Enter the Dragon: The Dynamic and Multifunctional Evolution of Anguimorpha Lizard Venoms

While snake venoms have been the subject of intense study, comparatively little work has been done on lizard venoms. In this study, we have examined the structural and functional diversification of anguimorph lizard venoms and associated toxins, and related these results to dentition and predatory ecology. Venom composition was shown to be highly variable across the 20 species of Heloderma, Lanthanotus, and Varanus included in our study. While kallikrein enzymes were ubiquitous, they were also a particularly multifunctional toxin type, with differential activities on enzyme substrates and also ability to degrade alpha or beta chains of fibrinogen that reflects structural variability. Examination of other toxin types also revealed similar variability in their presence and activity levels. The high level of venom chemistry variation in varanid lizards compared to that of helodermatid lizards suggests that venom may be subject to different selection pressures in these two families. These results not only contribute to our understanding of venom evolution but also reveal anguimorph lizard venoms to be rich sources of novel bioactive molecules with potential as drug design and development lead compounds

Managing sedentary behavior to reduce the risk of diabetes and cardiovascular disease

Modern human environments are vastly different from those of our forebears. Rapidly advancing technology in transportation, communications, workplaces, and home entertainment confer a wealth of benefits, but increasingly come with costs to human health. Sedentary behavior—too much sitting as distinct from too little physical activity—contributes adversely to cardiometabolic health outcomes and premature mortality. Findings from observational epidemiology have been synthesized in meta-analyses, and evidence is now shifting into the realm of experimental trials with the aim of identifying novel mechanisms and potential causal relationships. We discuss recent observational and experimental evidence that makes a compelling case for reducing and breaking up prolonged sitting time in both the primary prevention and disease management contexts. We also highlight future research needs, the opportunities for developing targeted interventions, and the potential of population-wide initiatives designed to address too much sitting as a health risk

Search for a diffuse flux of astrophysical muon neutrinos with the IceCube 40-string detector

The IceCube Neutrino Observatory is a 1 km(3) detector currently taking data at the South Pole. One of the main strategies used to look for astrophysical neutrinos with IceCube is the search for a diffuse flux of high-energy neutrinos from unresolved sources. A hard energy spectrum of neutrinos from isotropically distributed astrophysical sources could manifest itself as a detectable signal that may be differentiated from the atmospheric neutrino background by spectral measurement. This analysis uses data from the IceCube detector collected in its half completed configuration which operated between April 2008 and May 2009 to search for a diffuse flux of astrophysical muon neutrinos. A total of 12 877 upward-going candidate neutrino events have been selected for this analysis. No evidence for a diffuse flux of astrophysical muon neutrinos was found in the data set leading to a 90% C. L. upper limit on the normalization of an E-2 astrophysical nu(mu) flux of 8.9 x 10(-9) GeV cm(-2) s(-1) sr(-1). The analysis is sensitive in the energy range between 35 TeV and 7 PeV. The 12 877 candidate neutrino events are consistent with atmospheric muon neutrinos measured from 332 GeV to 84 TeV and no evidence for a prompt component to the atmospheric neutrino spectrum is found

Measurement of acoustic attenuation in South Pole ice

Using the South Pole Acoustic Test Setup (SPATS) and a retrievable transmitter deployed in holes drilled for the IceCube experiment, we have measured the attenuation of acoustic signals by South Pole ice at depths between 190 m and 500 m. Three data sets, using different acoustic sources, have been analyzed and give consistent results. The method with the smallest systematic uncertainties yields an amplitude attenuation coefficient α = 3.20 ± 0.57 km−1 between 10 and 30 kHz, considerably larger than previous theoretical estimates. Expressed as an attenuation length, the analyses give a consistent result for λ ≡ 1/α of ∼300 m with 20% uncertainty. No significant depth or frequency dependence has been found

A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer

Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.536 T > C; Ile163Thr-substitution in PSA) is associated with reduced prostate cancer risk, however, the functional relevance is unknown. Here, we identify that the SNP variant-induced change in PSA biochemical activity mediates prostate cancer pathogenesis. The ‘Thr’ PSA variant leads to small subcutaneous tumours, supporting reduced prostate cancer risk. However, ‘Thr’ PSA also displays higher metastatic potential with pronounced osteolytic activity in an experimental metastasis in-vivo model. Biochemical characterisation of this PSA variant demonstrates markedly reduced proteolytic activity that correlates with differences in in-vivo tumour burden. The SNP is associated with increased risk for aggressive disease and prostate cancer-specific mortality in three independent cohorts, highlighting its critical function in mediating metastasis. Carriers of this SNP allele have reduced serum total PSA and a higher free/total PSA ratio that could contribute to late biopsy decisions and delay in diagnosis. Our results provide a molecular explanation for the prominent 19q13.3 KLK locus, rs17632542 SNP, association with a spectrum of prostate cancer clinical outcomes

The course of the superficial peroneal nerve in relation to the ankle position: anatomical study with ankle arthroscopic implications

Despite the fact that the superficial peroneal nerve is the only nerve in the human body that can be made visible; iatrogenic damage to this nerve is the most frequently reported complication in anterior ankle arthroscopy. One of the methods to visualize the nerve is combined ankle plantar flexion and inversion. In the majority of cases, the superficial peroneal nerve can be made visible. The portals for anterior ankle arthroscopy are however created with the ankle in the neutral or slightly dorsiflexed position and not in combined plantar flexion and inversion. The purpose of this study was to undertake an anatomical study to the course of the superficial peroneal nerve in different positions of the foot and ankle. We hypothesize that the anatomical localization of the superficial peroneal nerve changes with different foot and ankle positions. In ten fresh frozen ankle specimens, a window, only affecting the skin, was made at the level of the anterolateral portal for anterior ankle arthroscopy in order to directly visualize the superficial peroneal nerve, or if divided, its terminal branches. Nerve movement was assessed from combined 10° plantar flexion and inversion to 5° dorsiflexion, standardized by the Telos stress device. Also for the 4th toe flexion, flexion of all the toes and for skin tensioning possible nerve movement was determined. The mean superficial peroneal nerve movement was 2.4 mm to the lateral side when the ankle was moved from 10° plantar flexion and inversion to the neutral ankle position and 3.6 mm to the lateral side from 10° plantar flexion and inversion to 5° dorsiflexion. Both displacements were significant (P < 0.01). The nerve consistently moves lateral when the ankle is manoeuvred from combined plantar flexion and inversion to the neutral or dorsiflexed position. If visible, it is therefore advised to create the anterolateral portal medial from the preoperative marking, in order to prevent iatrogenic damage to the superficial peroneal nerve

A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer

Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.536 T &gt; C; Ile163Thr-substitution in PSA) is associated with reduced prostate cancer risk, however, the functional relevance is unknown. Here, we identify that the SNP variant-induced change in PSA biochemical activity mediates prostate cancer pathogenesis. The ‘Thr’ PSA variant leads to small subcutaneous tumours, supporting reduced prostate cancer risk. However, ‘Thr’ PSA also displays higher metastatic potential with pronounced osteolytic activity in an experimental metastasis in-vivo model. Biochemical characterisation of this PSA variant demonstrates markedly reduced proteolytic activity that correlates with differences in in-vivo tumour burden. The SNP is associated with increased risk for aggressive disease and prostate cancer-specific mortality in three independent cohorts, highlighting its critical function in mediating metastasis. Carriers of this SNP allele have reduced serum total PSA and a higher free/total PSA ratio that could contribute to late biopsy decisions and delay in diagnosis. Our results provide a molecular explanation for the prominent 19q13.3 KLK locus, rs17632542 SNP, association with a spectrum of prostate cancer clinical outcomes.</p

Quaternary palaeoenvironmental proxies and processes : papers in honour of Professor Alayne Street-Perrott

This special issue comprises a series of papers written by former PhD students, as well as friends and colleagues, to celebrate the career of Alayne Street-Perrott, who is currently Professor of Physical Geography at Swansea University. Alayne's research career has been exceptional, marked by novel, cutting-edge research of the very highest quality in several disciplines, which addresses ‘big’ questions in Quaternary Science. She has promoted the importance of tropical environments through international cooperation and leadership, and developed fundamental concepts. She has made an immense contribution to our understanding of global change in the Quaternary, raising the discipline to new levels of scientific rigour

Print Culture Landscapes 1880-1922

This chapter outlines of the developments in Irish print culture between the Revival and the Civil War in 1922. Using new archival sources it touches on the themes of commercialisation, religion, and aesthetics to give a snapshot of some representative examples of a vast and changing print media. This media existed in a globalised market and was structured along transnational lines, swapping commentators and ideas across national borders. This essay looks at women writers of the Revival itself, Victorian travel books, academic debates, Irish writers in decadent journals, working-class writing, and Catholic publications, amongst others, to offer an insight into types of material being produced and a flavour of the debates contained in the print culture landscape of the period