The role of photosynthesis in choosing optimal agro-technical factors of autumn canola production

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Antipsychotic drug use in pregnancy: A multinational study from ten countries

Aim: To compare the prevalence and trends of antipsychotic drug use during pregnancy between countries across four continents

Identification of Genes Contributing to the Virulence of Francisella tularensis SCHU S4 in a Mouse Intradermal Infection Model

Background: Francisella tularensis is a highly virulent human pathogen. The most virulent strains belong to subspecies tularensis and these strains cause a sometimes fatal disease. Despite an intense recent research effort, there is very limited information available that explains the unique features of subspecies tularensis strains that distinguish them from other F. tularensis strains and that explain their high virulence. Here we report the use of targeted mutagenesis to investigate the roles of various genes or pathways for the virulence of strain SCHU S4, the type strain of subspecies tularensis. Methodology/Principal Findings: The virulence of SCHU S4 mutants was assessed by following the outcome of infection after intradermal administration of graded doses of bacteria. By this route, the LD\u2085\u2080 of the SCHU S4 strain is one CFU. The virulence of 20 in-frame deletion mutants and 37 transposon mutants was assessed. A majority of the mutants did not show increased prolonged time to death, among them notably \u394pyrB and \u394recA. Of the remaining, mutations in six unique targets, tolC, rep, FTT0609, FTT1149c, ahpC, and hfq resulted in significantly prolonged time to death and mutations in nine targets, rplA, wbtI, iglB, iglD, purL, purF, ggt, kdtA, and glpX, led to marked attenuation with an LD\u2085\u2080 of >10\ub3 CFU. In fact, the latter seven mutants showed very marked attenuation with an LD\u2085\u2080 of 6510\u2077 CFU. Conclusions/Significance: The results demonstrate that the characterization of targeted mutants yielded important information about essential virulence determinants that will help to identify the so far little understood extreme virulence of F. tularensis subspecies tularensis.Peer reviewed: YesNRC publication: Ye

Mapping of a YscY Binding Domain within the LcrH Chaperone That Is Required for Regulation of Yersinia Type III Secretion

Type III secretion systems are used by many animal and plant interacting bacteria to colonize their host. These systems are often composed of at least 40 genes, making their temporal and spatial regulation very complex. Some type III chaperones of the translocator class are important regulatory molecules, such as the LcrH chaperone of Yersinia pseudotuberculosis. In contrast, the highly homologous PcrH chaperone has no regulatory effect in native Pseudomonas aeruginosa or when produced in Yersinia. In this study, we used LcrH-PcrH chaperone hybrids to identify a discrete region in the N terminus of LcrH that is necessary for YscY binding and regulatory control of the Yersinia type III secretion machinery. PcrH was unable to bind YscY and the homologue Pcr4 of P. aeruginosa. YscY and Pcr4 were both essential for type III secretion and reciprocally bound to both substrates YscX of Yersinia and Pcr3 of P. aeruginosa. Still, Pcr4 was unable to complement a ΔyscY null mutant defective for type III secretion and yop-regulatory control in Yersinia, despite the ability of YscY to function in P. aeruginosa. Taken together, we conclude that the cross-talk between the LcrH and YscY components represents a strategic regulatory pathway specific to Yersinia type III secretion

The YopD Translocator of Yersinia pseudotuberculosis Is a Multifunctional Protein Comprised of Discrete Domains

To establish an infection, Yersinia pseudotuberculosis utilizes a plasmid-encoded type III translocon to microinject several anti-host Yop effectors into the cytosol of target eukaryotic cells. YopD has been implicated in several key steps during Yop effector translocation, including maintenance of yop regulatory control and pore formation in the target cell membrane through which effectors traverse. These functions are mediated, in part, by an interaction with the cognate chaperone, LcrH. To gain insight into the complex molecular mechanisms of YopD function, we performed a systematic mutagenesis study to search for discrete functional domains. We highlighted amino acids beyond the first three N-terminal residues that are dispensable for YopD secretion and confirmed that an interaction between YopD and LcrH is essential for maintenance of yop regulatory control. In addition, discrete domains within YopD that are essential for both pore formation and translocation of Yop effectors were identified. Significantly, other domains were found to be important for effector microinjection but not for pore formation. Therefore, YopD is clearly essential for several discrete steps during efficient Yop effector translocation. Recognition of this modular YopD domain structure provides important insights into the function of YopD

2017 Global Initiative for Chronic Obstructive Lung Disease reclassifies half of COPD subjects to lower risk group

Marieann Högman,1 Johanna Sulku,2,3 Björn Ställberg,4,5 Christer Janson,1 Kristina Bröms,3,4 Hans Hedenström,6 Karin Lisspers,4,5 Andrei Malinovschi6 1Department of Medical Sciences, Respiratory, Allergy and Sleep Research, 2Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, 3Center for Research & Development, Uppsala University/Region Gävleborg, Gävle, 4Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, 5Center for Clinical Research, Uppsala University, County Council Dalarna, Falun, 6Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden Background: Unlike the 2014 guidelines, the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have removed lung function from the risk assessment algorithm of patients with COPD. The aim of this investigation was to analyze the proportion of subjects who would change to a lower risk group when applying GOLD2017 and determine if they exhibit different characteristics in terms of inflammation, symptoms and comorbidity compared to the subjects who would remain in a high-risk group. Subjects and methods: A total of 571 subjects with physician-diagnosed and spirometry-verified COPD were included in the present study. The data consisted of measurements of lung function, inflammatory markers, together with questionnaires that covered comorbidities, COPD symptoms and medication. Results: From group C, 53% of the subjects would be reclassified to the lower risk group A, and from group D, 47% of the subjects would be reclassified to the lower risk group B when using GOLD2017 instead of GOLD2014. Compared to the subjects who would remain in group D, those who would change to group B were more often men (56% vs 72%); of an older age, mean (SD), 71 (8) years vs 68 (7) years; had more primary care contact (54% vs 33%); had lower levels of blood neutrophils, geometrical mean (95% CI), 5.3 (5.0, 5.7) vs 4.6 (4.3, 4.9); reported less anxiety/depression (20% vs 34%); experienced less asthma (29% vs 46%) and had fewer symptoms according to the COPD assessment test,16 (5) vs 21 (7). All p-values were <0.05. Conclusion: The removal of spirometry from risk assessment in GOLD2017 would lead to the reclassification of approximately half of the subjects in the risk groups C and D to the lower risk groups A and B. There are differences in age, gender, health care contacts, inflammation, comorbidity and symptom burden among those changing from group D to group B. The effects of reclassification and changes in eventual treatment for disease control and symptom burden need further investigation. Keywords: COPD, lung function test, eosinophils, neutrophils, comorbidity, GOL