PMI 5011 regulates the ubiquitin proteasome system in skeletal muscle

Insulin resistance in type 2 diabetes is associated with impaired glucose and protein metabolism in skeletal muscle. The impaired insulin signaling in skeletal muscle affects muscle mass by tilting the balance between skeletal muscle protein synthesis and degradation toward degradation, a process that is primarily regulated by the ubiquitin-proteasome system. Studies have shown that an extensively characterized ethanol extract of Artemisia dracunculus L (Russian Tarragon), termed PMI 5011, enhances insulin signaling in human primary skeletal muscle cells and in a rodent model of insulin resistance. The aim of this project is to determine if the effect of PMI 5011 on insulin signaling extends to regulation of ubiquitin-proteasome activity in skeletal muscle. To evaluate the effect of PMI 5011 on the ubiquitin-proteasome system, we used two in vitro models of insulin resistance in C2C12 myotubes and the KKAy mouse model of insulin resistance in vivo. Our studies show that PMI 5011 enhances the inhibitory effect of insulin on proteasome activity and ubiquitylation in skeletal muscle in vitro and in vivo. In addition, PMI 5011 inhibits non-proteasomal protein degradation in vivo, indicating that PMI 5011 is a potent inhibitor of skeletal muscle protein degradation. PMI 5011 also regulates the expression of Atrogin-1 and MuRF-1, muscle-specific ubiquitin ligases that are required for ubiquitin-dependent protein degradation in skeletal muscle. Both Atrogin-1 and MuRF-1 gene and protein expression is elevated with impaired insulin signaling and our studies show that PMI 5011 reduces the expression of these ligases while enhancing Akt phosphorylation. In summary, these studies demonstrate that PMI 5011 regulates the ubiquitin-proteasome in insulin resistant states in vitro and in vivo. PMI 5011 may therefore be a therapeutic target for enhancing insulin sensitivity leading to conservation of muscle mass in type 2 diabetes

Physical Characteristics, Hematology, and Serum Chemistry of Freeranging Gray Wolves, Canis lupus, in Southcentral Alaska

Examination of morphometric characteristics and blood parameters has become a widely used tool for assessing the physiological and nutritional status of wild and captive animals. During 1976 through 1984, 155 Gray Wolves (Canis lupus) were chemically immobilized in south-central Alaska. Of those, we obtained physical measurements from 132 and blood samples from 121 individuals. Also, 208 carcasses of harvested and dead radiocollared Wolves were weighed and measured. We obtained blood samples from three of the fresh carcasses. We measured age, body weight, skull length and width, and upper and lower canine length. We analyzed blood serum for Ca, P, Fe, chlorides, creatinine, glucose, lactic dehydrogenase, alkaline phosphatase, glutamic oxalic transaminase, triglyceride, beta globulin, serum urea nitrogen, and uric acid. We obtained packed cell volume and hemoglobin values from whole blood. We classified samples by season, sex, and age. Seasonal differences were observed for physical measurements, packed cell volume, alkaline phosphatase, and serum urea nitrogen. Age differences were observed for physical measurements, hemoglobin, packed cell volume, alkaline phosphatase, P, Ca, creatinine, serum urea nitrogen, and percent femur bone marrow fat. However, differences among sexes were observed for physical measurements only. These data provide a baseline for physical condition, hematology, and serum chemistry for free-ranging Gray Wolves

A Search for a Sub-Earth Sized Companion to GJ 436 and a Novel Method to Calibrate Warm Spitzer IRAC Observations

We discovered evidence for a possible additional 0.75 R_Earth transiting planet in the NASA EPOXI observations of the known M dwarf exoplanetary system GJ 436. Based on an ephemeris determined from the EPOXI data, we predicted a transit event in an extant Spitzer Space Telescope 8 micron data set of this star. Our subsequent analysis of those Spitzer data confirmed the signal of the predicted depth and at the predicted time, but we found that the transit depth was dependent on the aperture used to perform the photometry. Based on these suggestive findings, we gathered new Warm Spitzer Observations of GJ 436 at 4.5 microns spanning a time of transit predicted from the EPOXI and Spitzer 8 micron candidate events. The 4.5 micron data permit us to rule out a transit at high confidence, and we conclude that the earlier candidate transit signals resulted from correlated noise in the EPOXI and Spitzer 8 micron observations. In the course of this investigation, we developed a novel method for correcting the intrapixel sensitivity variations of the 3.6 and 4.5 micron channels of the Infrared Array Camera (IRAC) instrument. We demonstrate the sensitivity of Warm Spitzer observations of M dwarfs to confirm sub-Earth sized planets. Our analysis will inform similar work that will be undertaken to use Warm Spitzer observations to confirm rocky planets discovered by the Kepler mission.Comment: 22 pages, 8 figures, accepted for publication in PAS

How satisfied are carers/families with a night team service, as part of 24/7 hospice at home care?

Background. Rennie Grove Hospice Care (RGHC) runs a 24/7 service with an on call night team. Through an independent study, carer’s levels of service satisfaction with the night team were investigated. Methods. A questionnaire was sent to carers (n=268) who had a relative die under the care of RGHC within the last 6 weeks to one year, 84 completed questionnaires were returned. Follow-up face-to-face semi-structured interviews were carried out with carers (n=18). Quantitative data was analysed using SPSS v 22, while qualitative data was thematically analysed. Results. The carer questionnaire reported that 71% thought the speed of the response by the night team was fast. Overall satisfaction with telephone call response was high with 82% very satisfied. Cares also agreed strongly that the telephone calls provided good quality of care (90%), good follow-up care (88%), that they were given sufficient time (88%), and received useful advice (83%). For a visit, 93% of carers were highly satisfied and 7% satisfied. Carers strongly agreed that they were given sufficient time (90%), and were confident in the care provided (90%), care was useful (87%) and follow-up was good (84%), worries were reduced (81%) and they had a say in decisions made (81%). During the interviews, carers described the night service as: supportive, amazing, caring, reassuring, professional, kind and compassionate, excellent, loving, calm. Carers perceived the service to be holistic and rated the service highly for supporting them to ensure family members could be cared for at home, as preferred. For comparison, of those dying in hospital, only 46% were highly satisfied. Carer wellbeing scores were lower than the national average, but reported similar levels of anxiety. Conclusions. A night team service can provide excellent, reassuring and holistic care that meets the care needs and wishes of the patient and family

Flow cytometric and immunohistochemical detection of in vivo BrdU-labeled cells in mouse fat depots

This study has determined the natural frequency and localization of progenitor/stem cells within fat depots in situ based on their ability to retain DNA nucleotide label (BrdU). Neonate and mature male C57BL6/J mice were injected intraperitoneally with BrdU- and label-retaining cells (LRC) were quantified in fat depots by immunohistochemical, immunofluorescent, and flow cytometric methods. In neonates, LRC constituted 27% of the cells in inguinal fat (iWAT) and 65% in interscapular brown fat (BAT) after Day 10 and 26% of the cells in epididymal fat (eWAT) after Day 28. After 52 days, the LRC accounted for 0.72% of iWAT, 0.53% of eWAT and 1.05% of BAT, respectively. The BrdU-labeled cells localized to two areas: single cells distributed among adipocytes or those adjacent to the blood vessels wall. In mature C57BL6/J mice, flow cytometric analysis determined that a majority of the LRC were also positive for stem cell antigen-1 (Sca-1). © 2008 Elsevier Inc. All rights reserved

Low False-Positive Rate of Kepler Candidates Estimated From A Combination Of Spitzer And Follow-Up Observations

(Abridged) NASA's Kepler mission has provided several thousand transiting planet candidates, yet only a small subset have been confirmed as true planets. Therefore, the most fundamental question about these candidates is the fraction of bona fide planets. Estimating the rate of false positives of the overall Kepler sample is necessary to derive the planet occurrence rate. We present the results from two large observational campaigns that were conducted with the Spitzer telescope during the the Kepler mission. These observations are dedicated to estimating the false positive rate (FPR) amongst the Kepler candidates. We select a sub-sample of 51 candidates, spanning wide ranges in stellar, orbital and planetary parameter space, and we observe their transits with Spitzer at 4.5 microns. We use these observations to measures the candidate's transit depths and infrared magnitudes. A bandpass-dependent depth alerts us to the potential presence of a blending star that could be the source of the observed eclipse: a false-positive scenario. For most of the candidates (85%), the transit depths measured with Kepler are consistent with the depths measured with Spitzer as expected for planetary objects, while we find that the most discrepant measurements are due to the presence of unresolved stars that dilute the photometry. The Spitzer constraints on their own yield FPRs between 5-40%, depending on the KOIs. By considering the population of the Kepler field stars, and by combining follow-up observations (imaging) when available, we find that the overall FPR of our sample is low. The measured upper limit on the FPR of our sample is 8.8% at a confidence level of 3 sigma. This observational result, which uses the achromatic property of planetary transit signals that is not investigated by the Kepler observations, provides an independent indication that Kepler's false positive rate is low.Comment: 33 pages, 16 figures, 3 tables; accepted for publication in ApJ on February 7, 201

Dynamic Volunteer Engagement and Impactful Educational Outreach Taking Us into the Next 50 Years of the Extension Master Gardener Program

According to the 2021 Extension Master Gardener (EMG) National Summary, the EMG Volunteer Program had an estimated 84,700 volunteers throughout the United States. These volunteers helped communities garden and grow food, provided opportunities to engage in activities that improved physical and mental health, and worked on projects that addressed environmental issues. In total, these programs contributed 3.1 million hours of education to local communities and $88 million dollars in value to the public. However, the COVID-19 pandemic presented challenges for the program, with many states implementing reduced requirements and increased flexibility for volunteers. The workshop “Dynamic Volunteer Engagement and Impactful Educational Outreach Taking Us Into the Next 50 Years of the EMG Program” at the 2022 ASHS conference discussed how to engage EMG volunteers despite the limitations of limited in-person contact. The workshop featured three Extension educators and EMG coordinators who shared their experiences and strategies for engaging volunteers during the pandemic. Topics discussed included engaging volunteers in local food systems and community gardens, engaging students in horticulture at an earlier age, and digital volunteer opportunities. Overall, the workshop provided valuable insights and facilitated discussions on how to adapt and continue the EMG program during challenging times