Experimental arthritis is dependent on mouse mast cell protease-5

© 2017 by The American Society for Biochemistry and Molecular Biology, Inc. The constitutive heparin+ (HP) mast cells (MCs) in mice express mouseMCprotease (mMCP)-5 and carboxypeptidaseA (mMC-CPA). The amino acid sequence ofmMCP-5is most similar to that of human chymase-1, as are the nucleotide sequences of their genes and transcripts. Using a homologous recombination approach, a C57BL/6 mouse line was created that possessed a disrupted mMCP-5 gene. The resulting mice were fertile and had no obvious developmental abnormality. Lack of mMCP-5 protein did not alter the granulation of the IL-3/IL-9-dependent mMCP-2+ MCs in the jejunal mucosa of Trichinella spiralisinfected mice. In contrast, the constitutive HP+ MCs in the tongues of mMCP-5-null mice were poorly granulated and lacked mMC-CPA protein. Bone marrow-derived MCs were readily developed from the transgenic mice using IL-3. Although these MCs contained high levels of mMC-CPA mRNA, they also lacked the latter exopeptidase. mMCP-5 protein is therefore needed to target translated mMC-CPA to the secretory granule along with HP-containing serglycin proteoglycans. Alternately, mMCP-5 is needed to protect mMC-CPA from autolysis in the cell's granules. Fibronectin was identified as a target of mMCP-5, and the exocytosis ofmMCP-5from theMCs in the mouse's peritoneal cavity resulted in the expression of metalloproteinase protease-9, which has been implicated in arthritis. In support of the latter finding, experimental arthritis was markedly reduced in mMCP-5-null mice relative to wildtype mice in two disease models

What is the real impact of acute kidney injury?

Background: Acute kidney injury (AKI) is a common clinical problem. Studies have documented the incidence of AKI in a variety of populations but to date we do not believe the real incidence of AKI has been accurately documented in a district general hospital setting. The aim here was to describe the detected incidence of AKI in a typical general hospital setting in an unselected population, and describe associated short and long-term outcomes. Methods: A retrospective observational database study from secondary care in East Kent (adult catchment population of 582,300). All adult patients (18 years or over) admitted between 1st February 2009 and 31st July 2009, were included. Patients receiving chronic renal replacement therapy (RRT), maternity and day case admissions were excluded. AKI was defined by the acute kidney injury network (AKIN) criteria. A time dependent risk analysis with logistic regression and Cox regression was used for the analysis of in-hospital mortality and survival. Results: The incidence of AKI in the 6 month period was 15,325 pmp/yr (adults) (69% AKIN1, 18% AKIN2 and 13% AKIN3). In-hospital mortality, length of stay and ITU utilisation all increased with severity of AKI. Patients with AKI had an increase in care on discharge and an increase in hospital readmission within 30 days. Conclusions: This data comes closer to the real incidence and outcomes of AKI managed in-hospital than any study published in the literature to date. Fifteen percent of all admissions sustained an episode of AKI with increased subsequent short and long term morbidity and mortality, even in those with AKIN1. This confers an increased burden and cost to the healthcare economy, which can now be quantified. These results will furnish a baseline for quality improvement projects aimed at early identification, improved management, and where possible prevention, of AKI

Discolouring the Amazon Rainforest: how deforestation is affecting butterfly coloration

This is the author accepted manuscript. The final version is available from Springer via the DOI in this record .Butterflies are among the most colourful organisms in the world and colour plays a central role in many of their life-history strategies. However, the efficacy of coloration strategies in these and other animals could be affected by sudden environmental changes, including anthropogenic disturbances such as habitat loss and fragmentation. Here we investigate the effect of forest disturbance gradients on the colours of fruit-feeding butterflies in the Amazon Rainforest. The disturbance gradients tested represented habitat-size (continuous primary forests versus forest fragments of 1, 10 and 100 ha) and succession gradients (continuous primary forests, 30 year old secondary forests, and three year old early successional forests). Using digital image analysis, we obtained intrinsic measures of butterfly colour patches corresponding to hue, saturation, brightness, in addition to measures of the contrast among patches and of the overall wing-colour diversity corresponding to 220 individuals, belonging to 60 species. Our results showed that butterflies in the secondary forest and continuous primary forest are more colourful than those found in early succession and fragments of forests. Individuals occurring in forests of early succession showed higher average values of hue and saturation, but lower brightness. Accompanying changes in colour composition, wing-colour diversity among species was lower in human-disturbed habitats, such as those of early forest succession and secondary forest. Forest fragments have smaller effects on butterfly colour composition, indicating that well-structured forest habitats can house butterfly assemblages with more diverse phenotypic features and colours. We show how high deforestation rates in recent years is linked with negative changes in functional coloration strategies (e.g. camouflage, warning colours), something that has to date been poorly explored or demonstrated for butterflies. Specifically, human interference has apparently placed butterflies under strong selection for lower diversity in their colours and range of defensive strategies. Those species that are most colourful are the first to be locally extinguished, likely due to removal of native vegetation and increased exposure to predators, and more broadly owing to inhospitable environmental conditions. This illustrates an accelerated loss of local fauna and a “discolouration” of the Amazonian butterflies due to anthropogenic impacts.Thomas Lovejoy research fellowshi

Do acute elevations of serum creatinine in primary care engender an increased mortality risk?

Background: The significant impact Acute Kidney Injury (AKI) has on patient morbidity and mortality emphasizes the need for early recognition and effective treatment. AKI presenting to or occurring during hospitalisation has been widely studied but little is known about the incidence and outcomes of patients experiencing acute elevations in serum creatinine in the primary care setting where people are not subsequently admitted to hospital. The aim of this study was to define this incidence and explore its impact on mortality. Methods: The study cohort was identified by using hospital data bases over a six month period. Inclusion criteria: People with a serum creatinine request during the study period, 18 or over and not on renal replacement therapy. The patients were stratified by a rise in serum creatinine corresponding to the Acute Kidney Injury Network (AKIN) criteria for comparison purposes. Descriptive and survival data were then analysed. Ethical approval was granted from National Research Ethics Service (NRES) Committee South East Coast and from the National Information Governance Board. Results: The total study population was 61,432. 57,300 subjects with ‘no AKI’, mean age 64.The number (mean age) of acute serum creatinine rises overall were, ‘AKI 1’ 3,798 (72), ‘AKI 2’ 232 (73), and ‘AKI 3’ 102 (68) which equates to an overall incidence of 14,192 pmp/year (adult). Unadjusted 30 day survival was 99.9% in subjects with ‘no AKI’, compared to 98.6%, 90.1% and 82.3% in those with ‘AKI 1’, ‘AKI 2’ and ‘AKI 3’ respectively. After multivariable analysis adjusting for age, gender, baseline kidney function and co-morbidity the odds ratio of 30 day mortality was 5.3 (95% CI 3.6, 7.7), 36.8 (95% CI 21.6, 62.7) and 123 (95% CI 64.8, 235) respectively, compared to those without acute serum creatinine rises as defined. Conclusions: People who develop acute elevations of serum creatinine in primary care without being admitted to hospital have significantly worse outcomes than those with stable kidney function

Sensory Measurements: Coordination and Standardization

Do sensory measurements deserve the label of “measurement”? We argue that they do. They fit with an epistemological view of measurement held in current philosophy of science, and they face the same kinds of epistemological challenges as physical measurements do: the problem of coordination and the problem of standardization. These problems are addressed through the process of “epistemic iteration,” for all measurements. We also argue for distinguishing the problem of standardization from the problem of coordination. To exemplify our claims, we draw on olfactory performance tests, especially studies linking olfactory decline to neurodegenerative disorders

Carbon and nitrogen isotopic ratios of urine and faeces as novel nutritional biomarkers of meat and fish intake

Purpose Meat and fish consumption are associated with changes in the risk of chronic diseases. Intake is mainly assessed using self-reporting, as no true quantitative nutritional biomarker is available. The measurement of plasma fatty acids, often used as an alternative, is expensive and time-consuming. As meat and fish differ in their stable isotope ratios, δ13C and δ15N have been proposed as biomarkers. However, they have never been investigated in controlled human dietary intervention studies. Objective In a short-term feeding study, we investigated the suitability of δ13C and δ15N in blood, urine and faeces as biomarkers of meat and fish intake. Methods The dietary intervention study (n = 14) followed a randomised cross-over design with three eight-day dietary periods (meat, fish and half-meat–half-fish). In addition, 4 participants completed a vegetarian control period. At the end of each period, 24-h urine, fasting venous blood and faeces were collected and their δ13C and δ15N analysed. Results There was a significant difference between diets in isotope ratios in faeces and urine samples, but not in blood samples (Kruskal–Wallis test, p < 0.0001). In pairwise comparisons, δ13C and δ15N were significantly higher in urine and faecal samples following a fish diet when compared with all other diets, and significantly lower following a vegetarian diet. There was no significant difference in isotope ratio between meat and half-meat–half-fish diets for blood, urine or faecal samples. Conclusions The results of this study show that urinary and faecal δ13C and δ15N are suitable candidate biomarkers for short-term meat and fish intake

Do Doctors Vote?

BACKGROUND: Organizational leaders and scholars have issued calls for the medical profession to refocus its efforts on fulfilling the core tenets of professionalism. A key element of professionalism is participation in community affairs. OBJECTIVE: To measure physician voting rates as an indicator of civic participation. DESIGN: Cross-sectional survey of a subgroup of physicians from a nationally representative household survey of civilian, noninstitutionalized adult citizens. PARTICIPANTS: A total of 350,870 participants in the Current Population Survey (CPS) November Voter Supplement from 1996–2002, including 1,274 physicians and 1,886 lawyers; 414,989 participants in the CPS survey from 1976–1982, including 2,033 health professionals. MEASUREMENTS: Multivariate logistic regression models were used to compare adjusted physician voting rates in the 1996–2002 congressional and presidential elections with those of lawyers and the general population and to compare voting rates of health professionals in 1996–2002 with those in 1976–1992. RESULTS: After multivariate adjustment for characteristics known to be associated with voting rates, physicians were less likely to vote than the general population in 1998 (odds ratio 0.76; 95% confidence interval [CI] 0.59–0.99), 2000 (odds ratio 0.64; 95% CI 0.44–0.93), and 2002 (odds ratio 0.62; 95% CI 0.48–0.80) but not 1996 (odds ratio 0.83; 95% CI 0.59–1.17). Lawyers voted at higher rates than the general population and doctors in all four elections (P < .001). The pooled adjusted odds ratio for physician voting across the four elections was 0.70 (CI 0.61–0.81). No substantial changes in voting rates for health professionals were observed between 1976–1982 and 1996–2002. CONCLUSIONS: Physicians have lower adjusted voting rates than lawyers and the general population, suggesting reduced civic participation

Ethnic differences in mental health among incarcerated youths: do Moroccan immigrant boys show less psychopathology than native Dutch boys?

Psychiatric disorders are highly prevalent among incarcerated youth. However, whereas ethnic minority youths are overrepresented in the juvenile justice system, limited research is available on their mental health. In this study, differences in mental health problems between incarcerated adolescents of native Dutch and Moroccan origin, were examined. Child Behavior Checklist and Youth Self-Report scores were compared between incarcerated adolescents of native Dutch and Moroccan origin. Their scores were also compared to those of native Dutch and Moroccan immigrant youths in the general, non-incarcerated population. Native Dutch incarcerated adolescents showed higher levels of various mental health problems than incarcerated adolescents with a Moroccan background. Compared to the general population, incarcerated youths showed higher levels of mental health problems, but this deviation was much larger for native Dutch than for Moroccan immigrant youths. These ethnic differences in mental health problems could not be explained by ethnic differences in socio-economic background and social desirable answering tendencies. Incarcerated youths of Moroccan origin show less psychopathology than incarcerated native Dutch youths, which might be explained by disparities in sentencing procedures

The role of input noise in transcriptional regulation

Even under constant external conditions, the expression levels of genes fluctuate. Much emphasis has been placed on the components of this noise that are due to randomness in transcription and translation; here we analyze the role of noise associated with the inputs to transcriptional regulation, the random arrival and binding of transcription factors to their target sites along the genome. This noise sets a fundamental physical limit to the reliability of genetic control, and has clear signatures, but we show that these are easily obscured by experimental limitations and even by conventional methods for plotting the variance vs. mean expression level. We argue that simple, global models of noise dominated by transcription and translation are inconsistent with the embedding of gene expression in a network of regulatory interactions. Analysis of recent experiments on transcriptional control in the early Drosophila embryo shows that these results are quantitatively consistent with the predicted signatures of input noise, and we discuss the experiments needed to test the importance of input noise more generally.Comment: 11 pages, 5 figures minor correction