Functions of S100 proteins Donato, R; Cannon, B R; Sorci, G ...
Current molecular medicine
13, Številka:
1
Journal Article
Recenzirano
The S100 protein family consists of 24 members functionally distributed into three main subgroups: those that only exert intracellular regulatory effects, those with intracellular and extracellular ...functions and those which mainly exert extracellular regulatory effects. S100 proteins are only expressed in vertebrates and show cell-specific expression patterns. In some instances, a particular S100 protein can be induced in pathological circumstances in a cell type that does not express it in normal physiological conditions. Within cells, S100 proteins are involved in aspects of regulation of proliferation, differentiation, apoptosis, Ca2+ homeostasis, energy metabolism, inflammation and migration/invasion through interactions with a variety of target proteins including enzymes, cytoskeletal subunits, receptors, transcription factors and nucleic acids. Some S100 proteins are secreted or released and regulate cell functions in an autocrine and paracrine manner via activation of surface receptors (e.g. the receptor for advanced glycation end-products and toll-like receptor 4), G-protein-coupled receptors, scavenger receptors, or heparan sulfate proteoglycans and N-glycans. Extracellular S100A4 and S100B also interact with epidermal growth factor and basic fibroblast growth factor, respectively, thereby enhancing the activity of the corresponding receptors. Thus, extracellular S100 proteins exert regulatory activities on monocytes/macrophages/microglia, neutrophils, lymphocytes, mast cells, articular chondrocytes, endothelial and vascular smooth muscle cells, neurons, astrocytes, Schwann cells, epithelial cells, myoblasts and cardiomyocytes, thereby participating in innate and adaptive immune responses, cell migration and chemotaxis, tissue development and repair, and leukocyte and tumor cell invasion.
Ethiopia's economy is dominated by agriculture which is mainly rain-fed and subsistence. Climate change is expected to have an adverse impact particularly on crop production. Previous studies have ...shown large discrepancies in the magnitude and sometimes in the direction of the impact on crop production. We assessed the impact of climate change on growth and yield of maize and wheat in Ethiopia using a multi-crop model ensemble. The multi-model ensemble (n = 48) was set up using the agroecosystem modelling framework Expert-N. The framework is modular which facilitates combining different submodels for plant growth and soil processes. The multi-model ensemble was driven by climate change projections representing the mid of the century (2021-2050) from ten contrasting climate models downscaled to finer resolution. The contributions of different sources of uncertainty in crop yield prediction were quantified. The sensitivity of crop yield to elevated CO2, increased temperature, changes in precipitations and N fertilizer were also assessed. Our results indicate that grain yields were very sensitive to changes in CO2, temperature and N fertilizer amounts where the responses were higher for wheat than maize. The response to change in precipitation was weak, which we attribute to the high water holding capacity of the soils due to high organic carbon contents at the study sites. This may provide the sufficient buffering capacity for extended time periods with low amounts of precipitation. Under the changing climate, wheat productivity will be a major challenge with a 36 to 40% reduction in grain yield by 2050 while the impact on maize was modest. A major part of the uncertainty in the projected impact could be attributed to differences in the crop growth models. A considerable fraction of the uncertainty could also be traced back to different soil water dynamics modeling approaches in the model ensemble, which is often ignored. Uncertainties varied among the studied crop species and cultivars as well. The study highlights significant impacts of climate change on wheat yield in Ethiopia whereby differences in crop growth models causes the large part of the uncertainties.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have ...emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings.
A “switch” from oxidative phosphorylation (OXPHOS) to aerobic glycolysis is a hallmark of T cell activation and is thought to be required to meet the metabolic demands of proliferation. However, why ...proliferating cells adopt this less efficient metabolism, especially in an oxygen-replete environment, remains incompletely understood. We show here that aerobic glycolysis is specifically required for effector function in T cells but that this pathway is not necessary for proliferation or survival. When activated T cells are provided with costimulation and growth factors but are blocked from engaging glycolysis, their ability to produce IFN-γ is markedly compromised. This defect is translational and is regulated by the binding of the glycolysis enzyme GAPDH to AU-rich elements within the 3′ UTR of IFN-γ mRNA. GAPDH, by engaging/disengaging glycolysis and through fluctuations in its expression, controls effector cytokine production. Thus, aerobic glycolysis is a metabolically regulated signaling mechanism needed to control cellular function.
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•T cells do not require aerobic glycolysis to fuel proliferation or survival•Glycolysis is specifically required for effector cytokine production in T cells•When not engaged in glycolysis, GAPDH binds to cytokine mRNA•Changes in available GAPDH regulate cytokine mRNA translation
Contrary to previous understanding, activated T cells switch from oxidative phosphorylation to aerobic glycolysis not to promote proliferation but instead to augment the production of the antimicrobial protein IFN-γ, which is regulated by the glycolytic enzyme GAPDH.
For a future sustainable hydrogen economy, the electrocatalysis of hydrogen oxidation/evolution reactions (HOR/HER) needs to be better understood. In order to describe the strong alteration of ...HOR/HER rates on platinum group metals (PGM) in acidic and alkaline media, at least two prominent descriptors based on a Pt-H
ad
binding energy model and a bifunctional model are frequently discussed in the literature. A clear discrimination of these both descriptors for PGM-based multi-metallic materials, yet, remains a critical challenge. To solve this dilemma, we have made use of the oxophilic and structural properties of cobalt atoms in Pt-based nano-materials to tune their catalytic HOR performance in alkaline media. More precisely, we have designed Pt
x
Co
1−
x
nanoparticles with various structural motifs. Remarkably, the surface rearrangement of Pt
x
Co
1−
x
nanoparticles along the uniform alloy, Pt-rich shell, and Co-segregated core-shell motifs is controlled by the electrochemical environment. To identify the elemental distribution of Co and Pt atoms, a new descriptor is presented in this work, the so-called
Q
(Hupd)/
Q
(Co
z
+
) ratio. The coverage of OH
ad
species can be controlled by the coverage of oxophilic Co surface atoms to investigate the bifunctional mechanism on the HOR kinetics in alkaline media. Thus, we are able to correlate the HOR exchange current densities with tuneable Co coverage on the particle surface to mimic
e.g.
the coverage of "Co(hydr)oxide clusters". On the other hand, the strain effect to modify the Pt-H
ad
binding energy is solely investigated on a Pt-rich shell induced by a Co-rich particle core. Despite the separation of these critical model parameters, cobalt as an oxophilic component strongly bonds OH
ad
species at the bimetallic particle surface and modifies the HOR kinetics. In contrast, the induced lattice strain in the Pt-enriched shell of dealloyed core-shell nanoparticles leads to an increase of the Pt surface area-based specific exchange current density
j
0
spec
by a factor of ∼2 compared to pure Pt. Based on our results, we provide deeper insights into the kinetics and mechanism of the HOR on Pt
x
Co
1−
x
catalysts with different structural nanoparticle motifs in an alkaline environment.
Bifunctional mechanism and Pt-H
ad
binding energy can be discriminated by a new descriptor,
Q
(Hupd) :
Q
(Co
z
+
) ratio to tailor the HOR activity on a Pt-Co surface in alkaline environment.
Cancer is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of standard anticancer therapies. The ketogenic ...diet, a high-fat, low-carbohydrate diet with adequate amounts of protein, appears to sensitize most cancers to standard treatment by exploiting the reprogramed metabolism of cancer cells, making the diet a promising candidate as an adjuvant cancer therapy.
To critically evaluate available preclinical and clinical evidence regarding the ketogenic diet in the context of cancer therapy. Furthermore, we highlight important mechanisms that could explain the potential antitumor effects of the ketogenic diet.
The ketogenic diet probably creates an unfavorable metabolic environment for cancer cells and thus can be regarded as a promising adjuvant as a patient-specific multifactorial therapy. The majority of preclinical and several clinical studies argue for the use of the ketogenic diet in combination with standard therapies based on its potential to enhance the antitumor effects of classic chemo- and radiotherapy, its overall good safety and tolerability and increase in quality of life. However, to further elucidate the mechanisms of the ketogenic diet as a therapy and evaluate its application in clinical practice, more molecular studies as well as uniformly controlled clinical trials are needed.
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•Ketogenic diets (KDs) can enhance the efficacy of classical antitumor therapies.•Effect of KDs on proliferation is tumor type dependent.•Application of KDs to cancer patients is generally well tolerated.•Low-carbohydrate and KDs increase quality of life of cancer patients.•More standardized studies are needed before KDs can be advised for cancer patients.
Background
Damage control surgery is a management sequence initiated to reduce the risk of death in severely injured patients presenting with physiological derangement. Damage control principles have ...emerged as an approach in non‐trauma abdominal emergencies in order to reduce mortality compared with primary definitive surgery.
Methods
A PubMed/MEDLINE literature review was conducted of data available over the past decade (up to August 2013) to gain information on current understanding of damage control surgery for abdominal surgical emergencies. Future directions for research are discussed.
Results
Damage control surgery facilitates a strategy for life‐saving intervention for critically ill patients by abbreviated laparotomy with subsequent reoperation for delayed definitive repair after physiological resuscitation. The six‐phase strategy (including damage control resuscitation in phase 0) is similar to that for severely injured patients, although non‐trauma indications include shock from uncontrolled haemorrhage or sepsis. Minimal evidence exists to validate the benefit of damage control surgery in general surgical abdominal emergencies. The collective published experience over the past decade is limited to 16 studies including a total of 455 (range 3–99) patients, of which the majority are retrospective case series. However, the concept has widespread acceptance by emergency surgeons, and appears a logical extension from pathophysiological principles in trauma to haemorrhage and sepsis. The benefits of this strategy depend on careful patient selection. Damage control surgery has been performed for a wide range of indications, but most frequently for uncontrolled bleeding during elective surgery, haemorrhage from complicated gastroduodenal ulcer disease, generalized peritonitis, acute mesenteric ischaemia and other sources of intra‐abdominal sepsis.
Conclusion
Damage control surgery is employed in a wide range of abdominal emergencies and is an increasingly recognized life‐saving tactic in emergency surgery performed on physiologically deranged patients.
Bail‐out option when patient in extremis
Intestinal dysbiosis has been associated with acute gastrointestinal GvHD and poor outcome following allogeneic stem cell transplantation (ASCT). To assess the effect of a switch in 2012 from ...ciprofloxacin/metronidazole to rifaximin for gut decontamination on intestinal microbiota composition and ASCT outcome, we retrospectively analyzed 394 patients receiving ASCT from September 2008 through June 2015. In 131 and 90 patients, respectively, urinary 3-indoxyl sulfate levels and intestinal enterococcal load were measured before conditioning and weekly within the first 28 days after ASCT. The use of rifaximin correlated with lower enterococcal positivity (6.9 vs 21.9%, P=0.05) and higher urinary 3-indoxyl sulfate concentrations (10.5 vs 4.6 μmoL/mmoL crea, P<0.001) after ASCT. Patients on rifaximin showed lower 1-year transplant-related mortality (P=0.04) and higher overall survival (P=0.008). Treatment of infectious complications with systemic antibiotics did not abrogate the beneficial effects of rifaximin on intestinal microbiota composition in the early course of ASCT and outcome. The data underscore the importance of maintaining a diverse population of symbiotic and mutualistic bacteria in the gut on ASCT outcome.
We have developed a biomechanical energy harvester that generates electricity during human walking with little extra effort. Unlike conventional human-powered generators that use positive muscle ...work, our technology assists muscles in performing negative work, analogous to regenerative braking in hybrid cars, where energy normally dissipated during braking drives a generator instead. The energy harvester mounts at the knee and selectively engages power generation at the end of the swing phase, thus assisting deceleration of the joint. Test subjects walking with one device on each leg produced an average of 5 watts of electricity, which is about 10 times that of shoe-mounted devices. The cost of harvesting--the additional metabolic power required to produce 1 watt of electricity--is less than one-eighth of that for conventional human power generation. Producing substantial electricity with little extra effort makes this method well-suited for charging powered prosthetic limbs and other portable medical devices.
Psychosocial stress contributes to the development of anxiety and depression. Recent clinical studies have reported increased inflammatory leukocytes in circulation of individuals with stress-related ...psychiatric disorders. Parallel to this, our work in mice shows that social stress causes release of inflammatory monocytes into circulation. In addition, social stress caused the development of prolonged anxiety that was dependent on inflammatory monocytes in the brain. Therefore, we hypothesize that chronic stress drives the production of inflammatory monocytes that are actively recruited to the brain by microglia, and these monocytes augment neuroinflammatory signaling and prolong anxiety. Here we show that repeated social defeat stress in mice activated threat appraisal centers in the brain that spatially coincided with microglial activation and endothelial facilitation of monocyte recruitment. Moreover, microglial depletion with a CSF1R antagonist prior to stress prevented the recruitment of monocytes to the brain and abrogated the development of anxiety. Cell-specific transcriptional profiling revealed that microglia selectively enhanced CCL2 expression, while monocytes expressed the pro-inflammatory cytokine interleukin-1β (IL-1β). Consistent with these profiles, the recruited inflammatory monocytes with stress adhered to IL-1R1
neurovascular endothelial cells and this interaction was blocked by microglial depletion. Furthermore, disruption of IL-1β signaling by caspase-1
specifically within bone marrow-derived cells revealed that monocytes promoted anxiogenesis through stimulation of neurovascular IL-1R1 by IL-1β. Collectively, the development of anxiety during stress was caused by microglial recruitment of IL-1β-producing monocytes, which stimulated brain endothelial IL-1R1. Thus, monocyte IL-1β production represents a novel mechanism that underlies behavioral complications associated with stress-related psychiatric disorders.
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