False-negative results using Neisseria gonorrhoeae porA pseudogene PCR - a clinical gonococcal isolate with an N. meningitidis porA sequence, Australia, March 2011

The gonococcal porA pseudogene is a popular target for in-house Neisseria gonorrhoeae PCR methods. With this study we present two novel findings: the first case of an N. gonorrhoeae porA pseudogene PCR false-negative result caused by sequence variation, and in the same organism, the first description of a clinical N. gonorrhoeae strain harbouring an N. meningitidis porA sequence

Origin and evolution of the light nuclides

After a short historical (and highly subjective) introduction to the field, I discuss our current understanding of the origin and evolution of the light nuclides D, He-3, He-4, Li-6, Li-7, Be-9, B-10 and B-11. Despite considerable observational and theoretical progress, important uncertainties still persist for each and every one of those nuclides. The present-day abundance of D in the local interstellar medium is currently uncertain, making it difficult to infer the recent chemical evolution of the solar neighborhood. To account for the observed quasi-constancy of He-3 abundance from the Big Bang to our days, the stellar production of that nuclide must be negligible; however, the scarce observations of its abundance in planetary nebulae seem to contradict this idea. The observed Be and B evolution as primaries suggests that the source composition of cosmic rays has remained quasi-constant since the early days of the Galaxy, a suggestion with far reaching implications for the origin of cosmic rays; however, the main idea proposed to account for that constancy, namely that superbubbles are at the source of cosmic rays, encounters some serious difficulties. The best explanation for the mismatch between primordial Li and the observed "Spite-plateau" in halo stars appears to be depletion of Li in stellar envelopes, by some yet poorly understood mechanism. But this explanation impacts on the level of the recently discovered early ``Li-6 plateau'', which (if confirmed), seriously challenges current ideas of cosmic ray nucleosynthesis.Comment: 18 pages, 9 figs. Invited Review in "Symposium on the Composition of Matter", honoring Johannes Geiss on the occasion of his 80th birthday (Grindelwald, Switzerland, Sept. 2006), to be published in Space Science Series of ISS

Protease-anti-protease compartmentalization in SARS-CoV-2 ARDS: Therapeutic implications

Background Interleukin-6 (IL-6) is elevated in SARS-CoV-2 infection. IL-6 regulates acute-phase proteins, such as alpha-1 antitrypsin (AAT), a key lung anti-protease. We investigated the protease-anti-protease balance in the circulation and pulmonary compartments in SARS-CoV-2 acute respiratory distress syndrome (ARDS) compared to non-SARS-CoV-2 ARDS (nsARDS) and the effects of tocilizumab (IL-6 receptor antagonist) on anti-protease defence in SARS-CoV-2 infection. Methods Levels and activity of AAT and neutrophil elastase (NE) were measured in plasma, airway tissue and tracheal secretions (TA) of people with SARS-CoV-2 ARDS or nsARDS. AAT and IL-6 levels were evaluated in people with moderate SARS-CoV-2 infection who received standard of care +/- tocilizumab. Findings AAT plasma levels doubled in SARS-CoV-2 ARDS. In lung parenchyma AAT levels were increased, as was the percentage of neutrophils involved in NET formation. A protease-anti-protease imbalance was detected in TA with active NE and no active AAT. The airway anti-protease, secretory leukoprotease inhibitor was decreased in SARS-CoV-2-infected lungs and cleaved in TA. In nsARDS, plasma AAT levels were elevated but TA samples had less AAT cleavage, with no detectable active NE in most samples. Induction of AAT in ARDS occurred mainly through IL-6. Tocilizumab down-regulated AAT during SARS-CoV-2 infection. Interpretation There is a protease-anti-protease imbalance in the airways of SARS-CoV-2-ARDS patients. This imbalance is a target for anti-protease therapy. Funding NIH Serological Sciences Network, National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases

Looking forward through the past: identification of 50 priority research questions in palaeoecology

1. Priority question exercises are becoming an increasingly common tool to frame future agendas in conservation and ecological science. They are an effective way to identify research foci that advance the field and that also have high policy and conservation relevance. 2. To date, there has been no coherent synthesis of key questions and priority research areas for palaeoecology, which combines biological, geochemical and molecular techniques in order to reconstruct past ecological and environmental systems on time-scales from decades to millions of years. 3. We adapted a well-established methodology to identify 50 priority research questions in palaeoecology. Using a set of criteria designed to identify realistic and achievable research goals, we selected questions from a pool submitted by the international palaeoecology research community and relevant policy practitioners. 4. The integration of online participation, both before and during the workshop, increased international engagement in question selection. 5. The questions selected are structured around six themes: human–environment interactions in the Anthropocene; biodiversity, conservation and novel ecosystems; biodiversity over long time-scales; ecosystem processes and biogeochemical cycling; comparing, combining and synthesizing information from multiple records; and new developments in palaeoecology. 6. Future opportunities in palaeoecology are related to improved incorporation of uncertainty into reconstructions, an enhanced understanding of ecological and evolutionary dynamics and processes and the continued application of long-term data for better-informed landscape management

Search for annual and diurnal rate modulations in the LUX experiment

Various dark matter models predict annual and diurnal modulations of dark matter interaction rates in Earth-based experiments as a result of the Earth’s motion in the halo. Observation of such features can provide generic evidence for detection of dark matter interactions. This paper reports a search for both annual and diurnal rate modulations in the LUX dark matter experiment using over 20 calendar months of data acquired between 2013 and 2016. This search focuses on electron recoil events at low energies, where leptophilic dark matter interactions are expected to occur and where the DAMA experiment has observed a strong rate modulation for over two decades. By using the innermost volume of the LUX detector and developing robust cuts and corrections, we obtained a stable event rate of 2.3±0.2  cpd/keVee/tonne, which is among the lowest in all dark matter experiments. No statistically significant annual modulation was observed in energy windows up to 26  keVee. Between 2 and 6  keVee, this analysis demonstrates the most sensitive annual modulation search up to date, with 9.2σ tension with the DAMA/LIBRA result. We also report no observation of diurnal modulations above 0.2  cpd/keVee/tonne amplitude between 2 and 6  keVee.Various dark matter models predict annual and diurnal modulations of dark matter interaction rates in Earth-based experiments as a result of the Earth's motion in the halo. Observation of such features can provide generic evidence for detection of dark matter interactions. This paper reports a search for both annual and diurnal rate modulations in the LUX dark matter experiment using over 20 calendar months of data acquired between 2013 and 2016. This search focuses on electron recoil events at low energies, where leptophilic dark matter interactions are expected to occur and where the DAMA experiment has observed a strong rate modulation for over two decades. By using the innermost volume of the LUX detector and developing robust cuts and corrections, we obtained a stable event rate of 2.3$\pm$0.2~cpd/keV$_{\text{ee}}$/tonne, which is among the lowest in all dark matter experiments. No statistically significant annual modulation was observed in energy windows up to 26~keV$_{\text{ee}}$. Between 2 and 6~keV$_{\text{ee}}$, this analysis demonstrates the most sensitive annual modulation search up to date, with 9.2$\sigma$ tension with the DAMA/LIBRA result. We also report no observation of diurnal modulations above 0.2~cpd/keV$_{\text{ee}}$/tonne amplitude between 2 and 6~keV$_{\text{ee}}$

Type 2 diabetes – an autoinflammatory disease driven by metabolic stress

Type 2 diabetes has traditionally been viewed as a metabolic disorder characterised by chronic high glucose levels, insulin resistance, and declining insulin secretion from the pancreas. Modern lifestyle, with abundant nutrient supply and reduced physical activity, has resulted in dramatic increases in the rates of obesity-associated disease conditions, including diabetes. The associated excess of nutrients induces a state of systemic low-grade chronic inflammation that results from production and secretion of inflammatory mediators from the expanded pool of activated adipocytes. Here, we review the mechanisms by which obesity induces adipose tissue dysregulation, detailing the roles of adipose tissue secreted factors and their action upon other cells and tissues central to glucose homeostasis and type 2 diabetes. Furthermore, given the emerging importance of adipokines, cytokines and chemokines in disease progression, we suggest that type 2 diabetes should now be viewed as an autoinflammatory disease, albeit one that is driven by metabolic dysregulation

Increased variability of stimulus-driven cortical responses is associated with genetic variability in children with and without dyslexia

Individuals with dyslexia exhibit increased brainstem variability in response to sound. It is unknown as to whether increased variability extends to neocortical regions associated with audition and reading, extends to visual stimuli, and whether increased variability characterizes all children with dyslexia or, instead, a specific subset of children. We evaluated the consistency of stimulus-evoked neural responses in children with (N = 20) or without dyslexia (N = 12) as measured by magnetoencephalography (MEG). Approximately half of the children with dyslexia had significantly higher levels of variability in cortical responses to both auditory and visual stimuli in multiple nodes of the reading network. There was a significant and positive relationship between the number of risk alleles at rs6935076 in the dyslexia-susceptibility gene KIAA0319 and the degree of neural variability in primary auditory cortex across all participants. This gene has been linked with neural variability in rodents and in typical readers. These findings indicate that unstable representations of auditory and visual stimuli in auditory and other reading-related neocortical regions are present in a subset of children with dyslexia and support the link between the gene KIAA0319 and the auditory neural variability across children with or without dyslexia. Keywords: KIAA0319, gene, reading, neural variability, subgroups, mechanism

Increased variability of stimulus-driven cortical responses is associated with genetic variability in children with and without dyslexia

Individuals with dyslexia exhibit increased brainstem variability in response to sound. It is unknown as to whether increased variability extends to neocortical regions associated with audition and reading, extends to visual stimuli, and whether increased variability characterizes all children with dyslexia or, instead, a specific subset of children. We evaluated the consistency of stimulus-evoked neural responses in children with (N = 20) or without dyslexia (N = 12) as measured by magnetoencephalography (MEG). Approximately half of the children with dyslexia had significantly higher levels of variability in cortical responses to both auditory and visual stimuli in multiple nodes of the reading network. There was a significant and positive relationship between the number of risk alleles at rs6935076 in the dyslexia-susceptibility gene KIAA0319 and the degree of neural variability in primary auditory cortex across all participants. This gene has been linked with neural variability in rodents and in typical readers. These findings indicate that unstable representations of auditory and visual stimuli in auditory and other reading-related neocortical regions are present in a subset of children with dyslexia and support the link between the gene KIAA0319 and the auditory neural variability across children with or without dyslexia. Keywords: KIAA0319; gene; reading; neural variability; subgroups; mechanismsMGH Institute of Health ProfessionsHalis Foundation for Dyslexia Researc

MOCVD Routes to Tl2Ba2Can-1CunO4+2nSuperconductor and Dielectric Insulator Thin Films

The evolution of HTS device technologies will benefit from the development of MOCVD (Metal-organic Chemical Vapor Deposition) routes to high quality HTS films as well as to those of insulators with low dielectric loss and close HTS lattice matches. Reviewed here are research efforts at precursor design focusing on Ba sources. A novel low pressure TGA technique is used to compare volatilities of MOCVD precursors and to quantify the role of gas phase diffusion in film growth. To form high quality Tl2Ba2Can-1CunO4+2n (n = 2.3) films. BaCaCuO(F) films are first deposited by MOCVD using the liquid precursors Ba(hfa)2[MATH]mep, Ca(hfa)2[MATH]tet, and solid Cu(dpm)2 (hfa = hexafluoroacetylacetonate, dpm = dipivaloylmethanate. mep = methylethylpentaglyme, tet = tetraglyme). The film growth psocess is shown to be mass transport-limited, and an interesting ligand exchange process is identified. The superconducting TBCCO phase is formed following an ex-situ anneal in the presence of Tl2O at temperatures from 820-900°C. Transport properties of TBCCO-2223 films include a Tc as high as 115K. Jc of 2x105 A/cm2 (77K), and Rs of 0.35m[MATH] (5K, 10 GHz). The MOCVD growth of low loss, lattice-matched dielectric NdGaO3, PrGaO3, Sr2AlTaO6, and SrPrGaO4 films is also discussed. High quality YBa2Cu3O7-x films have been grown upon MOCVD-derived PrGaO3 substrates