Do schistosome vaccine trials in mice have an intrinsic flaw that generates spurious protection data?

The laboratory mouse has been widely used to test the efficacy of schistosome vaccines and a long list of candidates has emerged from this work, many of them abundant internal proteins. These antigens do not have an additive effect when co-administered, or delivered as SWAP homogenate, a quarter of which comprises multiple candidates; the observed protection has an apparent ceiling of 40–50 %. We contend that the low level of maturation of penetrating cercariae (~32 % for Schistosoma mansoni) is a major limitation of the model since 68/100 parasites fail to mature in naïve mice due to natural causes. The pulmonary capillary bed is the obstacle encountered by schistosomula en route to the portal system. The fragility of pulmonary capillaries and their susceptibility to a cytokine-induced vascular leak syndrome have been documented. During lung transit schistosomula burst into the alveolar spaces, and possess only a limited capacity to re-enter tissues. The acquired immunity elicited by the radiation attenuated (RA) cercarial vaccine relies on a pulmonary inflammatory response, involving cytokines such as IFNγ and TNFα, to deflect additional parasites into the alveoli. A principal difference between antigen vaccine protocols and the RA vaccine is the short interval between the last antigen boost and cercarial challenge of mice (often two weeks). Thus, after antigen vaccination, challenge parasites will reach the lungs when both activated T cells and cytokine levels are maximal in the circulation. We propose that “protection” in this situation is the result of physiological effects on the pulmonary blood vessels, increasing the proportion of parasites that enter the alveoli. This hypothesis will explain why internal antigens, which are unlikely to interact with the immune response in a living schistosomulum, plus a variety of heterologous proteins, can reduce the level of maturation in a non-antigen-specific way. These proteins are “successful” precisely because they have not been selected for immunological silence. The same arguments apply to vaccine experiments with S. japonicum in the mouse model; this schistosome species seems a more robust parasite, even harder to eliminate by acquired immune responses. We propose a number of ways in which our conclusions may be tested

Water-induced modulation of Helicobacter pylori virulence properties

While the influence of water in Helicobacter pylori culturability and membrane integrity has been extensively studied, there are little data concerning the effect of this environment on virulence properties. Therefore, we studied the culturability of water-exposed H. pylori and determined whether there was any relation with the bacterium’s ability to adhere, produce functional components of pathogenicity and induce inflammation and alterations in apoptosis in an experimental model of human gastric epithelial cells. H. pylori partially retained the ability to adhere to epithelial cells even after complete loss of culturability. However, the microorganism is no longer effective in eliciting in vitro host cell inflammation and apoptosis, possibly due to the non-functionality of the cag type IV secretion system. These H. pylori-induced host cell responses, which are lost along with culturability, are known to increase epithelial cell turnover and, consequently, could have a deleterious effect on the initial H. pylori colonisation process. The fact that adhesion is maintained by H. pylori to the detriment of other factors involved in later infection stages appears to point to a modulation of the physiology of the pathogen after water exposure and might provide the microorganism with the necessary means to, at least transiently, colonise the human stomach.FCT (SFRH/BD/24579/2005) (to NMG

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

Reaction and colonization of common bean genotypes by Curtobacterium flaccumfaciens pv. Flaccumfaciens

Bacterial wilt is one of the main diseases of common beans and the use of cultivars with some level of resistance is fundamental for an adequate disease management. The reaction of 54 common bean genotypes to Curtobacterium flaccumfaciens pv. flaccumfaciens (Cff) was evaluated, and the colonization of cultivars and obstruction of primary xylem vessels at the petiole base were assessed. In greenhouse and laboratory tests, resistance was detected in the cultivars IAC Diplomata, IAC Alvorada, IAC Imperador, IPR Corujinha, and IPR Tangará, and in the lines P5-4-4-1 and C4-5-4-1-2. The Cff colonization rate was also slower in the resistant cultivars (IAC Diplomata, IAC Carioca Tybatã, and IAC Carioca Pyatã) and the percentage of obstruction of primary xylem vessels at the petiole base lower than in the susceptible cultivars (IAC Carioca and Pérola).A murcha-de-curtobacterium é umas principais doenças do feijoeiro e o uso de cultivares com níveis de resistência é fundamental para o manejo adequado da doença. A reação de 54 genótipos de feijoeiro comum a um isolado de Curtobacterium flaccumfaciens pv. flaccumfaciens (Cff) foi avaliada, assim como a colonização de cultivares e a obstrução de vasos de xilema primário da base de pecíolos de plantas inoculadas foram quantificadas. Ensaios conduzidos em casa-de-vegetação e laboratório evidenciaram resistência nas cultivares IAC Diplomata, IAC Alvorada, IAC Imperador, IPR Corujinha e IPR Tangará e nas linhagens P5-4-4-1 e C4-5-4-1-2. Uma menor velocidade de colonização por Cff também foi evidenciada nas cultivares resistentes (IAC Diplomata, IAC Carioca Tybatã e IAC Carioca Pyatã), assim como uma menor porcentagem de obstrução dos vasos de xilema primários na base de pecíolos, em comparação às cultivares suscetíveis (IAC Carioca e Pérola).Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Instituto Agronômico de CampinasInstituto Agronômico do ParanáUNESP Faculdade de Ciências Agronômicas Departamento de Proteção Vegeta

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

Use of direct and iterative solvers for estimation of SNP effects in genome-wide selection

The aim of this study was to compare iterative and direct solvers for estimation of marker effects in genomic selection. One iterative and two direct methods were used: Gauss-Seidel with Residual Update, Cholesky Decomposition and Gentleman-Givens rotations. For resembling different scenarios with respect to number of markers and of genotyped animals, a simulated data set divided into 25 subsets was used. Number of markers ranged from 1,200 to 5,925 and number of animals ranged from 1,200 to 5,865. Methods were also applied to real data comprising 3081 individuals genotyped for 45181 SNPs. Results from simulated data showed that the iterative solver was substantially faster than direct methods for larger numbers of markers. Use of a direct solver may allow for computing (co)variances of SNP effects. When applied to real data, performance of the iterative method varied substantially, depending on the level of ill-conditioning of the coefficient matrix. From results with real data, Gentleman-Givens rotations would be the method of choice in this particular application as it provided an exact solution within a fairly reasonable time frame (less than two hours). It would indeed be the preferred method whenever computer resources allow its use

Determinants of the exclusive breastfeeding abandonment: psychosocial factors

OBJECTIVE To assess the determinants of exclusive breastfeeding abandonment. METHODS Longitudinal study based on a birth cohort in Viçosa, MG, Southeastern Brazil. In 2011/2012, 168 new mothers accessing the public health network were followed. Three interviews, at 30, 60, and 120 days postpartum, with the new mothers were conducted. Exclusive breastfeeding abandonment was analyzed in the first, second, and fourth months after childbirth. The Edinburgh Postnatal Depression Scale was applied to identify depressive symptoms in the first and second meetings, with a score of ≥ 12 considered as the cutoff point. Socioeconomic, demographic, and obstetric variables were investigated, along with emotional conditions and the new mothers’ social network during pregnancy and the postpartum period. RESULTS The prevalence of exclusive breastfeeding abandonment at 30, 60, and 120 days postpartum was 53.6% (n = 90), 47.6% (n = 80), and 69.6% (n = 117), respectively, and its incidence in the fourth month compared with the first was 48.7%. Depressive symptoms and traumatic delivery were associated with exclusive breastfeeding abandonment in the second month after childbirth. In the fourth month, the following variables were significant: lower maternal education levels, lack of homeownership, returning to work, not receiving guidance on breastfeeding in the postpartum period, mother’s negative reaction to the news of pregnancy, and not receiving assistance from their partners for infant care. CONCLUSIONS Psychosocial and sociodemographic factors were strong predictors of early exclusive breastfeeding abandonment. Therefore, it is necessary to identify and provide early treatment to nursing mothers with depressive symptoms, decreasing the associated morbidity and promoting greater duration of exclusive breastfeeding. Support from health professionals, as well as that received at home and at work, can assist in this process