•Polarized macrophage phenotypes induce cytokine storms and immune paralysis in sepsis.•Macrophage polarization can induce cytokine storm and immune paralysis in sepsis.•Targeted regulation of ...macrophage polarization is a new immunotherapy for sepsis.
Sepsis is a life-threatening clinical syndrome caused by infection. Its pathogenesis is complex and entails coagulation dysfunction, inflammation, and immune disorders. Macrophages are important components of innate and adaptive immunity that are highly heterogeneous and plastic. They can polarize into a multi-dimensional spectrum of phenotypes with different functions relating to immune regulation in response to changes in the microenvironment of specific tissues. We reviewed studies that examined the role of macrophage polarization with a focus on the classical activated (M1-like) and alternative activated (M2-like) macrophages as the two main phenotypes involved in the host immune response to sepsis. A complex regulatory network is involved in the process of macrophage polarization, which is influenced by a variety of signaling molecules, transcription factors, epigenetic modifications, and metabolic reprogramming. M1-like macrophages release large quantities of pro-inflammatory mediators, while M2-like macrophages release large quantities of anti-inflammatory mediators. An imbalance between M1-like and M2-like macrophages induces the occurrence and development of sepsis. Therefore, targeted regulation of the process of macrophage polarization could be a useful approach to normalize the immune balance of the host, offering a new treatment modality for different stages of sepsis.
Bergmann's and Allen's rules were defined to describe macroecological patterns across latitudinal gradients. Bergmann observed a positive association between body size and latitude for endothermic ...species while Allen described shorter appendages as latitude increases. Almost two centuries later, there is still ongoing discussion about these patterns. Temperature, the common variable in these two rules, varies predictably across both latitude and elevation. Although these rules have been assessed extensively in mammals across latitude, particularly in regions with strong seasonality, studies on tropical montane mammals are scarce. We here test for these patterns and assess the variation of several other locomotory, diet-associated, body condition, and thermoregulatory traits across elevation in the Mountain Treeshrew (Tupaia montana) on tropical mountains in Borneo. Based on morphological measurements from both the field and scientific collections, we found a complex pattern: Bergmann's rule was not supported in our tropical mountain system, since skull length, body size, and weight decreased from the lowest elevations (<1000 m) to middle elevations (2000-2500 m), and then increased from middle elevations to highest elevations. Allen's rule was supported for relative tail length, which decreased with elevation, but not for ear and hindfoot length, with the former remaining constant and the latter increasing with elevation. This evidence together with changes in presumed diet-related traits (rostrum length, zygomatic breadth and upper tooth row length) along elevation suggest that selective pressures other than temperature, are playing a more important role shaping the morphological variation across the distribution of the Mountain Treeshrew. Diet, food acquisition, predation pressure, and/or intra- and inter-specific competition, are some of the potential factors driving the phenotypic variation of this study system. The lack of variation in body condition might suggest local adaptation of this species across its elevational range, perhaps due to generalist foraging strategies. Finally, a highly significant temporal effect was detected in several traits but not in others, representing the first phenotypic variation temporal trends described on treeshrews.
This book is the first in a projected series on Evolutionary Cell Biology , the intent of which is to demonstrate the essential role of cellular mechanisms in transforming the genotype into the ...phenotype by transforming gene activity into evolutionary change in morphology. This book — Cells in Evolutionary Biology — evaluates the evolution of cells themselves and the role cells have been viewed to play as agents of change at other levels of biological organization. Chapters explore Darwin’s use of cells in his theory of evolution and how Weismann’s theory of the separation of germ plasm from body cells brought cells to center stage in understanding how acquired changes to cells within generations are not passed on to future generations.
Chapter 7 of this book is freely available as a downloadable Open Access PDF under a Creative Commons Attribution-Non Commercial-No Derivatives 3.0 license. https://s3-us-west-2.amazonaws.com/tandfbis/rt-files/docs/Open+Access+Chapters/9781315155968_oachapter7.pdf
Numerous studies have demonstrated that dispersal is dependent on both disperser phenotype and the local environment. However, there is substantial variability in the observed strength and direction ...of phenotype‐ and environment‐dependent dispersal. This has been hypothesized to be the result of interactive effects among the multiple phenotypic and environmental factors that influence dispersal.
Here, our goal was to test the hypothesis that these interactions are responsible for generating variation in dispersal behaviour.
We achieved these goals by conducting a large, 2‐year, mark–release–recapture study of the backswimmer Notonecta undulata in an array of 36 semi‐natural ponds. We measured the effects of multiple phenotypic (sex and body size) and environmental (population density and sex ratio) factors, on both dispersal probability and dispersal distance.
We found support for the hypothesis that interactive effects influence dispersal and produce variability in phenotype‐ and environment‐dependent dispersal: dispersal probability was dependent on the three‐way interaction between sex, body mass and population density. Small males displayed strong, positive density dependence in their dispersal behaviour, while large males and females overall did not respond strongly to density. Small notonectids, regardless of sex, were more likely to disperse, but this effect was strongest at high population densities. Finally, the distance dispersed by backswimmers was a negative function of population density, a pattern which we hypothesize could be related to: (a) individuals from high and low density patches having different dispersal strategies, or (b) the effect of density on dispersal capacity.
These results suggest that phenotype‐by‐environment interactions strongly influence dispersal. Since phenotype‐ and environment‐dependent dispersal has different consequences for ecological and evolutionary dynamics (e.g. metapopulation persistence and local adaptation) than random dispersal, interactive effects may have wide‐reaching impacts on populations and communities. We therefore argue that more investment should be made into estimating the effects of multiple, interacting factors on dispersal and determining whether similar interactive effects are acting across systems.
Dispersal is central to many topics in ecology including metapopulation persistence and the coexistence of species with competitors and predators. Yet, we lack a full understanding of how dispersal behaviour is shaped by phenotype, the environment, and their interaction. In this paper, the authors estimate the effects of multiple factors on dispersal in a natural context and find support for the hypothesis that interactions among factors are important determinants of dispersal patterns.
Cellular senescence, first described in vitro in 1961, has become a focus for biotech companies that target it to ameliorate a variety of human conditions. Eminently characterized by a permanent ...proliferation arrest, cellular senescence occurs in response to endogenous and exogenous stresses, including telomere dysfunction, oncogene activation and persistent DNA damage. Cellular senescence can also be a controlled programme occurring in diverse biological processes, including embryonic development. Senescent cell extrinsic activities, broadly related to the activation of a senescence-associated secretory phenotype, amplify the impact of cell-intrinsic proliferative arrest and contribute to impaired tissue regeneration, chronic age-associated diseases and organismal ageing. This Review discusses the mechanisms and modulators of cellular senescence establishment and induction of a senescence-associated secretory phenotype, and provides an overview of cellular senescence as an emerging opportunity to intervene through senolytic and senomorphic therapies in ageing and ageing-associated diseases.
Aging leads to increased cellular senescence and is associated with decreased potency of tissue‐specific stem/progenitor cells. Here, we have done an extensive analysis of cardiac progenitor cells ...(CPCs) isolated from human subjects with cardiovascular disease, aged 32–86 years. In aged subjects (>70 years old), over half of CPCs are senescent (p16INK4A, SA‐β‐gal, DNA damage γH2AX, telomere length, senescence‐associated secretory phenotype SASP), unable to replicate, differentiate, regenerate or restore cardiac function following transplantation into the infarcted heart. SASP factors secreted by senescent CPCs renders otherwise healthy CPCs to senescence. Elimination of senescent CPCs using senolytics abrogates the SASP and its debilitative effect in vitro. Global elimination of senescent cells in aged mice (INK‐ATTAC or wild‐type mice treated with D + Q senolytics) in vivo activates resident CPCs and increased the number of small Ki67‐, EdU‐positive cardiomyocytes. Therapeutic approaches that eliminate senescent cells may alleviate cardiac deterioration with aging and restore the regenerative capacity of the heart.
Phytoplankton exist in genetically diverse populations, but are often studied as single lineages (single strains), so that interpreting single-lineage studies relies critically on understanding how ...microbial growth differs with social milieu, defined as the presence or absence of conspecifics. The properties of lineages grown alone often fail to predict the growth of these same lineages in the presence of conspecifics, and this discrepancy points towards an opportunity to improve our understanding of the factors that affect lineage growth rates. We demonstrate that different lineages of a marine picoplankter modulate their maximum lineage growth rate in response to the presence of non-self conspecifics, even when resource competition is effectively absent. This explains why growth rates of lineages in isolation do not reliably predict their growth rates in mixed culture, or the lineage composition of assemblages under conditions of rapid growth. The diversity of growth strategies observed here are consistent with lineage-specific energy allocation that depends on social milieu. Since lineage growth is only one of many traits determining fitness in natural assemblages, we hypothesize that intraspecific variation in growth strategies should be common, with more strategies possible in ameliorated environments that support higher maximum growth rates, such as high CO
for many marine picoplankton.
Senescence is a cellular state in which cells undergo persistent cell cycle arrest in response to nonlethal stress. In the treatment of cancer, senescence induction is a potent method of suppressing ...tumour cell proliferation. In spite of this, senescent cancer cells and adjacent nontransformed cells of the tumour microenvironment can remain metabolically active, resulting in paradoxical secretion of pro‐inflammatory factors, collectively termed the senescence‐associated secretory phenotype (SASP). The SASP plays a critical role in tumorigenesis, affecting numerous processes including invasion, metastasis, epithelial‐to‐mesenchymal transition (EMT) induction, therapy resistance and immunosuppression. With increasing evidence, it is becoming clear that cell type, tissue of origin and the primary cellular stressor are key determinants in how the SASP will influence tumour development and progression, including whether it will be pro‐ or antitumorigenic. In this review, we will focus on recent evidence regarding therapy‐induced senescence (TIS) from anticancer agents, including chemotherapy, radiation, immunotherapy, and targeted therapies, and how each therapy can trigger the SASP, which in turn influences treatment efficacy. We will also discuss novel pharmacological manipulation of senescent cancer cells and the SASP, which offers an exciting and contemporary approach to cancer therapeutics. With future research, these adjuvant options may help to mitigate many of the negative side effects and protumorigenic roles that are currently associated with TIS in cancer.
In response to therapy or other stimuli, cancer cells can undergo cellular senescence, a stress response leading to cell cycle arrest. An unintended consequence of cellular senescence is a perturbed, pro‐inflammatory cancer cell secretome, the senescence‐associated secretory phenotype (SASP). Here, we explore the role of SASP in promoting tumorigenesis and treatment resistance, with particular focus on mechanisms of therapy‐induced senescence (TIS).
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