Myosin-1C uses a novel phosphoinositide-dependent pathway for nuclear localization

Accurate control of macromolecule transport between nucleus and cytoplasm underlines several essential biological processes, including gene expression. According to the canonical model, nuclear import of soluble proteins is based on nuclear localization signals and transport factors. We challenge this view by showing that nuclear localization of the actin-dependent motor protein Myosin-1C (Myo1C) resembles the diffusion–retention mechanism utilized by inner nuclear membrane proteins. We show that Myo1C constantly shuttles in and out of the nucleus and that its nuclear localization does not require soluble factors, but is dependent on phosphoinositide binding. Nuclear import of Myo1C is preceded by its interaction with the endoplasmic reticulum, and phosphoinositide binding is specifically required for nuclear import, but not nuclear retention, of Myo1C. Our results therefore demonstrate, for the first time, that membrane association and binding to nuclear partners is sufficient to drive nuclear localization of also soluble proteins, opening new perspectives to evolution of cellular protein sorting mechanisms.Peer reviewe

A seismological phenomenon preceding the 2017 Ms7.0 Jiuzhaigou earthquake

On 8 August 2017, a Ms7.0 earthquake occurred in Jiuzhaigou in the Sichuan Province of China. In this study, we obtained the vertical continuous data recorded at 12 nearby broadband seismometers from April to December 2017, in order to characterize the temporal and spatial variations in the vertical ground motion prior to the onset of the earthquake. Using the self-mutual information method, we determined that from July to August 2017, the self-mutual information value of the vertical ground motion increased at several stations. The spatiotemporal evolution also shows that the region of highest value migrates from south to north toward the earthquake epicenter. Among them, the change of SPA (the station closest to the epicenter) is the most prominent. We believe that this phenomenon is related to the formation of the Jiuzhaigou earthquake. Our work, in combination with other published works, indicates that the Jiuzhaigou earthquake was caused by the continued eastward movement and obstruction of the Qinghai Tibet Plateau by the Sichuan Basin, and the movement of Longmenshan fault is also one of the causes of the earthquake

Antiviral biflavonoids from Radix Wikstroemiae (Liaogewanggen)

<p>Abstract</p> <p>Background</p> <p><it>Radix Wikstroemiae </it>is a common Chinese herbal medicine. The ethyl acetate fraction of the ethanolic extract of <it>W. indica </it>possesses potent <it>in vitro </it>antiviral activity against respiratory syncytial virus (RSV). This study aims to identify the antiviral components of the active fraction.</p> <p>Methods</p> <p>The active fraction of the <it>Radix Wikstroemiae </it>extract was isolated with chromatographic methods such as silica gel, Sephadex LH-20 and semi-preparative high performance liquid chromatography (HPLC) columns. The structures of the isolated compounds were determined based on spectroscopic analyses. The <it>in vitro </it>antiviral activity of the compounds against RSV was tested with the cytopathic effect (CPE) reduction assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method.</p> <p>Results</p> <p>Four biflavonoids, namely neochamaejasmin B, genkwanol B, genkwanol C and stelleranol, were isolated and characterized. Genkwanol B, genkwanol C and stelleranol, which are stereo isomers of spirobiflavonoids, showed potent anti-RSV activity whereas neochamaejasmin B did not.</p> <p>Conclusion</p> <p>Neochamaejasmin B, genkwanol B, genkwanol C and stelleranol were isolated from <it>Radix Wikstroemiae </it>and the complete absolute configurations of five chiral carbons in stelleranol were substantiated for the first time. Furthermore, the anti-RSV activity of genkwanol B, genkwanol C and stelleranol was reported for the first time.</p

A seismological phenomenon preceding the 2017 Ms7.0 Jiuzhaigou earthquake

On 8 August 2017, a Ms7.0 earthquake occurred in Jiuzhaigou in the Sichuan Province of China. In this study, we obtained the vertical continuous data recorded at 12 nearby broadband seismometers from April to December 2017, in order to characterize the temporal and spatial variations in the vertical ground motion prior to the onset of the earthquake. Using the self-mutual information method, we determined that from July to August 2017, the self-mutual information value of the vertical ground motion increased at several stations. The spatiotemporal evolution also shows that the region of highest value migrates from south to north toward the earthquake epicenter. Among them, the change of SPA (the station closest to the epicenter) is the most prominent. We believe that this phenomenon is related to the formation of the Jiuzhaigou earthquake. Our work, in combination with other published works, indicates that the Jiuzhaigou earthquake was caused by the continued eastward movement and obstruction of the Qinghai Tibet Plateau by the Sichuan Basin, and the movement of Longmenshan fault is also one of the causes of the earthquake

Internalin profiling and multilocus sequence typing suggest four Listeria innocua subgroups with different evolutionary distances from Listeria monocytogenes

<p>Abstract</p> <p>Background</p> <p>Ecological, biochemical and genetic resemblance as well as clear differences of virulence between <it>L. monocytogenes </it>and <it>L. innocua </it>make this bacterial clade attractive as a model to examine evolution of pathogenicity. This study was attempted to examine the population structure of <it>L. innocua </it>and the microevolution in the <it>L. innocua</it>-<it>L. monocytogenes </it>clade via profiling of 37 internalin genes and multilocus sequence typing based on the sequences of 9 unlinked genes <it>gyrB</it>, <it>sigB</it>, <it>dapE</it>, <it>hisJ</it>, <it>ribC</it>, <it>purM</it>, <it>gap</it>, <it>tuf </it>and <it>betL</it>.</p> <p>Results</p> <p><it>L. innocua </it>was genetically monophyletic compared to <it>L. monocytogenes</it>, and comprised four subgroups. Subgroups A and B correlated with internalin types 1 and 3 (except the strain 0063 belonging to subgroup C) and internalin types 2 and 4 respectively. The majority of <it>L. innocua </it>strains belonged to these two subgroups. Subgroup A harbored a whole set of <it>L. monocytogenes</it>-<it>L. innocua </it>common and <it>L. innocua</it>-specific internalin genes, and displayed higher recombination rates than those of subgroup B, including the relative frequency of occurrence of recombination versus mutation (ρ/θ) and the relative effect of recombination versus point mutation (r/m). Subgroup A also exhibited a significantly smaller exterior/interior branch length ratio than expected under the coalescent model, suggesting a recent expansion of its population size. The phylogram based on the analysis with correction for recombination revealed that the time to the most recent common ancestor (TMRCA) of <it>L. innocua </it>subgroups A and B were similar. Additionally, subgroup D, which correlated with internalin type 5, branched off from the other three subgroups. All <it>L. innocua </it>strains lacked seventeen virulence genes found in <it>L. monocytogenes </it>(except for the subgroup D strain L43 harboring <it>inlJ </it>and two subgroup B strains bearing <it>bsh</it>) and were nonpathogenic to mice.</p> <p>Conclusions</p> <p><it>L. innocua </it>represents a young species descending from <it>L. monocytogenes </it>and comprises four subgroups: two major subgroups A and B, and one atypical subgroup D serving as a link between <it>L. monocytogenes </it>and <it>L. innocua </it>in the evolutionary chain. Although subgroups A and B appeared at approximately the same time, subgroup A seems to have experienced a recent expansion of the population size with higher recombination frequency and effect than those of subgroup B, and might represent the possible evolutionary direction towards adaptation to enviroments. The evolutionary history in the <it>L. monocytogenes</it>-<it>L. innocua </it>clade represents a rare example of evolution towards reduced virulence of pathogens.</p

Antibiotic Resistance in Salmonella Typhimurium Isolates Recovered From the Food Chain Through National Antimicrobial Resistance Monitoring System Between 1996 and 2016

Salmonella is a major foodborne pathogen which causes widespread contamination and infection worldwide. Salmonella Typhimurium is one of the leading serovars responsible for human and animal salmonellosis, globally. The increasing rate of antibiotic resistance in Salmonella Typhimurium poses a significant global concern, and an improved understanding of the distribution of antibiotic resistance patterns in Salmonella Typhimurium is essential for choosing the suitable antibiotic for the treatment of infections. To evaluate the roles of animal and human in antibiotic resistance dissemination, this study aims to categorize 11,447 S. Typhimurium strains obtained across the food-chain, including food animals, retail meats and humans for 21 years in the United States by analyzing minimum inhibitory concentrations (MICs) values for 27 antibiotics. Random Forest Algorithm and Hierarchical Clustering statistics were used to group the strains according to their minimum inhibitory concentration values. Classification and Regression Tree analysis was used to identify the best classifier for human- and animal-populations’ isolates. We found the persistent population or multi-drug resistant strains of S. Typhimurium across the four time periods (1996∼2000, 2001∼2005, 2006∼2010, 2011∼2016). Importantly, we also detected that there was more diversity in the MIC patterns among S. Typhimurium strains isolated between 2011 and 2016, which suggests significant emergence of diversified multi-drug resistant strains. The most frequently observed (43%) antibiotic resistance patterns found in S. Typhimurium were tetra-resistant pattern ASSuT (ampicillin, streptomycin, sulfonamides, and tetracycline) and the penta-resistant pattern ACSSuT (ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline). Animals (mainly swine and bovine) are the major source for these two frequently found antibiotic resistance patterns. The occurrence of antibiotic resistant strains from humans and chicken is alarming. Strains were mostly susceptible to fluoroquinolones. Together, this study helped in understanding the expansion of dynamics of antibiotic resistance of S. Typhimurium and recommended fluoroquinolones as a possible treatment options against S. Typhimurium infection

B cells Using Calcium Signaling for Specific and Rapid Detection of Escherichia coli O-157:H-7

A rapid and sensitive detection technology is highly desirable for specific detection of E. coli O-157:H-7, one of the leading bacterial pathogens causing foodborne illness. In this study, we reported the rapid detection of E. coli O-157: H-7 by using calcium signaling of the B cell upon cellular membrane anchors anti-E. coli O-157: H-7 IgM. The binding of E. coli O-157:H-7 to the IgM on B cell surface activates the B cell receptor (BCR)-induced Ca2+ signaling pathway and results in the release of Ca2+ within seconds. The elevated intracellular Ca2+ triggers Fura-2, a fluorescent Ca2+ indicator, for reporting the presence of pathogens. The Fura-2 is transferred to B cells before detection. The study demonstrated that the developed B cell based biosensor was able to specifically detect E. coli O-157:H-7 at the low concentration within 10 min in pure culture samples. Finally, the B cell based biosensor was used for the detection of E. coli O-157:H-7 in ground beef samples. With its short detection time and high sensitivity at the low concentration of the target bacteria, this B cell biosensor shows promise in future application of the high throughput and rapid food detection, biosafety and environmental monitoring

BolA-like protein (IbaG) promotes biofilm formation and pathogenicity of Vibrio parahaemolyticus

Vibrio parahaemolyticus is a gram-negative halophilic bacterium widespread in temperate and tropical coastal waters; it is considered to be the most frequent cause of Vibrio-associated gastroenteritis in many countries. BolA-like proteins, which reportedly affect various growth and metabolic processes including flagellar synthesis in bacteria, are widely conserved from prokaryotes to eukaryotes. However, the effects exerted by BolA-like proteins on V. parahaemolyticus remain unclear, and thus require further investigation. In this study, our purpose was to investigate the role played by BolA-like protein (IbaG) in the pathogenicity of V. parahaemolyticus. We used homologous recombination to obtain the deletion strain ΔibaG and investigated the biological role of BolA family protein IbaG in V. parahaemolyticus. Our results showed that IbaG is a bacterial transcription factor that negatively modulates swimming capacity. Furthermore, overexpressing IbaG enhanced the capabilities of V. parahaemolyticus for swarming and biofilm formation. In addition, inactivation of ibaG in V. parahaemolyticus SH112 impaired its capacity for colonizing the heart, liver, spleen, and kidneys, and reduced visceral tissue damage, thereby leading to diminished virulence, compared with the wild-type strain. Finally, RNA-sequencing revealed 53 upregulated and 71 downregulated genes in the deletion strain ΔibaG. KEGG enrichment analysis showed that the two-component system, quorum sensing, bacterial secretion system, and numerous amino acid metabolism pathways had been altered due to the inactivation of ibaG. The results of this study indicated that IbaG exerts a considerable effect on gene regulation, motility, biofilm formation, and pathogenicity of V. parahaemolyticus. To the best of our knowledge, this is the first systematic study on the role played by IbaG in V. parahaemolyticus infections. Thus, our findings may lead to a better understanding of the metabolic processes involved in bacterial infections and provide a basis for the prevention and control of such infections

Notch2 blockade enhances hematopoietic stem cell mobilization and homing

Despite use of newer approaches, some patients being considered for autologous hematopoietic cell transplantation (HCT) may only mobilize limited numbers of hematopoietic progenitor cells (HPCs) into blood, precluding use of the procedure, or being placed at increased risk of complications due to slow hematopoietic reconstitution. Developing more efficacious HPC mobilization regimens and strategies may enhance the mobilization process and improve patient outcome. Although Notch signaling is not essential for homeostasis of adult hematopoietic stem cells (HSCs), Notch-ligand adhesive interaction maintains HSC quiescence and niche retention. Using Notch receptor blocking antibodies, we report that Notch2 blockade, but not Notch1 blockade, sensitizes hematopoietic stem cells and progenitors (HSPCs) to mobilization stimuli and leads to enhanced egress from marrow to the periphery. Notch2 blockade leads to transient myeloid progenitor expansion without affecting HSC homeostasis and self-renewal. We show that transient Notch2 blockade or Notch2-loss in mice lacking Notch2 receptor lead to decreased CXCR4 expression by HSC but increased cell cycling with CXCR4 transcription being directly regulated by the Notch transcriptional protein RBPJ. In addition, we found that Notch2-blocked or Notch2-deficient marrow HSPCs show an increased homing to the marrow, while mobilized Notch2-blocked, but not Notch2-deficient stem cells and progenitors, displayed a competitive repopulating advantage and enhanced hematopoietic reconstitution. These findings suggest that blocking Notch2 combined with the current clinical regimen may further enhance HPC mobilization and improve engraftment during HCT