Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes

Residual cognitive deficits 50 years after lead poisoning during childhood

The long term neurobehavioural consequences of childhood lead poisoning are not known. In this study adult subjects with a documented history of lead poisoning before age 4 and matched controls were examined with an abbreviated battery of neuropsychological tests including measures of attention, reasoning, memory, motor speed, and current mood. The subjects exposed to lead were inferior to controls on almost all of the cognitive tasks. This pattern of widespread deficits resembles that found in children evaluated at the time of acute exposure to lead rather than the more circumscribed pattern typically seen in adults exposed to lead. Despite having completed as many years of schooling as controls, the subjects exposed to lead were lower in lifetime occupational status. Within the exposed group, performance on the neuropsychological battery and occupational status were related, consistent with the presumed impact of limitations in neuropsychological functioning on everyday life. The results suggest that many subjects exposed to lead suffered acute encephalopathy in childhood which resolved into a chronic subclinical encephalopathy with associated cognitive dysfunction still evident in adulthood. These findings lend support to efforts to limit exposure to lead in childhood

Patient reported barriers are associated with low physical and mental well-being in patients with co-morbid diabetes and chronic kidney disease

BACKGROUND:Little is known about how patient reported barriers to health care impact the quality of life (HRQoL) of patients with comorbid disease. We investigated patient reported barriers to health care and low physical and mental well-being among people with diabetes and chronic kidney disease (CKD). METHODS:Adults with diabetes and CKD (estimated Glomerular Filtration Rate < 60 ml/min/1.73m2) were recruited and completed a questionnaire on barriers to health care, the 12-Item HRQoL Short Form Survey and clinical assessment. Low physical and mental health status were defined as mean scores < 50. Logistic regression models were used. RESULTS:Three hundred eight participants (mean age 66.9 ± 11 years) were studied. Patient reported 'impact of the disease on family and friends' (OR 2.07; 95% CI 1.14 to 3.78), 'feeling unwell' (OR 4.23; 95% CI 1.45 to 12.3) and 'having other life stressors that make self-care a low priority' (OR 2.59; 95% CI 1.20 to 5.61), were all associated with higher odds of low physical health status. Patient reported 'feeling unwell' (OR 2.92; 95% CI 1.07 to 8.01), 'low mood' (OR 2.82; 95% CI 1.64 to 4.87) and 'unavailability of home help' (OR 1.91; 95% CI 1.57 to 2.33) were all associated with higher odds of low mental health status. The greater the number of patient reported barriers the higher the odds of low mental health but not physical health status. CONCLUSIONS:Patient reported barriers to health care were associated with lower physical and mental well-being. Interventions addressing these barriers may improve HRQoL among people with comorbid diabetes and CKD.Edward Zimbudzi, Clement Lo, Sanjeeva Ranasinha, Gregory Fulcher, Martin Gallagher, Stephen Jan, Peter G. Kerr, Helena J. Teede, Kevan R. Polkinghorne, Grant Russell, Rowan G. Walker, and Sophia Zounga

Continuum-mechanical, Anisotropic Flow model for polar ice masses, based on an anisotropic Flow Enhancement factor

A complete theoretical presentation of the Continuum-mechanical, Anisotropic Flow model, based on an anisotropic Flow Enhancement factor (CAFFE model) is given. The CAFFE model is an application of the theory of mixtures with continuous diversity for the case of large polar ice masses in which induced anisotropy occurs. The anisotropic response of the polycrystalline ice is described by a generalization of Glen's flow law, based on a scalar anisotropic enhancement factor. The enhancement factor depends on the orientation mass density, which is closely related to the orientation distribution function and describes the distribution of grain orientations (fabric). Fabric evolution is governed by the orientation mass balance, which depends on four distinct effects, interpreted as local rigid body rotation, grain rotation, rotation recrystallization (polygonization) and grain boundary migration (migration recrystallization), respectively. It is proven that the flow law of the CAFFE model is truly anisotropic despite the collinearity between the stress deviator and stretching tensors.Comment: 22 pages, 5 figure

Current assessment of the Red Rectangle band problem

In this paper we discuss our insights into several key problems in the identification of the Red Rectangle Bands (RRBs). We have combined three independent sets of observations in order to try to define the constraints guiding the bands. We provide a summary of the general behavior of the bands and review the evidence for a molecular origin of the bands. The extent, composition, and possible absorption effects of the bands are discussed. Comparison spectra of the strongest band obtained at three different spectral resolutions suggests that an intrinsic line width of individual rotational lines can be deduced. Spectroscopic models of several relatively simple molecules were examined in order to investigate where the current data are weak. Suggestions are made for future studies to enhance our understanding of these enigmatic bands

The importance of long‐term experiments in agriculture: their management to ensure continued crop production and soil fertility; the Rothamsted experience

Summary Long‐term field experiments that test a range of treatments and are intended to assess the sustainability of crop production, and thus food security, must be managed actively to identify any treatment that is failing to maintain or increase yields. Once identified, carefully considered changes can be made to the treatment or management, and if they are successful yields will change. If suitable changes cannot be made to an experiment to ensure its continued relevance to sustainable crop production, then it should be stopped. Long‐term experiments have many other uses. They provide a field resource and samples for research on plant and soil processes and properties, especially those properties where change occurs slowly and affects soil fertility. Archived samples of all inputs and outputs are an invaluable source of material for future research, and data from current and archived samples can be used to develop models to describe soil and plant processes. Such changes and uses in the Rothamsted experiments are described, and demonstrate that with the appropriate crop, soil and management, acceptable yields can be maintained for many years, with either organic manure or inorganic fertilizers. Highlights Long‐term experiments demonstrate sustainability and increases in crop yield when managed to optimize soil fertility. Shifting individual response curves into coincidence increases understanding of the factors involved. Changes in inorganic and organic pollutants in archived crop and soil samples are related to inputs over time. Models describing soil processes are developed from current and archived soil data