New Binding Mechanisms Drove The Emerging Pathology Of Zika Virus

Dr. Meghan May gives an overview presentation of the Zika virus epidemic in the Americas, genetic diversity of emergent lineages of the Zika virus, cell binding and Zika’s emergent pathology, and future directions for research and clinical treatment of the Zika virus.https://dune.une.edu/biomed_facpres/1004/thumbnail.jp

A Comprehensive Systems Biology Approach to Studying Zika Virus

Zika virus (ZIKV) is responsible for an ongoing and intensifying epidemic in the Western Hemisphere. We examined the complete predicted proteomes, glycomes, and selectomes of 33 ZIKV strains representing temporally diverse members of the African lineage, the Asian lineage, and the current outbreak in the Americas. Derivation of the complete selectome is an 'omics' approach to identify distinct evolutionary pressures acting on different features of an organism. Employment of the M8 model did not show evidence of global diversifying selection acting on the ZIKV polyprotein; however, a mixed effect model of evolution showed strong evidence (P<0.05) for episodic diversifying selection acting on specific sites. Single nucleotide polymorphisms (SNPs) were predictably frequent across strains relative to the derived consensus sequence. None of the 9 published detection procedures utilize targets that share 100% identity across the 33 strains examined, indicating that ZIKV escape from molecular detection is predictable. The predicted O-linked glycome showed marked diversity across strains; however, the N-linked glycome was highly stable. All Asian and American strains examined were predicted to include glycosylation of E protein ASN154, a modification proposed to mediate neurotropism, whereas the modification was not predicted for African strains. SNP diversity, episodic diversifying selection, and differential glycosylation, particularly of ASN154, may have major biological implications for ZIKV disease. Taken together, the systems biology perspective of ZIKV indicates: a.) The recently emergent Asian/American N-glycotype is mediating the new and emerging neuropathogenic potential of ZIKV; and b.) further divergence at specific sites is predictable as endemnicity is established in the Americas

Characterization of Pontibacter altruii, sp. nov., isolated from a human blood culture

The genus Pontibacter is a recent addition to the family Cytophagaceae, phylum Bacteroidetes. Previous reports of its cultivation and molecular detection are from a variety of environmental sources, including marine and desert habitats. We report the first description of a Pontibacter sp., which was initially identified as Elizabethkingia meningoseptica, isolated from a human clinical specimen. On the basis of 16S rRNA gene sequence, unique mass spectral profile and phenotypic characterization, this isolate represents a novel species within the genus Pontibacter that has been named Pontibacter altruii, sp. nov., strain Grand Forks

Induction of β-Lactamase Activity and Decreased β-Lactam Susceptibility by CO2 in Clinical Bacterial Isolates

Antimicrobial susceptibility testing of clinical isolates is a crucial step toward appropriate treatment of infectious diseases. The clinical isolate Francisella philomiragia 14IUHPL001, recently isolated from a 63-year-old woman with atypical pneumonia, featured decreased susceptibility to β-lactam antibiotics when cultivated in 5% CO2. Quantitative β-lactamase assays demonstrated a significant (P < 0.0001) increase in enzymatic activity between bacteria cultivated in 5% CO2 over those incubated in ambient air. The presence of β-lactamase genes blaTEM and blaSHV was detected in the clinical isolate F. philomiragia 14IUHPL001 by PCR, and the genes were positively identified by nucleotide sequencing. Expression of blaTEM and blaSHV was detected by reverse transcription-PCR during growth at 5% CO2 but not during growth in ambient air. A statistically significant alkaline shift was observed following cultivation of F. philomiragia 14IUHPL001 in both ambient air and 5% CO2, allowing desegregation of the previously reported effects of acidic pH from the currently reported effect of 5% CO2 on blaTEM and blaSHV β-lactamases. To ensure that the observed phenomenon was not unique to F. philomiragia, we evaluated a clinical isolate of blaTEM-carrying Haemophilus influenzae and found parallel induction of blaTEM gene expression and β-lactamase activity at 5% CO2 relative to ambient air. IMPORTANCE β-Lactamase induction and concurrent β-lactam resistance in respiratory tract pathogens as a consequence of growth in a physiologically relevant level of CO2 are of clinical significance, particularly given the ubiquity of TEM and SHV β-lactamase genes in diverse bacterial pathogens. This is the first report of β-lactamase induction by 5% CO2

Retrospective survey for sialidase activity in Mycoplasma pneumoniae isolates from cases of community-acquired pneumonia

<p>Abstract</p> <p>Background</p> <p>Sialidase is a well-known virulence factor of other respiratory pathogens, but was only recently documented to occur in some species of <it>Mycoplasma</it>. The sialidase activity expressed can vary quantitatively among strains within a species of mycoplasma, from undetectable to amounts that correlate positively with strain virulence. Very few isolates of <it>Mycoplasma pneumoniae </it>had ever been examined for sialidase activity, so it was unknown whether sialidase may contribute to diseases involving this species.</p> <p>Findings</p> <p>No sialidase activity was detected by spectrofluorometric assay of 15 laboratory strains and 91 clinical isolates of <it>M. pneumoniae </it>banked over many years from patients having radiologically-confirmed, uncomplicated community-acquired pneumonia.</p> <p>Conclusions</p> <p>The annotated genome of strain M129 (GenBank <ext-link ext-link-id="NC_000912" ext-link-type="gen">NC_000912</ext-link>, <ext-link ext-link-id="ATCC29342" ext-link-type="gen">ATCC 29342</ext-link>), also isolated from a patient with pneumonia, accurately represents the absence of sialidase genes from strains of <it>M. pneumoniae </it>typically associated with uncomplicated community-acquired pneumonia. A possible involvement of sialidase in neurologic or other extra-respiratory manifestations of <it>M. pneumoniae </it>mycoplasmosis remains to be investigated.</p

A Novel Mechanism for Zika Virus Host-Cell Binding

Zika virus (ZIKV) recently emerged in the Western Hemisphere with previously unrecognized or unreported clinical presentations. Here, we identify two putative binding mechanisms of ancestral and emergent ZIKV strains featuring the envelope (E) protein residue asparagine 154 (ASN154) and viral phosphatidylserine (PS). Synthetic peptides representing the region containing ASN154 from strains PRVABC59 (Puerto Rico 2015) and MR_766 (Uganda 1947) were exposed to neuronal cells and fibroblasts to model ZIKV E protein/cell interactions and bound MDCK or Vero cells and primary neurons significantly. Peptides significantly inhibited Vero cell infectivity by ZIKV strains MR_766 and PRVABC59, indicating that this region represents a putative binding mechanism of ancestral African ZIKV strains and emergent Western Hemisphere strains. Pretreatment of ZIKV strains MR_766 and PRVABC59 with the PS-binding protein annexin V significantly inhibited replication of PRVABC59 but not MR_766, suggesting that Western hemisphere strains may additionally be capable of utilizing PS-mediated entry to infect host cells. These data indicate that the region surrounding E protein ASN154 is capable of binding fibroblasts and primary neuronal cells and that PS-mediated entry may be a secondary mechanism for infectivity utilized by Western Hemisphere strains

Francisella tularensis in the United States

Subpopulations A.I and A.II. of Francisella tularensis subsp. tularensis are associated with unique biotic and abiotic factors that maintain disease foci

The Grizzly, September 30, 1996

Helen Zia Speaks on Views of an Asian American Feminist • New Committee Formed to Reduce Vandalism • The 1996-1997 Freshman Class Officers • Graduate School Presentation to be Held Next Wednesday • Gilicinski addresses The Color of Atoms • Research Funding and Presentations • Opinions: My Kingdom for a Phone; War Cries Have Begun; Mourning Tupac Shakur; It\u27s Not Your Fault; Are There Elections This Year?; The Ruby is Not Dead • The S.U.N. is Rising • Family Day • Test Your Strength • Let\u27s Vacate and do Service! • Conserve, Conserve, Conserve! Using Your Energy to Save Energy • Powerful Voir Dire Presents Thought-Provoking Look at Society • Women\u27s Soccer Has Rough Week • Bears Win Fourth in a Row • Volleyball Finds Winning Ways • Men\u27s Soccer Falls to 3-6 • Field Hockey Nets First Winhttps://digitalcommons.ursinus.edu/grizzlynews/1386/thumbnail.jp

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019