Authors:Ulrike Escher, Eliezer Giladi, Ildikò R. Dunay, Stefan Bereswill, Illana Gozes, and Markus M. Heimesaat
The octapeptide NAP is well known for its neuroprotective properties. We here investigated whether NAP treatment could alleviate pro-inflammatory immune responses during experimental subacute ileitis. To address this, mice with a human gut microbiota were perorally infected with one cyst of Toxoplasma gondii (day 0) and subjected to intraperitoneal synthetic NAP treatment from day 1 until day 8 postinfection (p.i.). Whereas placebo (PLC) control animals displayed subacute ileitis at day 9 p.i., NAP-treated mice exhibited less pronounced pro-inflammatory immune responses as indicated by lower numbers of intestinal mucosal T and B lymphocytes and lower interferon (IFN)-γ concentrations in mesenteric lymph nodes. The NAP-induced anti-inflammatory effects were not restricted to the intestinal tract but could also be observed in extra-intestinal including systemic compartments, given that pro-inflammatory cytokines were lower in liver, kidney, and lung following NAP as compared to PLC application, whereas at day 9 p.i., colonic and serum interleukin (IL)-10 concentrations were higher in the former as compared to the latter. Remarkably, probiotic commensal bifidobacterial loads were higher in the ileal lumen of NAP as compared to PLC-treated mice with ileitis. Our findings thus further support that NAP might be regarded as future treatment option directed against intestinal inflammation.
In community ecology, randomization tests with problem specific test statistics (e.g., nestedness, functional diversity, etc.) are often applied. Researchers in such studies may want not only to detect the significant departure from randomness, but also to measure the effect size (i.e., the magnitude of this departure). Measuring the effect size is necessary, for instance, when the roles of different assembly forces (e.g., environmental filtering, competition) are compared among sites. The standard method is to calculate standardized effect size (SES), i.e., to compute the departure from the mean of random communities divided by their standard deviations. Standardized effect size is a useful measure if the test statistic (e.g., nestedness index, phylogenetic or functional diversity) in the random communities follows a symmetric distribution. In this paper, I would like to call attention to the fact that SES may give us misleading information if the distribution is asymmetric (skewed). For symmetric distribution median and mean values are equal (i.e., SES = 0 indicates p = 0.5). However, this condition does not hold for skewed distributions. For symmetric distributions departure from the mean shows the extremity of the value, regardless of the sign of departure, while in asymmetric distributions the same deviation can be highly probable and extremely improbable, depending on its sign. To avoid these problems, I recommend checking symmetry of null-distribution before calculating the SES value. If the distribution is skewed, I recommend either log-transformation of the test statistic, or using probit-transformed p-value as effect size measure.
Authors:Andreas Hahn, Rebecca Hinz, Thomas Meyer, Ulrike Loderstädt, Ottmar Herchenröder, Christian G. Meyer, Norbert Georg Schwarz, and Hagen Frickmann
Introduction: German sex workers have illegally established a prevention strategy, which consists of testing potential sexual partners with human immunodeficiency virus (HIV)-specific rapid diagnostic tests (RDTs) prior to engaging in unprotected sexual intercourse eventually performed in case of a negative test result. Based on a recently established modeling approach, the effectiveness of this strategy regarding the risk of HIV exposure was compared with protection provided by condom use.
Methods: Based on a literature search, the following assumptions were used for the calculations: an averaged 80% exposure risk reduction with a condom used during sexual intercourse, usage of a well-characterized 4th-generation HIV RDT, and a 10 day post-infection period without any measurable viral load in peripheral blood followed by a seroconversion period of about 3 weeks with 12.3% test sensitivity (antigen-specific) and only afterwards 97.3% (antibody-specific) test sensitivity.
Results: In most constellations, the HIV exposure risk in case of RDT-based prevention was lower than with condom use.
Conclusions: The RDT-based HIV exposure prevention as established by sex workers is effective in most situations. A notable weakness of the strategy is the RDTs' poor sensitivity in spite of a high transmission risk during the seroconversion stage.
Authors:Christian Zimmermann, Marius Schild, Clemens Kunz, Kurt Zimmermann, and Sabine Kuntz
Probiotics are considered to have a beneficial impact on humans, but in some cases, administration of live microorganisms might be risky. In the present study, immunomodulatory effects of different Escherichia coli strains and their supernatants were examined under different inflammatory conditions with living and heat-inactivated strains. HT-29 cells were incubated with E. coli strains (S2-G1, S2-G3, S2-G4 and S2-G8) and their supernatants with or without stimulation with tumor necrosis factor alpha (TNF-α) or interleukin (IL)-1β. Quantification of IL-8 secretion and gene expression was performed by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). IL-8 secretion by TNF-α- and IL-1β-stimulated cells was attenuated by all four live strains. In contrast, heat inactivation resulted in an elevated IL-8 expression and secretion in unstimulated cells and did not maintain the anti-inflammatory effect of live bacteria in cytokine-stimulated cells. The supernatant of the live S2-G3 led to an elevated IL-8 secretion in unstimulated and IL-1β-stimulated cells but not in TNF-α-stimulated cells. Live bacteria of all strains might induce an immunosuppressive effect after stimulation of HT-29 cells, whereas heat inactivation and the supernatant seem to induce an elevated immune response. These findings might have an impact depending on the indication and purpose of administration.
Methicillin-resistant Staphylococcus aureus (MRSA) poses an infection risk for international military deployments. In the presented mini-review, the history of MRSA in the medical service and modern warfare is highlighted. To allow rapid diagnosis, various molecular diagnostic point-of-care solutions are available. Most evaluation studies, however, are focused on screening swabs rather than clinical materials and evaluation data from harsh environments are widely lacking. Accordingly, studies with complex sample materials under difficult environmental conditions, e.g., in the desert or in the tropics, are desirable to close this gap of knowledge regarding the diagnostic reliability of such modern molecular point-of-care devices.
Authors:Markus M. Heimesaat, Ulrike Escher, Anne Grunau, Ulrike Fiebiger, and Stefan Bereswill
Within 1 week following high-dose Toxoplasma gondii infection, mice develop lethal necrotizing ileitis. However, data from a subacute T. gondii-induced ileitis model are scarce. Therefore, mice harboring a human gut microbiota were perorally infected with one cyst of T. gondii. Within 9 days post-infection, the intestinal microbiota composition shifted towards higher loads of commensal enterobacteria and enterococci. Following T. gondii infection, mice were clinically only mildly affected, whereas ≈60% of mice displayed fecal blood and mild-to-moderate ileal histopathological changes. Intestinal inflammation was further characterized by increased apoptotic intestinal epithelial cells, which were accompanied by elevated proliferating gut epithelial cell numbers. As compared to naive controls, infected mice displayed elevated numbers of intestinal T lymphocytes and regulatory T-cells and increased pro-inflammatory mediator secretion. Remarkably, T. gondii-induced apoptotic and pro-inflammatory immune responses were not restricted to the gut, but could also be observed in extra-intestinal compartments including kidney, liver, and lung. Strikingly, low-dose T. gondii infection resulted in increased serum levels of pro- and anti-inflammatory cytokines. In conclusion, the here presented subacute ileitis model following peroral low-dose T. gondii infection of humanized mice allows for detailed investigations of the molecular mechanism underlying the “ménage à trois” of pathogens, human gut microbiota, and immunity.
Authors:E. Addicott, S. Laurance, M. Lyons, D. Butler, and J. Neldner
Plant communities in extensive landscapes are often mapped remotely using detectable patterns based on vegetation structure and canopy species with a high relative cover. A plot-based classification which includes species with low relative canopy cover and ignores vegetation structure, may result in plant communities not easily reconcilable with the landscape patterns represented in mapping. In our study, we investigate the effects on classification outcomes if we (1) remove rare species based on canopy cover, and (2) incorporate vegetation structure by weighting species’ cover by different measures of vegetation height. Using a dataset of 101 plots of savanna vegetation in north-eastern Australia we investigated first, the effect of removing rare species using four cover thresholds (1, 5, 8 and 10% contribution to total cover) and second, weighting species by four height measures including actual height as well as continuous and categorical transformations. Using agglomerative hierarchical clustering we produced a classification for each dataset and compared them for differences in: patterns of plot similarity, clustering, species richness and evenness, and characteristic species. We estimated the ability of each classification to predict species cover using generalised linear models. We found removing rare species at any cover threshold produced characteristic species appearing to correspond to landscape scale changes and better predicted species cover in grasslands and shrublands. However, in woodlands it made no difference. Using actual height of vegetation layer maintained vegetation structure, emphasised canopy and then sub-canopy species in clustering, and predicted species cover best of the height-measures tested. Thus, removing rare species and weighting species by height are useful techniques for identifying plant communities from plot-based classifications which are conceptually consistent with those in landscape scale mapping. This increases the confidence of end-users in both the classifications and the maps, thus enhancing their use in land management decisions.
Authors:Sobiya Shafique, Shazia Shafique, and Aqeel Ahmad
Pakistan holds the position of top chilies producers. So Capsicum annuum L. production in Pakistan should be promoted by combating against diseases. The only solution is to cultivate resistant varieties. Presently six chili varieties were treated with Fusarium oxysporum Schlecht. and screened for the most resistant and the most susceptible varieties. Representative varieties were evaluated for their biochemical and transcriptional profiles to discover the bases of antifungal-resistance. Results concluded that the most resistant variety was “Dandicut” and the most susceptible was “Ghotki”. Tannins, coumarins, flavonoids, phenolics, Riboflavins and saponins were observed in higher quantities in Dandicut as compared to Ghotki. Defense related enzymes i.e. polyphenol oxidase, phenyl ammonia lyase and peroxidase were found in elevated amounts in Dandicut than in Ghotki. Transcriptional results showed that defense related genes i.e. PR2a, acidic glucanase; Chitinase 3, acidic; Osmotin-like PR5 and Metallothionein 2b-like had higher expressional rates in Dandicut. Pearson’s correlation coefficient revealed stronger direct interaction in signal transduction and salicylic acid pathway. Resistance of chili varieties is salicylic acid based. Results obtained from this study not only help to improve chili production in Pakistan but also facilitate variety development operations. Moreover, it also constructed a scale to evaluate innate resistance among varieties.
Authors:David Olusoga Ogbolu, O. A. Terry Alli, Mark Alexander Webber, Adeolu Sunday Oluremi, and Omoboriowo Moses Oloyede
β-Lactam antibiotics are widely used to treat urinary tract infections in Nigeria. This study aimed to determine the presence and characteristics of extended spectrum β-lactamases in commonly isolated uropathogenic Gram-negative bacteria (GNB) in Nigeria.
Fifty non-duplicate GNB isolates consisting of Escherichia coli, 19; Klebsiella pneumoniae, 21; and Pseudomonas aeruginosa, 10 were obtained from three tertiary hospitals in Nigeria. The antibiotic susceptibility testing of all isolates to a panel of antibiotics including minimum inhibitory concentrations (MICs) and extended spectrum β-lactamases was determined. Polymerase chain reactions and sequencing were used to detect β-lactam genes.
Polymerase chain reactions and sequencing identified varying extended spectrum β-lactamases (ESBLs) encoding genes for 24 isolates (48.0%). Cefotaximase-Munich (CTX-M) 15 was the dominant gene with 20/24 of the isolates positive at 83.3%; multiple genes (2 to 6 ESBL genes) were found in 20 of the isolates. The isolates encoded other genes such as CTX-M-14, 33.3%; sulfhydryl variable (SHV) variants, 58.3%; oxacillinase (OXA) variants, 70.8%; OXA-10, 29.2%; and Vietnamese extended β-lactamase (VEB) 1, 25.0%. There was no difference between the MIC50 and MIC90 of all the isolates.
The high-level multidrug resistance of uropathogens to third generation cephalosporins including other antibiotics used in this study is strongly associated with carriage of ESBLs, predominantly CTX-M-15, as well as CTX-X-M-14, OXA-10, and VEB-1.