Immunomodulatory properties of mesenchymal stem cells : a review based on an interdisciplinary meeting held at the Kennedy Institute of Rheumatology Division, London, UK, 31 October 2005

Peer reviewedPublisher PD

Rare germline copy number variants (CNVs) and breast cancer risk

Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance. Dennis et al. investigate potential breast cancer associations with rare germline copy number variants (CNVs) by conducting a genome-wide analysis in a large breast cancer case-control dataset. The authors detected associations with exonic deletions in established breast cancer susceptibility genes and suggestive associations for a number of non-coding CNVs.Peer reviewe

The Impact of Beef Cattle Projects on Youth Leadership Life Skills Development

Highlights of a study designed to determine the leadership life skills development (YLLSD) of youth beef cattle exhibitors and to determine if there is a relationship between YLLSD and participation in the beef project are discussed in this paper. The study was conducted using a correlational, ex post facto design. A sample of 374 individuals was randomly selected from a population of 4,229 national junior cattle exhibitors of the National Junior Angus Association. The population frame consisted of junior members ages 18 to 21. Participants’ YLLSD scores ranged from 40 to 90 with a composite mean of 73.02. Significant relationships existed between YLLSD scores and shows per year, hours working with projects per week, and years of beef project exhibition

The Antarctic Submillimeter Telescope and Remote Observatory (AST/RO)

AST/RO, a 1.7 m diameter telescope for astronomy and aeronomy studies at wavelengths between 200 and 2000 microns, was installed at the South Pole during the 1994-1995 Austral summer. The telescope operates continuously through the Austral winter, and is being used primarily for spectroscopic studies of neutral atomic carbon and carbon monoxide in the interstellar medium of the Milky Way and the Magellanic Clouds. The South Pole environment is unique among observatory sites for unusually low wind speeds, low absolute humidity, and the consistent clarity of the submillimeter sky. Four heterodyne receivers, an array receiver, three acousto-optical spectrometers, and an array spectrometer are installed. A Fabry-Perot spectrometer using a bolometric array and a Terahertz receiver are in development. Telescope pointing, focus, and calibration methods as well as the unique working environment and logistical requirements of the South Pole are described.Comment: 57 pages, 15 figures. Submitted to PAS

Predicting Outcome in dogs with Primary Immune-Mediated Hemolytic Anemia: Results of a Multicenter Case Registry

BACKGROUND: Outcome prediction in dogs with immune‐mediated hemolytic anemia (IMHA) is challenging and few prognostic indicators have been consistently identified. OBJECTIVES: An online case registry was initiated to: prospectively survey canine IMHA presentation and management in the British Isles; evaluate 2 previously reported illness severity scores, Canine Hemolytic Anemia Score (CHAOS) and Tokyo and to identify independent prognostic markers. ANIMALS: Data from 276 dogs with primary IMHA across 10 referral centers were collected between 2008 and 2012. METHODS: Outcome prediction by previously reported illness‐severity scores was tested using univariate logistic regression. Independent predictors of death in hospital or by 30‐days after admission were identified using multivariable logistic regression. RESULTS: Purebreds represented 89.1% dogs (n = 246). Immunosuppressive medications were administered to 88.4% dogs (n = 244), 76.1% (n = 210) received antithrombotics and 74.3% (n = 205) received packed red blood cells. Seventy‐four per cent of dogs (n = 205) were discharged from hospital and 67.7% (n = 187) were alive 30‐days after admission. Two dogs were lost to follow‐up at 30‐days. In univariate analyses CHAOS was associated with death in hospital and death within 30‐days. Tokyo score was not associated with either outcome measure. A model containing SIRS‐classification, ASA classification, ALT, bilirubin, urea and creatinine predicting outcome at discharge was accurate in 82% of cases. ASA classification, bilirubin, urea and creatinine were independently associated with death in hospital or by 30‐days. CONCLUSIONS AND CLINICAL IMPORTANCE: Markers of kidney function, bilirubin concentration and ASA classification are independently associated with outcome in dogs with IMHA. Validation of this score in an unrelated population is now warranted

Colistin resistance mutations in phoQ can sensitize Klebsiella pneumoniae to IgM-mediated complement killing

International audienceAbstract Due to multi-drug resistance, physicians increasingly use the last-resort antibiotic colistin to treat infections with the Gram-negative bacterium Klebsiella pneumoniae. Unfortunately, K. pneumoniae can also develop colistin resistance. Interestingly, colistin resistance has dual effects on bacterial clearance by the immune system. While it increases resistance to antimicrobial peptides, colistin resistance has been reported to sensitize certain bacteria for killing by human serum. Here we investigate the mechanisms underlying this increased serum sensitivity, focusing on human complement which kills Gram-negatives via membrane attack complex (MAC) pores. Using in vitro evolved colistin resistant strains and a fluorescent MAC-mediated permeabilization assay, we showed that two of the three tested colistin resistant strains, Kp209_CSTR and Kp257_CSTR, were sensitized to MAC. Transcriptomic and mechanistic analyses focusing on Kp209_CSTR revealed that a mutation in the phoQ gene locked PhoQ in an active state, making Kp209_CSTR colistin resistant and MAC sensitive. Detailed immunological assays showed that complement activation on Kp209_CSTR in human serum required specific IgM antibodies that bound Kp209_CSTR but did not recognize the wild-type strain. Together, our results show that developing colistin resistance affected recognition of Kp209_CSTR and its killing by the immune system

Do psychosocial interventions have an impact on maternal perception of perinatal depression?

YesPoor perinatal mental health, in particular depression, affects at least 10% of new mothers in the UK. Current best practice recommends the use of talking therapies or medication, however, many women choose not to use medication or are deterred from accessing NHS services for example due to immigration status. Those who can access NHS treatment often face a long waiting list to see a clinician or therapist. Untreated perinatal depression impacts on the health and wellbeing of mothers and babies, consequently it is essential that alternative psychosocial interventions delivered by non-clinicians are considered. A systematic review was conducted on seven quantitative studies examining the effect of psychosocial interventions in reducing maternal symptoms of depression. Interventions focused either on physical activity or peer support, measuring depression scores on a validated screening tool. The review concludes that antenatal group peer support may benefit women in the antenatal period and that postnatal peer telephone support may be helpful for primiparous women but further large scale research is required

Use of bioengineered human commensal gut bacteria-derived microvesicles for mucosal plague vaccine delivery and immunization

Plague caused by the Gram-negative bacterium, Yersinia pestis, is still endemic in parts of the world today. Protection against pneumonic plague is essential to prevent the development and spread of epidemics. Despite this, there are currently no licensed plague vaccines in the western world. Here we describe the means of delivering biologically active plague vaccine antigens directly to mucosal sites of plague infection using highly stable microvesicles (outer membrane vesicles; OMVs) that are naturally produced by the abundant and harmless human commensal gut bacterium Bacteroides thetaiotaomicron (Bt). Bt was engineered to express major plague protective antigens in its OMVs, specifically Fraction 1 (F1) in the outer membrane and LcrV (V antigen) in the lumen, for targeted delivery to the gastrointestinal (GI) and respiratory tracts in a non-human primate (NHP) host. Our key findings were that Bt OMVs stably expresses F1 and V plague antigens, particularly the V antigen, in the correct, immunogenic form. When delivered intranasally V-OMVs elicited substantive and specific immune and antibody responses, both in the serum [immunoglobulin (Ig)G] and in the upper and lower respiratory tract (IgA); this included the generation of serum antibodies able to kill plague bacteria. Our results also showed that Bt OMV-based vaccines had many desirable characteristics, including: biosafety and an absence of any adverse effects, pathology or gross alteration of resident microbial communities (microbiotas); high stability and thermo-tolerance; needle-free delivery; intrinsic adjuvanticity; the ability to stimulate both humoral and cell-mediated immune responses; and targeting of primary sites of plague infection

Bats Use Magnetite to Detect the Earth's Magnetic Field

While the role of magnetic cues for compass orientation has been confirmed in numerous animals, the mechanism of detection is still debated. Two hypotheses have been proposed, one based on a light dependent mechanism, apparently used by birds and another based on a “compass organelle” containing the iron oxide particles magnetite (Fe3O4). Bats have recently been shown to use magnetic cues for compass orientation but the method by which they detect the Earth's magnetic field remains unknown. Here we use the classic “Kalmijn-Blakemore” pulse re-magnetization experiment, whereby the polarity of cellular magnetite is reversed. The results demonstrate that the big brown bat Eptesicus fuscus uses single domain magnetite to detect the Earths magnetic field and the response indicates a polarity based receptor. Polarity detection is a prerequisite for the use of magnetite as a compass and suggests that big brown bats use magnetite to detect the magnetic field as a compass. Our results indicate the possibility that sensory cells in bats contain freely rotating magnetite particles, which appears not to be the case in birds. It is crucial that the ultrastructure of the magnetite containing magnetoreceptors is described for our understanding of magnetoreception in animals