Complex anatomic variation in the brachial region

Authors describe a case of a complex anatomic variation discovered during dissection of the humeral region. On the right side, brachial artery followed a superficial course. Musculocutaneous nerve did not pierce coracobrachialis muscle but instead passed below the muscle before continuing in the forearm. On the left side, a communication between musculocutaneous and median nerve was dissected. Those variations are analytically presented with a brief review on their anatomic and clinical implications. Considerations on their embryological origin are attempted

Vertebral artery variations revised: origin, course, branches and embryonic development

Background: The vertebral artery originates from the subclavian artery and is divided into four segments. The aim of this study is to investigate the anatomical variations in the course and branches of the vertebral artery. Materials and methods: A research was performed via PubMed database, using the terms: “variations of vertebral artery AND cadaveric study”, “variations of vertebral artery AND cadavers” and “anomalies of vertebral artery AND cadavers”. Results: A total of 24 articles met the inclusion criteria, 13 of them referring to variations of the origin of the vertebral artery, 9 to variations of the course and 3 to variations of its branches. On a total sample of 1192 cadavers of different populations, origin of the left vertebral artery directly from the aortic arch was observed at 6.7%. In addition, among 311 cadavers, 17.4% were found with partially or fully ossified foramen of the atlas for the passage of the vertebral artery, while the bibliographic review also showed variants at the exit site of the artery from the transverse foramen of the axis. Conclusions: Despite the fact that variations of both the course and the branches of vertebral artery are in most cases asymptomatic, good knowledge of anatomy and its variants is of particular importance for the prevention of vascular complications during surgical and radiological procedures in the cervix area

Type Ia supernovae and the ^{12}C+^{12}C reaction rate

The experimental determination of the cross-section of the ^{12}C+^{12}C reaction has never been made at astrophysically relevant energies (E<2 MeV). The profusion of resonances throughout the measured energy range has led to speculation that there is an unknown resonance at E\sim1.5 MeV possibly as strong as the one measured for the resonance at 2.14 MeV. We study the implications that such a resonance would have for the physics of SNIa, paying special attention to the phases that go from the crossing of the ignition curve to the dynamical event. We use one-dimensional hydrostatic and hydrodynamic codes to follow the evolution of accreting white dwarfs until they grow close to the Chandrasekhar mass and explode as SNIa. In our simulations, we account for a low-energy resonance by exploring the parameter space allowed by experimental data. A change in the ^{12}C+^{12}C rate similar to the one explored here would have profound consequences for the physical conditions in the SNIa explosion, namely the central density, neutronization, thermal profile, mass of the convective core, location of the runaway hot spot, or time elapsed since crossing the ignition curve. For instance, with the largest resonance strength we use, the time elapsed since crossing the ignition curve to the supernova event is shorter by a factor ten than for models using the standard rate of ^{12}C+^{12}C, and the runaway temperature is reduced from \sim8.14\times10^{8} K to \sim4.26\times10^{8} K. On the other hand, a resonance at 1.5 MeV, with a strength ten thousand times smaller than the one measured at 2.14 MeV, but with an {\alpha}/p yield ratio substantially different from 1 would have a sizeable impact on the degree of neutronization of matter during carbon simmering. We conclude that a robust understanding of the links between SNIa properties and their progenitors will not be attained until the ^{12}C+^{12}C reaction rate is measured at energies \sim1.5 MeV.Comment: 15 pages, 6 tables, 10 figures, accepted for Astronomy and Astrophysic

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

Investigating antibody neutralization of lyssaviruses using lentiviral pseudotypes: a cross-species comparison

Cross-neutralization between rabies virus (RABV) and two European bat lyssaviruses (EBLV-1 and -2) was analysed using lentiviral pseudotypes as antigen vectors. Glycoprotein (G-protein) cDNA from RABV challenge virus standard-11 (CVS-11) and EBLV-1 and -2 were cloned and co-expressed with human immunodeficiency virus (HIV) or murine leukemia virus (MLV) gag–pol and packageable green fluorescent protein (GFP) or luciferase reporter genes in human cells. The harvested lentiviral (HIV) vector infected over 40 % of baby hamster kidney (BHK) target cells, providing high-titre pseudotype stocks. Tests on blinded antibody-positive (n=15) and -negative (n=45) sera, predetermined by the fluorescent antibody virus neutralization (FAVN) test approved by the World Health Organization (WHO) and Office International des Epizooties (OIE), revealed that the CVS-11 pseudotype assay had 100 % concordance with FAVN and strongly correlated with neutralization titres (r2=0.89). Cross-neutralization tests using sera from RABV-vaccinated humans and animals on pseudotypes with CVS-11, EBLV-1 and EBLV-2 envelopes showed that the relative neutralization titres correlated broadly with the degree of G-protein diversity. Pseudotypes have three major advantages over live-virus neutralization tests: (i) they can be handled in low-biohazard-level laboratories; (ii) the use of reporter genes such as GFP or β-galactosidase will allow the assay to be undertaken at low cost in laboratories worldwide; (iii) each assay requires <10 μl serum. This robust microassay will improve our understanding of the protective humoral immunity that current rabies vaccines confer against emerging lyssaviruses, and will be applicable to surveillance studies, thus helping to control the spread of rabies

gMOOCs – Flow and Persuasion to Gamify MOOCs

Gamification has gained great interest recently in several fields. However, while the literature reports that a gamification design relying on external motivation only can lead users to cognitive dissonance, most gamification approaches use points, badges and leaderboards as dominant game elements. We present our developed testable predictions with the aim of investigating additional motivational theories (flow and persuasion) to argue for a deeper integration of gamification and the learning content at hand. Relying on expert selected game elements, we consequently derive design considerations to create gMOOCs, gamified massive online open courses, designed according to the principles of flow and persuasion. Our findings are the basis of our experiment and a contribution to the development of a new theoretical design for gamificatio

Cyclin-dependent-like kinase 5 is required for pain signaling in human sensory neurons and mouse models

Cyclin-dependent-like kinase 5 (Cdkl5) gene mutations lead to an X-linked disorder that is characterized by infantile epileptic encephalopathy, developmental delay and hypotonia. However, we found that a substantial percentage of these patients also report a previously unrecognised anamnestic deficiency in pain perception. Consistent with a role in nociception, we discovered that Cdkl5 is expressed selectively in nociceptive dorsal root ganglia (DRG) neurons in mice and in iPS-derived human nociceptors. CDKL5 deficient mice display defective epidermal innervation and conditional deletion of Cdkl5 in DRG sensory neurons impairs nociception, phenocopying CDKL5 deficiency disorder in patients. Mechanistically, Cdkl5 interacts with CaMKIIα to control outgrowth as well as TRPV1-dependent signaling, which are disrupted in both Cdkl5 mutant murine DRG and human iPS-derived nociceptors. Together, these findings unveil a previously unrecognized role for Cdkl5 in nociception, proposing an original regulatory mechanism for pain perception with implications for future therapeutics in CDKL5 deficiency disorder

The latent stem cell population is retained in the hippocampus of transgenic Huntington's disease mice but not wild-type mice

The demonstration of the brain's ability to initiate repair in response to disease or injury has sparked considerable interest in therapeutic strategies to stimulate adult neurogenesis. In this study we examined the effect of a progressive neurodegenerative condition on neural precursor activity in the subventricular zone (SVZ) and hippocampus of the R6/1 transgenic mouse model of Huntington's disease (HD). Our results revealed an age-related decline in SVZ precursor numbers in both wild-type (WT) and HD mice. Interestingly, hippocampal precursor numbers declined with age in WT mice, although we observed maintenance in hippocampal precursor number in the HD animals in response to advancement of the disease. This maintenance was consistent with activation of a recently identified latent hippocampal precursor population. We found that the small latent stem cell population was also maintained in the HD hippocampus at 33 weeks, whereas it was not present in the WT. Our findings demonstrate that, despite a loss of neurogenesis in the HD hippocampus in vivo, there is a unique maintenance of the precursor and stem cells, which may potentially be activated to ameliorate disease symptoms

Fusion measurements of 12C+12C at energies of astrophysical interest

The cross section of the 12C+12C fusion reaction at low energies is of paramount importance for models of stellar nucleosynthesis in different astrophysical scenarios, such as Type Ia supernovae and Xray superbursts, where this reaction is a primary route for the production of heavier elements. In a series of experiments performed at Argonne National Laboratory, using Gammasphere and an array of Silicon detectors, measurements of the fusion cross section of 12C+12C were successfully carried out with the γ and charged-particle coincidence technique in the center-of-mass energy range of 3-5 MeV. These were the first background-free fusion cross section measurements for 12C+12C at energies of astrophysical interest. Our results are consistent with previous measurements in the high-energy region; however, our lowest energy measurement indicates a fusion cross section slightly lower than those obtained with other techniques