Bacillus
spp. are widely used in animal production for their probiotic properties. In many animal species, feed supplementation with specific
Bacillus
strains can provide numerous benefits including ...improvement in digestibility, the gut microbiota and immune modulation, and growth performance. Bacilli are fed to animals as spores that can sustain the harsh feed processing and long storage. However, the spores are metabolically quiescent and it is widely accepted that probiotics should be in a metabolically active state to perform certain probiotic functions like secretion of antimicrobial compounds and enzymes, synthesis of short chain fatty acids, and competition for essential nutrients. These functions should become active in the host gastrointestinal tract (GIT) soon after digestion of spores in order to contribute to microbiota and host metabolism. Considering that bacterial spores are metabolically dormant and many health benefits are provided by vegetative cells, it is of particular interest to discuss the life cycle of
Bacillus
in animal GIT. This review aims to capture the main characteristics of spores and vegetative cells and to discuss the latest knowledge in the life cycle of beneficial
Bacillus
in various intestinal environments. Furthermore, we review how the life cycle may influence probiotic functions of
Bacillus
and their benefits for human and animal health.
Ecological theory predicts that populations which receive immigrants are less vulnerable to extinction than those that do not receive immigrants (the "rescue effect"). A parallel but opposite process ...may also exist, where emigration increases the risk of local extinction (the "abandon-ship effect"). Using a natural microcosm of plant-specialist frogs from Madagascar, empirical evidence for both processes is provided. Populations receiving immigrants were less extinction-prone than those without immigration, and those populations losing individuals through emigration were more extinction-prone than those in which no emigration occurred. The number of immigrants and emigrants was also elevated and depressed (respectively) in patches that did not go extinct. These data provide some of the first definitive empirical evidence for the rescue effect and provide suggestive initial data on the abandon-ship effect. Both of these processes may be important to understanding the dynamics of populations.
Since its publication in 1929, the story of Doña Bárbara has haunted the collective Latin-American imagination, and has been adapted variously both for the small and big screen. Doña Bárbara ...Unleashed explores how Rómulo Gallegos's original story has been kept alive yet altered by subsequent screen adaptations; the book illustrates how film and telenovela adaptations have reinterpreted the story of Doña Bárbara in order to mirror changes in societal norms, such as the role of women in Latin American societies, and audience expectations. Particular attention is given to how spectators in the twenty-first century have played a crucial role influencing the alterations to which Gallegos's original plot has been subjected. Doña Bárbara Unleashed offers an original way of studying screen adaptations by engaging several adaptations of the same source text in dialogue with each other, rather simply comparing adaptations to the source text. This is a ground-breaking study that further develops readings through more traditional theories of screen adaptations with approaches emerging from fandom studies and audience responses.
To cause infections microbes need to evade host defense systems, one of these being the evolutionarily old and important arm of innate immunity, the alternative pathway of complement. It can attack ...all kinds of targets and is tightly controlled in plasma and on host cells by plasma complement regulator factor H (FH). FH binds simultaneously to host cell surface structures such as heparin or glycosaminoglycans via domain 20 and to the main complement opsonin C3b via domain 19. Many pathogenic microbes protect themselves from complement by recruiting host FH. We analyzed how and why different microbes bind FH via domains 19-20 (FH19-20). We used a selection of FH19-20 point mutants to reveal the binding sites of several microbial proteins and whole microbes (Haemophilus influenzae, Bordetella pertussis, Pseudomonas aeruginosa, Streptococcus pneumonia, Candida albicans, Borrelia burgdorferi, and Borrelia hermsii). We show that all studied microbes use the same binding region located on one side of domain 20. Binding of FH to the microbial proteins was inhibited with heparin showing that the common microbial binding site overlaps with the heparin site needed for efficient binding of FH to host cells. Surprisingly, the microbial proteins enhanced binding of FH19-20 to C3b and down-regulation of complement activation. We show that this is caused by formation of a tripartite complex between the microbial protein, FH, and C3b. In this study we reveal that seven microbes representing different phyla utilize a common binding site on the domain 20 of FH for complement evasion. Binding via this site not only mimics the glycosaminoglycans of the host cells, but also enhances function of FH on the microbial surfaces via the novel mechanism of tripartite complex formation. This is a unique example of convergent evolution resulting in enhanced immune evasion of important pathogens via utilization of a "superevasion site."
Age-specific type-distribution of high-risk human papillomavirus (hrHPV) in cervical precancerous lesions is subject to change in the HPV vaccination era. Knowing the pre-vaccination ...type-distribution helps to anticipate changes induced by mass vaccination and optimize screening.
We recruited 1279 women referred to colposcopy for abnormal cytology into a population-based study on HPV type distribution in diagnostic cervical samples (ISRCTN10933736). The HPV genotyping findings were grouped as: HPV16/18+, other hrHPV+ (HPV31/33/35/39/45/51/52/56/58/59/66/68), non-vaccine targeted hrHPV+ (HPV35/39/51/56/59/66/68), low-risk HPV, and HPV negative. We estimated the HPV group-specific prevalence rates according to diagnostic histopathological findings in the age groups of <30 (n = 339), 30–44.9 (n = 614), and ≥45 (n = 326).
Altogether 503 cases with high grade squamous intraepithelial lesion or worse (HSIL+) were diagnosed. More than half, 285 (56.7%) of HSIL+ cases were associated with HPV16/18: 64.3% (101/157) in women <30 years (reference group), 58.4% (157/269) in women 30–44.9 years (risk ratio (RR) 0.91, 95% confidence interval (95% CI) 0.78–1.06), and 35.1% (27/77) in women ≥45 years of age (RR 0.55, 95% CI 0.39–0.75). Conversely, other hrHPV's were associated with 191 (38.0%) of HSIL+: 31.9% (50/157) in women <30, 36.8% (99/269) in women 30–44.9 years, 54.6% (42/77) and in women ≥45 (RR 1.71, 95% CI 1.26–2.33). The proportion of non-vaccine targeted hrHPV and HPV negative HSIL+ increased with advancing age.
Pre-vaccination HPV type distribution in HSIL+ was distinctly polarised by age with HPV16/18 attributed disease being markedly more prevalent in women aged <30. In the older women the other hrHPV types, however, dominated suggesting a need for more age-dependent screening strategies.
•HPV distribution was markedly polarised by age in women referred to colposcopy.•HPV16/18 was twice as common in women <30 years than in women ≥45 with HSIL lesions.•In women ≥45 years other high-risk HPVs were more common in HSIL lesions.•In women ≥45 years approximately 10% of HSIL lesions were negative for high-risk HPV.
Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV ...vaccine. In total, 552 women (16-23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrollment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy = 100%; 95% CI:12-100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.
The cestode family Taeniidae consists of 2 genera, Taenia and Echinococcus, which both have been the focus of intensive taxonomic and epidemiological studies because of their zoonotic importance. ...However, a comprehensive molecular phylogeny of this family has yet to be reconstructed. In this study, 54 isolates representing 9 Taenia species were characterized using DNA sequences in the mitochondrial cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 (nad1) genes. Phylogenetic relationships within the family Taeniidae were inferred by combining cox1 and nad1 sequence data of the present and previous studies. In the phylogenetic analysis, the genus Echinococcus was shown to be monophyletic, but Taenia proved to be paraphyletic due to the position of T. mustelae as a probable sister taxon of Echinococcus. This indicates that T. mustelae should form a genus of its own. Taenia ovis krabbei was placed distant from T. ovis ovis, as a sister taxon of T. multiceps, supporting its recognition as a distinct species, T. krabbei. High intraspecific sequence variation within both T. polyacantha and T. taeniaeformis suggests the existence of cryptic sister species.
Regulation of intestinal T-cell responses is crucial for immune homeostasis and prevention of inflammatory bowel disease (IBD). A vital cytokine in regulating intestinal T cells is transforming ...growth factor-β (TGFβ), which is secreted by cells as a latent complex that requires activation to function. However, how TGFβ activation is regulated in the human intestine, and how such pathways are altered in IBD is completely unknown. Here we show that a key activator of TGFβ, integrin αvβ8, is highly expressed on human intestinal dendritic cells (DCs), specifically on the CD1c
but not the CD141
intestinal DC subset. Expression was significantly upregulated on intestinal DC from IBD patients, indicating that inflammatory signals may upregulate expression of this key TGFβ-activating molecule. Indeed, we found that the Toll-like receptor 4 ligand lipopolysaccharide upregulates integrin αvβ8 expression and TGFβ activation by human DC. We also show that DC expression of integrin αvβ8 enhanced induction of FOXP3 in CD4
T cells, suggesting functional importance of integrin αvβ8 expression by human DC. These results show that microbial signals enhance the TGFβ-activating ability of human DC via regulation of integrin αvβ8 expression, and that intestinal inflammation may drive this pathway in patients with IBD.
Summary Background The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated ...precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis. Methods Women (15–25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov , number NCT00122681. Findings Mean follow-up was 34·9 months (SD 6·4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92·9% (96·1% CI 79·9–98·3) in the primary analysis and 98·1% (88·4–100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30·4% (16·4–42·1) in the TVC and 70·2% (54·7–80·9) in the TVC-naive. Corresponding values against CIN3+ were 33·4% (9·1–51·5) in the TVC and 87·0% (54·9–97·7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54·0% (34·0–68·4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC. Interpretation The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes. Funding GlaxoSmithKline Biologicals.
Recently, new non-alcohol-based hand disinfection formulae have come to the market. Although they have passed the EN1500 test, data on their clinical efficacy compared with alcohol-based hand rubs ...are scarce, mainly covering benzalkonium chloride (BAC).
To test the efficacy of silver-polymer-based, lactic-acid-based and BAC-based hand disinfectant foams and an alcohol-based hand rub gel to reduce bacterial counts on the fingertips of healthcare workers working on hospital wards.
Each of the 84 participants tested one of the four products during their morning shift on a hospital ward using the ‘fingertips on Petri dish’ method before and after rubbing their hands with the product. After incubation, two independent readers assessed bacterial counts on the culture plates.
The alcohol-based hand rub efficiently reduced bacteria on testers' fingertips in the test situation, whereas the lactic-acid- and BAC-based disinfectants did not have any detectable efficacy. The silver-polymer-based formula had some effect but requires further study.
Non-alcohol-based hand rubs require careful consideration and further study before they can be accepted for clinical use.
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