Regional Climate Trends and Scenarios for the U.S. National Climate Assessment Part 4. Climate of the U.S. Great Plains

This document is one of series of regional climate descriptions designed to provide input that can be used in the development of the National Climate Assessment (NCA). As part of a sustained assessment approach, it is intended that these documents will be updated as new and well-vetted model results are available and as new climate scenario needs become clear. It is also hoped that these documents (and associated data and resources) are of direct benefit to decision makers and communities seeking to use this information in developing adaptation plans. There are nine reports in this series, one each for eight regions defined by the NCA, and one for the contiguous U.S. The eight NCA regions are the Northeast, Southeast, Midwest, Great Plains, Northwest, Southwest, Alaska, and Hawai‘i/Pacific Islands. These documents include a description of the observed historical climate conditions for each region and a set of climate scenarios as plausible futures – these components are described in more detail below. While the datasets and simulations in these regional climate documents are not, by themselves, new, (they have been previously published in various sources), these documents represent a more complete and targeted synthesis of historical and plausible future climate conditions around the specific regions of the NCA. There are two components of these descriptions. One component is a description of the historical climate conditions in the region. The other component is a description of the climate conditions associated with two future pathways of greenhouse gas emissions

Development of a gene silencing DNA vector derived from a broad host range geminivirus

<p>Abstract</p> <p>Background</p> <p>Gene silencing is proving to be a powerful tool for genetic, developmental, and physiological analyses. The use of viral induced gene silencing (VIGS) offers advantages to transgenic approaches as it can be potentially applied to non-model systems for which transgenic techniques are not readily available. However, many VIGS vectors are derived from Gemini viruses that have limited host ranges. We present a new, unipartite vector that is derived from a curtovirus that has a broad host range and will be amenable to use in many non-model systems.</p> <p>Results</p> <p>The construction of a gene silencing vector derived from the geminivirus <it>Beet curly top virus </it>(BCTV), named pWSRi, is reported. Two versions of the vector have been developed to allow application by biolistic techniques or by agro-infiltration. We demonstrate its ability to silence nuclear genes including ribulose bisphosphate carboxylase small subunit (<it>rbcS</it>), <it>transketolase</it>, the sulfur allele of magnesium chelatase (<it>ChlI</it>), and two homeotic transcription factors in spinach or tomato by generating gene-specific knock-down phenotypes. Onset of phenotypes occurred 3 to 12 weeks post-inoculation, depending on the target gene, in organs that developed after the application. The vector lacks movement genes and we found no evidence for significant spread from the site of inoculation. However, viral amplification in inoculated tissue was detected and is necessary for systemic silencing, suggesting that signals generated from active viral replicons are efficiently transported within the plant.</p> <p>Conclusion</p> <p>The unique properties of the pWSRi vector, the ability to silence genes in meristem tissue, the separation of virus and silencing phenotypes, and the broad natural host range of BCTV, suggest that it will have wide utility.</p

Indirect Effects of Early Parenting on Adult Antisocial Outcomes via Adolescent Conduct Disorder Symptoms and Callous-Unemotional Traits

Parental harsh punishment and warmth have been associated with child and adolescent conduct disorder (CD) symptoms and callous-unemotional (CU) traits (i.e., lack of guilt, empathy, and deficient affect); however, it is unclear whether the effect of these parenting behaviors on antisocial outcomes persists into adulthood. Thus, the present study aimed to test whether adolescent CD symptoms and CU traits mediate the effect of parental harsh punishment and warmth on adult antisocial outcomes (i.e., antisocial personality disorder (ASPD), externalizing psychopathology, partner violence, and violent and substance crime). Participants included the high-risk control and normative samples from the Fast Track project (N = 753, male = 58%, African American = 46%). Harsh punishment during kindergarten through grades 1–2 predicted higher adolescent CD symptoms, and directly observed warmth during kindergarten through grades 1–2 predicted lower adolescent CU traits. Adolescent CD symptoms predicted greater adult substance crime, and adolescent CU traits predicted greater adult ASPD symptoms and externalizing psychopathology. Further, adolescent CD symptoms indirectly accounted for the effect of parental harsh punishment on adult substance crime, and adolescent CU traits indirectly accounted for the effect of parental warmth on ASPD symptoms and externalizing psychopathology. Findings support the importance of early interventions targeting parenting behaviors to reduce risk for the development of antisocial behavior, and inform developmental models of antisocial behavior in adolescence through adulthood.The Fast Track project has been supported by National Institute of Mental Health (NIMH) Grants R18MH48043, R18MH50951, R18MH50952, R18MH50953, R01MH062988, K05MH00797, and K05MH01027; National Institute on Drug Abuse (NIDA) Grants R01DA016903, K05DA15226, RC1DA028248, and P30DA023026; National Institute of Child Health and Human Development Grant R01HD093651; and Department of Education Grant S184U30002. The Center for Substance Abuse Prevention also provided support through a memorandum of agreement with the NIMH. Additional support for this study was provided by a B.C. Children's Hospital Research Institute Investigator Grant Award and a Canada Foundation for Innovation award to Robert J. McMahon

Erythropoietin supports the survival of prostate cancer, but not growth and bone metastasis

Erythropoietin (Epo) is used in clinical settings to enhance hematopoietic function and to improve the quality of life for patients undergoing chemotherapy by reducing fatigue and the need for transfusions. However, several meta‐analyses have revealed that Epo treatments are associated with an increased risk of mortality in cancer patients. In this study, we examined the role of Epo in prostate cancer (PCa) progression, using in vitro cell culture systems and in vivo bone metastatic assays. We found that Epo did not stimulate the proliferation of PCa cell lines, but did protect PCa cells from apoptosis. In animal models of PCa metastasis, no evidence was found to support the hypothesis that Epo enhances metastasis. Together, these findings suggest that Epo may be useful for treating severe anemia in PCa patients without increasing metastatic risk. J. Cell. Biochem. 114: 2471–2478, 2013. © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100159/1/jcb24592.pd

Metformin increases cortisol regeneration by 11βHSD1 in obese men with and without type 2 diabetes mellitus

CONTEXT:The mechanism of action of metformin remains unclear. Given the regulation of the cortisol-regenerating enzyme 11βhydroxysteroid dehydrogenase 1 (11βHSD1) by insulin and the limited efficacy of selective 11βHSD1 inhibitors to lower blood glucose when co-prescribed with metformin, we hypothesized that metformin reduces 11βHSD1 activity.OBJECTIVE:To determine whether metformin regulates 11βHSD1 activity in vivo in obese men with and without type 2 diabetes mellitus.DESIGN:Double-blind, randomized, placebo-controlled, crossover study.SETTING:A hospital clinical research facility.PARTICIPANTS:Eight obese nondiabetic (OND) men and eight obese men with type 2 diabetes (ODM).INTERVENTION:Participants received 28 days of metformin (1 g twice daily), placebo, or (in the ODM group) gliclazide (80 mg twice daily) in random order. A deuterated cortisol infusion at the end of each phase measured cortisol regeneration by 11βHSD1. Oral cortisone was given to measure hepatic 11βHSD1 activity in the ODM group. The effect of metformin on 11βHSD1 was also assessed in human hepatocytes and Simpson-Golabi-Behmel syndrome adipocytes.MAIN OUTCOME MEASURES:The effect of metformin on whole-body and hepatic 11βHSD1 activity.RESULTS:Whole-body 11βHSD1 activity was approximately 25% higher in the ODM group than the OND group. Metformin increased whole-body cortisol regeneration by 11βHSD1 in both groups compared with placebo and gliclazide and tended to increase hepatic 11βHSD1 activity. In vitro, metformin did not increase 11βHSD1 activity in hepatocytes or adipocytes.CONCLUSIONS:Metformin increases whole-body cortisol generation by 11βHSD1 probably through an indirect mechanism, potentially offsetting other metabolic benefits of metformin. Co-prescription with metformin should provide a greater target for selective 11βHSD1 inhibitors

Tsunami waves extensively resurfaced the shorelines of an early Martian ocean

It has been proposed that ~3.4 billion years ago an ocean fed by enormous catastrophic floods covered most of the Martian northern lowlands. However, a persistent problem with this hypothesis is the lack of definitive paleoshoreline features. Here, based on geomorphic and thermal image mapping in the circum-Chryse and northwestern Arabia Terra regions of the northern plains, in combination with numerical analyses, we show evidence for two enormous tsunami events possibly triggered by bolide impacts, resulting in craters ~30 km in diameter and occurring perhaps a few million years apart. The tsunamis produced widespread littoral landforms, including run-up water- ice-rich and bouldery lobes, which extended tens to hundreds of kilometers over gently sloping plains and boundary cratered highlands, as well as backwash channels where wave retreat occurred on highland-boundary surfaces. The ice-rich lobes formed in association with the younger tsunami, showing that their emplacement took place following a transition into a colder global climatic regime that occurred after the older tsunami event. We conclude that, on early Mars, tsunamis played a major role in generating and resurfacing coastal terrains

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status