Detection of Bacterial Membrane Vesicles by NOD-Like Receptors

Bacterial membrane vesicles (BMVs) are nanoparticles produced by both Gram-negative and Gram-positive bacteria that can function to modulate immunity in the host. Both outer membrane vesicles (OMVs) and membrane vesicles (MVs), which are released by Gram-negative and Gram-positive bacteria, respectively, contain cargo derived from their parent bacterium, including immune stimulating molecules such as proteins, lipids and nucleic acids. Of these, peptidoglycan (PG) and lipopolysaccharide (LPS) are able to activate host innate immune pattern recognition receptors (PRRs), known as NOD-like receptors (NLRs), such as nucleotide-binding oligomerisation domain-containing protein (NOD) 1, NOD2 and NLRP3. NLR activation is a key driver of inflammation in the host, and BMVs derived from both pathogenic and commensal bacteria have been shown to package PG and LPS in order to modulate the host immune response using NLR-dependent mechanisms. Here, we discuss the packaging of immunostimulatory cargo within OMVs and MVs, their detection by NLRs and the cytokines produced by host cells in response to their detection. Additionally, commensal derived BMVs are thought to shape immunity and contribute to homeostasis in the gut, therefore we also highlight the interactions of commensal derived BMVs with NLRs and their roles in limiting inflammatory diseases.     

Glia in Neurodegeneration: The Housekeeper,the Defender and the Perpetrator

Over the past decade, research has unveiled the intimate relationship between neuroinflammation and neurodegeneration. Microglia and astrocytes react to brain insult by setting up a multimodal inflammatory state and act as the primary defenders and executioners of neuroinflammatory structural and functional changes. Microglia and astrocytes also play critical roles in the maintenance of normal brain function. This intricate balance of homeostatic and neuroinflammatory functions can influence the onset and the course of neurodegenerative diseases. The emergent role of the microglial-astrocytic axis in neurodegenerative disease presents many druggable targets that may have broad therapeutic benefits across neurodegenerative disease. Here, we provide a brief review of the basal function of both microglia and astrocytes, how they are changed in disease states, the significant differences between mouse and human glia, and use of human induced pluripotent stem cells derived from patients to study cell autonomous changes in human astrocytes and microglia.     

The Effect of Thiol Structure on Allyl Sulfide Photodegradable Hydrogels and their Application as a Degradable Scaffold for Organoid Passaging

Intestinal organoids are useful in vitro models for basic and translational studies aimed at understanding and treating disease. However, their routine culture relies on animal-derived matrices that limit translation to clinical applications. In fact, there are few fully defined, synthetic hydrogel systems that allow for the expansion of intestinal organoids. Here, an allyl sulfide photodegradable hydrogel is presented, achieving rapid degradation through radical addition-fragmentation chain transfer (AFCT) reactions, to support routine passaging of intestinal organoids. Shear rheology to first characterize the effect of thiol and allyl sulfide crosslink structures on degradation kinetics is used. Irradiation with 365 nm light (5 mW cm⁻²) in the presence of a soluble thiol (glutathione at 15 × 10⁻³ m ), and a photoinitiator (lithium phenyl-2,4,6-trimethylbenzoylphosphinate at 1 × 10⁻³ m ), leads to complete hydrogel degradation in less than 15 s. Allyl sulfide hydrogels are used to support the formation of epithelial colonies from single intestinal stem cells, and rapid photodegradation is used to achieve repetitive passaging of stem cell colonies without loss in morphology or organoid formation potential. This platform could support long-term culture of intestinal organoids, potentially replacing the need for animal-derived matrices, while also allowing systematic variations to the hydrogel properties tailored for the organoid of interest.     

Measures of Population Ageing in Australia from 1950 to 2050

This study utilises annual historic and forecasted population figures from the UN World Population Prospects (2015 Revision) to describe Australia’s population changes for the period 1950–2050. A number of population indices have been employed to describe these changes. Specifically, we constructed population pyramids and computed measures including economic dependency ratios, support ratios, ageing/Billeter indices and coefficients of inflow, outflow and exchange of productive populations. Our results suggest that a combination of factors including declining fertility and mortality have contributed to Australia’s ageing population. The implications of these changes are broad and raise major challenges for Australia’s economy and infrastructure. To tackle both the drivers and impacts of population ageing, multi-faceted approaches are needed together with prompt evaluation to ensure that current and future challenges posed by population changes in Australia are fully contained.     

Review of Learning process in psychoanalytic supervision: Complexities and challenges.

Reviews the book, Learning process in psychoanalytic supervision: Complexities and challenges by Paul A. DeWald (see record 1987-97784-000). This book is a wonderful contribution to the field of supervision. It is the only book available that presents the actual supervision sessions of one ongoing supervisee with one long-term psychoanalytic patient as they were transcribed. DeWald also offers a review of the supervisory literature, his view of the supervisory process, his supervisory reports, and a chapter from the supervisee discussing her experience. The book is refreshing in that the supervisor does not present himself as perfect, and he does acknowledge mistakes he made in the comments after each set of process notes. There are some criticisms of the book to be made. First, the reviewer was not able to determine the frequency of the patient's sessions or the supervisory sessions. Second, the author's framework is classically Freudian. While this is not a problem, it is important that the reader be aware of the point of view. Third, the author seems ambivalent about the role of the patient's ethnicity and culture in her neurotic stance. These comments aside, Learning process in psychoanalytic supervision is an excellent book, and certainly one any supervisor would want to read. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Colorimetric Nanofibers as Optical Sensors

Sensors play a major role in many applications today, ranging from biomedicine to safety equipment, where they detect and warn us about changes in the environment. Nanofibers, characterized by high porosity, flexibility, and a large specific surface area, are the ideal material for ultrasensitive, fast‐responding, and user‐friendly sensor design. Indeed, a large specific surface area increases the sensitivity and response time of the sensor as the contact area with the analyte is enlarged. Thanks to the flexibility of membranes, nanofibrous sensors cannot only be applied in high‐end analyte detection, but also in personal, daily use. Many different nanofibrous sensors have already been designed; albeit, the most straightforward and easiest‐to‐interpret sensor response is a visual change in color, which is of particular interest in the case of warning signals. Recently, many researchers have focused on the design of so‐called colorimetric nanofibers, which typically involve the incorporation of a colorimetric functionality into the nanofibrous matrix. Many different strategies have been used and explored for colorimetric nanofibrous sensor design, which are outlined in this feature article. The many examples and applications demonstrate the value of colorimetric nanofibers for advanced optical sensor design, and could provide directions for future research in this area.     

专家言论：心有多大，舞台就有多大!

今年春天,技师大旧V(Vinnie Nguyen,大旧粤语大块头的意思)接到了一个有趣的改装挑战:使用指定的器材,打造一辆SQ音响改装样板车。因为顶尖级的改装店都应邀参加了这项先锋音响改装样板车竞赛,所以,大旧V同时还要与另外的13名使用相同器材的参赛者PK,要一举夺魁有多难可想而知。     

Complexity control in a mixture model by the Hardy-Weinberg equilibrium

A method of complexity control in multinomial mixture modeling of multiple-marker genotype data, imposing the Hardy-Weinberg equilibrium (HWE) between the genotype values, is studied. This is a very natural restriction, and known to hold at population level under modest assumptions. The hypothesis under study is that imposing this restriction will prevent overfitting and lead to a better model. This is shown to indeed be case. Experimental results on chromosomes 1 and 17 of the HapMap data demonstrate that the restricted model generalizes better to unseen data, and also finds clusters that correspond better to the ethnic groups of the HapMap, when compared with a model without the HWE restriction.