Potato virus M (PVM) is a member of the genus Carlavirus of the family Betaflexviridae and causes large economic losses of nightshade crops. Several previous studies have elucidated the population structure, evolutionary timescale and adaptive evolution of PVM. However, the synonymous codon usage pattern of PVM remains unclear. In this study, we performed comprehensive analyses of the codon usage and composition of PVM based on 152 nucleotide sequences of the coat protein (CP) gene and 125 sequences of the cysteine-rich nucleic acid binding protein (NABP) gene. We observed that the PVM CP and NABP coding sequences were GC-and AU-rich, respectively, whereas U- and G-ending codons were preferred in the PVM CP and NABP coding sequences. The lower codon usage of the PVM CP and NABP coding sequences indicated a relatively stable and conserved genomic composition. Natural selection and mutation pressure shaped the codon usage patterns of PVM, with natural selection being the most important factor. The codon adaptation index (CAI) and relative codon deoptimization index (RCDI) analysis revealed that the greatest adaption of PVM was to pepino, followed by tomato and potato. Moreover, similarity Index (SiD) analysis showed that pepino had a greater impact on PVM than tomato and potato. Our study is the first attempt to evaluate the codon usage pattern of the PVM CP and NABP genes to better understand the evolutionary changes of a carlavirus.

Introduction Traumatic brain injury (TBI) is considered as the most robust environmental risk factor for Alzheimer’s disease (AD). Besides direct neuronal injury and neuroinflammation, vascular impairment is also a hallmark event of the pathological cascade after TBI. However, the vascular connection between TBI and subsequent AD pathogenesis remains underexplored. Methods In a closed-head mild TBI (mTBI) model in mice with controlled cortical impact, we examined the time courses of microvascular injury, blood–brain barrier (BBB) dysfunction, gliosis and motor function impairment in wild type C57BL/6 mice. We also evaluated the BBB integrity, amyloid pathology as well as cognitive functions after mTBI in the 5xFAD mouse model of AD. Results mTBI induced microvascular injury with BBB breakdown, pericyte loss, basement membrane alteration and cerebral blood flow reduction in mice, in which BBB breakdown preceded gliosis. More importantly, mTBI accelerated BBB leakage, amyloid pathology and cognitive impairment in the 5xFAD mice. Discussion Our data demonstrated that microvascular injury plays a key role in the pathogenesis of AD after mTBI. Therefore, restoring vascular functions might be beneficial for patients with mTBI, and potentially reduce the risk of developing AD.

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.

: 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 (Aβ) 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 Aβ. 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.

Introduction: Traumatic brain injury (TBI) is considered as the most robust environmental risk factor for Alzheimer's disease (AD). Besides direct neuronal injury and neuroinflammation, vascular impairment is also a hallmark event of the pathological cascade after TBI. However, the vascular connection between TBI and subsequent AD pathogenesis remains underexplored. Methods:We established a closed-head mild TBI (mTBI) model in mice with controlled cortical impact, and examined the time courses of microvascular injury, blood-brain barrier (BBB) dysfunction, gliosis and motor function impairment in wild type C57BL/6 mice. We also determined the brain clearance of βamyloid, as well as amyloid pathology and cognitive functions after mTBI in the 5xFAD mouse model of AD.Results: mTBI induced microvascular injury with BBB breakdown, pericyte loss and cerebral blood flow reduction in mice, which preceded gliosis. mTBI also impaired brain amyloid clearance via the vascular pathways. More importantly, mTBI accelerated amyloid pathology and cognitive impairment in the 5xFAD mice.Discussion: Our data demonstrated that microvascular injury plays a key role in the pathogenesis of AD after mTBI. Therefore, restoring vascular functions might be beneficial for patients with mTBI, and potentially reduce the risk of developing AD. Ethics approval and consent to participateThe animal experiments were approved by the Institutional Animal Care and Use Committee at the University of Southern California per NIH guidelines. BackgroundAlzheimer's disease (AD) is an age-related progressive neurodegenerative condition, manifesting amyloid plaque and neurofibrillary tangle formation, neurovascular and neuroimmune dysfunctions, and cognitive impairment [1,2]. While advanced aging increases the likelihood of AD, genetic inheritance and environmental risk factors also contribute significantly [3]. For example, Traumatic brain injury (TBI) is considered as the most robust environmental risk factor for AD [4]. TBI is a leading cause of death and disability, particularly in young adults, resulting in a great impact on productivity and dependence on health care in later life [5,6]. Both clinical and preclinical studies have demonstrated that TBI triggers multiple neurodegenerative cascades, including axonal and dendritic damage, excitatory toxicity, neuroinflammation and cell death [7,8], as well as cerebrovascular impairment such as edema, circulatory insufficiency, and blood-brain barrier (BBB) breakdown [9,10], exhibiting a high similarity with AD [6,11]. TBI is highly prevalent during military service and contact sports, and doubles the risk of developing AD and dementia [12,13]. More importantly, it also exacerbates certain pathological events that are specific to AD, including the brain's overproduction and accumulation of β-amyloid (Aβ), and neurofibrillary tangles consisting of hyperphosphorylated Tau [14]. Yet the underlying mechanisms remain elusive.Histological and neuroimaging assessments have demonstrated that microvascular injury with...