Early-initiated childhood reading for pleasure: associations with better cognitive performance, mental well-being and brain structure in young adolescence.

BACKGROUND: Childhood is a crucial neurodevelopmental period. We investigated whether childhood reading for pleasure (RfP) was related to young adolescent assessments of cognition, mental health, and brain structure. METHODS: We conducted a cross-sectional and longitudinal study in a large-scale US national cohort (10 000 + young adolescents), using the well-established linear mixed model and structural equation methods for twin study, longitudinal and mediation analyses. A 2-sample Mendelian randomization (MR) analysis for potential causal inference was also performed. Important factors including socio-economic status were controlled. RESULTS: Early-initiated long-standing childhood RfP (early RfP) was highly positively correlated with performance on cognitive tests and significantly negatively correlated with mental health problem scores of young adolescents. These participants with higher early RfP scores exhibited moderately larger total brain cortical areas and volumes, with increased regions including the temporal, frontal, insula, supramarginal; left angular, para-hippocampal; right middle-occipital, anterior-cingulate, orbital areas; and subcortical ventral-diencephalon and thalamus. These brain structures were significantly related to their cognitive and mental health scores, and displayed significant mediation effects. Early RfP was longitudinally associated with higher crystallized cognition and lower attention symptoms at follow-up. Approximately 12 h/week of youth regular RfP was cognitively optimal. We further observed a moderately significant heritability of early RfP, with considerable contribution from environments. MR analysis revealed beneficial causal associations of early RfP with adult cognitive performance and left superior temporal structure. CONCLUSIONS: These findings, for the first time, revealed the important relationships of early RfP with subsequent brain and cognitive development and mental well-being.

NSDHL-containing duplication at Xq28 in a male patient with autism spectrum disorder: a case report.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which genetics plays a key aetiological role. The gene encoding NAD(P)H steroid dehydrogenase-like protein (NSDHL) is expressed in developing cortical neurons and glia, and its mutation may result in intellectual disability or congenital hemidysplasia. CASE PRESENTATION: An 8-year-old boy presented with a 260-kb NSDHL-containing duplication at Xq28 (151,868,909 - 152,129,300) inherited from his mother. His clinical features included defects in social communication and interaction, restricted interests, attention deficit, impulsive behaviour, minor facial anomalies and serum free fatty acid abnormality. CONCLUSION: This is the first report of an ASD patient with a related NSDHL-containing duplication at Xq28. Further studies and case reports are required for genetic research to demonstrate that duplication as well as mutation can cause neurodevelopmental diseases.

PDGFRß Cells Rapidly Relay Inflammatory Signal from the Circulatory System to Neurons via Chemokine CCL2.

Acute infection, if not kept in check, can lead to systemic inflammatory responses in the brain. Here, we show that within 2 hr of systemic inflammation, PDGFRß mural cells of blood vessels rapidly secrete chemokine CCL2, which in turn increases total neuronal excitability by promoting excitatory synaptic transmission in glutamatergic neurons of multiple brain regions. By single-cell RNA sequencing, we identified Col1a1 and Rgs5 subgroups of PDGFRß cells as the main source of CCL2. Lipopolysaccharide (LPS)- or Poly(I:C)-treated pericyte culture medium induced similar effects in a CCL2-dependent manner. Importantly, in Pdgfrb-Cre;Ccl2fl/fl mice, LPS-induced increase in excitatory synaptic transmission was significantly attenuated. These results demonstrate in vivo that PDGFRß cells function as initial sensors of external insults by secreting CCL2, which relays the signal to the central nervous system. Through their gateway position in the brain, PDGFRß cells are ideally positioned to respond rapidly to environmental changes and to coordinate responses.

Alterations in plasma cytokine levels in chinese children with autism spectrum disorder.

Genetic alterations, together with environmental risk factors during infancy and childhood, contribute significantly to the etiology of autism spectrum disorder (ASD), a heterogeneous neurodevelopmental condition characterized by impairments in social interaction and restricted, repetitive behaviors. Mounting evidence points to a critical contribution of immunological risk factors to the development of ASD. By affecting multiple neurodevelopmental processes, immune system dysfunction could act as a point of convergence between genetics and environmental factors in ASD. Previous studies have shown altered cytokine levels in individuals with ASD, but research in Asian populations are limited. Here, we measured the plasma levels of 11 candidate cytokines in ASD and typically developing (TD) children. The cohort included 41 TD children and 87 children with ASD, aged 1-6 years. We found that as compared to the TD group, children with ASD had higher plasma levels of Eotaxin, TGF-ß1 and TNF-α. The increase in TGF-ß1 level was most significant in males, while the increase in Eotaxin was most significant in females. Eotaxin level negatively correlated with the social affect score (SA) in ADOS, while TNF-α level positively correlated with total development quotient (DQ), measured using GMDS. These pilot findings suggest potentially important roles of Eotaxin, TGF-ß1 and TNF-α in ASD in the Chinese population. Autism Res 2018, 11: 989-999. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Alteration of immune system function is an important risk factor for autism spectrum disorder (ASD). Here we found that the levels of cytokines, including Eotaxin, TGF-ß1 and TNF-α, are elevated in Chinese children with ASD, as compared to typically developing children. The change in TGF-ß1 level was most prominent in boys, while that of Eotaxin was more significant in girls. These results provide evidence for changes in cytokine profile in Chinese children with ASD.

High activity of the stress promoter contributes to susceptibility to stress in the tree shrew.

Stress is increasingly present in everyday life in our fast-paced society and involved in the pathogenesis of many psychiatric diseases. Corticotrophin-releasing-hormone (CRH) plays a pivotal role in regulating the stress responses. The tree shrews are highly vulnerable to stress which makes them the promising animal models for studying stress responses. However, the mechanisms underlying their high stress-susceptibility remained unknown. Here we confirmed that cortisol was the dominate corticosteroid in tree shrew and was significantly increased after acute stress. Our study showed that the function of tree shrew CRH - hypothalamic-pituitary-adrenal (HPA) axis was nearly identical to human that contributed little to their hyper-responsiveness to stress. Using CRH transcriptional regulation analysis we discovered a peculiar active glucocorticoid receptor response element (aGRE) site within the tree shrew CRH promoter, which continued to recruit co-activators including SRC-1 (steroid receptor co-activator-1) to promote CRH transcription under basal or forskolin/dexamethasone treatment conditions. Basal CRH mRNA increased when the aGRE was knocked into the CRH promoter in human HeLa cells using CAS9/CRISPR. The aGRE functioned critically to form the "Stress promoter" that contributed to the higher CRH expression and susceptibility to stress. These findings implicated novel molecular bases of the stress-related diseases in specific populations.

Distribution of corticotropin-releasing factor in the tree shrew brain.

Corticotropin-releasing factor (CRF) in the brain plays an important role in regulations of physiological and behavioral processes, yet CRF distribution in tree shrew brain has not been thoroughly and systematically reported. Here we examined the distribution of CRF immunoreactivity in the brain of tree shrews (Tupaia belangeri chinensis) using immunohistochemical techniques. CRF-immunoreactive (-ir) cells and fibers were present in the rhinencephalon, telencephalon, diencephalon, mesencephalon, metencephalon and myelencephalon of saline- and colchicine-treated tree shrews. Laminar distribution of CRF-ir cells was found in the main olfactory bulb and neocortex. Compared with saline-treated tree shrews, a larger number of CRF-ir cells in colchicine-treated tree shrews were found in the bed nucleus of the stria terminalis, paraventricular hypothalamic nucleus, medial preoptic area, dorsomedial hypothalamic nucleus, reuniens thalamic nucleus, inferior colliculus, Edinger-Westphal nucleus, median raphe nucleus, locus coeruleus, parabrachial nucleus, dorsal tegmental nucleus, lateral reticular nucleus, and inferior olive. CRF-ir fibers from the hypothalamic paraventricular nucleus projected toward and through the internal zone of the median eminence. In addition, density of CRF immunoreactivity is significantly different in the bed nucleus of the stria terminalis, central amygdaloid nucleus, suprachiasmatic nucleus, median raphe nucleus, Edinger-Westphal nucleus, locus coeruleus and inferior olive between tree shrews and rats after saline or colchicine treatment. Our findings provide, for the first time, the comprehensive description of CRF immunoreactivity and whole brain mapping of CRF in tree shrews, which is an anatomical basis for the participation of CRF system in the regulation of numerous behaviors.

The theoretical 3D structure of Bacillus thuringiensis Cry5Ba.

Cry5Ba is a delta-endotoxin produced by Bacillus thuringiensis PS86A1 NRRL B-18900. It is active against nematodes and has great potential for nematode control. Here, we predict the first theoretical model of the three-dimensional (3D) structure of a Cry5Ba toxin by homology modeling on the structure of the Cry1Aa toxin, which is specific to Lepidopteran insects. Cry5Ba resembles the previously reported Cry1Aa toxin structure in that they share a common 3D structure with three domains, but there are some distinctions, with the main differences being located in the loops of domain I. Cry5Ba exhibits a changeable extending conformation structure, and this special structure may also be involved in pore-forming and specificity determination. A fuller understanding of the 3D structure will be helpful in the design of mutagenesis experiments aimed at improving toxicity, and lead to a deep understanding of the mechanism of action of nematicidal toxins.

[Cloning and expression of the cry1Ac-tchiB fusion gene from Bacillus thuringinesis and Tobacco and its insecticidal synergistic effect].

A new fusion gene cry1Ac-tchiB was constructed to enhance the toxicity of crystal proteins, the cry1Ac gene of Bacillus thuringiensis strain 4.0718 was combined with a tchiB (deleted signal peptide and Enterokinase site sequence). In this process, the Enterokinase site sequence was inserted into the midst of these two genes. Then the combined fragment carrying the upstream promoter region and the downstream terminator region of cry1Ac gene were cloned into the shuttle vector pHT315. And after a series of enzyme digestions and subclonings two new expression vector pHUAccB6 and pHUAccB7 were obtained. The two vectors were transformed into B. thuringiensis acrystalliferous strain XBU001 with electroporation to obtain the recombinant strain HAccB6 and HAccB7. The fusion gene was expressed and the expression product was detected by SDS-PAGE. The result indicated that the recombinant Cry1Ac-tchiB protein accumulated to the level of 61.38% of total bacterial proteins. Cry1Ac protein accumulated to the level of 42% of total bacterial proteins. Chitinase activities is 5.2 time more than that of the control strain. Under Atomic Force Microscopy and SEM of crystals protein, there were some bipy ramidal crystals with a size of 1.5 x 3.0 microm. Bioassay showed that the fusion crystals from recombinant strain HAccB6 and HAccB7 were high toxic against third-instar larvae of Helicourpa armigora with the LC50 (after 72h) value of 9.10 micro/mL and 11.34 micro/mL.The constructed fusion proteins had more toxicity than Cry1Ac crystal proteins. The study will enhances the toxicity of B. thuringiensis Cry toxins protein and makes a ground for constructing the fusion genes of B. thuringiensis cry gene and other foreign toxin genes and the recombinant strain with high toxicity.

[Analysis of insecticidal crystal proteins from Bacillus thuringiensis strain 4.0718 through two-dimensional gel electrophoresis and MALDI-TOF-mass spectrometry].

The present study analyses the insecticidal crystal proteins (ICPs) from Bacillus thuringiensis strain 4.0718 through two-dimensional electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS). By comparing and optimizing the composition of lysis solution, the volume of sample loading and the protocol for isoelectric focusing, a well-focused 2-DE map with high resolution and reproducibility was achieved for the first time. And after an tryptic enzymolisis and a test of part of protein spots by means of MALDI-TOF-MS, the peptides mass fingerprint (PMF) was obtained and, by referring to Swiss-Prot, Cry1Ac and Cry2Aa contained in Bt 4.0718 were identified, with their molecular weights 134160 Da and 71097 Da respectively.

[Cloning and superexpression of cry1Ac gene from 20kb DNA associated with Bacillus thuringiensis Cry1A Crystal Protein].

The CrylA Crystal Protein from Bacillus thuringiensis is associated with DNA, but the role and sequences of these DNA molecules are unknown. CrylA bipyramidal crystals from B. thuringiensis strain 4.0718 was selectively dissolved and associated DNA was extracted from protoxin. The DNA was digested with Nde I to obtain 3 to 5 kb fragments and then the fragments were subcloned into pMD18-T vector, screening of recombinants were done by PCR-RFLP and sequencing. The ORF of cry1Ac gene was amplified by primers designed and then subcloned. The 3.5 kb BamH I and Sal I fragments of pMDX35 was inserted into the pET30a vector, giving 8.9 kb recombinant plasmid, pETX35. ETX35 strain were obtained by transformed pETX35 into B121 (DE3). A 141 kD fusion protein was superexpressed as inclusion bodies. Quantitative protein analysis indicated that the amount of 141 kD protein was above the level of 51.36% of total cellular protein. Plasmid pHTX42 constructed from shuttle vector pHT304 was transformed B. thuringiensis acrystalliferous strain XBU001 with electroporation to obtain the recombinant HTX42. The recombinant protein was found with a molecular mass of 130 kD on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Scanning analysis indicated that the expressed protein accounted up to 79.28% of total cellular proteins and accumulated in the cells mounted up to 64.13% of cellular dry weight. Under Atomic Force Microscopy (AFM), typical bipyramidal crystals from HTX42 strain were found with a size of 1.2 microm x 2.0 microm. Bioassay showed that these inclusion bodies of ETX35 strain and crystals from HTX42 strain were highly toxic against the larvae of Plutella xylostella. On such a base, constructing insecticidal recombinant and analyzing the source, structure, and function of the 20 kb DNA can be further achieved.