Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol-Preferring (P) Rats

Background Most alcoholics experience periods of voluntary alcohol abstinence or imposed alcohol deprivation followed by a return to alcohol drinking. This study examined whether varenicline (VAR) reduces alcohol intake during a return to drinking after periods of alcohol deprivation in rats selectively bred for high alcohol drinking (the alcohol preferring or “P” rats). Methods Alcohol-experienced P rats were given 24-hour access to food and water and scheduled access to alcohol (15% and 30% v/v) for 2 h/d. After 4 weeks, rats were deprived of alcohol for 2 weeks, followed by reaccess to alcohol for 2 weeks, and this pattern was repeated for a total of 3 cycles. Rats were fed either vehicle (VEH) or VAR, in doses of 0.5, 1.0, or 2.0 mg/kg BW, at 1 hour prior to onset of the daily alcohol reaccess period for the first 5 days of each of the 3 alcohol reaccess cycles. Results Low-dose VAR (0.5 mg/kg BW) reduced alcohol intake during the 5 days of drug treatment in alcohol reaccess cycles 1 and 2. Higher doses of VAR (1.0 mg/kg BW and 2.0 mg/kg BW) reduced alcohol intake during the 5 days of treatment in all 3 alcohol reaccess cycles. The decrease in alcohol intake disappeared with termination of VAR treatment in all alcohol reaccess cycles. Conclusions The results demonstrate that VAR decreases alcohol intake during multiple cycles of alcohol reaccess following alcohol deprivation in rats and suggests that it may prevent a return to heavy alcohol drinking during a lapse from alcohol abstinence in humans with alcohol use disorder

Lactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expression

Chemical inhibitors of histone deacetylase (HDAC) activity are used as experimental tools to induce histone hyperacetylation and deregulate gene transcription, but it is not known whether the inhibition of HDACs plays any part in the normal physiological regulation of transcription. Using both in vitro and in vivo assays, we show that lactate, which accumulates when glycolysis exceeds the cell’s aerobic metabolic capacity, is an endogenous HDAC inhibitor, deregulating transcription in an HDAC-dependent manner. Lactate is a relatively weak inhibitor (IC(50) 40 mM) compared to the established inhibitors trichostatin A and butyrate, but the genes deregulated overlap significantly with those affected by low concentrations of the more potent inhibitors. HDAC inhibition causes significant up and downregulation of genes, but genes that are associated with HDAC proteins are more likely to be upregulated and less likely to be downregulated than would be expected. Our results suggest that the primary effect of HDAC inhibition by endogenous short-chain fatty acids like lactate is to promote gene expression at genes associated with HDAC proteins. Therefore, we propose that lactate may be an important transcriptional regulator, linking the metabolic state of the cell to gene transcription

Quantized Majorana conductance

Majorana zero-modes hold great promise for topological quantum computing. Tunnelling spectroscopy in electrical transport is the primary tool to identify the presence of Majorana zero-modes, for instance as a zero-bias peak (ZBP) in differential-conductance. The Majorana ZBP-height is predicted to be quantized at the universal conductance value of 2e2/h at zero temperature. Interestingly, this quantization is a direct consequence of the famous Majorana symmetry, 'particle equals antiparticle'. The Majorana symmetry protects the quantization against disorder, interactions, and variations in the tunnel coupling. Previous experiments, however, have shown ZBPs much smaller than 2e2/h, with a recent observation of a peak-height close to 2e2/h. Here, we report a quantized conductance plateau at 2e2/h in the zero-bias conductance measured in InSb semiconductor nanowires covered with an Al superconducting shell. Our ZBP-height remains constant despite changing parameters such as the magnetic field and tunnel coupling, i.e. a quantized conductance plateau. We distinguish this quantized Majorana peak from possible non-Majorana origins, by investigating its robustness on electric and magnetic fields as well as its temperature dependence. The observation of a quantized conductance plateau strongly supports the existence of non-Abelian Majorana zero-modes in the system, consequently paving the way for future braiding experiments.Comment: 5 figure

Electric field tunable superconductor-semiconductor coupling in Majorana nanowires

We study the effect of external electric fields on superconductor-semiconductor coupling by measuring the electron transport in InSb semiconductor nanowires coupled to an epitaxially grown Al superconductor. We find that the gate voltage induced electric fields can greatly modify the coupling strength, which has consequences for the proximity induced superconducting gap, effective g-factor, and spin-orbit coupling, which all play a key role in understanding Majorana physics. We further show that level repulsion due to spin-orbit coupling in a finite size system can lead to seemingly stable zero bias conductance peaks, which mimic the behavior of Majorana zero modes. Our results improve the understanding of realistic Majorana nanowire systems.Comment: 10 pages, 5 figures, supplemental information as ancillary fil

Observations of the atmosphere and surface state over Terra Nova Bay, Antarctica, using unmanned aerial systems

In September 2012 five Aerosonde unmanned aircraft were used to make measurements of the atmospheric state over the Terra Nova Bay polynya, Antarctica, to explore the details of air–sea ice–ocean coupling. A total of 14 flights were completed in September 2012. Ten of the flight missions consisted of two unmanned aerial systems (UAS) sampling the atmosphere over Terra Nova Bay on 5 different days, with one UAS focusing on the downwind evolution of the air mass and a second UAS flying transects roughly perpendicular to the low-level winds. The data from these coordinated UAS flights provide a comprehensive three-dimensional data set of the atmospheric state (air temperature, humidity, pressure, and wind) and surface skin temperature over Terra Nova Bay. The remaining UAS flights during the September 2012 field campaign included two local flights near McMurdo Station for flight testing, a single UAS flight to Terra Nova Bay, and a single UAS flight over the Ross Ice Shelf and Ross Sea polynya. A data set containing the atmospheric and surface data as well as operational aircraft data have been submitted to the United States Antarctic Program Data Coordination Center (USAP-DCC)

Designing an intervention to help people with colorectal adenomas reduce their intake of red and processed meat and increase their levels of physical activity: a qualitative study

Background: most cases of colorectal cancer (CRC) arise from adenomatous polyps and malignant potential is greatest in high risk adenomas. There is convincing observational evidence that red and processed meat increase the risk of CRC and that higher levels of physical activity reduce the risk. However, no definitive randomised trial has demonstrated the benefit of behaviour change on reducing polyp recurrence and no consistent advice is currently offered to minimise patient risk. This qualitative study aimed to assess patients' preferences for dietary and physical activity interventions and ensure their appropriate and acceptable delivery to inform a feasibility trial.Methods: patients aged 60-74 included in the National Health Service Bowel Cancer Screening Programme (NHSBCSP) were selected from a patient tracking database. After a positive faecal occult blood test (FOBt), all had been diagnosed with an intermediate or high risk adenoma (I/HRA) at colonoscopy between April 2008 and April 2010. Interested patients and their partners were invited to attend a focus group or interview in July 2010. A topic guide, informed by the objectives of the study, was used. A thematic analysis was conducted in which transcripts were examined to ensure that all occurrences of each theme had been accounted for and compared.Results: two main themes emerged from the focus groups: a) experiences of having polyps and b) changing behaviour. Participants had not associated polyp removal with colorectal cancer and most did not remember being given any information or advice relating to this at the time. Heterogeneity of existing diet and physical activity levels was noted. There was a lack of readiness to change behaviour in many people in the target population.Conclusion: this study has demonstrated the difficulties involved in developing interventions to change dietary and physical activity behaviour in this population. The need to tailor the intervention to individuals, the lack of knowledge about the aetiology of colon cancer and the lack of motivation to change behaviour are critical factors

Correction for Johansson et al., An open challenge to advance probabilistic forecasting for dengue epidemics.

Correction for “An open challenge to advance probabilistic forecasting for dengue epidemics,” by Michael A. Johansson, Karyn M. Apfeldorf, Scott Dobson, Jason Devita, Anna L. Buczak, Benjamin Baugher, Linda J. Moniz, Thomas Bagley, Steven M. Babin, Erhan Guven, Teresa K. Yamana, Jeffrey Shaman, Terry Moschou, Nick Lothian, Aaron Lane, Grant Osborne, Gao Jiang, Logan C. Brooks, David C. Farrow, Sangwon Hyun, Ryan J. Tibshirani, Roni Rosenfeld, Justin Lessler, Nicholas G. Reich, Derek A. T. Cummings, Stephen A. Lauer, Sean M. Moore, Hannah E. Clapham, Rachel Lowe, Trevor C. Bailey, Markel García-Díez, Marilia Sá Carvalho, Xavier Rodó, Tridip Sardar, Richard Paul, Evan L. Ray, Krzysztof Sakrejda, Alexandria C. Brown, Xi Meng, Osonde Osoba, Raffaele Vardavas, David Manheim, Melinda Moore, Dhananjai M. Rao, Travis C. Porco, Sarah Ackley, Fengchen Liu, Lee Worden, Matteo Convertino, Yang Liu, Abraham Reddy, Eloy Ortiz, Jorge Rivero, Humberto Brito, Alicia Juarrero, Leah R. Johnson, Robert B. Gramacy, Jeremy M. Cohen, Erin A. Mordecai, Courtney C. Murdock, Jason R. Rohr, Sadie J. Ryan, Anna M. Stewart-Ibarra, Daniel P. Weikel, Antarpreet Jutla, Rakibul Khan, Marissa Poultney, Rita R. Colwell, Brenda Rivera-García, Christopher M. Barker, Jesse E. Bell, Matthew Biggerstaff, David Swerdlow, Luis Mier-y-Teran-Romero, Brett M. Forshey, Juli Trtanj, Jason Asher, Matt Clay, Harold S. Margolis, Andrew M. Hebbeler, Dylan George, and Jean-Paul Chretien, which was first published November 11, 2019; 10.1073/pnas.1909865116. The authors note that the affiliation for Xavier Rodó should instead appear as Catalan Institution for Research and Advanced Studies (ICREA) and Climate and Health Program, Barcelona Institute for Global Health (ISGlobal). The corrected author and affiliation lines appear below. The online version has been corrected