Arresting metastasis within the microcirculation.

The behaviour of circulating tumour cells in the microcirculation remains poorly understood. Growing evidence suggests that biomechanical adaptations and interactions with blood components, i.e. immune cells and platelets within capillary beds, may add more complexity to CTCs journey towards metastasis. Revisiting how these mediators impact the ability of circulating tumour cells to survive and metastasise, will be vital to understand the role of microcirculation and advance our knowledge on metastasis

Bladder perforations in children

Context: Bladder perforations in children occur due to several different reasons.Aim: In this clinical series study, we focused on bladder perforations due to the pelvic injury, and our aim also was to create awareness for a rare type of bladder injuries.Setting and Design: This was a retrospective study of the patients who were treated in our clinic for bladder perforation between 2006 and 2011.Subjects and Methods: We reviewed the documents of childhood bladder perforations, and demographic and clinical characteristics of the patients were obtained. No statistical analyses were used because of the limited number of cases.Results: There were ten patients who suffered from bladder perforation in 5‑year period; 5 were male, and 5 were female. The mean age of the patients was 4.35 years. Four patients (40%) experienced iatrogenic perforation and six patients (60%) experienced perforation due to the accident. Common symptoms were hematuria, abdominal tenderness, and inability to urinate. Three patients were diagnosed via emergency laparotomy, without any radiological examinations performed before surgery. Four patients suffered from the intraperitoneal perforation, three patients suffered from extraperitoneal injury and three of them both of intraperitoneal and extraperitoneal injuries. Mean recovery time for patients was 15 days. One patient developed a urinary tract infection and one newborn died due to accompanying morbidities. Nine patients were discharged from the hospital.Conclusion: If the patients had a pelvic injury, surgeons must pay attention for the bladder perforation. Isolated bladder perforations are rare, and they are generally associated with iatrogenic injuries. Clinicians should pay attention to findings such as anuria, inability to insert a urinary catheter, and free fluid in the abdomen in order to diagnose the bladder perforation in newborns. Novice surgeons should pay more attention to avoid causing iatrogenic bladder perforation during inguinal hernia repair.Keywords: Bladder, child, iatrogenic, perforation, traum

Voltage imaging reveals the dynamic electrical signatures of human breast cancer cells

Cancer cells feature a resting membrane potential (Vm) that is depolarized compared to normal cells, and express active ionic conductances, which factor directly in their pathophysiological behavior. Despite similarities to ‘excitable’ tissues, relatively little is known about cancer cell Vm dynamics. Here high-throughput, cellular-resolution Vm imaging reveals that Vm fluctuates dynamically in several breast cancer cell lines compared to non-cancerous MCF-10A cells. We characterize Vm fluctuations of hundreds of human triple-negative breast cancer MDA-MB-231 cells. By quantifying their Dynamic Electrical Signatures (DESs) through an unsupervised machine-learning protocol, we identify four classes ranging from "noisy” to “blinking/waving“. The Vm of MDA-MB-231 cells exhibits spontaneous, transient hyperpolarizations inhibited by the voltage-gated sodium channel blocker tetrodotoxin, and by calcium-activated potassium channel inhibitors apamin and iberiotoxin. The Vm of MCF-10A cells is comparatively static, but fluctuations increase following treatment with transforming growth factor-β1, a canonical inducer of the epithelial-to-mesenchymal transition. These data suggest that the ability to generate Vm fluctuations may be a property of hybrid epithelial-mesenchymal cells or those originated from luminal progenitors

Novel degradable photocatalysts for wastewater treatment

The weakening of the manmade load on the environment has become a global goal of humanity. The accumulation of toxic substances in effl uents can increase the acceleration of pollution of the planet’s watersheds, resulting in biota pollution. To solve this problem, it is necessary to create photocatalysts that cause self-excitation under the ignition of light. Also, important parameters of photocatalysts are simple synthesis and low cost. This article demonstrates a one-step approach to the synthesis of carbon nanostructures (CNS) with photocatalytic activity. For this purpose, the “green chemistry ” method is used – hydrothermal treatment of various polysaccharides (sodium dextran sulfate (SDS), starch, pectin), which opens up the possibility of recycling products. A comprehensive study of the properties of the synthesized CNS has been carried out. To study the optical properties of CNS, absorption and luminescence spectroscopy, and IR spectroscopy, have been used. The CNS obtained have been successfully used in the processes of photocatalytic destruction of a model of the organic dye tartrazine, which is widely used in the fi ber and textile industries. The eff ect of lyophilization on the photocatalytic properties of СNS has been studied, and cytotoxicity has been evaluated

Nanoneedle-mediated stimulation of cell mechanotransduction machinery

Biomaterial substrates can be engineered to present topographical signals to cells which, through interactions between the material and active components of the cell membrane, regulate key cellular processes and guide cell fate decisions. However, targeting mechanoresponsive elements that reside within the intracellular domain is a concept that has only recently emerged. Here, we show that mesoporous silicon nanoneedle arrays interact simultaneously with the cell membrane, cytoskeleton, and nucleus of primary human cells, generating distinct responses at each of these cellular compartments. Specifically, nanoneedles inhibit focal adhesion maturation at the membrane, reduce tension in the cytoskeleton, and lead to remodeling of the nuclear envelope at sites of impingement. The combined changes in actin cytoskeleton assembly, expression and segregation of the nuclear lamina, and localization of Yes-associated protein (YAP) correlate differently from what is canonically observed upon stimulation at the cell membrane, revealing that biophysical cues directed to the intracellular space can generate heretofore unobserved mechanosensory responses. These findings highlight the ability of nanoneedles to study and direct the phenotype of large cell populations simultaneously, through biophysical interactions with multiple mechanoresponsive components

Fast fluorescence microscopy for imaging the dynamics of embryonic development

Live imaging has gained a pivotal role in developmental biology since it increasingly allows real-time observation of cell behavior in intact organisms. Microscopes that can capture the dynamics of ever-faster biological events, fluorescent markers optimal for in vivo imaging, and, finally, adapted reconstruction and analysis programs to complete data flow all contribute to this success. Focusing on temporal resolution, we discuss how fast imaging can be achieved with minimal prejudice to spatial resolution, photon count, or to reliably and automatically analyze images. In particular, we show how integrated approaches to imaging that combine bright fluorescent probes, fast microscopes, and custom post-processing techniques can address the kinetics of biological systems at multiple scales. Finally, we discuss remaining challenges and opportunities for further advances in this field

Cross-Jurisdictional Analysis of Administrative Health Data and Primary Care Electronic Medical Records in Canada

Over the last 30 years, public investments have created and supported administrative health data resources and repositories in Canada to support population health, health services and health policy research. Together, these repositories represent the building blocks of a world-class data platform that enables evidence-informed clinical, managerial and policy decisions. But because Canada’s universal health care system is managed at the provincial level, these repositories have limited capacity to share and use data across jurisdictional boundaries. Challenges with timely access to data remain and differences between jurisdictions affect the quality, scope, and impact of work that could be done. There are considerable benefits to be obtained from collaboration seeking to compare and/or combine health data across jurisdictional borders, despite the limitations in sharing the data. To ensure that Canadians continue to have access to high-quality health care and benefit from effective health policies, researchers and system planners must have access to and be able to make effective use of administrative health data. The purpose of this paper is to describe how we approached and addressed challenges in data access, data governance and data architecture in a Canadian cross-jurisdictional research study

A Novel Pathway of TEF Regulation Mediated by MicroRNA-125b Contributes to the Control of Actin Distribution and Cell Shape in Fibroblasts

BACKGROUND: Thyrotroph embryonic factor (TEF), a member of the PAR bZIP family of transcriptional regulators, has been involved in neurotransmitter homeostasis, amino acid metabolism, and regulation of apoptotic proteins. In spite of its relevance, nothing is known about the regulation of TEF. PRINCIPAL FINDINGS: p53-dependent genotoxic agents have been shown to be much more harmful for PAR bZIP-deficient mice as compared to wild type animals. Here we demonstrate that TEF expression is controlled by p53 through upregulation of microRNA-125b, as determined by both regulating the activity of p53 and transfecting cells with microRNA-125b precursors. We also describe a novel role for TEF in controlling actin distribution and cell shape in mouse fibroblasts. Lack of TEF is accompanied by dramatic increase of cell area and decrease of elongation (bipolarity) and dispersion (multipolarity). Staining of actin cytoskeleton also showed that TEF (-/-) cells are characterized by appearance of circumferential actin bundles and disappearance of straight fibers. Interestingly, transfection of TEF (-/-) fibroblasts with TEF induced a wild type-like phenotype. Consistent with our previous findings, transfection of wild type fibroblasts with miR-125b promoted a TEF (-/-)-like phenotype, and a similar but weaker effect was observed following exogenous expression of p53. CONCLUSIONS/SIGNIFICANCE: These findings provide the first evidence of TEF regulation, through a miR-125b-mediated pathway, and describes a novel role of TEF in the maintenance of cell shape in fibroblasts

Posterior Association Networks and Functional Modules Inferred from Rich Phenotypes of Gene Perturbations

Combinatorial gene perturbations provide rich information for a systematic exploration of genetic interactions. Despite successful applications to bacteria and yeast, the scalability of this approach remains a major challenge for higher organisms such as humans. Here, we report a novel experimental and computational framework to efficiently address this challenge by limiting the ‘search space’ for important genetic interactions. We propose to integrate rich phenotypes of multiple single gene perturbations to robustly predict functional modules, which can subsequently be subjected to further experimental investigations such as combinatorial gene silencing. We present posterior association networks (PANs) to predict functional interactions between genes estimated using a Bayesian mixture modelling approach. The major advantage of this approach over conventional hypothesis tests is that prior knowledge can be incorporated to enhance predictive power. We demonstrate in a simulation study and on biological data, that integrating complementary information greatly improves prediction accuracy. To search for significant modules, we perform hierarchical clustering with multiscale bootstrap resampling. We demonstrate the power of the proposed methodologies in applications to Ewing's sarcoma and human adult stem cells using publicly available and custom generated data, respectively. In the former application, we identify a gene module including many confirmed and highly promising therapeutic targets. Genes in the module are also significantly overrepresented in signalling pathways that are known to be critical for proliferation of Ewing's sarcoma cells. In the latter application, we predict a functional network of chromatin factors controlling epidermal stem cell fate. Further examinations using ChIP-seq, ChIP-qPCR and RT-qPCR reveal that the basis of their genetic interactions may arise from transcriptional cross regulation. A Bioconductor package implementing PAN is freely available online at http://bioconductor.org/packages/release/bioc/html/PANR.html