Nerve growth factor nonresponsive pheochromocytoma cells: altered internalization results in signaling dysfunction.

Variant rat pheochromocytoma (PC12) cells which fail to respond to nerve growth factor (NGF) (PC12nnr5) (Green, S. H., R. E. Rydel, J. L. Connoly, and L. A. Greene. 1986. J. Cell Biol. 102:830-843) bind NGF at both high and low affinity sites. Although still undefined at the molecular level, these have been referred to as type I (high) and type II (low) receptors. They are apparently composed of two membrane-bound proteins, p75 and the protooncogene trk, both of which bind NGF, and apparently contribute singularly or in concert to the two observed affinities, and to the promotion of the NGF effects. In native PC12 cells, only the high affinity receptors are apparently capable of mediating internalization and degradation. PC12nnr5 cells also display type I binding, but the subsequent internalization is not the same fashion as in the parental cell line, nor is it subjected to lysosomal degradation. Rather it is initially sequestered during the first 15 min, and is eventually released intact into the medium. In contrast, EGF is bound, internalized, and degraded by PC12nnr5 cells, albeit less efficiently than in the parent cells. These observations argue that the defect(s) preventing the PC12nnr5 variants from responding to NGF prevents competent internalization, which in the case of NGF, may be required for the full expression of activity. The absence of trk, as one alteration in PC12nnr5 cells (Loeb, D. M., J. Maragos, D. Martin-Zanca, M. V. Chao, L. F. Parada, and L. A. Greene. 1991. Cell. 66:961-966), is consistent with this conclusion

Reliability of Community Health Worker Collected Data for Planning and Policy in a Peri-Urban Area of Kisumu, Kenya

A general introduction of this article is as follows: Reliable and timely health information is an essential foundation of public health action and health systems strengthening, both nationally and internationally (Aqil et al. in Health Policy Plan 24(3): 217–228, 2009; Bradshaw et al. in initial burden of disease estimates for South Africa, 2000. South African Medical Research Council, Cape Town, 2003). The need for sound information is especially urgent in the case of emergent diseases and other acute health threats, where rapid awareness, investigation and response can save lives and prevent broader national outbreaks and even global pandemics (Aqil et al. in Health Policy Plan 24(3): 217–228, 2009). The government of Kenya, through the ministry of public health and sanitation has rolled out the community health strategy as a way of improving health care at the household level. This involves community health workers collecting health status data at the household level, which is then used for dialogue at all the levels to inform decisions and actions towards improvement in health status. A lot of health interventions have involved the community health workers in reaching out to the community, hence successfully implementing these health interventions. Large scale involvement of community health workers in government initiatives and most especially to collect health data for use in the health systems has been minimal due to the assumption that the data may not be useful to the government, because its quality is uncertain. It was therefore necessary that the validity and reliability of the data collected by community health workers be determined, and whether this kind of data can be used for planning and policy formulation for the communities from which it is collected. This would go a long way to settle speculation on whether the data collected by these workers is valid and reliable for use in determining the health status, its causes and distribution, of a community. Our general objective of this article is to investigate the validity and reliability of Community Based Information, and we deal with research question “What is the reliability of data collected at the Community level by Community health workers?”. The methods which we use to find an reliable answer to this question is “Ten percent of all households visited by CHWs for data collection were recollected by a technically trained team. Test/retest method was applied to the data to establish reliability. The Kappa score, sensitivity, specificity and positive predictive values were also used to measure reliability”. Finally our findings are as follows: Latrine availability and Antenatal care presented good correspondence between the two sets of data. This was also true for exclusive breast feeding indicator. Measles immunization coverage showed less consistency than the rest of the child health indicators. At last we conclude and recommend that CHWs can accurately and reliably collect household data which can be used for health decisions and actions especially in resource poor settings where other approaches to population based data are too expensive

Improving the delivery of care for patients with diabetes through understanding optimised team work and organisation in primary care

Peer reviewedPublisher PD

Changes in climate extremes, fresh water availability and vulnerability to food insecurity projected at 1.5°C and 2°C global warming with a higher-resolution global climate model

This is the final version. Available on open access from the Royal Society via the DOI in this recordData accessibility: This article has no additional data.We projected changes in weather extremes, hydrological impacts and vulnerability to food insecurity at global warming of 1.5°C and 2°C relative to pre-industrial, using a new global atmospheric general circulation model HadGEM3A-GA3.0 driven by patterns of sea-surface temperatures and sea ice from selected members of the 5th Coupled Model Intercomparison Project (CMIP5) ensemble, forced with the RCP8.5 concentration scenario. To provide more detailed representations of climate processes and impacts, the spatial resolution was N216 (approx. 60 km grid length in mid-latitudes), a higher resolution than the CMIP5 models. We used a set of impacts-relevant indices and a global land surface model to examine the projected changes in weather extremes and their implications for freshwater availability and vulnerability to food insecurity. Uncertainties in regional climate responses are assessed, examining ranges of outcomes in impacts to inform risk assessments. Despite some degree of inconsistency between components of the study due to the need to correct for systematic biases in some aspects, the outcomes from different ensemble members could be compared for several different indicators. The projections for weather extremes indices and biophysical impacts quantities support expectations that the magnitude of change is generally larger for 2°C global warming than 1.5°C. Hot extremes become even hotter, with increases being more intense than seen in CMIP5 projections. Precipitation-related extremes show more geographical variation with some increases and some decreases in both heavy precipitation and drought. There are substantial regional uncertainties in hydrological impacts at local scales due to different climate models producing different outcomes. Nevertheless, hydrological impacts generally point towards wetter conditions on average, with increased mean river flows, longer heavy rainfall events, particularly in South and East Asia with the most extreme projections suggesting more than a doubling of flows in the Ganges at 2°C global warming. Some areas are projected to experience shorter meteorological drought events and less severe low flows, although longer droughts and/or decreases in low flows are projected in many other areas, particularly southern Africa and South America. Flows in the Amazon are projected to decline by up to 25%. Increases in either heavy rainfall or drought events imply increased vulnerability to food insecurity, but if global warming is limited to 1.5°C, this vulnerability is projected to remain smaller than at 2°C global warming in approximately 76% of developing countries. At 2°C, four countries are projected to reach unprecedented levels of vulnerability to food insecurity. This article is part of the theme issue 'The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.European Union FP7Joint UK BEIS/Defra Met Office Hadley Centre Climate Programm

The role of SPARC in extracellular matrix assembly

SPARC is a collagen-binding matricellular protein. Expression of SPARC in adult tissues is frequently associated with excessive deposition of collagen and SPARC-null mice fail to generate a robust fibrotic response to a variety of stimuli. This review summarizes recent advancements in the characterization of the binding of SPARC to collagens and describes the results of studies that implicate a function for SPARC in the regulation of the assembly of basal lamina and fibrillar collagen in the ECM. Potential cellular mechanisms that underlie SPARC activity in ECM deposition are also explored

Computerized ICU Data Management Pitfalls and Promises

journal articleBiomedical Informatic

Soil methane sink capacity response to a long-term wildfire chronosequence in Northern Sweden

Boreal forests occupy nearly one fifth of the terrestrial land surface and are recognised as globally important regulators of carbon (C) cycling and greenhouse gas emissions. Carbon sequestration processes in these forests include assimilation of CO2 into biomass and subsequently into soil organic matter, and soil microbial oxidation of methane (CH4). In this study we explored how ecosystem retrogression, which drives vegetation change, regulates the important process of soil CH4 oxidation in boreal forests. We measured soil CH4 oxidation processes on a group of 30 forested islands in northern Sweden differing greatly in fire history, and collectively representing a retrogressive chronosequence, spanning 5000 years. Across these islands the build-up of soil organic matter was observed to increase with time since fire disturbance, with a significant correlation between greater humus depth and increased net soil CH4 oxidation rates. We suggest that this increase in net CH4 oxidation rates, in the absence of disturbance, results as deeper humus stores accumulate and provide niches for methanotrophs to thrive. By using this gradient we have discovered important regulatory controls on the stability of soil CH4 oxidation processes that could not have not been explored through shorter-term experiments. Our findings indicate that in the absence of human interventions such as fire suppression, and with increased wildfire frequency, the globally important boreal CH4 sink could be diminished

Facilitating Stable Representations: Serial Dependence in Vision

We tested whether the intervening time between multiple glances influences the independence of the resulting visual percepts. Observers estimated how many dots were present in brief displays that repeated one, two, three, four, or a random number of trials later. Estimates made farther apart in time were more independent, and thus carried more information about the stimulus when combined. In addition, estimates from different visual field locations were more independent than estimates from the same location. Our results reveal a retinotopic serial dependence in visual numerosity estimates, which may be a mechanism for maintaining the continuity of visual perception in a noisy environment