Transformation and fate of microphytobenthos carbon in subtropical, intertidal sediments: potential for long-term carbon retention revealed by ¹³C-labeling

Microphytobenthos (MPB) are ubiquitous in coastal sediments, but the fate of their production (carbon biomass) is poorly defined. The processing and fate of MPB-derived carbon in subtropical intertidal sediments was investigated through in situ labeling with ¹³C-bicarbonate. Of the added ¹³C, 100% was fixed within ~ 4 h, suggesting that MPB productivity was limited by inorganic carbon availability. Although there was rapid transfer of ¹³C to bacteria (within 12 h), a relatively small fraction of ¹³C was transferred to heterotrophs (up to 12.5% of total fixed ¹³C into bacteria and 0.01% into foraminifera). MPB was the major reservoir for ¹³C throughout the study, suggesting that production of extracellular polymeric substances was limited and/or MPB recycled ¹³C. This retention of ¹³C was reflected in remarkably slow estimated turnover times for the MPB community (66–100 d). Over 31 d, ~ 70% of the ¹³C was lost from sediments. This was primarily via resuspension (~ 55%), enhanced by elevated freshwater flow following rainfall. A further ~ 13% was lost via fluxes of dissolved inorganic carbon during inundation. However, ¹³C losses via dissolved organic carbon fluxes from inundated sediments (0.5%) and carbon dioxide fluxes from exposed sediments (<0.1%) were minimal. The retention of ~ 30% of the carbon fixed by MPB within one tidal exposure after > 30 d, despite high resuspension, demonstrates the potentially substantial longer term retention of MPB-derived carbon in unvegetated sediments and suggests that MPB may contribute to carbon burial ("blue carbon")

Evidence for Pervasive Adaptive Protein Evolution in Wild Mice

The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans

Extracting science from surveys of our Galaxy

Our knowledge of the Galaxy is being revolutionised by a series of photometric, spectroscopic and astrometric surveys. Already an enormous body of data is available from completed surveys, and data of ever increasing quality and richness will accrue at least until the end of this decade. To extract science from these surveys we need a class of models that can give probability density functions in the space of the observables of a survey -- we should not attempt to "invert" the data from the space of observables into the physical space of the Galaxy. Currently just one class of model has the required capability, so-called "torus models". A pilot application of torus models to understanding the structure of the Galaxy's thin and thick discs has already produced two significant results: a major revision of our best estimate of the Sun's velocity with respect to the Local Standard of Rest, and a successful prediction of the way in which the vertical velocity dispersion in the disc varies with distance from the Galactic plane.Comment: 13 pages. Invited review to appear in Pramana - journal of physics (Indian Academy of Sciences

Treatment of enteric fever (typhoid and paratyphoid fever) with cephalosporins

Background Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low‐ and middle‐income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first‐line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug‐resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first‐line antimicrobials, such as chloramphenicol, has re‐appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain. Objectives To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the WHO ICTRP and ClinicalTrials.gov up to 24 November 2021. We also searched reference lists of included trials, contacted researchers working in the field, and contacted relevant organizations. Selection criteria We included randomized controlled trials (RCTs) in adults and children with enteric fever that compared a cephalosporin to another antimicrobial, a different cephalosporin, or a different treatment duration of the intervention cephalosporin. Enteric fever was diagnosed on the basis of blood culture, bone marrow culture, or molecular tests. Data collection and analysis We used standard Cochrane methods. Our primary outcomes were clinical failure, microbiological failure and relapse. Our secondary outcomes were time to defervescence, duration of hospital admission, convalescent faecal carriage, and adverse effects. We used the GRADE approach to assess certainty of evidence for each outcome. Main results We included 27 RCTs with 2231 total participants published between 1986 and 2016 across Africa, Asia, Europe, the Middle East and the Caribbean, with comparisons between cephalosporins and other antimicrobials used for the treatment of enteric fever in children and adults. The main comparisons are between antimicrobials in most common clinical use, namely cephalosporins compared to a fluoroquinolone and cephalosporins compared to azithromycin. Cephalosporin (cefixime) versus fluoroquinolones Clinical failure, microbiological failure and relapse may be increased in patients treated with cefixime compared to fluoroquinolones in three small trials published over 14 years ago: clinical failure (risk ratio (RR) 13.39, 95% confidence interval (CI) 3.24 to 55.39; 2 trials, 240 participants; low‐certainty evidence); microbiological failure (RR 4.07, 95% CI 0.46 to 36.41; 2 trials, 240 participants; low‐certainty evidence); relapse (RR 4.45, 95% CI 1.11 to 17.84; 2 trials, 220 participants; low‐certainty evidence). Time to defervescence in participants treated with cefixime may be longer compared to participants treated with fluoroquinolones (mean difference (MD) 1.74 days, 95% CI 0.50 to 2.98, 3 trials, 425 participants; low‐certainty evidence). Cephalosporin (ceftriaxone) versus azithromycin Ceftriaxone may result in a decrease in clinical failure compared to azithromycin, and it is unclear whether ceftriaxone has an effect on microbiological failure compared to azithromycin in two small trials published over 18 years ago and in one more recent trial, all conducted in participants under 18 years of age: clinical failure (RR 0.42, 95% CI 0.11 to 1.57; 3 trials, 196 participants; low‐certainty evidence); microbiological failure (RR 1.95, 95% CI 0.36 to 10.64, 3 trials, 196 participants; very low‐certainty evidence). It is unclear whether ceftriaxone increases or decreases relapse compared to azithromycin (RR 10.05, 95% CI 1.93 to 52.38; 3 trials, 185 participants; very low‐certainty evidence). Time to defervescence in participants treated with ceftriaxone may be shorter compared to participants treated with azithromycin (mean difference of −0.52 days, 95% CI −0.91 to −0.12; 3 trials, 196 participants; low‐certainty evidence). Cephalosporin (ceftriaxone) versus fluoroquinolones It is unclear whether ceftriaxone has an effect on clinical failure, microbiological failure, relapse, and time to defervescence compared to fluoroquinolones in three trials published over 28 years ago and two more recent trials: clinical failure (RR 3.77, 95% CI 0.72 to 19.81; 4 trials, 359 participants; very low‐certainty evidence); microbiological failure (RR 1.65, 95% CI 0.40 to 6.83; 3 trials, 316 participants; very low‐certainty evidence); relapse (RR 0.95, 95% CI 0.31 to 2.92; 3 trials, 297 participants; very low‐certainty evidence) and time to defervescence (MD 2.73 days, 95% CI −0.37 to 5.84; 3 trials, 285 participants; very low‐certainty evidence). It is unclear whether ceftriaxone decreases convalescent faecal carriage compared to the fluoroquinolone gatifloxacin (RR 0.18, 95% CI 0.01 to 3.72; 1 trial, 73 participants; very low‐certainty evidence) and length of hospital stay may be longer in participants treated with ceftriaxone compared to participants treated with the fluoroquinolone ofloxacin (mean of 12 days (range 7 to 23 days) in the ceftriaxone group compared to a mean of 9 days (range 6 to 13 days) in the ofloxacin group; 1 trial, 47 participants; low‐certainty evidence). Authors' conclusions Based on very low‐ to low‐certainty evidence, ceftriaxone is an effective treatment for adults and children with enteric fever, with few adverse effects. Trials suggest that there may be no difference in the performance of ceftriaxone compared with azithromycin, fluoroquinolones, or chloramphenicol. Cefixime can also be used for treatment of enteric fever but may not perform as well as fluoroquinolones. We are unable to draw firm general conclusions on comparative contemporary effectiveness given that most trials were small and conducted over 20 years previously. Clinicians need to take into account current, local resistance patterns in addition to route of administration when choosing an antimicrobial

Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity

Despite progress in defining human leukocyte antigen (HLA) alleles for anti-citrullinated-protein-autoantibody-positive (ACPA(+)) rheumatoid arthritis (RA), identifying HLA alleles for ACPA-negative (ACPA(-)) RA has been challenging because of clinical heterogeneity within clinical cohorts. We imputed 8,961 classical HLA alleles, amino acids, and SNPs from Immunochip data in a discovery set of 2,406 ACPA(-) RA case and 13,930 control individuals. We developed a statistical approach to identify and adjust for clinical heterogeneity within ACPA(-) RA and observed independent associations for serine and leucine at position 11 in HLA-DRbeta1 (p = 1.4 x 10(-13), odds ratio [OR] = 1.30) and for aspartate at position 9 in HLA-B (p = 2.7 x 10(-12), OR = 1.39) within the peptide binding grooves. These amino acid positions induced associations at HLA-DRB1( *)03 (encoding serine at 11) and HLA-B( *)08 (encoding aspartate at 9). We validated these findings in an independent set of 427 ACPA(-) case subjects, carefully phenotyped with a highly sensitive ACPA assay, and 1,691 control subjects (HLA-DRbeta1 Ser11+Leu11: p = 5.8 x 10(-4), OR = 1.28; HLA-B Asp9: p = 2.6 x 10(-3), OR = 1.34). Although both amino acid sites drove risk of ACPA(+) and ACPA(-) disease, the effects of individual residues at HLA-DRbeta1 position 11 were distinct (p \u3c 2.9 x 10(-107)). We also identified an association with ACPA(+) RA at HLA-A position 77 (p = 2.7 x 10(-8), OR = 0.85) in 7,279 ACPA(+) RA case and 15,870 control subjects. These results contribute to mounting evidence that ACPA(+) and ACPA(-) RA are genetically distinct and potentially have separate autoantigens contributing to pathogenesis. We expect that our approach might have broad applications in analyzing clinical conditions with heterogeneity at both major histocompatibility complex (MHC) and non-MHC regions

Role of carbonate burial in Blue Carbon budgets

Calcium carbonates (CaCO3) often accumulate in mangrove and seagrass sediments. As CaCO3 production emits CO2, there is concern that this may partially offset the role of Blue Carbon ecosystems as CO2sinks through the burial of organic carbon (Corg). A global collection of data on inorganic carbon burial rates (Cinorg, 12% of CaCO3 mass) revealed global rates of 0.8 TgCinorg yr−1 and 15–62 TgCinorg yr−1 in mangrove and seagrass ecosystems, respectively. In seagrass, CaCO3burial may correspond to an offset of 30% of the net CO2 sequestration. However, a mass balance assessment highlights that the Cinorg burial is mainly supported by inputs from adjacent ecosystems rather than by local calcification, and that Blue Carbon ecosystems are sites of net CaCO3 dissolution. Hence, CaCO3 burial in Blue Carbon ecosystems contribute to seabed elevation and therefore buffers sea-level rise, without undermining their role as CO2 sinks

Decay constants, semi-leptonic and non-leptonic decays in a Bethe-Salpeter Model

We evaluate the decay constants for the B and $D$ mesons and the form factors for the semileptonic decays of the B meson to $D$ and $D^*$ mesons in a Bethe-Salpeter model. From data we extract $V_{cb}=0.039 \pm 0.002$ from ${\bar B} \to D^* l {\bar{\nu}}$ and $V_{cb}=0.037 \pm 0.004$ from ${\bar B} \to D l {\bar{\nu}}$ decays. The form factors are then used to obtain non-leptonic decay partial widths for $B\to D \pi (K)$ and $B \to D D (D_s)$ in the factorization approximation.Comment: 15 Pages, 3 Postscript figures (available also from [email protected]

The landscape of gifted and talented education in England and Wales: How are teachers implementing policy?

This is an Author's Accepted Manuscript of an article published in Research Papers in Education, 27(2), 167-186, 2012, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/02671522.2010.509514.This paper explores the evidence relating to how primary schools are responding to the ‘gifted and talented’ initiative in England and Wales. A questionnaire survey which invited both closed and open-ended responses was carried out with a national sample of primary schools. The survey indicated an increasing proportion of coordinators, compared with a survey carried out in 1996, were identifying their gifted and talented children as well as having associated school policies. However, the survey also highlighted a number of issues which need addressing if the initiative is to achieve its objective of providing the best possible educational opportunities for children. For example, it was found that a significant number of practitioners were not aware of the existence of the National Quality Standards for gifted and talented education, provided by the UK government in 2007, and the subject-specific criteria provided by the UK’s Curriculum Authority for identification and provision have been largely ignored. The process of identifying children to be placed on the ‘gifted and talented’ register seems haphazard and based on pragmatic reasons. Analysis of teachers’ responses also revealed a range of views and theoretical positioning held by them, which have implications for classroom practice. As the ‘gifted and talented’ initiative in the UK is entering a second decade, and yet more significant changes in policy are introduced, pertinent questions need to be raised and given consideration

Sleep diplomacy alone will widen sleep disparities - Authors' reply.

Timothy Daly argues that preexisting sleep disparities according to socioeconomic status will make behavioural approaches and lifestyle advice widen sleep disparities. Although we fully agree that strong public policy measures must be implemented to reduce socioeconomic status inequalities in brain health,1 and in particular those that might impact sleep problems, there is good evidence reporting the success of behavioural interventions to improve sleep conditions in different populations.2 Specific interventions have been proposed in lowsocioeconomic status populations, which should also be included in our sleep diplomacy3 category.Fil: Golombek, Diego Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; ArgentinaFil: Booi, Laura. Trinity College; Irlanda. Leeds Beckett University; Reino UnidoFil: Campbell, Dominic. Trinity College; IrlandaFil: Dawson, Walter D.. Trinity College; Irlanda. University of California; Estados Unidos. Global Brain Health Institute; Estados Unidos. Oregon Health and Science University; Estados Unidos. Portland State University; Estados UnidosFil: Eyre, Harris. University of California; Estados Unidos. Rice University; Estados UnidosFil: Lawlor, Brian. Trinity College; IrlandaFil: Ibañez, Agustin Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; Argentina. Trinity College; Irlanda. University of California; Estados Unidos. Global Brain Health Institute; Estados Unidos. Universidad Adolfo Ibañez; Chil

Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants