Ammonia-oxidizing archaea are ubiquitous in marine and terrestrial environments and now thought to be significant contributors to carbon and nitrogen cycling. The isolation of Candidatus ..."Nitrosopumilus maritimus" strain SCM1 provided the opportunity for linking its chemolithotrophic physiology with a genomic inventory of the globally distributed archaea. Here we report the 1,645,259-bp closed genome of strain SCM1, revealing highly copper-dependent systems for ammonia oxidation and electron transport that are distinctly different from known ammonia-oxidizing bacteria. Consistent with in situ isotopic studies of marine archaea, the genome sequence indicates N. maritimus grows autotrophically using a variant of the 3-hydroxypropionate/4-hydroxybutryrate pathway for carbon assimilation, while maintaining limited capacity for assimilation of organic carbon. This unique instance of archaeal biosynthesis of the osmoprotectant ectoine and an unprecedented enrichment of multicopper oxidases, thioredoxin-like proteins, and transcriptional regulators points to an organism responsive to environmental cues and adapted to handling reactive copper and nitrogen species that likely derive from its distinctive biochemistry. The conservation of N. maritimus gene content and organization within marine metagenomes indicates that the unique physiology of these specialized oligophiles may play a significant role in the biogeochemical cycles of carbon and nitrogen.
Restructuring of metals by chiral molecules represents an important route to inducing and controlling enantioselective surface chemistry. Tartaric acid adsorption on Cu(110) has served as a useful ...system for understanding many aspects of chiral molecule adsorption and ordering on a metal surface, and a number of chiral and achiral unit cells have been reported. Herein, we show that given the appropriate annealing treatment, singly deprotonated tartaric acid monolayers can restructure the Cu metal itself, and that the resulting structure is both highly ordered and chiral. Molecular resolution scanning tunneling microscopy reveals that singly deprotonated tartaric acid extracts Cu atoms from the Cu(110) surface layer and incorporates them into highly ordered, chiral adatom arrays capped by a continuous molecular layer. Further evidence for surface restructuring comes from images of atom-deep trenches formed in the Cu(110) surface during the process. These trenches also run in low symmetry directions and are themselves chiral. Simulated scanning tunneling microscopy images are consistent with the appearance of the added atom rows and etched trenches. The chiral imprinting results in a long-range, highly ordered ( 2 − 1 6 7 ) unit cell covering the whole surface as confirmed by low energy electron diffraction. Details of the restructuring mechanism were further investigated via time-lapse imaging at elevated temperature. This work reveals the stages of nanoscale surface restructuring and offers an interesting method for chiral modification of an achiral metal surface.
The initial stage in the oxidation of Cu single crystal surfaces has been studied on a surface structure spread single crystal (S4C) exposing a continuous distribution of all Cu(hkl) surface ...orientations lying within 10° polar angle of the (111) plane, Cu(111) ± 10°-S4C. The uptake of oxygen across the Cu(111) ± 10°-S4C during exposure to O2 at 300 K has been measured using spatially resolved X-ray photoelectron spectroscopy (XPS), and the resulting Cu2O surface oxide layer has been imaged using scanning tunneling microscopy (STM). Uptake of oxygen is dependent on surface step density and increases with increasing polar angle relative to the (111) pole. In contrast, the oxygen uptake does not depend on the crystallographic orientation of the step edge or, in other words, the kink density along the step edge. STM images reveal that once oxidation of the step edges begins, all of the boundaries of the Cu2O step oxide layer are oriented along (100) step edges in the Cu(111) terrace independent of the initial orientation of the step. In other words, the oxidizing step edges have no memory of their original orientation, and thus, the step growth depends only on step density and not on the kink density along the step edge. The combined use of both spatially resolved XPS and atomic scale imaging with STM on a Cu(111) ± 10°-S4C has provided unique insight into the origins of structure-sensitive surface chemistry.
The introduction and widespread adoption of induced pluripotent stem cell (iPSC) technology has opened new avenues for craniofacial regenerative medicine. Neural crest cells (NCCs) are the precursor ...population to many craniofacial structures, including dental and periodontal structures, and iPSC-derived NCCs may, in the near future, offer an unlimited supply of patient-specific cells for craniofacial repair interventions.
Here, we used an established protocol involving simultaneous Wnt signaling activation and TGF-β signaling inhibition to differentiate three human iPSC lines to cranial NCCs. We then derived a mesenchymal progenitor cell (NCC-MPCs) population with chondrogenic and osteogenic potential from cranial NCCs and investigated their similarity to widely studied human postnatal dental or periodontal stem/progenitor cells. NCC-MPCs were quite distinct from both their precursor cells (NCCs) and bone-marrow mesenchymal stromal cells, a stromal population of mesodermal origin. Despite their similarity with dental stem/progenitor cells, NCC-MPCs were clearly differentiated by a core set of 43 genes, including ACKR3 (CXCR7), whose expression (both at transcript and protein level) appear to be specific to NCC-MPCs.
Altogether, our data demonstrate the feasibility of craniofacial mesenchymal progenitor derivation from human iPSCs through a neural crest-intermediate and set the foundation for future studies regarding their full differentiation repertoire and their in vivo existence.
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•We define the transcriptome of neural crest cells derived from human iPS cells.•iPS cell-derived neural crest cells can differentiate to putative craniofacial mesenchymal progenitors.•These progenitors possess chondrogenic and osteogenic potential.•CXCR7 and PTPRB expression is specific to mesenchymal progenitors compared to dental stem/progenitor cells.
Autocatalytic reaction mechanisms are observed in a range of important chemical processes including catalysis, radical-mediated explosions, and biosynthesis. Because of their complexity, the ...microscopic details of autocatalytic reaction mechanisms have been difficult to study on surfaces and heterogeneous catalysts. Autocatalytic decomposition reactions of S,S- and R,R-tartaric acid (TA) adsorbed on Cu(110) offer molecular-level insight into aspects of these processes, which until now, were largely a matter of speculation. The decomposition of TA/Cu(110) is initiated by a slow, irreversible process that forms vacancies in the adsorbed TA layer, followed by a vacancy-mediated, explosive decomposition process that yields CO2 and small hydrocarbon products. Initiation of the explosive decomposition of TA/Cu(110) has been studied by measurement of the reaction kinetics, time-resolved low energy electron diffraction (LEED), and time-resolved scanning tunneling microscopy (STM). Initiation results in a decrease in the local coverage of TA and a concomitant increase in the areal vacancy concentration. Observations of explosive TA decomposition on the Cu(651)S surface suggest that initiation does not occur at structural defects in the surface, as has been suggested in the past. Once the vacancy concentration reaches a critical value, the explosive, autocatalytic decomposition step dominates the TA decomposition rate. The onset of the explosive decomposition of TA on Cu(110) is accompanied by the extraction of Cu atoms from the surface to form a (±6,7; ∓2,1) overlayer that is readily observable using LEED and STM. The explosive decomposition step is second-order in vacancy concentration and accelerates with increasing extent of reaction.
It has been proposed that the Chronic Kidney Disease Epidemiology Collaboration formula estimates glomerular filtration rate more accurately than the Modification of Diet in Renal Disease formula. ...With the very high incidence of diabetes and end-stage kidney disease in Indigenous Australians, accurate estimation of glomerular filtration rate is vital in early detection of kidney disease. We aimed to assess the performance of the Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease and Cockcroft-Gault formulas in Indigenous Australians with and without diabetes.
Indigenous Australians with (n = 224) or without (n = 340) Type 2 diabetes had a reference glomerular filtration rate measure using plasma disappearance of iohexol (measured glomerular filtration rate) over 4 h. Serum creatinine was measured by an enzymatic method. Performance was assessed by bias (measured glomerular filtration rate - estimated glomerular filtration rate) and accuracy (percentage of estimated glomerular filtration rate within 30% of measured glomerular filtration rate).
The median measured glomerular filtration rate (interquartile range) in participants with or without diabetes was 97 (68-119) and 108 (90-122) ml min(-1) 1.73 m(-2) , respectively. The Chronic Kidney Disease Epidemiology Collaboration formula had smaller bias and greater accuracy than the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall, for participants both with and without diabetes. However, for estimated glomerular filtration rate > 90 ml min(-1) 1.73 m(-2) , the Chronic Kidney Disease Epidemiology Collaboration formula had greater bias in participants with diabetes, underestimating measured glomerular filtration rate by 7.4 vs. 1.0 ml min(-1) 1.73 m(-2) in those without diabetes. The Chronic Kidney Disease Epidemiology Collaboration formula was less accurate across the whole range of estimated glomerular filtration rates in participants with vs. those without diabetes (87.1% vs. 93.3%).
The Chronic Kidney Disease Epidemiology Collaboration formula outperforms the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall in Indigenous Australians with and without diabetes. However, the Chronic Kidney Disease Epidemiology Collaboration formula has greater bias in people with diabetes compared with those without diabetes, especially in those with normal renal function.
Improving the quality and safety of perioperative care is a global priority. The Enhanced Peri-Operative Care for High-risk patients (EPOCH) trial was a stepped-wedge cluster randomised trial of a ...quality improvement (QI) programme to improve 90-day survival for patients undergoing emergency abdominal surgery in 93 hospitals in the UK National Health Service.
The aim of this process evaluation is to describe how the EPOCH intervention was planned, delivered and received, at both cluster and local hospital levels. The QI programme comprised of two interventions: a care pathway and a QI intervention to aid pathway implementation, focussed on stakeholder engagement, QI teamwork, data analysis and feedback and applying the model for improvement. Face-to-face training and online resources were provided to support senior clinicians in each hospital (QI leads) to lead improvement. For this evaluation, we collated programme activity data, administered an exit questionnaire to QI leads and collected ethnographic data in six hospitals. Qualitative data were analysed with thematic or comparative analysis; quantitative data were analysed using descriptive statistics.
The EPOCH trial did not demonstrate any improvement in survival or length of hospital stay. Whilst the QI programme was delivered as planned at the cluster level, self-assessed intervention fidelity at the hospital level was variable. Seventy-seven of 93 hospitals responded to the exit questionnaire (60 from a single QI lead response on behalf of the team); 33 respondents described following the QI intervention closely (35%) and there were only 11 of 37 care pathway processes that > 50% of respondents reported attempting to improve. Analysis of qualitative data suggests QI leads were often attempting to deliver the intervention in challenging contexts: the social aspects of change such as engaging colleagues were identified as important but often difficult and clinicians frequently attempted to lead change with limited time or organisational resources.
Significant organisational challenges faced by QI leads shaped their choice of pathway components to focus on and implementation approaches taken. Adaptation causing loss of intervention fidelity was therefore due to rational choices made by those implementing change within constrained contexts. Future large-scale QI programmes will need to focus on dedicating local time and resources to improvement as well as on training to develop QI capabilities.
ISRCTN80682973 https://doi.org/10.1186/ISRCTN80682973 Registered 27 February 2014 and Lancet protocol 13PRT/7655.
ABSTRACT
Objective
To describe the detailed associations of albuminuria among a contemporary cohort of Aboriginal and Torres Strait Islander people to inform strategies for chronic kidney disease ...prevention and management.
Methods
A cross‐sectional analysis of Indigenous participants of the eGFR Study.
Measures
Clinical, biochemical and anthropometric measures were collected (including body‐circumferences, blood pressure (BP); triglycerides, HbA1c, liver function tests, creatinine; urine‐ microscopic‐haem, albumin: creatinine ratio (ACR), prescriptions‐ angiotensin converting enzyme inhibitor or angiotensin receptor II antagonist (ACEI/ARB). Albuminuria and diabetes were defined by an ACR>3.0 mg/mmol, and HbA1c≥48 mmol/mol or prior history respectively. Waist: hip ratio (WHR), and estimated glomerular filtration rate (eGFR) were calculated. ACR was non‐normally distributed; a logarithmic transformation was applied (in base 2), with each unit increase in log2‐albuminuria representing a doubling of ACR.
Results
591 participants were assessed (71% Aboriginal, 61.6% female, mean age 45.1 years, BMI 30.2 kg/m2, WHR 0.94, eGFR 99.2 ml/min/1.73m2). The overall prevalence of albuminuria, diabetes, microscopic‐haem and ACEI/ARB use was 41.5%, 41.5%, 17.8% and 34.7% respectively; 69.3% of adults with albuminuria and diabetes received an ACEI/ARB. Using multivariable linear regression modelling, the potentially modifiable factors independently associated with log2‐albuminuria were microscopic‐haem, diabetes, WHR, systolic BP, alkaline phosphatase (all positive) and eGFR (inverse).
Conclusion
Albuminuria is associated with diabetes, central obesity and haematuria. High ACEI/ARB prescribing for adults with diabetes and albuminuria was observed. Further understanding of the links between fat deposition, haematuria and albuminuria is required.
Summary at a Glance
The authors reported a strong cross‐sectional association of log2‐albuminuria with abdominal obesity, diabetes and microscopic‐haem among Indigenous Australian participants who are relatively younger than other populations with chronic kidney disease.
Because lobular carcinoma in situ is thought to be an incidental finding at breast pathology, the finding of lobular carcinoma in situ at core biopsy poses a diagnostic dilemma of ...radiologic-pathologic concordance. The purpose of this article is to describe the radiologic-pathologic correlation of calcifications associated with lobular carcinoma in situ of the breast.
Between July 1999 and July 2000, seven excisional biopsies resulted in findings of lobular carcinoma in situ of mammographic calcifications. The radiographic features of the calcifications were characterized by the Breast Imaging Reporting and Data System lexicon, and pathologic features were reviewed.
Two forms of lobular carcinoma in situ were associated with calcifications: the classic form with small, uniform cells, and the pleomorphic form with larger cells frequently associated with central necrosis. On mammography, all calcifications were clustered, punctate, high density, and smaller than or equal to 0.5 mm, although mammographically visible calcifications found in the pleomorphic type tended to be larger and more dense. Additionally, infiltrating lobular carcinoma was found after surgical excision in two (40%) of five patients with pleomorphic lobular carcinoma in situ.
Calcifications can be associated with lobular carcinoma in situ and therefore concordant at stereotactic core biopsy. The classic form may be incidental and clinically innocuous. The pleomorphic form is morphologically similar to ductal carcinoma in situ and may have a greater tendency for invasion.
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