| 1. |
- Alvarez, Francisco J., et al.
(författare)
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Diverse Nitrogen Sources in Seminal Fluid Act in Synergy To Induce Filamentous Growth of Candida albicans
- 2015
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Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 81:8, s. 2770-2780
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Tidskriftsartikel (refereegranskat)abstract
- The pathogenic fungus Candida albicans is the leading cause of vulvovaginal candidiasis (VVC). VVC represents a major quality- of-life issue for women during their reproductive years, a stage of life where the vaginal epithelium is subject to periodic hormonally induced changes associated with menstruation and concomitant exposure to serum as well as potential intermittent contact with seminal fluid. Seminal fluid potently triggers Candida albicans to switch from yeastlike to filamentous modes of growth, a developmental response tightly linked to virulence. Conversely, vaginal fluid inhibits filamentation. Here, we used artificial formulations of seminal and vaginal fluids that faithfully mimic genuine fluids to assess the contribution of individual components within these fluids to filamentation. The high levels of albumin, amino acids, and N-acetylglucosamine in seminal fluid act synergistically as potent inducers of filamentous growth, even at atmospheric levels of CO2 and reduced temperatures (30 degrees C). Using a simplified in vitro model that mimics the natural introduction of seminal fluid into the vulvovaginal environment, a pulse of artificial seminal fluid (ASF) was found to exert an enduring potential to overcome the inhibitory efficacy of artificial vaginal fluid (AVF) on filamentation. These findings suggest that a transient but substantial change in the nutrient levels within the vulvovaginal environment during unprotected coitus can induce resident C. albicans cells to engage developmental programs associated with virulent growth.
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| 2. |
- Boban, Mirta, et al.
(författare)
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A nuclear ubiquitin-proteasome pathway targets the inner nuclear membrane protein Asi2 for degradation
- 2014
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 127:16, s. 3603-3613
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Tidskriftsartikel (refereegranskat)abstract
- The nuclear envelope consists of inner and outer nuclear membranes. Whereas the outer membrane is an extension of the endoplasmic reticulum, the inner nuclear membrane (INM) represents a unique membranous environment containing specific proteins. The mechanisms of integral INM protein degradation are unknown. Here, we investigated the turnover of Asi2, an integral INM protein in Saccharomyces cerevisiae. We report that Asi2 is degraded by the proteasome independently of the vacuole and that it exhibited a half-life of similar to 45 min. Asi2 exhibits enhanced stability in mutants lacking the E2 ubiquitin conjugating enzymes Ubc6 or Ubc7, or the E3 ubiquitin ligase Doa10. Consistent with these data, Asi2 is post-translationally modified by poly-ubiquitylation in a Ubc7- and Doa10-dependent manner. Importantly Asi2 degradation is significantly reduced in a sts1-2 mutant that fails to accumulate proteasomes in the nucleus, indicating that Asi2 is degraded in the nucleus. Our results reveal a molecular pathway that affects the stability of integral proteins of the inner nuclear membrane and indicate that Asi2 is subject to protein quality control in the nucleus.
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| 3. |
- Boban, Mirta, et al.
(författare)
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Atypical Ubiquitylation in Yeast Targets Lysine-less Asi2 for Proteasomal Degradation
- 2015
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 290:4, s. 2489-2495
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Tidskriftsartikel (refereegranskat)abstract
- Proteins are typically targeted for proteasomal degradation by the attachment of a polyubiquitin chain to epsilon-amino groups of lysine residues. Non-lysine ubiquitylation of proteasomal substrates has been considered an atypical and rare event limited to complex eukaryotes. Here we report that a fully functional lysine-less mutant of an inner nuclear membrane protein in yeast, Asi2, is polyubiquitylated and targeted for proteasomal degradation. Efficient degradation of lysine-free Asi2 requires E3-ligase Doa10 and E2 enzymes Ubc6 and Ubc7, components of the endoplasmic reticulum-associated degradation pathway. Together, our data suggest that non-lysine ubiquitylation may be more prevalent than currently considered.
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| 4. |
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| 5. |
- Chernomoretz, Ariel, et al.
(författare)
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The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium inaugural meeting report
- 2016
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Ingår i: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium is a novel, interdisciplinary initiative comprised of experts across many fields, including genomics, data analysis, engineering, public health, and architecture. The ultimate goal of the MetaSUB Consortium is to improve city utilization and planning through the detection, measurement, and design of metagenomics within urban environments. Although continual measures occur for temperature, air pressure, weather, and human activity, including longitudinal, cross-kingdom ecosystem dynamics can alter and improve the design of cities. The MetaSUB Consortium is aiding these efforts by developing and testing metagenomic methods and standards, including optimized methods for sample collection, DNA/RNA isolation, taxa characterization, and data visualization. The data produced by the consortium can aid city planners, public health officials, and architectural designers. In addition, the study will continue to lead to the discovery of new species, global maps of antimicrobial resistance (AMR) markers, and novel biosynthetic gene clusters (BGCs). Finally, we note that engineered metagenomic ecosystems can help enable more responsive, safer, and quantified cities.
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| 6. |
- Chng, Kern Rei, et al.
(författare)
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Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment
- 2020
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26, s. 941-951
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Tidskriftsartikel (refereegranskat)abstract
- Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections. Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.
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| 7. |
- Danko, David, et al.
(författare)
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A global metagenomic map of urban microbiomes and antimicrobial resistance
- 2021
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 184:13, s. 3376-3393
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Tidskriftsartikel (refereegranskat)abstract
- We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.
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| 8. |
- Darkahi, Bahman, et al.
(författare)
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Effectiveness of antibiotic prophylaxis in cholecystectomy : a prospective population-based study of 1171 cholecystectomies
- 2012
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 47:10, s. 1242-1246
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Tidskriftsartikel (refereegranskat)abstract
- Background.The aim of this study was to assess the benefit from antibiotic prophylaxis (AP) during cholecystectomy in a population-based cohort study.Methods.All cholecystectomies performed in Uppsala County, 2003-2005, were registered prospectively according to a standardized protocol. High-risk procedures (HP) were defined as operations for acute cholecystitis and procedures including exploration of the common bile duct. Infections requiring surgical or percutaneous drainage and non-surgical infections that prolonged hospital stay were defined as major infectious complications (IC).Results. Altogether 1171 patients underwent cholecystectomy. AP was given to 130 of 867 (15%) of the patients undergoing low-risk procedures (LP) and 205 of 304 (67%) of those undergoing H-R P. Major IC were seen in 6 of 205 (3%) of the patients undergoing H-R P with AP and 1 of 99 of the patients undergoing H-R P without AP. No major IC was seen after L-R P. Minor IC were seen after 5 of 205 (2%) HP with AP, 1 of 99 (1%) HP without AP, 0 of 130 (0%) LP with AP, and 2 of 737 (0.3%) LP without AP. In univariate logistic analysis, the overall risk for IC was found to be higher with AP (p < 0.05), but the increase did not remain significant if adjusting for age, gender, ASA class, H-R P/L-R P and surgical approach or limiting the analysis to major IC.Conclusion. There is no benefit from AP in uncomplicated procedures. The effectiveness of antibiotic prophylaxis in complicated cholecystectomy must be evaluated in randomized controlled trials.
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| 9. |
- Davis, Monica M., et al.
(författare)
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Wild-Type Drosophila melanogaster as a Model Host to Analyze Nitrogen Source Dependent Virulence of Candida albicans
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:11, s. e27434-
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Tidskriftsartikel (refereegranskat)abstract
- The fungal pathogen Candida albicans is a common cause of opportunistic infections in humans. We report that wild-type Drosophila melanogaster (OrR) flies are susceptible to virulent C. albicans infections and have established experimental conditions that enable OrR flies to serve as model hosts for studying C. albicans virulence. After injection into the thorax, wild-type C. albicans cells disseminate and invade tissues throughout the fly, leading to lethality. Similar to results obtained monitoring systemic infections in mice, well-characterized cph1Δ efg1Δ and csh3Δ fungal mutants exhibit attenuated virulence in flies. Using the OrR fly host model, we assessed the virulence of C. albicans strains individually lacking functional components of the SPS sensing pathway. In response to extracellular amino acids, the plasma membrane localized SPS-sensor (Ssy1, Ptr3, and Ssy5) activates two transcription factors (Stp1 and Stp2) to differentially control two distinct modes of nitrogen acquisition (host protein catabolism and amino acid uptake, respectively). Our results indicate that a functional SPS-sensor and Stp1 controlled genes required for host protein catabolism and utilization, including the major secreted aspartyl protease SAP2, are required to establish virulent infections. By contrast, Stp2, which activates genes required for amino acid uptake, is dispensable for virulence. These results indicate that nutrient availability within infected hosts directly influences C. albicans virulence.
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| 10. |
- Gustafsson, Jan-Eric, 1949, et al.
(författare)
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School, Learning and Mental Health : A systematic review
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten presenterar resultaten från en systematisk översikt av forskning om skola, lärande och barns psykiska hälsa. Kungliga Vetenskapsakademiens Hälsoutskottet har givit uppdraget att genomföra en sådan översikt till en arbetsgrupp som har arbetat med uppdraget från hösten 2008 till mars 2009. Det första syftet med översikten är att genomföra en kartläggning av forskning inom det breda fält som behandlar frågor om skola, lärande och barns och ungdomars psykiska hälsa. Det andra syftet är att genomföra en narrativ syntes av forskning som undersökt orsaksförhållanden mellan psykisk hälsa å ena sidan och skolresultat och lärande å den andra sidan. Det tredje syftet är att redovisa resultat från forskning som har studerat svenska barns och ungdomars erfarenheter och upplevelser av skola och undervisningssituationer. För att uppnå de första två syftena genomfördes systematiska litteratursökningar i bibliografiska databaser av artiklar publicerade i vetenskapliga internationella tidskrifter inom olika discipliner. Det tredje syftet undersöktes med litteratursökningar av kvalitativa svenska studier i bibliografiska databaser. Slutsatser På grundval dels av kartläggningen av forskning om skola, lärande och psykisk hälsa, dels av de två fördjupade översikterna kan följande slutsatser dras: • Omfattningen av forskning som undersöker relationerna mellan olika aspekter av skola och psykisk hälsa är begränsad och i synnerhet gäller detta forskning som undersöker organisationsfaktorer och undervisnings-faktorer, aktiviteter, läroplaners utformning, resurser, specialpedagogiskt stöd, och olika former av betyg och bedömning. • Tidiga svårigheter i skolan och i synnerhet läs- och skrivsvårigheter kan orsaka internaliserande och externaliserande psykiska problem. • Svårigheter i skola och psykiska problem tenderar att vara stabila över tid. • Skolrelaterade hälsoproblem tenderar att minska när eleverna börjar på gymnasiet och får tillgång till nya områden av aktiviteter, roller och valmöjligheter. • Att genomföra stora ansträngningar utan att detta leder till resultat är relaterat till utveckling av depression. Problem i skolan med skolresultat och prestationer orsakar inter-naliserande symptom för flickor under tonåren. • Det finns samband mellan olika typer av psykiska problem och de är också relaterade till ett brett spektrum av somatiska och psykosomatiska symptom. • Internaliserande och externaliserande psykiska problem har negativa effekter på skolprestationer genom mekanismer som är delvis ålders- och genusspecifika. • Kompetenser och prestationer i skolan är relaterade till psykisk hälsa. • Goda resultat i skolan har en positiv effekt på självuppfattning. • En god självuppfattning bidrar inte direkt till bättre resultat, men andra faktorer som är relaterade till självuppfattning (motivation och upplevd inre/yttre kontroll) påverkar lärande och resultat • Relationer med klasskamrater och lärare bidrar till processer som kopplar skolmisslyckande till psykisk ohälsa. Relationer med kamrater och lärare kan också skydda mot utvecklingen av psykiska problem. • Jämförelser med klasskamrater påverkar självuppfattningen, med effekter som varierar beroende på gruppsammansättning och typ av skola.
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