Pericellular colocalisation and interactive properties of type VI collagen and perlecan in the intervertebral disc

The aim of this study was to immunolocalise type VI collagen and perlecan and determine their interactive properties in the intervertebral disc (IVD). Confocal laser scanning microscopy co-localised perlecan with type VI collagen as pericellular components of IVD cells and translamellar cross-bridges in ovine and murine IVDs. These cross-bridges were significantly less abundant in the heparin sulphate deficient Hspg2 exon 3 null mouse IVD than in wild type. This association of type VI collagen with elastic components provides clues as to its roles in conveying elastic recoil properties to annular tissues. Perlecan and type VI collagen were highly interactive in plasmon resonance studies. Pericellular colocalisation of perlecan and type VI collagen provides matrix stabilisation and cell-matrix communication which allows IVD cells to perceive and respond to perturbations in their biomechanical microenvironment. Perlecan, at the cell surface, provides an adhesive interface between the cell and its surrounding extracellular matrix. Elastic microfibrillar structures regulate tensional connective tissue development and function. The 2010 Global Burden of Disease study examined 291 disorders and identified disc degeneration and associated low back pain as the leading global musculoskeletal disorder emphasising its massive socioeconomic impact and the need for more effective treatment strategies. A greater understanding of how the IVD achieves its unique biomechanical functional properties is of great importance in the development of such therapeutic measures

Fibrinogen adsorption and platelet adhesion to silica surfaces with stochastic nanotopography

In this study, the effect of surface nanoscale roughness on fibrinogen adsorption and platelet adhesion was investigated. Nanorough silica surfaces with a low level of surface roughness (10 nm Rrms) were found to support the same level of fibrinogen adsorption as the planar silica surfaces, while nanorough silica surfaces with higher levels of surface roughness (15 nm Rrms) were found to support significantly less fibrinogen adsorption. All surfaces analyzed were found to support the same level of platelet adhesion; however, platelets were rounded in morphology on the nanorough silica surfaces while platelets were spread with a well-developed actin cytoskeleton on the planar silica. Unique quartz crystal microbalance with dissipation monitoring (QCM-D) responses was observed for the interactions between platelets and each of the surfaces. The QCM-D data indicated that platelets were more weakly attached to the nanorough silica surfaces compared with the planar silica. These data support the role of surface nanotopography in directing platelet-surface interactions even when the adsorbed fibrinogen layer is able to support the same level of platelet adhesion

Taylor approximations of operator functions

This survey on approximations of perturbed operator functions addresses recent advances and some of the successful methods.Comment: 12 page

Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles

How people with dementia and their families decide about moving to a care home and support their needs: development of a decision aid, a qualitative study

yesBackground: People with dementia and their relatives find decisions about the person with dementia living in a care home difficult. Methods: We interviewed 20 people with dementia or family carers around the time of this decision in order to design a decision-aid. Results: Decision-makers balanced the competing priorities of remaining somewhere familiar, family’s wish they remain at home, reduction of risk and effects on carer’s and person with dementia’s physical health. The person with dementia frequently resented their lack of autonomy as decisions about care home moves were made after insight and judgment were impaired. Family consultation usually helped carers but sometimes exacerbated tensions. Direct professional support was appreciated where it was available. There is a need for healthcare professionals to facilitate these conversations around decision-making and to include more than signposting to other organisations. Conclusions: There is a need for a healthcare professional facilitated decision-aid. This should detail what might change for the person with dementia and their carer, possible resources and alternatives and assist in facilitating discussion with the wider family; further research will develop and test a tool to facilitate decision making about place of care needs

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies

Ladder Use Ability, Behavior and Exposure by Age and Gender

This study aimed to quantify and compare ladder use ability and behavior in younger and older men and women from three ladder use behavior experiments. The experimental tasks comprised (1) changing a lightbulb on a household stepladder under two cognitive demands (single and dual task), (2) clearing a simulated roof gutter on a straight ladder and (3) querying ladder choice in different exigency scenarios. Ladder use ability and behavior data were captured from recorded time, performance, motion capture and user choice data. In addition, this study surveyed ladder use frequency and habitual behaviors. The experimental findings indicate that older adults require more time to complete ladder tasks; younger adults display riskier ladder use behaviors; men and women display similar ladder use ability; and men are more willing to climb riskier ladders. The survey found older adults to report more frequent ladder use than younger adults, and men use straight ladders more frequently than women. These results suggest that the reported higher ladder fall rates experienced by older adults and men are linked to increased ladder use exposure and riskier ladder choice. This knowledge can help guide population-specific interventions to reduce ladder falls in both young and older people

De Novo Engineering of Metal–Organic Framework-Printed In Vitro Diagnostic Devices for Specific Capture and Release of Tumor Cells

Herein, a paper-based in vitro diagnostic device (IVD) is developed via inkjet printing of de novo engineered, boronic acid-rich metal–organic frameworks (BMOFs). The newly developed BMOFs simultaneously possess crystalline and amorphous structure, mesopore size, large surface area, and retain a high level of boronic acid integration. After printing the BMOFs on the filter paper, the BMOF-printed paper IVD shows a rapid response time (40 min) towards cancer cell capture and its maximum cell capture capacity reaches approximately (4.5 ±1.1) ×104 cells cm−2. Furthermore, the BMOF-printed IVD shows nine times higher capture ability of cancer cells than non-cancerous cells, suggesting its excellent selectivity. Importantly, the pH-tunable affinity of BMOF to glucose enables its dual-responsive behavior without affecting cell viability. In addition, a desired cell pattern could be achieved by directly drawing BMOFs onto a silicon substrate, highlighting its capacity as a miniaturized device for tumor cell capture and analysis. This simple and label-free nanoplatform enables new opportunities for designing MOF-based smart devices for diverse biomedical applications such as a cost-effective IVD technologies for cancer diagnosis, genotyping, and prognosis

Oxygen-Vacancy Engineering of Cerium-Oxide Nanoparticles for Antioxidant Activity

© 2019 American Chemical Society. To address an important challenge in the engineering of antioxidant nanoparticles, the present work devised a surface-to-bulk migration of oxygen vacancies in the oxygen radical-scavenging cerium-oxide nanoparticles. The study highlights the significance of surface oxygen vacancies in the intended cellular internalization and, subsequently, the radical scavenging activity of the nanoparticles inside the cells. The findings advise future development of therapeutic antioxidant nanomaterials to also include engineering of the particles for enhanced surface defects not only for the accessibility of their oxygen vacancies but also, equally important, rendering them bioavailable for cellular uptake