A frotarsius chatrathi, first tarsiiform primate (? Tarsiidae) from Africa

Tarsiiform primates have long been regarded as a Laurasian group, with an extensive fossil record in the Eocene of North America and EuropeI and two important but less well-known records from Asia

Mycobacterial CYP121 as a target for anti-TB drug discovery

Despite the introduction of the first line treatment regimen forty years ago and the continuous trials since that time to introduce new regimens, tuberculosis (TB) is considered to be the cause of considerable mortality worldwide. Recent research highlighted the Mycobacterium tuberculosis (Mtb)CYP450s as potential drug targets. This article reviews mycobacterial CYP121 as a target for anti-TB drug discovery

International consensus on (ICON) anaphylaxis

ICON: Anaphylaxis provides a unique perspective on the principal evidence-based anaphylaxis guidelines developed and published independently from 2010 through 2014 by four allergy/immunology organizations. These guidelines concur with regard to the clinical features that indicate a likely diagnosis of anaphylaxis -- a life-threatening generalized or systemic allergic or hypersensitivity reaction. They also concur about prompt initial treatment with intramuscular injection of epinephrine (adrenaline) in the mid-outer thigh, positioning the patient supine (semi-reclining if dyspneic or vomiting), calling for help, and when indicated, providing supplemental oxygen, intravenous fluid resuscitation and cardiopulmonary resuscitation, along with concomitant monitoring of vital signs and oxygenation. Additionally, they concur that H1-antihistamines, H2-antihistamines, and glucocorticoids are not initial medications of choice. For self-management of patients at risk of anaphylaxis in community settings, they recommend carrying epinephrine auto-injectors and personalized emergency action plans, as well as follow-up with a physician (ideally an allergy/immunology specialist) to help prevent anaphylaxis recurrences. ICON: Anaphylaxis describes unmet needs in anaphylaxis, noting that although epinephrine in 1 mg/mL ampules is available worldwide, other essentials, including supplemental oxygen, intravenous fluid resuscitation, and epinephrine auto-injectors are not universally available. ICON: Anaphylaxis proposes a comprehensive international research agenda that calls for additional prospective studies of anaphylaxis epidemiology, patient risk factors and co-factors, triggers, clinical criteria for diagnosis, randomized controlled trials of therapeutic interventions, and measures to prevent anaphylaxis recurrences. It also calls for facilitation of global collaborations in anaphylaxis research. In addition to confirming the alignment of major anaphylaxis guidelines, ICON: Anaphylaxis adds value by including summary tables and citing 130 key references. It is published as an information resource about anaphylaxis for worldwide use by healthcare professionals, academics, policy-makers, patients, caregivers, and the public

Calogero model with Yukawa like interaction

We study an extension of one dimensional Calogero model involving strongly coupled and electrically charged particles. Besides Calogero term $\frac{g}{2x^{2}}$, there is an extra factor described by a Yukawa like coupling modeling short distance interactions. Mimicking Calogero analysis and using developments in formal series of the wave function $\Psi (x)$ factorised as $x^{\epsilon}\Phi (x)$ with $\epsilon (\epsilon -1) =g$, we develop a technique to approach the spectrum of the generalized system and show that information on full spectrum is captured by $\Phi (x)$ and $\Phi ^{\prime \prime}(x)$ at the singular point $x=0$ of the potential. Convergence of $\int dx| \Psi (x) | ^{2}$ requires $\epsilon >-{1/2}$ and is shown to be sensitive to the zero mode of $\Phi (x)$ at $x=0$. \textbf{Key words}: \textit{Hamitonian systems, quantum integrability, Calogero model, Yukawa like potential.}Comment: 12 pages, 1 figur

Hadronic shift in pionic hydrogen

The hadronic shift in pionic hydrogen has been redetermined to be $\epsilon_{1s}=7.086\,\pm\,0.007(stat)\,\pm\,0.006(sys)$\,eV by X-ray spectroscopy of ground state transitions applying various energy calibration schemes. The experiment was performed at the high-intensity low-energy pion beam of the Paul Scherrer Institut by using the cyclotron trap and an ultimate-resolution Bragg spectrometer with bent crystals.Comment: 10 pages, 6 figure

Early Holocene fauna from a new subfossil site: A first assessment from Christmas River, south central Madagascar

We report on faunal remains recovered during recent explorations at ‘Christmas River’, the only subfossil locality known from Madagascar’s south central plateau. Recovered remains of several extinct taxa date to approximately 10,000 14C years before present (BP), including crocodiles, tortoises, the elephant bird Aepyornis, the carnivoran Cryptoprocta spelea, the lemurs Archaeolemur majori, Pachylemur insignis, and Megaladapis edwardsi, and abundant remains of the dwarf hippopotamus, Hippopotamus lemerlei. The presence of southern - limited, forest - dependent species at Christmas River supports the hypothesis that forest once extended, perhaps discontinuously, across the central highlands towards the west. One theory is that sites in the north central highlands, which are higher in elevation, maintained more mesic conditions during Plio - Quaternary climate shifts than those of the lower elevation sites of the south central highlands. Thus, elevation above sea level may have acted as a filter that limited species dispersal across the island in the past. Such a scenario would explain the distinction between more humid, higher elevation, northern highland subfossil communities versus more arid, lower elevation, southern subfossil communities. Continued exploration at Christmas River thus provides a remarkable opportunity for deciphering ecological changes that have taken place in south central Madagascar during the Holocene.RÉSUMÉMadagascar est reconnue comme l’une des régions les plus sensibles du monde en ce qui concerne les menaces pesant sur sa biodiversité, et cela à cause de niveaux d’endémisme inégalés, d’une diversité variée et d’un impact humain important sur l’environnement. Suite à la colonisation par l’Homme il y a plus de 2000 ans, des extinctions de masse de la faune et un important recul forestier ont eu lieu en laissant des marques sur les écosystèmes modernes qui sont dans un état de bouleversement écologique. Certaines plantes endémiques, par exemple, ont perdu d’importantes espèces mutualistes, des animaux ont été obligés d’exploiter d’autres ressources ou habiter des endroits auxquels ils sont mal adaptés. La diversité des plantes et des animaux a diminué, est menacée ou a même complètement disparue de certaines routes de dissémination. Bien que l’Homme soit largement incriminé dans son rôle de déclencheur de ces extinctions massives, les transformations anthropiques qui ont contribué au changement du climat sont controversées. Les hautes - terres de Madagascar sont actuellement dominées par des zones herbeuses étendues qui agissent comme des barrières empêchant les mouvements de la faune de part et d’autre de l’île. Nous suggérons qu’une forêt humide plus ou moins continue devait s’étendre sur les hautes-terres. Des informations paléoécologiques des hautes - terres du Centre sud sontènécessaires pour évaluer cette hypothèse afin de démêler la contribution relative des facteurs climatiques et anthropiques dans les changements paléoécologiques de la région. Cependant, les stations de subfossiles étaient jusqu’alors inconnues dans cette région. Nous présentons ici les résultats de recherches réalisées sur les restes fauniques découverts au cours de fouilles récentes à Christmas River, la seule station de subfossiles connue des hautes - terres du Centre sud de Madagascar. Des restes de plusieurs espèces datant approximativement de 10,000 14C B.P. ont été identifiés dont des restes appartenant à des espèces de crocodile, de tortue, de l’Aepyornis, du carnivore Cryptoprocta spelea, des lémuriens Archaeolemur majori, Pachylemur insignis et Megaladapis edwardsi ainsi que de nombreux restes de l’hippopotame nain Hippopotamus lemerlei. La présence à Christmas River d’espèces sylvicoles endémiques du Sud appuie l’hypothèse de l’existence d’une forêt, certainement discontinue, mais qui s’étendait sur les hautes - terres centrales en se poursuivant vers l’ouest. Une théorie a proposé que les sites septentrionaux des hautes - terres centrales, à des altitudes plus élevées, maintenaient des conditions plus humides au cours des changements du Plio - quaternaire que les sites méridionaux de ces hautes - terres centrales. Ainsi, dans le passé, l’altitude a du agir comme un filtre qui empêchait la dispersion des espèces d’un endroit à l’autre de l’île. Un tel scénario expliquerait la distinction entre les communautés subfossiles du nord des hautes - terres qui étaient plus humides à haute altitude et les communautés subfossiles du sud aride à basse altitude. La poursuite de l’exploration à Christmas River constitue une occasion unique pour décoder les changements écologiques qui sont intervenus dans le Sud de cette région centrale de Madagascar au cours de l’Holocène

Craniodental Morphology and Systematics of a New Family of Hystricognathous Rodents (Gaudeamuridae) from the Late Eocene and Early Oligocene of Egypt

BACKGROUND: Gaudeamus is an enigmatic hystricognathous rodent that was, until recently, known solely from fragmentary material from early Oligocene sites in Egypt, Oman, and Libya. Gaudeamus' molars are similar to those of the extant cane rat Thryonomys, and multiple authorities have aligned Gaudeamus with Thryonomys to the exclusion of other living and extinct African hystricognaths; recent phylogenetic analyses have, however, also suggested affinities with South American caviomorphs or Old World porcupines (Hystricidae). METHODOLOGY/PRINCIPAL FINDINGS: Here we describe the oldest known remains of Gaudeamus, including largely complete but crushed crania and complete upper and lower dentitions. Unlike younger Gaudeamus species, the primitive species described here have relatively complex occlusal patterns, and retain a number of plesiomorphic features. Unconstrained parsimony analysis nests Gaudeamus and Hystrix within the South American caviomorph radiation, implying what we consider to be an implausible back-dispersal across the Atlantic Ocean to account for Gaudeamus' presence in the late Eocene of Africa. An analysis that was constrained to recover the biogeographically more plausible hypothesis of caviomorph monophyly does not place Gaudeamus as a stem caviomorph, but rather as a sister taxon of hystricids. CONCLUSIONS/SIGNIFICANCE: We place Gaudeamus species in a new family, Gaudeamuridae, and consider it likely that the group originated, diversified, and then went extinct over a geologically brief period of time during the latest Eocene and early Oligocene in Afro-Arabia. Gaudeamurids are the only known crown hystricognaths from Afro-Arabia that are likely to be aligned with non-phiomorph members of that clade, and as such provide additional support for an Afro-Arabian origin of advanced stem and basal crown members of Hystricognathi

Problem-based teaching in engineering education

The aerospace industry requires highly educated, motivated engineers capable of working with increasingly complex processes and equipment, rapidly-changing requirements, and the need to constantly improve production efficiency. Colleges and universities throughout the world strive to provide training to young professionals for jobs in high-tech industries and to provide not only core technical knowledge, but also training on how to approach problems creatively and to generate novel solutions to problems. Problem-based learning (PBL) contributes to solving this problem. This paper reviews the literature on PBL, studies its benefits and drawbacks, and presents the positive results achieved by its implementation in the training of engineering students at Tomsk Polytechnic University

A role for Syk-kinase in the control of the binding cycle of the β2 integrins (CD11/CD18) in human polymorphonuclear neutrophils

A fine control of β2 integrin (CD11/CD18)-mediated firm adhesion of human neutrophils to the endothelial cell monolayer is required to allow ordered emigration. To elucidate the molecular mechanisms that control this process, intracellular protein tyrosine signaling subsequent to β2 integrin-mediated ligand binding was studied by immunoprecipitation and Western blotting techniques. The 72-kDa Syk-kinase, which was tyrosine-phosphorylated upon adhesion, was found to coprecipitate with CD18, the β-subunit of the β2 integrins. Moreover, inhibition of Syk-kinase by piceatannol enhanced adhesion and spreading but diminished N-formyl-Met-Leu-Phe-induced chemotactic migration. The enhancement of adhesiveness was associated with integrin clustering, which results in increased integrin avidity. In contrast, piceatannol had no effect on the surface expression or on the affinity of β2 integrins. Altogether, this suggests that Syk-kinase controls alternation of β2 integrin-mediated ligand binding with integrin detachment

Frequentist Interpretation of Probability

Three series of azole piperazine derivatives that mimic dicyclotyrosine (cYY), the natural substrate of the essential Mycobacterium tuberculosis cytochrome P450 CYP121A1, were prepared and evaluated for binding affinity and inhibitory activity (MIC) against M. tuberculosis. Series A replaces one phenol group of cYY with a C3-imidazole moiety, series B includes a keto group on the hydrocarbon chain preceding the series A imidazole, whilst series C explores replacing the keto group of the piperidone ring of cYY with a CH2-imidazole or CH2-triazole moiety to enhance binding interaction with the heme of CYP121A1. The series displayed moderate to weak type II binding affinity for CYP121A1, with the exception of series B 10a, which displayed mixed type I binding. Of the three series, series C imidazole derivatives showed the best, although modest, inhibitory activity against M. tuberculosis (17d MIC = 12.5 μg/mL, 17a 50 μg/mL). Crystal structures were determined for CYP121A1 bound to series A compounds 6a and 6b that show the imidazole groups positioned directly above the haem iron with binding between the haem iron and imidazole nitrogen of both compounds at a distance of 2.2 Å. A model generated from a 1.5 Å crystal structure of CYP121A1 in complex with compound 10a showed different binding modes in agreement with the heterogeneous binding observed. Although the crystal structures of 6a and 6b would indicate binding with CYP121A1, the binding assays themselves did not allow confirmation of CYP121A1 as the target