The Drosophila Caspase DRONC Cleaves following Glutamate or Aspartate and Is Regulated by DIAP1, HID, and GRIM

The caspase family of cysteine proteases plays important roles in bringing about apoptotic cell death. All caspases studied to date cleave substrates COOH-terminal to an aspartate. Here we show that the Drosophila caspase DRONC cleaves COOH-terminal to glutamate as well as aspartate. DRONC autoprocesses itself following a glutamate residue, but processes a second caspase, drICE, following an aspartate. DRONC prefers tetrapeptide substrates in which aliphatic amino acids are present at the P2 position, and the P1 residue can be either aspartate or glutamate. Expression of a dominant negative form of DRONC blocks cell death induced by the Drosophila cell death activators reaper, hid, and grim, and DRONC overexpression in flies promotes cell death. Furthermore, the Drosophila cell death inhibitor DIAP1 inhibits DRONC activity in yeast, and DIAP1's ability to inhibit DRONC-dependent yeast cell death is suppressed by HID and GRIM. These observations suggest that DRONC acts to promote cell death. However, DRONC activity is not suppressed by the caspase inhibitor and cell death suppressor baculovirus p35. We discuss possible models for DRONC function as a cell death inhibitor

Ultramafic xenoliths from the Bearpaw Mountains, Montana, USA: evidence for multiple metasomatic events in the lithospheric mantle beneath the Wyoming craton

Ultramafic xenoliths in Eocene minettes of the Bearpaw Mountains volcanic field (Montana, USA), derived from the lower lithosphere of the Wyoming craton, can be divided based on textural criteria into tectonite and cumulate groups. The tectonites consist of strongly depleted spinel lherzolites, harzburgites and dunites. Although their mineralogical compositions are generally similar to those of spinel peridotites in off-craton settings, some contain pyroxenes and spinels that have unusually low Al2O3 contents more akin to those found in cratonic spinel peridotites. Furthermore, the tectonite peridotites have whole-rock major element compositions that tend to be significantly more depleted than non-cratonic mantle spinel peridotites (high MgO, low CaO, Al2O3 and TiO2) and resemble those of cratonic mantle. These compositions could have been generated by up to 30% partial melting of an undepleted mantle source. Petrographic evidence suggests that the mantle beneath the Wyoming craton was re-enriched in three ways: (1) by silicate melts that formed mica websterite and clinopyroxenite veins; (2) by growth of phlogopite from K-rich hydrous fluids; (3) by interaction with aqueous fluids to form orthopyroxene porphyroblasts and orthopyroxenite veins. In contrast to their depleted major element compositions, the tectonite peridotites are mostly light rare earth element (LREE)-enriched and show enrichment in fluid-mobile elements such as Cs, Rb, U and Pb on mantle-normalized diagrams. Lack of enrichment in high field strength elements (HFSE; e.g. Nb, Ta, Zr and Hf) suggests that the tectonite peridotites have been metasomatized by a subduction-related fluid. Clinopyroxenes from the tectonite peridotites have distinct U-shaped REE patterns with strong LREE enrichment. They have 143Nd/144Nd values that range from 0·5121 (close to the host minette values) to 0·5107, similar to those of xenoliths from the nearby Highwood Mountains. Foliated mica websterites also have low 143Nd/144Nd values (0·5113) and extremely high 87Sr/86Sr ratios in their constituent phlogopite, indicating an ancient (probably mid-Proterozoic) enrichment. This enriched mantle lithosphere later contributed to the formation of the high-K Eocene host magmas. The cumulate group ranges from clinopyroxene-rich mica peridotites (including abundant mica wehrlites) to mica clinopyroxenites. Most contain >30% phlogopite. Their mineral compositions are similar to those of phenocrysts in the host minettes. Their whole-rock compositions are generally poorer in MgO but richer in incompatible trace elements than those of the tectonite peridotites. Whole-rock trace element patterns are enriched in large ion lithophile elements (LILE; Rb, Cs, U and Pb) and depleted in HFSE (Nb, Ta Zr and Hf) as in the host minettes, and their Sr–Nd isotopic compositions are also identical to those of the minettes. Their clinopyroxenes are LREE-enriched and formed in equilibrium with a LREE-enriched melt closely resembling the minettes. The cumulates therefore represent a much younger magmatic event, related to crystallization at mantle depths of minette magmas in Eocene times, that caused further metasomatic enrichment of the lithosphere

Trends and Associated Factors of Use of Opioid, Heroin, and Cannabis Among Patients for Emergency Department Visits in Nevada: 2009–2017

To examine trends and contributing factors of opioid, heroin, and cannabis-associated emergency department (ED) visits in Nevada. The 2009 to 2017 Nevada State ED database (n = 7,950,554 ED visits) were used. Use of opioid, heroin, and cannabis, respectively, was identified by the International Classification of Diseases, 9th & 10th Revisions. Three multivariable models, one for each of the 3 dependent variables, were conducted. Independent variables included year, insurance status, race/ethnicity, use of other substance, and mental health conditions. The number of individuals with opioid, heroin, cannabis-associated ED visits increased 3%, 10%, and 23% annually from 2009 to 2015, particularly among 21 to 29 age group, females, and African Americans. Use of other substance (odds ratio [OR] = 3.91; 95% confidence interval [CI] = 3.84, 3.99; reference - no use of other substance), mental health conditions (OR = 2.48; 95% CI = 2.43, 2.53; reference – without mental health conditions), Medicaid (OR = 1.41; 95% CI = 1.38, 1.44; reference – non-Medicaid), Medicare (OR = 1.44; 95% CI = 1.39, 1.49; reference – non-Medicare) and uninsured patients (OR = 1.52; 95% CI = 1.49, 1.56; reference - insured) were predictors of all three substance-associated ED visits. With a steady increase in trends of opioid, heroin, and cannabis-associated ED visits in recent years, the main contributing factors include patient sociodemographic factors, mental health conditions, and use of other substances

Ten-Year Trends of Utilizing Palliative Care and Palliative Procedures in Patients With Gastric Cancer in the United States From 2009 to 2018 - A Nationwide Database Study

Objectives: Little is known about the current status and the changing trends of hospitalization and palliative care consultation of patients with gastric cancer in the United States. The aim of this study was to evaluate the changing trend in the number of hospitalization, palliative care consultation, and palliative procedures in the US during a recent 10-year period using a nationwide database. Methods: This was a retrospective study that analyzed the National Inpatient Sample (NIS) database of 2009–2018. Patients aged more than 18 years who were diagnosed with a gastric cancer using International Classification of Diseases (ICD)-9 and 10 codes were included. Palliative care consultation included palliative care (ICD-9, V66.7; ICD-10, Z51.5) and advanced care planning (ICD-9, V69.89; ICD-10, Z71.89). Palliative procedures included percutaneous or endoscopic bypass, gastrostomy or enterostomy, dilation, drainage, nutrition, and irrigation for palliative purpose. Results and discussion: A total of 86,430 patients were selected and analyzed in this study. Using a compound annual growth rate (CAGR) approach, the annual number of hospitalizations of gastric cancer patients was found to be decreased during 2009–2018 (CAGR: -0.8%, P = 0.0084), while utilization rates of palliative care and palliative procedures increased (CAGR: 9.3 and 1.6%, respectively; P \u3c 0.0001). Multivariable regression analysis revealed that palliative care consultation was associated with reduced total hospital charges (−$34,188, P \u3c 0.0001). Conclusion: Utilization of palliative care consultation to patients with gastric cancer may reduce use of medical resources and hospital costs

Predictors of Hospitalization Among Newly Admitted Skilled Nursing Facility Residents: Rethinking the Role of Functional Decline

Purpose: Hospital transfer from a skilled nursing facility (SNF) is costly, and many are potentially preventable. This study examines: 1) whether functional decline is a predictor of hospital transfer, and 2) the magnitude of relationships between predictors (functional impairment and chronic medical illness) and hospital transfer from SNFs. Methods: We used Minimum Data Set (MDS) Version 2.0 in the state of Michigan between 2007 and 2009. In total, 196,662 new SNF admissions were observed. Multilevel generalized estimating equations and regression models were performed for each functional and clinical domain while adjusting for demographic variables and change in activities of daily living (ADL). Results: 65% of recently admitted SNF residents experienced functional decline after SNF admission, and 58% were readmitted to a hospital. Residents who needed extensive assistance or were completely dependent in their functional domains had pressure ulcers, deteriorated mood or lower cognitive performance scale scores. These residents experienced higher chances of hospital transfer. However, a deteriorated ADL played a significant role in all multivariate models, indicating that a decline in ADL is a stronger predictor of hospital transfer than other functional or clinical predictors. Conclusion: Although all functional impairments and chronic medical illness can be associated with hospital transfer, functional decline may be the most important predictor of hospital transfer in patients newly admitted to an SNF

The Two-Fluid Dynamics and Energetics of the Asymmetric Magnetic Reconnection in Laboratory and Space Plasmas

Magnetic reconnection is a fundamental process in magnetized plasma where magnetic energy is converted to plasma energy. Despite huge differences in the physical size of the reconnection layer, remarkably similar characteristics are observed in both laboratory and magnetosphere plasmas. Here we present the comparative study of the dynamics and physical mechanisms governing the energy conversion in the laboratory and space plasma in the context of two-fluid physics, aided by numerical simulations. In strongly asymmetric reconnection layers with negligible guide field, the energy deposition to electrons is found to primarily occur in the electron diffusion region where electrons are demagnetized and diffuse. A large potential well is observed within the reconnection plane and ions are accelerated by the electric field toward the exhaust region. The present comparative study identifies the robust two-fluid mechanism operating in systems over six orders of magnitude in spatial scales and over a wide range of collisionality

Dissociation Between the Growing Opioid Demands and Drug Policy Directions Among the U.S. Older Adults with Degenerative Joint Diseases

We aim to examine temporal trends of orthopedic operations and opioid-related hospital stays among seniors in the nation and states of Oregon and Washington where marijuana legalization was accepted earlier than any others. As aging society advances in the United States (U.S.), orthopedic operations and opioid-related hospital stays among seniors increase in the nation. A serial cross-sectional cohort study using the healthcare cost and utilization project fast stats from 2006 through 2015 measured annual rate per 100,000 populations of orthopedic operations by age groups (45–64 vs 65 and older) as well as annual rate per 100,000 populations of opioid-related hospital stays among 65 and older in the nation, Oregon and Washington states from 2008 through 2017. Orthopedic operations (knee arthroplasty, total or partial hip replacement, spinal fusion or laminectomy) and opioid-related hospital stays were measured. The compound annual growth rate (CAGR) was used to quantify temporal trends of orthopedic operations by age groups as well as opioid-related hospital stays and was tested by Rao–Scott correction of χ2 for categorical variables. The CAGR (4.06%) of orthopedic operations among age 65 and older increased (P...) (See full abstract in article

Laboratory Study of Collisionless Magnetic Reconnection

A concise review is given on the past two decades' results from laboratory experiments on collisionless magnetic reconnection in direct relation with space measurements, especially by Magnetospheric Multiscale (MMS) mission. Highlights include spatial structures of electromagnetic fields in ion and electron diffusion regions as a function of upstream symmetry and guide field strength; energy conversion and partition from magnetic field to ions and electrons including particle acceleration; electrostatic and electromagnetic kinetic plasma waves with various wavelengths; and plasmoid-mediated multiscale reconnection. Combined with the progress in theoretical, numerical, and observational studies, the physics foundation of fast reconnection in colisionless plasmas has been largely established, at least within the parameter ranges and spatial scales that were studied. Immediate and long-term future opportunities based on multiscale experiments and space missions supported by exascale computation are discussed, including dissipation by kinetic plasma waves, particle heating and acceleration, and multiscale physics across fluid and kinetic scales.Comment: 40 pages, 15 figure