Metabolic Effects Of Duodenojejunal Bypass Surgery In A Rat Model Of Type 1 Diabetes

Background Metabolic surgery has beneficial metabolic effects, including remission of type 2 diabetes. We hypothesized that duodenojejunal bypass (DJB) surgery can protect against development of type 1 diabetes (T1D) by enhancing regulation of cellular and molecular pathways that control glucose homeostasis. Methods BBDP/Wor rats, which are prone to develop spontaneous autoimmune T1D, underwent loop DJB (n = 15) or sham (n = 15) surgery at a median age of 41 days, before development of diabetes. At T1D diagnosis, a subcutaneous insulin pellet was implanted, oral glucose tolerance test was performed 21 days later, and tissues were collected 25 days after onset of T1D. Pancreas and liver tissues were assessed by histology and RT-qPCR. Fecal microbiota composition was analyzed by 16S V4 sequencing. Results Postoperatively, DJB rats weighed less than sham rats (287.8 vs 329.9 g,P = 0.04). In both groups, 14 of 15 rats developed T1D, at similar age of onset (87 days in DJB vs 81 days in sham,P = 0.17). There was no difference in oral glucose tolerance, fasting and stimulated plasma insulin and c-peptide levels, and immunohistochemical analysis of insulin-positive cells in the pancreas. DJB rats needed 1.3 +/- 0.4 insulin implants vs 1.9 +/- 0.5 in sham rats (P = 0.002). Fasting and glucose stimulated glucagon-like peptide 1 (GLP-1) secretion was elevated after DJB surgery. DJB rats had reduced markers of metabolic stress in liver. After DJB, the fecal microbiome changed significantly, including increases inAkkermansiaandRuminococcus, while the changes were minimal in sham rats. Conclusion DJB does not protect against autoimmune T1D in BBDP/Wor rats, but reduces the need for exogenous insulin and facilitates other metabolic benefits including weight loss, increased GLP-1 secretion, reduced hepatic stress, and altered gut microbiome

Selection of Saccharomyces cerevisiae strains for efficient very high gravity bio-ethanol fermentation processes

An optimized very high gravity (VHG) glucose medium supplemented with low cost nutrient sources was used to evaluate bio-ethanol production by 11 Saccharomyces cerevisiae strains. The industrial strains PE-2 and CA1185 exhibited the best overall fermentation performance, producing an ethanol titre of 19.2% (v/v) corresponding to a batch productivity of 2.5 g l-1 h-1, while the best laboratory strain (CEN.PK 113-7D) produced 17.5% (v/v) ethanol with a productivity of 1.7 g l-1 h-1. The results presented here emphasize the biodiversity found within S. cerevisiae species and that naturally adapted strains, such as PE-2 and CA1185, are likely to play a key role in facilitating the transition from laboratory technological breakthroughs to industrialscale bio-ethanol fermentations.Fundação para a Ciência e a Tecnologia (FCT) - PTDC/BIO/66151/2006, SFRH/ BD/64776/2009, SFRH/BPD/44328/ 200

The Young Supernova Experiment: Survey Goals, Overview, and Operations

Time domain science has undergone a revolution over the past decade, with tens of thousands of new supernovae (SNe) discovered each year. However, several observational domains, including SNe within days or hours of explosion and faint, red transients, are just beginning to be explored. Here, we present the Young Supernova Experiment (YSE), a novel optical time-domain survey on the Pan-STARRS telescopes. Our survey is designed to obtain well-sampled $griz$ light curves for thousands of transient events up to $z \approx 0.2$. This large sample of transients with 4-band light curves will lay the foundation for the Vera C. Rubin Observatory and the Nancy Grace Roman Space Telescope, providing a critical training set in similar filters and a well-calibrated low-redshift anchor of cosmologically useful SNe Ia to benefit dark energy science. As the name suggests, YSE complements and extends other ongoing time-domain surveys by discovering fast-rising SNe within a few hours to days of explosion. YSE is the only current four-band time-domain survey and is able to discover transients as faint $\sim$21.5 mag in $gri$ and $\sim$20.5 mag in $z$, depths that allow us to probe the earliest epochs of stellar explosions. YSE is currently observing approximately 750 square degrees of sky every three days and we plan to increase the area to 1500 square degrees in the near future. When operating at full capacity, survey simulations show that YSE will find $\sim$5000 new SNe per year and at least two SNe within three days of explosion per month. To date, YSE has discovered or observed 8.3% of the transient candidates reported to the International Astronomical Union in 2020. We present an overview of YSE, including science goals, survey characteristics and a summary of our transient discoveries to date.Comment: ApJ, in press; more information at https://yse.ucsc.edu

SN 2023ixf in Messier 101: Photo-ionization of Dense, Close-in Circumstellar Material in a Nearby Type II Supernova

We present UV/optical observations and models of supernova (SN) 2023ixf, a type II SN located in Messier 101 at 6.9 Mpc. Early-time ("flash") spectroscopy of SN 2023ixf, obtained primarily at Lick Observatory, reveals emission lines of H I, He I/II, C IV, and N III/IV/V with a narrow core and broad, symmetric wings arising from the photo-ionization of dense, close-in circumstellar material (CSM) located around the progenitor star prior to shock breakout. These electron-scattering broadened line profiles persist for $\sim$8 days with respect to first light, at which time Doppler broadened features from the fastest SN ejecta form, suggesting a reduction in CSM density at $r \gtrsim 10^{15}$ cm. The early-time light curve of SN2023ixf shows peak absolute magnitudes (e.g., $M_{u} = -18.6$ mag, $M_{g} = -18.4$ mag) that are $\gtrsim 2$ mag brighter than typical type II supernovae, this photometric boost also being consistent with the shock power supplied from CSM interaction. Comparison of SN 2023ixf to a grid of light curve and multi-epoch spectral models from the non-LTE radiative transfer code CMFGEN and the radiation-hydrodynamics code HERACLES suggests dense, solar-metallicity, CSM confined to $r = (0.5-1) \times 10^{15}$ cm and a progenitor mass-loss rate of $\dot{M} = 10^{-2}$ M$_{\odot}$yr$^{-1}$. For the assumed progenitor wind velocity of $v_w = 50$ km s$^{-1}$, this corresponds to enhanced mass-loss (i.e., ``super-wind'' phase) during the last $\sim$3-6 years before explosion.Comment: 18 pages, 8 figures. Submitted to ApJ

Roaring to softly whispering : X-Ray emission after ∼3.7 yr at the location of the transient AT2018cow and implications for accretion-powered scenarios

We present the first deep X-ray observations of luminous fast blue optical transient (LFBOT) AT 2018cow at ∼3.7 yr since discovery, together with the reanalysis of the observation at δ t ∼ 220 days. X-ray emission is significantly detected at a location consistent with AT 2018cow. The very soft X-ray spectrum and sustained luminosity are distinct from the spectral and temporal behavior of the LFBOT in the first ∼100 days and would possibly signal the emergence of a new emission component, although a robust association with AT 2018cow can only be claimed at δ t ∼ 220 days, while at δ t ∼ 1350 days contamination of the host galaxy cannot be excluded. We interpret these findings in the context of the late-time panchromatic emission from AT 2018cow, which includes the detection of persistent, slowly fading UV emission with ν L ν ≈ 1039 erg s−1. Similar to previous works (and in analogy with arguments for ultraluminous X-ray sources), these late-time observations are consistent with thin disks around intermediate-mass black holes (with M • ≈ 103–104 M ☉) accreting at sub-Eddington rates. However, differently from previous studies, we find that smaller-mass black holes with M • ≈ 10–100 M ☉ accreting at ≳the Eddington rate cannot be ruled out and provide a natural explanation for the inferred compact size (R out ≈ 40 R ☉) of the accretion disk years after the optical flare. Most importantly, irrespective of the accretor mass, our study lends support to the hypothesis that LFBOTs are accretion-powered phenomena and that, specifically, LFBOTs constitute electromagnetic manifestations of super-Eddington accreting systems that evolve to ≲Eddington over a ≈100-day timescale

Radio analysis of SN2004C reveals an unusual CSM density profile as a harbinger of core collapse

We present extensive multifrequency Karl G. Jansky Very Large Array (VLA) and Very Long Baseline Array (VLBA) observations of the radio-bright supernova (SN) IIb SN 2004C that span ∼40–2793 days post-explosion. We interpret the temporal evolution of the radio spectral energy distribution in the context of synchrotron self-absorbed emission from the explosion's forward shock as it expands in the circumstellar medium (CSM) previously sculpted by the mass-loss history of the stellar progenitor. VLBA observations and modeling of the VLA data point to a blastwave with average velocity ∼0.06 c that carries an energy of ≈1049 erg. Our modeling further reveals a flat CSM density profile ρCSM ∝ R−0.03±0.22 up to a break radius Rbr ≈ (1.96 ± 0.10) × 1016 cm, with a steep density gradient following ρCSM ∝ R−2.3±0.5 at larger radii. We infer that the flat part of the density profile corresponds to a CSM shell with mass ∼0.021 M☉, and that the progenitor's effective mass-loss rate varied with time over the range (50–500) × 10−5 M☉ yr−1 for an adopted wind velocity vw = 1000 km s−1 and shock microphysical parameters epsilone = 0.1, epsilonB = 0.01. These results add to the mounting observational evidence for departures from the traditional single-wind mass-loss scenarios in evolved, massive stars in the centuries leading up to core collapse. Potentially viable scenarios include mass loss powered by gravity waves and/or interaction with a binary companion

Can medical therapy mimic the clinical efficacy or physiological effects of bariatric surgery?

The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal–jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A ‘medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals