Cardiac connexins Cx43 and Cx45: formation of diverse gap junction channels with diverse electrical properties

HeLa cells expressing rat connexin43 (Cx43) and/or mouse Cx45 were studied with the dual voltage-clamp technique. Different types of cell pairs were established and their gap junction properties determined, i.e. the dependence of the instantaneous and steady-state conductances (g j,inst, g j,ss) on the transjunctional voltage (V j) and the kinetics of inactivation of the gap junction current (I j). Pairs of singly transfected cells showed homogeneous behaviour at both V j polarities. Homotypic Cx43-Cx43 and Cx45-Cx45 cell pairs yielded distinct symmetrical functions g j,inst=f(V j) and g j,ss=f(V j). Heterotypic Cx43-Cx45 preparations exhibited asymmetric functions g j,inst=f(V j) and g j,ss=f(V j) suggesting that connexons Cx43 and Cx45 gate with positive and negative V j, respectively. Preparations containing a singly (Cx43 or Cx45) or doubly (Cx43/45) transfected cell showed quasi-homogeneous behaviour at one V j polarity and heterogeneous behaviour at the other polarity. The former yielded Boltzmann parameters intermediate between those of Cx43-Cx43, Cx45-Cx45 and Cx43-Cx45 preparations; the latter could not be explained by homotypic and heterotypic combinations of homomeric connexons. Each pair of doubly transfected cells (Cx43/Cx45) yielded unique functions g j,inst=f(V j) and g j,ss=f(V j). This can not be explained by combinations of homomeric connexons. We conclude that Cx43 and Cx45 form homomeric-homotypic, homomeric-heterotypic channels as well as heteromeric-homotypic and heteromeric-heterotypic channels. This has implications for the impulse propagation in specific areas of the hear

Patient and Family Caregivers’ Experiences of Living With a Jejunostomy Feeding Tube After Surgery for Esophagogastric Cancer

BACKGROUND: Jejunostomy feeding tubes (JFTs) can be used to provide nutrition support to patients who have had surgery for esophagogastric cancer. Although previous research reports how patients cope with a gastrostomy tube, little is known about the impact of having a JFT. The aim of this qualitative study was to explore how patients and their informal caregivers experience living with a JFT in the first months following surgery. METHODS: Participants were purposively sampled from a cohort of patients recruited to a trial investigating home enteral nutrition vs standard care after esophagogastric surgery for cancer. The sampling framework considered age, sex, and marital status. Informal caregivers were also invited to participate. Interviews were audio recorded, transcribed verbatim, and anonymized. Inductive thematic analysis was used to identify key themes related to living with a JFT. RESULTS: Fifteen patient interviews were conducted; 8 also included a family caregiver. Analysis of the data resulted in 2 main themes: "challenges" and "facilitators" when living with a JFT. While "physical effects," "worries" and "impact on routine" were the main challenges, "support," "adaptation" and "perceived benefit" were what motivated continuation of the intervention. CONCLUSION: Findings suggest that participants coped well with a JFT, describing high levels of compliance with stoma care and the feeding regimen. Nonetheless, disturbed sleep patterns and stoma-related problems proved troublesome. A better understanding of these practical challenges, from the patient and family caregiver perspective, should guide healthcare teams in providing proactive support to avoid preventable problems

Influence of V5/6-His Tag on the Properties of Gap Junction Channels Composed of Connexin43, Connexin40 or Connexin45

HeLa cells expressing wild-type connexin43, connexin40 or connexin45 and connexins fused with a V5/6-His tag to the carboxyl terminus (CT) domain (Cx43-tag, Cx40-tag, Cx45-tag) were used to study connexin expression and the electrical properties of gap junction channels. Immunoblots and immunolabeling indicated that tagged connexins are synthesized and targeted to gap junctions in a similar manner to their wild-type counterparts. Voltage-clamp experiments on cell pairs revealed that tagged connexins form functional channels. Comparison of multichannel and single-channel conductances indicates that tagging reduces the number of operational channels, implying interference with hemichannel trafficking, docking and/or channel opening. Tagging provoked connexin-specific effects on multichannel and single-channel properties. The Cx43-tag was most affected and the Cx45-tag, least. The modifications included (1) V j-sensitive gating of I j (V j, gap junction voltage; I j, gap junction current), (2) contribution and (3) kinetics of I j deactivation and (4) single-channel conductance. The first three reflect alterations of fast V j gating. Hence, they may be caused by structural and/or electrical changes on the CT that interact with domains of the amino terminus and cytoplasmic loop. The fourth reflects alterations of the ion-conducting pathway. Conceivably, mutations at sites remote from the channel pore, e.g., 6-His-tagged CT, affect protein conformation and thus modify channel properties indirectly. Hence, V5/6-His tagging of connexins is a useful tool for expression studies in vivo. However, it should not be ignored that it introduces connexin-dependent changes in both expression level and electrophysiological propertie

Iron and silicon isotope behaviour accompanying weathering in Icelandic soils, and the implications for iron export from peatlands

peer reviewe

Cardiac induced localised motion of the human torso detected by a long period grating fibre optic sensing scheme

Cardiovascular health of the human population is a major concern for medical clinicians, with cardiovascular diseases responsible for 48% of all deaths worldwide, according to the World Health Organisation. Therefore the development of new practicable and economical diagnostic tools to scrutinise the cardiovascular health of humans is a major driver for clinicians. We offer a new technique to obtain seismocardiographic signals covering both ballistocardiography (below 20Hz) and audible heart sounds (20Hz upwards). The detection scheme is based upon an array of curvature/displacement sensors using fibre optic long period gratings interrogated using a variation of the derivative spectroscopy interrogation technique. © 2014 SPIE

Expanding the phenotypic associations of globular glial tau subtypes

AbstractIntroductionClinicopathologic correlation in non-Alzheimer's tauopathies is variable, despite refinement of pathologic diagnostic criteria. In the present study, the clinical and neuroimaging characteristics of globular glial tauopathy (GGT) were examined to determine whether subtyping according to consensus guidelines improves clinicopathologic correlation.MethodsConfirmed GGT cases (n = 11) were identified from 181 frontotemporal tauopathy cases. Clinical and neuroimaging details were collected, and cases sub-typed according to the consensus criteria for GGT diagnosis. Relationships between clinical syndrome and GGT subtype were investigated.ResultsIn total, 11 patients (seven males, four females, mean age = 67.3 +/− 10.6 years) with GGT were included. Most, but not all, presented with behavioral variant frontotemporal dementia, but none had amyotrophic lateral sclerosis. Subtyping of GGT proved to be difficult and did not improve clinicopathologic correlation.DiscussionSub-classification of GGT pathology may be difficult and did not improve clinicopathologic correlation. Better biomarkers of tau pathology are needed

Completeness of the eutherian mammal fossil record and implications for reconstructing mammal evolution through the Cretaceous/Paleogene mass extinction

There is a well-established discrepancy between paleontological and molecular data regarding the timing of the origin and diversification of placental mammals. Molecular estimates place interordinal diversification dates in the Cretaceous, whilst no unambiguous crown placental fossils have been found prior to the end-Cretaceous mass extinction. Here, the completeness of the eutherian fossil record through geological time is evaluated in order to assess the suggestion that a poor fossil record is largely responsible for the difference in estimates of placental origins. The completeness of fossil specimens was measured using the Character Completeness Metric, a metric that quantifies the completeness of fossil taxa as the percentage of phylogenetic characters that are available to be scored for any given taxon. Our dataset was comprised of 33 published cladistic matrices representing 445 genera, of which 333 were coded at the species-level. There was no significant difference in eutherian completeness across the Cretaceous/Palaeogene boundary. This suggests that the lack of placental mammal fossils in the Cretaceous is not due to a poor fossil record, but more likely represents a genuine absence of placental mammals in the Cretaceous. This result supports the ‘explosive model’ of early placental evolution, whereby placental mammals originated around the time of the Cretaceous/Palaeogene boundary and diversified soon after the event. No correlation was found between the completeness pattern observed in this study and those of previous completeness studies on birds and sauropodomorph dinosaurs, suggesting that different factors affect the preservation of these groups. No correlations were found with various isotope proxy measures, but Akaike Information Criterion analysis found that eutherian Character Completeness Metric scores were best explained by models involving the marine carbonate strontium isotope ratios (87Sr/86Sr), suggesting that the tectonic activity might play a role in controlling the completeness of the eutherian fossil record