Bradyrhizobium japonicum senses iron through the status of haem to regulate iron homeostasis and metabolism

The Irr protein from the bacterium Bradyrhizobium japonicum is expressed under iron limitation to mediate iron control of haem biosynthesis. The regulatory input to Irr is the status of haem and its precursors iron and protoporphyrin at the site of haem synthesis. Here, we show that Irr controls the expression of iron transport genes and many other iron-regulated genes not directly involved in haem synthesis. Irr is both a positive and negative effector of gene expression, and in at least some cases the control is direct. Loss of normal iron responsiveness of those genes in an irr mutant, as well as a lower total cellular iron content, suggests that Irr is required for the correct perception of the cellular iron status. Degradation of Irr in iron replete cells requires haem. Accordingly, control of Irr-regulated genes by iron was aberrant in a haem-defective strain, and iron replete mutant cells behave as if they are iron-limited. In addition, the haem mutant had an abnormally high cellular iron content. The findings indicate that B. japonicum senses iron via the status of haem biosynthesis in an Irr-dependent manner to regulate iron homeostasis and metabolism

Gender differences in the incidence of and risk factors for hip fracture: A 16-year longitudinal study in a southern European population

Objectives To analyze independently in men and women the incidence rate of and risk factors for hip fracture in a southern European population. Illiteracy, dementia, clinically significant depression and disability were factors to receive special emphasis. Study design A community sample of 4803 individuals aged over 55 years was assessed in a two-phase case-finding study in Zaragoza, Spain, and was followed up for 16 years. Medical history and psychiatric history were collected with standardized instruments, including the History and Aetiology Schedule, the Geriatric Mental State (GMS) scale, and a Risk Factors Questionnaire. Operational criteria were used to define covariates, including diagnostic criteria for both dementia and depression. The statistical analysis included calculations of incidence rate, IR; women/men incidence rate ratio (IRR); and Hazard Ratios (HR) in multivariate Cox proportional hazards regression models. Main outcome measures Cases of hip fracture (International Classification of Diseases, WHO) identified in the treating hospitals, validated by blinded researchers. Results Hip fractures were more frequent among women than men (IRR = 3.1). Illiteracy (HR = 1.55) and depression (HR = 1.44) increased the risk in women, and smoking (HR = 2.13) and disability in basic activities of daily living (HR = 3.14) increased the risk in men. Dementia was associated with an increased risk in an univariate analysis, but the association disappeared (power = 85% in men, 95% in women) when disability was included in the multivariate models. Conclusions The IR of hip fractures was three times higher among women. Illiteracy and clinically significant depression among women and active smoking and disability (HR = 3.14) among men independently increased the risk, but dementia did not

A review of wearable motion tracking systems used in rehabilitation following hip and knee replacement

Clinical teams are under increasing pressure to facilitate early hospital discharge for total hip replacement and total knee replacement patients following surgery. A wide variety of wearable devices are being marketed to assist with rehabilitation following surgery. A review of wearable devices was undertaken to assess the evidence supporting their efficacy in assisting rehabilitation following total hip replacement and total knee replacement. A search was conducted using the electronic databases including Medline, CINAHL, Cochrane, PsycARTICLES, and PubMed of studies from January 2000 to October 2017. Five studies met the eligibility criteria, and all used an accelerometer and a gyroscope for their technology. A review of the studies found very little evidence to support the efficacy of the technology, although they show that the use of the technology is feasible. Future work should establish which wearable technology is most valuable to patients, which ones improve patient outcomes, and the most economical model for deploying the technolog

Can current moisture responses predict soil CO2 efflux under altered precipitation regimes? A synthesis of manipulation experiments.

As a key component of the carbon cycle, soil CO2 efflux (SCE) is being increasingly studied to improve our mechanistic understanding of this important carbon flux. Predicting ecosystem responses to climate change often depends on extrapolation of current relationships between ecosystem processes and their climatic drivers to conditions not yet experienced by the ecosystem. This raises the question of to what extent these relationships remain unaltered beyond the current climatic window for which observations are available to constrain the relationships. Here, we evaluate whether current responses of SCE to fluctuations in soil temperature and soil water content can be used to predict SCE under altered rainfall patterns. Of the 58 experiments for which we gathered SCE data, 20 were discarded because either too few data were available or inconsistencies precluded their incorporation in the analyses. The 38 remaining experiments were used to test the hypothesis that a model parameterized with data from the control plots (using soil temperature and water content as predictor variables) could adequately predict SCE measured in the manipulated treatment. Only for 7 of these 38 experiments was this hypothesis rejected. Importantly, these were the experiments with the most reliable data sets, i.e., those providing high-frequency measurements of SCE. Regression tree analysis demonstrated that our hypothesis could be rejected only for experiments with measurement intervals of less than 11 days, and was not rejected for any of the 24 experiments with larger measurement intervals. This highlights the importance of high-frequency measurements when studying effects of altered precipitation on SCE, probably because infrequent measurement schemes have insufficient capacity to detect shifts in the climate dependencies of SCE. Hence, the most justified answer to the question of whether current moisture responses of SCE can be extrapolated to predict SCE under altered precipitation regimes is ?no? ? as based on the most reliable data sets available. We strongly recommend that future experiments focus more strongly on establishing response functions across a broader range of precipitation regimes and soil moisture conditions. Such experiments should make accurate measurements of water availability, should conduct high-frequency SCE measurements, and should consider both instantaneous responses and the potential legacy effects of climate extremes. This is important, because with the novel approach presented here, we demonstrated that, at least for some ecosystems, current moisture responses could not be extrapolated to predict SCE under altered rainfall conditions

Can current moisture responses predict soil CO2 efflux under altered precipitation regimes? A synthesis of manipulation experiments

As a key component of the carbon cycle, soil CO2 efflux (SCE) is being increasingly studied to improve our mechanistic understanding of this important carbon flux. Predicting ecosystem responses to climate change often depends on extrapolation of current relationships between ecosystem processes and their climatic drivers to conditions not yet experienced by the ecosystem. This raises the question of to what extent these relationships remain unaltered beyond the current climatic window for which observations are available to constrain the relationships. Here, we evaluate whether current responses of SCE to fluctuations in soil temperature and soil water content can be used to predict SCE under altered rainfall patterns. Of the 58 experiments for which we gathered SCE data, 20 were discarded because either too few data were available or inconsistencies precluded their incorporation in the analyses. The 38 remaining experiments were used to test the hypothesis that a model parameterized with data from the control plots (using soil temperature and water content as predictor variables) could adequately predict SCE measured in the manipulated treatment. Only for 7 of these 38 experiments was this hypothesis rejected. Importantly, these were the experiments with the most reliable data sets, i.e., those providing high-frequency measurements of SCE. Regression tree analysis demonstrated that our hypothesis could be rejected only for experiments with measurement intervals of less than 11 days, and was not rejected for any of the 24 experiments with larger measurement intervals. This highlights the importance of high-frequency measurements when studying effects of altered precipitation on SCE, probably because infrequent measurement schemes have insufficient capacity to detect shifts in the climate dependencies of SCE. Hence, the most justified answer to the question of whether current moisture responses of SCE can be extrapolated to predict SCE under altered precipitation regimes is 'no' - as based on the most reliable data sets available. We strongly recommend that future experiments focus more strongly on establishing response functions across a broader range of precipitation regimes and soil moisture conditions. Such experiments should make accurate measurements of water availability, should conduct high-frequency SCE measurements, and should consider both instantaneous responses and the potential legacy effects of climate extremes. This is important, because with the novel approach presented here, we demonstrated that, at least for some ecosystems, current moisture responses could not be extrapolated to predict SCE under altered rainfall conditions

A Single Nucleotide Change Affects Fur-Dependent Regulation of sodB in H. pylori

Helicobacter pylori is a significant human pathogen that has adapted to survive the many stresses found within the gastric environment. Superoxide Dismutase (SodB) is an important factor that helps H. pylori combat oxidative stress. sodB was previously shown to be repressed by the Ferric Uptake Regulator (Fur) in the absence of iron (apo-Fur regulation) [1]. Herein, we show that apo regulation is not fully conserved among all strains of H. pylori. apo-Fur dependent changes in sodB expression are not observed under iron deplete conditions in H. pylori strains G27, HPAG1, or J99. However, Fur regulation of pfr and amiE occurs as expected. Comparative analysis of the Fur coding sequence between G27 and 26695 revealed a single amino acid difference, which was not responsible for the altered sodB regulation. Comparison of the sodB promoters from G27 and 26695 also revealed a single nucleotide difference within the predicted Fur binding site. Alteration of this nucleotide in G27 to that of 26695 restored apo-Fur dependent sodB regulation, indicating that a single base difference is at least partially responsible for the difference in sodB regulation observed among these H. pylori strains. Fur binding studies revealed that alteration of this single nucleotide in G27 increased the affinity of Fur for the sodB promoter. Additionally, the single base change in G27 enabled the sodB promoter to bind to apo-Fur with affinities similar to the 26695 sodB promoter. Taken together these data indicate that this nucleotide residue is important for direct apo-Fur binding to the sodB promoter

Ribonucleotide reductases of Salmonella Typhimurium : transcriptional regulation and differential role in pathogenesis

Ribonucleotide reductases (RNRs) are essential enzymes that carry out the de novo synthesis of deoxyribonucleotides by reducing ribonucleotides. There are three different classes of RNRs (I, II and III), all having different oxygen dependency and biochemical characteristics. Salmonella enterica serovar Typhimurium (S. Typhimurium) harbors class Ia, class Ib and class III RNRs in its genome. We have studied the transcriptional regulation of these three RNR classes in S. Typhimurium as well as their differential function during infection of macrophage and epithelial cells. Deletion of both NrdR and Fur, two main transcriptional regulators, indicates that Fur specifically represses the class Ib enzyme and that NrdR acts as a global repressor of all three classes. A Fur recognition sequence within the nrdHIEF promoter has also been described and confirmed by electrophoretic mobility shift assays (EMSA). In order to elucidate the role of each RNR class during infection, S. Typhimurium single and double RNR mutants (as well as Fur and NrdR mutants) were used in infection assays with macrophage and epithelial cell lines. Our results indicate class Ia to be mainly responsible for deoxyribonucleotide production during invasion and proliferation inside macrophages and epithelial cells. Neither class Ib nor class III seem to be essential for growth under these conditions. However, class Ib is able to maintain certain growth in an nrdAB mutant during the first hours of macrophage infection. Our results suggest that, during the early stages of macrophage infection, class Ib may contribute to deoxyribonucleotide synthesis by means of both an NrdR and a Fur-dependent derepression of nrdHIEF due to hydrogen peroxide production and DNA damage associated with the oxidative burst, thus helping to overcome the host defenses

Precision Newborn Screening for Lysosomal Disorders

Purpose: The implementation of newborn screening for lysosomal disorders has uncovered overall poor specificity, psychosocial harm experienced by caregivers, and costly follow-up testing of false-positive cases. We report an informatics solution proven to minimize these issues. Methods: The Kentucky Department for Public Health outsourced testing for mucopolysaccharidosis type I (MPS I) and Pompe disease, conditions recently added to the recommended uniform screening panel, plus Krabbe disease, which was added by legislative mandate. A total of 55,161 specimens were collected from infants born over 1 year starting from February 2016. Testing by tandem mass spectrometry was integrated with multivariate pattern recognition software (Collaborative Laboratory Integrated Reports), which is freely available to newborn screening programs for selection of cases for which a biochemical second-tier test is needed. Results: Of five presumptive positive cases, one was affected with infantile Krabbe disease, two with Pompe disease, and one with MPS I. The remaining case was a heterozygote for the latter condition. The false-positive rate was 0.0018% and the positive predictive value was 80%. Conclusion: Postanalytical interpretive tools can drastically reduce false-positive outcomes, with preliminary evidence of no greater risk of false-negative events, still to be verified by long-term surveillance

Diffusion imaging quality control via entropy of principal direction distribution

Diffusion MR imaging has received increasing attention in the neuroimaging community, as it yields new insights into the microstructural organization of white matter that are not available with conventional MRI techniques. While the technology has enormous potential, diffusion MRI suffers from a unique and complex set of image quality problems, limiting the sensitivity of studies and reducing the accuracy of findings. Furthermore, the acquisition time for diffusion MRI is longer than conventional MRI due to the need for multiple acquisitions to obtain directionally encoded Diffusion Weighted Images (DWI). This leads to increased motion artifacts, reduced signal-to-noise ratio (SNR), and increased proneness to a wide variety of artifacts, including eddy-current and motion artifacts, “venetian blind” artifacts, as well as slice-wise and gradient-wise inconsistencies. Such artifacts mandate stringent Quality Control (QC) schemes in the processing of diffusion MRI data. Most existing QC procedures are conducted in the DWI domain and/or on a voxel level, but our own experiments show that these methods often do not fully detect and eliminate certain types of artifacts, often only visible when investigating groups of DWI's or a derived diffusion model, such as the most-employed diffusion tensor imaging (DTI). Here, we propose a novel regional QC measure in the DTI domain that employs the entropy of the regional distribution of the principal directions (PD). The PD entropy quantifies the scattering and spread of the principal diffusion directions and is invariant to the patient's position in the scanner. High entropy value indicates that the PDs are distributed relatively uniformly, while low entropy value indicates the presence of clusters in the PD distribution. The novel QC measure is intended to complement the existing set of QC procedures by detecting and correcting residual artifacts. Such residual artifacts cause directional bias in the measured PD and here called dominant direction artifacts. Experiments show that our automatic method can reliably detect and potentially correct such artifacts, especially the ones caused by the vibrations of the scanner table during the scan. The results further indicate the usefulness of this method for general quality assessment in DTI studies

How do care-provider and home exercise program characteristics affect patient adherence in chronic neck and back pain: a qualitative study

<p>Abstract</p> <p>Background</p> <p>The aim of this study is to explore perceptions of people with chronic neck or low back pain about how characteristics of home exercise programs and care-provider style during clinical encounters may affect adherence to exercises.</p> <p>Methods</p> <p>This is a qualitative study consisting of seven focus groups, with a total of 34 participants presenting chronic neck or low back pain. The subjects were included if they were receiving physiotherapy treatment and were prescribed home-based exercises.</p> <p>Results</p> <p>Two themes emerged: home-based exercise programme conditions and care provider's style. In the first theme, the participants described their positive and negative experiences regarding time consumption, complexity and effects of prescribed exercises. In the second theme, participants perceived more bonding to prescribed exercises when their care provider presented knowledge about the disease, promoted feedback and motivation during exercise instruction, gave them reminders to exercise, or monitored their results and adherence to exercises.</p> <p>Conclusions</p> <p>Our experiential findings indicate that patient's adherence to home-based exercise is more likely to happen when care providers' style and the content of exercise programme are positively experienced. These findings provide additional information to health care providers, by showing which issues should be considered when delivering health care to patients presenting chronic neck or back pain.</p