Comparative transcriptomics and proteomics analysis of citrus fruit, to improve understanding of the effect of low temperature on maintaining fruit quality during lengthy post-harvest storage

Fruit quality is a very complex trait that is affected by both genetic and non-genetic factors. Generally, low temperature (LT) is used to delay fruit senescence and maintain fruit quality during post-harvest storage but the molecular mechanisms involved are poorly understood. Hirado Buntan Pummelo (HBP; Citrus grandis × C. paradis) fruit were chosen to explore the mechanisms that maintain citrus fruit quality during lengthy LT storage using transcriptome and proteome studies based on digital gene expression (DGE) profiling and two-dimensional gel electrophoresis (2-DE), respectively. Results showed that LT up-regulated stress-responsive genes, arrested signal transduction, and inhibited primary metabolism, secondary metabolism and the transportation of metabolites. Calcineurin B-like protein (CBL)–CBL-interacting protein kinase complexes might be involved in the signal transduction of LT stress, and fruit quality is likely to be regulated by sugar-mediated auxin and abscisic acid (ABA) signalling. Furthermore, ABA was specific to the regulation of citrus fruit senescence and was not involved in the LT stress response. In addition, the accumulation of limonin, nomilin, methanol, and aldehyde, together with the up-regulated heat shock proteins, COR15, and cold response-related genes, provided a comprehensive proteomics and transcriptomics view on the coordination of fruit LT stress responses

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

DECIPHERING THE HOST-PATHOGEN INTERACTIONS DURING ENTEROVIRUS-A71 INFECTION IN MOTOR NEURON CELLS: ROLE OF PERIPHERIN AND ITS INTERACTING PARTNERS

Ph.DDOCTOR OF PHILOSOPHY (SOM

Recent progress and challenges in drug development to fight Hand, Foot and Mouth Disease

Expert Opinion on Drug Discovery153359-37

Enterovirus-A71 exploits peripherin and Rac1 to invade the central nervous system

10.15252/embr.202051777EMBO REPORTS22

Enterovirus‐A71 exploits peripherin and Rac1 to invade the central nervous system

Enterovirus‐A71 (EV‐A71) has been associated with severe neurological forms of hand, foot, and mouth disease (HFMD). EV‐A71 infects motor neurons at neuromuscular junctions (NMJs) to invade the central nervous system (CNS). Here, we investigate the role of peripherin (PRPH) during EV‐A71 infection, a type III intermediate neurofilament involved in neurodegenerative conditions. In mice infected with EV‐A71, PRPH co‐localizes with viral particles in the muscles at NMJs and in the spinal cord. In motor neuron‐like and neuroblastoma cell lines, surface‐expressed PRPH facilitates viral entry, while intracellular PRPH influences viral genome replication through interactions with structural and non‐structural viral components. Importantly, PRPH does not play a role during infection with coxsackievirus A16, another causative agent of HFMD rarely associated with neurological complications, suggesting that EV‐A71 ability to exploit PRPH represents a unique attribute for successful CNS invasion. Finally, we show that EV‐A71 also exploits some of the many PRPH‐interacting partners. Of these, small GTP‐binding protein Rac1 represents a potential druggable host target to limit neuroinvasion of EV‐A71

A Single Amino Acid Substitution in Structural Protein VP2 Abrogates the Neurotropism of Enterovirus A-71 in Mice

10.3389/fmicb.2022.821976FRONTIERS IN MICROBIOLOGY1

Dissemination of Pseudomonas aeruginosa blaNDM-1-positive ST308 clone in Singapore

Pseudomonas aeruginosa ST308 clone has been reported to carry carbapenemase genes such as blaIMP and blaVIM but has been rarely associated with blaNDM-1. A total of 199 P. aeruginosa ST308 clinical and environmental isolates obtained between April 2019 and November 2020 from a tertiary-care hospital in Singapore were characterized using whole-genome sequencing. In addition, 71 blaNDM-1-positive ST308 whole-genome sequences from two other local tertiary-care hospitals in Singapore and 83 global blaNDM-1-negative ST308 whole-genome sequences in public databases were included to assess phylogenetic relationships and perform genome analyses. Phylogenetic analysis and divergent time estimation revealed that blaNDM-1-positive P. aeruginosa ST308 was introduced into Singapore in 2005 (95 % highest posterior density: 2001 to 2008). Core genome, resistome, and analyses of all local blaNDM-1-positive ST308 isolates showed chromosomal integration of multiple antibiotic resistance genes (ARGs) [aac(3)-Id, aac(6')-Il, aadA6, aadA11, dfrB5, msr(E), floR, sul2, and qnrVC1], which was absent in global blaNDM-1-negative ST308 sequences. Most ARGs and virulence genes were conserved across isolates originating from the three different local hospitals. Close genetic relatedness of the blaNDM-1-positive ST308 clinical and environmental isolates suggests cocirculation between the hospital environment and human hosts with the hospital environment as a potential reservoir. Core genome single nucleotide polymorphism analyses revealed possible clonal transmission of blaNDM-1-positive ST308 isolates between the three hospitals over 7 years. Bloodstream isolates accounted for six of 95 (6.3%) clinical isolates. This study reports the introduction of a pathogenic blaNDM-1-positive P. aeruginosa ST308 more than a decade ago in Singapore and warrants surveillance for wider dissemination.National Medical Research Council (NMRC)Published versionThis research is supported by the Singapore Ministry of Health's (MOH) National Medical Research Council (NMRC) under its NMRC Collaborative Grant: Collaborative Solutions Targeting Antimicrobial Resistance Threats in Health Systems (CoSTAR-HS) (NMRC CG21APR2005), NMRC Clinician Scientist Award (MOH-000276), and NMRC Clinician Scientist Individual Research Grant (MOH-CIRG18Nov-0034). Additional support was provided by the German Federal Ministry of Health (BMG) COVID-19 Research and Development Funding to the World Health Organization (WHO; award 70826)

Genetic and epigenetic silencing of SCARA5 may contribute to human hepatocellular carcinoma by activating FAK signaling

The epigenetic silencing of tumor suppressor genes is a crucial event during carcinogenesis and metastasis. Here, in a human genome-wide survey, we identified scavenger receptor class A, member 5 (SCARA5) as a candidate tumor suppressor gene located on chromosome 8p. We found that SCARA5 expression was frequently downregulated as a result of promoter hypermethylation and allelic imbalance and was associated with vascular invasion in human hepatocellular carcinoma (HCC). Furthermore, SCARA5 knockdown via RNAi markedly enhanced HCC cell growth in vitro, colony formation in soft agar, and invasiveness, tumorigenicity, and lung metastasis in vivo. By contrast, SCARA5 overexpression suppressed these malignant behaviors. Interestingly, SCARA5 was found to physically associate with focal adhesion kinase (FAK) and inhibit the tyrosine phosphorylation cascade of the FAK-Src-Cas signaling pathway. Conversely, silencing SCARA5 stimulated the signaling pathway via increased phosphorylation of certain tyrosine residues of FAK, Src, and p130Cas; it was also associated with activation of MMP9, a tumor metastasis–associated enzyme. Taken together, these data suggest that the plasma membrane protein SCARA5 can contribute to HCC tumorigenesis and metastasis via activation of the FAK signaling pathway