Polygenic risk scores (PRS) have shown promise in predicting human complex traits and diseases. Here, we present PRS-CS, a polygenic prediction method that infers posterior effect sizes of single ...nucleotide polymorphisms (SNPs) using genome-wide association summary statistics and an external linkage disequilibrium (LD) reference panel. PRS-CS utilizes a high-dimensional Bayesian regression framework, and is distinct from previous work by placing a continuous shrinkage (CS) prior on SNP effect sizes, which is robust to varying genetic architectures, provides substantial computational advantages, and enables multivariate modeling of local LD patterns. Simulation studies using data from the UK Biobank show that PRS-CS outperforms existing methods across a wide range of genetic architectures, especially when the training sample size is large. We apply PRS-CS to predict six common complex diseases and six quantitative traits in the Partners HealthCare Biobank, and further demonstrate the improvement of PRS-CS in prediction accuracy over alternative methods.
Linking human behavior to resting-state brain function is a central question in systems neuroscience. In particular, the functional timescales at which different types of behavioral factors are ...encoded remain largely unexplored. The behavioral counterparts of static functional connectivity (FC), at the resolution of several minutes, have been studied but behavioral correlates of dynamic measures of FC at the resolution of a few seconds remain unclear. Here, using resting-state fMRI and 58 phenotypic measures from the Human Connectome Project, we find that dynamic FC captures task-based phenotypes (e.g., processing speed or fluid intelligence scores), whereas self-reported measures (e.g., loneliness or life satisfaction) are equally well explained by static and dynamic FC. Furthermore, behaviorally relevant dynamic FC emerges from the interconnections across all resting-state networks, rather than within or between pairs of networks. Our findings shed new light on the timescales of cognitive processes involved in distinct facets of behavior.
Nitrogen (N) is one of the most required mineral elements for plant growth, and potassium (K) plays a vital role in nitrogen metabolism, both elements being widely applied as fertilizers in ...agricultural production. However, the exact relationship between K and nitrogen use efficiency (NUE) remains unclear. Apple dwarf rootstock seedlings (M9T337) were used to study the impacts of different K levels on plant growth, nitrogen metabolism, and carbon (C) assimilation in water culture experiments for 2 years. The results showed that both deficiency and excess K inhibited the growth and root development of M9T337 seedlings. When the K supply concentration was 0 mM and 12 mM, the biomass of each organ, root-shoot ratio, root activity and NO
3
–
ion flow rate decreased significantly, net photosynthetic rate (
P
n
) and photochemical efficiency (
F
v
/
F
m
) being lower. Meanwhile, seedlings treated with 6 mM K
+
had higher N and C metabolizing enzyme activities and higher nitrate transporter gene expression levels (
NRT1.1
;
NRT2.1
).
13
C and
15
N labeling results showed that deficiency and excess K could not only reduce
15
N absorption and
13
C assimilation accumulation of M9T337 seedlings, but also reduced the
15
N distribution ratio in leaves and
13
C distribution ratio in roots. These results suggest that appropriate K supply (6 mM) was optimal as it enhanced photoassimilate transport from leaves to roots and increased NUE by influencing photosynthesis, C and N metabolizing enzyme activities, nitrate assimilation gene activities, and nitrate transport.
Vitamin D has been associated with a variety of human complex traits and diseases in observational studies, but a causal relationship remains unclear. To examine a putative causal effect of vitamin D ...across phenotypic domains and disease categories, we conducted Mendelian randomization (MR) analyses using genetic instruments associated with circulating 25-hydroxyvitamin D 25(OH)D concentrations. We leveraged genome-wide significant 25(OH)D-associated SNPs (N = 138) from a meta-analysis combining a vitamin D GWAS conducted in 401,460 white British UK Biobank (UKBB) participants and an independent vitamin D GWAS including 42,274 samples of European ancestry, and examined 190 large-scale health-related GWAS spanning a broad spectrum of complex traits, diseases and biomarkers. We applied multiple MR methods to estimate the causal effect of vitamin D while testing and controlling for potential biases from horizontal pleiotropy. Consistent with previous findings, genetically predicted increased 25(OH)D levels significantly decreased the risk of multiple sclerosis (OR = 0.824; 95% CI 0.689-0.986). The protective effect estimate was consistent across different MR methods and four different multiple sclerosis GWAS with varying sample sizes and genotyping platforms. On the contrary, we found limited evidence in support of a causal effect of 25(OH)D on anthropometric traits, obesity, cognitive function, sleep behavior, breast and prostate cancer, and autoimmune, cardiovascular, metabolic, neurological and psychiatric traits and diseases, and blood biomarkers. Our results may inform ongoing and future randomized clinical trials of vitamin D supplementation.
Inhibitory interneurons orchestrate information flow across the cortex and are implicated in psychiatric illness. Although interneuron classes have unique functional properties and spatial ...distributions, the influence of interneuron subtypes on brain function, cortical specialization, and illness risk remains elusive. Here, we demonstrate stereotyped negative correlation of somatostatin and parvalbumin transcripts within human and non-human primates. Cortical distributions of somatostatin and parvalbumin cell gene markers are strongly coupled to regional differences in functional MRI variability. In the general population (n = 9,713), parvalbumin-linked genes account for an enriched proportion of heritable variance in in-vivo functional MRI signal amplitude. Single-marker and polygenic cell deconvolution establish that this relationship is spatially dependent, following the topography of parvalbumin expression in post-mortem brain tissue. Finally, schizophrenia genetic risk is enriched among interneuron-linked genes and predicts cortical signal amplitude in parvalbumin-biased regions. These data indicate that the molecular-genetic basis of brain function is shaped by interneuron-related transcripts and may capture individual differences in schizophrenia risk.
Humans survive and thrive through social exchange. Yet, social dependency also comes at a cost. Perceived social isolation, or loneliness, affects physical and mental health, cognitive performance, ...overall life expectancy, and increases vulnerability to Alzheimer's disease-related dementias. Despite severe consequences on behavior and health, the neural basis of loneliness remains elusive. Using the UK Biobank population imaging-genetics cohort (n = ~40,000, aged 40-69 years when recruited, mean age = 54.9), we test for signatures of loneliness in grey matter morphology, intrinsic functional coupling, and fiber tract microstructure. The loneliness-linked neurobiological profiles converge on a collection of brain regions known as the 'default network'. This higher associative network shows more consistent loneliness associations in grey matter volume than other cortical brain networks. Lonely individuals display stronger functional communication in the default network, and greater microstructural integrity of its fornix pathway. The findings fit with the possibility that the up-regulation of these neural circuits supports mentalizing, reminiscence and imagination to fill the social void.
Outlier removal is a fundamental data processing task to ensure the quality of scanned point cloud data (PCD), which is becoming increasing important in industrial applications and reverse ...engineering. Acquired scanned PCD is usually noisy, sparse and temporarily incoherent. Thus the processing of scanned data is typically an ill-posed problem. In the paper, we present a simple and effective method based on two geometrical characteristics constraints to trim the noisy points. One of the geometrical characteristics is the local density information and another is the deviation from the local fitting plane. The local density based method provides a preprocessing step, which could remove those sparse outlier and isolated outlier. The non-isolated outlier removal in this paper depends on a local projection method, which placing those points onto objects. There is no doubt that the deviation of any point from the local fitting plane should be a criterion to reduce the noisy points. The experimental results demonstrate the ability to remove the noisy point from various man-made objects consisting of complex outlier.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Table FW has more putrescible fraction and fewer impurities than kitchen FW.•Three anaerobic digestion scenarios are compared with incineration practice.•AD followed by composting digestate is best ...in most of the impact categories.•AD followed by gasifying digestate outputs the largest electricity.•Gas engine emission, and water consumption should be lowered.
A life cycle assessment (LCA) was conducted to determine the best solution for dealing with the food waste (FW) generated in Singapore eateries. Since the representativeness of the life cycle inventory (LCI) data determined the overall quality of the LCA, this study made a significant endeavor to capture the local specificities, such as waste composition, water supply and treatment plant operation. Characterization data showed that eatery FW from Singapore contained 16% non-biodegradable impurities (such as plastic and metal) and a higher methane generation potential was found in FW from the dining table than in FW from the kitchen. Based on the FW chemical element composition, mass balances were established for the four examined scenarios, including incineration (Inci), anaerobic digestion (AD) followed by composting (ADcom), AD followed by incineration (ADinci) and AD followed by gasification (ADgas). Because of the environmental benefits from compost production in addition to electricity generation, ADcom outperformed other scenarios in all impact categories except Eutro (eutrophication), GW (global warming) and POC (photochemical ozone creation). The best score of GW was observed in ADgas, mainly ascribed to the highest electricity output and the carbon sequestration of biochar. The disadvantages of the AD scenarios in Eutro and POC were associated with NOx and CO emissions from the biogas engine. Finally, the sensitivity analysis demonstrated that better environmental profiles could be achieved if improvements can be made by minimizing water usage, mitigating gas engine pollution, and diverting as much FW as possible from incineration plants to AD plants. However, based on the local context, source separation was not an urgent issue for improving the sustainability of eatery FW management.
Aim
This study aimed to investigate effects of renal denervation (RDN) on pressure overload‐induced cardiac remodelling in rats and the related mechanisms.
Methods
Adult male Sprague‐Dawley rats ...underwent transverse aortic constriction (TAC) to generate cardiac remodelling. RDN was performed 1 week after TAC. The animals were divided into four groups: control group, TAC group, TAC+RDN group and control+RDN group. Rats in all groups were studied at 3 and 10 weeks after TAC respectively. Echocardiography and histology were used to evaluate cardiac function and pathological changes. TUNEL staining and western blotting were used to assess apoptosis. Western blotting and transmission electron microscopy (TEM) were used to evaluate autophagy.
Results
Three weeks after TAC, the TAC rats exhibited cardiac hypertrophy with normal cardiac function and no myocardial interstitial fibrosis or apoptosis, accompanied by a lower LC3 II level and fewer autophagic vacuoles in the left ventricles, both in the presence and absence of chloroquine (CQ), indicating suppressed autophagy at this stage. RDN ameliorated these pathological changes and attenuated the decrease in autophagy. Ten weeks after TAC, the TAC rats had decreased cardiac function, obvious cardiac interstitial fibrosis and apoptosis, with increased autophagy. RDN prevented these pathological changes, coincident with attenuation of increased autophagy.
Conclusion
Autophagy was suppressed at the early stage but activated at the late stage of TAC‐induced cardiac remodelling. RDN attenuated the pathological changes of TAC rats, accompanied by attenuation of the changes in autophagy. Thus, RDN ameliorated TAC‐induced cardiac remodelling partially associated with biphasic modulation of autophagy.
The aims of the present study were to investigate the effects of angiotensin receptor neprilysin inhibitors (ARNi) on the susceptibility of ventricular arrhythmias (VAs) in rats with myocardial ...infarction (MI) and to explore the related mechanisms.A total of 32 adult male Sprague-Dawley rats were divided into 3 groups: a control group, MI group, and MI+ARNi group. MI was generated by ligation of the left anterior descending coronary artery. ARNi was given at 68 mg/kg/day for 4 weeks after MI surgery. At 4 weeks after MI, electrical programmed stimulation (EPS) was performed in all groups for the evaluation of VAs, and echocardiography was used to evaluate cardiac function. Indicators of sympathetic neural remodeling and cardiac remodeling were detected to further explore the related mechanisms.Four weeks after MI, rats in the ARNi group exhibited low susceptibility of VAs in comparison with that in the MI group, which was coincident with the attenuation of sympathetic nerve remodeling, amelioration of cardiac fibrosis, and regulation of Cx43 expression.ARNi is effective in reducing VAs in rats with ischemic cardiomyopathy, which is associated with attenuating sympathetic nerve remodeling and myocardial fibrosis.
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