Integrating rare pathogenic variant prioritization with gene-based association analysis to identify novel genes and relevant multimodal traits for Alzheimer's disease.

Introduction: Increasing evidence has highlighted rare variants in Alzheimer's disease (AD). However, insufficient sample sizes, especially in underrepresented ethnic groups, hinder their investigation. Additionally, their impact on endophenotypes remains largely unexplored.

Engineering of cytosine base editors with DNA damage minimization and editing scope diversification.

Cytosine base editors (CBEs), which enable precise C-to-T substitutions, have been restricted by potential safety risks, including DNA off-target edits, RNA off-target edits and additional genotoxicity such as DNA damages induced by double-strand breaks (DSBs). Though DNA and RNA off-target edits have been ameliorated via various strategies, evaluation and minimization of DSB-associated DNA damage risks for most CBEs remain to be resolved. Here we demonstrate that YE1, an engineered CBE variant with minimized DNA and RNA off-target edits, could induce prominent DSB-associated DNA damage risks, manifested as γH2AX accumulation in human cells.

TadA reprogramming to generate potent miniature base editors with high precision.

Although miniature CRISPR-Cas12f systems were recently developed, the editing efficacy and targeting range of derived miniature cytosine and adenine base editors (miniCBEs and miniABEs) have not been comprehensively addressed. Moreover, functional miniCBEs have not yet be established. Here we generate various Cas12f-derived miniCBEs and miniABEs with improved editing activities and diversified targeting scopes.

TadA orthologs enable both cytosine and adenine editing of base editors.

Cytidine and adenosine deaminases are required for cytosine and adenine editing of base editors respectively, and no single deaminase could enable concurrent and comparable cytosine and adenine editing. Additionally, distinct properties of cytidine and adenosine deaminases lead to various types of off-target effects, including Cas9-indendepent DNA off-target effects for cytosine base editors (CBEs) and RNA off-target effects particularly severe for adenine base editors (ABEs). Here we demonstrate that 25 TadA orthologs could be engineered to generate functional ABEs, CBEs or ACBEs via single or double mutations, which display minimized Cas9-independent DNA off-target effects and genotoxicity, with orthologs B5ZCW4, Q57LE3, E8WVH3, Q13XZ4 and B3PCY2 as promising candidates for further engineering.

Effects of Forest Type on Nutrient Fluxes in Throughfall, Stemflow, and Litter Leachate within Acid-Polluted Locations in Southwest China.

Although new inputs of acidic anions are decreasing, soil acidification still deserves more academic attention because of the effects of historical stores of SO already absorbed into soils. Forest canopy has large, species-specific effects on rainwater chemistry, for which the hydrological mechanism remains unclear. We investigated precipitation, throughfall, stemflow, and litter leachate across three forest types in a severely acid-polluted site located in Southwest China.

Integration of Multimodal Data for Deciphering Brain Disorders.

The accumulation of vast amounts of multimodal data for the human brain, in both normal and disease conditions, has provided unprecedented opportunities for understanding why and how brain disorders arise. Compared with traditional analyses of single datasets, the integration of multimodal datasets covering different types of data (i.e.

Effects of natural and artificial restoration on plant community characteristics of alpine cutting blank in Western Sichuan, China.

To investigate the plant community characteristics of alpine cutting blanks under different restoration approaches, we conducted a field survey on cutting blanks experienced either natural restoration (40 years) or artificial restoration (30, 40 and 50 years) in western Sichuan, with natural forests as the reference. Our results showed that after 40 years natural succession, cutting blank was replaced by the secondary shrub of , while artificial restoration plantation was dominated by var. .

Nitrogen Fertilization Modified the Responses of Seedlings to Elevated CO in Subtropical China.

There are very few studies about the effects of relatively higher CO concentration (e.g., 1000 μmol·mol) or plus N fertilization on woody plants.

Docking sites inside Cas9 for adenine base editing diversification and RNA off-target elimination.

Base editing tools with diversified editing scopes and minimized RNA off-target activities are required for broad applications. Nevertheless, current Streptococcus pyogenes Cas9 (SpCas9)-based adenine base editors (ABEs) with minimized RNA off-target activities display constrained editing scopes with efficient editing activities at positions 4-8. Here, functional ABE variants with diversified editing scopes and reduced RNA off-target activities are identified using domain insertion profiling inside SpCas9 and with different combinations of TadA variants.

Elevated O alters soil bacterial and fungal communities and the dynamics of carbon and nitrogen.

Although many studies have reported the negative effects of elevated O on plant physiological characteristics, the influence of elevated O on below-ground processes and soil microbial functioning is less studied. In this study, we examined the effects of elevated O on soil properties, soil microbial biomass, as well as microbial community composition using high-throughput sequencing. Throughout one growing season, one-year old seedlings of two important endemic trees in subtropical China: Taxus chinensis (Pilger) Rehd.

Effects of elevated O on physiological and biochemical responses in three kinds of trees native to subtropical forest in China during non-growing period.

Numerous studies have documented the negative effects of ozone (O) on tree species in growing season, however, little is done in non-growing season. Three evergreen tree species, Phoebe bournei (Hemsl.) Yang (P.

How important is woody tissue photosynthesis in EuCahetus dunnii Maiden and Osmanthus fragrans (Thunb.) Lour. under O stress?

Numerous studies have demonstrated the negative effects of elevated O on leaf photosynthesis. Within trees, a portion of respired CO is assimilated by woody tissue photosynthesis, but its response to elevated O remains unclear. Saplings of two evergreen tree species, EuCahetus dunnii Maiden (E.

Physiological and biochemical responses of Machilus ichangensis Rehd. et Wils and Taxus chinensis (Pilger) Rehd. to elevated O in subtropical China.

Considerable researches have documented the negative effects of ozone on woody species in North America and Europe; however, little is known about how woody tree species respond to elevated O in subtropical China, and most of the previous studies were conducted using pot experiment. In the present study, Machilus ichangensis Rehd. et Wils (M.

Effects of grazing intensity on soil labile organic carbon fractions in a desert steppe area in Inner Mongolia.

Grazing can cause changes in soil carbon (C) level. This study aimed to elucidate the response of soil labile organic carbon (SLOC) under four different grazing intensities: non grazing (NG), 0 sheep·ha(-1); light grazing (LG), 0.91 sheep·ha(-1); moderate grazing (MG), 1.

Response of soil respiration to soil temperature and moisture in a 50-year-old oriental arborvitae plantation in China.

China possesses large areas of plantation forests which take up great quantities of carbon. However, studies on soil respiration in these plantation forests are rather scarce and their soil carbon flux remains an uncertainty. In this study, we used an automatic chamber system to measure soil surface flux of a 50-year-old mature plantation of Platycladus orientalis at Jiufeng Mountain, Beijing, China.