Macrophages are found in normal kidney and in increased numbers in diseased kidney, where they act as key players in renal injury, inflammation, and fibrosis. Macrophages are highly heterogeneous ...cells and exhibit distinct phenotypic and functional characteristics in response to various stimuli in the local microenvironment in different types of kidney disease. In kidney tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce pro-inflammatory macrophages, which contribute to further tissue injury, inflammation, and subsequent fibrosis. Apoptotic cells and anti-inflammatory factors in post-inflammatory tissues induced anti-inflammatory macrophages, which can mediate kidney repair and regeneration. This review summarizes the role of macrophages with different phenotypes in kidney injury, inflammation, and fibrosis in various acute and chronic kidney diseases. Understanding alterations of kidney microenvironment and the factors that control the phenotype and functions of macrophages may offer an avenue for the development of new cellular and cytokine/growth factor-based therapies as alternative treatment options for patients with kidney disease.
Sierra Leone came to world attention in the 1990s when a catastrophic civil war linked to the diamond trade was reported globally. This fleeting and particular interest, however, obscured two crucial ...processes in this small West African state. On the one hand, while the civil war was momentous, brutal and affected all Sierra Leoneans, it was also just one element in the long and faltering attempt to build a nation and state given the country's immensely problematic pre-colonial and British colonial legacies. On the other, the aftermath of the war precipitated a huge international effort to construct a 'liberal peace', with mixed results, and thus made Sierra Leone a laboratory for post-Cold War interventions. Sierra Leone examines 225 years of its history and fifty years of independence, placing state- society relations at the centre of an original and revealing investigation of those who have tried to rule or change Sierra Leone and its inhabitants and the responses engendered. It interweaves the historical narrative with sketches of politicians, anecdotes, the landscape and environment and key turning-points, alongside theoretical and other comparisons with the rest of Africa. It is a new contribution to the debate for those who already know Sierra Leone and a solid point of entry for those who wish to know.
Inferring species interactions from co-occurrence data is one of the most controversial tasks in community ecology. One difficulty is that a single pairwise interaction can ripple through an ...ecological network and produce surprising indirect consequences. For example, the negative correlation between two competing species can be reversed in the presence of a third species that outcompetes both of them. Here, I apply models from statistical physics, called Markov networks or Markov random fields, that can predict the direct and indirect consequences of any possible species interaction matrix. Interactions in these models can be estimated from observed co-occurrence rates via maximum likelihood, controlling for indirect effects. Using simulated landscapes with known interactions, I evaluated Markov networks and six existing approaches. Markov networks consistently outperformed the other methods, correctly isolating direct interactions between species pairs even when indirect interactions or abiotic factors largely overpowered them. Two computationally efficient approximations, which controlled for indirect effects with partial correlations or generalized linear models, also performed well. Null models showed no evidence of being able to control for indirect effects, and reliably yielded incorrect inferences when such effects were present.
There are relatively few publications that assess capacity decline in enough commercial cells to quantify cell-to-cell variation, but those that do show a surprisingly wide variability. Capacity ...curves cross each other often, a challenge for efforts to measure the state of health and predict the remaining useful life (RUL) of individual cells. We analyze capacity fade statistics for 24 commercial pouch cells, providing an estimate for the time to 5% failure. Our data indicate that RUL predictions based on remaining capacity or internal resistance are accurate only once the cells have already sorted themselves into “better” and “worse” ones. Analysis of our failure data, using maximum likelihood techniques, provide uniformly good fits for a variety of definitions of failure with normal and with 2- and 3-parameter Weibull probability density functions, but we argue against using a 3-parameter Weibull function for our data. pdf fitting parameters appear to converge after about 15 failures, although business objectives should ultimately determine whether data from a given number of batteries provides sufficient confidence to end lifecycle testing. Increased efforts to make batteries with more consistent lifetimes should lead to improvements in battery cost and safety.
•Very wide spread in capacity fade for 24 nominally identical pouch cells.•Failure data fit with 3 different functions, 5 definitions of failure.•Testing should end when desired confidence intervals are reached.
Tissue macrophages are crucial players in homeostasis, inflammation, and immunity. They are characterized by heterogeneity and plasticity, due to which they display a continuum of phenotypes with ...M1/M2 presenting 2 extremes of this continuum. M2 macrophages are usually termed in the literature as anti-inflammatory and wound healing. Substantial progress has been made in elucidating the biology of M2 macrophages and their potential for clinical translation. In this review we discuss the current state of knowledge in M2 macrophage research with an emphasis on kidney disease. We explore their therapeutic potential and the challenges in using them as cellular therapies. Some new regulators that shape macrophage polarization and potential areas for future research are also examined.
Macrophages in Renal Disease YIPING WANG; HARRIS, David C. H
Journal of the American Society of Nephrology,
2011, 2011-Jan, 2011-01-00, 20110101, Volume:
22, Issue:
1
Journal Article
Peer reviewed
Open access
Macrophages have heterogeneous phenotypes as they exercise their twofold role in the development and recovery of renal diseases. Some subpopulations of macrophages (M1) have a pathogenic function in ...renal inflammation, making them a logical target for elimination. Alternatively, M2 macrophage subpopulations resolve inflammation and repair injury, making them a potential therapeutic tool against renal injury. Here, we summarize recent findings regarding macrophage plasticity, and the various strategies for targeting or utilizing macrophages to treat renal disease. We highlight, in particular, the potential of renoprotective M2 macrophages to resolve inflammation and repair the kidney.
Human adipose tissue is an ideal autologous source of mesenchymal stem cells (MSCs) for various regenerative medicine and tissue engineering strategies. Aged patients are one of the primary target ...populations for many promising applications. It has long been known that advanced age is negatively correlated with an organism's reparative and regenerative potential, but little and conflicting information is available about the effects of age on the quality of human adipose tissue derived MSCs (hAT-MSCs).
To study the influence of age, the expansion and in vitro differentiation potential of hAT-MSCs from young (<30 years), adult (35-50 years) and aged (>60 years) individuals were investigated. MSCs were characterized for expression of the genes p16(INK4a) and p21 along with measurements of population doublings (PD), superoxide dismutase (SOD) activity, cellular senescence and differentiation potential.
Aged MSCs displayed senescent features when compared with cells isolated from young donors, concomitant with reduced viability and proliferation. These features were also associated with significantly reduced differentiation potential in aged MSCs compared to young MSCs.
In conclusion, advancing age negatively impacts stem cell function and such age related alterations may be detrimental for successful stem cell therapies.
Abstract
Several cell-surface receptors for neurotoxic forms of amyloid-β (Aβ) have been described, but their molecular interactions with Aβ assemblies and their relative contributions to mediating ...Alzheimer’s disease pathology have remained uncertain. Here, we used super-resolution microscopy to directly visualize Aβ-receptor interactions at the nanometer scale. We report that one documented Aβ receptor, PrP
C
, specifically inhibits the polymerization of Aβ fibrils by binding to the rapidly growing end of each fibril, thereby blocking polarized elongation at that end. PrP
C
binds neurotoxic oligomers and protofibrils in a similar fashion, suggesting that it may recognize a common, end-specific, structural motif on all of these assemblies. Finally, two other Aβ receptors, FcγRIIb and LilrB2, affect Aβ fibril growth in a manner similar to PrP
C
. Our results suggest that receptors may trap Aβ oligomers and protofibrils on the neuronal surface by binding to a common molecular determinant on these assemblies, thereby initiating a neurotoxic signal.
Background In the context of clinical research, investigators have historically selected the outcomes that they consider to be important, but these are often discordant with patients’ priorities. ...Efforts to define and report patient-centered outcomes are gaining momentum, though little work has been done in nephrology. We aimed to identify patient and caregiver priorities for outcomes in hemodialysis. Study Design Nominal group technique. Setting & Participants Patients on hemodialysis therapy and their caregivers were purposively sampled from 4 dialysis units in Australia (Sydney and Melbourne) and 7 dialysis units in Canada (Calgary). Methodology Identification and ranking of outcomes. Analytical Approach Mean rank score (of 10) for top 10 outcomes and thematic analysis. Results 82 participants (58 patients, 24 caregivers) aged 24 to 87 (mean, 58.4) years in 12 nominal groups identified 68 outcomes. The 10 top-ranked outcomes were fatigue/energy (mean rank score, 4.5), survival (defined by patients as resilience and coping; 3.7), ability to travel (3.6), dialysis-free time (3.3), impact on family (3.2), ability to work (2.5), sleep (2.3), anxiety/stress (2.1), decrease in blood pressure (2.0), and lack of appetite/taste (1.9). Mortality ranked only 14th and was not regarded as the complement of survival. Caregivers ranked mortality, anxiety, and depression higher than patients, whereas patients ranked ability to work higher. Four themes underpinned their rankings: living well, ability to control outcomes, tangible and experiential relevance, and severity and intrusiveness. Limitations Only English-speaking participants were eligible. Conclusions Although trials in hemodialysis have typically focused on outcomes such as death, adverse events, and biological markers, patients tend to prioritize outcomes that are more relevant to their daily living and well-being. Researchers need to consider interventions that are likely to improve these outcomes and measure and report patient-relevant outcomes in trials, and clinicians may become more patient-orientated by using these outcomes in their clinical encounters.
Hutchinson's n‐dimensional hypervolume concept underlies many applications in contemporary ecology and evolutionary biology. Estimating hypervolumes from sampled data has been an ongoing challenge ...due to conceptual and computational issues.
We present new algorithms for delineating the boundaries and probability density within n‐dimensional hypervolumes. The methods produce smooth boundaries that can fit data either more loosely (Gaussian kernel density estimation) or more tightly (one‐classification via support vector machine). Further, the algorithms can accept abundance‐weighted data, and the resulting hypervolumes can be given a probabilistic interpretation and projected into geographic space.
We demonstrate the properties of these methods on a large dataset that characterises the functional traits and geographic distribution of thousands of plants. The methods are available in version ≥2.0.7 of the hypervolume r package.
These new algorithms provide: (i) a more robust approach for delineating the shape and density of n‐dimensional hypervolumes; (ii) more efficient performance on large and high‐dimensional datasets; and (iii) improved measures of functional diversity and environmental niche breadth.
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