Study of the Bcl-2 Interactome by BiFC reveals differences in the activation mechanism of Bax and Bak

Evasion of apoptosis is one of the hallmarks of cancer cells. Proteins of the Bcl-2 family are key regulators of the intrinsic pathway of apoptosis, and alterations in some of these proteins are frequently found in cancer cells. Permeabilization of the outer mitochondrial membrane, regulated by pro- and antiapoptotic members of the Bcl-2 family of proteins, is essential for the release of apoptogenic factors leading to caspase activation, cell dismantlement, and death. Mitochondrial permeabilization depends on the formation of oligomers of the effector proteins Bax and Bak after an activation event mediated by BH3-only proteins and regulated by antiapoptotic members of the Bcl-2 family. In the present work, we have studied interactions between different members of the Bcl-2 family in living cells via the BiFC technique. Despite the limitations of this technique, present data suggest that native proteins of the Bcl-2 family acting inside living cells establish a complex network of interactions, which would fit nicely into “mixed” models recently proposed by others. Furthermore, our results point to differences in the regulation of Bax and Bak activation by proteins of the antiapoptotic and BH3-only subfamilies. We have also applied the BiFC technique to explore the different molecular models proposed for Bax and Bak oligomerization. Bax and Bak’s mutants lacking the BH3 domain were still able to associate and give BiFC signals, suggesting the existence of alternative surfaces of interaction between two Bax or Bak molecules. These results agree with the widely accepted symmetric model for the dimerization of these proteins and also suggest that other regions, different from the α6 helix, could be involved in the oligomerization of BH3-in groove dimers

Dynamical simulation of the injection of vortices into a Majorana edge mode

The chiral edge modes of a topological superconductor can transport fermionic quasiparticles, with Abelian exchange statistics, but they can also transport non-Abelian anyons: Majorana zero-modes bound to a {\pi}-phase domain wall that propagates along the boundary. Such an edge vortex is injected by the application of an h/2e flux bias over a Josephson junction. Existing descriptions of the injection process rely on the instantaneous scattering approximation of the adiabatic regime, where the internal dynamics of the Josephson junction is ignored. Here we go beyond that approximation in a time-dependent many-body simulation of the injection process, followed by a braiding of the mobile edge vortex with an immobile Abrikosov vortex in the bulk of the superconductor. Our simulation sheds light on the properties of the Josephson junction needed for a successful implementation of a flying Majorana qubit.Comment: 13 pages 12 figure

Regression of Late Onset Choroidal Metastasis from a Breast Carcinoma with Letrozole

We report the case of a 50-year-old woman with a history of diabetes mellitus who underwent left breast lumpectomy and ipsilateral lymphadenectomy in 1994 because of an infiltrating ductal carcinoma. Chemotherapy followed by radiotherapy to the breast and nodal areas were performed. In 2010, in a routine screening for diabetic retinopathy, two choroidal elevated masses above and below the optic nerve associated to serous retinal detachment of her right eye were noted. The patient was asymptomatic. Carcinoma was positive for hormone receptor. Hormone treatment with letrozole was established. Complete regression of the choroidal metastasis was observed 3 months later. Ophthalmologic screening in asymptomatic patients with breast cancer has the advantage of being a noninvasive procedure and enables an early treatment in isolated cases. However, some studies are an argument against the usefulness of eye screening due to the low incidence of asymptomatic choroidal metastasis and the cost that involves performing it routinely in a large number of patients. Aromatase inhibitors are well-tolerated drugs that may be a powerful tool in the management of metastatic breast cancer that express hormone receptors

The prognostic role of circulating tumor cells (CTCs) in lung cancer

© 2018 Kapeleris, Kulasinghe, Warkiani, Vela, Kenny, O'Byrne and Punyadeera. Lung cancer affects over 1. 8 million people worldwide and is the leading cause of cancer related mortality globally. Currently, diagnosis of lung cancer involves a combination of imaging and invasive biopsies to confirm histopathology. Non-invasive diagnostic techniques under investigation include "liquid biopsies" through a simple blood draw to develop predictive and prognostic biomarkers. A better understanding of circulating tumor cell (CTC) dissemination mechanisms offers promising potential for the development of techniques to assist in the diagnosis of lung cancer. Enumeration and characterization of CTCs has the potential to act as a prognostic biomarker and to identify novel drug targets for a precision medicine approach to lung cancer care. This review will focus on the current status of CTCs and their potential diagnostic and prognostic utility in this setting

Streptococcus caprae sp. nov., isolated from Iberian ibex (Capra pyrenaica hispanica)

Biochemical and molecular genetic studies were performed on a novel Gram-stain-positive, catalase-negative, coccus-shaped organism isolated from tonsil samples of two Iberian ibexes. The micro-organism was identified as a streptococcal species based on its cellular, morphological and biochemical characteristics. 16S rRNA gene sequence comparison studies confirmed its identification as a member of the genus Streptococcus, but the organism did not correspond to any species of this genus. The nearest phylogenetic relative of the unknown coccus from ibex was Streptococcus porci 2923-03T (96.6 % 16S rRNA gene sequence similarity). Analysis based on rpoB and sodA gene sequences revealed sequence similarity values lower than 86.0 and 83.8 %, respectively, from the type strains of recognized Streptococcus species. The novel bacterial isolate was distinguished from Streptococcus porci and other Streptococcus species using biochemical tests. Based on both phenotypic and phylogenetic findings, it is proposed that the unknown bacterium be classified as representing a novel species of the genus Streptococcus, for which the name Streptococcus caprae sp. nov. is proposed. The type strain is DICM07-02790-1CT (= CECT 8872T = CCUG 67170T)

Sleep quality in patients with heart failure in the spanish population: A cross-sectional study

Background: Heart failure is a major problem in western societies. Sleep Disorders maintain a bidirectional relationship with heart failure, as shown by studies conducted in other countries. This study aims to describe the quality of sleep in Spanish patients with heart failure. Materials and methods: We carried out a cross-sectional study to analyze the quality of sleep in a sample of 203 patients with a diagnosis of heart failure admitted to an Internal Medicine Service. The Pittsburg Sleep Quality Index (PSQI) was used to evaluate sleep quality in our sample over a one-month period. Results: 75% of the sample presented sleep disorders. The most common problems included the interruption of sleep (73.5% nocturia and 30% breathing difficulties); 35% had poor sleep efficiency; 33% showed a decrease in daytime performance; 84% had used hypnotics at some point to induce sleep and 35% used them regularly. Conclusions: This is the first study to report on the perceived sleep quality of patients with heart failure in Spain. Self-perception of sleep quality differed from that estimated by the PSQI. The prevalence of the use of sleep-inducing medication was very high. The diurnal dysfunction generated by sleep disorders in a heart failure environment can contribute to the development of self-care and cognitive deterioration problems

Short term ex-vivo expansion of circulating head and neck tumour cells.

Minimally invasive techniques are required for the identification of head and neck cancer (HNC) patients who are at an increased risk of metastasis, or are not responding to therapy. An approach utilised in other solid cancers is the identification and enumeration of circulating tumour cells (CTCs) in the peripheral blood of patients. Low numbers of CTCs has been a limiting factor in the HNC field to date. Here we present a methodology to expand HNC patient derived CTCs ex-vivo. As a proof of principle study, 25 advanced stage HNC patient bloods were enriched for circulating tumour cells through negative selection and cultured in 2D and 3D culture environments under hypoxic conditions (2% O2, 5% CO2). CTCs were detected in 14/25 (56%) of patients (ranging from 1-15 CTCs/5 mL blood). Short term CTC cultures were successfully generated in 7/25 advanced stage HNC patients (5/7 of these cultures were from HPV+ patients). Blood samples from which CTC culture was successful had higher CTC counts (p = 0.0002), and were predominantly from HPV+ patients (p = 0.007). This is, to our knowledge, the first pilot study to culture HNC CTCs ex-vivo. Further studies are warranted to determine the use of short term expansion in HNC and the role of HPV in promoting culture success

Learning Terrain Dynamics: A Gaussian Process Modeling and Optimal Control Adaptation Framework Applied to Robotic Jumping

The complex dynamics characterizing deformable terrain presents significant impediments toward the real-world viability of locomotive robotics, particularly for legged machines. We explore vertical, robotic jumping as a model task for legged locomotion on presumed-uncharacterized, nonrigid terrain. By integrating Gaussian process (GP)-based regression and evaluation to estimate ground reaction forces as a function of the state, a 1-D jumper acquires the capability to learn forcing profiles exerted by its environment in tandem with achieving its control objective. The GP-based dynamical model initially assumes a baseline rigid, noncompliant surface. As part of an iterative procedure, the optimizer employing this model generates an optimal control strategy to achieve a target jump height. Experiential data recovered from execution on the true surface model are applied to train the GP, in turn, providing the optimizer a more richly informed dynamical model of the environment. The iterative control-learning procedure was rigorously evaluated in experiment, over different surface types, whereby a robotic hopper was challenged to jump to several different target heights. Each task was achieved within ten attempts, over which the terrain's dynamics were learned. With each iteration, GP predictions of ground forcing became incrementally refined, rapidly matching experimental force measurements. The few-iteration convergence demonstrates a fundamental capacity to both estimate and adapt to unknown terrain dynamics in application-realistic time scales, all with control tools amenable to robotic legged locomotion

Streptococcus porcorum sp. nov., isolated from domestic and wild pigs

Seven isolates of an unidentified Gram-stain-positive, catalase-negative, coccus-shaped organism isolated from domestic and wild pigs were characterized by phenotypic and molecular-genetic methods. Based on cellular morphology and biochemical criteria, the isolates were tentatively assigned to the genus Streptococcus, although the organisms did not appear to correspond to any recognized species. Comparative 16S rRNA gene sequencing showed that the unknown bacterium was phylogenetically closely related to, but distinct from, Streptococcus suis (97.5 % 16S rRNA gene sequence similarity to the type strain). rpoB and sodA sequence analysis showed minimum interspecies divergence from phylogenetically close 16S rRNA gene sequence-based relatives of 13.8 and 18.6 %, respectively. DNA-DNA hybridization of a strain of the unidentified organism demonstrated 8-18 % reassociation with S. suis NCTC 10234(T). The novel bacterium could be distinguished from S. suis and other Streptococcus species using biochemical tests. On the basis of phenotypic and phylogenetic evidence, it is proposed that the unknown isolates from domestic and wild animals be assigned to a novel species of the genus Streptococcus, Streptococcus porcorum sp. nov. The type strain is 682-03(T) (= CCUG 58479(T) = CECT 7593(T))