The AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways and may have therapeutic importance for treating obesity, insulin resistance, type 2 diabetes (T2D), ...non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). Given the ubiquitous expression of AMPK, it has been a challenge to evaluate which tissue types may be most beneficially poised for mediating the positive metabolic effects of AMPK-centered treatments. In this review we evaluate the metabolic phenotypes of transgenic mouse models in which AMPK expression and function have been manipulated, and the impact this has on controlling lipid metabolism, glucose homeostasis, and inflammation. This information may be useful for guiding the development of AMPK-targeted therapeutics to treat chronic metabolic diseases.
Volatility and viscosity are important properties of organic aerosols (OA),
affecting aerosol processes such as formation, evolution, and partitioning of
OA. Volatility distributions of ambient OA ...particles have often been
measured, while viscosity measurements are scarce. We have previously
developed a method to estimate the glass transition temperature (Tg) of
an organic compound containing carbon, hydrogen, and oxygen. Based on
analysis of over 2400 organic compounds including oxygenated organic
compounds, as well as nitrogen- and sulfur-containing organic compounds, we
extend this method to include nitrogen- and sulfur-containing compounds
based on elemental composition. In addition, parameterizations are developed
to predict Tg as a function of volatility and the atomic
oxygen-to-carbon ratio based on a negative correlation between Tg and
volatility. This prediction method of Tg is applied to ambient
observations of volatility distributions at 11 field sites. The
predicted Tg values of OA under dry conditions vary mainly from 290 to 339 K
and the predicted viscosities are consistent with the results of ambient
particle-phase-state measurements in the southeastern US and the Amazonian
rain forest. Reducing the uncertainties in measured volatility distributions
would improve predictions of viscosity, especially at low relative humidity.
We also predict the Tg of OA components identified via positive matrix
factorization of aerosol mass spectrometer (AMS) data. The predicted viscosity of
oxidized OA is consistent with previously reported viscosity of secondary organic aerosols (SOA) derived
from α-pinene, toluene, isoprene epoxydiol (IEPOX), and diesel fuel.
Comparison of the predicted viscosity based on the observed volatility
distributions with the viscosity simulated by a chemical transport model
implies that missing low volatility compounds in a global model can lead to
underestimation of OA viscosity at some sites. The relation between
volatility and viscosity can be applied in the molecular corridor or
volatility basis set approaches to improve OA simulations in chemical
transport models by consideration of effects of particle viscosity in OA
formation and evolution.
Immune-mediated necrotising myopathy (IMNM) is a relatively recently described form of idiopathic inflammatory myopathy (IIM) that is characterised by progressive proximal weakness and few ...extra-muscular manifestations. Prominent myonecrosis, muscle fibre regeneration and a relative paucity of intramuscular lymphocytes are seen histologically. Immunological mechanisms are believed to underpin the pathogenesis, and intense immunotherapy is frequently required. Disease is often severe and neuromuscular recovery may be poor. Recently there has been an impressive international research effort to understand and characterise this emerging condition, although much remains unknown. Significant advances in the field include the discovery of specific autoantibodies, increased understanding of the risk factors, clinical characteristics and treatment options owing to a wealth of observational studies, and the development of novel classification criteria. Herein we review the current evidence regarding the pathophysiology, clinical presentation, histological features and serological profiles associated with this condition. Diagnostic approaches are discussed, including the role of muscle MRI and antibodies targeting 3‑hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and signal-recognition peptide (SRP), and a review of current treatment recommendations is provided.
The Royal Society of Chemistry is committed to investigating and addressing the barriers and biases which face women in the chemical sciences. The cornerstone of this is a thorough analysis of data ...regarding submissions, review and citations for Royal Society of Chemistry journals from January 2014 until July 2018, since the number and impact of publications and citations are an important factor when seeking research funding and for the progression of academic career. We have applied standard statistical techniques to multiple data sources to perform this analysis, and have investigated whether interactions between variables are significant in affecting various outcomes (author gender; reviewer gender; reviewer recommendations and submission outcome) in addition to considering variables individually. By considering several different data sources, we found that a baseline of approximately a third of chemistry researchers are female overall, although this differs considerably with Chemistry sub-discipline. Rather than one dominant bias effect, we observe complex interactions and a gradual trickle-down decrease in this female percentage through the publishing process and each of these female percentages is less than the last: authors of submissions; authors of RSC submissions which are not rejected without peer review; authors of accepted RSC publications; authors of cited articles. The success rate for female authors to progress through each of these publishing stages is lower than that for male authors. There is a decreasing female percentage when progressing through from first authors to corresponding authors to reviewers, reflecting the decreasing female percentage with seniority in Chemistry research observed in the "Diversity landscape of the chemical sciences" report. Highlights and actions from this analysis form the basis of an accompanying report to be released from the Royal Society of Chemistry.
Characterisation of gender differences throughout peer-review publication process as revealed by thorough analysis of Royal Society of Chemistry submissions, publications and citation data.
Growth differentiation factor 15 (GDF15) is a member of the TGFβ superfamily whose expression is increased in response to cellular stress and disease as well as by metformin. Elevations in GDF15 ...reduce food intake and body mass in animal models through binding to glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL) and the recruitment of the receptor tyrosine kinase RET in the hindbrain. This effect is largely independent of other appetite-regulating hormones (for example, leptin, ghrelin or glucagon-like peptide 1). Consistent with an important role for the GDF15-GFRAL signalling axis, some human genetic studies support an interrelationship with human obesity. Furthermore, findings in both mice and humans have shown that metformin and exercise increase circulating levels of GDF15. GDF15 might also exert anti-inflammatory effects through mechanisms that are not fully understood. These unique and distinct mechanisms for suppressing food intake and inflammation makes GDF15 an appealing candidate to treat many metabolic diseases, including obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, cardiovascular disease and cancer cachexia. Here, we review the mechanisms regulating GDF15 production and secretion, GDF15 signalling in different cell types, and how GDF15-targeted pharmaceutical approaches might be effective in the treatment of metabolic diseases.
Bright fluorophores in the near‐infrared and shortwave infrared (SWIR) regions of the electromagnetic spectrum are essential for optical imaging in vivo. In this work, we utilized a 7‐dimethylamino ...flavylium heterocycle to construct a panel of novel red‐shifted polymethine dyes, with emission wavelengths from 680 to 1045 nm. Photophysical characterization revealed that the 1‐ and 3‐methine dyes display enhanced photostability and the 5‐ and 7‐methine dyes exhibit exceptional brightness for their respective spectral regions. A micelle formulation of the 7‐methine facilitated SWIR imaging in mice. This report presents the first polymethine dye designed and synthesized for SWIR in vivo imaging.
Moving beyond the NIR: A series of polymethine dyes containing a 7‐dimethylamino flavylium heterocycle were designed and synthesized. These dyes display distinctly red‐shifted absorption and emission. The flavylium heptamethine dye is a bright shortwave infrared (SWIR) emitter and was employed for in vivo SWIR imaging.
Recently, it has been discovered that the working memory deficits induced by exposure to chronic stress can be prevented by treating stressed animals with minocycline, a putative inhibitor of ...microglial activity. One of the pressing issues that now requires clarification is exactly how exposure to chronic stress modifies microglial morphology, this being a significant issue as microglial morphology is tightly coupled with their function. To examine how chronic stress alters microglial morphology, we digitally reconstructed microglia within the rat medial prefrontal cortex. Our analysis revealed that stress increased the internal complexity of microglia, enhancing ramification (i.e. branching) without altering the overall area occupied by the cell and that this effect was more pronounced in larger cells. We subsequently determined that minocycline treatment largely abolished the pro-ramifying effects of stress. With respect to mechanisms, we could not find any evidence of increased inflammation or neurodegeneration (interleukin-1β, MHC-II, CD68, terminal deoxynucleotidyl transferase dUTP nick end labeling, and activated caspase-3). We did, however, find that chronic stress markedly increased the expression of β1-integrin (CD29), a protein previously implicated in microglial ramification. Together, these findings highlight that increased ramification of microglia may represent an important neurobiological mechanism through which microglia mediate the behavioral effects of chronic psychological stress.
Mitochondrial respiration in plants provides energy for biosynthesis, and its balance with photosynthesis determines the rate of plant biomass accumulation. We describe recent advances in our ...understanding of the mitochondrial respiratory machinery of cells, including the presence of a classical oxidative phosphorylation system linked to the cytosol by transporters, discussed alongside nonphosphorylating (and, therefore, non-energy conserving) bypasses that alter the efficiency of ATP synthesis and play a role in oxidative stress responses in plants. We consider respiratory regulation in the context of the contrasting roles mitochondria play in different tissues, from photosynthetic leaves to nutrient-acquiring roots. We focus on the molecular nature of this regulation at transcriptional and post-transcriptional levels that allow the respiratory apparatus of plants to help shape organ development and the response of plants to environmental stress. We highlight the challenges for future research considering spatial and temporal changes of respiration in response to changing climatic conditions.
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