The Inflammatory Response of Primary Bovine Mammary Epithelial Cells to Staphylococcus aureus Strains Is Linked to the Bacterial Phenotype

Staphylococcus aureus is a major mastitis-causing pathogen in dairy cows. The latex agglutination-based Staphaurex test allows bovine S. aureus strains to be grouped into Staphaurex latex agglutination test (SLAT)-negative [SLAT(-)] and SLAT-positive [SLAT(+)] isolates. Virulence and resistance gene profiles within SLAT(-) isolates are highly similar, but differ largely from those of SLAT(+) isolates. Notably, specific genetic changes in important virulence factors were detected in SLAT(-) isolates. Based on the molecular data, it is assumed that SLAT(+) strains are more virulent than SLAT(-) strains. The objective of this study was to investigate if SLAT(-) and SLAT(+) strains can differentially induce an immune response with regard to their adhesive capacity to epithelial cells in the mammary gland and in turn, could play a role in the course of mastitis. Primary bovine mammary epithelial cells (bMEC) were challenged with suspensions of heat inactivated SLAT(+) (n = 3) and SLAT(-) (n = 3) strains isolated from clinical bovine mastitis cases. After 1, 6, and 24 h, cells were harvested and mRNA expression of inflammatory mediators (TNF-α, IL-1β, IL-8, RANTES, SAA, lactoferrin, GM-CSF, COX-2, and TLR-2) was evaluated by reverse transcription and quantitative PCR. Transcription (ΔΔCT) of most measured factors was induced in challenged bMEC for 6 and 24 h. Interestingly, relative mRNA levels were higher (P<0.05) in response to SLAT(+) compared to SLAT(-) strains. In addition, adhesion assays on bMEC also showed significant differences between SLAT(+) and SLAT(-) strains. The present study clearly shows that these two S. aureus strain types cause a differential immune response of bMEC and exhibit differences in their adhesion capacity in vitro. This could reflect differences in the severity of mastitis that the different strain types may induce.

Deficit actual tool use in schizophrenia is linked to structural alterations in key regions of planning and executing of tool use and connecting fibers

Introduction: Schizophrenia patients frequently suffer from complex motor abnormalities including fine and gross motor disturbances, abnormal involuntary movements, neurological soft signs and parkinsonism. These symptoms occur early in the course of the disease, continue in chronic patients and may deteriorate with antipsychotic medication. Furthermore gesture performance is impaired in patients, including the pantomime of tool use. Whether schizophrenia patients would show difficulties of actual tool use has not yet been investigated. Human tool use is complex and relies on a network of distinct and distant brain areas. We therefore aim to test if schizophrenia patients had difficulties in tool use and to assess associations with structural brain imaging using voxel based morphometry (VBM) and tract based spatial statistics (TBSS). Methode: In total, 44 patients with schizophrenia (DSM-5 criteria; 59% men, mean age 38) underwent structural MR imaging and performed the Tool-Use test. The test examines the use of a scoop and a hammer in three conditions: pantomime (without the tool), demonstration (with the tool) and actual use (with a recipient object). T1-weighted images were processed using SPM8 and DTI-data using FSL TBSS routines. To assess structural alterations of impaired tool use we first compared gray matter (GM) volume in VBM and white matter (WM) integrity in TBSS data of patients with and without difficulties of actual tool use. Next we explored correlations of Tool use scores and VBM and TBSS data. Group comparisons were family wise error corrected for multiple tests. Correlations were uncorrected (p < 0.001) with a minimum cluster threshold of 17 voxels (equivalent to a map-wise false positive rate of alpha < 0.0001 using a Monte Carlo procedure). Results: Tool use was impaired in schizophrenia (43.2% pantomime, 11.6% demonstration, 11.6% use). Impairment was related to reduced GM volume and WM integrity. Whole brain analyses detected an effect in the SMA in group analysis. Correlations of tool use scores and brain structure revealed alterations in brain areas of the dorso-dorsal pathway (superior occipital gyrus, superior parietal lobule, and dorsal premotor area) and the ventro-dorsal pathways (middle occipital gyrus, inferior parietal lobule) the action network, as well as the insula and the left hippocampus. Furthermore, significant correlations within connecting fiber tracts - particularly alterations within the bilateral corona radiata superior and anterior as well as the corpus callosum -were associated with Tool use performance. Conclusions: Tool use performance was impaired in schizophrenia, which was associated with reduced GM volume in the action network. Our results are in line with reports of impaired tool use in patients with brain lesions particularly of the dorso-dorsal and ventro-dorsal stream of the action network. In addition an effect of tool use on WM integrity was shown within fiber tracts connecting regions important for planning and executing tool use. Furthermore, hippocampus is part of a brain system responsible for spatial memory and navigation.The results suggest that structural brain alterations in the common praxis network contribute to impaired tool use in schizophrenia.

Does upward social mobility increase life satisfaction? A longitudinal analysis using British and Swiss panel data

A main assumption of social production function theory is that status is a major determinant of subjective well-being (SWB). From the perspective of the dissociative hypothesis, however, upward social mobility may be linked to identity problems, distress, and reduced levels of SWB because upwardly mobile people lose their ties to their class of origin. In this paper, we examine whether or not one of these arguments holds. We employ the United Kingdom and Switzerland as case studies because both are linked to distinct notions regarding social inequality and upward mobility. Longitudinal multilevel analyses based on panel data (UK: BHPS, Switzerland: SHP) allow us to reconstruct individual trajectories of life satisfaction (as a cognitive component of SWB) along with events of intragenerational and intergenerational upward mobility—taking into account previous levels of life satisfaction, dynamic class membership, and well-studied determinants of SWB. Our results show some evidence for effects of social class and social mobility on well-being in the UK sample, while there are no such effects in the Swiss sample. The UK findings support the idea of dissociative effects in terms of a negative effect of intergenerational upward mobility on SWB.

3D documentation and visualization of external injury findings by integration of simple photography in CT/MRI data sets (IprojeCT).

This study evaluated the feasibility of documenting patterned injury using three dimensions and true colour photography without complex 3D surface documentation methods. This method is based on a generated 3D surface model using radiologic slice images (CT) while the colour information is derived from photographs taken with commercially available cameras. The external patterned injuries were documented in 16 cases using digital photography as well as highly precise photogrammetry-supported 3D structured light scanning. The internal findings of these deceased were recorded using CT and MRI. For registration of the internal with the external data, two different types of radiographic markers were used and compared. The 3D surface model generated from CT slice images was linked with the photographs, and thereby digital true-colour 3D models of the patterned injuries could be created (Image projection onto CT/IprojeCT). In addition, these external models were merged with the models of the somatic interior. We demonstrated that 3D documentation and visualization of external injury findings by integration of digital photography in CT/MRI data sets is suitable for the 3D documentation of individual patterned injuries to a body. Nevertheless, this documentation method is not a substitution for photogrammetry and surface scanning, especially when the entire bodily surface is to be recorded in three dimensions including all external findings, and when precise data is required for comparing highly detailed injury features with the injury-inflicting tool.

Measuring the promise of open data: Development of the Impact Monitoring Framework

It is a challenge to measure the impact of releasing data to the public since the effects may not be directly linked to particular open data activities or substantial impact may only occur several years after publishing the data. This paper proposes a framework to assess the impact of releasing open data by applying the Social Return on Investment (SROI) approach. SROI was developed for organizations intended to generate social and environmental benefits thus fitting the purpose of most open data initiatives. We link the four steps of SROI (input, output, outcome, impact) with the 14 high-value data categories of the G8 Open Data Charter to create a matrix of open data examples, activities, and impacts in each of the data categories. This Impact Monitoring Framework helps data providers to navigate the impact space of open data laying out the conceptual basis for further research.

The Challenge of Prenatal Diagnostic Work-Up of Maternally Inherited X-Linked Opitz G/BBB: Case Report and Literature Review

Background. Prenatal diagnosis of Optiz G/BBB syndrome (OS) is challenging because the characteristic clinical features, such as facial and genitourinary anomalies, may be subtle at sonography and rather unspecific. Furthermore, molecular testing of the disease gene is not routinely performed, unless a specific diagnosis is suggested. Method. Both familial and ultrasound data were used to achieve the diagnosis of X-linked OS (XLOS), which was confirmed by molecular testing of MID1 gene (Xp22.3) at birth. Results. Sequencing of MID1 gene disclosed the nucleotide change c.1285 +1 G>T, previously associated with XLOS. Conclusions. This case illustrates current challenges of the prenatal diagnostic work-up of XLOS and exemplifies how clinical investigation, including family history, and accurate US foetal investigations can lead to the correct diagnosis.

Are functional and genetic components of platelets linked to coronary artery disease: A case-control study

Coronary artery disease (CAD) is a multifactorial disease process involving behavioral, inflammatory, clinical, thrombotic, and genetic components. Previous epidemiologic studies focused on identifying behavioral and demographic risk factors of CAD, but none focused on platelets. Current platelet literature lacks the known effects of platelet function and platelet receptor polymorphisms on CAD. This case-control analysis addressed these issues by analyzing data collected for a previous study. Cases were individuals who had undergone CABG and thus had been diagnosed with CAD, while the controls were volunteers presumed to be CAD free. The platelet function variables analyzed included fibrinogen Von Willebrand Factor activity (VWF), shear-induced platelet aggregation (SIPA), sCD40L, and mean platelet volume; and the platelet polymorphisms studied included PIA, α2 807, Ko, Kozak, and VNTR. Univariate analysis found fibrinogen, VWF, SIPA, and PIA to be independent risk factors of CAD. Logistic regression was used to build a predictive model for CAD using the platelet function and platelet polymorphism data adjusted for age, sex, race, and current smoking status. A model containing only platelet polymorphisms and their respective receptor densities, found polymorphisms within GPIbα to be associated with CAD, yielding an 86% (95% C.I. 0.97–3.55) increased risk with the presence of at least 1 polymorphism in Ko, Kozak, or VNTR. Another model included both platelet function and platelet polymorphism data. Fibrinogen, the receptor density of GPIbα, and the polymorphism in GPIa-IIa (α2 807) were all associated with CAD with odds ratios of 1.10, 1.04, and 2.30 for fibrinogen (10mg/dl increase), GPIbα receptors (1 MFI increase), and GPIa-IIa, respectively. In addition, risk estimates and 99% confidence intervals adjusted for race were calculated to determine if the presence of a platelet receptor polymorphism was associated with CAD. The results were as follows: PIA (1.64, 0.74–3.65); α2 807 (1.35, 0.77–2.37); Ko (1.71, 0.70–4.16); Kozak (1.17, 0.54–2.52); and VNTR (1.24, 0.52–2.91). Although not statistically significant, all platelet polymorphisms were associated with an increased risk for CAD. These exploratory findings indicate that platelets do appear to have a role in atherosclerosis and that anti-platelet drugs targeting GPI-IIa and GPIbα may be better treatment candidates for individuals with CAD. ^

Left, right and interval bivariate censored data: Evaluating screening mammography in the presence of lead -time bias, length bias and over-detection

Of the large clinical trials evaluating screening mammography efficacy, none included women ages 75 and older. Recommendations on an upper age limit at which to discontinue screening are based on indirect evidence and are not consistent. Screening mammography is evaluated using observational data from the SEER-Medicare linked database. Measuring the benefit of screening mammography is difficult due to the impact of lead-time bias, length bias and over-detection. The underlying conceptual model divides the disease into two stages: pre-clinical (T0) and symptomatic (T1) breast cancer. Treating the time in these phases as a pair of dependent bivariate observations, (t0,t1), estimates are derived to describe the distribution of this random vector. To quantify the effect of screening mammography, statistical inference is made about the mammography parameters that correspond to the marginal distribution of the symptomatic phase duration (T1). This shows the hazard ratio of death from breast cancer comparing women with screen-detected tumors to those detected at their symptom onset is 0.36 (0.30, 0.42), indicating a benefit among the screen-detected cases. ^

Stable isotope analysis and temperature reconstruction data from DSDP Hole 94-609B and ODP Hole 162-984B

The Greenland ice sheet is accepted as a key factor controlling the Quaternary glacial scenario. However, the origin and mechanisms of major Arctic glaciation starting at 3.15 Ma and culminating at 2.74 Ma are still controversial. For this phase of intense cooling Ravelo et al. proposed a complex gradual forcing mechanism. In contrast, our new submillennial-scale paleoceanographic records from the Pliocene North Atlantic suggest a far more precise timing and forcing for the initiation of northern hemisphere glaciation (NHG), since it was linked to a 2-3 °C surface water warming during warm stages from 2.95 to 2.82 Ma. These records support previous models, claiming that the final closure of the Panama Isthmus (3.0- ~2.5 Ma induced an increased poleward salt and heat transport. Associated strengthening of North Atlantic Thermohaline Circulation and in turn, an intensified moisture supply to northern high latitudes resulted in the build-up of NHG, finally culminating in the great, irreversible climate crash at marine isotope stage G6 (2.74 Ma). In summary, there was a two-step threshold mechanism that marked the onset of NHG with glacial-to-interglacial cycles quasi-persistent until today.

Plant-wax, alkenone and major element analyses of ODP Site 659 for the Last Glacial cycle and associated coretop data

We present a hydrologic reconstruction of the Sahara-Sahel transition, covering the complete last glacial cycle (130 ka), based on a combination of plant-wax-specific hydrogen (dD) and carbon isotopes (d13C). The dD and d13C signatures of long-chain n-alkanes from ODP Site 659 off NW Africa reveal a significant anti-correlation. Complementary to published pollen data, we infer that this plant-wax signal reflects sensitive responses of the vegetation cover to precipitation changes in the Sahel region, as well as varying contributions from biomes north of the Sahara (C3 domain) by North-East Trade Winds (NETW). During arid phases, especially the northern parts of the Sahel likely experienced crucial water stress, which resulted in a pronounced contraction of the vegetation cover, thus reducing the amount of C4 plant waxes from the region. The increase in NETW strength during dry periods further promoted a more pronounced C3-plant-wax signal derived from the North African C3 plant domain. During humid periods, the C4-dominated Sahelian environments spread northward into the Saharan realm, in association with lower NETW inputs of C3 plant waxes. Arid-humid cycles deduced from plant-wax dD are in accordance with concomitant changes in weathering intensity reflected in varying major element distributions. Environmental shifts are generally linked to periods with large fluctuations in Northern Hemisphere summer insolation. During Marine Isotope Stages 2 and 3, when insolation variability was low, coupling of the hydrologic regime to alkenone-based estimates of NE Atlantic sea-surface temperatures becomes apparent.

Seagrass and associated benthic community data derived from field surveys at Low Isles, Great Barrier Reef, conducted July-August, 1997

The distribution of seagrass and associated benthic communities on the reef and lagoon of Low Isles, Great Barrier Reef, was mapped between the 29 July and 29 August 1997. For this survey, observers walked or free-dived at survey points positioned approximately 50 m apart along a series of transects. Visual estimates of above-ground seagrass biomass and % cover of each benthos and substrate type were recorded at each survey point. A differential handheld global positioning system (GPS) was used to locate each survey point (accuracy ±3m). A total of 349 benthic survey points were examined. To assist with mapping meadow/habitat type boundaries, an additional 177 field points were assessed and a georeferenced 1:12,000 aerial photograph (26th August 1997) was used as a secondary source of information. Bathymetric data (elevation below Mean Sea Level) measured at each point assessed and from Ellison (1997) supplemented information used to determine boundaries, particularly in the subtidal lagoon. 127.8 ±29.6 hectares was mapped. Seagrass and associated benthic community data was derived by haphazardly placing 3 quadrats (0.25m**2) at each survey point. Seagrass above ground biomass (standing crop, grams dry weight (g DW m**-2)) was determined within each quadrat using a non-destructive visual estimates of biomass technique and the seagrass species present identified. In addition, the cover of all benthos was measured within each of the 3 quadrats using a systematic 5 point method. For each quadrat, frequency of occurrence for each benthic category was converted to a percentage of the total number of points (5 per quadrat). Data are presented as the average of the 3 quadrats at each point. Polygons of discrete seagrass meadow/habitat type boundaries were created using the on-screen digitising functions of ArcGIS (ESRI Inc.), differentiated on the basis of colour, texture, and the geomorphic and geographical context. The resulting seagrass and benthic cover data of each survey point and for each seagrass meadow/habitat type was linked to GPS coordinates, saved as an ArcMap point and polygon shapefile, respectively, and projected to Universal Transverse Mercator WGS84 Zone 55 South.

Benthic and substrate cover data derived from photo-transect surveys in Heron Reef

Underwater georeferenced photo-transect survey was conducted on September 23 - 27, 2007 at different sections of the reef flat, reef crest and reef slope in Heron Reef. For this survey a snorkeler or diver swam over the bottom while taking photos of the benthos at a set height using a standard digital camera and towing a surface float GPS which was logging its track every five seconds. A standard digital compact camera was placed in an underwater housing and fitted with a 16 mm lens which provided a 1.0 m x 1.0 m footprint, at 0.5 m height above the benthos. Horizontal distance between photos was estimated by three fin kicks of the survey diver/snorkeler, which corresponded to a surface distance of approximately 2.0 - 4.0 m. The GPS was placed in a dry-bag and logged its position as it floated at the surface while being towed by the photographer. A total of 3,586 benthic photos were taken. A floating GPS setup connected to the swimmer/diver by a line enabled recording of coordinates of each benthic. Approximation of coordinates of each benthic photo was done based on the photo timestamp and GPS coordinate time stamp, using GPS Photo Link Software (www.geospatialexperts.com). Coordinates of each photo were interpolated by finding the gps coordinates that were logged at a set time before and after the photo was captured. Benthic or substrate cover data was derived from each photo by randomly placing 24 points over each image using the Coral Point Count excel program (Kohler and Gill, 2006). Each point was then assigned to 1 out of 80 cover types, which represented the benthic feature beneath it. Benthic cover composition summary of each photo scores was generated automatically using CPCE program. The resulting benthic cover data of each photo was linked to gps coordinates, saved as an ArcMap point shapefile, and projected to Universal Transverse Mercator WGS84 Zone 56 South.

Strontium isotope data from DSDP Sites 32-305 and 62-463 and ODP Sites 113-689 and 113-690

Fluctuations in oxygen (d18O) and carbon (d13C) isotope values of benthic foraminiferal calcite from the tropical Pacific and Southern Oceans indicate rapid reversals in the dominant mode and direction of the thermohaline circulation during a 1 m.y. interval (71-70 Ma) in the Maastrichtian. At the onset of this change, benthic foraminiferal d18O values increased and were highest in low-latitude Pacific Ocean waters, whereas benthic and planktic foraminiferal d13C values decreased and benthic values were lowest in the Southern Ocean. Subsequently, benthic foraminiferal d18O values in the Indo-Pacific decreased, and benthic and planktic d13C values increased globally. These isotopic patterns suggest that cool intermediate-depth waters, derived from high-latitude regions, penetrated temporarily to the tropics. The low benthic d13C values at the Southern Ocean sites, however, suggest that these cool waters may have been derived from high northern rather than high southern latitudes. Correlation with eustatic sea-level curves suggests that sea-level change was the most likely mechanism to change the circulation and/or source(s) of intermediate-depth waters. We thus propose that oceanic circulation during the latest Cretaceous was vigorous and that competing sources of intermediate- and deep-water formation, linked to changes in climate and sea level, may have alternated in importance.