed that strain FT127WT belongs to genus Massilia and shares 98.5% similarity with Massilia buxea A9T as its closest neighbor. The genome size of strain FT127WT was 6.65 Mbp with G + C content of 65.3%. The calculated pairwise OrthoANIu values and digital DNA-DNA hybridization values between strain FT127WT and each of strains M. buxea KCTC 52429T, Massilia armeniaca ZMN-3T, Massilia plicata DSM 17505T and Massilia namucuonensis CGMCC 1.11014T were less than 83.1% and 26.6%, respectively. The reconstructed phylogenomic tree based on concatenated 92 core genes showed that strain FT127WT clusters closely with M. namucuonensis CGMCC 1.11014T. The respiratory quinone of strain FT127WT was Q-8. The major fatty acids were C16:1 ω7c, C16:0 and C12:0. The polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol and one unidentified phospholipid. Combining above all characteristics, strain FT127WT should represent a novel species within genus Massilia, for which the name Massilia aquatica sp. nov. (type strain FT127WT = GDMCC 1.1690T = KACC 21482T) is proposed.

Pilot Study to Measure Deficits in Proprioception in Children With Somatodyspraxia.

IMPORTANCE: Given the importance of proprioception in motor coordination, the identification of sensory deficits contributing to motor challenges is crucial for appropriate intervention; however, objective proprioceptive tests are not currently available in pediatric clinical practice. OBJECTIVE: To pilot test methods for assessing proprioception in children. Children with somatodyspraxia were predicted to have reduced proprioceptive awareness compared with age-matched control children. DESIGN: Observational study. SETTING: Individual clinic. PARTICIPANTS: Ten children identified as having somatodyspraxia and 10 typically developing children, ages 6-8 yr. OUTCOMES AND MEASURES: Spatial awareness and force perception were assessed by having the children match arm positions and grip and pinch forces using electronic dynamometers. RESULTS: All children were able to complete the proprioceptive assessments. Of those identified as having somatodyspraxia, 90% showed deficits in at least one area of proprioception. Children with somatodyspraxia performed more poorly on spatial awareness and force perception tests than typically developing children (p < .05). CONCLUSIONS AND RELEVANCE: Children with dyspraxia have difficulties with spatial awareness and force perception, confirming a somatosensory contribution to dyspraxia. WHAT THIS ARTICLE ADDS: This article presents a framework and methods to measure proprioception in children. These methods will allow occupational therapy practitioners to quantify the proprioceptive deficits common in children with dyspraxia.

[Epidemiological status and risk factors of hyperuricemia in rural area of the Three Gorges].

OBJECTIVE: To explore the epidemiological status and risk factors of hyperuricemia in rural area of the Three Gorges. METHODS: A cross-sectional survey was carried out in rural area of Yiling District, Yichang City, which was located north-west bank of Xiling Gorge in 2007. A standard structure questionnaire was used to collect demographic data, social-economic status and life-style features. Fasting venous blood was collected and serum uric acid (SUA) was determined. Hyperuricemia was defined as SUA levels ≥ 417 µ mol/L (70 mg/L) in men and ≥ 357 µmol/L (60 mg/L) in women. Multiple logistic regression analysis was used to analysed the risk factors of hyperuricemia. RESULTS: A total of 9354 participants aged 35 and above were included, 19.9% (1866/9354) participants were the Three Gorges migrants. Serum uric acid level in men was significantly higher than that in women [(285.1 ± 80.2) µmol/L vs. (210.3 ± 65.0) µmol/L,P < 0.01].Serum uric acid level increased significantly in both genders in proportion to increase of age, and was higher in men than in women in all age groups (all P < 0.01). The age-adjusted prevalence was significantly higher in men than in women (5.6% vs. 3.3%, P < 0.01), and was also higher in men aged 35-44 and aged 45-54 than in women (both P < 0.01). There was no significance in prevalence of hyperuricemia in both men and women aged 55-64 and aged ≥ 65. After adjusting age, gender, educational level, migration and occupation, the multiple logistic regression analysis showed that the prevalence of hyperuricemia was higher in alcohol drinking participants than that of non-alcohol drinking participants (OR = 2.06, 95%CI:1.59-2.67, P < 0.01), and in participants used to consume less green vegetables and fruits than in participants consuming more green vegetables and fruits (OR = 1.77, 95% CI:1.27-2.47, P < 0.01). CONCLUSIONS: The prevalence of hyperuricemia is relatively low in rural area of the Three Gorges.Alcohol drinking and low intake of green vegetables and fruits are the risk factors of hyperuricemia in this population.

Striatal CDK5 Regulates Cholinergic Neuron Activation and Dyskinesia-like Behaviors through BK Channels.

Disturbance of the cholinergic system plays a crucial role in the pathological progression of neurological diseases that cause dyskinesia-like behaviors. However, the molecular mechanisms underlying this disturbance remain elusive. Here, we showed that cyclin-dependent kinase 5 (Cdk5) was reduced in cholinergic neurons of midbrain according to the single-nucleus RNA sequencing analysis. Serum levels of CDK5 also decreased in patients with Parkinson's disease accompanied by motor symptoms. Moreover, Cdk5 deficiency in cholinergic neurons triggered paw tremors, abnormal motor coordination, and motor balance deficits in mice. These symptoms occurred along with cholinergic neuron hyperexcitability and increases in the current density of large-conductance Ca2+-activated K+ channels (BK channels). Pharmacological inhibition of BK channels restrained the excessive intrinsic excitability of striatal cholinergic neurons in Cdk5-deficient mice. Furthermore, CDK5 interacted with BK channels and negatively regulated BK channel activity via phosphorylation of threonine-908. Restoration of CDK5 expression in striatal cholinergic neurons reduced dyskinesia-like behaviors in ChAT-Cre;Cdk5f/f mice. Together, these findings indicate that CDK5-induced phosphorylation of BK channels involves in cholinergic-neuron-mediated motor function, providing a potential new therapeutic target for treating dyskinesia-like behaviors arising from neurological diseases.