Summary
One decade has passed since seminal publications described macrophage infiltration into adipose tissue (AT) as a key contributor to inflammation and obesity‐related insulin resistance. ...Currently, a PubMed search for ‘adipose tissue inflammation’ reveals over 3500 entries since these original reports. We now know that resident macrophages in lean AT are alternatively activated, M2‐like, and play a role in AT homeostasis. In contrast, the macrophages in obese AT are dramatically increased in number and are predominantly classically activated, M1‐like, and promote inflammation and insulin resistance. Mediators of AT macrophage (ATM) phenotype include adipokines and fatty acids secreted from adipocytes as well as cytokines secreted from other immune cells in AT. There are several mechanisms that could explain the large increase in ATMs in obesity. These include recruitment‐dependent mechanisms such as adipocyte death, chemokine release, and lipolysis of fatty acids. Newer evidence also points to recruitment‐independent mechanisms such as impaired apoptosis, increased proliferation, and decreased egress. Although less is known about the homeostatic function of M2‐like resident ATMs, recent evidence suggests roles in AT expansion, thermoregulation, antigen presentation, and iron homeostasis. The field of immunometabolism has come a long way in the past decade, and many exciting new discoveries are bound to be made in the coming years that will expand our understanding of how AT stands at the junction of immune and metabolic co‐regulation.
While there is now an established recognition of microplastic pollution in the oceans, and the detrimental effects this may have on marine animals, the ocean depth at which such contamination is ...ingested by organisms has still not been established. Here, we detect the presence of ingested microplastics in the hindguts of Lysianassoidea amphipod populations, in six deep ocean trenches from around the Pacific Rim (Japan, Izu-Bonin, Mariana, Kermadec, New Hebrides and the Peru-Chile trenches), at depths ranging from 7000 m to 10 890 m. This illustrates that microplastic contaminants occur in the very deepest reaches of the oceans. Over 72% of individuals examined (65 of 90) contained at least one microparticle. The number of microparticles ingested per individual across all trenches ranged from 1 to 8. The mean and standard error of microparticles varied per trench, from 0.9 ± 0.4 (New Hebrides Trench) to 3.3 ± 0.7 (Mariana Trench). A subsample of microfibres and fragments analysed using FTIR were found to be a collection of plastic and synthetic materials (Nylon, polyethylene, polyamide, polyvinyl alcohol, polyvinylchloride, often with inorganic filler material), semi-synthetic (rayon and lyocell) and natural fibre (ramie). Notwithstanding, this study reports the deepest record of microplastic ingestion, indicating that anthropogenic debris is bioavailable to organisms at some of the deepest locations in the Earth's oceans.
Pioneering electron microscopy studies defined two primary populations of ribosomes in eukaryotic cells: one freely dispersed through the cytoplasm and the other bound to the surface of the ...endoplasmic reticulum (ER). Subsequent investigations revealed a specialized function for each population, with secretory and integral membrane protein-encoding mRNAs translated on ER-bound ribosomes, and cytosolic protein synthesis was widely attributed to free ribosomes. Recent findings have challenged this view, and transcriptome-scale studies of mRNA distribution and translation have now demonstrated that ER-bound ribosomes also function in the translation of a large fraction of mRNAs that encode cytosolic proteins. These studies suggest a far more expansive role for the ER in transcriptome expression, where membrane and secretory protein synthesis represents one element of a multifaceted and dynamic contribution to post-transcriptional gene expression.
Macrophages comprise a majority of the resident immune cells in adipose tissue (AT) and regulate both tissue homeostasis in the lean state and metabolic dysregulation in obesity. Since the AT ...environment rapidly changes based upon systemic energy status, AT macrophages (ATMs) must adapt phenotypically and metabolically. There is a distinct dichotomy in the polarization and bioenergetics of in vitro models, with M2 macrophages utilizing oxidative phosphorylation (OX PHOS) and M1 macrophages utilizing glycolysis. Early studies suggested differential polarization of ATMs, with M2‐like macrophages predominant in lean AT and M1‐like macrophages in obese AT. However, recent studies show that the phenotypic plasticity of ATMs is far more complicated, which is also reflected in their bioenergetics. Multiple ATM populations exist along the M2 to M1 continuum and appear to utilize both glycolysis and OX PHOS in obesity. The significance of the dual fuel bioenergetics is unclear and may be related to an intermediate polarization, their buffering capacity, or the result of a mixed population of distinct polarized ATMs. Recent evidence also suggests that ATMs of lean mice serve as a substrate buffer or reservoir to modulate lipid, catecholamine, and iron availability. Furthermore, recent models of weight loss and weight cycling reveal additional roles for ATMs in systemic metabolism. Evaluating ATM phenotype and intracellular metabolism together may more accurately illuminate the consequences of ATM accumulation in obese AT, lending further insight into obesity‐related comorbidities in humans.
Nocturnal worsening of asthma symptoms is a common feature of asthma. Physical exercise training improves general asthma control; however, there is no evidence showing the effects of physical ...exercise on nocturnal asthma symptoms. Indeed, asthma patients with daytime and nighttime symptoms are physiologically different, and thus the effects of physical exercise on asthma may also be different in these two groups. The objective of this systematic review is to explore the effects of physical exercise on nocturnal asthma symptoms.
Searches were conducted in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL and SPORTdiscus (last search on November 2017). Authors from studies that did not report nocturnal symptoms but used questionnaires and/or diaries were contacted for detailed information. Studies that provided results on nocturnal symptoms before and after physical activity intervention were included. Prevalence of nocturnal symptoms was calculated for each study from the percentage of study participants with nocturnal symptoms before and after intervention.
Eleven studies were included (5 with children and 6 with adults). The prevalence of nocturnal symptoms at baseline ranged from 0% to 63% among children and from 50-73% among adults. In children and adults with nocturnal asthma, aerobic physical exercise reduced the prevalence and frequency of nocturnal symptoms.
Aerobic physical exercise improves nocturnal asthma in children and adults by reducing the prevalence and frequency of nocturnal symptoms. Physical exercise training could be used with conventional treatments to improve quality of life and asthma control in patients with nocturnal worsening of asthma.
A critical contributor to the health consequences of the obesity epidemic is dysregulated adipose tissue (AT) homeostasis. While white, brown, and beige AT function is altered in obesity-related ...disease, white AT is marked by progressive inflammation and adipocyte dysfunction and has been the focus of extensive “immunometabolism” research in the past decade. The exact triggering events initiating and sustaining AT inflammation are still under study, but it has been shown that reducing inflammation improves insulin action in AT. Scientific efforts seeking interventions to mitigate obesity-associated AT inflammation continue, and many groups are now determining how lean healthy AT homeostasis is maintained in order to leverage these mechanisms as therapeutic targets. Such studies have revealed that an elaborate network of immune cells, cytokines, and other cellular mediators coordinate AT function. Recent studies elucidated the involvement of the innate immune system in AT homeostasis (e.g., beiging and insulin sensitivity), including M2-like macrophages, eosinophils, innate lymphoid type 2 cells, and several others. In this review, we summarize the existing literature on innate type 2 inflammation in AT; additionally, we draw attention to areas of debate where seemingly conflicting data promises to yield more surprising and elegant biology as studies continue to dissect AT physiology.
We use the kinematics of ∼200 000 giant stars that lie within ∼1.5 kpc of the plane to measure the vertical profile of mass density near the Sun. We find that the dark mass contained within the ...isodensity surface of the dark halo that passes through the Sun ((6 ± 0.9) × 1010 M⊙), and the surface density within 0.9 kpc of the plane ((69 ± 10) M⊙ pc−2) are almost independent of the (oblate) halo's axis ratio q. If the halo is spherical, 46 per cent of the radial force on the Sun is provided by baryons, and only 4.3 per cent of the Galaxy's mass is baryonic. If the halo is flattened, the baryons contribute even less strongly to the local radial force and to the Galaxy's mass. The dark matter density at the location of the Sun is 0.0126 q
−0.89 M⊙ pc−3 = 0.48 q
−0.89 GeV cm−3. When combined with other literature results we find hints for a mildly oblate dark halo with q ≃ 0.8. Our value for the dark mass within the solar radius is larger than that predicted by cosmological dark-matter-only simulations but in good agreement with simulations once the effects of baryonic infall are taken into account. Our mass models consist of three double-exponential discs, an oblate bulge and a Navarro–Frenk–White dark matter halo, and we model the dynamics of the RAVE (RAdial Velocity Experiment) stars in the corresponding gravitational fields by finding distribution functions f J
that depend on three action integrals. Statistical errors are completely swamped by systematic uncertainties, the most important of which are the distance to the stars in the photometric and spectroscopic samples and the solar distance to the Galactic Centre. Systematics other than the flattening of the dark halo yield overall uncertainties ∼15 per cent.
Messenger RNAs (mRNAs) encode information in both their primary sequence and their higher order structure. The independent contributions of factors like codon usage and secondary structure to ...regulating protein expression are difficult to establish as they are often highly correlated in endogenous sequences. Here, we used 2 approaches, global inclusion of modified nucleotides and rational sequence design of exogenously delivered constructs, to understand the role of mRNA secondary structure independent from codon usage. Unexpectedly, highly expressed mRNAs contained a highly structured coding sequence (CDS). Modified nucleotides that stabilize mRNA secondary structure enabled high expression across a wide variety of primary sequences. Using a set of eGFP mRNAs with independently altered codon usage and CDS structure, we find that the structure of the CDS regulates protein expression through changes in functional mRNA half-life (i.e., mRNA being actively translated). This work highlights an underappreciated role of mRNA secondary structure in the regulation of mRNA stability.
Abstract
Motivation
Linkage and quantitative trait loci (QTL) maps are critical tools for the study of the genetic basis of complex traits. With the advances in sequencing technology over the past ...decade, linkage map densities have been increasing dramatically, while the visualization tools have not kept pace. LinkageMapView is a free add-on package written in R that produces high resolution, publication-ready visualizations of linkage and QTL maps. While there is software available to generate linkage map graphics, none are freely available, produce publication quality figures, are open source and can run on all platforms. LinkageMapView can be integrated into map building pipelines as it seamlessly incorporates output from R/qtl and also accepts simple text or comma delimited files. There are numerous options within the package to build highly customizable maps, allow for linkage group comparisons, and annotate QTL regions.
Availability and implementation
https://cran.r-project.org/web/packages/LinkageMapView/
PDF
