Explore the vast range of titles available.

Background Women with a history of gestational diabetes mellitus (GDM) have a 7-fold higher risk of developing type 2 diabetes (T2D). It is estimated that 20-50% of women with GDM history will progress to T2D within 10 years after delivery. Intensive lactation could be negatively associated with this risk, but the mechanisms behind a protective effect remain unknown. Methods In this study, we utilized a prospective GDM cohort of 1010 women without T2D at 6-9 weeks postpartum (study baseline) and tested for T2D onset up to 8 years post-baseline (n=980). Targeted metabolic profiling was performed on fasting plasma samples collected at both baseline and follow-up (1-2 years post-baseline) during research exams in a subset of 350 women (216 intensive breastfeeding, IBF vs. 134 intensive formula feeding or mixed feeding, IFF/Mixed). The relationship between lactation intensity and circulating metabolites at both baseline and follow-up were evaluated to discover underlying metabolic responses of lactation and to explore the link between these metabolites and T2D risk. Results We observed that lactation intensity was strongly associated with decreased glycerolipids (TAGs/DAGs) and increased phospholipids/sphingolipids at baseline. This lipid profile suggested decreased lipogenesis caused by a shift away from the glycerolipid metabolism pathway towards the phospholipid/sphingolipid metabolism pathway as a component of the mechanism underlying the benefits of lactation. Longitudinal analysis demonstrated that this favorable lipid profile was transient and diminished at 1-2 years postpartum, coinciding with the cessation of lactation. Importantly, when stratifying these 350 women by future T2D status during the follow-up (171 future T2D vs. 179 no T2D), we discovered that lactation induced robust lipid changes only in women who did not develop incident T2D. Subsequently, we identified a cluster of metabolites that strongly associated with future T2D risk from which we developed a predictive metabolic signature with a discriminating power (AUC) of 0.78, superior to common clinical variables (i.e., fasting glucose, AUC 0.56 or 2-h glucose, AUC 0.62). Conclusions In this study, we show that intensive lactation significantly alters the circulating lipid profile at early postpartum and that women who do not respond metabolically to lactation are more likely to develop T2D. We also discovered a 10-analyte metabolic signature capable of predicting future onset of T2D in IBF women. Our findings provide novel insight into how lactation affects maternal metabolism and its link to future diabetes onset. Trial registration ClinicalTrials.gov NCT01967030 .

Glycine and β-alanine activate glycine receptors (GlyRs), with glycine known to enhance insulin secretion from pancreatic islet β cells, primarily through GlyR activation. However, the effects of GlyR activation on β cell proliferation have not been examined. Here, we aim to investigate the potential proliferative effects of glycine and β-alanine on islets. In vitro experiments on mouse and human islets revealed that glycine and β-alanine, via GlyR activation, stimulated the proliferation of β cells and α cells, without affecting insulin or glucagon secretion. Further analysis indicated the involvement of the PI3K/mTORC1/p70S6K signaling pathway in this process. Inhibition of GlyRs and PI3K/mTORC1/p70S6K signaling attenuated proliferative effects of glycine and β-alanine. In vivo and ex vivo studies supported these findings, showing increased β and α cell mass after 12 weeks of oral administration of glycine and β-alanine, with no changes in insulin secretion or glucose homeostasis under normal conditions. However, during an acute insulin resistance induced by insulin receptor antagonist S961, glycine and β-alanine enhanced insulin secretion and reduced blood glucose levels by increasing β cell secretory capacity. These findings demonstrate glycine and β-alanine in vivo and in vitro promote islet cell proliferation via GlyR activation and the PI3K/mTORC1/p70S6K pathway, potentially providing a target to enhance islet capacity.

GWAS have shown that the common R325W variant of SLC30A8 (ZnT8) increases the risk of type 2 diabetes (T2D). However, ZnT8 haploinsufficiency is protective against T2D in humans, counterintuitive to earlier work in humans and mouse models. Therefore, whether decreasing ZnT8 activity is beneficial or detrimental to β cell function, especially under conditions of metabolic stress, remains unknown. In order to examine whether the existence of human islet amyloid polypeptide (hIAPP), a coresident of the insulin granule, affects the role of ZnT8 in regulating β cell function, hIAPP-expressing transgenics were generated with reduced ZnT8 (ZnT8B+/- hIAPP) or null ZnT8 (ZnT8B-/- hIAPP) expression specifically in β cells. We showed that ZnT8B-/- hIAPP mice on a high-fat diet had intensified amyloid deposition and further impaired glucose tolerance and insulin secretion compared with control, ZnT8B-/-, and hIAPP mice. This can in part be attributed to impaired glucose sensing and islet cell synchronicity. Importantly, ZnT8B+/- hIAPP mice were also glucose intolerant and had reduced insulin secretion and increased amyloid aggregation compared with controls. These data suggest that loss of or reduced ZnT8 activity in β cells heightened the toxicity induced by hIAPP, leading to impaired β cell function and glucose homeostasis associated with metabolic stress.

Supernovae are astrophysical explosions that can be as bright as a billion stars for a few weeks, occurring roughly once every 100years in a galaxy similar to our own. Many supernovae herald the death of massive stars thatare roughly eight solar masses or more. Others, called typeIa supernovae, arethe thermonuclear incineration of white dwarf stars, the dead cores of stars likeour Sun aer they have exhausted their nuclear fuel. Besides providing dazzling reworks, supernovae are vital in many other ways, from synthesizing the heavy elements that are crucial for life as we know it, to injecting material and energy into galaxies.

The Carnegie Supernova Project-II (CSP-II) was an NSF-funded, four-year program to obtain optical and near-infrared observations of a “Cosmology” sample of ∼100 Type Ia supernovae located in the smooth Hubble flow (0.03 ≲ z ≲ 0.10). Light curves were also obtained of a “Physics” sample composed of 90 nearby Type Ia supernovae at z ≤ 0.04 selected for near-infrared spectroscopic timeseries observations. The primary emphasis of the CSP-II is to use the combination of optical and near-infrared photometry to achieve a distance precision of better than 5%. In this paper, details of the supernova sample, the observational strategy, and the characteristics of the photometric data are provided. In a companion paper, the near-infrared spectroscopy component of the project is presented.

Type Ia supernovae are thermonuclear explosions of white dwarf stars. They play a central role in the chemical evolution of the Universe and are an important measure of cosmological distances. However, outstanding questions remain about their origins. Despite extensive efforts to obtain natal information from their earliest signals, observations have thus far failed to identify how the majority of them explode. Here, we present infant-phase detections of SN 2018aoz from a very low brightness of −10.5 AB absolute magnitude, revealing a hitherto unseen plateau in the B band that results in a rapid redward colour evolution between 1.0 and 12.4 hours after the estimated epoch of first light. The missing B -band flux is best explained by line-blanket absorption from Fe-peak elements in the outer 1% of the ejected mass. The observed B  −  V colour evolution of the supernova also matches the prediction from an over-density of Fe-peak elements in the same outer 1% of the ejected mass, whereas bluer colours are expected from a purely monotonic distribution of Fe-peak elements. The presence of excess nucleosynthetic material in the extreme outer layers of the ejecta points to enhanced surface nuclear burning or extended subsonic mixing processes in some normal type Ia SN explosions. Very early observations of a type Ia supernova—from within one hour of explosion—show a red colour that develops and rapidly disappears. These data provide information on the initial explosion mechanism: surface nuclear burning on the white dwarf or extreme mixing of the nuclear burning process.

New observations suggest that two highly debated mechanisms for type Ia supernovae — our standard distance 'candles' for astrophysical objects — may both be correct.

The Carnegie Supernova Project-II (CSP-II) was an NSF-funded, four-year program to obtain optical and near-infrared observations of a \"Cosmology\" sample of ∼100 Type Ia supernovae located in the smooth Hubble flow (0.03 z 0.10). Light curves were also obtained of a \"Physics\" sample composed of 90 nearby Type Ia supernovae at z ≤ 0.04 selected for near-infrared spectroscopic timeseries observations. The primary emphasis of the CSP-II is to use the combination of optical and near-infrared photometry to achieve a distance precision of better than 5%. In this paper, details of the supernova sample, the observational strategy, and the characteristics of the photometric data are provided. In a companion paper, the near-infrared spectroscopy component of the project is presented.

The Carnegie Supernova Project-II (CSP-II) was an NSF-funded, four-year program to obtain optical and near-infrared observations of a \"Cosmology\" sample of ~100 Type Ia supernovae located in the smooth Hubble flow (0.03 $\\lesssim$ z $\\lesssim$ 0.10). Light curves were also obtained of a \"Physics\" sample composed of 90 nearby Type Ia supernovae at z ≤ 0.04 selected for near-infrared spectroscopic timeseries observations. The primary emphasis of the CSP-II is to use the combination of optical and near-infrared photometry to achieve a distance precision of better than 5%. Here in this paper, details of the supernova sample, the observational strategy, and the characteristics of the photometric data are provided. In a companion paper, the near-infrared spectroscopy component of the project is presented.

The habitability of exoplanets can be strongly influenced by the presence of an exomoon, and in some cases the exomoon itself could be a possible place for life to develop. For moons outside of the habitable zone, significant tidal heating may raise their surface temperature enough to be considered habitable. Tidal heating of a moon depends on numerous factors such as eccentricity, semimajor axis, size of parent planet, and presence of additional moons. In this work, we explore the degree of tidal heating possible for multi-moon systems in resonance using a combination of semi-analytic and numerical models. This demonstrates that even for a moon with zero initial eccentricity, when it moves into resonance with an outer moon, it can generate significant eccentricity and associated tidal heating. Depending on the mass ratio of the two moons, this resonance can either be short-lived (\\(\\leq200\\) Myr) or continue to be driven by the tidal migration of the moons. This tidal heating can also assist in making the exomoons easier to discover, and we explore two scenarios: secondary eclipses and outgassing of volcanic species. We then consider hypothetical moons orbiting known planetary systems to identify which will be beast suited for finding exomoons with these methods. We conclude with a discussion of current and future instrumentation and missions to better understand how practical it will be to make exomoon discoveries in these ways.