Association between de novo variants of nuclear-encoded mitochondrial-related genes and undiagnosed developmental disorder and autism.

BACKGROUND: Evidence suggests that mitochondrial abnormalities increase the risk of two neurodevelopmental disorders: undiagnosed developmental disorder (UDD) and autism spectrum disorder (ASD). However, which nuclear-encoded mitochondrial-related genes (NEMGs) were associated with UDD-ASD is unclear. AIM: To explore the association between de novo variants (DNVs) of NEMGs and UDD-ASD. DESIGN: Comprehensive analysis based on DNVs of NEMGs identified in patients (31 058 UDD probands and 10 318 ASD probands) and 4262 controls. METHODS: By curating NEMGs and cataloging publicly published DNVs in NEMGs, we compared the frequency of DNVs in cases and controls. We also applied a TADA-denovo model to highlight disease-associated NEMGs and characterized them based on gene intolerance, functional networks and expression patterns. RESULTS: Compared with levels in 4262 controls, an excess of protein-truncating variants and deleterious missense variants in 1421 cataloged NEMGs from 41 376 patients (31 058 UDD and 10 318 ASD probands) was observed. Overall, 3.23% of de novo deleterious missense variants and 3.20% of de novo protein-truncating variants contributed to 1.1% and 0.39% of UDD-ASD cases, respectively. We prioritized 130 disease-associated NEMGs and showed distinct expression patterns in the developing human brain. Disease-associated NEMGs expression was enriched in both excitatory and inhibitory neuronal lineages from the developing human cortex. CONCLUSIONS: Rare genetic alterations of disease-associated NEMGs may play a role in UDD-ASD development and lay the groundwork for a better understanding of the biology of UDD-ASD.

[Detection of drug resistance genes of mycobacterium tuberculosis by rolling circle amplification technique with multicolor fluorescent probes].

The aim of this study was to construct a simple, rapid and ultra-sensitive optical biosensing technique based on rolling circle amplification (RCA), and to apply it to multiple detection of drug-resistant genes of mycobacterium tuberculosis. The common mutation sites of isoniazid, rifampicin and streptomycin resistance genes are katG315 (AGC➝ACC), rpoB531 (CAC➝TAC) and rpsL43 (AAG➝AGG). For these three gene sites, from February 2020 to May 2021, in the Department of Laboratory Medicine of the First Affiliated Hospital of Army Military Medical University, the padlock probe (PLP), primers and capture probes were designed. And a solid-phase RCA constant temperature amplification reaction system based on magnetic beads was constructed and the experimental parameters were optimized. The RCA products were accurately captured by the multicolor fluorescent probes (Cy3/Cy5/ROX), and the single-tube multiple detection of three mutation genes was realized. The sensitivity, specificity and linear range of this method were further verified. The results showed that the response range of katG315 in the same reaction system ranged from 1.0 pmol/L to 0.1 nmol/L. The response range of rpoB531 and rpsL43 ranged from 1.0 pmol/L to 50.0 pmol/L and 1.0 pmol/L to 20.0 pmol/L, and the method had good specificity and sensitivity, and could accurately identify single base mutations in mixed targets, with the minimum detection limit as low as 1.0 pmol/L. The recoveries of simulated serum samples were 95.0%-105.2%. In conclusion, the constant temperature amplification multiple detection method constructed in this study can quickly realize the single-tube multiple detection of three drug resistance mutation sites. This technology is low-cost, simple and rapid, and does not rely on large equipment, providing a new analysis method for pathogen drug resistance gene detection.

Improvement of feed intake, digestibility, plasma metabolites, and lactation performance of dairy cows fed mixed silage of sugar beet pulp and rice straw inoculated with lactic acid bacteria.

A study was conducted to investigate the inclusion effects of sugar beet pulp and rice straw mixture silage with inoculation (BRMS), in place of whole-plant corn silage (CS), on the dry matter intake, total-tract nutrient digestibility, plasma metabolites, rumen fermentation, and lactation performance in high-production dairy cows. Sixteen multiparous Holstein cows (body weight, 622 ± 35 kg; days in milk, 90 ± 11 d; mean ± standard deviation) were used in our experiments; the experiments were based on a repeated 4 × 4 Latin square design for 21 d, and each experimental period consisted of 14 d of adaptation, followed by 7 d of data collection. The 4 dietary treatments used were (dry matter basis): (1) 0% BRMS and 28.6% CS (0BRMS); (2) 4.3% BRMS and 24.3% CS (15BRMS); (3) 8.60% BRMS and 20.0% CS (30BRMS); and (4) 12.9% BRMS and 15.7% CS (45BRMS). The increasing inclusion of dietary BRMS was observed to linearly increase the total volatile fatty acids and the propionate concentration. The dry matter intake and digestibility values of neutral detergent fiber and acid detergent fiber increased linearly as the percentage of BRMS increased up to 45%. Milk yield linearly increased with the increase in the content of BRMS (39.0, 39.8, 40.9, and 40.3 kg/d for 0BRMS, 15BRMS, 30BRMS, and 45BRMS, respectively). The increasing inclusion of dietary BRMS induced a decrease in the ammonia nitrogen and milk urea nitrogen concentration, leading to a linear increase in milk protein production (1.15, 1.26, 1.35, and 1.27 kg/d for 0BRMS, 15BRMS, 30BRMS, and 45BRMS, respectively). In conclusion, the diets with the replacement of CS with BRMS up to 45% were beneficial to the production performance of high-production dairy cows, indicating that this method may be an appropriate use of sugar beet pulp and rice straw.

Characterization of physiological traits during development of the recalcitrant seeds of Quercus serrata.

We investigated how developmental stage affects seed traits, including the relative level of desiccation tolerance of Quercus serrata. We tested the hypothesis that the relative level of desiccation tolerance is a quantitative trait associated with seed development and that a maximum relative level of desiccation tolerance is reached during development. Seed growth and physiological traits of Q. serrata from a subtropical forest were examined in detail during the developmental process. During seed development, the relative level of desiccation tolerance and other seed traits of Q. serrata varied. Dry matter accumulation in seed components increased rapidly beginning in mid-August, and moisture content declined. At the peak period of seed dispersal in late September, seeds were fully mature, with 100% germination. Relative level of desiccation tolerance increased up to the point of peak dispersal; however, at this time seeds were still recalcitrant. Post-mature development was accompanied by further increases in seed dry matter and decreases in moisture content, which led to a decrease in seed germination and relative level of desiccation tolerance. Our results suggest that in species with recalcitrant seeds, the relative level of desiccation tolerance and other seed traits are quantitative at the intraspecific level. The relative level of desiccation tolerance for recalcitrant seeds does not increase infinitely during phase II of development. There is a maximum relative level of desiccation tolerance in recalcitrant seeds within a species.

[An analysis of insomnia and its influencing factors in patients with acute coronary syndrome].

Objective: To investigate the current situation of insomnia in patients with acute coronary syndrome (ACS), and analyze the influencing factors of insomnia in the ACS patients, so as to provide information on the development of new strategies for the treatment of insomnia in ACS patients. Methods: This is a multicenter and prospective observational study. A total of 771 ACS patients who met the criteria were selected from March 2013 to June 2015. The baseline social demographic information, sleep quality questionnaire, general anxiety disorder scale-7(GAD-7),patient health questionnaire-9(PHQ-9), short-form 12 health survey questionnaire(SF-12), and enhancing recovery in coronary heart disease patients social inventory(ESSI) were completed within 7 days after admission. Logistic regression analyses were used to analyze the influencing factors of insomnia in ACS patients. Results: A total of 741 subjects with valid questionnaires were collected, including 510 males (68.8%) and 231 females (31.2%). Among them, 487 (65.7%) subjects had at least one insomnia symptom: 308 (41.6%) subjects had difficulty in falling asleep, 369 (49.8%) subjects were easy to wake at night, 116 (15.7%) subjects woke up earlier than they expected, 74 (10.0%) subjects experienced both woke up earlier and difficulty in falling asleep, and 53 (7.2%) subjects woke up earlier, woke up at night and had difficulty in falling asleep at the same time. Logistic regression analyses showed that before admission physical activity (OR =0.636, 95%CI 0.411-0.984), depression (OR=1.908, 95%CI 1.101-3.305) and low social support (OR=0.278, 95%CI 1.198-3.301) were independent factors of insomnia in ACS patients. Conclusions: Nearly 2/3 ACS patients have symptoms of insomnia. Difficulty in falling asleep and easy to wake up at night are the most common manifestations. Physical activity, depression and social support independently are associated with insomnia.

Genome-Wide Association Analysis of Neonatal White Matter Microstructure.

A better understanding of genetic influences on early white matter development could significantly advance our understanding of neurological and psychiatric conditions characterized by altered integrity of axonal pathways. We conducted a genome-wide association study (GWAS) of diffusion tensor imaging (DTI) phenotypes in 471 neonates. We used a hierarchical functional principal regression model (HFPRM) to perform joint analysis of 44 fiber bundles. HFPRM revealed a latent measure of white matter microstructure that explained approximately 50% of variation in our tractography-based measures and accounted for a large proportion of heritable variation in each individual bundle. An intronic SNP in PSMF1 on chromosome 20 exceeded the conventional GWAS threshold of 5 x 10-8 (p = 4.61 x 10-8). Additional loci nearing genome-wide significance were located near genes with known roles in axon growth and guidance, fasciculation, and myelination.

[Comparison of clinical efficacy of robotic, laparoscopic and open surgery in the treatment of severe rectal prolapse].

Objective: To analyze and compare the efficacy of robotic, laparoscopic and open dorsal mesh rectopexy in the treatment of severe rectal prolapse. Methods: A retrospective cohort study was performed. Patients who had a full-thickness rectum pulled out of the anus before surgery and the length was greater than 8 cm, and underwent transabdominal dorsal mesh rectopexy were enrolled in the study. Those who had urinary or sexual dysfunction before surgery, could not perform sexual function scores due to lack of a fixed sexual partner or sexual activity after surgery, underwent laparotomy again during the perioperative period, were transferred to laparotomy during robotic or laparoscopic surgery, or had no complete information, were excluded. A total of 61 patients with severe rectal prolapse in the First Affiliated Hospital of Zhengzhou University from 2014 to 2018 were enrolled and divided into robotic group (20 cases), laparoscopic group (20 cases) and open group (21 cases) according to the operative procedure based on patients' will. Perioperative parameters were compared among the 3 groups. The International Prostatic Symptoms Score Scale (IPSS, higher score indicates more severe urinary dysfunction), the International Index of Erectile Function questionnaire (IIEF-15, lower score indicates more severe male sexual dysfunction) and the Female Sexual Function Index (FSFI-19, lower score indicates more severe female sexual dysfunction) were used to evaluate and compare the urinary and sexual function before and after operation. Results: There were no significant differences in baseline data among the 3 groups (all P>0.05). In the robotic, laparoscopic and open groups respectively, the operative time was (176.3±13.8) minutes, (160.2±12.1) minutes and (134.2±12.1) minutes; intraoperative blood loss was (58.5±18.9) ml, (67.9±15.7) ml and (114.2±8.4) ml; the first time to ambulation was (19.9±6.8) hours, (24.0±8.9) hours and (37.7±11.4) hours; the first time to gas passage was (31.8±6.8) hours, (35.7±8.9) hours and (49.2±11.2) hours; the hospitalization time was (11.0±1.4) days, (11.4±1.4) days and (13.3±2.1) days; whose differences among 3 groups were all significant (all P<0.001). While no significant differences in morbidity of complication and recurrence among 3 groups were observed (all P>0.05). In the robotic, laparoscopic and open groups respectively, the preoperative IPSS score was (4.2±1.7), (4.4±1.3), and (4.7±1.8); the IPSS score at postoperative 3-month was (8.5±2.5), (9.9±1.7), and (12.2±3.1); IPSS score at postoperative 12-month was (4.3±1.6), (5.8±1.3), and (6.3±1.5), respectively. Compared to preoperative score, postoperative IPSS score increased obviously, then decreased gradually (P<0.001). Preoperative male IIEE score was (22.8±1.8), (22.1±2.1), and (22.6±1.5). In the robotic, laparoscopic and open groups respectively, male IIEE score at postoperative 6-month was (19.6±2.1), (17.1±2.1), and (15.0±2.1); male IIEE score at postoperative 12-month was (22.4±1.6), (19.9±1.5), (17.9±1.8), respectively. Preoperative female FSFI score was (26.4±3.4), (26.6±3.2), and (26.6±3.0); female FSFI score at postoperative 6-month was (21.5±3.3), (18.9±2.9), (17.0±2.6); female FSFI score at postoperative 12-month was (26.1±2.7), (22.7±3.2), and (21.2±2.3), respectively. Postoperative male IIEE score and female FSFI score decreased significantly and then increased gradually with time, whose differences were all significant (all P<0.05). Postoperative IPSS, IIEE, and FSFI scores in the robotic group were superior to those in the laparoscopic and open groups (all P<0.05). Conclusion: Robotic surgery is safe and effective in the treatment of severe rectal prolapse, and is more advantageous in preserving urinary function and sexual function.

Effect of miR-26a on diabetic rats with myocardial injury by targeting PTEN.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Effect of miR-26a on diabetic rats with myocardial injury by targeting PTEN, by S.-S. Cai, X.-W. Tao, Y. Long, K. Xia, Y. Zhang, published in Eur Rev Med Pharmacol Sci 2019; 23 (3 Suppl): 304-311-DOI: 10.26355/eurrev_201908_18661-PMID: 31389595" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18661.

[Efficacy comparison of primary percutaneous coronary intervention by drug-coated balloon angioplasty or drug-eluting stenting in acute myocardial infarction patients with de novo coronary lesions].

Objective: To compare the safety profile, angiographic and clinical outcomes between drug-coated balloon(DCB) only strategy versus drug eluting stent(DES) implantation in primary percutaneous coronary intervention(PCI) for acute myocardial infarction(AMI) patients. Methods: A total of 380 AMI patients who underwent primary PCI in Beijing Chaoyang Hospital from January 2016 to May 2019 were enrolled. They were allocated into DEB group(n=180) or DES group(n=200). The Primary endpoint was the major adverse cardiac events(MACE) in hospital and within 3 months after discharge, the composite event of cardiac death, non-fatal myocardial infarction(MI), target vessel revascularization(TVR) and in stent thrombosis. The secondary endpoints included: (1)TIMI blood flow grade and myocardial perfusion grade (TMP grade) of infarct-related vessels before and after PCI. (2)The degree of ST segment resolution(STR) between half hour and two hours after PCI, and STR was represented by percentage of summed ST-segment reduction between baseline and post-PCI. Using the most significant lead of ST segment elevation, calculating the rate of decline in the ST segment after treatment; or the most significant lead of the ST segment depression, to calculate the rate of recovery in the ST segment after treatment. STR<50% was defined as incomplete STR. (3)The occurrence of coronary artery dissection during operation. (4)The peak value of myocardial enzymes. (5)The incidence of bleeding in hospital and within 3 months after discharge. The inverse probability weighting method based on propensity score (IPTW) was used to compare the effects of the two treatments on MACE occurrence in the logistic regression model. Results: There was no significant difference in sex, age, risk factors of coronary heart disease, type and site of AMI, interventional therapy data(P>0.05) between the two groups. The ratio of bifurcation lesions in DCB group was significantly higher than that in DES group, and the diameter of the DCB was smaller while the length was longer than that of DES (all P<0.05). One death occurred in each group during hospitalization. Compared with the DES group, the incidence of MI ï¼»2.8%(5/180) vs. 0.5% (1/200), P=0.10ï¼½ and TVR ï¼»2.8%(5/180) vs. 0.5%(1/200), P=0.10ï¼½ in the DCB group during hospitalization showed an increasing trend, and were mostly associated with delayed coronary dissection. The incidence of MACE was similar between the two groups (3.3%(6/180) and 1.0%(2/200), P=0.15) during hospitalization. There was no MACE occurred in the two groups within 3 months after discharge. There was no significant difference between the two groups in TIMI grade, TMP grade, incomplete STR rate and peak value of myocardial enzyme (all P>0.05). The incidence of coronary artery dissection was significantly higher in DCB group than in DES group (8.3%(15/180) and 3.0%(6/200), P=0.02), but most of them were type B or A dissection and did not need special treatment. There was no significant difference in bleeding event between the two groups(P=0.91). Logistic regression analysis showed that there was no difference in the risk of MACE during hospitalization between DES and DCB groups for AMI patients receiving PCI (compared with DCB, OR=0.35, 95%CI 0.08-1.43, P=0.13). Conclusions: The initial safety and efficacy profiles of DCB are similar with those of DES for the AMI patients during PCI. The study highlights that the incidence of coronary dissection (type A or B) is higher post DCB treatment than post DES, but it does not affect blood flow. However, the incidence of in-hospital MI due to delayed coronary dissection trends to be higher post DCB. So we should pay close attention to the risk of delayed coronary dissection after DCB in AMI patients with de novo lesion.

Screen time and sleep disorder in preschool children: identifying the safe threshold in a digital world.

OBJECTIVES: Sleep disorder is a common problem in children that can jeopardize their health and well-being. With the popularity of electronic devices such as portable tablets and smartphones in the 21st century, children are spending much more time on screen, but the impact of such change on children's sleep disorder has been less investigated so far. This study aims to examine the dose-response association between time spent on different electronic devices and children's sleep disorder. STUDY DESIGN: The design of this study is a cross-sectional study. METHODS: We randomly selected 2278 children aged 3-6 years from 15 kindergartens in Tongling, China. The potentially non-linear association between screen-viewing time (i.e. television [TV], computer, iPad, Phone) and the risk of sleep disorder was examined using a logistic generalized additive model. RESULTS: We observed a J-shaped association between TV viewing time and the risk of sleep disorder, with a threshold of 1 h/day. For each 1 h/day increment in TV viewing time over the threshold, the risk of sleep disorder increased by 12.35% (95% confidence interval: 1.87-23.92%). This association seemed to be greater for girls than boys and for TV viewing at weekend than on weekdays, but the difference was not statistically significant (P-value>0.05). We did not find adequate evidence of an adverse effect of more time spent on computer, iPad and Phone. CONCLUSIONS: This study suggests a positive but non-linear relationship between time spent on watching TV and sleep disorder in Chinese preschool children. Setting the TV viewing time limit less than 1 h/day may help reduce the risk of developing sleep disorder. Further investigation is also needed to examine and compare the effects of heavy use of other electronic devices on sleep disorder.

Altered Brain Structure in Infants with Turner Syndrome.

Turner syndrome (TS) is a genetic disorder affecting approximately 1:2000 live-born females. It results from partial or complete X monosomy and is associated with a range of clinical issues including a unique cognitive profile and increased risk for certain behavioral problems. Structural neuroimaging studies in adolescents, adults, and older children with TS have revealed altered neuroanatomy but are unable to identify when in development differences arise. In addition, older children and adults have often been exposed to years of growth hormone and/or exogenous estrogen therapy with potential implications for neurodevelopment. The study presented here is the first to test whether brain structure is altered in infants with TS. Twenty-six infants with TS received high-resolution structural MRI scans of the brain at 1 year of age and were compared to 47 typically developing female and 39 typically developing male infants. Results indicate that the typical neuroanatomical profile seen in older individuals with TS, characterized by decreased gray matter volumes in premotor, somatosensory, and parietal-occipital cortex, is already present at 1 year of age, suggesting a stable phenotype with origins in the prenatal or early postnatal period.

Effect of miR-26a on diabetic rats with myocardial injury by targeting PTEN.

OBJECTIVE: To investigate the effect of micro ribonucleic acid (miR)-26a on diabetes-induced myocardial injury in rats by targeting the gene of phosphate and tension homology detected on chromosome ten (PTEN). MATERIALS AND METHODS: Male Wistar rats aged 8-9 weeks old were divided into the control group (n=10), GK group (n=10), and miR-26a agomir group (n=10) according to the body weight. MiRanda and TargetScan target gene prediction software were used to predict and analyze the target gene of miR-26a-5p. The expressions of miR-26a and PTEN in the myocardial tissues of the diabetic rats were detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Hematoxylin-eosin (HE) staining was adopted to observe the pathological changes in the myocardial tissues. In addition, the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was conducted to detect myocardial apoptosis, while the expression of PTEN protein was detected via immunohistochemistry, and the protein expressions of PTEN, b-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and cysteinyl aspartate specific proteinase-3 (Caspase-3) were tested by Western blotting. RESULTS: TargetScan database analysis results showed that miR-26a-5p and PTEN 3'UTR had 6 pairs of complementary bases with the same sequence. Compared with those in the control group, the messenger RNA (mRNA) expression of PTEN in the GK group was notably increased (p<0.05), while that of miR-26a was substantially reduced (p<0.05). In comparison with those in the GK group, the mRNA expression of PTEN was significantly decreased, but that of miR-26a was significantly raised in miR-26a agomir group (p<0.05). Through observation under an optical microscope, it was manifested that in the control group, the myocardial fibers were intact with clear texture but no fracture, and the solid necrosis did not appear in myocardial cells. In the GK group, the myocardial fibers were disorderedly arranged and incomplete with an unclear edge and burrs. The myocardial fibers in the miR-26a agomir group were more regular, with less breakage and solid necrosis. According to TUNEL staining results, the TUNEL-stained brown granules in rats in the GK group were remarkably increased, relative to the control group (p<0.05). Compared with the GK group, miR-26a agomir group had markedly decreased the TUNEL-stained brown particles (p<0.05). It was found in immunohistochemical results that PTEN protein was in lighter color after staining in the control group, with a clear myocardial cell stripe structure. Compared with that in control group, PTEN protein in the GK group was in deeper color after staining, and in comparison with that in the GK group, the color of PTEN protein in miR-26a agomir group became significantly lighter. Moreover, the Western blotting results demonstrated that, compared with those in the control group, the Caspase-3 and Bax protein expressions in the GK group were significantly raised, while Bcl-2 protein expression was notably reduced (p<0.05). Besides, in comparison with the GK group, miR-26a agomir group evidently elevated Caspase-3 and Bax protein expressions and a notably increased Bcl-2 protein expression (p<0.05). CONCLUSIONS: We showed that miR-26a can protect against myocardial injury in diabetic rats by regulating PTEN.

(CAG)n loci as genetic modifiers of age at onset in patients with spinocerebellar ataxia type 1 from mainland China.

BACKGROUND AND PURPOSE: The expanded repeat length in ATXN1 negatively correlates with age at onset (AAO) of spinocerebellar ataxia type 1 (SCA1) but can explain only part of it, indicating that other factors affect AAO. Some studies have explored the influence of non-causative CAG repeats on the AAO of SCA patients. However, studies on Chinese SCA1 patients regarding candidate modifier factors involved in the variability in AAO are rare. METHODS: In all, 152 Chinese SCA1 patients who were genotyped for ATXN1 and nine other (CAG)n -containing genes were enrolled. Regression analysis was performed to determine the effect of the expanded allele of ATXN1 (linear and quadratic effects) on AAO. Then, different models were used to explore the modulatory effect of nine other (CAG)n -containing genes. RESULTS: Our results verified the negative effect of the expanded allele in ATXN1 by regression analysis. Some (CAG)n -containing genes including TBP, ATN1 and HTT modified AAO with variance ranging from 0.8% to 3.8% and tended to decrease or delay AAO. However, no modifier effects of ATXN2, ATXN3, CACNA1A, ATXN7, KCNN3, RAI1 and normal ATXN1 alleles in trans were detected. CONCLUSION: By using interaction analyses, TBP, ATN1 and HTT were determined to have modifying effects. Our study revealed that differences in modulation may be due to ethnic and geographic diversity across different populations. Furthermore, the variability of AAO was not completely explained by the genetic modifiers examined here, suggesting that other genetic or environmental factors are involved in these diseases.

Novel mutations in mevalonate kinase cause disseminated superficial actinic porokeratosis.

BACKGROUND: Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant disease. In our previous research, we found that a linkage region of DSAP in a large family is located at 12q23·2-q24·1. Subsequently, the mevalonate kinase gene (MVK) was shown to be pathogenic in DSAP. OBJECTIVES: To elucidate the mechanism by which MVK mutations lead to keratinocyte apoptosis and DSAP, and to report a new missense mutation, c.566 C>T (p.A189V), in MVK in a Chinese DSAP pedigree. METHODS: The half-life of wild-type (WT) MVK protein and mutants was assessed using cycloheximide treatment of cells. Dimerization of MVK was analysed by coimmunoprecipitation and glutathione S transferase pull-down assay. MVK kinase activity, production of cell cholesterol, mitochondrial complex activity and apoptosis were detected, using the corresponding commercial kits, in cells overexpressing MVK WT and mutants. RESULTS: Mechanically, we demonstrated that both the pathogenic p.A189V mutant and a sporadic mutation p.H312R (c.935A>G), which we reported previously, have rapid degradation, decreased kinase activity and reduced production of cell cholesterol. Also, we found the p.H312R mutation confers on the MVK protein an inability to dimerize. Further, we demonstrated that the mutants are impaired in mitochondrial function and lead to increased apoptosis. CONCLUSIONS: Our results provide an important basis for elucidating the mechanism by which MVK missense mutations contribute to DSAP.

Effect of magnetization boundary condition on cavity magnon polariton of YIG thin film.

Motivated by recent studies of cavity magnon polariton (CMP), we extended a previous theoretical work to generalize microwave transmission calculation with various magnetization boundary condition of YIG thin film embedded in cavity. It is found that numerical implementation given in this paper can be easily applied to other magnetization boundary condition and extended to magnetic multilayers. Numerical results show that ferromagnetic resonance mode of microwave transmission spectrum, which is absent in previous calculation, can be recovered by altering the pinning condition of surface spins. The demonstrated reliability of our theory opens attractive perspectives for studying CMP of thin film with complicated surface magnetization distribution and magnetic multilayers.

Analysis of (CAG)n expansion in ATXN1, ATXN2 and ATXN3 in Chinese patients with multiple system atrophy.

Multiple system atrophy (MSA) is a complex and multifactorial neurodegenerative disease, and its pathogenesis remains uncertain. Patients with MSA or spinocerebellar ataxia (SCA) show overlapping clinical phenotypes. Previous studies have reported that intermediate or long CAG expansions in SCA genes have been associated with other neurodegenerative disease. In this study, we screened for the number of CAG repeats in ATXN1, 2 and 3 in 200 patients with MSA and 314 healthy controls to evaluate possible associations between (CAG)n in these three polyQ-related genes and MSA. Our findings indicated that longer repeat lengths in ATXN2 were associated with increased risk for MSA in Chinese individuals. No relationship was observed between CAG repeat length in the three examined genes and age at onset (AO) of MSA.

Superresolution Microscopy of Single Rare-Earth Emitters in YAG and H3 Centers in Diamond.

We demonstrate superresolution imaging of single rare-earth emitting centers, namely, trivalent cerium, in yttrium aluminum garnet crystals by means of stimulated emission depletion (STED) microscopy. The achieved all-optical resolution is ≈50 nm. Similar results were obtained on H3 color centers in diamond. In both cases, STED resolution is improving slower than the conventional inverse square-root dependence on the depletion beam intensity. In the proposed model of this effect, the anomalous behavior is caused by excited state absorption and the interaction of the emitter with nonfluorescing crystal defects in its local surrounding.

Experimental study on TGF-ß1-mediated CD147 expression in oral submucous fibrosis.

OBJECTIVE: Although previous evidence indicates that CD147 is closely involved in the progression of organ fibrosis and various signaling pathways have been proven to regulate its expression, the role of CD147 in oral submucous fibrosis (OSF) remains largely unknown. METHODS: In this study, we investigated the expression of CD147 and transforming growth factor ß1 (TGF-ß1) in human samples of an OSF tissue array by immunohistopathology. Pearson's correlation analysis was conducted to explore the correlation between CD147 and TGF-ß1. Immunofluorescence and Western blotting were used to investigate to levels of CD147 in Human Oral Keratinocytes (HOKs) followed by TGF-ß1 or LY2157299, an inhibitor of TGF-ß1 receptor and arecoline stimulation. RESULTS: We found that CD147 was highly expressed in both HOKs and the fibrotic oral mucosa and that this expression was correlated with TGF-ß1 expression. Additionally, CD147 levels were significantly associated with the fibrosis stage. The TGF-ß1 signaling pathway was found to be mainly responsible for CD147 up-regulation after arecoline treatment whereas inhibition of TGF-ß1 down-regulated CD147 expression. CONCLUSION: Our findings suggest arecoline promotes CD147 expression via the TGF-ß1 signaling pathway in HOKs, whereas overexpression of CD147 may promote OSF progression.

Genome-wide association analysis identifies common variants influencing infant brain volumes.

Genome-wide association studies (GWAS) of adolescents and adults are transforming our understanding of how genetic variants impact brain structure and psychiatric risk, but cannot address the reality that psychiatric disorders are unfolding developmental processes with origins in fetal life. To investigate how genetic variation impacts prenatal brain development, we conducted a GWAS of global brain tissue volumes in 561 infants. An intronic single-nucleotide polymorphism (SNP) in IGFBP7 (rs114518130) achieved genome-wide significance for gray matter volume (P=4.15 × 10-10). An intronic SNP in WWOX (rs10514437) neared genome-wide significance for white matter volume (P=1.56 × 10-8). Additional loci with small P-values included psychiatric GWAS associations and transcription factors expressed in developing brain. Genetic predisposition scores for schizophrenia and ASD, and the number of genes impacted by rare copy number variants (CNV burden) did not predict global brain tissue volumes. Integration of these results with large-scale neuroimaging GWAS in adolescents (PNC) and adults (ENIGMA2) suggests minimal overlap between common variants impacting brain volumes at different ages. Ultimately, by identifying genes contributing to adverse developmental phenotypes, it may be possible to adjust adverse trajectories, preventing or ameliorating psychiatric and developmental disorders.