Genetic dissection of ten photosynthesis-related traits based on InDel- and SNP-GWAS in soybean.

KEY MESSAGE: A total of 416 InDels and 112 SNPs were significantly associated with soybean photosynthesis-related traits. GmIWS1 and GmCDC48 might be related to chlorophyll fluorescence and gas-exchange parameters, respectively. Photosynthesis is one of the main factors determining crop yield. A better understanding of the genetic architecture for photosynthesis is of great significance for soybean yield improvement. Our previous studies identified 5,410,112 single nucleotide polymorphisms (SNPs) from the resequencing data of 219 natural soybean accessions. Here, we identified 634,106 insertions and deletions (InDels) from these 219 accessions and used these InDel variations to perform principal component and linkage disequilibrium analysis of this population. The genome-wide association study (GWAS) were conducted on six chlorophyll fluorescence parameters (chlorophyll content, light energy absorbed per reaction center, quantum yield for electron transport, probability that a trapped exciton moves an electron into the electron transport chain beyond primary quinone acceptor, maximum quantum yield of photosystem II primary photochemistry in the dark-adapted state, performance index on absorption basis) and four gas-exchange parameters (intercellular carbon dioxide concentration, stomatal conductance, net photosynthesis rate, transpiration rate) and revealed 416 significant InDels and 112 significant SNPs. Based on GWAS results, GmIWS1 (encoding a transcription elongation factor) and GmCDC48 (encoding a cell division cycle protein) with the highest expression in the mapping region were determined as the candidate genes responsible for chlorophyll fluorescence and gas-exchange parameters, respectively. Further identification of favorable haplotypes with higher photosynthesis, seed weight and seed yield were carried out for GmIWS1 and GmCDC48. Overall, this study revealed the natural variations and candidate genes underlying the photosynthesis-related traits based on abundant phenotypic and genetic data, providing valuable insights into the genetic mechanisms controlling photosynthesis and yield in soybean.

Modulation of cellular machineries by Zika virus-encoded proteins.

The strain of Zika virus (ZIKV) that circulated during the 2015 epidemic in Brazil has been associated with more than 2000 cases of microcephaly from September 2015 through November 2016. The viral genome determines the biology and pathogenesis of a virus and the virus employs its own gene products to evade host immune surveillance, manipulate cellular machineries, and establish efficient replication. Therefore, understanding the functions of virus-encoded protein not only aids the knowledge of ZIKV biology but also guides the development of anti-ZIKV drugs. In this review, we focus on 10 proteins encoded by ZIKV and summarize their functions in ZIKV replication and pathogenesis according to studies published in the past 6 years.

The Diversity Distribution and Climatic Niche of Samara Species in China.

Studying the distribution of samara species is of ecological and economic significance. This information helps us with understanding species dispersal mechanisms, evaluating the risk of invasive species, and the management of ecological forests. However, limited research has explored, on a large scale, the geographic distribution of samara species and their influential abiotic factors. Here, we use the distribution data of 835 vascular samara species and growth form data to explore their geographic patterns in China and the environmental determinants. We divided China into 984 grid cells and examined the relationship between the proportion of samara species and climate variables using both ordinary and spatial linear regressions for each grid cell. Total samara species richness is higher in southern China in low altitude regions and the proportion of woody samara species is significantly higher than that of herbaceous samara species. The proportion of woody samara species is higher in the northeast regions where precipitation is sufficient, winters are dry and mild, and temperature seasonality and land surface relief degree values are high. Annual precipitation and temperature seasonality are the most important climatic drivers for the distribution of woody samara species. In contrast, herbaceous samara species prefer to distribute to the areas where climate is warm and dry but have higher temperature seasonality. Temperature related variables (mean annual temperature, mean diurnal range, and temperature seasonality) are the most important drivers for the distribution of herbaceous samara species. Samara species can better adapt to climatic regions with large temperature fluctuations and dry winters. The present distribution patterns of samara species are formed by the combined adaptation of fruit traits and growth form to climate. This work contributes to predictions of the global distribution of samara species under future climate change scenarios and conservation and management for the samara species.

Protocol for in utero injection to investigate Zika virus-related fetal microcephaly in mice.

Zika virus (ZIKV) is linked to congenital defects including microcephaly. An infection model that can recapitulate most microcephaly-related phenotypes is crucial for understanding ZIKV pathogenesis. Here, we present a protocol to generate ZIKV from an infectious clone through a reverse genetic system and subsequently perform embryonic brain infection with the rescued ZIKV in pregnant mice. We optimized several aspects of the procedures including virus rescue and in utero injection. This protocol facilitates reproducible investigation of virus-induced cortical development defects. For complete details on the use and execution of this protocol, please refer to Zeng et al. (2020).

Microglia and its Genetics in Alzheimer's Disease.

Alzheimer's Disease (AD) is the most prevalent form of dementia across the world. While its discovery and pathological manifestations are centered on protein aggregations of amyloid- beta (Aß) and hyperphosphorylated tau protein, neuroinflammation has emerged in the last decade as a main component of the disease in terms of both pathogenesis and progression. As the main innate immune cell type in the central nervous system (CNS), microglia play a very important role in regulating neuroinflammation, which occurs commonly in neurodegenerative conditions, including AD. Under inflammatory response, microglia undergo morphological changes and status transition from homeostatic to activated forms. Different microglia subtypes displaying distinct genetic profiles have been identified in AD, and these signatures often link to AD risk genes identified from the genome-wide association studies (GWAS), such as APOE and TREM2. Furthermore, many AD risk genes are highly enriched in microglia and specifically influence the functions of microglia in pathogenesis, e.g. releasing inflammatory cytokines and clearing Aß. Therefore, building up a landscape of these risk genes in microglia, based on current preclinical studies and in the context of their pathogenic or protective effects, would largely help us to understand the complex etiology of AD and provide new insight into the unmet need for effective treatment.

Functional Mapping of AGO-Associated Zika Virus-Derived Small Interfering RNAs in Neural Stem Cells.

Viral interfering RNA (viRNA) has been identified from several viral genomes via directly deep RNA sequencing of the virus-infected cells, including zika virus (ZIKV). Once produced by endoribonuclease Dicer, viRNAs are loaded onto the Argonaute (AGO) family proteins of the RNA-induced silencing complexes (RISCs) to pair with their RNA targets and initiate the cleavage of target genes. However, the identities of functional ZIKV viRNAs and their viral RNA targets remain largely unknown. Our recent study has shown that ZIKV capsid protein interacted with Dicer and antagonized its endoribonuclease activity, which requires its histidine residue at the 41st amino acid. Accordingly, the engineered ZIKV-H41R loss-of-function (LOF) mutant virus no longer suppresses Dicer enzymatic activity nor inhibits miRNA biogenesis in NSCs. By combining AGO-associated RNA sequencing, deep sequencing analysis in ZIKV-infected human neural stem cells (NSCs), and miRanda target scanning, we defined 29 ZIKV derived viRNA profiles in NSCs, and established a complex interaction network between the viRNAs and their viral targets. More importantly, we found that viRNA production from the ZIKV mRNA is dependent on Dicer function and is a limiting factor for ZIKV virulence in NSCs. As a result, much higher levels of viRNAs generated from the ZIKV-H41R virus-infected NSCs. Therefore, our mapping of viRNAs to their RNA targets paves a way to further investigate how viRNAs play the role in anti-viral mechanisms, and perhaps other unknown biological functions.

The Zika Virus Capsid Disrupts Corticogenesis by Suppressing Dicer Activity and miRNA Biogenesis.

Zika virus (ZIKV) causes microcephaly and disrupts neurogenesis. Dicer-mediated miRNA biogenesis is required for embryonic brain development and has been suggested to be disrupted upon ZIKV infection. Here we mapped the ZIKV-host interactome in neural stem cells (NSCs) and found that Dicer is specifically targeted by the capsid from ZIKV, but not other flaviviruses, to facilitate ZIKV infection. We identified a capsid mutant (H41R) that loses this interaction and does not suppress Dicer activity. Consistently, ZIKV-H41R is less virulent and does not inhibit neurogenesis in vitro or corticogenesis in utero. Epidemic ZIKV strains contain capsid mutations that increase Dicer binding affinity and enhance pathogenicity. ZIKV-infected NSCs show global dampening of miRNA production, including key miRNAs linked to neurogenesis, which is not observed after ZIKV-H41R infection. Together these findings show that capsid-dependent suppression of Dicer is a major determinant of ZIKV immune evasion and pathogenesis and may underlie ZIKV-related microcephaly.

Molecular phylogeny of Hiptage (Malpighiaceae) reveals a new species from Southwest China.

Hiptage is an Asia-endemic genus of Malpighiaceae currently placed in the tetrapteroid clade, representing one of the seven inter-continent dispersions from New to Old World. A molecular phylogeny based on sequences of the internal transcribed spacer (ITS) region was recovered for the first time for the genus. Our results showed that the most recent common ancestor of Hiptage probably originated in the South Indo-China Peninsula and diversified in this region. Based on phylogenetic evidence and relevant morphological traits, we propose a new species; Hiptage incurvatum is characterised by mericarps with arcuate anterior lateral wings, two large glands on the dorsal sepals, and small glands on the remaining sepals. The new species is from Mt. Cangshan, Dali City (25°35'N, 100°02'E) in North Yunnan, Southwest China and is notable for its occurrence at high altitude, 1400 m (the highest distribution currently known for the genus). The implications of this unusual species for the dispersal and evolution of the genus are discussed.

Recent Advances in Animal Models of Zika Virus Infection.

An infection by Zika virus (ZIKV), a mosquito-borne flavivirus, broke out in South American regions in 2015, and recently showed a tendency of spreading to North America and even worldwide. ZIKV was first detected in 1947 and only 14 human infection cases were reported until 2007. This virus was previously observed to cause only mild flu-like symptoms. However, recent ZIKV infections might be responsible for the increasing cases of neurological disorders such as Guillain-Barré syndrome and congenital defects, including newborn microcephaly. Therefore, researchers have established several animal models to study ZIKV transmission and pathogenesis, and test therapeutic candidates. This review mainly summarizes the reported animal models of ZIKV infection, including mice and non-human primates.

Novel Role of vBcl2 in the Virion Assembly of Kaposi's Sarcoma-Associated Herpesvirus.

The viral Bcl-2 homolog (vBcl2) of Kaposi's sarcoma-associated herpesvirus (KSHV) displays efficient antiapoptotic and antiautophagic activity through its central BH3 domain, which functions to prolong the life span of virus-infected cells and ultimately enhances virus replication and latency. Independent of its antiapoptotic and antiautophagic activity, vBcl2 also plays an essential role in KSHV lytic replication through its amino-terminal amino acids (aa) 11 to 20. Here, we report a novel molecular mechanism of vBcl2-mediated regulation of KSHV lytic replication. vBcl2 specifically bound the tegument protein open reading frame 55 (ORF55) through its amino-terminal aa 11 to 20, allowing their association with virions. Consequently, the vBcl2 peptide derived from vBcl2 aa 11 to 20 effectively disrupted the interaction between vBcl2 and ORF55, inhibiting the incorporation of the ORF55 tegument protein into virions. This study provides new insight into vBcl2's function in KSHV virion assembly that is separable from its inhibitory role in host apoptosis and autophagy.IMPORTANCE KSHV, an important human pathogen accounting for a large percentage of virally caused cancers worldwide, has evolved a variety of stratagems for evading host immune responses to establish lifelong persistent infection. Upon viral infection, infected cells can go through programmed cell death, including apoptosis and autophagy, which plays an effective role in antiviral responses. To counter the host response, KSHV vBcl2 efficiently blocks apoptosis and autophagy to persist for the life span of virus-infected cells. Besides its anti-programmed-cell-death activity, vBcl2 also interacts with the ORF55 tegument protein for virion assembly in infected cells. Interestingly, the vBcl2 peptide disrupts the vBcl2-ORF55 interaction and effectively inhibits KSHV virion assembly. This study indicates that KSHV vBcl2 harbors at least three genetically separable functions to modulate both host cell death signaling and virion production and that the vBcl2 peptide can be developed as an anti-KSHV therapeutic application.

Enantioselective Michael Addition of Photogenerated o-Quinodimethanes to Enones Catalyzed by Chiral Amino Acid Esters.

The first example of a photoexcitated amine-catalyzed process for asymmetric Michael addition of o-quinodimethanes to enones is described. In the presence of simple chiral amino acid esters, a variety of Michael adducts were generally obtained in good yields and excellent stereoselectivities. This strategy can be successfully applied to 3-substituted-2-cyclohexenones and provides an asymmetric access to all-carbon quaternary centers. Furthermore, the high stereocontrol was explained by means of density-functional theory (DFT) calculations.

Brønsted acid cocatalysis in photocatalytic intramolecular coupling of tertiary amines: efficient synthesis of 2-arylindols.

We report herein a highly efficient intramolecular coupling reaction of tertiary amines and ketones (α,ß-unsaturated ketones) by using a Brønsted acid as a cocatalyst, affording 2-arylindols in good to excellent yields (up to 92%) under visible light irradiation at room temperature.