Pristionchus uniformis, should I stay or should I go? Recent host range expansion in a European nematode

Pristionchus pacificus has been developed as a model system in evolutionary developmental biology, evolutionary ecology, and population genetics. This species has a well-known ecological association with scarab beetles. Generally, Pristionchus nematodes have a necromenic association with their beetle hosts. Arrested dauer larvae invade the insect and wait for the host's death to resume development. Only one Pristionchus species is known to frequently associate with a non-scarab beetle. Pristionchus uniformis has been isolated from the chrysomelid Leptinotarsa decemlineata, also known as the Colorado potato beetle, in Europe and North America, but is also found on scarab beetles. This unusual pattern of association with two unrelated groups of beetles on two continents requires the involvement of geographical and host range expansion events. Here, we characterized a collection of 81 P. uniformis isolates from North America and Europe and from both scarab beetles and L. decemlineata. We used population genetic and phylogenetic analyses of the mitochondrial gene nd2 to reconstruct the genetic history of P. uniformis and its beetle association. Olfactory tests on beetles chemical extracts showed that P. uniformis has a unique chemoattractive profile toward its beetle hosts. Our results provide evidence for host range expansion through host-switching events in Europe where P. uniformis was originally associated with scarab beetles and the nematode's subsequent invasion of North America

Partition-Induced Vector Chromatography in Microfluidic Devices

The transport of Brownian particles in a slit geometry in the presence of an arbitrary two-dimensional periodic energy landscape and driven by an external force or convected by a flow field is investigated by means of macrotransport theory. Analytical expressions for the probability distribution and the average migration angle of the particles are obtained under the Fick-Jackobs approximation. The migration angle is shown to differ from the orientation angle of the driving field and to strongly depend on the physical properties of the suspended species, thus providing the basis for vector chormatography, in which different species move in different directions and can be continuously fractionated. The potential of microfluidic devices as a platform for partition-induced vector chromatography is demonstrated by considering the particular case of a piece-wise constant, periodic potential that, in equilibrium, induces the spontaneous partition of different species into high and low concentration stripes, and which can be easily fabricated by patterning physically or chemically one of the surfaces of a channel. The feasibility to separate different particles of the same and different size is shown for systems in which partition is induced via 1g-gravity and Van der Waals interactions in physically and chemically patterned channels, respectively

Extracellular Vesicles in Musculoskeletal Pathologies and Regeneration

The incidence of musculoskeletal diseases is steadily increasing with aging of the population. In the past years, extracellular vesicles (EVs) have gained attention in musculoskeletal research. EVs have been associated with various musculoskeletal pathologies as well as suggested as treatment option. EVs play a pivotal role in communication between cells and their environment. Thereby, the EV cargo is highly dependent on their cellular origin. In this review, we summarize putative mechanisms by which EVs can contribute to musculoskeletal tissue homeostasis, regeneration and disease, in particular matrix remodeling and mineralization, pro-angiogenic effects and immunomodulatory activities. Mesenchymal stromal cells (MSCs) present the most frequently used cell source for EV generation for musculoskeletal applications, and herein we discuss how the MSC phenotype can influence the cargo and thus the regenerative potential of EVs. Induced pluripotent stem cell-derived mesenchymal progenitor cells (iMPs) may overcome current limitations of MSCs, and iMP-derived EVs are discussed as an alternative strategy. In the last part of the article, we focus on therapeutic applications of EVs and discuss both practical considerations for EV production and the current state of EV-based therapies

Interprofessional anatomy education in the United Kingdom and Ireland: perspectives from students and teachers

There is increasing recognition of multiprofessional learning in anatomy and its role in medical and healthcare professions. This study utilized two components to investigate anatomy interprofessional education (AIPE) in the United Kingdom and Ireland. First, a survey involving qualitative and quantitative components asked Heads of Anatomy to report on their institutions’ uptake of AIPE. Second, a series of case studies explored the experiences of students by using evaluation forms and an in-depth analysis of thematic concepts to understand the learners’ perspectives on designing and delivering AIPE. Out of the 13 institutions that took part in the survey, eight did not offer an AIPE program. Between the remaining five institutions that deliver AIPE programs, 10 different modules are offered with the majority involving healthcare professions. The AIPE component is rated highly by students. The themes from the case studies highlight how valuable AIPE is from the student perspective both in terms of engaging them in anatomy as well as in the broader skills of teamwork and communication. The case studies also revealed how AIPE can be engaging for groups of students who might not have previously had access to cadaveric anatomy, for example, engineers and archeologists. The results of this study have implications for curriculum design in medicine and healthcare but also for further engagement of professional groups from non-healthcare backgrounds. Anat Sci Educ 8:360–370. © 2015 American Association of Anatomists

Kinetic Mechanism of the Ca2+-Dependent Switch-On and Switch-Off of Cardiac Troponin in Myofibrils

The kinetics of Ca2+-dependent conformational changes of human cardiac troponin (cTn) were studied on isolated cTn and within the sarcomeric environment of myofibrils. Human cTnC was selectively labeled on cysteine 84 with N-((2-(iodoacetoxy)ethyl)-N-methyl)amino-7-nitrobenz-2-oxa-1,3-diazole and reconstituted with cTnI and cTnT to the cTn complex, which was incorporated into guinea pig cardiac myofibrils. These exchanged myofibrils, or the isolated cTn, were rapidly mixed in a stopped-flow apparatus with different [Ca2+] or the Ca2+-buffer 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid to determine the kinetics of the switch-on or switch-off, respectively, of cTn. Activation of myofibrils with high [Ca2+] (pCa 4.6) induced a biphasic fluorescence increase with rate constants of >2000 s−1 and ∼330 s−1, respectively. At low [Ca2+] (pCa 6.6), the slower rate was reduced to ∼25 s−1, but was still ∼50-fold higher than the rate constant of Ca2+-induced myofibrillar force development measured in a mechanical setup. Decreasing [Ca2+] from pCa 5.0–7.9 induced a fluorescence decay with a rate constant of 39 s−1, which was approximately fivefold faster than force relaxation. Modeling the data indicates two sequentially coupled conformational changes of cTnC in myofibrils: 1), rapid Ca2+-binding (kB ≈ 120 μM−1 s−1) and dissociation (kD ≈ 550 s−1); and 2), slower switch-on (kon = 390s−1) and switch-off (koff = 36s−1) kinetics. At high [Ca2+], ∼90% of cTnC is switched on. Both switch-on and switch-off kinetics of incorporated cTn were around fourfold faster than those of isolated cTn. In conclusion, the switch kinetics of cTn are sensitively changed by its structural integration in the sarcomere and directly rate-limit neither cardiac myofibrillar contraction nor relaxation

Spontaneous regression of Merkel cell carcinoma in a patient with chronic lymphocytic leukemia: a case report

© 2009 Turk et al; licensee Cases Network Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Long-Term Exercise Training Attenuates Age-Related Diastolic Dysfunction: Association of Myocardial Collagen Cross-Linking

The incidence of diastolic heart failure increases dramatically with age. We investigated the impact of long-term exercise training on age-related diastolic dysfunction. Old (25-month-old) male Fischer 344 rats were studied after 12 weeks of treadmill exercise training or sedentary cage life (N=7, in each group). We determined cardiac performance using a pressure-volume conductance catheter and magnetic resonance imaging. Collagen volume fraction (CVF) and myocardial collagen solubility by pepsin as an index of advanced glycation end products (AGEs) cross-linked collagen were measured. The maximal slope of systolic pressure increment (+dP/dt) and the slope of end-systolic pressure-volume relation were higher, and end diastolic volume (EDV), ΔEDV (the percentage of the EDV increment-to-baseline EDV) and the slope of end-diastolic pressure-volume relation were lower in training group. The maximal slope of diastolic pressure decrement (-dP/dt) and time constant of LV pressure decay (τ) had no difference. AGEs cross-linked collagen, not CVF was reduced by exercise training. Long-term exercise training appears to attenuate age-related deterioration in cardiac systolic function and myocardial stiffness and could be reduce in pathologic AGEs cross-linked collagen in myocardium

Application and Validation of PFGE for Serovar Identification of Leptospira Clinical Isolates

Serovar identification of clinical isolates of Leptospira is generally not performed on a routine basis, yet the identity of an infecting serovar is valuable from both epidemiologic and public health standpoints. Only a small number of reference laboratories worldwide have the capability to perform the cross agglutinin absorption test (CAAT), the reference method for serovar identification. Pulsed-field gel electrophoresis (PFGE) is an alternative method to CAAT that facilitates rapid identification of leptospires to the serovar level. We employed PFGE to evaluate 175 isolates obtained from humans and animals submitted to the Centers for Disease Control and Prevention (CDC) between 1993 and 2007. PFGE patterns for each isolate were generated using the NotI restriction enzyme and compared to a reference database consisting of more than 200 reference strains. Of the 175 clinical isolates evaluated, 136 (78%) were identified to the serovar level by the database, and an additional 27 isolates (15%) have been identified as probable new serovars. The remaining isolates yet to be identified are either not represented in the database or require further study to determine whether or not they also represent new serovars. PFGE proved to be a useful tool for serovar identification of clinical isolates of known serovars from different geographic regions and a variety of different hosts and for recognizing potential new serovars

Isolation and Characterization of New Leptospira Genotypes from Patients in Mayotte (Indian Ocean)

Leptospirosis has been recognized as an increasing public health problem affecting poor people from developing countries and tropical regions. However, the epidemiology of leptospirosis remains poorly understood in remote parts of the world. In this study of patients from the island of Mayotte, we isolated 22 strains from the blood of patients during the acute phase of illness. The pathogenic Leptospira strains were characterized by serology and various molecular typing methods. Based on serological data, serogroup Mini appears to be the dominant cause of leptospirosis in Mayotte. Further molecular characterization of these isolates allowed the identification of 10 pathogenic Leptospira genotypes that could correspond to previously unknown serovars. Further progress in our understanding of the epidemiology of Leptospira circulating genotypes in highly endemic regions should contribute to the development of novel strategies for the diagnosis and prevention of this neglected emerging disease