抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

/pdf/an-integrated-encyclopedia-of-dna-elements-in-the-human-52ukbi8ats.pdf

An integrated encyclopedia of DNA elements in the human genome

Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets

RNA-Seq is a recently developed approach to transcriptome profiling that uses deep-sequencing technologies. Studies using this method have already altered our view of the extent and complexity of eukaryotic transcriptomes. RNA-Seq also provides a far more precise measurement of levels of transcripts and their isoforms than other methods. This article describes the RNA-Seq approach, the challenges associated with its application, and the advances made so far in characterizing several eukaryote transcriptomes.

/pdf/rna-seq-a-revolutionary-tool-for-transcriptomics-bj1lajhogb.pdf

RNA-Seq: a revolutionary tool for transcriptomics

Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

• The co-doping of Mn and V and the co-doping of Mn and Ti can significantly improve the adsorption of small gas molecules such as NH 3 , NO, and NO 2 on the CoCr 2 O 4 catalyst. • The barriers of the NH 3 dehydrogenation reaction and the NH 2 NO decomposition process on the Mn, V co-doped and Mn, Ti co-doped CoCr 2 O 4 catalysts are significantly reduced. • The co-doping of Mn and Ti can effectively improve the water resistance and sulfur resistance of the CoCr 2 O 4 catalyst. Being based on the first-principles calculation method of density functional theory, our work calculated the optimized configuration of CoCr 2 O 4 (100) before and after co-doping of Mn and V(Ti). The adsorption behaviors of NH 3 , NO, NO 2 and other gas molecules on the catalyst before and after doping were simulated. The optimized structures and related energy distribution of NH 3 dehydrogenation reaction and SCR reaction on Mn 0.1 Co 0.9 V 0.1 Cr 1.9 O 4 and Mn 0.1 Co 0.9 Ti 0.1 Cr 1.9 O 4 catalysts were also fully studied. Our results reveal that the co-doping of heteroatom towards CoCr 2 O 4 (100) may result in electron migration and lattice dislocations as well as improving the surface acid activity. Therefore, the co-doping of Mn and V or Mn and Ti are believed to improve the adsorption of NH 3 , NO, NO 2 and other gas molecules on the CoCr 2 O 4 catalyst and significantly reduce the activation energy barrier of the NH 3 dehydrogenation reaction and the SCR reaction. Furthermore, we studied the adsorption of SO 2 and H 2 O on the co-doped catalyst, which exhibited that the co-doping of Mn and Ti may effectively improve the water and sulfur resistance of the catalyst. Our research are expected to be full of important theoretical guiding significance for the development, preparation and modification of cobalt-chromium spinel catalysts. The adsorption of NH 3 , NO, NO 2 and other small gas molecules on the surface of the CoCr 2 O 4 (100) catalyst co-doped with Mn, V and Mn, Ti and the reaction mechanism of NH 3 -SCR are revealed. 

Study on the mechanism of NOx reduction by NH3-SCR over Mn and M(M=V,Ti) co-doped CoCr2O4 catalyst

Rare coding variants as risk modifiers of the 22q11.2 deletion implicate postnatal cortical development in syndromic schizophrenia

Although gene expansion plays an important role in evolution, its identification remains a challenge due to potential errors in genome assembly and annotation. Here, we describe a detailed step-by-step protocol for gene annotation, prediction of genomic gene expansion, and its computational and experimental validation. Finally, we also detail steps to discover functionality of each copy of replicated genes. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2021). 

https://doi.org/10.1016/j.xpro.2022.101692

Protocol for gene annotation, prediction, and validation of genomic gene expansion

Frailty is characterized by increased vulnerability to disability and high risk for mortality in older adults. Identification of factors that contribute to frailty resilience is an important step in the development of effective therapies that protect against frailty. First, a reliable quantification of frailty resilience is needed. We developed a novel measure of frailty resilience, the Frailty Resilience Score (FRS), that integrates frailty genetic risk, age, and sex. Application of FRS to the LonGenity cohort (n=467, mean age 74.4) demonstrated its validity compared to phenotypic frailty and its utility as a reliable predictor of overall survival. In a multivariable adjusted analysis, one standard deviation increase in FRS predicted a 38% reduction in the hazard of mortality, independent of baseline frailty (p<0.001). Additionally, FRS was used to identify a proteomic profile of frailty resilience. FRS was shown to be a reliable measure of frailty resilience that can be applied to biological studies of resilience.

Frailty Resilience Score: A Novel Measure of Frailty Resilience Associated with Protection from Frailty and Survival.

At over 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth, reaching over 80,000 kg1. In spite of its very large number of cells, the bowhead is not highly cancer-prone, an incongruity termed Peto’s Paradox2. This has been explained by the evolution of additional tumor suppressor genes in larger animals, which is supported by research on elephants demonstrating expansion of the p53 gene3–5. However, we show here that bowhead whale fibroblasts undergo oncogenic transformation after disruption of fewer tumor suppressors than required for human fibroblasts. Instead, analysis of DNA repair revealed that bowhead cells repair double-strand breaks with uniquely high efficiency and accuracy compared to other mammals. Further, we identified two proteins, CIRBP and RPA2, that are present at high levels in bowhead fibroblasts and increase the efficiency and fidelity of DNA repair in human cells. These results suggest that rather than possessing additional tumor suppressor genes as barriers to oncogenesis, the bowhead whale relies on more accurate and efficient DNA repair to preserve genome integrity. This strategy that does not eliminate cells but repairs them, may be critical for the long and cancer-free lifespan of the bowhead whale. Our work demonstrates the value of studying long-lived organisms in identifying novel longevity mechanisms and their potential for translation to humans.

/pdf/dna-repair-and-anti-cancer-mechanisms-in-the-longest-living-3j0sy39u.pdf

Zhengdong D. Zhang

Papers

Study on the mechanism of NOx reduction by NH3-SCR over Mn and M(M=V,Ti) co-doped CoCr2O4 catalyst

Rare coding variants as risk modifiers of the 22q11.2 deletion implicate postnatal cortical development in syndromic schizophrenia

Protocol for gene annotation, prediction, and validation of genomic gene expansion

Frailty Resilience Score: A Novel Measure of Frailty Resilience Associated with Protection from Frailty and Survival.

DNA repair and anti-cancer mechanisms in the longest-living mammal: the bowhead whale