Elucidating the aetiology of human Campylobacter coli infections

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Attentional differences in a driving hazard perception task in adults with autism spectrum disorders

The current study explored attentional processing of social and non social stimuli in ASD within the context of a driving hazard perception task. Participants watched videos of road scenes and detected hazards while their eye movements were recorded. Although individuals with ASD demonstrated relatively good detection of driving hazards, they were slower to orient to hazards. Greater attentional capture in the time preceding the hazards’ onset was associated with lower verbal IQ. The findings suggest that individuals with ASD may distribute and direct their attention diferently when identifying driving hazards

Using sequence data to identify alternative routes and risk of infection: a case-study of campylobacter in Scotland

<b>Background:</b> Genetic typing data are a potentially powerful resource for determining how infection is acquired. In this paper MLST typing was used to distinguish the routes and risks of infection of humans with Campylobacter jejuni from poultry and ruminant sources.<p></p> <b>Methods:</b> C. jejuni samples from animal and environmental sources and from reported human cases confirmed between June 2005 and September 2006 were typed using MLST. The STRUCTURE software was used to assign the specific sequence types of the sporadic human cases to a particular source. We then used mixed case-case logistic regression analysis to compare the risk factors for being infected with C. jejuni from different sources.<p></p> <b>Results:</b> A total of 1,599 (46.3%) cases were assigned to poultry, 1,070 (31.0%) to ruminant and 67 (1.9%) to wild bird sources; the remaining 715 (20.7%) did not have a source that could be assigned with a probability of greater than 0.95. Compared to ruminant sources, cases attributed to poultry sources were typically among adults (odds ratio (OR) = 1.497, 95% confidence intervals (CIs) = 1.211, 1.852), not among males (OR = 0.834, 95% CIs = 0.712, 0.977), in areas with population density of greater than 500 people/km(2) (OR = 1.213, 95% CIs = 1.030, 1.431), reported in the winter (OR = 1.272, 95% CIs = 1.067, 1.517) and had undertaken recent overseas travel (OR = 1.618, 95% CIs = 1.056, 2.481). The poultry assigned strains had a similar epidemiology to the unassigned strains, with the exception of a significantly higher likelihood of reporting overseas travel in unassigned strains.<p></p> <b>Conclusions:</b> Rather than estimate relative risks for acquiring infection, our analyses show that individuals acquire C. jejuni infection from different sources have different associated risk factors. By enhancing our ability to identify at-risk groups and the times at which these groups are likely to be at risk, this work allows public health messages to be targeted more effectively. The rapidly increasing capacity to conduct genetic typing of pathogens makes such traced epidemiological analysis more accessible and has the potential to substantially enhance epidemiological risk factor studies

The FIELDS Instrument Suite for Solar Probe Plus: Measuring the Coronal Plasma and Magnetic Field, Plasma Waves and Turbulence, and Radio Signatures of Solar Transients.

NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products

Efficient, non‐toxic anion transport by synthetic carriers in cells and epithelia

Transmembrane anion transporters (anionophores) have potential for new modes of biological activity, including therapeutic applications. In particular they might replace the activity of defective anion channels in conditions such as cystic fibrosis. However, data on the biological effects of anionophores are scarce, and it remains uncertain whether such molecules are fundamentally toxic. Here, we report a biological study of an extensive series of powerful anion carriers. Fifteen anionophores were assayed in single cells by monitoring anion transport in real time through fluorescence emission from halide-sensitive yellow fluorescent protein. A bis-(p-nitrophenyl)ureidodecalin shows especially promising activity, including deliverability, potency and persistence. Electrophysiological tests show strong effects in epithelia, close to those of natural anion channels. Toxicity assays yield negative results in three cell lines, suggesting that promotion of anion transport may not be deleterious to cells. We therefore conclude that synthetic anion carriers are realistic candidates for further investigation as treatments for cystic fibrosis.info:eu-repo/semantics/publishe

The Prevalence of Campylobacter amongst a Free-Range Broiler Breeder Flock Was Primarily Affected by Flock Age

Campylobacter successfully colonizes broiler chickens, but little is known about the longer term natural history of colonization, since most flocks are slaughtered at an immature age. In this study, the prevalence and genetic diversity of Campylobacter colonizing a single free-range broiler breeder flock was investigated over the course of a year. The age of the flock was the most important factor in determining both the prevalence and diversity of Campylobacter over time. There was no correlation with season, temperature, the amount of rain and sunshine, or the dynamics of colonization amongst geographically and temporally matched broiler flocks. The higher prevalence rates coincided with the age at which broiler chickens are typically slaughtered, but then in the absence of bio-security or other intervention methods, and despite changes in flock management, the prevalence fell to significantly lower levels for the remainder of the study. The genetic diversity of Campylobacter increased as the flock aged, implying that genotypes were accumulated within the flock and may persist for a long time. A better understanding of the ecology of Campylobacter within commercial chicken flocks will allow the design of more effective farm-based interventions

PD-1 Regulates Neural Damage in Oligodendroglia-Induced Inflammation

We investigated the impact of immune regulatory mechanisms involved in the modulation of the recently presented, CD8+ lymphocyte mediated immune response in a mouse model of oligodendropathy-induced inflammation (PLPtg-mutants). The focus was on the role of the co-inhibitory molecule PD-1, a CD28-related receptor expressed on activated T- and B-lymphocytes associated with immune homeostasis and autoimmunity. PLPtg/PD-1-deficient double mutants and the corresponding bone marrow chimeras were generated and analysed using immunohistochemistry, light- and electron microscopy, with particular emphasis on immune-cell number and neural damage. In addition, the immune cells in both the CNS and the peripheral immune system were investigated by IFN-gamma elispot assays and spectratype analysis. We found that mice with combined pathology exhibited significantly increased numbers of CD4+ and CD8+ T-lymphocytes in the CNS. Lack of PD-1 substantially aggravated the pathological phenotype of the PLPtg mutants compared to genuine PLPtg mutants, whereas the PD-1 deletion alone did not cause alterations in the CNS. CNS T-lymphocytes in PLPtg/PD-1-/- double mutants exhibited massive clonal expansions. Furthermore, PD-1 deficiency was associated with a significantly higher propensity of CNS but not peripheral CD8+ T-cells to secrete proinflammatory cytokines. PD-1 could be identified as a crucial player of tissue homeostasis and immune-mediated damage in a model of oligodendropathy-induced inflammation. Alterations of this regulatory pathway lead to overt neuroinflammation of high pathogenetic impact. Our finding may have implications for understanding the mechanisms leading to the high clinical variability of polygenic or even monogenic disorders of the nervous system

Computational Design of a PDZ Domain Peptide Inhibitor that Rescues CFTR Activity

The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial chloride channel mutated in patients with cystic fibrosis (CF). The most prevalent CFTR mutation, ΔF508, blocks folding in the endoplasmic reticulum. Recent work has shown that some ΔF508-CFTR channel activity can be recovered by pharmaceutical modulators (“potentiators” and “correctors”), but ΔF508-CFTR can still be rapidly degraded via a lysosomal pathway involving the CFTR-associated ligand (CAL), which binds CFTR via a PDZ interaction domain. We present a study that goes from theory, to new structure-based computational design algorithms, to computational predictions, to biochemical testing and ultimately to epithelial-cell validation of novel, effective CAL PDZ inhibitors (called “stabilizers”) that rescue ΔF508-CFTR activity. To design the “stabilizers”, we extended our structural ensemble-based computational protein redesign algorithm to encompass protein-protein and protein-peptide interactions. The computational predictions achieved high accuracy: all of the top-predicted peptide inhibitors bound well to CAL. Furthermore, when compared to state-of-the-art CAL inhibitors, our design methodology achieved higher affinity and increased binding efficiency. The designed inhibitor with the highest affinity for CAL (kCAL01) binds six-fold more tightly than the previous best hexamer (iCAL35), and 170-fold more tightly than the CFTR C-terminus. We show that kCAL01 has physiological activity and can rescue chloride efflux in CF patient-derived airway epithelial cells. Since stabilizers address a different cellular CF defect from potentiators and correctors, our inhibitors provide an additional therapeutic pathway that can be used in conjunction with current methods

Results of endoscopic transsphenoidal pituitary surgery in 40 patients with a growth hormone-secreting macroadenoma

Contains fulltext : 96290.pdf (Publisher’s version ) (Open Access)OBJECTIVE: Transsphenoidal pituitary surgery (TS) is the primary treatment of choice for patients with acromegaly. Macroadenomas (>1 cm) are more difficult to resect than microadenomas (remission rate +/- 50% compared to +/- 90%). Besides the conventional microscopic TS, the more recently introduced endoscopic technique is nowadays frequently used. However, no large series reporting on its results have yet been published. We evaluated the outcome of endoscopic TS in 40 patients with a growth hormone (GH)-secreting macroadenoma treated in our hospital between 1998 and 2007. METHODS: Medical records were retrospectively reviewed. Remission was defined as disappearance of clinical symptoms of acromegaly, normal serum insulin-like growth factor-1 levels (</=2 SD) and serum GH levels suppressed to <2 mU/l after an oral glucose tolerance test within the first 4 months after TS. RESULTS: In four patients TS aimed at debulking of the tumour. In the remaining 36 patients, remission was achieved in 20 patients. In the first 5 years remission was achieved in 6 out of 18 patients (33%) compared to 14 out of 22 patients (63%) in the following 5 years (p = 0.06). Thirteen patients had a mild perioperative complication. Before TS 15 patients received hormonal substitution therapy compared to 12 patients (33%) after TS. CONCLUSION: Endoscopic TS is a good primary therapeutic option for patients with a GH-secreting macroadenoma, resulting in a remission rate of up to 63% in experienced hands. This technique can potentially improve the outcome of TS in these patients

An exploration of secondary students' mental states when learning about acids and bases

This study explored factors of students’ mental states, including emotion, intention, internal mental representation, and external mental representation, which can affect their learning performance. In evaluating students’ mental states during the science learning process and the relationship between mental states and learning achievement, valid, reliable, and scalable measures of students’ mental states and learning achievement are needed. This paper presents the development of the Mental State Conceptual Learning Inventory (MSCLI) to identify students’ mental states before and after learning about acids and bases. This instrument is time efficient and convenient and can be administered to large student samples so that teachers and researchers can gain profound insights into their students’ learning of acids and bases in science class. The results of this study indicate that students’ mental states are highly correlated with their achievement. As a whole, low-achieving students tended to have negative emotions and low intentions, were not good at internal visualization, and were unable to interpret graphics and draw pictures. In contrast, high-achieving students had positive emotions and intentions when learning life-related topics about acids and bases, and were good at internal visualization and drawing and interpreting graphics