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Human brain is a complex organ comprising multiple cell types of differing function. Although histological evaluation remains the mainstay approach for evaluating tissue, comprehensive molecular characterization is now possible due to advanced -omic approaches. microRNAs (miRNAs) are small (~22 nt) RNA molecules that regulate gene expression and mediate cellular differentiation in normal brain development. miRNAs also make excellent tissue markers due to their abundance, cell-type and disease-stage specificity, and stability in solid/liquid clinical samples. To advance our knowledge of miRNA-mediated gene regulation in human brain, we generated comprehensive miRNA expression profiles from 117 fresh normal brain samples through barcoded small RNA sequencing; tissues included neocortex, allocortex, white matter, cerebellum, olfactory bulb, optic nerve, pineal gland and spinal cord. FASTQ sequence files were annotated using state-of-the-art sequence annotation available through the Renwick lab. Following data pre-processing, high expression analysis of miRNA profiles showed that miR-9 was the highest expressed miRNA in neocortex, cerebellum and olfactory bulb, whereas miR-22 was highest expressed in cingulate cortex, optic nerve and spinal cord; interestingly, miR-29 was the highest expressed miRNA in hippocampus. Our analyses showed a trend towards unique miRNA signatures in different anatomical areas of the brain. Our next step is to perform miRNA fluorescence in situ hybridization on formalin-fixed paraffin-embedded tissues using a novel method developed in the Renwick lab. Accurate miRNA characterization of normal tissues will provide a firm basis for understanding miRNA changes in neurological diseases.
This presentation will enable the learner to:
1.Describe the function of miRNAs and their suitability as tissue/cell specific signatures
2.Describe the miRNA expression trends in profiling various anatomical regions of the central nervous system
Estimating the feed intake of grazing herbivores is critical for determining their nutrition, overall productivity and utilization of grassland resources. A 17-day indoor feeding experiment was conducted to evaluate the potential use of Medicago sativa as a natural supplement for estimating the total feed intake of sheep. A total of 16 sheep were randomly assigned to four diets (four sheep per diet) containing a known amount of M. sativa together with up to seven forages common to typical steppes. The diets were: diet 1, M. sativa + Leymus chinensis + Puccinellia distans; diet 2, species in diet 1 + Phragmites australis; diet 3, species in diet 2 + Chenopodium album + Elymus sibiricus; and diet 4, species in diet 3 + Artemisia scoparia + Artemisia tanacetifolia. After faecal marker concentrations were corrected by individual sheep recovery, treatment mean recovery or overall recovery, the proportions of M. sativa and other dietary forages were estimated from a combination of alkanes and long-chain alcohols using a least-square procedure. Total intake was the ratio of the known intake of M. sativa to its estimated dietary proportion. Each dietary component intake was obtained using total intake and the corresponding dietary proportions. The estimated values were compared with actual values to assess the estimation accuracy. The results showed that M. sativa exhibited a distinguishable marker pattern in comparison to the other dietary forage species. The accuracy of the dietary composition estimates was significantly (P < 0.001) affected by both diet diversity and the faecal recovery method. The proportion of M. sativa and total intake across all diets could be accurately estimated using the individual sheep or the treatment mean recovery methods. The largest differences between the estimated and observed total intake were 2.6 g and 19.2 g, respectively, representing only 0.4% and 2.6% of the total intake. However, they were significantly (P < 0.05) biased for most diets when using the overall recovery method. Due to the difficulty in obtaining individual sheep recovery under field conditions, treatment mean recovery is recommended. This study suggests that M. sativa, a natural roughage instead of a labelled concentrate, can be utilized as a dietary supplement to accurately estimate the total feed intake of sheep indoors and further indicates that it has potential to be used in steppe grassland of northern China, where the marker patterns of M. sativa differ markedly from commonly occurring plant species.
Guangxi, a province in southwestern China, has the second highest reported number of HIV/AIDS cases in China. This study aimed to develop an accurate and effective model to describe the tendency of HIV and to predict its incidence in Guangxi. HIV incidence data of Guangxi from 2005 to 2016 were obtained from the database of the Chinese Center for Disease Control and Prevention. Long short-term memory (LSTM) neural network models, autoregressive integrated moving average (ARIMA) models, generalised regression neural network (GRNN) models and exponential smoothing (ES) were used to fit the incidence data. Data from 2015 and 2016 were used to validate the most suitable models. The model performances were evaluated by evaluating metrics, including mean square error (MSE), root mean square error, mean absolute error and mean absolute percentage error. The LSTM model had the lowest MSE when the N value (time step) was 12. The most appropriate ARIMA models for incidence in 2015 and 2016 were ARIMA (1, 1, 2) (0, 1, 2)12 and ARIMA (2, 1, 0) (1, 1, 2)12, respectively. The accuracy of GRNN and ES models in forecasting HIV incidence in Guangxi was relatively poor. Four performance metrics of the LSTM model were all lower than the ARIMA, GRNN and ES models. The LSTM model was more effective than other time-series models and is important for the monitoring and control of local HIV epidemics.
The seasonality of individual influenza subtypes/lineages and the association of influenza epidemics with meteorological factors in the tropics/subtropics have not been well understood. The impact of the 2009 H1N1 pandemic on the prevalence of seasonal influenza virus remains to be explored. Using wavelet analysis, the periodicities of A/H3N2, seasonal A/H1N1, A/H1N1pdm09, Victoria and Yamagata were identified, respectively, in Panzhihua during 2006–2015. As a subtropical city in southwestern China, Panzhihua is the first industrial city in the upper reaches of the Yangtze River. The relationship between influenza epidemics and local climatic variables was examined based on regression models. The temporal distribution of influenza subtypes/lineages during the pre-pandemic (2006–2009), pandemic (2009) and post-pandemic (2010–2015) years was described and compared. A total of 6892 respiratory specimens were collected and 737 influenza viruses were isolated. A/H3N2 showed an annual cycle with a peak in summer–autumn, while A/H1N1pdm09, Victoria and Yamagata exhibited an annual cycle with a peak in winter–spring. Regression analyses demonstrated that relative humidity was positively associated with A/H3N2 activity while negatively associated with Victoria activity. Higher prevalence of A/H1N1pdm09 and Yamagata was driven by lower absolute humidity. The role of weather conditions in regulating influenza epidemics could be complicated since the diverse viral transmission modes and mechanism. Differences in seasonality and different associations with meteorological factors by influenza subtypes/lineages should be considered in epidemiological studies in the tropics/subtropics. The development of subtype- and lineage-specific prevention and control measures is of significant importance.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Extensive insecticide use has led to the resistance of mosquitoes to these insecticides, posing a major barrier to mosquito control. Previous Solexa high-throughput sequencing of Culex pipiens pallens in the laboratory has revealed that the abundance of a novel microRNA (miRNA), miR-13664, was higher in a deltamethrin-sensitive (DS) strain than a deltamethrin-resistant (DR) strain. Real-time quantitative PCR revealed that the miR-13664 transcript level was lower in the DR strain than in the DS strain. MiR-13664 oversupply in the DR strain increased the susceptibility of these mosquitoes to deltamethrin, whereas inhibition of miR-13664 made the DS strain more resistant to deltamethrin. Results of bioinformatic analysis, quantitative reverse-transcriptase polymerase chain reaction, luciferase assay and miR mimic/inhibitor microinjection revealed CpCYP314A1 to be a target of miR-13664. In addition, downregulation of CpCYP314A1 expression in the DR strain reduced the resistance of mosquitoes to deltamethrin. Taken together, our results indicate that miR-13664 could regulate deltamethrin resistance by interacting with CpCYP314A1, providing new insights into mosquito resistance mechanisms.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
We present a review of our recent studies of Bias Temperature Instability (BTI) in Metal-Oxide-Semiconductor Field-Effect-Transistors (MOSFETs) fabricated with different material systems, highlighting the reliability opportunities and challenges of each novel device family. We discuss first the intrinsic reliability improvement offered by SiGe and Ge p-channel technologies, if a Si cap is used to passivate the channel, in order to fabricate a standard SiO2/HfO2 gate stack. We focus on SiGe gate stack optimizations for maximum BTI reliability, and on a simple physics-based model able to reproduce the experimental trends. This model framework is then used to understand the suboptimal BTI reliability and excessive time-dependent variability induced by oxide defect charging in different high-mobility channel gate stacks, such as Ge/GeOx/high-k and InGaAs/high-k. Finally we discuss how to pursue a reduction of charge trapping in alternative material systems in order to boost the device reliability and minimize time-dependent variability.
This study aimed to evaluate the ability of positron emission tomography with contrast-enhanced computed tomography to correctly stage head and neck squamous cell carcinomas, in comparison with pathological staging.
Positron emission tomography computed tomography was used to determine the tumour–node–metastasis classification and overall cancer stage in 85 head and neck squamous cell carcinoma patients who underwent pre-operative imaging using this modality and primary surgery between July 2010 and January 2013. Staging by positron emission tomography computed tomography was retrospectively compared with staging using pathological specimens. Agreement between imaging stage and pathological stage was examined by univariate and multivariate analysis both overall and for each primary tumour site.
This imaging modality was 87.5 per cent sensitive and 44.8 per cent specific in identifying regional cervical metastases, and had false positive and false negative rates of 18.8 per cent and 8.2 per cent, respectively. The positive predictive and negative predictive values were 75.4 per cent and 65.0 per cent, respectively. Univariate and multivariate analyses revealed a significant agreement between positron emission tomography computed tomography and pathological node classification in older patients and for the oral cavity primary tumour site. There was significant agreement between both methods in the overall classification only for tumours classified as T3 or greater.
Positron emission tomography computed tomography should be used with caution for the pre-operative staging of head and neck cancers because of its high false positive and false negative rates.
We derive zphot for sources in the entire (~0.4 deg2) H-HDF-N field with the EAzY code, based on PSF-matched broad-band (U band to IRAC 4.5 μm) photometry. Our catalog consists of a total of 131,678 sources. We find σNMAD = 0.029 for non-X-ray sources. We also classify each object as a star or galaxy through SED fitting. Furthermore, we match our catalog with the 2 Ms CDF-N main X-ray catalog. For the 462 matched non-stellar X-ray sources, we improve their zphot quality (σNMAD = 0.035) by adding three additional AGN templates. We make our photometry and zphot catalog publicly available.
Batch cultures of mixed rumen micro-organisms were used to evaluate varying enzyme products with high xylanase activity (EPX), four of which were recombinant single xylanase activity developmental enzyme products (EPX1–EPX4, products of xylanase genes derived from Trichoderma harzianum, Trichoderma reesei, Orpinomyces and Aspergillus oryzae, respectively), for their potential to improve in vitro ruminal fermentation of three forages [maize (Zea mays) stover (MS), rice (Oryza sativa) straw (RS) and Guimu No. 1 grass (Pennisetum americanum×Pennisetum purpureum, GM)]. The enzyme product EPX5, derived from Trichoderma longibrachiatum, was used as a positive control that could improve in vitro fermentation of forages. Enzymes were supplied at dose rates of 0 (control), 20 (low), 50 (medium) and 80 (high) enzymic units of xylanase/g of dry matter (DM). There were no interactions between EPX and dose for the fermentation characteristics evaluated. Increasing EPX dose linearly increased gas production (GP) kinetic characters [i.e. asymptotic GP (VF), half time when GP is half of the theoretical maximum GP (t0·5), and initial fractional rate of degradation (FRD0)] and methane (CH4) production from RS and GM at 24 h, and increased degradability of DM at 24 h for MS and RS. A linear increase in degradability of neutral detergent fibre (NDF) of the three forages at 24 h was observed with increasing dose of EPX, but at 48 h only NDF degradability of RS was increased. There were differences in the effects of EPX on degradability of DM and NDF from RS at 24 h, with EPX4 having the highest and EPX1 having the lowest. In addition, increasing EPX dose linearly increased acetate proportion at 24 h and total volatile fatty acids (TVFA) at 48 h in MS. Increasing EPX dose linearly increased TVFA at 24 h, and ammonia-nitrogen (NH3-N) concentration at 48 h in RS. For GM, linear or quadratic effects of dose on acetate and butyrate concentration were observed at 24 and 48 h. The present study indicates that applying EPX to low-quality forages has the potential to improve rumen degradability and utilization. Furthermore, EPX from different sources differed in their effects when applied at the same dose rate, with the responses being forage-specific. For RS, the EPX derived from A. oryzae showed the greatest positive effects on forage degradation; whereas for MS and GM, the source of micro-organism where EPX gene was derived did not affect the degradation, with little difference among the EPX evaluated.
To compare the behaviour of sows and the physiological indices of their offspring in stall and group-housing systems, 28 sows were randomly distributed into two systems with 16 sows in stalls, and the other 12 sows were divided into three groups with four sows per pen. The area per sow in stalls and groups was 1.2 and 2.5 m2, respectively. Back fat depth of the sow was measured. Salivary cortisol concentration of the sows, colostrum composition and piglets’ serum biochemical indicators were evaluated. The behaviour of the sows, including agonistic behaviour, non-agonistic social behaviour, stereotypical behaviour and other behaviours at weeks 2, 9 and 14 of pregnancy were analysed. The results showed no differences in the back fat depth of sows. Colostrum protein, triglyceride, triiodothyronine, thyroxine and prolactin concentrations in the whey also demonstrated no significant differences between the two housing systems. Salivary cortisol concentration was significantly higher in the sows housed in groups than the sows in stalls. The concentrations of serum total cholesterol and low-density lipoprotein (LDL) cholesterol were significantly higher in the offspring of sows housed in groups (P=0.006 and 0.005, respectively). The GLM procedure for repeated measures analysis showed the frequency of drinking, and non-agonistic social behaviour was significantly higher in the sows housed in groups than the sows in stalls; yet the frequency of agonistic and sham chewing demonstrated the opposite direction. The duration of standing was significantly longer in the sows housed in groups, but the sitting and stereotypical behaviour duration were significantly shorter compared with the sows in stalls. These results indicated that group housing has no obvious influence on the colostrum composition of sows; however, it was better for sows to express their non-agonistic social behaviour and reduce the frequency of agonistic behaviour and stereotypical behaviour. Meanwhile, group housing during gestation significantly increased serum total cholesterol and LDL cholesterol of offspring.
We investigated the seasonality of tuberculosis (TB) in Wuhan, China, to evaluate the increased risk of disease transmission during each season and to develop an effective TB control strategy. We applied spectral analysis to the weekly prevalence data of sputum smear positive (SSP) and sputum smear negative (SSN) pulmonary TB reported from 2006 to 2010. Cases of both SSP and SSN feature 1·0- and 0·5-year periodic modes. The least squares method was used to fit curves to the two periodic modes for SSP and SSN data. The curves demonstrated dominant peaks in spring similar to cases reported previously for other locations. Notably for SSP, dominant peaks were also observed in summer. The spring peaks of SSP and SSN were explained in terms of poorly ventilated and humid rooms and vitamin D deficiency. For the summer peaks of SSP, summer influenza epidemics in Wuhan may contribute to the increase in TB prevalence.
Gattini and CSTAR have been installed at Dome A, Antarctica, which provide time-series photometric data for a large number of pulsating variable stars. We present the study for several variable stars with the data collected with the two facilities in 2009 to demonstrate the scientific potential of observations from Dome A for asteroseismology.
Fisheries bycatch threatens populations of marine megafauna such as marine mammals, turtles, seabirds, sharks and rays, but fisheries impacts on non-target populations are often difficult to assess due to factors such as data limitation, poorly defined management objectives and lack of quantitative bycatch reduction targets. Limit reference points can be used to address these issues and thereby facilitate adoption and implementation of mitigation efforts. Reference points based on catch data and life history analysis can identify sustainability limits for bycatch with respect to defined population goals even when data are quite limited. This can expedite assessments for large numbers of species and enable prioritization of management actions based on mitigation urgency and efficacy. This paper reviews limit reference point estimators for marine megafauna bycatch, with the aim of highlighting their utility in fisheries management and promoting best practices for use. Different estimators share a common basic structure that can be flexibly applied to different contexts depending on species life history and available data types. Information on demographic vital rates and abundance is required; of these, abundance is the most data-dependent and thus most limiting factor for application. There are different approaches for handling management risk stemming from uncertainty in reference point and bycatch estimates. Risk tolerance can be incorporated explicitly into the reference point estimator itself, or probability distributions may be used to describe uncertainties in bycatch and reference point estimates, and risk tolerance may guide how those are factored into the management process. Either approach requires simulation-based performance testing such as management strategy evaluation to ensure that management objectives can be achieved. Factoring potential sources of bias into such evaluations is critical. This paper reviews the technical, operational, and political challenges to widespread application of reference points for management of marine megafauna bycatch, while emphasizing the importance of developing assessment frameworks that can facilitate sustainable fishing practices.
An improved 2D device model is generated to simulate the DC properties of hydrogen- terminated diamond MISFETs by taking into account the effect of electric field on hole mobility. At high lateral field, the mobility degrades due to velocity saturation and at high transverse field, the mobility decreases because of strong surface phonon scattering. As either field increases to a certain level (∼ 1MV/cm), the mobility becomes independent of doping concentration and the maximum transverse field appears at the boundary between surface acceptor region and bulk. The threshold voltage is found to be a strong function of gate length and can change from negative to positive, which will change the operation mode of the device. In addition, the simulation also shows that the transconductance reaches a maximum value at 80nm gate length but decreases after further shrinkage, which might be also related to the velocity saturation effect induced by large lateral field.