Chemical Speciation of Copper in a Salt Marsh Estuary and Bioavailability to Thaumarchaeota

The concentrations of dissolved copper (Cud), copper-binding ligands, thiourea-type thiols, and humic substances (HSCu) were measured in estuarine waters adjacent to Sapelo Island, Georgia, USA, on a monthly basis from April to December 2014. Here we present the seasonal cycle of copper speciation within the estuary and compare it to the development of an annually occurring bloom of Ammonia Oxidizing Archaea (AOA), which require copper for many enzymes. Two types of complexing ligands (L1 and L2) were found to dominate with mean complex stabilities (log KCuL′) of 14.5 and 12.8. Strong complexation resulted in lowering the concentration of free cupric ion (Cu2+) to femtomolar (fM) levels throughout the study and to sub-fM levels during the summer months. A Thaumarchaeota bloom during this period suggests that this organism manages to grow at very low Cu2+ concentrations. Correlation of the concentration of the L1 ligand class with a thiourea-type thiol and the L2 ligand class with HSCu provide an interesting dimension to the identity of the ligand classes. Due to the stronger complex stability, 82–99% of the copper was bound to L1. Thiourea-type thiols typically form Cu(I) species, which would suggest that up to ~90% copper could be present as Cu(I) in this region. In view of the very low concentration of free copper (pCu > 15 at the onset and during the bloom) and a reputedly high requirement for copper, it is likely that the Thaumarchaeota are able to access thiol-bound copper directly

Reflexive Cones

Reflexive cones in Banach spaces are cones with weakly compact intersection with the unit ball. In this paper we study the structure of this class of cones. We investigate the relations between the notion of reflexive cones and the properties of their bases. This allows us to prove a characterization of reflexive cones in term of the absence of a subcone isomorphic to the positive cone of \ell_{1}. Moreover, the properties of some specific classes of reflexive cones are investigated. Namely, we consider the reflexive cones such that the intersection with the unit ball is norm compact, those generated by a Schauder basis and the reflexive cones regarded as ordering cones in a Banach spaces. Finally, it is worth to point out that a characterization of reflexive spaces and also of the Schur spaces by the properties of reflexive cones is given.Comment: 23 page

Timing storytime to maximize children\u27s ability to retain new vocabulary

\ua9 2021 The AuthorsShared storybook reading is a key aid to vocabulary acquisition during childhood. However, word learning research has tended to use unnaturalistic (explicit) training regimes. Using a storybook paradigm, we examined whether children (particularly those with weaker vocabularies) are more likely to retain new words if they learn them closer to sleep. Parents read their children (5- to 7-year-olds; N = 237) an alien adventure story that contained 12 novel words with illustrations at one of two training times: at bedtime or 3–5 h before bedtime. Using online tasks, parents tested their children\u27s ability to recall the new words (production) and associate them with pictures (comprehension) immediately after hearing the story and again the following morning. As hypothesized, we replicated two findings. First, children showed overnight improvements in their ability to produce and comprehend new words when tested again the next day. Second, children with better existing vocabulary knowledge showed larger overnight gains in new word comprehension. Counter to expectations, overnight gains in comprehension were larger if the story was read 3–5 h before bedtime rather than at bedtime. These ecologically valid findings are consistent with theories that characterize word learning as a prolonged process supported by mechanisms such as consolidation and retrieval practice, with existing vocabulary knowledge acting as an important source of variability in retention. The findings provide preliminary evidence that encountering new words in stories later in the day (but not too close to sleep) may help to harness vocabulary growth and may be more beneficial than leaving shared storybook reading just for bedtime

A randomised trial of an internet weight control resource: The UK Weight Control Trial [ISRCTN58621669]

BACKGROUND: Obesity treatment is notoriously unsuccessful and one of the barriers to successful weight loss reported by patients is a lack of social support. The Internet offers a novel and fast approach to the delivery of health information, enabling 24-hour access to help and advice. However, much of the health information available on the Internet is unregulated or not written by qualified health professionals to provide unbiased information. The proposed study aims to compare a web-based weight loss package with traditional dietary treatment of obesity in participants. The project aims to deliver high quality information to the patient and to evaluate the effectiveness of this information, both in terms of weight loss outcomes and cost-effectiveness. METHODS: This study is a randomised controlled trial of a weight loss package against usual care provided within General Practice (GP) surgeries in Leeds, UK. Participants will be recruited via posters placed in participating practices. A target recruitment figure of 220 will enable 180 people to be recruited (allowing for 22% dropout). Participants agreeing to take part in the study will be randomly allocated using minimisation to either the intervention group, receiving access to the Internet site, or the usual care group. The primary outcome of the study will be the ability of the package to promote change in BMI over 6 and 12 months compared with traditional treatment. Secondary outcomes will be the ability of the Internet package to promote change in reported lifestyle behaviours. Data will be collected on participant preferences, adherence to treatment, health care use and time off work. Difference in cost between groups in provision of the intervention and the cost of the primary outcome will also be estimated. CONCLUSION: A positive result from this study would enhance the repertoire of treatment approaches available for the management of obesity. A negative result would be used to inform the research agenda and contribute to redefining future strategies for tackling obesity

Andersen-Tawil Syndrome Presenting with Complete Heart Block

Andersen-Tawil syndrome (ATS) is a rare autosomal dominant neuromuscular disorder due to mutations in the KCNJ2 gene. The classical phenotype of ATS consists of a triad of periodic paralysis, cardiac conduction abnormalities and dysmorphic features. Episodes of either muscle weakness or cardiac arrhythmia may predominate however, and dysmorphic features may be subtle, masking the true breadth of the clinical presentation, and posing a diagnostic challenge. The severity of cardiac involvement varies but includes reports of life-threatening events or sudden cardiac death, usually attributed to ventricular tachyarrhythmias. We report the first case of advanced atrioventricular (AV) block in ATS and highlight clinical factors that may delay diagnosis

Genome-Wide Studies of Histone Demethylation Catalysed by the Fission Yeast Homologues of Mammalian LSD1

In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1+ gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1¿ strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression

Coupling Lipid Nanoparticle Structure and Automated Single Particle Composition Analysis to Design Phospholipase Responsive Nanocarriers

Lipid nanoparticles (LNPs) are versatile structures with tunable physicochemical properties that are ideally suited as a platform for vaccine delivery and RNA therapeutics. A key barrier to LNP rational design is the inability to relate composition and structure to intracellular processing and function. Here we combine Single Particle Automated Raman Trapping Analysis (SPARTA®) with small angle scattering (SAXS / SANS) techniques to link LNP composition with internal structure and morphology and to monitor dynamic LNP - phospholipase D (PLD) interactions. Our analysis demonstrates that phospholipase D, a key intracellular trafficking mediator, can access the entire LNP lipid membrane to generate stable, anionic LNPs. PLD activity on vesicles with matched amounts of enzyme substrate was an order of magnitude lower, indicating that the LNP lipid membrane structure can be used to control enzyme interactions. This represents an opportunity to design enzyme-responsive LNP solutions for stimuli-responsive delivery and diseases where PLD is dysregulated

4D, N = 1 Supersymmetry Genomics (II)

We continue the development of a theory of off-shell supersymmetric representations analogous to that of compact Lie algebras such as SU(3). For off-shell 4D, N = 1 systems, quark-like representations have been identified [1] in terms of cis-Adinkras and trans-Adinkras and it has been conjectured that arbitrary representations are composites of $n_c$-cis and $n_t$-trans representations. Analyzing the real scalar and complex linear superfield multiplets, these "chemical enantiomer" numbers are found to be $n_c$ = $n_t$ = 1 and $n_c$ = 1, $n_t$ = 2, respectively.Comment: 40 pages, 8 figures, sequel to "4D, N = 1 Supersymmetry Genomics (I)" [arxiv: 0902.3830

第28号

Background Perioperative fluid strategies influence clinical outcomes following major surgery. Many intravenous fluid preparations are based on simple solutions, such as normal saline, that feature an electrolyte composition that differs from that of physiological plasma. Buffered fluids have a theoretical advantage of containing a substrate that acts to maintain the body’s acid-base status - typically a bicarbonate or a bicarbonate precursor such as maleate, gluconate, lactate, or acetate. Buffered fluids also provide additional electrolytes, including potassium, magnesium, and calcium, more closely matching the electrolyte balance of plasma. The putative benefits of buffered fluids have been compared with those of non-buffered fluids in the context of clinical studies conducted during the perioperative period. This review was published in 2012, and was updated in 2017. Objectives To review effects of perioperative intravenous administration of buffered versus non-buffered fluids for plasma volume expansion or maintenance, or both, on clinical outcomes in adults undergoing all types of surgery. Search methods We electronically searched the Clinicaltrials.gov major trials registry, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 6) in the Cochrane Library, MEDLINE (1966 to June 2016), Embase (1980 to June 2016), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to June 2016). We handsearched conference abstracts and, when possible, contacted leaders in the field. We reran the search in May 2017. We added one potential new study of interest to the list of ‘Studies awaiting classification' and will incorporate this trial into formal review findings when we prepare the review update. Selection criteria Only randomized controlled trials that compared buffered versus non-buffered intravenous fluids for surgical patients were eligible for inclusion. We excluded other forms of comparison such as crystalloids versus colloids and colloids versus different colloids. Data collection and analysis Two review authors screened references for eligibility, extracted data, and assessed risks of bias. We resolved disagreements by discussion and consensus, in collaboration with a third review author. We contacted trial authors to request additional information when appropriate. We presented pooled estimates for dichotomous outcomes as odds ratios (ORs) and for continuous outcomes as mean differences (MDs), with 95% confidence intervals (CIs). We analysed data via Review Manager 5.3 using fixed-effect models, and when heterogeneity was high (I² > 40%), we used random-effects models. Main results This review includes, in total, 19 publications of 18 randomized controlled trials with a total of 1096 participants. We incorporated five of those 19 studies (330 participants) after the June 2016 update. Outcome measures in the included studies were thematically similar, covering perioperative electrolyte status, renal function, and acid-base status; however, we found significant clinical and statistical heterogeneity among the included studies. We identified variable protocols for fluid administration and total volumes of fluid administered to patients intraoperatively. Trial authors variably reported outcome data at disparate time points and with heterogeneous patient groups. Consequently, many outcome measures are reported in small group sizes, reducing overall confidence in effect size, despite relatively low inherent bias in the included studies. Several studies reported orphan outcome measures. We did not include in the results of this review one large, ongoing study of saline versus Ringer's solution. We found insufficient evidence on effects of fluid therapies on mortality and postoperative organ dysfunction (defined as renal insufficiency leading to renal replacement therapy); confidence intervals were wide and included both clinically relevant benefit and harm: mortality (Peto OR 1.85, 95% CI 0.37 to 9.33; I² = 0%; 3 trials, 6 deaths, 276 participants; low-quality evidence); renal insufficiency (OR 0.82, 95% CI 0.34 to 1.98; I² = 0%; 4 trials, 22 events, 276 participants; low-quality evidence). We noted several metabolic differences, including a difference in postoperative pH measured at end of surgery of 0.05 units - lower in the non-buffered fluid group (12 studies with a total of 720 participants; 95% CI 0.04 to 0.07; I² = 61%). However, this difference was not maintained on postoperative day one. We rated the quality of evidence for this outcome as moderate. We observed a higher postoperative serum chloride level immediately after operation, with use of non-buffered fluids reported in 10 studies with a total of 530 participants (MD 6.77 mmol/L, 95% CI 3.38 to 10.17), and this difference persisted until day one postoperatively (five studies with a total of 258 participants; MD 8.48 mmol/L, 95% CI 1.08 to 15.88). We rated the quality of evidence for this outcome as moderate. Authors' conclusions Current evidence is insufficient to show effects of perioperative administration of buffered versus non-buffered crystalloid fluids on mortality and organ system function in adult patients following surgery. Benefits of buffered fluid were measurable in biochemical terms, particularly a significant reduction in postoperative hyperchloraemia and metabolic acidosis. Small effect sizes for biochemical outcomes and lack of correlated clinical follow-up data mean that robust conclusions on major morbidity and mortality associated with buffered versus non-buffered perioperative fluid choices are still lacking. Larger studies are needed to assess these relevant clinical outcomes

Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease : a prospective cohort study

Background : Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function. Patients and methods : In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates. Results : During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 (95% confidence interval (CI): 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables (age, CRP, diabetes and a history of cardiovascular disease) both sTNFRs remained independently associated to outcomes (HR: sTNFR1: 1.51, 95% CI: 1.30-1.77; sTNFR2: 1.13, 95% CI: 1.06-1.20). A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1. Conclusion : sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease