Primitive Early Eocene bat from Wyoming and the evolution of flight and echolocation

Bats ( Chiroptera) represent one of the largest and most diverse radiations of mammals, accounting for one- fifth of extant species(1). Although recent studies unambiguously support bat monophyly(2-4) and consensus is rapidly emerging about evolutionary relationships among extant lineages(5-8), the fossil record of bats extends over 50 million years, and early evolution of the group remains poorly understood(5,7-9). Here we describe a new bat from the Early Eocene Green River Formation of Wyoming, USA, with features that are more primitive than seen in any previously known bat. The evolutionary pathways that led to flapping flight and echolocation in bats have been in dispute(7-18), and until now fossils have been of limited use in documenting transitions involved in this marked change in lifestyle. Phylogenetically informed comparisons of the new taxon with other bats and non- flying mammals reveal that critical morphological and functional changes evolved incrementally. Forelimb anatomy indicates that the new bat was capable of powered flight like other Eocene bats, but ear morphology suggests that it lacked their echolocation abilities, supporting a 'flight first' hypothesis for chiropteran evolution. The shape of the wings suggests that an undulating gliding - fluttering flight style may be primitive for bats, and the presence of a long calcar indicates that a broad tail membrane evolved early in Chiroptera, probably functioning as an additional airfoil rather than as a prey-capture device. Limb proportions and retention of claws on all digits indicate that the new bat may have been an agile climber that employed quadrupedal locomotion and under- branch hanging behaviour.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62816/1/nature06549.pd

Engaging Undergraduates in Science Research: Not Just About Faculty Willingness.

Despite the many benefits of involving undergraduates in research and the growing number of undergraduate research programs, few scholars have investigated the factors that affect faculty members' decisions to involve undergraduates in their research projects. We investigated the individual factors and institutional contexts that predict faculty members' likelihood of engaging undergraduates in their research project(s). Using data from the Higher Education Research Institute's 2007-2008 Faculty Survey, we employ hierarchical generalized linear modeling to analyze data from 4,832 science, technology, engineering, and mathematics (STEM) faculty across 194 institutions to examine how organizational citizenship behavior theory and social exchange theory relate to mentoring students in research. Key findings show that faculty who work in the life sciences and those who receive government funding for their research are more likely to involve undergraduates in their research project(s). In addition, faculty at liberal arts or historically Black colleges are significantly more likely to involve undergraduate students in research. Implications for advancing undergraduate research opportunities are discussed

Synergistic roles of climate warming and human occupation in Patagonian megafaunal extinctions during the Last Deglaciation

The causes of Late Pleistocene megafaunal extinctions (60,000 to 11,650 years ago, hereafter 60 to 11.65 ka) remain contentious, with major phases coinciding with both human arrival and climate change around the world. The Americas provide a unique opportunity to disentangle these factors as human colonization took place over a narrow time frame (~15 to 14.6 ka) but during contrasting temperature trends across each continent. Unfortunately, limited data sets in South America have so far precluded detailed comparison. We analyze genetic and radiocarbon data from 89 and 71 Patagonian megafaunal bones, respectively, more than doubling the high-quality Pleistocene megafaunal radiocarbon data sets from the region.We identify a narrowmegafaunal extinction phase 12,280 ± 110 years ago, some 1 to 3 thousand years after initial human presence in the area. Although humans arrived immediately prior to a cold phase, the Antarctic Cold Reversal stadial, megafaunal extinctions did not occur until the stadial finished and the subsequent warming phase commenced some 1 to 3 thousand years later. The increased resolution provided by the Patagonian material reveals that the sequence of climate and extinction events in North and South America were temporally inverted, but in both cases, megafaunal extinctions did not occur until human presence and climate warming coincided. Overall, metapopulation processes involving subpopulation connectivity on a continental scale appear to have been critical for megafaunal species survival of both climate change and human impacts.Fil: Metcalf, Jessica L.. University of Adelaide; Australia. State University of Colorado Boulder; Estados UnidosFil: Turney, Chris. University of New South Wales; AustraliaFil: Barnett, Ross. University of Oxford; Reino Unido. Universidad de Copenhagen; DinamarcaFil: Martin, Fabiana. Universidad de Magallanes. Instituto de la Patagonia. Centro de Estudios del Hombre Austral; ChileFil: Bray, Sarah C.. University of Adelaide; Australia. University of South Australia; AustraliaFil: Vilstrup, Julia T.. Universidad de Copenhagen; DinamarcaFil: Orlando, Ludovic. Universidad de Copenhagen; DinamarcaFil: Salas-Gismondi, Rodolfo. Université de Montpellier. Institut des Sciences de l’Evolution; Francia. Universidad Nacional Mayor de San Marcos; PerúFil: Loponte, Daniel Marcelo. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medina, Matias Eduardo. Centro de Estudios Históricos ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Nigris, Mariana Eleonor. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Civalero, Maria Teresa. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernández, Pablo Marcelo. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gasco, Alejandra Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Paleoecología Humana; ArgentinaFil: Duran, Victor Alberto. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Paleoecología Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Seymour, Kevin L.. Royal Ontario Museum. Department of Natural History; CanadáFil: Otaola, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; ArgentinaFil: Gil, Adolfo Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla; ArgentinaFil: Paunero, Rafael. Universidad Nacional de La Plata; ArgentinaFil: Prevosti, Francisco Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de Catamarca. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Secretaría de Industria y Minería. Servicio Geológico Minero Argentino. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Provincia de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja; ArgentinaFil: Bradshaw, Corey J. A.. University of Adelaide; AustraliaFil: Wheeler, Jane C.. Instituto de Investigación y Desarrollo de Camélidos Sudamericanos; PerúFil: Borrero, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; ArgentinaFil: Austin, Jeremy J.. University of Adelaide; AustraliaFil: Cooper, Alan. University of Adelaide; Australia. University of Oxford; Reino Unid

3, 3′-Diindolylmethane Exhibits Antileukemic Activity In Vitro and In Vivo through a Akt-Dependent Process

3,3′-diindolylmethane (DIM), one of the active products derived from Brassica plants, is a promising antitumor agent. The present study indicated that DIM significantly induced apoptosis in U937 human leukemia cells in dose- and time-dependent manners. These events were also noted in other human leukemia cells (Jurkat and HL-60) and primary human leukemia cells (AML) but not in normal bone marrow mononuclear cells. We also found that DIM-induced lethality is associated with caspases activation, myeloid cell leukemia-1 (Mcl-1) down-regulation, p21cip1/waf1 up-regulation, and Akt inactivation accompanied by c-jun NH2-terminal kinase (JNK) activation. Enforced activation of Akt by a constitutively active Akt construct prevented DIM-mediated caspase activation, Mcl-1 down-regulation, JNK activation, and apoptosis. Conversely, DIM lethality was potentiated by the PI3K inhibitor LY294002. Interruption of the JNK pathway by pharmacologic or genetic approaches attenuated DIM-induced caspases activation, Mcl-1 down-regulation, and apoptosis. Lastly, DIM inhibits tumor growth of mouse U937 xenograft, which was related to induction of apoptosis and inactivation of Akt, as well as activation of JNK. Collectively, these findings suggest that DIM induces apoptosis in human leukemia cell lines and primary human leukemia cells, and exhibits antileukemic activity in vivo through Akt inactivation and JNK activation

The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines

<p>Abstract</p> <p>Background</p> <p>Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. Despite the fact that the melanoma cell preparations used in a recent vaccine trial (Mel37) were gamma-irradiated (200 Gy), approximately 25% of the preparations failed quality control release criteria which required that the irradiated cells incorporate ³H-thymidine at no more than 5% the level seen in the non-irradiated cells. We have, therefore, investigated ultraviolet (UV)-irradiation as a possible adjunct to, or replacement for gamma-irradiation.</p> <p>Methods</p> <p>Melanoma cells were gamma- and/or UV-irradiated. ³H-thymidine uptake was used to assess proliferation of the treated and untreated cells. Caspase-3 activity and DNA fragmentation were measured as indicators of apoptosis. Immunohistochemistry and Western blot analysis was used to assess antigen expression.</p> <p>Results</p> <p>UV-irradiation, either alone or in combination with gamma-irradiation, proved to be extremely effective in controlling the proliferation of melanoma cells. In contrast to gamma-irradiation, UV-irradiation was also capable of inducing significant levels of apoptosis. UV-irradiation, but not gamma-irradiation, was associated with the loss of tyrosinase expression. Neither form of radiation affected the expression of gp100, MART-1/MelanA, or S100.</p> <p>Conclusion</p> <p>These results indicate that UV-irradiation may increase the safety of autologous melanoma vaccines, although it may do so at the expense of altering the antigenic profile of the irradiated tumor cells.</p

Genomics, Exometabolomics, and Metabolic Probing Reveal Conserved Proteolytic Metabolism of Thermoflexus hugenholtzii and Three Candidate Species From China and Japan

Thermoflexus hugenholtzii JAD2 , the only cultured representative of the Chloroflexota order Thermoflexales, is abundant in Great Boiling Spring (GBS), NV, United States, and close relatives inhabit geothermal systems globally. However, no defined medium exists for T. hugenholtzii JAD2 and no single carbon source is known to support its growth, leaving key knowledge gaps in its metabolism and nutritional needs. Here, we report comparative genomic analysis of the draft genome of T. hugenholtzii JAD2 and eight closely related metagenome-assembled genomes (MAGs) from geothermal sites in China, Japan, and the United States, representing “Candidatus Thermoflexus japonica,” “Candidatus Thermoflexus tengchongensis,” and “Candidatus Thermoflexus sinensis.” Genomics was integrated with targeted exometabolomics and C metabolic probing of T. hugenholtzii. The Thermoflexus genomes each code for complete central carbon metabolic pathways and an unusually high abundance and diversity of peptidases, particularly Metallo- and Serine peptidase families, along with ABC transporters for peptides and some amino acids. The T. hugenholtzii JAD2 exometabolome provided evidence of extracellular proteolytic activity based on the accumulation of free amino acids. However, several neutral and polar amino acids appear not to be utilized, based on their accumulation in the medium and the lack of annotated transporters. Adenine and adenosine were scavenged, and thymine and nicotinic acid were released, suggesting interdependency with other organisms in situ. Metabolic probing of T. hugenholtzii JAD2 using C-labeled compounds provided evidence of oxidation of glucose, pyruvate, cysteine, and citrate, and functioning glycolytic, tricarboxylic acid (TCA), and oxidative pentose-phosphate pathways (PPPs). However, differential use of position-specific C-labeled compounds showed that glycolysis and the TCA cycle were uncoupled. Thus, despite the high abundance of Thermoflexus in sediments of some geothermal systems, they appear to be highly focused on chemoorganotrophy, particularly protein degradation, and may interact extensively with other microorganisms in situ. T T T 13 T T 13 1

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe