The Paleocene cephalopod fauna from pebble point, Victoria (Australia)-fulcrum between two Eras

Three species belonging to three genera of early Cenozoic nautilid cephalopods are described from Paleocene aged beds of the Pebble Point and Dilwyn formations, Victoria, Australia: Aturoidea distans Teichert, Eutrephoceras victorianum Teichert, both previously known from these deposits, and Nautilus praepompilius Shimansky, previously unknown from Australia. Here we present new occurrence and paleoecological information about these three taxa based on previously and newly collected specimens from Pebble Point Formation beds, as well as presenting the first paleotemperature analyses for Australian nautiloid cephalopods of any age. We sampled for shell carbonates from the single known specimen of Nautilus praepompililus, as well as from a specimen of Aturoidea distans from the Pebble Point beds. The A. distans samples showed temperature of calcification to have been between 20 and 25°C; and for N. praepompilius the temperatures were between 18 and 21°C. There were too few samples to provide statistical analyses, yet the implication is that these two taxa inhabited different depths during calcification. For comparison, we have sampled shell carbonates from the only known extant site where two different nautilid genera coexist, Manus Island, Papua New Guinea. There, specimens of Nautilus pompilius and Allonautilus scrobiculatus calcified (1984 specimens) at temperatures of 12 to 17°C, conforming to previous measurements in the literature and significantly colder than any of the Paleocene specimens sampled here

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY challenge

Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation

yesInflammation of adipose tissue in obesity is associated with increased IL-1β, IL-6 and TNF-α secretion and proposed to contribute to insulin resistance. AMP-activated protein kinase (AMPK) regulates nutrient metabolism and is reported to have anti-inflammatory actions in adipose tissue, yet the mechanisms underlying this remain poorly characterised. The effect of AMPK activation on cytokine-stimulated proinflammatory signalling was therefore assessed in cultured adipocytes. AMPK activation inhibited IL-1β-stimulated CXCL10 secretion, associated with reduced interleukin-1 receptor associated kinase-4 (IRAK4) phosphorylation and downregulated MKK4/JNK and IKK/IκB/NFκB signalling. AMPK activation inhibited TNF-α-stimulated IKK/IκB/NFκB signalling but had no effect on JNK phosphorylation. The JAK/STAT3 pathway was also suppressed by AMPK after IL-6 stimulation and during adipogenesis. Adipose tissue from AMPKα1−/− mice exhibited increased JNK and STAT3 phosphorylation, supporting suppression of these distinct proinflammatory pathways by AMPK in vivo. The inhibition of multiple pro-inflammatory signalling pathways by AMPK may underlie the reported beneficial effects of AMPK activation in adipose tissue.British Heart Foundatio