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Over the past two decades, with recognition that the ocean's sea-ice cover is neither insensitive to climate change nor a barrier to light and matter, research in sea-ice biogeochemistry has accelerated significantly, bringing together a multi-disciplinary community from a variety of fields. This disciplinary diversity has contributed a wide range of methodological techniques and approaches to sea-ice studies, complicating comparisons of the results and the development of conceptual and numerical models to describe the important biogeochemical processes occurring in sea ice. Almost all chemical elements, compounds, and biogeochemical processes relevant to Earth system science are measured in sea ice, with published methods available for determiningbiomass, pigments, net community production, primary production, bacterial activity, macronutrients, numerous natural and anthropogenic organic compounds, trace elements, reactive and inert gases, sulfur species, the carbon dioxide system parameters, stable isotopes, and water-ice-Atmosphere fluxes of gases, liquids, and solids. For most of these measurements, multiple sampling and processing techniques are available, but to date there has been little intercomparison or intercalibration between methods. In addition, researchers collect different types of ancillary data and document their samples differently, further confounding comparisons between studies. These problems are compounded by the heterogeneity of sea ice, in which even adjacent cores can have dramatically different biogeochemical compositions. We recommend that, in future investigations, researchers design their programs based on nested sampling patterns, collect a core suite of ancillary measurements, and employ a standard approach for sample identification and documentation. In addition, intercalibration exercises are most critically needed for measurements of biomass, primary production, nutrients, dissolved and particulate organic matter (including exopolymers), the CO2 system, air-ice gas fluxes, and aerosol production. We also encourage the development of in situ probes robust enough for long-Term deployment in sea ice, particularly for biological parameters, the CO2 system, and other gases.

Abstract Background Venous thromboembolism (VTE) is a major health and financial burden. VTE impacts health outcomes in surgical and non-surgical patients. VTE prophylaxis is underutilized, particularly amongst high risk medical patients. We conducted a multicentre clinical audit to determine the extent to which appropriate VTE prophylaxis in acutely ill hospitalized medical patients could be improved via implementation of a multifaceted nurse facilitated educational program. Methods This multicentre clinical audit of 15 Australian hospitals was conducted in 2007-208. The program incorporated a baseline audit to determine the proportion of patients receiving appropriate VTE prophylaxis according to best practice recommendations issued by the Australian and New Zealand Working Party on the Management and Prevention of Venous Thromboembolism (ANZ-WP recommendations), followed by a 4-month education intervention program and a post intervention audit. The primary endpoint was to compare the proportion of patients being appropriately managed based on their risk profile between the two audits. Results A total of 8774 patients (audit 1; 4399 and audit 2; 4375) were included in the study, most (82.2% audit 1; and 81.0% audit 2) were high risk based on ANZ-WP recommendations. At baseline 37.9% of high risk patients were receiving appropriate thromboprophylaxis. This increased to 54.1% in the post intervention audit (absolute improvement 16%; 95% confidence interval [CI] 11.7%, 20.5%). As a result of the nurse educator program, the likelihood of high risk patients being treated according to ANZ-WP recommendations increased significantly (OR 1.96; 1.62, 2.37). Conclusion Utilization of VTE prophylaxis amongst hospitalized medical patients can be significantly improved by implementation of a multifaceted educational program coordinated by a dedicated nurse practitioner.

This study examined medical and psychosocial characteristics of 440 patients (mean age 58 years, 21% women) with coronary artery disease at baseline and at 3-month and 12-month follow-ups. All patients were participants in the Multicenter Lifestyle Demonstration Project, aimed at improving diet (low fat, whole foods, plant-based), exercise, stress management, and social support. Spousal participation was encouraged. Both genders evidenced significant improvements in their diet, exercise, and stress management practices, which they maintained over the course of the study. Both women and men also showed significant medical (e.g., plasma lipids, blood pressure, body weight, exercise capacity) and psychosocial (e.g., quality of life) improvement. Despite their worse medical, psychosocial, and sociodemographic status at baseline, women's improvement was similar to that of men's. These results demonstrate that a multi-component lifestyle change program focusing on diet, exercise, stress management, and social support can be successfully implemented at hospitals in diverse regions of the United States. Furthermore, this program may be particularly beneficial for women with coronary artery disease who generally have higher mortality and morbidity than men after a heart attack, angioplasty, or bypass surgery. [ABSTRACT FROM AUTHOR]

Psychrophily is a phenotype describing microbial growth at low temperatures; elucidating the biomolecular and genomic adaptations necessary for survival in the cold is important for understanding life in extreme environments on Earth and in outer space. We used comparative genomics and temperature growth experiments of bacteria from the family Colwelliaceae to identify genomic factors correlated with optimal growth temperature (OGT). A phylogenomic analysis of 67 public and 39 newly sequenced strains revealed three main clades of Colwelliaceae. Temperature growth experiments revealed significant differences in mean OGT by clade, wherein strains of Colwelliaceae had similar growth rates at -1 °C but varied in their ability to tolerate 17 °C. Using amino acid compositional indices, a multiple linear regression model was constructed to predict the OGT of these organisms (RMSE 5.2 °C). Investigation of Colwelliaceae functional genes revealed a putative cold-adaptive gene cassette that was present in psychrophilic strains but absent in a closely related strain with a significantly higher OGT. This study also presents genomic evidence suggesting that the clade of Colwelliaceae containing Colwellia hornerae should be investigated as a new genus. These contributions offer key insights into the psychrophily phenotype and its underlying genomic foundation in the family Colwelliaceae., (© 2024. The Author(s), under exclusive licence to Springer Nature Japan KK.)

Prokaryotic laccases are emergent biocatalysts. However, they have not been broadly found and characterized in bacterial organisms, especially in lactic acid bacteria. Recently, a prokaryotic laccase from the lactic acid bacterium Pediococcus acidilactici 5930, which can degrade biogenic amines, was discovered. Thus, our study aimed to shed light on laccases from lactic acid bacteria focusing on two Pediococcus laccases, P. acidilactici 5930 and Pediococcus pentosaceus 4816, which have provided valuable information on their biochemical activities on redox mediators and biogenic amines. Both laccases are able to oxidize canonical substrates as ABTS, ferrocyanide and 2,6-DMP, and non-conventional substrates as biogenic amines. With ABTS as a substrate, they prefer an acidic environment and show sigmoidal kinetic activity, and are rather thermostable. Moreover, this study has provided the first structural view of two lactic acid bacteria laccases, revealing new structural features not seen before in other well-studied laccases, but which seem characteristic for this group of bacteria. We believe that understanding the role of laccases in lactic acid bacteria will have an impact on their biotechnological applications and provide a framework for the development of engineered lactic acid bacteria with enhanced properties., (© 2021 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

Periprocedural patient instruction and coordination is an important piece in achieving safe outcomes for patients needing procedures and receiving anticoagulants for atrial fibrillation. Balancing the needs for anticoagulation versus bleeding during the procedure requires clinical reasoning and preparation. In this article, the current guidelines for use of anticoagulants with atrial fibrillation, the relevant pharmacology, and the use of standardized tools to quantify the risks of thrombus or bleeding in the procedures will be discussed. In addition, resources for examining the optimal practice for these case types will be provided. Perianesthesia health care providers are pivotal to lead relevant stakeholders in the perianesthesia setting work together to create protocols and individual plans of care for this patient population., (Copyright © 2018 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Sulfolane is an industrial solvent and emerging organic contaminant affecting groundwater around the world, but little is known about microbes capable of biodegrading sulfolane or the pathways involved. We combined DNA-based stable isotope probing (SIP) with genome-resolved metagenomics to identify microorganisms associated with sulfolane biodegradation in a contaminated subarctic aquifer. In addition to 16S rRNA gene amplicon sequencing, we performed shotgun metagenomics on the 13 C-labeled DNA to obtain functional and taxonomic information about the active sulfolane-degrading community. We identified the primary sulfolane degrader, comprising ~85% of the labeled community in the amplicon sequencing dataset, as closely related to Rhodoferax ferrireducens strain T118. We obtained a 99.8%-complete metagenome-assembled genome for this strain, allowing us to identify putative pathways of sulfolane biodegradation. Although the 4S dibenzothiophene desulfurization pathway has been proposed as an analog for sulfolane biodegradation, we found only a subset of the required genes, suggesting a novel pathway specific to sulfolane. DszA, the enzyme likely responsible for opening the sulfolane ring structure, was encoded on both the chromosome and a plasmid. This study demonstrates the power of integrating DNA-SIP with metagenomics to characterize emerging organic contaminant degraders without culture bias and expands the known taxonomic distribution of sulfolane biodegradation.

The Mesomycetozoea branch near the animal-fungal divergence and are believed to be important to understanding the origins of multicellularity. In 2012, a free-living saprotrophic mesomycetozoean was isolated from the sub-Arctic Bering Sea. A hybrid assembly using Illumina and Nanopore sequences yielded 2,688 contigs with a total length of 125,635,304 bases.

Background: Horizontal gene transfer, the transfer and incorporation of genetic material between different species of organisms, has an important but poorly quantified role in the adaptation of microbes to their environment. Previous work has shown that genome size and the number of horizontally transferred genes are strongly correlated. Here we consider how genome size confuses the quantification of horizontal gene transfer because the number of genes an organism accumulates over time depends on its evolutionary history and ecological context (e.g., the nutrient regime for which it is adapted)., Results: We investigated horizontal gene transfer between archaea and bacteria by first counting reciprocal BLAST hits among 448 bacterial and 57 archaeal genomes to find shared genes. Then we used the DarkHorse algorithm, a probability-based, lineage-weighted method (Podell & Gaasterland, 2007), to identify potential horizontally transferred genes among these shared genes. By removing the effect of genome size in the bacteria, we have identified bacteria with unusually large numbers of shared genes with archaea for their genome size. Interestingly, archaea and bacteria that live in anaerobic and/or high temperature conditions are more likely to share unusually large numbers of genes. However, high salt was not found to significantly affect the numbers of shared genes. Numbers of shared (genome size-corrected, reciprocal BLAST hits) and transferred genes (identified by DarkHorse) were strongly correlated. Thus archaea and bacteria that live in anaerobic and/or high temperature conditions are more likely to share horizontally transferred genes. These horizontally transferred genes are over-represented by genes involved in energy conversion as well as the transport and metabolism of inorganic ions and amino acids., Conclusions: Anaerobic and thermophilic bacteria share unusually large numbers of genes with archaea. This is mainly due to horizontal gene transfer of genes from the archaea to the bacteria. In general, these transfers are from archaea that live in similar oxygen and temperature conditions as the bacteria that receive the genes. Potential hotspots of horizontal gene transfer between archaea and bacteria include hot springs, marine sediments, and oil wells. Cold spots for horizontal transfer included dilute, aerobic, mesophilic environments such as marine and freshwater surface waters., Competing Interests: The authors declare there are no competing interests.

Fungi are important parasites of primary producers and nutrient cyclers in aquatic ecosystems. In the Pacific-Arctic domain, fungal parasitism is linked to light intensities and algal stress that can elevate disease incidence on algae and reduce diatom concentrations. Fungi are vastly understudied in the marine realm and knowledge of their function is constrained by the current understanding of fungal distribution and drivers on global scales. To investigate the spatial distribution of fungi in the western Arctic and sub-Arctic, we used high throughput methods to sequence 18S rRNA, cloned and sequenced 28S rRNA and microscopically counted chytrid-infected diatoms. We identified a broad distribution of fungal taxa predominated by Chytridiomycota and Dikarya. Phylogenetic analysis of our Chytridiomycota clones placed Arctic marine fungi sister to the order Lobulomycetales. This clade of fungi predominated in fungal communities under ice with low snowpack. Microscopic examination of fixed seawater and sea ice samples revealed chytrids parasitizing diatoms collected across the Arctic that notably infected 25% of a single diatom species in the Bering Sea. The Pezizomycotina comprised > 95% of eukaryotic sequence reads in Greenland, providing preliminary evidence for osmotrophs being a substitute for algae as the base of food webs., (© 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Drug-induced liver injury (DILI) can result from both idiosyncratic and intrinsic mechanisms. This article discusses the clinical impact of DILI from a broad range of medications as well as herbal and dietary supplements. Risk factors for idiosyncratic DILI (IDILI) are the result of multiple host, environmental, and compound factors. Some triggers of IDILI often seen in critical care include antibiotics, antiepileptic medications, statins, novel anticoagulants, proton pump inhibitors, inhaled anesthetics, nonsteroidal anti-inflammatory agents, methotrexate, sulfasalazine, and azathioprine. The mechanism of IDILI due to these medications varies, and the resulting damage can be cholestatic, hepatocellular, or mixed. The primary treatment of IDILI is to discontinue the causative agent. DILI due to acetaminophen is intrinsic because the liver damage is predictably aligned with the dose ingested. Acute acetaminophen ingestion can be treated with activated charcoal or N-acetylcysteine. Future areas of research include identification of mitochondrial stress biomarkers and of the patients at highest risk for DILI., (©2016 American Association of Critical-Care Nurses.)

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world's oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits.

Rationale, Aims and Objectives: Acute myocardial infarctions (MIs) or heart attacks are the result of a complete or an incomplete occlusion of the lumen of the coronary artery with a thrombus. Prompt diagnosis and early coronary intervention results in maximum myocardial salvage, hence time to treat is of the essence. Adequate, accurate and complete information is vital during the early stages of admission of an MI patient and can impact significantly on the quality and safety of patient care. This study aimed to record how clinical information between different clinical teams during the journey of a patient in the MI care pathway is captured and to review the flow of information within this care pathway., Method: A prospective, descriptive, structured observational study to assess (i) current clinical information systems (CIS) utilization and (ii) real-time information availability within an acute cardiac care setting was carried out. Completeness and availability of patient information capture across four key stages of the MI care pathway were assessed prospectively., Results: Thirteen separate information systems were utilized during the four phases of the MI pathway. Observations revealed fragmented CIS utilization, with users accessing an average of six systems to gain a complete set of patient information. Data capture was found to vary between each pathway stage and in both patient cohort risk groupings. The highest level of information completeness (100%) was observed only in the discharge stage of the MI care pathway. The lowest level of information completeness (58%) was observed in the admission stage., Conclusion: The study highlights fragmentation, CIS duplication, and discrepancies in the current clinical information capture and data transfer across the MI care pathway in an acute cardiac care setting. The development of an integrated and user-friendly electronic data capture and transfer system would reduce duplication and would facilitate efficient and complete information provision at the point of care., (© 2012 John Wiley & Sons Ltd.)

GTPase activating proteins (GAPs) from pathogenic bacteria and eukaryotic host organisms deactivate Rab GTPases by supplying catalytic arginine and glutamine fingers in trans and utilizing the cis-glutamine in the DXXGQ motif of the GTPase for binding rather than catalysis. Here, we report the transition state mimetic structure of the Legionella pneumophila GAP LepB in complex with Rab1 and describe a comprehensive structure-based mutational analysis of potential catalytic and recognition determinants. The results demonstrate that LepB does not simply mimic other GAPs but instead deploys an expected arginine finger in conjunction with a novel glutamic acid finger, which forms a salt bridge with an indispensible switch II arginine that effectively locks the cis-glutamine in the DXXGQ motif of Rab1 in a catalytically competent though unprecedented transition state configuration. Surprisingly, a heretofore universal transition state interaction with the cis-glutamine is supplanted by an elaborate polar network involving critical P-loop and switch I serines. LepB further employs an unusual tandem domain architecture to clamp a switch I tyrosine in an open conformation that facilitates access of the arginine finger to the hydrolytic site. Intriguingly, the critical P-loop serine corresponds to an oncogenic substitution in Ras and replaces a conserved glycine essential for the canonical transition state stereochemistry. In addition to expanding GTP hydrolytic paradigms, these observations reveal the unconventional dual finger and non-canonical catalytic network mechanisms of Rab GAPs as necessary alternative solutions to a major impediment imposed by substitution of the conserved P-loop glycine.

Colwellia is a genus of mostly psychrophilic halophilic Gammaproteobacteria frequently isolated from polar marine sediments and sea ice. In exploring the capacity of Colwellia psychrerythraea 34H to survive and grow in the liquid brines of sea ice, we detected a duplicated 37 kbp genomic island in its genome based on the abnormally high G + C content. This island contains an operon encoding for heterotetrameric sarcosine oxidase and is located adjacent to several genes used in the serial demethylation of glycine betaine, a compatible solute commonly used for osmoregulation, to dimethylglycine, sarcosine, and glycine. Molecular clock inferences of important events in the adaptation of C. psychrerythraea 34H to compatible solute utilization reflect the geological evolution of the polar regions. Validating genomic predictions, C. psychrerythraea 34H was shown to grow on defined media containing either choline or glycine betaine, and on a medium with sarcosine as the sole organic source of carbon and nitrogen. Growth by 8 of 9 tested Colwellia species on a newly developed sarcosine-based defined medium suggested that the ability to catabolize glycine betaine (the catabolic precursor of sarcosine) is likely widespread in the genus Colwellia. This capacity likely provides a selective advantage to Colwellia species in cold, salty environments like sea ice, and may have contributed to the ability of Colwellia to invade these extreme niches.

Background: This systematic review identifies and evaluates techniques that aid the implementation of novel clinical information systems (CIS) within healthcare., Methods: We searched electronic databases (MEDLINE, EMBASE, PsycINFO and HMIC Health Management Information Consortium). Desktop reviews for all potentially eligible studies were also conducted via reference lists and forward citation searches. 14,198 abstracts were identified through the initial electronic search. 63 articles were retained following title and abstract reviews, and submitted for full text evaluation. Of these, 18 papers met eligibility criteria., Results: The 5 techniques that emerged from the review and that can assist CIS implementation were: system piloting, eliciting acceptance, use of simulation, training and education, and provision of incentives. These techniques were evaluated with a range of study endpoints (including system utilisation, clinical effectiveness, user satisfaction, attitudes towards system training, and attitudes towards implementation). Consideration of the clinical context in which the CIS was implemented was a consistent theme in the evidence-base., Conclusions: Although some evidence is available for the effectiveness of the 5 implementation techniques found in this review, the variable endpoints and the non-comparable study designs mean that the evidence-base needs further developing. We discuss the potential role of simulation and clinical leadership, particularly in relation to surgeons, in CIS implementation and we propose practical advice for CIS implementation and evaluation within hospital settings., (Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

When groups of related bacterial genomes are compared, the number of core genes found in all genomes is usually much less than the mean genome size, whereas the size of the pangenome (the set of genes found on at least one of the genomes) is much larger than the mean size of one genome. We analyze 172 complete genomes of Bacilli and compare the properties of the pangenomes and core genomes of monophyletic subsets taken from this group. We then assess the capabilities of several evolutionary models to predict these properties. The infinitely many genes (IMG) model is based on the assumption that each new gene can arise only once. The predictions of the model depend on the shape of the evolutionary tree that underlies the divergence of the genomes. We calculate results for coalescent trees, star trees, and arbitrary phylogenetic trees of predefined fixed branch length. On a star tree, the pangenome size increases linearly with the number of genomes, as has been suggested in some previous studies, whereas on a coalescent tree, it increases logarithmically. The coalescent tree gives a better fit to the data, for all the examples we consider. In some cases, a fixed phylogenetic tree proved better than the coalescent tree at reproducing structure in the gene frequency spectrum, but little improvement was gained in predictions of the core and pangenome sizes. Most of the data are well explained by a model with three classes of gene: an essential class that is found in all genomes, a slow class whose rate of origination and deletion is slow compared with the time of divergence of the genomes, and a fast class showing rapid origination and deletion. Although the majority of genes originating in a genome are in the fast class, these genes are not retained for long periods, and the majority of genes present in a genome are in the slow or essential classes. In general, we show that the IMG model is useful for comparison with experimental genome data both for species level and widely divergent taxonomic groups. Software implementing the described formulae is provided at http://github.com/rec3141/pangenome.

Background: Comparison of complete genomes of Bacteria and Archaea shows that gene content varies considerably and that genomes evolve quite rapidly via gene duplication and deletion and horizontal gene transfer. We analyze a diverse set of 92 Bacteria and 79 Archaea in order to investigate the processes governing the origin and evolution of families of related genes within genomes., Results: Genes were clustered into related groups using similarity criteria derived from BLAST. Most clusters contained genes from only one or a small number of genomes, and relatively few core clusters were found that spanned all genomes. Gene clusters found in larger numbers of genomes tended to have larger numbers of genes per genome; however, clusters with unusually large numbers of genes per genome were found among both narrowly and widely distributed clusters. Larger genomes were found to have larger mean gene family sizes and a greater proportion of families of very large size. We used a model of birth, death, and innovation to predict the distribution of gene family sizes. The key parameter is r, the ratio of duplications to deletions. It was found that the model can give a good fit to the observed distribution only if there are several classes of genes with different values of r. The preferred model in most cases had three classes of genes., Conclusions: There appears to be a rapid rate of origination of new gene families within individual genomes. Most of these gene families are deleted before they spread to large numbers of genomes, which suggests that they may not be generally beneficial to the organisms. The family size distribution is best described by a large fraction of families that tend to have only one or two genes and a small fraction of families of multi-copy genes that are highly prone to duplication. Larger families occur more frequently in larger genomes, indicating higher r in these genomes, possibly due to a greater tolerance for non-beneficial gene duplicates. The smallest genomes contain very few multi-copy families, suggesting a high rate of deletion of all but the most beneficial genes in these genomes.

Background: There is a widely held expectation that screening for disease has adverse emotional impacts. The aim of the current review is to estimate the short (< 4 weeks) and longer term (> 4 weeks) emotional impact of such screening., Methods: Studies selected for inclusion were (a) randomised controlled trials in which (b) participants in one arm underwent screening and received test results, and those in a control arm did not, and (c) emotional outcomes were assessed in both arms. MEDLINE via PubMed (1950 to present), EMBASE (1980 to present), PsycINFO (1985 to present) using OVID SP, and CINAHL (1982 to present) via EBSCO were searched, using strategies developed with keywords and medical subject headings. Data were extracted on emotional outcomes, type of screening test and test results., Results: Of the 12 studies that met the inclusion criteria, six involved screening for cancer, two for diabetes, and one each for abdominal aortic aneurysms, peptic ulcer, coronary heart disease and osteoporosis. Five studies reported data on anxiety, five [corrected] on depression, two on general distress and eight on quality of life assessed between one week and 13 years after screening (median = 1.3 years).Meta-analyses revealed no significant impact of screening on longer term anxiety (pooled SMD 0.01, 95% CI -0.10, 0.11), depression (pooled SMD -0.04, 95% CI -.12, 0.20), or quality of life subscales (mental and self-assessed health pooled SMDs, respectively: 0.03; -0.01, (95% CI -.02, 0.04; 0.00, 95% CI -.04, 0.03)., Conclusion: Screening does not appear to have adverse emotional impacts in the longer term (> 4 weeks). Too few studies assessed outcomes before four weeks to comment on the shorter term emotional impact of screening.

Purpose: Much concern has been expressed that feedback of personalized genetic risk information may lead to fatalism, i.e., a lack of perceived control over the risk. This review aimed to assess the strength of evidence for such a view., Method: Electronic databases were searched to find eligible studies, which comprised randomized, controlled trials and analog studies, in which participants in one arm received either real or imagined personalized genetic risk information and assessed perceived control in relation to the treatability or preventability of the health problem., Results: Inspection of 1340 abstracts resulted in 5 studies meeting the inclusion criteria, involving the prediction of obesity, heart disease, depression, and diabetes. Meta-analyses of the clinical studies revealed no impact of personalized genetic risk information on perceived control in either the short term (pooled standardized mean difference 0.09, 95% confidence interval, -0.51 to 0.70) or longer term (pooled standardized mean difference 0.00, confidence interval, -0.20 to 0.21). Similarly, no impact on perceived control was evident in the three analog studies (pooled standardized mean difference 0.02, confidence interval, -0.17 to 0.20)., Conclusion: Few studies have assessed empirically the impact of personalized genetic risk information on fatalism, assessed using perceptions of control over the risk. Limited evidence suggests feedback of genetic risk information may have little impact on such beliefs.

The case of a 19-year-old woman with benign cementoblastoma is described along with a brief review of the literature and clinopathology of the lesion. This lesion developed a more aggressive nature. A discussion of treatment and rationale is included.

The structure of bacterial communities in first-year spring and summer sea ice differs from that in source seawaters, suggesting selection during ice formation in autumn or taxon-specific mortality in the ice during winter. We tested these hypotheses by weekly sampling (January-March 2004) of first-year winter sea ice (Franklin Bay, Western Arctic) that experienced temperatures from -9 degrees C to -26 degrees C, generating community fingerprints and clone libraries for Bacteria and Archaea. Despite severe conditions and significant decreases in microbial abundance, no significant changes in richness or community structure were detected in the ice. Communities of Bacteria and Archaea in the ice, as in under-ice seawater, were dominated by SAR11 clade Alphaproteobacteria and Marine Group I Crenarchaeota, neither of which is known from later season sea ice. The bacterial ice library contained clones of Gammaproteobacteria from oligotrophic seawater clades (e.g. OM60, OM182) but no clones from gammaproteobacterial genera commonly detected in later season sea ice by similar methods (e.g. Colwellia, Psychrobacter). The only common sea ice bacterial genus detected in winter ice was Polaribacter. Overall, selection during ice formation and mortality during winter appear to play minor roles in the process of microbial succession that leads to distinctive spring and summer sea ice communities.

Estrogen receptor alpha (ER) is a ligand-dependent transcription factor. Upon binding estrogen, ER recruits coactivator complexes with histone acetyltransferase or methyltransferase activities to activate downstream target genes. In addition to histones, coactivators can modify ER itself and other proteins in the transactivation complex. Here, we show that ER is directly methylated at lysine 302 (K302) by the SET7 methyltransferase. SET7-mediated methylation stabilizes ER and is necessary for the efficient recruitment of ER to its target genes and for their transactivation. The SET7-ER complex structure reveals the molecular basis for ER peptide recognition and predicts that modifications or mutations of nearby residues would affect K302 methylation. Indeed, a breast cancer-associated mutation at K303 (K303R) alters methylation at K302 in vitro and in vivo. These findings raise the possibility that generation, recognition, and removal of modifications within the ER hinge region generate "ER modification cassettes" that yield distinct patterns for signaling downstream events.

Histone modifications have important roles in transcriptional control, mitosis and heterochromatin formation. G9a and G9a-like protein (GLP) are euchromatin-associated methyltransferases that repress transcription by mono- and dimethylating histone H3 at Lys9 (H3K9). Here we demonstrate that the ankyrin repeat domains of G9a and GLP bind with strong preference to N-terminal H3 peptides containing mono- or dimethyl K9. X-ray crystallography revealed the basis for recognition of the methylated lysine by a partial hydrophobic cage with three tryptophans and one acidic residue. Substitution of key residues in the cage eliminated the H3 tail interaction. Hence, G9a and GLP contain a new type of methyllysine binding module (the ankyrin repeat domains) and are the first examples of protein (histone) methyltransferases harboring in a single polypeptide the activities that generate and read the same epigenetic mark.

Histone methylation is crucial for regulating chromatin structure, gene transcription and the epigenetic state of the cell. LSD1 is a lysine-specific histone demethylase that represses transcription by demethylating histone H3 on lysine 4 (ref. 1). The LSD1 complex contains a number of proteins, all of which have been assigned roles in events upstream of LSD1-mediated demethylation apart from BHC80 (also known as PHF21A), a plant homeodomain (PHD) finger-containing protein. Here we report that, in contrast to the PHD fingers of the bromodomain PHD finger transcription factor (BPTF) and inhibitor of growth family 2 (ING2), which bind methylated H3K4 (H3K4me3), the PHD finger of BHC80 binds unmethylated H3K4 (H3K4me0), and this interaction is specifically abrogated by methylation of H3K4. The crystal structure of the PHD finger of BHC80 bound to an unmodified H3 peptide has revealed the structural basis of the recognition of H3K4me0. Knockdown of BHC80 by RNA inhibition results in the de-repression of LSD1 target genes, and this repression is restored by the reintroduction of wild-type BHC80 but not by a PHD-finger mutant that cannot bind H3. Chromatin immunoprecipitation showed that BHC80 and LSD1 depend reciprocally on one another to associate with chromatin. These findings couple the function of BHC80 to that of LSD1, and indicate that unmodified H3K4 is part of the 'histone code'. They further raise the possibility that the generation and recognition of the unmodified state on histone tails in general might be just as crucial as post-translational modifications of histone for chromatin and transcriptional regulation.

Terminal restriction fragment length polymorphism (T-RFLP) analysis is a widespread technique for rapidly fingerprinting microbial communities. Users of T-RFLP frequently overlook the resolving power of well-chosen restriction endonucleases and often fail to report how they chose their enzymes. REPK (Restriction Endonuclease Picker) assists in the rational choice of restriction endonucleases for T-RFLP by finding sets of four restriction endonucleases that together uniquely differentiate user-designated sequence groups. With REPK, users can provide their own sequences (of any gene, not just 16S rRNA), specify the taxonomic rank of interest and choose from a number of filtering options to further narrow down the enzyme selection. Bug tracking is provided, and the source code is open and accessible under the GNU Public License v.2, at http://code.google.com/p/repk. The web server is available without access restrictions at http://rocaplab.ocean.washington.edu/tools/repk.

RNAi is a collection of processes mediated by small RNAs that silence gene expression in a sequence-specific manner. Studies of processes as divergent as post-transcriptional gene silencing, transcriptional silencing through RNA-directed DNA methylation, or heterochromatin formation, and even RNA-guided DNA elimination have converged on a core pathway. This review will highlight recent structural and mechanistic studies illustrating siRNA and miRNA processing, RISC formation, the execution of RNAi by RISC, and the regulation of these pathways, with a specific focus on vertebrate systems., (2006 Wiley-Liss, Inc.)

It is unclear whether patients with coronary artery disease (CAD) and diabetes mellitus (DM) can make comprehensive lifestyle changes that produce similar changes in coronary risk factors and quality of life compared with patients with CAD and without DM. We examined medical characteristics, lifestyle, and quality of life by diabetic status and gender in the Multicenter Lifestyle Demonstration Project (MLDP), a study of 440 nonsmoking patients with CAD (347 men, 55 with DM; 15.9%; 93 women, 36 with DM; 38.7%). Patients met in groups to improve lifestyle (plant-based, low-fat diet; exercise; stress management) for 1 year. Follow-ups were conducted at 3 and 12 months. At baseline, body mass and systolic blood pressure were significantly higher among patients with DM. Men with DM had a worse medical history (e.g., hypertension, hyperlipidemia, and family history of CAD) than did those without DM. Patients with DM, especially women, reported poorer quality of life than did patients without DM. The 2 groups of patients were able to adhere to the recommended lifestyle, as demonstrated by significant improvements in weight (mean -5 kg), body fat, low-density lipoprotein cholesterol, exercise capacity, and quality of life. No significant changes in triglycerides and high-density lipoprotein cholesterol were noted. By the end of 12 months, improvements in glucose-lowering medications (i.e., discontinuation or a change from insulin to oral hypoglycemic agents) were noted for 19.8% (n = 18) of patients with DM. In conclusion, patients with CAD and DM are able to follow a comprehensive lifestyle change program and show similar improvements in coronary risk factors and quality of life as those without DM.

In humans and rodents, the lysosomal catabolism of core Man(3)GlcNAc(2) N-glycan structures is catalyzed by the concerted action of several exoglycosidases, including a broad specificity lysosomal alpha-mannosidase (LysMan), core-specific alpha1,6-mannosidase, beta-mannosidase, and cleavage at the reducing terminus by a di-N-acetylchitobiase. We describe here the first cloning, expression, purification, and characterization of a novel human glycosylhydrolase family 38 alpha-mannosidase with catalytic characteristics similar to those established previously for the core-specific alpha1,6-mannosidase (acidic pH optimum, inhibition by swainsonine and 1,4-dideoxy-1,4-imino-d-mannitol, and stimulation by Co(2+) and Zn(2+)). Substrate specificity studies comparing the novel human alpha-mannosidase with human LysMan revealed that the former enzyme efficiently cleaved only the alpha1-6mannose residue from Man(3)GlcNAc but not Man(3)GlcNAc(2) or other larger high mannose oligosaccharides, indicating a requirement for chitobiase action before alpha1,6-mannosidase activity. In contrast, LysMan cleaved all of the alpha-linked mannose residues from high mannose oligosaccharides except the core alpha1-6mannose residue. alpha1,6-Mannosidase transcripts were ubiquitously expressed in human tissues, and expressed sequence tag searches identified homologous sequences in murine, porcine, and canine databases. No expressed sequence tags were identified for bovine alpha1,6-mannosidase, despite the identification of two sequence homologs in the bovine genome. The lack of conservation in 5'-flanking sequences for the bovine alpha1,6-mannosidase genes may lead to defective transcription similar to transcription defects in the bovine chitobiase gene. These results suggest that the chitobiase and alpha1,6-mannosidase function in tandem for mammalian lysosomal N-glycan catabolism.

Structural and biochemical studies have begun to elucidate the pathway of RNA silencing that leads to the formation of the RISC complex. The outstanding feature of this pathway is the precise recognition and processing of double-stranded RNA. We present a review of recent structures that illustrate the molecular mechanisms contributing to these two related functions, highlighting models of Drosha, Dicer, and RISC function.

Mars is a compelling astrobiological target, and a human mission would provide an opportunity to collect immense amounts of scientific data. Exploration alone, however, cannot justify the increased risk. Instead, three factors drive a human mission: economics, education, and exploration. A human mission has a unique potential to inspire the next generation of young people to enter critically needed science and engineering disciplines. A mission is economically feasible, and the research and development program put in place for a human mission would propel growth in related high-technology industries. The main hurdles are human physiological responses to 1-2 years of radiation and microgravity exposure. However, enabling technologies are sufficiently mature in these areas that they can be developed within a few decade timescale. Hence, the decision of whether or not to undertake a human mission to Mars is a political decision, and thus, educational and economic benefits are the crucial factors., (c2005 Elsevier Ltd. All rights reserved.)

The functional significance of mono-, di-, and tri-methylation of lysine residues within histone proteins is under investigation. Evidence from several model organisms suggests that different methylated states of H3 Lys(9) (H3K9) are generated by specific histone methyltransferases (MTases) to mark distinct types of silent chromatin. Sequence alignment of all histone lysine MTases with known product specificity suggested that a key residue in the active site determines how many methyl groups they add. We examined this possibility both in vitro and in vivo and found that a Phe at the position equivalent to Phe(281) of Neurospora crassa DIM-5 or Phe(1205) of human G9a allows the enzyme to perform di and tri-methylation, whereas a Tyr at this position is restrictive, inhibiting tri-methylation and thus yielding a mono- or di-MTase. Phe to Tyr mutants of both DIM-5 and G9a restrict product specificity in vitro and in vivo without compromising overall catalysis. These mutants were employed to probe the biological significance of mono-, di-, and tri-methylation of H3K9 in both mouse embryonic stem cells and N. crassa. G9a F1205Y, when expressed in G9a (-/-) embryonic stem cells, rescued only H3K9 mono-methylation, but not di-methylation, to wild-type levels yet silenced Mage-a gene expression. When expressed in dim-5 strains, DIM-5 F281Y generated significant levels of mono- and di-H3K9 methylation (which are not observed in wild type Neurospora) as well as tri-methyl H3K9. The altered DIM-5 rescued the growth defect characteristic of dim-5 N. crassa but did not fully rescue the gross DNA hypomethylation of dim-5 strains.