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Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disease and is caused by heterozygous germ-line mutations in either PKD1 (85%) or PKD2 (15%). It is characterised by the formation of numerous fluid-filled renal cysts and leads to adult-onset kidney failure in ~50% of patients by 60 years. Kidney cysts in ADPKD are focal and sporadic, arising from the clonal proliferation of collecting-duct principal cells, but in only 1–2% of nephrons for reasons that are not clear. Previous studies have demonstrated that further postnatal reductions in PKD1 (or PKD2) dose are required for kidney cyst formation, but the exact triggering factors are not clear. A growing body of evidence suggests that DNA damage, and activation of the DNA damage response pathway, are altered in ciliopathies. The aims of this review are to: (i) analyse the evidence linking DNA damage and renal cyst formation in ADPKD; (ii) evaluate the advantages and disadvantages of biomarkers to assess DNA damage in ADPKD and finally, (iii) evaluate the potential effects of current clinical treatments on modifying DNA damage in ADPKD. These studies will address the significance of DNA damage and may lead to a new therapeutic approach in ADPKD.
The effects of pantothenic acid (PA) and folic acid (FA) addition on digestibility coefficient, ruminal fermentation and urinary purine derivative (PD) excretion in dairy bulls were evaluated. Eight rumen-cannulated Holstein dairy bulls were allocated to a replicated 4 × 4 Latin square design according to a 2 × 2 factorial arrangement. Diets were supplemented with two levels of FA (0 or 8.0 mg/kg dietary dry matter [DM]) and two of PA (0 or 60 mg/kg DM). The PA × FA interaction was not significant for all variables. Both supplements increased DM intake and average daily gain, but decreased a feed conversion ratio. Digestibility of DM, organic matter, crude protein and neutral detergent fibre increased, but ether extract digestibility was unchanged for both supplements. Digestibility of acid detergent fibre only increased with FA supplementation. For both supplements, ruminal pH and ammonia nitrogen (N) decreased, but total volatile fatty acid (VFA) concentration increased. Acetate proportion only increased with FA supplementation. Propionate proportion decreased for both supplements. Consequently, the acetate to propionate ratio increased. For both supplements, activity of xylanase and pectinase, population of Ruminococcus albus, R. flavefaciens, Fibrobacter succinogenes and Ruminobacter amylophilus and total PD excretion increased. Additionally, activity of carboxymethylcellulase, cellobiase, α-amylase and protease, and population of total bacteria, fungi, protozoa, methanogens, Butyrivibrio fibrisolvens and Prevotella ruminicola increased with FA addition. The results suggested that PA and FA supplementation stimulated ruminal microbial growth and enzyme activity, resulting in an increased digestibility coefficient and ruminal total VFA concentration in dairy bulls.
There is evidence indicating that using the current UK energy feeding system to ration the present sheep flocks may underestimate their nutrient requirements. The objective of the present study was to address this issue by developing updated maintenance energy requirements for the current sheep flocks and evaluating if these requirements were influenced by a range of dietary and animal factors. Data (n = 131) used were collated from five experiments with sheep (5 to 18 months old and 29.0 to 69.8 kg BW) undertaken at the Agri-Food and Biosciences Institute of the UK from 2013 to 2017. The trials were designed to evaluate the effects of dietary type, genotype, physiological stage and sex on nutrient utilization and energetic efficiencies. Energy intake and output data were measured in individual calorimeter chambers. Energy balance (Eg) was calculated as the difference between gross energy intake and a sum of fecal energy, urine energy, methane energy and heat production. Data were analysed using the restricted maximum likelihood analysis to develop the linear relationship between Eg or heat production and metabolizable energy (ME) intake, with the effects of a range of dietary and animal factors removed. The net energy (NEm) and ME (MEm) requirements for maintenance derived from the linear relationship between Eg and ME intake were 0.358 and 0.486 MJ/kg BW0.75, respectively, which are 40% to 53% higher than those recommended in energy feeding systems currently used to ration sheep in the USA and the UK. Further analysis of the current dataset revealed that concentrate supplement, sire type or physiological stage had no significant effect on the derived NEm values. However, female lambs had a significantly higher NEm (0.352 v. 0.306 or 0.288 MJ/kg BW0.75) or MEm (0.507 v. 0.441 or 0.415 MJ/kg BW0.75) than those for male or castrated lambs. The present results indicate that using present energy feeding systems in the UK developed over 40 years ago to ration the current sheep flocks could underestimate maintenance energy requirements. There is an urgent need to update these systems to reflect the higher metabolic rates of the current sheep flocks.
Structure and optical properties have been successfully determined for a series of niobium- and tantalum-containing layered alkaline-earth silicate compounds, Ba3(Nb6−xTax)Si4O26 (x = 0.6, 1.8, 3.0, 4.2, 5.4). The structure of this solid solution was found to be hexagonal P-62m (No. 189), with Z = 1. With x increases from 0.6 to 5.4, the lattice parameter a increases from 8.98804(8) to 9.00565(9) Å and c decreases from 7.83721(10) to 7.75212(12) Å. As a result, the volume decreases from 548.304(11) to 544.479(14) Å3. The (Nb/Ta)O6 distorted octahedra form continuous chains along the c-axis. These (Nb/Ta)O6 chains are in turn linked with the Si2O7 groups to form distorted pentagonal channels in which Ba ions were found. These Ba2+ ions have full occupancy and a 13-fold coordination environment with neighboring oxygen sites. Another salient feature of the structure is the linear Si–O–Si chains. When x in Ba3(Nb6−xTax)Si4O26 increases, the bond valence sum (BVS) values of the Ba sites increase slightly (2.09–2.20), indicating the size of the cage becoming progressively smaller (over-bonding). While SiO cages are also slightly smaller than ideal (BVS range from 4.16 to 4.19), the (Nb/Ta)O6 octahedral cages are slightly larger than ideal (BVS range from 4.87 to 4.90), giving rise to an under-bonding situation. The bandgaps of the solid solution members were measured between 3.39 and 3.59 eV, and the x = 3.0 member was modeled by density functional theory techniques to be 3.07 eV. The bandgaps of these materials indicate that they are potential candidates for ultraviolet photocatalyst.
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
This paper considers the integrated guidance and control (IGC) problem for impact angle constrained interception against manoeuvring targets with actuator saturation constraint. Based on the backstepping technique, an adaptive IGC law is presented to address this problem, where a fixed-time differentiator is proposed to estimate the derivatives of virtual control inputs to avoid the inherent problem of “explosion of complexity” suffered by the typical backstepping. Furthermore, an auxiliary first-order filter is introduced into the IGC law to cope with the actuator saturation constraint. The stability of the closed-loop system is strictly proved. Finally, the superiority of the proposed IGC law is verified by comparison simulations.
Rubber seed oil (RO) that is rich in polyunsaturated fatty acids (FA) can improve milk production and milk FA profiles of dairy cows; however, the responses of digestion and ruminal fermentation to RO supplementation in vivo are still unknown. This experiment was conducted to investigate the effect of RO and flaxseed oil (FO) supplementation on nutrients digestibility, rumen fermentation parameters and rumen FA profile of dairy cows. Forty-eight mid-lactation Holstein dairy cows were randomly assigned to one of four treatments for 8 weeks, including basal diet (CON) or the basal dietary supplemented with 4% RO, 4% FO or 2% RO plus 2% FO on a DM basis. Compared with CON, dietary oil supplementation improved the total tract apparent digestibility of DM, neutral detergent fibre and ether extracts ( P < 0.05). Oil treatment groups had no effects on ruminal digesta pH value, ammonia N and microbial crude protein ( P > 0.05), whereas oil groups significantly changed the volatile fatty acid (VFA) profile by increasing the proportion of propionate whilst decreasing total VFA concentration, the proportion of acetate and the ratio of acetate to propionate ( P < 0.05). However, there were no differences in VFA proportions between the three oil groups (P > 0.05). In addition, dietary oil supplementation increased the total unsaturated FA proportion in the rumen by enhancing the proportion of trans-11 C18:1 vaccenic acid (VA), cis-9, trans-11 conjugated linoleic acid (CLA) and α-linolenic acid (ALA) ( P < 0.05). These results indicate that dietary supplementation with RO and FO could improve nutrients digestibility, ruminal fermentation and ruminal FA profile by enhancing the VA, cis-9, trans-11 CLA and ALA composition of lactating dairy cows. These findings provide a theoretical basis for the application of RO in livestock production.
Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.
To compare the epidemiologic features (e.g. settings and transmission mode) and patient clinical characteristics associated with outbreaks of different norovirus (Nov) strains, we retrospectively analysed data of Nov outbreaks occurring in Guangzhou, China from 2012 to 2018. The results suggested that outbreaks of Nov GII.2, GII.17 and GII.4 Sydney exhibited different outbreak settings, transmission modes and symptoms. GII.2 outbreaks mainly occurred in kindergartens, elementary and high schools and were transmitted mainly through person-to-person contact. By contrast, GII.4 Sydney outbreaks frequently occurred in colleges and were primarily associated with foodborne transmission. Cases from GII.2 and GII.17 outbreaks reported vomiting more frequently than those from outbreaks associated with GII.4 Sydney.
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.
Optimizing the dietary calcium (Ca) level is essential to maximize the eggshell quality, egg production and bone formation in poultry. This study aimed to establish the Ca requirements of egg-type duck breeders from 23 to 57 weeks of age on egg production, eggshell, incubation, tibial, plasma and ovary-related indices, as well as the expression of matrix protein-related genes. Totally, 450 Longyan duck breeders aged 21 weeks of age were allotted randomly into five treatments, each with six replicates of 15 individually caged birds. The data collection started from 23 weeks of age and continued over the following 35 weeks. The five groups corresponded to five dietary treatments containing either 2.8%, 3.2%, 3.6%, 4.0% or 4.4% Ca. The tested dietary Ca levels increased (linear, P <0.01) egg production and egg mass, and linearly improved (P <0.01) the feed conversion ratio (FCR). Increasing the dietary Ca levels from 2.8% to 4.4% increased (P <0.01) the eggshell thickness and eggshell content. The tested Ca levels showed a quadratic effect on eggshell thickness and ovarian weight (P <0.01); the highest values were obtained with the Ca levels 4.0% and 3.6%, respectively. Dietary Ca levels affected the small yellow follicles (SYF) number and SYF weight/ovarian weight, and the linear response (P <0.01) was significant vis-à-vis SYF number. In addition, dietary Ca levels increased (P <0.05) the tibial dry weight, breaking strength, mineral density and ash content. Plasma and tibial phosphorus concentration exhibited a quadratic (P <0.01) response to dietary Ca levels. Plasma calcitonin concentration linearly (P <0.01) increased as dietary Ca levels increased. The relative expression of carbonic anhydrase 2 in the uterus rose (P <0.01) with the increment of dietary Ca levels, and the highest value was obtained with 3.2% Ca. In conclusion, Longyan duck breeders fed a diet with 4.0% Ca had superior eggshell and tibial quality, while those fed a diet with 3.6% Ca had the heaviest ovarian weights. The regression model indicated that the dietary Ca levels 3.86%, 3.48% and 4.00% are optimal levels to obtain maximum eggshell thickness, ovarian weight and tibial mineral density, respectively.
Baissogryllidae is an extinct family of the insect superfamily Grylloidea, previously known from Late Jurassic – Early Cretaceous time. A new genus and species, Sinagryllus xinjiangensis gen. et sp. nov., is described here based on a well-preserved forewing from the Lower Jurassic Sangonghe Formation of Xinjiang, northwestern China. It can be attributed to Baissogryllidae based on the combination of the following characteristics: a true mirror in the male tegminal stridulatory apparatus; and a distinct widening of the area between CuA2, lateral part of the diagonal vein, and proximal part of the proximal branch of MP+CuA1. This find represents not only the earliest record of Baissogryllidae, but also the first fossil wing of Grylloidea reported from China.
Coal mine dust is produced from complex materials which consist of organic sedimentary phases, inorganic minerals, and trace elements. The dust varies in its chemical compositions and is capable of causing lung injury when inhaled. The purpose of this study was to perform scanning electron microscopy combined with energy dispersive spectrometry, wavelength dispersive spectrometry and X-ray diffraction analyses of three coal dusts and examine their effects on rat lung alveolar macrophages (AM) in cell culture. The coal dusts were obtained from coal surfaces of anthracite, meager and fat coal mines. AM were harvested by bronchoalveolar lavage from adult male Wistar rats and were cultured in Eagle's medium at 37°C.
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.
Music or other background sounds are often played in barns as environmental enrichment for animals on farms or to mask sudden disruptive noises. Previous studies looking at the effects of this practice on non-human animal well-being and productivity have found contradictory results. However, there is still a lack of discussion on whether piglets have the ability to distinguish different types of music. In this study, we exposed piglets to different music conditions to investigate whether the piglets preferred certain music types, in which case those types would have the potential to be used as environmental enrichment. In total, 30 piglets were tested for music type preference to determine whether growing pigs respond differently to different types of music. We used music from two families of instruments (S: string, W: wind) and with two tempos (S: slow, 65 beats/min (bpm); F: fast, 200 bpm), providing four music-type combinations (SS: string-slow; SF: string-fast; WS: wind-slow; WF: wind-fast). The piglets were given a choice between two chambers, one with no music and the other with one of the four types of music, and their behaviour was observed. The results showed that SS and WF music significantly increased residence time (P<0.01) compared with the other music conditions. Compared with the control group (with no music), the different music conditions led to different behavioural responses, where SS music significantly increased lying (P<0.01) and exploration behaviour (P<0.01); SF music significantly increased tail-wagging behaviour (P<0.01); WS music significantly increased exploration (P<0.01); and WF music significantly increased walking, lying, standing and exploration (all P<0.01). The results also showed that musical instruments and tempo had little effect on most of the behaviours. Fast-tempo music significantly increased walking (P=0.02), standing (P<0.01) and tail wagging (P=0.04) compared with slow-tempo music. In conclusion, the results of this experiment show that piglets are more sensitive to tempo than to musical instruments in their response to musical stimulation and seem to prefer SS and WF music to the other two types. The results also suggest a need for further research on the effect of music types on animals.
Alanyl-glutamine (Ala-Gln), a highly soluble and stable glutamine dipeptide, is known to improve gut integrity and function. The aim of this study was to evaluate whether dietary Ala-Gln supplementation could improve growth performance, intestinal development and digestive-absorption function in weaned piglets. A total of 100 purebred Yorkshire piglets weaned at 21 days of age were assigned randomly to four dietary treatment groups and fed a basal diet (control group) or a basal diet containing 0.15%, 0.30% and 0.45% Ala-Gln, respectively. Compared with the control group, piglets fed the Ala-Gln diets had higher average daily gain and lower feed : gain and diarrhea rate (P < 0.05). Moreover, dietary Ala-Gln supplementation increased villous height and villous height : crypt depth ratio in duodenum and jejunum (P < 0.05), as well as the activities of maltase and lysozyme in jejunum mucosa (P < 0.05). In addition, a decrease in serum diamine oxidase activity and crypt depth in duodenum and jejunum was observed in piglets fed the Ala-Gln diets (P < 0.05). Serum cytosolic phospholipase A2 (cPLA2) concentration and gene expression of cPLA2, Na+-dependent glucose transporter 1, glucose transporter 2 and peptide transporter 1 in jejunum were increased by feeding Ala-Gln diets relative to control diet (P < 0.05). These results indicated that feeding Ala-Gln diet has beneficial effects on the growth performance of weaned piglets, which associated with maintaining intestinal morphology and digestive-absorption function.
Heading date (HD) and flowering date (FD) are critical for yield potential and stability, so understanding their genetic foundation is of great significance in wheat breeding. Three related recombinant inbred line populations with a common female parent were developed to identify quantitative trait loci (QTL) for HD and FD in four environments. In total, 25 putative additive QTL and 20 pairwise epistatic effect QTL were detected in four environments. The additive QTL were distributed across 17 wheat chromosomes. Of these, QHd-1A, QHd-1D, QHd-2B, QHd-3B, QHd-4A, QHd-4B and QHd-6D were major and stable QTL for HD. QFd-1A, QFd-2B, QFd-4A and QFd-4B were major and stable QTL for FD. In addition, an epistatic interaction test showed that epistasis played important roles in controlling wheat HD and FD. Genetic relationships between HD/FD and five yield-related traits (YRTs) were characterized and ten QTL clusters (C1–C10) simultaneously controlling YRTs and HD/FD were identified. The present work laid a genetic foundation for improving yield potential in wheat molecular breeding programmes.
Muons produced by the Bethe–Heitler process from laser wakefield accelerated electrons interacting with high
materials have velocities close to the laser wakefield. It is possible to accelerate those muons with laser wakefield directly. Therefore for the first time we propose an all-optical ‘Generator and Booster’ scheme to accelerate the produced muons by another laser wakefield to supply a prompt, compact, low cost and controllable muon source in laser laboratories. The trapping and acceleration of muons are analyzed by one-dimensional analytic model and verified by two-dimensional particle-in-cell (PIC) simulation. It is shown that muons can be trapped in a broad energy range and accelerated to higher energy than that of electrons for longer dephasing length. We further extrapolate the dependence of the maximum acceleration energy of muons with the laser wakefield relativistic factor
and the relevant initial energy
. It is shown that a maximum energy up to 15.2 GeV is promising with
on the existing short pulse laser facilities.
The fate of a contracting liquid filament depends on the Ohnesorge number (
), the initial aspect ratio (
) and surface perturbation. Generally, it is believed that there exists a critical aspect ratio
such that longer filaments break up and shorter ones recoil into a single drop. Through computational and experimental studies, we report a transitional regime for filaments with a broad range of intermediate aspect ratios, where there exist multiple
thresholds at which a novel breakup mode alternates with no-break mode. We develop a simple model considering the superposition of capillary waves, which can predict the complicated new phase diagram. In this model, the breakup results from constructive interference between the capillary waves that originate from the ends of the filament.