Ecomorphology reveals Euler spiral of mammalian whiskers

Whiskers are present in many species of mammals. They are specialised vibrotactile sensors that sit within strongly innervated follicles. Whisker size and shape will affect the mechanical signals that reach the follicle, and hence the information that reaches the brain. However, whisker size and shape have not been quantified across mammals before. Using a novel method for describing whisker curvature, this study quantifies whisker size and shape across 19 mammalian species. We find that gross two‐dimensional whisker shape is relatively conserved across mammals. Indeed, whiskers are all curved, tapered rods that can be summarised by Euler spiral models of curvature and linear models of taper, which has implications for whisker growth and function. We also observe that aquatic and semi‐aquatic mammals have relatively thicker, stiffer, and more highly tapered whiskers than arboreal and terrestrial species. In addition, smaller mammals tend to have relatively long, slender, flexible whiskers compared to larger species. Therefore, we propose that whisker morphology varies between larger aquatic species, and smaller scansorial species. These two whisker morphotypes are likely to induce quite different mechanical signals in the follicle, which has implications for follicle anatomy as well as whisker function

Describing whisker morphology of the Carnivora

One of the largest ecological transitions in carnivoran evolution was the shift from terrestrial to aquatic lifestyles, which has driven morphological diversity in skulls and other skeletal structures. In this paper, we investigate the association between those lifestyles and whisker morphology. However, comparing whisker morphology over a range of species is challenging since the number of whiskers and their positions on the mystacial pads vary between species. Also, each whisker will be at a different stage of growth and may have incurred damage due to wear and tear. Identifying a way to easily capture whisker morphology in a small number of whisker samples would be beneficial. Here, we describe individual and species variation in whisker morphology from two-dimensional scans in red fox, European otter and grey seal. A comparison of long, caudal whiskers shows inter-species differences most clearly. We go on to describe global whisker shape in 24 species of carnivorans, using linear approximations of curvature and taper, as well as traditional morphometric methods. We also qualitatively examine surface texture, or the presence of scales, using scanning electron micrographs. We show that gross whisker shape is highly conserved, with whisker curvature and taper obeying simple linear relationships with length. However, measures of whisker base radius, length, and maybe even curvature, can vary between species and substrate preferences. Specifically, the aquatic species in our sample have thicker, shorter whiskers that are smoother, with less scales present than those of terrestrial species. We suggest that these thicker whiskers may be stiffer and able to maintain their shape and position during underwater sensing, but being stiffer may also increase wear

Rationale and design of the PHOspholamban RElated CArdiomyopathy intervention STudy (i-PHORECAST)

Background: The p.Arg14del (c.40_42delAGA) phospholamban (PLN) pathogenic variant is a founder mutation that causes dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). Carriers are at increased risk of malignant ventricular arrhythmias and heart failure, which has been ascribed to cardiac fibrosis. Importantly, cardiac fibrosis appears to be an early feature of the disease, occurring in many presymptomatic carriers before the onset of overt disease. As with most monogenic cardiomyopathies, no evidence-based treatment is available for presymptomatic carriers. Aims: The PHOspholamban RElated CArdiomyopathy intervention STudy (iPHORECAST) is designed to demonstrate that pre-emptive treatment of presymptomatic PLN p.Arg14del carriers using eplerenone, a mineralocorticoid receptor antagonist with established antifibrotic effects, can reduce disease progression and postpone the onset of overt disease. Methods: iPHORECAST has a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) design. Presymptomatic PLN p.Arg14del carriers are randomised to receive either 50 mg eplerenone once daily or no treatment. The primary endpoint of the study is a multiparametric assessment of disease progression including cardiac magnetic resonance parameters (left and right ventricular volumes, systolic function and fibrosis), electrocardiographic parameters (QRS voltage, ventricular ectopy), signs and/or symptoms related to DCM and ACM, and cardiovascular death. The follow-up duration is set at 3 years. Baseline results: A total of 84 presymptomatic PLN p.Arg14del carriers (n = 42 per group) were included. By design, at baseline, all participants were in New York Heart Association (NHYA) class I and had a left ventricular ejection fraction > 45% and < 2500 ventricular premature contractions during 24-hour Holter monitoring. There were no statistically significant differences between the two groups in any of the baseline characteristics. The study is currently well underway, with the last participants expected to finish in 2021. Conclusion: iPHORECAST is a multicentre, prospective randomised controlled trial designed to address whether pre-emptive treatment of PLN p.Arg14del carriers with eplerenone can prevent or delay the onset of cardiomyopathy. iPHORECAST has been registered in the clinicaltrials.gov-register (number: NCT01857856)

Comparison of methods for handling missing data on immunohistochemical markers in survival analysis of breast cancer

Background:Tissue micro-arrays (TMAs) are increasingly used to generate data of the molecular phenotype of tumours in clinical epidemiology studies, such as studies of disease prognosis. However, TMA data are particularly prone to missingness. A variety of methods to deal with missing data are available. However, the validity of the various approaches is dependent on the structure of the missing data and there are few empirical studies dealing with missing data from molecular pathology. The purpose of this study was to investigate the results of four commonly used approaches to handling missing data from a large, multi-centre study of the molecular pathological determinants of prognosis in breast cancer.Patients and Methods:We pooled data from over 11 000 cases of invasive breast cancer from five studies that collected information on seven prognostic indicators together with survival time data. We compared the results of a multi-variate Cox regression using four approaches to handling missing data-complete case analysis (CCA), mean substitution (MS) and multiple imputation without inclusion of the outcome (MI) and multiple imputation with inclusion of the outcome (MI). We also performed an analysis in which missing data were simulated under different assumptions and the results of the four methods were compared.Results:Over half the cases had missing data on at least one of the seven variables and 11 percent had missing data on 4 or more. The multi-variate hazard ratio estimates based on multiple imputation models were very similar to those derived after using MS, with similar standard errors. Hazard ratio estimates based on the CCA were only slightly different, but the estimates were less precise as the standard errors were large. However, in data simulated to be missing completely at random (MCAR) or missing at random (MAR), estimates for MI were least biased and most accurate, whereas estimates for CCA were most biased and least accurate.Conclusion:In this study, empirical results from analyses using CCA, MS, MI and MI were similar, although results from CCA were less precise. The results from simulations suggest that in general MI is likely to be the best. Given the ease of implementing MI in standard statistical software, the results of MI and CCA should be compared in any multi-variate analysis where missing data are a problem. © 2011 Cancer Research UK. All rights reserved

Non-invasive mechanical ventilation for diagnostic bronchoscopy using a new face mask: an observational feasibility study

Contains fulltext : 89809.pdf (publisher's version ) (Closed access)PURPOSE: Bronchoscopy is an indispensable tool for invasive pulmonary evaluation with high diagnostic yield and low incidence of major complications. However, hypoxemia increases the risk of complications, in particular after bronchoalveolar lavage. Non-invasive positive pressure ventilation may prevent hypoxemia associated with bronchoalveolar lavage. The purpose of this study is to present a modified total face mask to aid bronchoscopy during non-invasive positive pressure ventilation. METHODS: A commercially available full face mask was modified to allow introduction of the bronchoscope without interfering with the ventilator circuit. Bronchoscopy with bronchoalveolar lavage was performed in 12 hypoxemic non-ICU patients during non-invasive positive pressure ventilation in the ICU. Results : Patients had severely impaired oxygen uptake as indicated by PaO(2)/FiO(2) ratio 192 +/- 23 mmHg before bronchoscopy. Oxygenation improved after initiation of non-invasive positive pressure ventilation. In all patients the procedure could be completed without subsequent complications, although in one patient SpO(2) decreased until 86% during bronchoscopy. A microbiological diagnosis could be established in 8 of 12 patients with suspected for infection. CONCLUSIONS: Our modified face mask for non-invasive positive pressure ventilation is a valuable tool to aid diagnostic bronchoscopy in hypoxemic patients.1 januari 201

In vitro template-change PCR to create single crossover libraries: a case study with B. thuringiensis Cry2A toxins

During evolution the creation of single crossover chimeras between duplicated paralogous genes is a known process for increasing diversity. Comparing the properties of homologously recombined chimeras with one or two crossovers is also an efficient strategy for analyzing relationships between sequence variation and function. However, no well-developed in vitro method has been established to create single-crossover libraries. Here we present an in vitro template-change polymerase change reaction that has been developed to enable the production of such libraries. We applied the method to two closely related toxin genes from B. thuringiensis and created chimeras with differing properties that can help us understand how these toxins are able to differentiate between insect species

Discovery of early-stage biomarkers for diabetic kidney disease using ms-based metabolomics (FinnDiane study)

Diabetic kidney disease (DKD) is a devastating complication that affects an estimated third of patients with type 1 diabetes mellitus (DM). There is no cure once the disease is diagnosed, but early treatment at a sub-clinical stage can prevent or at least halt the progression. DKD is clinically diagnosed as abnormally high urinary albumin excretion rate (AER). We hypothesize that subtle changes in the urine metabolome precede the clinically significant rise in AER. To test this, 52 type 1 diabetic patients were recruited by the FinnDiane study that had normal AER (normoalbuminuric). After an average of 5.5 years of follow-up half of the subjects (26) progressed from normal AER to microalbuminuria or DKD (macroalbuminuria), the other half remained normoalbuminuric. The objective of this study is to discover urinary biomarkers that differentiate the progressive form of albuminuria from non-progressive form of albuminuria in humans. Metabolite profiles of baseline 24 h urine samples were obtained by gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS) to detect potential early indicators of pathological changes. Multivariate logistic regression modeling of the metabolomics data resulted in a profile of metabolites that separated those patients that progressed from normoalbuminuric AER to microalbuminuric AER from those patients that maintained normoalbuminuric AER with an accuracy of 75% and a precision of 73%. As this data and samples are from an actual patient population and as such, gathered within a less controlled environment it is striking to see that within this profile a number of metabolites (identified as early indicators) have been associated with DKD already in literature, but also that new candidate biomarkers were found. The discriminating metabolites included acyl-carnitines, acyl-glycines and metabolites related to tryptophan metabolism. We found candidate biomarkers that were univariately significant different. This study demonstrates the potential of multivariate data analysis and metabolomics in the field of diabetic complications, and suggests several metabolic pathways relevant for further biological studies

International patellofemoral osteoarthritis consortium: Consensus statement on the diagnosis, burden, outcome measures, prognosis, risk factors and treatment

Objective: To present the current status of knowledge in the field of patellofemoral (PF) osteoarthritis (OA) and formulate a research agenda in order to guide future research on this topic. Design: A 1-day meeting was organized with the aim to bring together international experts in the field to discuss the current state of knowledge on PF OA. Experts from multiple disciplines were invited based on their scientific publications in the field of PF OA and interest in the subject. Topics discussed include the diagnosis, impact, prognosis, and treatment of PF OA. Methods: Following context-setting presentations, an interactive discussion was held in order to achieve consensus on the PF OA topics of interest: (1) diagnosis and definition; (2) burden; (3) outcome measures; (4) prognosis; (5) risk factors, and (6) treatment. Groups of meeting attendees reviewed the literature on these topics and narratively summarized the current state of knowledge, and each group formulated research agenda items relevant to the specific topics of interest. Each consortium member consequently ranked the importance of all items on a 0–10 Numerical Rating Scale (NRS) (10 = extremely important, to 0 = not at all important). Results: After ranking all formulated items on importance, 6 of the 28 research agenda items formulated received an average of 7.5 points on the NRS. The most highly ranked items covered the fields of treatment, diagnosis, and definition of PF OA. Conclusions: We recommend to develop clear clinical criteria for PF OA and to reach consensus on the definition of PF OA by both radiographs and MRI. Additionally, more understanding is necessary to be able to distinguish PF symptoms from those arising from the tibiofemoral joint. More insight is needed on effective treatment strategies for PF OA; specifically, tailoring nonpharmacological treatments to individuals with PF OA, and determining whether isolated PF OA requires different treatment strategies than combined PF and tibiofemoral OA

Growth Response of Drought-Stressed Pinus sylvestris Seedlings to Single- and Multi-Species Inoculation with Ectomycorrhizal Fungi

Many trees species form symbiotic associations with ectomycorrhizal (ECM) fungi, which improve nutrient and water acquisition of their host. Until now it is unclear whether the species richness of ECM fungi is beneficial for tree seedling performance, be it during moist conditions or drought. We performed a pot experiment using Pinus sylvestris seedlings inoculated with four selected ECM fungi (Cenococcum geophilum, Paxillus involutus, Rhizopogon roseolus and Suillus granulatus) to investigate (i) whether these four ECM fungi, in monoculture or in species mixtures, affect growth of P. sylvestris seedlings, and (ii) whether this effect can be attributed to species number per se or to species identity. Two different watering regimes (moist vs. dry) were applied to examine the context-dependency of the results. Additionally, we assessed the activity of eight extracellular enzymes in the root tips. Shoot growth was enhanced in the presence of S. granulatus, but not by any other ECM fungal species. The positive effect of S. granulatus on shoot growth was more pronounced under moist (threefold increase) than under dry conditions (twofold increase), indicating that the investigated ECM fungi did not provide additional support during drought stress. The activity of secreted extracellular enzymes was higher in S. granulatus than in any other species. In conclusion, our findings suggest that ECM fungal species composition may affect seedling performance in terms of aboveground biomass

Prospecting environmental mycobacteria: combined molecular approaches reveal unprecedented diversity

Background: Environmental mycobacteria (EM) include species commonly found in various terrestrial and aquatic environments, encompassing animal and human pathogens in addition to saprophytes. Approximately 150 EM species can be separated into fast and slow growers based on sequence and copy number differences of their 16S rRNA genes. Cultivation methods are not appropriate for diversity studies; few studies have investigated EM diversity in soil despite their importance as potential reservoirs of pathogens and their hypothesized role in masking or blocking M. bovis BCG vaccine. Methods: We report here the development, optimization and validation of molecular assays targeting the 16S rRNA gene to assess diversity and prevalence of fast and slow growing EM in representative soils from semi tropical and temperate areas. New primer sets were designed also to target uniquely slow growing mycobacteria and used with PCR-DGGE, tag-encoded Titanium amplicon pyrosequencing and quantitative PCR. Results: PCR-DGGE and pyrosequencing provided a consensus of EM diversity; for example, a high abundance of pyrosequencing reads and DGGE bands corresponded to M. moriokaense, M. colombiense and M. riyadhense. As expected pyrosequencing provided more comprehensive information; additional prevalent species included M. chlorophenolicum, M. neglectum, M. gordonae, M. aemonae. Prevalence of the total Mycobacterium genus in the soil samples ranged from 2.3×107 to 2.7×108 gene targets g−1; slow growers prevalence from 2.9×105 to 1.2×107 cells g−1. Conclusions: This combined molecular approach enabled an unprecedented qualitative and quantitative assessment of EM across soil samples. Good concordance was found between methods and the bioinformatics analysis was validated by random resampling. Sequences from most pathogenic groups associated with slow growth were identified in extenso in all soils tested with a specific assay, allowing to unmask them from the Mycobacterium whole genus, in which, as minority members, they would have remained undetected