Raman spectroscopy is commonly used in microplastics identification, but equipment variations yield inconsistent data structures that disrupt the development of communal analytical tools. We report a ...strategy to overcome the issue using a database of high-resolution, full-window Raman spectra. This approach enables customizable analytical tools to be easily createda feature we demonstrate by creating machine-learning classification models using open-source random-forest, K-nearest neighbors, and multi-layer perceptron algorithms. These models yield >95% classification accuracy when trained on spectroscopic data with spectroscopic data downgraded to 1, 2, 4, or 8 cm–1 spacings in Raman shift. The accuracy can be maintained even in non-ideal conditions, such as with spectroscopic sampling rates of 1 kHz and when microplastic particles are outside the focal plane of the laser. This approach enables the creation of classification models that are robust and adaptable to varied spectrometer setups and experimental needs.
Invariant natural killer T (iNKT) cells are evolutionarily conserved innate T cells that influence inflammatory responses. We have shown that iNKT cells, previously thought to be rare in humans, were ...highly enriched in human and murine adipose tissue, and that as adipose tissue expanded in obesity, iNKT cells were depleted, correlating with proinflammatory macrophage infiltration. iNKT cell numbers were restored in mice and humans after weight loss. Mice lacking iNKT cells had enhanced weight gain, larger adipocytes, fatty livers, and insulin resistance on a high-fat diet. Adoptive transfer of iNKT cells into obese mice or in vivo activation of iNKT cells via their lipid ligand, alpha-galactocylceramide, decreased body fat, triglyceride levels, leptin, and fatty liver and improved insulin sensitivity through anti-inflammatory cytokine production by adipose-derived iNKT cells. This finding highlights the potential of iNKT cell-targeted therapies, previously proven to be safe in humans, in the management of obesity and its consequences.
► iNKT cells are enriched in mamalian adipose tissue ► iNKT cells in adipose tissue are unique IL-10 producers ► Without iNKT cells, mice are fatter and more insulin resistant ► Restoring iNKT cells in obesity reverses type 2 diabetes
Natural killer (NK) cells are a population of lymphocytes which classically form part of the innate immune system. They are defined as innate lymphocytes, due to their ability to kill infected or ...transformed cells without prior activation. In addition to their cytotoxic abilities, NK cells are also rapid producers of inflammatory cytokines such as interferon gamma (IFN-γ) and are therefore a critical component of early immune responses. Due to these unique abilities, NK cells are a very important component of host protection, especially anti-tumour and anti-viral immunity. Obesity is a worldwide epidemic, with over 600 million adults and 124 million children now classified as obese. It is well established that individuals who are obese are at a higher risk of many acute and chronic conditions, including cancer and viral infections. Over the past 10 years, many studies have investigated the impact of obesity on NK cell biology, detailing systemic dysregulation of NK cell functions. More recently, several studies have investigated the role of NK cells in the homeostasis of adipose tissue and the pathophysiology of obesity. In this review, we will discuss in detail these studies and focus on emerging data detailing the metabolic mechanisms altering NK cells in obesity.
Wettability of microplastics may change due to chemical or physical transformations at their surface. In this work, we studied the adsorption of spherical nucleic acids (SNAs) with a gold ...nanoparticle core and linear DNA of the same sequence to probe the wettability of microplastics. Soaking microplastics in water at room temperature for 3 months resulted in the enhancement of SNA adsorption capacity and affinity, whereas linear DNA adsorption was the same on the fresh and soaked microplastics. Drying of the soaked microplastics followed by rehydration decreased the adsorption of the SNA, suggesting that the effect of soaking was reversible and related to physical changes instead of chemical changes of the microplastics. Raman spectroscopy data also revealed no chemical transformations of the soaked microplastics. Heating of microplastics over a short period induced a similar effect to long-term soaking. We propose that soaking or heating removes air entrapped in the nanosized pores at the water–plastic interface, increasing the contact surface area of the SNA to afford stronger adsorption. However, such wetted porosity would not change the adsorption of linear DNA because of its much smaller size.
It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure ...prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART.
Colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF), plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs) were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA). Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative) followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse), but only 1 of 10 mice infused with CD4+ T cells from PrEP Participant A (53 million input cells/mouse) experienced very low level viremia (201 copies/mL); sequence confirmation was unsuccessful. PrEP Participant A stopped ART and remained aviremic for 7.4 months, rebounding with HIV RNA of 36 copies/mL that rose to 59,805 copies/mL 6 days later. ART was restarted promptly. Rebound plasma HIV sequences were identical to those obtained during acute infection by single-genome sequencing. Mathematical modeling predicted that the latent reservoir size was approximately 200 cells prior to ATI and that only around 1% of individuals with a similar HIV burden may achieve lifelong ART-free remission. Furthermore, we observed that lymphocytes expressing the tumor marker CD30 increased in frequency weeks to months prior to detectable HIV-1 RNA in plasma. This study was limited by the small sample size, which was a result of the rarity of individuals presenting during hyperacute infection.
We report HIV relapse despite initiation of ART at one of the earliest stages of acute HIV infection possible. Near complete or complete loss of detectable HIV in blood and tissues did not lead to indefinite ART-free HIV remission. However, the small numbers of latently infected cells in individuals treated during hyperacute infection may be associated with prolonged ART-free remission.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Adipose-resident invariant natural killer T (iNKT) cells are key players in metabolic regulation. iNKT cells are innate lipid sensors, and their activation, using their prototypic ligand ...α-galactosylceramide (αGalCer), induces weight loss and restores glycemic control in obesity. Here, iNKT activation induced fibroblast growth factor 21 (FGF21) production and thermogenic browning of white fat. Complete metabolic analysis revealed that iNKT cell activation induced increased body temperature, V02, VC02, and fatty acid oxidation, without affecting food intake or activity. FGF21 induction played a major role in iNKT cell-induced weight loss, as FGF21 null mice lost significantly less weight after αGalCer treatment. The glucagon-like peptide 1 (GLP-1) receptor agonist, liraglutide, also activated iNKT cells in humans and mice. In iNKT-deficient mice, liraglutide promoted satiety but failed to induce FGF21, resulting in less weight loss. These findings reveal an iNKT cell-FGF21 axis that defines a new immune-mediated pathway that could be targeted for glycemic control and weight regulation.
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•iNKT cell activation leads to potent weight loss and glycemic control in obesity•iNKT-induced weight loss is induced by thermogenic browning of white fat•FGF21 induced by iNKT cells plays an important step in weight loss•GLP-1 activates iNKT cells, triggering FGF21 and contributing to weight loss
Activation of adipose-resident invariant natural killer (iNKT) cells induces weight loss and restores glycemic control in obesity. Lynch et al. investigate the underlying mechanism and unveil a pathway involving FGF21. GLP-1 therapy also activated the iNKT-FGF21 axis, which contributes to weight loss.
We present a new version of the Met Office Hadley Centre/Climatic Research Unit global surface temperature data set, HadCRUT5. HadCRUT5 presents monthly average near‐surface temperature anomalies, ...relative to the 1961–1990 period, on a regular 5° latitude by 5° longitude grid from 1850 to 2018. HadCRUT5 is a combination of sea‐surface temperature (SST) measurements over the ocean from ships and buoys and near‐surface air temperature measurements from weather stations over the land surface. These data have been sourced from updated compilations and the adjustments applied to mitigate the impact of changes in SST measurement methods have been revised. Two variants of HadCRUT5 have been produced for use in different applications. The first represents temperature anomaly data on a grid for locations where measurement data are available. The second, more spatially complete, variant uses a Gaussian process based statistical method to make better use of the available observations, extending temperature anomaly estimates into regions for which the underlying measurements are informative. Each is provided as a 200‐member ensemble accompanied by additional uncertainty information. The combination of revised input data sets and statistical analysis results in greater warming of the global average over the course of the whole record. In recent years, increased warming results from an improved representation of Arctic warming and a better understanding of evolving biases in SST measurements from ships. These updates result in greater consistency with other independent global surface temperature data sets, despite their different approaches to data set construction, and further increase confidence in our understanding of changes seen.
Plain Language Summary
We have produced a new version of a data set that measures changes of near‐surface temperature across the globe from 1850 to 2018, called HadCRUT5. We have included an improved data set of sea‐surface temperature, which better accounts for the effects of changes through time in how measurement were made from ships and buoys at sea. We have also included an expanded compilation of measurements made at weather stations on land. There are two variations of HadCRUT5, produced for different uses. The first, the “HadCRUT5 noninfilled data set,” maps temperature changes on a grid for locations close to where we have measurements. The second, the “HadCRUT5 analysis,” extends our estimates to locations further from the available measurements using a statistical technique that makes use of the spatial connectedness of temperature patterns. This improves the representation of less well observed regions in estimates of global, hemispheric and regional temperature change. Together, these updates and improvements reveal a slightly greater rise in near‐surface temperature since the nineteenth century, especially in the Northern Hemisphere, which is more consistent with other data sets. This increases our confidence in our understanding of global surface temperature changes since the mid‐19th century.
Key Points
We have created a new version of the Met Office Hadley Centre and Climatic Research Unit global surface temperature data set for 1850–2018
The new data set better represents sparsely observed regions of the globe and incorporates an improved sea‐surface temperature data set
This data set shows increased global average warming since the mid‐19th century and in recent years, consistent with other analyses
Mucosal associated invariant T (MAIT) cells are a population of unconventional innate T cells due to their non-MHC restriction and rapid effector responses. MAIT cells can recognise bacterial derived ...antigens presented on the MHC-like protein
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their semi-restricted T cell receptor (TCR). Upon TCR triggering MAIT cells rapidly produce a range of effector molecules including cytokines, lytic granules and chemokines. This rapid and robust effector response makes MAIT cells critical in host responses against many bacterial pathogens. MAIT cells can also respond independent of their TCR
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innate cytokines such as interleukin (IL)-18, triggering cytokine production, and are important in anti-viral responses. In addition to their protective role, MAIT cells have been implicated in numerous inflammatory diseases, including metabolic diseases often contributing to the pathogenesis
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their robust cytokine production. Effector cells such as MAIT cells require significant amounts of energy to support their potent responses, and the type of nutrients available can dictate the functionality of the cell. Although data on MAIT cell metabolism is just emerging, several recent studies are starting to define the intrinsic metabolic requirements and regulators of MAIT cells. In this review we will outline our current understanding of MAIT cell metabolism, and outline their role in metabolic disease, and how disease-related changes in extrinsic metabolism can alter MAIT cell responses.
In this paper we investigate the reputational penalties to managers of firms announcing earnings restatements. More specifically, we examine management turn-over and the subsequent employment of ...displaced managers at firms announcing earnings restatements during 1997 or 1998. In contrast to prior research (Beneish 1999; Agrawal et al. 1999), which does not find increased turnover following GAAP violations or revelation of corporate fraud, we find that 60 percent of restating firms experience a turnover of at least one top manager within 24 months of the restatement compared to 35 percent among age-, size-, and industry-matched firms. Moreover, the subsequent employment prospects of the displaced managers of restatement firms are poorer than those of the displaced managers of control firms. Our results hold after controlling for firm performance, bankruptcy, and other determinants of management turnover, and suggest that both corporate boards and the external labor market impose significant penalties on managers for violating GAAP. Also, in light of resource constraints at the SEC, our findings are encouraging as they suggest that private penalties for GAAP violations are severe and may serve as partial substitutes for public enforcement of GAAP violations.
Members of the interleukin-1 (IL-1) family are important mediators of obesity and metabolic disease and have been described to often play opposing roles. Here we report that the interleukin-36 ...(IL-36) subfamily can play a protective role against the development of disease. Elevated IL-36 cytokine expression is found in the serum of obese patients and negatively correlates with blood glucose levels among those presenting with type 2 diabetes. Mice lacking IL-36Ra, an IL-36 family signalling antagonist, develop less diet-induced weight gain, hyperglycemia and insulin resistance. These protective effects correlate with increased abundance of the metabolically protective bacteria Akkermansia muciniphila in the intestinal microbiome. IL-36 cytokines promote its outgrowth as well as increased colonic mucus secretion. These findings identify a protective role for IL-36 cytokines in obesity and metabolic disease, adding to the current understanding of the role the broader IL-1 family plays in regulating disease pathogenesis.
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