Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

Evaluation of commercial soy sauce koji strains of Aspergillus oryzae for γ-aminobutyric acid (GABA) production

In this study, four selected commercial strains of Aspergillus oryzae were collected from soy sauce koji. These A. oryzae strains designated as NSK, NSZ, NSJ and NST shared similar morphological characteristics with the reference strain (A. oryzae FRR 1675) which confirmed them as A. oryzae species. They were further evaluated for their ability to produce γ-aminobutyric acid (GABA) by cultivating the spore suspension in a broth medium containing 0.4 % (w/v) of glutamic acid as a substrate for GABA production. The results showed that these strains were capable of producing GABA; however, the concentrations differed significantly (P < 0.05) among themselves. Based on the A. oryzae strains, highest GABA concentration was obtained from NSK (194 mg/L) followed by NSZ (63 mg/L), NSJ (51.53 mg/L) and NST (31.66 mg/L). Therefore, A. oryzae NSK was characterized and the sequence was found to be similar to A. oryzae and A. flavus with 99 % similarity. The evolutionary distance (K nuc) between sequences of identical fungal species was calculated and a phylogenetic tree prepared from the K nuc data showed that the isolate belonged to the A. oryzae species. This finding may allow the development of GABA-rich ingredients using A. oryzae NSK as a starter culture for soy sauce production

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children &lt;18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p&lt;0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p&lt;0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p&lt;0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Conceptual phase of construction projects

An important topic addressed in the Emerson report in 1962 and the Latham report in 1994 is the issue of productivity in the construction industry. However, attention has only been focused on phases other than the conceptual phase of construction projects. The conceptual phase is of strategic importance in the project environment. Understanding this phase is a prerequisite for improving productivity on site. The paper discusses the conceptual phase of construction projects. An extensive literature review and interviews with four experienced practitioners from major client and construction organisations identified the definition, relationships and tasks for the conceptual phase. These characteristics of the conceptual phase will be the basis of an a priori hypothesis, which will be tested through a postal survey of 144 companies throughout Europe. Case studies will be carried out of six major projects: a nuclear power station, a petrochemical plant, a sewage treatment plant, an off-shore North Sea oil project, a major international airport, and a motorway project. © 1995

The influence of experimental silane primers on dentin bond strength and morphology: A laboratory and finite element analysis study

Statement of problem. The inconsistency of dentin bonding affects retention and microleakage. Purpose. The purpose of this laboratory and finite element analysis study was to investigate the effects on the formation of a hybrid layer of an experimental silane coupling agent containing primer solutions composed of different percentages of hydroxyethyl methacrylate. Material and methods. A total of 125 sound human premolars were restored in vitro. Simple class I cavities were formed on each tooth, followed by the application of different compositions of experimental silane primers (0%, 5%, 25%, and 50% of hydroxyethyl methacrylate), bonding agents, and dental composite resins. Bond strength tests and scanning electron microscopy analyses were performed. The laboratory experimental results were validated with finite element analysis to determine the pattern of stress distribution. Simulations were conducted by placing the restorative composite resin in a premolar tooth by imitating simple class I cavities. The laboratory and finite element analysis data were significantly different from each other, as determined by 1-way ANOVA. A post hoc analysis was conducted on the bond strength data to further clarify the effects of silane primers. Results. The strongest bond of hybrid layer (16.96 MPa) was found in the primer with 25% hydroxyethyl methacrylate, suggesting a barely visible hybrid layer barrier. The control specimens without the application of the primer and the primer specimens with no hydroxyethyl methacrylate exhibited the lowest strength values (8.30 MPa and 11.78 MPa) with intermittent and low visibility of the hybrid layer. These results were supported by finite element analysis that suggested an evenly distributed stress on the model with 25% hydroxyethyl methacrylate. Conclusions. Different compositions of experimental silane primers affected the formation of the hybrid layer and its resulting bond strength

Biomechanical analysis of rheumatoid arthritis of the wrist joint

The wrist is the most complex joint for virtual three-dimensional simulations, and the complexity is even more pronounced when dealing with skeletal disorders of the joint such, as rheumatoid arthritis (RA). In order to analyse the biomechanical difference between healthy and diseased joints, three-dimensional models of these two wrist conditions were developed from computed tomography images. These images consist of eight carpal bones, five metacarpal bones, the distal radius and ulna. The cartilages were developed based on the shape of the available articulations and ligaments were simulated via mechanical links. The RA model was developed accurately by simulating all ten common criteria of the disease related to the wrist. Results from the finite element (FE) analyses showed that the RA model produced three times higher contact pressure at the articulations compared to the healthy model. Normal physiological load transfer also changed from predominantly through the radial side to an increased load transfer approximately 5% towards the ulnar. Based on an extensive literature search, this is the first ever reported work that simulates the pathological conditions of the rheumatoid arthritis of the wrist joint