Molecular Determinants Responsible for the Subcellular Localization of HSV-1 UL4 Protein

The function of the herpes simplex virus type 1 （HSV-1） UL4 protein is still elusive. Our objective is to investigate the subcellular transport mechanism of the UL4 protein. In this study, fluorescence microscopy was employed to investigate the subcellular localization of UL4 and characterize the transport mechanism in living cells. By constructing a series of deletion mutants fused with enhanced yellow fluorescent protein （EYFP）, the nuclear export signals （NES） of UL4 were for the first time mapped to amino acid residues 178 to 186. In addition, the N-terminal 19 amino acids are identified to be required for the granule-like cytoplasmic pattem of UL4. Furthermore, the UL4 protein was demonstrated to be exported to the cytoplasm through the NES in a chromosomal region maintenance 1 （CRM1）-dependent manner involving RanGTP hydrolysis

Potential effects of CRM1 inhibition in mantle cell lymphoma

Mantle cell lymphoma （MCL） is an aggressive histotype of B-cell non-Hodgkin lymphoma. The disease has no known cure, which prompts the urgent need for novel therapeutic agents. Chromosomal region maintenance 1 （CRM1） may play a role in human neoplasia and serve as a novel target of cancer treatment. This study summarizes MCL pathogenesis and determines the involvement of CRM1 in the regulation of several vital signaling pathways contributing to MCL pathogenesis, including the pathways of cell cycle progression, DNA damage response, phosphoinositide kinase-3, nuclear factor-kB activation, and chromosomal stability. A preclinical study is also presented to compare the CRNI1 status in MCL cell lines and primary MCL cells with normal B cells, as well as the therapeutic efficiency of CRM1 inhibition in MCL in vitro and in vivo, which make these agents potential targets of novel MCL treatments.

Synteny search identifies carnivore Y chromosome for evolution of male specific genes

The explosive accumulation of mammalian genomes has provided a valuable resource to characterize the evo­lution of the Y chromosome.Unexpectedly,the Y-chromosome sequence has been characterized in only a small handful of species,with the majority being model organisms.Thus,identification of Y-linked scaffolds from un­ordered genome sequences is becoming more important.Here,we used a syntenic-based approach to generate the scaffolds of the male-specific region of the Y chromosome(MSY)from the genome sequence of 6 male car­nivore species.Our results identified 14,15,9,28,14 and 11 Y-linked scaffolds in polar bears,pacific walruses,red pandas,cheetahs,ferrets and tigers,covering 1.55 Mbp,2.62 Mbp,964 Kb,1.75 Mb,2.17 Mbp and 1.84 Mb MSY,respectively.All the candidate Y-linked scaffolds in 3 selected species(red pandas,polar bears and ti­gers)were successfully verified using polymerase chain reaction.We re-annotated 8 carnivore MSYs including these 6 Y-linked scaffolds and domestic dog and cat MSY;a total of 11 orthologous genes conserved in at least 7 of the 8 carnivores were identified.These 11 Y-linked genes have significantly higher evolutionary rates com­pared with their X-linked counterparts,indicating less purifying selection for MSY genes.Taken together,our study shows that the approach of synteny search is a reliable and easily affordable strategy to identify Y-linked scaffolds from unordered carnivore genomes and provides a preliminary evolutionary study for carnivore MSY genes.