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OBJECTIVES/GOALS: People living with HIV, despite antiretroviral therapy (ART), have increased burden of inflammatory and aging-related comorbidities such as periodontitis. Oral microbiota have been linked to periodontitis, but not in the context of HIV. We aim to compare relationships between the oral microbiome and periodontal disease in HIV+ vs healthy controls. METHODS/STUDY POPULATION: In an ongoing cohort study we have been recruiting pre- and post-menopausal women with HIV+ on ART for ≥6 months and HIV- controls matched by menopausal status (target n = 30 per arm; currently HIV+: n = 30 post- and 9 pre-M; HIV-: n = 15 post- and 6 pre-M). Patients age <18 or on antibiotics within 3 mos., except prophylaxis, are excluded. Patients provide saliva, then subgingival plaque collection during a dental examination through scaling from six index teeth. Standard CDC/AAP classifications of periodontitis are used. We will perform 16S rRNA and ITS sequencing to profile bacterial and fungal communities in saliva and plaque. Linear mixed effect regression and differential abundance analyses will be used to identify microbial and mycobial oral signatures of periodontal disease severity in HIV+ and HIV- populations. RESULTS/ANTICIPATED RESULTS: We found a markedly high prevalence of severe periodontal disease in HIV+ women despite ART (59%, compared to 11% in HIV- controls). In post-menopausal women with HIV, saliva bacterial α- and β-diversity in the saliva differed significantly with periodontal disease severity. Fungal α-diversity was also significantly lower in plaque from teeth with severe loss of tissue attachment (CAL ≥4 mm). We identified bacterial and fungal taxa significantly enriched in post-menopausal HIV+ women with severe compared to no or mild periodontitis. We hypothesize, similarly, associations between the oral microbiome and periodontitis in HIV- controls. However, we expect overall diversity metrics to be significantly altered in HIV+ compared to HIV- patients, indicating long-term dysbiosis despite treatment with ART. DISCUSSION/SIGNIFICANCE OF IMPACT: Contrasting associations between the oral microbiome and periodontal disease with respect to HIV will provide evidence for the role of microbiota in accelerated aging phenotype caused by HIV. Our results would also provide rationale for interventions targeting co-morbidities in people living with HIV to account for both inflammation and dysbiosis.
Studies in countries with high immunisation coverage suggest that the re-emergence of pertussis may be caused by a decreased duration of protection resulting from the replacement of whole-cell pertussis vaccine (WPV) with the acellular pertussis vaccine (APV). In China, WPV was introduced in 1978. The pertussis vaccination schedule advanced from an all-WPV schedule (1978–2007), to a mixed WPV/APV schedule (2008–2009), then to an all-APV schedule (2010–2016). Increases in the incidence of pertussis have been reported in recent years in Jinan and other cities in China. However, there have been few Chinese-population-based studies focused on the impact of schedule changes. We obtained annual pertussis incidences from 1956 to 2016 from the Jinan Notifiable Conditions Database. We used interrupted time series and segmented regression analyses to assess changes in pertussis incidence at the beginning of each year, and average annual changes during the intervention. Pertussis incidence decreased by 1.11 cases per 100 000 population (P = 0.743) immediately following WPV introduction in 1978 and declined significantly by 1.21 cases per 100 000 population per year (P < 0.0001) between 1978 and 2001. Immediately after APV replaced the fourth dose of WPV in 2008, the second and third doses in 2009, then replaced all four doses in 2010, pertussis incidence declined by 1.98, 1.98 and 1.08 cases per 100 000 population, respectively. However, the results were not statistically significant. There were significant increasing trends in pertussis incidence after APV replacements: 1.63, 1.77 and 1.78 cases/year in 2008–2016, 2009–2016 and 2010–2016, respectively. Our study shows that the impact of an all-WPV schedule may be less than the impacts of the sequential WPV/APV schedules. The short-term impact of APV was better than that of WPV; however, the duration of APV-induced protection was not ideal. The impact and duration of protective immunity resulting from APVs produced in China need further evaluation. Further research on the effectiveness of pertussis vaccination programme in Jinan, China is also necessary.
Background: Dystonia is a hyperkinetic condition that produces abnormal movements or postures. Its diagnostic procedure is often challenging and time consuming. Genetic testing provides an effective approach for diagnosis, but currently only very few dystonia genes have been identified. We propose that studying early-onset forms of dystonia with the use of whole-genome sequencing (WGS) will improve the identification of dystonia-relevant genes and mutations. Methods: We performed deep WGS using the Illumina HiSeq X technology in a mother-proband pair with dystonia. The mother has generalized dystonia (age of onset: 15) and the proband has myoclonic dystonia (age of onset: 11). Results: No pathogenic mutation was identified in any of the known dystonia genes. However, we identified a rare heterozygous frameshift mutation (p.K342fs*7) at LMNB1 that was shared between the mother and the proband. Duplication of LMNB1 is known to cause Adult-onset Demyelinating Leukodystrophy. A heterozygous deletion of LMNB1 has been reported in a patient with microcephaly and global developmental disorder. Conclusions: Further characterization of phenotypes in the participants and their family members is needed to confirm the relationship between mutation in LMNB1 and dystonia. This work provides a proof-of-principle that novel disease-relevant genes can potentially be identified using the proposed approach.
A new generation of high power laser facilities will provide laser pulses with extremely high powers of 10 petawatt (PW) and even 100 PW, capable of reaching intensities of
in the laser focus. These ultra-high intensities are nevertheless lower than the Schwinger intensity
at which the theory of quantum electrodynamics (QED) predicts that a large part of the energy of the laser photons will be transformed to hard Gamma-ray photons and even to matter, via electron–positron pair production. To enable the investigation of this physics at the intensities achievable with the next generation of high power laser facilities, an approach involving the interaction of two colliding PW laser pulses is being adopted. Theoretical simulations predict strong QED effects with colliding laser pulses of
focused to intensities
Using an age-structured process-based simulation model for diamondback moth (DBM), we model the population dynamics of this major Brassica pest using the cropping practices and climate of Guangdong, China. The model simulates two interacting sub-populations (demes), each representing a short season crop. The simulated DBM abundance, and hence pest problems, depend on planting regime, crop hygiene and biological control. A continuous supply of hosts, a low proportion of crop harvested and long residue times between harvest and replanting each exacerbate pest levels. Biological control provided by a larval parasitoid can reduce pest problems, but not eliminate them when climate is suitable for DBM and under certain planting practices. The classic Integrated Pest Management (IPM) method of insecticide application, when pest threshold is reached, proved effective and halved the number of insecticide sprays when compared with the typical practice of weekly insecticide application.
With brown adipose tissue (BAT) becoming a possible therapeutic target to counteract obesity, the prenatal environment could represent a critical window to modify BAT function and browning of white AT. We investigated if levels of uncoupling protein 1 (UCP1) and UCP1-mediated thermogenesis are altered in offspring exposed to prenatal obesity. Female CD-1 mice were fed a high-fat (HF) or standard-fat (SF) diet for 3 months before breeding. After weaning, all pups were placed on SF. UCP1 mRNA and protein levels were quantified using quantitative real-time PCR and Western blot analysis, respectively, in brown (BAT), subcutaneous (SAT) and visceral (VAT) adipose tissues at 6 months of age. Total and UCP1-dependent mitochondrial respiration were determined by high-resolution respirometry. A Student’s t-test and Mann–Whitney test were used (significance: P<0.05). UCP1 mRNA levels were not different between the HF and SF offspring. UCP1 protein levels, total mitochondrial respiration and UCP1-dependent respiration were significantly higher in BAT from HF males (P=0.02, P=0.04, P=0.005, respectively) and females (P=0.01, P=0.04, P=0.02, respectively). In SAT, the UCP1 protein was significantly lower in HF females (P=0.03), and the UCP1-dependent thermogenesis was significantly lower from HF males (P=0.04). In VAT, UCP1 protein levels and UCP1-dependent respiration were significantly lower only in HF females (P=0.03, P=0.04, respectively). There were no differences in total respiration in SAT and VAT. Prenatal exposure to maternal obesity leads to significant increases in UCP1 levels and function in BAT in offspring with little impact on UCP1 levels and function in SAT and VAT.
Chilling injury is an important natural stress that can threaten cotton production, especially at the sowing and seedling stages in early spring. It is therefore important for cotton production to improve chilling tolerance at these stages. The current work examines the potential for glycine betaine (GB) treatment of seeds to increase the chilling tolerance of cotton at the seedling stage. Germination under cold stress was increased significantly by GB treatment. Under low temperature, the leaves of seedlings from treated seeds exhibited a higher net photosynthetic rate (PN), higher antioxidant enzyme activity including superoxide dismutase, ascorbate peroxidase and catalase, lower hydrogen peroxide (H2O2) content and less damage to the cell membrane. Enzyme activity was correlated negatively with H2O2 content and degree of damage to the cell membrane but correlated positively with GB content. The experimental results suggested that although GB was only used to treat cotton seed, the beneficial effect caused by the preliminary treatment of GB could play a significant role during germination that persisted to at least the four-leaf seedling stage. Therefore, it is crucial that this method is employed in agricultural production to improve chilling resistance in the seedling stage by soaking the seeds in GB.
Nitrogen (N) application and irrigation to winter wheat may decrease leaf temperature and enhance photosynthesis: as a result, more photosynthates will be allocated to the grains, resulting in higher grain yields. To investigate this hypothesis, a 2-year field study was conducted with three levels of N fertilizer application (no fertilizer, N0; 240 kg N/ha, N1; 360 kg N/ha, N2) and two different water regimes (rainfed with no irrigation, R; irrigation at the over-wintering, stem elongation and grain filling stages, W). The results show that both N application and supplemental irrigation significantly increased grain yield with increases in both grain number/m2 and the 1000-grain weight, viz., WN2>WN1>WN0>RN2>RN1>RN0. In addition, application of N under both water regimes significantly increased flag leaf area, above-ground biomass and single stem productivity and decreased leaf temperature, which led to an increase in net photosynthesis rates and ribulose bisphosphate (RuBP) carboxylase activity. Moreover, analysis of the chlorophyll α fluorescence transient showed that N fertilizer application and supplemental irrigation significantly increased electron donor and acceptor performance of the photosystem II reaction centre.
Iron-deficiency anemia is a public health concern that frequently occurs in pregnant mammals and neonatal offspring. Ferrous N-carbamylglycinate chelate (Fe-CGly) is a newly designed iron fortifier with proven effects in iron-deficient rats and weanling piglets. However, the effects of this new compound on pregnant mammals are unknown. Therefore, this experiment was conducted to evaluate the effects of Fe-CGly on sow reproductive performance and iron status of both sows and neonatal piglets. A total of 40 large-white sows after second parity were randomly assigned to two groups (n=20). They were receiving a diet including 80 mg Fe/kg as FeSO4 or Fe-CGly, respectively, from day 85 of gestation to parturition. The serum (day 110 of pregnancy) and placentas of sows were sampled. Litter size, mean weight of live born piglets, birth (live) litter weight, number of live born piglets, and the number of still-born piglets, mummies, and weak-born piglets were recorded. Once delivered, eight litters were randomly selected from the 20 litters per treatment, and one new-born male piglet (1.503±0.142 kg) from each selected litter was slaughtered within 3 h after birth from the selected litters, without colostrum ingestion. The serum, longissimus muscle, liver and kidneys of the piglets were collected. The iron status of the serum samples and the messenger RNA level of iron-related genes in the placenta, liver and kidney were analyzed. The results showed that litter weight of live born piglets was higher (P=0.030) in the Fe-CGly group (19.86 kg) than in the FeSO4 group (17.34 kg). Fe-CGly significantly increased placental iron concentration (P<0.05) of sows. It also significantly increased iron saturation and reduced the total iron-binding capacity of piglets (P<0.05) at birth. However, the results revealed that supplementation of Fe-CGly in sows reduced liver and kidney iron concentration of neonatal piglets (P<0.05), indicating decreased iron storage. In addition, the concentration of iron in the colostrum was not significantly changed. Therefore, the present results suggested that replacement of maternal FeSO4 supplement with Fe-CGly in the late-gestating period for sows could improve litter birth weight, probably via enhanced iron transportation in the placenta.
Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia.
A total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids. They were also compared using a 75 g oral glucose tolerance test and the homeostasis model assessment of insulin resistance (HOMA-IR). Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).
Of the patients, 24.5% had IGT compared with none of the controls, and they also had significantly higher levels of fasting blood glucose and 2-h glucose after an oral glucose load, and were more insulin resistant. Compared with those patients with normal glucose tolerance, the IGT patients were older, had a later age of onset, higher waist or hip circumference and body mass index, higher levels of low-density lipoprotein and triglycerides and higher insulin resistance. Furthermore, IGT patients had higher PANSS total and negative symptom subscale scores, but no greater cognitive impairment except on the emotional intelligence index of the MCCB.
IGT occurs with greater frequency in FEDN schizophrenia, and shows association with demographic and anthropometric parameters, as well as with clinical symptoms but minimally with cognitive impairment during the early course of the disorder.
Little is known about the influence of meal timing and energy consumption patterns throughout the day on glucose regulation during pregnancy. We examined the association of maternal feeding patterns with glycaemic levels among lean and overweight pregnant women. In a prospective cohort study in Singapore, maternal 24-h dietary recalls, fasting glucose (FG) and 2-h postprandial glucose (2HPPG) concentrations were measured at 26–28 weeks of gestation. Women (n 985) were classified into lean (BMI<23 kg/m2) or overweight (BMI≥23 kg/m2) groups. They were further categorised as predominantly daytime (pDT) or predominantly night-time (pNT) feeders according to consumption of greater proportion of energy content from 07.00 to 18.59 hours or from 19.00 to 06.59 hours, respectively. On stratification by weight status, lean pNT feeders were found to have higher FG than lean pDT feeders (4·36 (sd 0·38) v. 4·22 (sd 0·35) mmol/l; P=0·002); however, such differences were not observed between overweight pDT and pNT feeders (4·49 (sd 0·60) v. 4·46 (sd 0·45) mmol/l; P=0·717). Using multiple linear regression with confounder adjustment, pNT feeding was associated with higher FG in the lean group (β=0·16 mmol/l; 95 % CI 0·05, 0·26; P=0·003) but not in the overweight group (β=0·02 mmol/l; 95 % CI −0·17, 0·20; P=0·879). No significant association was found between maternal feeding pattern and 2HPPG in both the lean and the overweight groups. In conclusion, pNT feeding was associated with higher FG concentration in lean but not in overweight pregnant women, suggesting that there may be an adiposity-dependent effect of maternal feeding patterns on glucose tolerance during pregnancy.
Experiments on the National Ignition Facility show that multi-dimensional effects currently dominate the implosion performance. Low mode implosion symmetry and hydrodynamic instabilities seeded by capsule mounting features appear to be two key limiting factors for implosion performance. One reason these factors have a large impact on the performance of inertial confinement fusion implosions is the high convergence required to achieve high fusion gains. To tackle these problems, a predictable implosion platform is needed meaning experiments must trade-off high gain for performance. LANL has adopted three main approaches to develop a one-dimensional (1D) implosion platform where 1D means measured yield over the 1D clean calculation. A high adiabat, low convergence platform is being developed using beryllium capsules enabling larger case-to-capsule ratios to improve symmetry. The second approach is liquid fuel layers using wetted foam targets. With liquid fuel layers, the implosion convergence can be controlled via the initial vapor pressure set by the target fielding temperature. The last method is double shell targets. For double shells, the smaller inner shell houses the DT fuel and the convergence of this cavity is relatively small compared to hot spot ignition. However, double shell targets have a different set of trade-off versus advantages. Details for each of these approaches are described.
Experimental data are presented showing maximum carbon C6+ ion energies obtained from nm-scaled targets in the relativistic transparent regime for laser intensities between 9 × 1019 and 2 × 1021 W/cm2. When combined with two-dimensional particle-in-cell simulations, these results show a steep linear scaling for carbon ions with the normalized laser amplitude a0 (
$a_0 \propto \sqrt ( I)$
). The results are in good agreement with a semi-analytic model that allows one to calculate the optimum thickness and the maximum ion energies as functions of a0 and the laser pulse duration τλ for ion acceleration in the relativistic-induced transparency regime. Following our results, ion energies exceeding 100 MeV/amu may be accessible with currently available laser systems.
Suicide in China has declined since the 1990s. However, there has been limited investigation of the potential spatiotemporal variation and social determinants of suicide during subsequent periods.
Annual suicide counts from 2006 to 2012 stratified by county, 5-year age group (⩾15 years) and gender were obtained from the Chinese Disease Surveillance Points system. Trends and geographic differentials were examined using multilevel negative binomial regression models to explore spatiotemporal variation in suicide, and the role of key sociodemographic factors associated with suicide.
The suicide rate (per 100 000) in China decreased from 14.7 to 9.1, 2006–2012. Rates of suicide were higher in males than females and increased substantially with age. Suicide rates were higher in rural areas compared with urban areas; however, urban–rural disparities reduced over time with a faster decline for rural areas. Within both urban and rural areas, higher rates of suicide were evident in areas with lower socio-economic circumstances (SEC) [rate ratio (RR) 1.85, 95% confidence interval (CI) 1.31–2.62]. Suicide rates varied more than twofold (median RR 2.06) across counties, and were highest in central and southwest regions of China. A high proportion of the divorced population, especially for younger females, was associated with lower suicide rates (RR 0.60, 95% CI 0.46–0.79).
Geographic variations for suicide should be taken into account in policy making, particularly for older males living in rural areas and urban areas with low SEC. Measures to reduce disparities in socio-economic level and alleviate family relation stress are current priorities.
In endangered and local pig breeds of small population sizes, production has to focus on alternative niche markets with an emphasis on specific product and meat quality traits to achieve economic competiveness. For designing breeding strategies on meat quality, an adequate performance testing scheme focussing on phenotyped selection candidates is required. For the endangered German pig breed ‘Bunte Bentheimer’ (BB), no breeding program has been designed until now, and no performance testing scheme has been implemented. For local breeds, mainly reared in small-scale production systems, a performance test based on in vivo indicator traits might be a promising alternative in order to increase genetic gain for meat quality traits. Hence, the main objective of this study was to design and evaluate breeding strategies for the improvement of meat quality within the BB breed using in vivo indicator traits and genetic markers. The in vivo indicator trait was backfat thickness measured by ultrasound (BFiv), and genetic markers were allele variants at the ryanodine receptor 1 (RYR1) locus. In total, 1116 records of production and meat quality traits were collected, including 613 in vivo ultrasound measurements and 713 carcass and meat quality records. Additionally, 700 pigs were genotyped at the RYR1 locus. Data were used (1) to estimate genetic (co)variance components for production and meat quality traits, (2) to estimate allele substitution effects at the RYR1 locus using a selective genotyping approach and (3) to evaluate breeding strategies on meat quality by combining results from quantitative-genetic and molecular-genetic approaches. Heritability for the production trait BFiv was 0.27, and 0.48 for backfat thickness measured on carcass. Estimated heritabilities for meat quality traits ranged from 0.14 for meat brightness to 0.78 for the intramuscular fat content (IMF). Genetic correlations between BFiv and IMF were higher than estimates based on carcass backfat measurements (0.39 v. 0.25). The presence of the unfavorable n allele was associated with increased electric conductivity, paler meat and higher drip loss. The allele substitution effect on IMF was unfavorable, indicating lower IMF when the n allele is present. A breeding strategy including the phenotype (BFiv) combined with genetic marker information at the RYR1 locus from the selection candidate, resulted in a 20% increase in accuracy and selection response when compared with a breeding strategy without genetic marker information.
Nanostructured anatase TiO2 is a promising material for gas sensing and photocatalysis. In order to modify its catalytic properties, the lanthanide (Ln) ions Eu3+, Gd3+, Nd3+ and Yb3+ were precipitated on the surface of TiO2 nanoparticles (NPs) by hydrothermal treatment. Results from Raman spectroscopy and X-ray diffraction (XRD) measurements show that the anatase structure of the TiO2 nanoparticles was preserved after hydrothermal treatment. SEM and TEM show a heterogeneous distribution in size and a nanocrystallite morphology of the TiO2 NPs (∼ 14 nm in size) and EDX confirmed the presence of the Ln-ion surface doping after hydrothermal treatment. An increase in photoluminescence (PL) was observed for the Ln-surface-doped TiO2 NPs when measurements were made in forming gas (5% H2 + 95% Ar) at 520 °C. In contrast, the PL measurements made at room temperature did not show any noticeable difference in forming gas or in ambient air. Our temperature-dependent PL results obtained in different gas environments are consistent with modification of oxygen-vacancies and hole-defects due to a combination of hydrothermal treatment and surface Ln-doping.
Pedogenic alteration of illite from red earth sediments in Jiujiang in subtropical China was investigated using X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM). Illite, hydroxy-interlayered vermiculite (HIV), kaolinite and mixed-layer illite-HIV (I-HIV) are present in the soils. The characteristic reflections of the clay phases were 14 Å, 10–14 Å, 10 Å, and 7 Å, respectively. After Mg-glycerol saturations, the 14 Å peak of the samples did not expand, and after heating at 350°C and 550°C it shifted to 13.8 Å and 12 Å respectively, with no residual 14 Å reflection, suggesting the occurrence of hydroxy-interlayered vermiculite. The randomly interstratified I-HIV clays were characterized by a broad peak at 10–14 Å, which did not change its position after Mg-glycerol saturation, but collapsed to 10 Å after heating at 350°C and 550°C. HRTEM analysis showed different lattice fringes of 12 Å, 10 Å and 7 Å . Mixed-layer I-HIV, HIV-K and illite-kaolinite (I-K) were observed in the HRTEM images which represented the intermediate phases during illite alteration. The merging of two 10 Å illite layers into a 12 Å HIV layer, lateral transformation of one HIV layer into one kaolinite layer and alteration of one illite layer into two kaolinite layers illustrated the mechanisms of illite-to-HIV, HIV-to-kaolinite and illite-tokaolinite transformation, respectively. The proposed pedogenic alteration of illite and the weathering sequence of the clay minerals in Jiujiang is illite → I-HIV → HIV → HIV-K → kaolinite. In addition, illite may transform directly to kaolinite.
The objective of the present study was to compare genetic gain and inbreeding coefficients of dairy cattle in organic breeding program designs by applying stochastic simulations. Evaluated breeding strategies were: (i) selecting bulls from conventional breeding programs, and taking into account genotype by environment (G×E) interactions, (ii) selecting genotyped bulls within the organic environment for artificial insemination (AI) programs and (iii) selecting genotyped natural service bulls within organic herds. The simulated conventional population comprised 148 800 cows from 2976 herds with an average herd size of 50 cows per herd, and 1200 cows were assigned to 60 organic herds. In a young bull program, selection criteria of young bulls in both production systems (conventional and organic) were either ‘conventional’ estimated breeding values (EBV) or genomic estimated breeding values (GEBV) for two traits with low (h2=0.05) and moderate heritability (h2=0.30). GEBV were calculated for different accuracies (rmg), and G×E interactions were considered by modifying originally simulated true breeding values in the range from rg=0.5 to 1.0. For both traits (h2=0.05 and 0.30) and rmg⩾0.8, genomic selection of bulls directly in the organic population and using selected bulls via AI revealed higher genetic gain than selecting young bulls in the larger conventional population based on EBV; also without the existence of G×E interactions. Only for pronounced G×E interactions (rg=0.5), and for highly accurate GEBV for natural service bulls (rmg>0.9), results suggests the use of genotyped organic natural service bulls instead of implementing an AI program. Inbreeding coefficients of selected bulls and their offspring were generally lower when basing selection decisions for young bulls on GEBV compared with selection strategies based on pedigree indices.