Effect of wheat distillers dried grains with solubles or sugar beet pulp on prevalence of Salmonella enterica Typhimurium in weaned pigs

Salmonella enterica Typhimurium (ST) is of concern in the swine industry with relevance for animal health and consumer safety. Nutritional strategies might help to reduce ST infection and transmission. This study examined the potential of wheat (Triticum aestivum) distillers dried grains with solubles (DDGS) and sugar beet (Beta vulgaris) pulp (SBP) to alter intestinal microbial communities and ST shedding using a Trojan model. Weaned pigs (n = 105; 28.5 ± 3.5 d of age) were separated into 3 treatment groups (7 pigs/pen) and fed a wheat-based control diet or the control diet formulated with 15% wheat DDGS or 6% SBP inclusion. Following 12 d of diet adaptation, 2 pigs/pen were inoculated with 2 x 109 cfu ST, resistant to novobiocin and nalidixic acid. Fecal swabs were taken from infected pigs and pen-mates (contact pigs) for 9 d following challenge, enriched in nutrient broth for 24 h, and plated on selective media to determine prevalence of ST. The ranges of prevalence of ST in feces were from 90 to 100% in challenged pigs and 74 to 78% in contact pigs. No influence of treatment on rectal temperature and prevalence of ST in contact pigs were observed. Fifteen contact pigs were euthanized per treatment group on 9 and 10 d postchallenge to enumerate in intestinal contents (ileum, cecum, and proximal colon), Lactobacillus spp., Enterobacteriaceae, and Clostridium clusters I, VI, and XVIa by quantitative PCR (qPCR) and to determine ST prevalence by selective culture. No significant effects of diet were observed with respect to ST prevalence in feces, ileum, cecum, colon, and lymph nodes of contact pigs. Compared with the control diet, DGGS and SBP diets showed a trend towards increased (P < 0.1) number of Lactobacillus species in the cecum and colon. Although both wheat DGGS and SBP tended to increase the Lactobacillus spp. neither of the feed ingredients affected ST prevalence

CRISPR/Cas9-induced (CTG⋅CAG)n repeat instability in the myotonic dystrophy type 1 locus: implications for therapeutic genome editing

Myotonic dystrophy type 1 (DM1) is caused by (CTG⋅CAG)n-repeat expansion within the DMPK gene and thought to be mediated by a toxic RNA gain of function. Current attempts to develop therapy for this disease mainly aim at destroying or blocking abnormal properties of mutant DMPK (CUG)n RNA. Here, we explored a DNA-directed strategy and demonstrate that single clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-cleavage in either its 5′ or 3′ unique flank promotes uncontrollable deletion of large segments from the expanded trinucleotide repeat, rather than formation of short indels usually seen after double-strand break repair. Complete and precise excision of the repeat tract from normal and large expanded DMPK alleles in myoblasts from unaffected individuals, DM1 patients, and a DM1 mouse model could be achieved at high frequency by dual CRISPR/Cas9-cleavage at either side of the (CTG⋅CAG)n sequence. Importantly, removal of the repeat appeared to have no detrimental effects on the expression of genes in the DM1 locus. Moreover, myogenic capacity, nucleocytoplasmic distribution, and abnormal RNP-binding behavior of transcripts from the edited DMPK gene were normalized. Dual sgRNA-guided excision of the (CTG⋅CAG)n tract by CRISPR/Cas9 technology is applicable for developing isogenic cell lines for research and may provide new therapeutic opportunities for patients with DM1

The Induction of IgM and IgG Antibodies against HLA or MICA after Lung Transplantation

The production of IgG HLA antibodies after lung transplantation (LTx) is considered to be a major risk factor for the development of chronic rejection, represented by the bronchiolitis obliterans syndrome (BOS). It has recently been observed that elevated levels of IgM HLA antibodies also correlates with the development of chronic rejection in heart and kidney transplantation. This study investigates the relationship between IgM and IgG antibodies against HLA and MICA after lung transplantation. Serum was collected from 49 patients once prior to transplantation and monthly for up to 1 year after lung transplantation was analyzed by Luminex to detect IgM and IgG antibodies against HLA and MICA. The presence of either IgM or IgG HLA and/or MICA antibodies prior to or after transplantation was not related to survival, gender, primary disease, or the development of BOS. Additionally, the production of IgG alloantibodies was not preceded by an increase in levels of IgM, and IgM levels were not followed by an increase in IgG. Under current immune suppressive regimen, although the presence of IgM antibodies does not correlate with BOS after LTx, IgM high IgG low HLA class I antibody titers were observed more in patients with BOS compared to patients without BOS

Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration

Staphylococcus aureus Panton-Valentine leukocidin is a pore-forming toxin targeting the human C5a receptor (hC5aR), enabling this pathogen to battle the immune response by destroying phagocytes through targeted lysis. The mechanisms that contribute to rapid cell lysis are largely unexplored. Here, we show that cell lysis may be enabled by a process of toxins targeting receptor clusters and present indirect evidence for receptor recycling that allows multiple toxin pores to be formed close together. With the use of live cell single-molecule super-resolution imaging, Forster resonance energy transfer and nanoscale total internal reflection fluorescence colocalization microscopy, we visualized toxin pore formation in the presence of its natural docking ligand. We demonstrate disassociation of hC5aR from toxin complexes and simultaneous binding of new ligands. This effect may free mobile receptors to amplify hyperinflammatory reactions in early stages of microbial infections and have implications for several other similar bicomponent toxins and the design of new antibiotics.Haapasalo, K., Wollman, A. J. M., de Haas, C. J. C., van Kessel, K. P. M., van Strijp, J. A. G., Leake, M. C. Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration.Peer reviewe

Влияние фенилгидразина и алкилсульфатов на осмотическую чувствительность эритроцитов млекопитающих

Показано, что чувствительность эритроцитов млекопитающих к гипертоническому стрессу при 37 °С после обработки фенилгидразином зависит от видовой принадлежности клеток. Установлено, что модификация фенилгидразином эритроцитов млекопитающих приводит к снижению антигемолитической активности алкилкилсульфатов в условиях гипертонического стресса.Показано, що чутливість еритроцитів ссавців до гіпертонічного стресу при 37 °С після обробки фенілгідразином залежить від видової приналежності клітин. Встановлено, що модифікація фенілгідразином еритроцитів ссавців призводить до зниження антигемолітичної активності алкілсульфатів в умовах гіпертонічного стресу.It is shown that the sensitivity of mammalian erythrocytes to hypertonic stress at 37 °C after the treatment with phenylhydrazine depends on the species of a cell. We have established that the modification with phenylhydrazine of mammalian erythrocytes leads to a decrease of the alkyl sulfates antihemolytic activity under hypertonic stress

Entanglement in nuclear quadrupole resonance

Entangled quantum states are an important element of quantum information techniques. We determine the requirements for states of quadrupolar nuclei with spins >1/2 to be entangled. It was shown that entanglement is achieved at low temperature by applying a magnetic field to a quadrupolar nuclei possess quadrupole moments, which interacts with the electricfield gradient produced by the charge distribution in their surroundings.Comment: 9 pages, 5 figure

Staphylococcus aureus Resistance to Human Defensins and Evasion of Neutrophil Killing via the Novel Virulence Factor Mprf Is Based on Modification of Membrane Lipids with l-Lysine

Defensins, antimicrobial peptides of the innate immune system, protect human mucosal epithelia and skin against microbial infections and are produced in large amounts by neutrophils. The bacterial pathogen Staphylococcus aureus is insensitive to defensins by virtue of an unknown resistance mechanism. We describe a novel staphylococcal gene, mprF, which determines resistance to several host defense peptides such as defensins and protegrins. An mprF mutant strain was killed considerably faster by human neutrophils and exhibited attenuated virulence in mice, indicating a key role for defensin resistance in the pathogenicity of S. aureus. Analysis of membrane lipids demonstrated that the mprF mutant no longer modifies phosphatidylglycerol with l-lysine. As this unusual modification leads to a reduced negative charge of the membrane surface, MprF-mediated peptide resistance is most likely based on repulsion of the cationic peptides. Accordingly, inactivation of mprF led to increased binding of antimicrobial peptides by the bacteria. MprF has no similarity with genes of known function, but related genes were identified in the genomes of several pathogens including Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Enterococcus faecalis. MprF thus constitutes a novel virulence factor, which may be of general relevance for bacterial pathogens and represents a new target for attacking multidrug resistant bacteria

The RMS Survey: Mid-Infrared Observations of Candidate Massive YSOs in the Southern Hemisphere

Abridged abstract: The Red MSX Source (RMS) survey is an ongoing effort to return a large, well-selected sample of massive young stellar objects (MYSOs) within our Galaxy. A series of ground-based follow-up observations are being undertaken in order to remove contaminant objects from our list of 2000 candidates, and to begin characterising these MYSOs. As a part of these follow-up observations, high resolution (~1") mid-IR imaging aids the identification of contaminant objects which are resolved (UCHII regions, PN) as opposed to those which are unresolved (YSOs, evolved stars) as well as identifying YSOs near UCHII regions and other multiple sources. We present 10.4 micron imaging observations for 346 candidate MYSOs in the RMS survey in the Southern Hemisphere, primarily outside the region covered by the GLIMPSE Spitzer Legacy Survey. These were obtained using TIMMI2 on the ESO 3.6m telescope in La Silla, Chile. Our photometric accuracy is of order 0.05Jy, and our astrometric accuracy is 0.8", which is an improvement over the nominal 2" accuracy of the MSX PSC.Comment: 9 page paper accepted to A&A. Online data for table 2 and figure 1 will be available in the published online version of this paper via A&A. The paper contains 7 figures and 3 table

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis

Abstract (provisional) Background Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. Methods This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. Discussion This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Trial registration: Current Controlled Trials ISRCTN7651747