The connection between the Southern Annular Mode and a feature-based perspective on Southern Hemisphere mid-latitude winter variability

This article provides a reconciling perspective on the two main, but contradictory, interpretations of the southern annular mode (SAM). SAM was originally thought to characterize meridional shifts in the storm track across the entire hemisphere. This perspective was later questioned, and SAM was interpreted as a statistical artifact depending on the choice of base region for the principal component analysis. Neither perspective, however, fully describes SAM. We show that SAM cannot be interpreted in terms of midlatitude variability, as SAM merely modulates the most poleward part of the cyclone tracks and only marginally influences the distribution of other weather-related features of the storm track (e.g., position of jet axes and Rossby wave breaking). Instead, SAM emerges as the leading pattern of geopotential variability due to strong correlations of sea level pressure around the Antarctic continent. As SAM correlates strongly both with the pan-Antarctic mean temperature and the meridional heat flux through 65°S, we hypothesize that SAM can be interpreted as a measure of the degree of the (de)coupling between Antarctica and the southern midlatitudes. As an alternative way of characterizing southern midlatitude variability, we seek domains in which the leading EOF patterns of both the geopotential and storm-track features yield a dynamically consistent picture. This approach is successful for the South Pacific. Here the leading variability patterns are closely related to the Pacific–South America pattern and point toward an NAO-like variability.publishedVersio

Modulating Nitric Oxide Dioxygenase and Nitrite Reductase of Cytoglobin through Point Mutations

Cytoglobin is a hexacoordinate hemoglobin with physiological roles that are not clearly understood. Previously proposed physiological functions include nitric oxide regulation, oxygen sensing, or/and protection against oxidative stress under hypoxic/ischemic conditions. Like many globins, cytoglobin rapidly consumes nitric oxide under normoxic conditions. Under hypoxia, cytoglobin generates nitric oxide, which is strongly modulated by the oxidation state of the cysteines. This gives a plausible role for this biochemistry in controlling nitric oxide homeostasis. Mutations to control specific properties of hemoglobin and myoglobin, including nitric oxide binding/scavenging and the nitrite reductase activity of various globins, have been reported. We have mapped these key mutations onto cytoglobin, which represents the E7 distal ligand, B2/E9 disulfide, and B10 heme pocket residues, and examined the nitric oxide binding, nitric oxide dioxygenase activity, and nitrite reductase activity. The Leu46Trp mutation decreases the nitric oxide dioxygenase activity &gt; 10,000-fold over wild type, an effect 1000 times greater than similar mutations with other globins. By understanding how particular mutations can affect specific reactivities, these mutations may be used to target specific cytoglobin activities in cell or animal models to help understand the precise role(s) of cytoglobin under physiological and pathophysiological conditions.</jats:p

The circularly permuted globin domain of androglobin exhibits atypical heme stabilization and nitric oxide interaction

In the decade since the discovery of androglobin, a multi-domain hemoglobin of metazoans associated with ciliogenesis and spermatogenesis, there has been little advance in the knowledge of the biochemical and structural properties of this unusual member of the hemoglobin superfamily. Using a method for aligning remote homologues, coupled with molecular modelling and molecular dynamics, we have identified a novel structural alignment to other hemoglobins. This has led to the first stable recombinant expression and characterization of the circularly permuted globin domain. Exceptional for eukaryotic globins is that a tyrosine takes the place of the highly conserved phenylalanine in the CD1 position, a critical point in stabilizing the heme. A disulfide bond, similar to that found in neuroglobin, forms a closed loop around the heme pocket, taking the place of androglobin's missing CD loop and further supporting the heme pocket structure. Highly unusual in the globin superfamily is that the heme iron binds nitric oxide as a five-coordinate complex similar to other heme proteins that have nitric oxide storage functions. With rapid autoxidation and high nitrite reductase activity, the globin appears to be more tailored toward nitric oxide homeostasis or buffering. The use of our multi-template profile alignment method to yield the first biochemical characterisation of the circularly permuted globin domain of androglobin expands our knowledge of the fundamental functioning of this elusive protein and provides a pathway to better define the link between the biochemical traits of androglobin with proposed physiological functions

Comparisons among ten models of acoustic backscattering used in aquatic ecosystem research

Author Posting. © Acoustical Society of America, 2015. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 138 (2015); 3742, doi:10.1121/1.4937607.Analytical and numerical scatteringmodels with accompanying digital representations are used increasingly to predict acoustic backscatter by fish and zooplankton in research and ecosystem monitoring applications. Ten such models were applied to targets with simple geometric shapes and parameterized (e.g., size and material properties) to represent biological organisms such as zooplankton and fish, and their predictions of acoustic backscatter were compared to those from exact or approximate analytical models, i.e., benchmarks. These comparisons were made for a sphere, spherical shell, prolate spheroid, and finite cylinder, each with homogeneous composition. For each shape, four target boundary conditions were considered: rigid-fixed, pressure-release, gas-filled, and weakly scattering. Target strength (dB re 1 m2) was calculated as a function of insonifying frequency (f = 12 to 400 kHz) and angle of incidence (θ = 0° to 90°). In general, the numerical models (i.e., boundary- and finite-element) matched the benchmarks over the full range of simulation parameters. While inherent errors associated with the approximate analytical models were illustrated, so were the advantages as they are computationally efficient and in certain cases, outperformed the numerical models under conditions where the numerical models did not convergeThis work was supported by the NOAA Fisheries Advanced Sampling Technologies Working Group, the Office of Naval Research, and the National Oceanic Partnership Program. Josiah S. Renfree

Creating equity in health research to drive more and better evidence.

Health research is rapidly changing with evidence being gathered through new agile methods. This evolution is critical but must be globally equitable so the poorest nations do not lose out. We must harness this change to better tackle the daily burden of diseases that affect the most impoverished populations and bring research capabilities to every corner of the world so that rapid and fair responses to new pathogen are possible; anywhere they appear. We must seize this opportunity to make research easier, better and more equitable. Currently too many nations are unable to generate the evidence or translate it to directly change health outcomes in their own communities. It is essential to act and harness this emerging change in how research data can be generated and shared, so that all nations sustainably gain from this development. There are positive examples to draw on from COVID-19, but we now need to act. Here we present an initiative to develop a new framework that can guide researchers in the design and execution of their studies. This highly agile system will work by adapting to risk and complexity in any given study, whilst generating quality, safe and ethical data

Streptococcus pneumoniae and Haemophilus influenzae in paediatric meningitis patients at Goroka General Hospital, Papua New Guinea : Serotype distribution and antimicrobial susceptibility in the pre-vaccine era

Background: Bacterial meningitis remains an important infection globally, with the greatest burden in children in low-income settings, including Papua New Guinea (PNG). We present serotype, antimicrobial susceptibility and outcome data from paediatric meningitis patients prior to introduction of Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines (PCVs) in PNG, providing a baseline for evaluation of immunisation programs. Methods: Cerebrospinal fluid (CSF) was collected from children admitted to Goroka General Hospital with suspected meningitis between 1996 and 2005. Culture and sensitivity was conducted, and pneumococci and H. influenzae were serotyped. Laboratory findings were linked to clinical outcomes. Results: We enrolled 1884 children. A recognised pathogen was identified in 375 children (19.9%). Streptococcus pneumoniae (n = 180) and Hib (n = 153) accounted for 88.8% of pathogens isolated. 24 different pneumococcal serogroups were identified; non-PCV types 2, 24 and 46 accounted for 31.6% of pneumococcal meningitis. 10- and 13-valent PCVs would cover 44.1% and 45.4% of pneumococcal meningitis respectively. Pneumococcal isolates were commonly resistant to penicillin (21.5%) and 23% of Hib isolates were simultaneously resistant to ampicillin, co-trimoxazole and chloramphenicol. The case fatality rate in patients with a recognised bacterial pathogen was 13.4% compared to 8.5% in culture-negative patients. Conclusions: If implemented in routine expanded programme of immunisation (EPI) with high coverage, current PCVs could prevent almost half of pneumococcal meningitis cases. Given the diversity of circulating serotypes in PNG serotype replacement is of concern. Ongoing surveillance is imperative to monitor the impact of vaccines. In the longer term vaccines providing broader protection against pneumococcal meningitis will be needed. © 2015 Greenhill et al

Rifampicin/Cotrimoxazole/Isoniazid Versus Mefloquine or Quinine + Sulfadoxine- Pyrimethamine for Malaria: A Randomized Trial

OBJECTIVES: Previous studies of a fixed combination including cotrimoxazole, rifampicin, and isoniazid (Cotrifazid) showed efficacy against resistant strains of Plasmodium falciparum in animal models and in small-scale human studies. We conducted a multicentric noninferiority trial to assess the safety and efficacy of Cotrifazid against drug-resistant malaria in Papua New Guinea. DESIGN: The trial design was open-label, block-randomised, comparative, and multicentric. SETTING: The trial was conducted in four primary care health facilities, two in urban and two in rural areas of Madang and East Sepik Province, Papua New Guinea. PARTICIPANTS: Patients of all ages with recurrent uncomplicated malaria were included. INTERVENTIONS: Patients were randomly assigned to receive Cotrifazid, mefloquine, or the standard treatment of quinine with sulfadoxine–pyrimethamine (SP). OUTCOME MEASURES: Incidence of clinical and laboratory adverse events and rate of clinical and/or parasitological failure at day 14 were recorded. RESULTS: The safety analysis population included 123 patients assigned to Cotrifazid, 123 to mefloquine, and 123 to quinine + SP. The Cotrifazid group experienced lower overall incidence of adverse events than the other groups. Among the efficacy analysis population (72 Cotrifazid, 71 mefloquine, and 75 quinine + SP), clinical failure rate (symptoms and parasite load) on day 14 was equivalent for the three groups (0% for Cotrifazid and mefloquine; 1% for quinine + SP), but parasitological failure rate (P. falciparum asexual blood-stage) was higher for Cotrifazid than for mefloquine or quinine + SP (9% [PCR corrected 8%] versus 0% and 3%, respectively [p = 0.02]). CONCLUSION: Despite what appears to be short-term clinical equivalence, the notable parasitological failure at day 14 in both P. falciparum and P. vivax makes Cotrifazid in its current formulation and regimen a poor alternative combination therapy for malaria

Plasmodium vivax and Mixed Infections Are Associated with Severe Malaria in Children: A Prospective Cohort Study from Papua New Guinea

In a study carried out in Papua New Guinea, Blaise Genton and colleagues show thatPlasmodium vivax is associated with severe malaria