The Role of Gut Adaptation in the Potent Effects of Multiple Bariatric Surgeries on Obesity and Diabetes

Bariatric surgical procedures such as vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most potent treatments available to produce sustained reductions in body weight and improvements in glucose regulation. While traditionally these effects are attributed to mechanical aspects of these procedures, such as restriction and malabsorption, a growing body of evidence from mouse models of these procedures points to physiological changes that mediate the potent effects of these surgeries. In particular, there are similar changes in gut hormone secretion, bile acid levels, and composition after both of these procedures. Moreover, loss of function of the nuclear bile acid receptor (FXR) greatly diminishes the effects of VSG. Both VSG and RYGB are linked to profound changes in the gut microbiome that also mediate at least some of these surgical effects. We hypothesize that surgical rearrangement of the gastrointestinal tract results in enteroplasticity caused by the high rate of nutrient presentation and altered pH in the small intestine that contribute to these physiological effects. Identifying the molecular underpinnings of these procedures provides new opportunities to understand the relationship of the gastrointestinal tract to obesity and diabetes as well as new therapeutic strategies to harness the effectiveness of surgery with less-invasive approaches

Hypothalamic Vitamin D Improves Glucose Homeostasis and Reduces Weight

Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weight, we hypothesized that activation of central VDR links vitamin D to the regulation of glucose and energy homeostasis. Indeed, we found that small doses of active vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3) (calcitriol), into the third ventricle of the brain improved glucose tolerance and markedly increased hepatic insulin sensitivity, an effect that is dependent upon VDR within the paraventricular nucleus of the hypothalamus. In addition, chronic central administration of 1,25D3 dramatically decreased body weight by lowering food intake in obese rodents. Our data indicate that 1,25D3-mediated changes in food intake occur through action within the arcuate nucleus. We found that VDR colocalized with and activated key appetite-regulating neurons in the arcuate, namely proopiomelanocortin neurons. Together, these findings define a novel pathway for vitamin D regulation of metabolism with unique and divergent roles for central nervous system VDR signaling. Specifically, our data suggest that vitamin D regulates glucose homeostasis via the paraventricular nuclei and energy homeostasis via the arcuate nuclei

Contribution of glycogen in supporting axon conduction in the peripheral and central nervous systems: the role of lactate

The role of glycogen in the central nervous system is intimately linked with the glycolytic pathway. Glycogen is synthesized from glucose, the primary substrate for glycolysis, and degraded to glucose-6-phosphate. The metabolic cost of shunting glucose via glycogen exceeds that of simple phosphorylation of glucose to glucose-6-phosphate by hexokinase; thus, there must be a metabolic advantage in utilizing this shunt pathway. The dogmatic view of glycogen as a storage depot persists, based on initial descriptions of glycogen supporting neural function in the face of aglycemia. The variable latency to conduction failure, dependent upon tissue glycogen levels, provided convincing evidence of the role played by glycogen in supporting neural function. Glycogen is located predominantly in astrocytes in the central nervous system, thus for glycogen to benefit neural elements, intercellular metabolic communication must exist in the form of astrocyte to neuron substrate transfer. Experimental evidence supports a model where glycogen is metabolized to lactate in astrocytes, with cellular expression of monocarboxylate transporters and enzymes appropriately located for lactate shuttling between astrocytes and neural elements, where lactate acts as a substrate for oxidative metabolism. Biosensor recordings have demonstrated a significant steady concentration of lactate present on the periphery of both central white matter and peripheral nerve under unstimulated baseline conditions, indicating continuous cellular efflux of lactate to the interstitium. The existence of this lactate pool argues we must reexamine the “on demand” shuttling of lactate between cellular elements, and suggests continuous lactate efflux surplus to immediate neural requirements

The Time-Domain Spectroscopic Survey: Understanding the Optically Variable Sky with SEQUELS in SDSS-III

The Time-Domain Spectroscopic Survey (TDSS) is an SDSS-IV eBOSS subproject primarily aimed at obtaining identification spectra of ~220,000 optically-variable objects systematically selected from SDSS/Pan-STARRS1 multi-epoch imaging. We present a preview of the science enabled by TDSS, based on TDSS spectra taken over ~320 deg^2 of sky as part of the SEQUELS survey in SDSS-III, which is in part a pilot survey for eBOSS in SDSS-IV. Using the 15,746 TDSS-selected single-epoch spectra of photometrically variable objects in SEQUELS, we determine the demographics of our variability-selected sample, and investigate the unique spectral characteristics inherent in samples selected by variability. We show that variability-based selection of quasars complements color-based selection by selecting additional redder quasars, and mitigates redshift biases to produce a smooth quasar redshift distribution over a wide range of redshifts. The resulting quasar sample contains systematically higher fractions of blazars and broad absorption line quasars than from color-selected samples. Similarly, we show that M-dwarfs in the TDSS-selected stellar sample have systematically higher chromospheric active fractions than the underlying M-dwarf population, based on their H-alpha emission. TDSS also contains a large number of RR Lyrae and eclipsing binary stars with main-sequence colors, including a few composite-spectrum binaries. Finally, our visual inspection of TDSS spectra uncovers a significant number of peculiar spectra, and we highlight a few cases of these interesting objects. With a factor of ~15 more spectra, the main TDSS survey in SDSS-IV will leverage the lessons learned from these early results for a variety of time-domain science applications.Comment: 17 pages, 14 figures, submitted to Ap

23 High Redshift Supernovae from the IfA Deep Survey: Doubling the SN Sample at z>0.7

We present photometric and spectroscopic observations of 23 high redshift supernovae spanning a range of z=0.34-1.03, 9 of which are unambiguously classified as Type Ia. These supernovae were discovered during the IfA Deep Survey, which began in September 2001 and observed a total of 2.5 square degrees to a depth of approximately m=25-26 in RIZ over 9-17 visits, typically every 1-3 weeks for nearly 5 months, with additional observations continuing until April 2002. We give a brief description of the survey motivations, observational strategy, and reduction process. This sample of 23 high-redshift supernovae includes 15 at z>0.7, doubling the published number of objects at these redshifts, and indicates that the evidence for acceleration of the universe is not due to a systematic effect proportional to redshift. In combination with the recent compilation of Tonry et al. (2003), we calculate cosmological parameter density contours which are consistent with the flat universe indicated by the CMB (Spergel et al. 2003). Adopting the constraint that Omega_total = 1.0, we obtain best-fit values of (Omega_m, Omega_Lambda)=(0.33, 0.67) using 22 SNe from this survey augmented by the literature compilation. We show that using the empty-beam model for gravitational lensing does not eliminate the need for Omega_Lambda > 0. Experience from this survey indicates great potential for similar large-scale surveys while also revealing the limitations of performing surveys for z>1 SNe from the ground.Comment: 67 pages, 12 figures, 12 tables, accepted for publication in the Astrophysical Journa

A guideline for the outpatient management of glycaemic control in people with cancer

Individuals with cancer are at increased risk of developing new onset diabetes mellitus and hyperglycaemia, and an estimated 20% of people with cancer already have an underlying diagnosis of diabetes mellitus. People with both cancer and diabetes may have an increased risk of toxicities, hospital admissions and morbidity, with hyperglycaemia potentially attenuating the efficacy of chemotherapy often secondary to dose reductions and early cessation. Numerous studies have demonstrated that hyperglycaemia is prognostic of worse overall survival and risk of cancer recurrence. These guidelines aim to provide the oncology/haemato-oncology and diabetes multidisciplinary teams with the tools to manage people with diabetes commencing anti-cancer/ glucocorticoid therapy, as well as identifying individuals without a known diagnosis of diabetes who are at risk of developing hyperglycaemia and new onset diabetes

Citizen Social Science for more integrative and effective climate action: a science-policy perspective

Governments are struggling to limit global temperatures below the 2°C Paris target with existing climate change policy approaches. This is because conventional climate policies have been predominantly (inter)nationally top-down, which limits citizen agency in driving policy change and influencing citizen behavior. Here we propose elevating Citizen Social Science (CSS) to a new level across governments as an advanced collaborative approach of accelerating climate action and policies that moves beyond conventional citizen science and participatory approaches. Moving beyond the traditional science-policy model of the democratization of science in enabling more inclusive climate policy change, we present examples of how CSS can potentially transform citizen behavior and enable citizens to become key agents in driving climate policy change. We also discuss the barriers that could impede the implementation of CSS and offer solutions to these. In doing this, we articulate the implications of increased citizen action through CSS in moving forward the broader normative and political program of transdisciplinary and co-productive climate change research and policy

Executive "Brake Failure" following deactivation of human frontal lobe

In the course of daily living, humans frequently encounter situations in which a motor activity, once initiated, becomes unnecessary or inappropriate. Under such circumstances, the ability to inhibit motor responses can be of vital importance. Although the nature of response inhibition has been studied in psychology for several decades, its neural basis remains unclear. Using transcranial magnetic stimulation, we found that temporary deactivation of the pars opercularis in the right inferior frontal gyrus selectively impairs the ability to stop an initiated action. Critically, deactivation of the same region did not affect the ability to execute responses, nor did it influence physiological arousal. These findings confirm and extend recent reports that the inferior frontal gyrus is vital for mediating response inhibition

Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders

The adverse effects of prenatal alcohol exposure constitute a continuum of disabilities (fetal alcohol spectrum disorders [FASD]). In 1996, the Institute of Medicine established diagnostic categories delineating the spectrum but not specifying clinical criteria by which diagnoses could be assigned. In 2005, the authors published practical guidelines operationalizing the Institute of Medicine categories, allowing for standardization of FASD diagnoses in clinical settings. The purpose of the current report is to present updated diagnostic guidelines based on a thorough review of the literature and the authors’ combined expertise based on the evaluation of >10 000 children for potential FASD in clinical settings and in epidemiologic studies in conjunction with National Institute on Alcohol Abuse and Alcoholism–funded studies, the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, and the Collaboration on FASD Prevalence. The guidelines were formulated through conference calls and meetings held at National Institute on Alcohol Abuse and Alcoholism offices in Rockville, MD. Specific areas addressed include the following: precise definition of documented prenatal alcohol exposure; neurobehavioral criteria for diagnosis of fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder; revised diagnostic criteria for alcohol-related birth defects; an updated comprehensive research dysmorphology scoring system; and a new lip/philtrum guide for the white population, incorporating a 45-degree view. The guidelines reflect consensus among a large and experienced cadre of FASD investigators in the fields of dysmorphology, epidemiology, neurology, psychology, developmental/behavioral pediatrics, and educational diagnostics. Their improved clarity and specificity will guide clinicians in accurate diagnosis of infants and children prenatally exposed to alcohol

The observed state of the water cycle in the early twenty-first century

Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 28 (2015): 8289–8318, doi:10.1175/JCLI-D-14-00555.1.This study quantifies mean annual and monthly fluxes of Earth’s water cycle over continents and ocean basins during the first decade of the millennium. To the extent possible, the flux estimates are based on satellite measurements first and data-integrating models second. A careful accounting of uncertainty in the estimates is included. It is applied within a routine that enforces multiple water and energy budget constraints simultaneously in a variational framework in order to produce objectively determined optimized flux estimates. In the majority of cases, the observed annual surface and atmospheric water budgets over the continents and oceans close with much less than 10% residual. Observed residuals and optimized uncertainty estimates are considerably larger for monthly surface and atmospheric water budget closure, often nearing or exceeding 20% in North America, Eurasia, Australia and neighboring islands, and the Arctic and South Atlantic Oceans. The residuals in South America and Africa tend to be smaller, possibly because cold land processes are negligible. Fluxes were poorly observed over the Arctic Ocean, certain seas, Antarctica, and the Australasian and Indonesian islands, leading to reliance on atmospheric analysis estimates. Many of the satellite systems that contributed data have been or will soon be lost or replaced. Models that integrate ground-based and remote observations will be critical for ameliorating gaps and discontinuities in the data records caused by these transitions. Continued development of such models is essential for maximizing the value of the observations. Next-generation observing systems are the best hope for significantly improving global water budget accounting.This research was funded by multiple grants from NASA’s Energy and Water Cycle Study (NEWS) program.2016-05-0