Fcgamma receptor-mediated phagocytosis in macrophages lacking the Src family tyrosine kinases Hck, Fgr, and Lyn.

Macrophage Fcgamma receptors (FcgammaRs) mediate the uptake and destruction of antibody-coated viruses, bacteria, and parasites. We examined FcgammaR signaling and phagocytic function in bone marrow-derived macrophages from mutant mice lacking the major Src family kinases expressed in these cells, Hck, Fgr, and Lyn. Many FcgammaR-induced functional responses and signaling events were diminished or delayed in these macrophages, including immunoglobulin (Ig)G-coated erythrocyte phagocytosis, respiratory burst, actin cup formation, and activation of Syk, phosphatidylinositol 3-kinase, and extracellular signal-regulated kinases 1 and 2. Significant reduction of IgG-dependent phagocytosis was not seen in hck(-)(/)-fgr(-)(/)- or lyn(-)(/)- cells, although the single mutant lyn(-)(/)- macrophages did manifest signaling defects. Thus, Src family kinases clearly have roles in two events leading to FcgammaR-mediated phagocytosis, one involving initiation of actin polymerization and the second involving activation of Syk and subsequent internalization. Since FcgammaR-mediated phagocytosis did occur at modest levels in a delayed fashion in triple mutant macrophages, these Src family kinases are not absolutely required for uptake of IgG-opsonized particles

Access Mars: Assessing Cave Capabilities Establishing Specific Solutions: Final Report

The human race has evolved, grown and expanded through the exploration of Earth. After initial steps on the Moon, our next challenge is to explore the solar system. Mars shows potential for both scientific discovery and future human settlement, and so is a prime candidate for the next leap of human exploration. Such a bold endeavor will be a driver for an unprecedented worldwide cooperative effort and the catalyst for a new era of international, intercultural and interdisciplinary human relations. Scientific and technological progress will also accelerate as mankind is ushered into a new era of space exploration. Currently proposed Mars missions have identified a number of challenges such as high levels of radiation, harsh climate and limited launch windows. Recently discovered lava tubes on Mars present potential solutions to some of these issues, but raise a variety of intriguing new challenges. These encompass not only technological and engineering considerations, but also legal, ethical and societal issues such as planetary protection and crew safety. This report assesses the feasibility of overcoming such challenges through the exploitation of Mars caves. This report reviews existing reference missions and identifies areas of further research essential for adapting mission architectures to utilize caves. Cave suitability is considered with respect to size, type, location and their potential to mitigate hazards. They are also assessed with respect to their potential for scientific work adhering to astrobiology guidelines and the search for extra-terrestrial life. This report compares surface and subsurface habitat options. Engineering challenges arising from the use of caves are addressed along with proposals for alternate architecture solutions. Mission analysis is conducted to determine the transit trajectory and define two possible mission scenarios with surface crews of 6 and 12 crew members. Different types of habitat are described and evaluated. An architecture for precursor missions is provided utilizing surface rovers, cargo delivery rovers and pressurized human transport vehicles. The implications of sub-surface operations on thermal control, communications and power systems are investigated with recommendations given. Crew selection, training methods and life support system solutions are also addressed. Literature suggests a low radiation environment within Martian caves, allowing for extended duration missions. The ACCESS Mars Team concludes that using lava tubes as human habitats is not merely a viable habitat solution for a Mars expedition, but also potentially more beneficial than proposed surface solutions

A Study of Brain Networks Associated with Swallowing Using Graph-Theoretical Approaches

Functional connectivity between brain regions during swallowing tasks is still not well understood. Understanding these complex interactions is of great interest from both a scientific and a clinical perspective. In this study, functional magnetic resonance imaging (fMRI) was utilized to study brain functional networks during voluntary saliva swallowing in twenty-two adult healthy subjects (all females, 23.1±1.52 years of age). To construct these functional connections, we computed mean partial correlation matrices over ninety brain regions for each participant. Two regions were determined to be functionally connected if their correlation was above a certain threshold. These correlation matrices were then analyzed using graph-theoretical approaches. In particular, we considered several network measures for the whole brain and for swallowing-related brain regions. The results have shown that significant pairwise functional connections were, mostly, either local and intra-hemispheric or symmetrically inter-hemispheric. Furthermore, we showed that all human brain functional network, although varying in some degree, had typical small-world properties as compared to regular networks and random networks. These properties allow information transfer within the network at a relatively high efficiency. Swallowing-related brain regions also had higher values for some of the network measures in comparison to when these measures were calculated for the whole brain. The current results warrant further investigation of graph-theoretical approaches as a potential tool for understanding the neural basis of dysphagia. © 2013 Luan et al

25 years of epidermal stem cell research.

This is a chronicle of concepts in the field of epidermal stem cell biology and a historic look at their development over time. The past 25 years have seen the evolution of epidermal stem cell science, from first fundamental studies to a sophisticated science. The study of epithelial stem cell biology was aided by the ability to visualize the distribution of stem cells and their progeny through lineage analysis studies. The excellent progress we have made in understanding epidermal stem cell biology is discussed in this article. The challenges we still face in understanding epidermal stem cells include defining molecular markers for stem and progenitor sub-populations, determining the locations and contributions of the different stem cell niches, and mapping regulatory pathways of epidermal stem cell proliferation and differentiation. However, our rapidly evolving understanding of epidermal stem cells has many potential uses that promise to translate into improved patient therapy

Critical care bed capacity in Asian countries and regions

Objective: To assess the number of adult critical care beds in Asian countries and regions in relation to population size. Design: Cross-sectional observational study. Setting: Twenty-three Asian countries and regions, covering 92.1% of the continent’s population. Participants: Ten low-income and lower-middle–income economies, five upper-middle–income economies, and eight high-income economies according to the World Bank classification. Interventions: Data closest to 2017 on critical care beds, including ICU and intermediate care unit beds, were obtained through multiple means, including government sources, national critical care societies, colleges, or registries, personal contacts, and extrapolation of data. Measurements and Main Results: Cumulatively, there were 3.6 critical care beds per 100,000 population. The median number of critical care beds per 100,000 population per country and region was significantly lower in low- and lower-middle–income economies (2.3; interquartile range, 1.4–2.7) than in upper-middle–income economies (4.6; interquartile range, 3.5–15.9) and high-income economies (12.3; interquartile range, 8.1–20.8) (p = 0.001), with a large variation even across countries and regions of the same World Bank income classification. This number was independently predicted by the World Bank income classification on multivariable analysis, and significantly correlated with the number of acute hospital beds per 100,000 population (r2 = 0.19; p = 0.047), the universal health coverage service coverage index (r2 = 0.35; p = 0.003), and the Human Development Index (r2 = 0.40; p = 0.001) on univariable analysis. Conclusions: Critical care bed capacity varies widely across Asia and is significantly lower in low- and lower-middle–income than in upper-middle–income and high-income countries and regions

The association between retinal vascular geometry changes and diabetic retinopathy and their role in prediction of progression: an exploratory study

Background: The study describes the relationship of retinal vascular geometry (RVG) to severity of diabetic retinopathy (DR), and its predictive role for subsequent development of proliferative diabetic retinopathy (PDR). Methods. The research project comprises of two stages. Firstly, a comparative study of diabetic patients with different grades of DR. (No DR: Minimal non-proliferative DR: Severe non-proliferative DR: PDR) (10:10: 12: 19). Analysed RVG features including vascular widths and branching angles were compared between patient cohorts. A preliminary statistical model for determination of the retinopathy grade of patients, using these features, is presented. Secondly, in a longitudinal predictive study, RVG features were analysed for diabetic patients with progressive DR over 7 years. RVG at baseline was examined to determine risk for subsequent PDR development. Results: In the comparative study, increased DR severity was associated with gradual vascular dilatation (p = 0.000), and widening of the bifurcating angle (p = 0.000) with increase in smaller-child-vessel branching angle (p = 0.027). Type 2 diabetes and increased diabetes duration were associated with increased vascular width (p = <0.05 In the predictive study, at baseline, reduced small-child vascular width (OR = 0.73 (95 CI 0.58-0.92)), was predictive of future progression to PDR. Conclusions: The study findings suggest that RVG alterations can act as novel markers indicative of progression of DR severity and establishment of PDR. RVG may also have a potential predictive role in determining the risk of future retinopathy progression. © 2014 Habib et al.; licensee BioMed Central Ltd