Local adaptation of a bacterium is as important as its presence in structuring a natural microbial community

This is the final version of the article. Available from Springer Nature via the DOI in this record.Local adaptation of a species can affect community composition, yet the importance of local adaptation compared with species presence per se is unknown. Here we determine how a compost bacterial community exposed to elevated temperature changes over 2 months as a result of the presence of a focal bacterium, Pseudomonas fluorescens SBW25, that had been pre-adapted or not to the compost for 48 days. The effect of local adaptation on community composition is as great as the effect of species presence per se, with these results robust to the presence of an additional strong selection pressure: an SBW25-specific virus. These findings suggest that evolution occurring over ecological time scales can be a key driver of the structure of natural microbial communities, particularly in situations where some species have an evolutionary head start following large perturbations, such as exposure to antibiotics or crop planting and harvesting.The work was funded by BBSRC, AXA Research fund and NERC. P.G. was supported by a Marie Curie Intra-European Fellowship within the European Commission 7th Framework Program (PIEF-GA-2010-272945), and acknowledges the Spanish MINECO support (AGL2014-59556-R). A.B. was supported by the Royal Society (UK). L.D.M. acknowledges the KU Leuven Research Fund support PF/2010/07

Transactivation of EGFR by LPS induces COX-2 expression in enterocytes

Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC

Early Detection of Tuberculosis Outbreaks among the San Francisco Homeless: Trade-Offs Between Spatial Resolution and Temporal Scale

BACKGROUND: San Francisco has the highest rate of tuberculosis (TB) in the U.S. with recurrent outbreaks among the homeless and marginally housed. It has been shown for syndromic data that when exact geographic coordinates of individual patients are used as the spatial base for outbreak detection, higher detection rates and accuracy are achieved compared to when data are aggregated into administrative regions such as zip codes and census tracts. We examine the effect of varying the spatial resolution in the TB data within the San Francisco homeless population on detection sensitivity, timeliness, and the amount of historical data needed to achieve better performance measures. METHODS AND FINDINGS: We apply a variation of space-time permutation scan statistic to the TB data in which a patient's location is either represented by its exact coordinates or by the centroid of its census tract. We show that the detection sensitivity and timeliness of the method generally improve when exact locations are used to identify real TB outbreaks. When outbreaks are simulated, while the detection timeliness is consistently improved when exact coordinates are used, the detection sensitivity varies depending on the size of the spatial scanning window and the number of tracts in which cases are simulated. Finally, we show that when exact locations are used, smaller amount of historical data is required for training the model. CONCLUSION: Systematic characterization of the spatio-temporal distribution of TB cases can widely benefit real time surveillance and guide public health investigations of TB outbreaks as to what level of spatial resolution results in improved detection sensitivity and timeliness. Trading higher spatial resolution for better performance is ultimately a tradeoff between maintaining patient confidentiality and improving public health when sharing data. Understanding such tradeoffs is critical to managing the complex interplay between public policy and public health. This study is a step forward in this direction

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Photocatalytic activity of nitrogen-doped TiO2-based nanowires: a photo-assisted Kelvin probe force microscopy study

The emerging industrial business partnerships, which feature cross-functional and cross-company development efforts, raise the barrier for the establishment of effective knowledge sharing practices in the larger organization. This chapter aims to highlight the role of knowledge as a key enabler for effective engineering activities in the light of such emerging enterprise collaboration models. Knowledge Enabled Engineering (KEE) is presented as an approach to enhance the extended organization’s capability to establish effective collaboration among its parts, in spite of different organizational structures, technologies or processes. KEE is analysed in its constituent parts, highlighting areas, methods and tools that are particularly interesting for leveraging companies’ knowledge sharing capabilities

Treatment of Helminth Co-Infection in Individuals with HIV-1: A Systematic Review of the Literature

Many people living in areas of the world most affected by the HIV/AIDS pandemic are also exposed to other common infections. Parasitic infections with helminths (intestinal worms) are common in Africa and affect over half of the population in some areas. There are plausible biological reasons why treating helminth infections in people with HIV may slow down the progression of HIV to AIDS. Thus, treating people with HIV for helminths in areas with a high prevalence of both HIV and helminth infections may be a feasible strategy to help people with HIV delay progression of their disease or initiation of antiretroviral therapy. After a comprehensive review of the available literature, we conclude that there is not enough evidence to determine whether treating helminth infections in people with HIV is beneficial

The association between baseline persistent pain and weight change in patients attending a specialist weight management service

To quantify the influence of baseline pain levels on weight change at one-year follow-up in patients attending a National Health Service specialist weight management programme.We compared one-year follow-up weight (body mass) change between patient sub-groups of none-to-mild, moderate, and severe pain at baseline. A mean sub-group difference in weight change of ≥5kg was considered clinically relevant.Of the 141 complete cases, n = 43 (30.5%) reported none-to-mild pain, n = 44 (31.2%) reported moderate pain, and n = 54 (38.3%) reported severe pain. Covariate-adjusted mean weight loss (95%CI) was similar for those with none-to-mild (8.1kg (4.2 to 12.0kg)) and moderate pain (8.3kg (4.9 to 11.7kg). The mean weight loss of 3.0kg (-0.4 to 6.4kg) for the severe pain group was 5.1kg (-0.6 to 10.7, p = 0.08) lower than the none-to-mild pain group and 5.3kg (0.4 to 10.2kg, p = 0.03) lower than the moderate pain group.Patients with severe pain upon entry to a specialist weight management service in England achieve a smaller mean weight loss at one-year follow-up than those with none-to-moderate pain. The magnitude of the difference in mean weight loss was clinically relevant, highlighting the importance of addressing severe persistent pain in obese patients undertaking weight management programmes

Dietary cadmium and risk of invasive postmenopausal breast cancer in the VITAL cohort.

This study does not support the hypothesis that dietary cadmium intake is a risk factor for breast cancer. However, non-differential measurement error in the estimate of cadmium intake is likely the most important factor that could have obscured an association

Effects of Dopamine on Sensitivity to Social Bias in Parkinson's Disease

Patients with Parkinson's disease (PD) sometimes develop impulsive compulsive behaviours (ICBs) due to their dopaminergic medication. We compared 26 impulsive and 27 non-impulsive patients with PD, both on and off medication, on a task that examined emotion bias in decision making. No group differences were detected, but patients on medication were less biased by emotions than patients off medication and the strongest effects were seen in patients with ICBs. PD patients with ICBs on medication also showed more learning from negative feedback and less from positive feedback, whereas off medication they showed the opposite effect

Downregulation of MIP-1α/CCL3 with praziquantel treatment in Schistosoma haematobium and HIV-1 co-infected individuals in a rural community in Zimbabwe

The results of our study show that the MIP-1alpha/CCL3 levels were positively associated with S. haematobium egg counts at baseline but not with HIV-1 infection status. MIP-1alpha/CCL3 levels were significantly reduced at three months post treatment with praziquantel. We therefore conclude that MIP-1alpha/CCL3 is produced during infection with S haematobium. S. haematobium infection is associated with increased MIP-1alpha/CCL3 levels in an egg intensity-dependent manner and treatment of S. haematobium is associated with a reduction in MIP-1alpha/CCL3