Molecular mechanisms regulating formation, trafficking and processing of annular gap junctions

Internalization of gap junction plaques results in the formation of annular gap junction vesicles. The factors that regulate the coordinated internalization of the gap junction plaques to form annular gap junction vesicles, and the subsequent events involved in annular gap junction processing have only relatively recently been investigated in detail. However it is becoming clear that while annular gap junction vesicles have been demonstrated to be degraded by autophagosomal and endo-lysosomal pathways, they undergo a number of additional processing events. Here, we characterize the morphology of the annular gap junction vesicle and review the current knowledge of the processes involved in their formation, fission, fusion, and degradation. In addition, we address the possibility for connexin protein recycling back to the plasma membrane to contribute to gap junction formation and intercellular communication. Information on gap junction plaque removal from the plasma membrane and the subsequent processing of annular gap junction vesicles is critical to our understanding of cell-cell communication as it relates to events regulating development, cell homeostasis, unstable proliferation of cancer cells, wound healing, changes in the ischemic heart, and many other physiological and pathological cellular phenomena

Opisthorchiasis and cholangiocarcinoma in South East Asia: an unresolved problem

The prevalence of cholangiocarcinoma (CCA) in Southeast Asia is much higher than other areas of the world. Eating raw, fermented or undercooked cyprinid fish, infected with the liver fluke, Opisthorchis viverrini sensu lato, results in chronic biliary inflammation, periductal fibrosis, and increased cancer risk. There may be associated glomerulonephritis. The process of infection is difficult to disrupt because eating practices have proven extremely difficult to change, and the life cycle of the fluke cannot be broken due to high prevalence in canine and feline reservoir hosts. Fecal analysis and ELISA tests can be used to diagnose opisthorchiasis. Diagnosis of CCA is complex, partly due to the lack of definitive imaging characteristics and also due to the difficulty of obtaining samples for cytology or histology. This cancer has proven to be resistant to common chemotherapy treatments and so the two avenues of treatment available are surgical resection and liver transplantation, both requiring early detection of the tumor for the best chances of success. Late presentation of symptoms reduces the chances of successful surgical intervention. While liver fluke infections can be treated with praziquantel, individuals will often become re-infected, and multiple reinfections can be more harmful than a singular, long term infection. A key research need is for the detection and characterization of novel biomarkers in all parts of the carcinogenic pathway for early diagnosis

The role of immune correlates of protection on the pathway to licensure, policy decision and use of group B Streptococcus vaccines for maternal immunization: considerations from World Health Organization consultations.

The development of a group B Streptococcus (GBS) vaccine for maternal immunization constitutes a global public health priority, to prevent GBS-associated early life invasive disease, stillbirth, premature birth, maternal sepsis, adverse neurodevelopmental consequences, and to reduce perinatal antibiotic use. Sample size requirements for the conduct of a randomized placebo-controlled trial to assess vaccine efficacy against the most relevant clinical endpoints, under conditions of appropriate ethical standards of care, constitute a significant obstacle on the pathway to vaccine availability. Alternatively, indirect evidence of protection based on immunologic data from vaccine and sero-epidemiological studies, complemented by data from opsonophagocytic in vitro assays and animal models, could be considered as pivotal data for licensure, with subsequent confirmation of effectiveness against disease outcomes in post-licensure evaluations. Based on discussions initiated by the World Health Organization we present key considerations about the potential role of correlates of protection towards an accelerated pathway for GBS vaccine licensure and wide scale use. Priority activities to support progress to regulatory and policy decision are outlined

The Braincase and Neurosensory Anatomy of an Early Jurassic Marine Crocodylomorph: Implications for Crocodylian Sinus Evolution and Sensory Transitions

This is the pre-peer reviewed version of the following article: Brusatte, S. L., Muir, A. , Young, M. T., Walsh, S. , Steel, L. and Witmer, L. M. (2016), The Braincase and Neurosensory Anatomy of an Early Jurassic Marine Crocodylomorph: Implications for Crocodylian Sinus Evolution and Sensory Transitions. Anat. Rec., 299: 1511-1530., which has been published in final form at doi:10.1002/ar.23462. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving." You are advised to consult the published version if you wish to cite from it

Multifunctional hybrid materials based on transparent poly(methyl methacrylate) reinforced by lanthanoid hydroxo clusters

Three pentanuclear lanthanoid hydroxo clusters of composition [Ln(OH)5(abzm)10], where Ln = Eu, Tb,Ho and abzm = di(4-allyloxy)benzoylmethanide, have been prepared. The structures have beencharacterised by means of IR, Raman, elemental analyses and X-ray diffraction, showing a pyramidalsquare-based cluster core. The clusters (Tb and Ho) exhibit Curie?Weiss Law behaviour, displayingantiferromagnetic ordering at low temperatures. The emission properties of the Eu cluster demonstratethe abzm- ligand is an efficient antenna (lex = 420 nm) only for the sensitisation of Eu luminescence inthe visible range, via energy transfer to the 5D0 state of the trivalent metal. The clusters have beenreacted in the presence of methyl methacrylate and azobisisobutyronitrile to prepare reinforcedpolymers via radical polymerisation. The obtained materials exhibit swelling upon immersion intoorganic solvents up to 110% of their original size, in agreement with the presence of cluster-crosslinked polymeric chains. Also, no loss of transparency was observed in the preparation of the materials. The characteristic red emission of the Eu cluster in also retained in the polymeric material

Particulate emissions from a 350 kW wood pellet heater

The particulate mass and size distribution was investigated for a biomass wood-pellet air heater with a direct comparison with an equivalent oil-fired burner using the same cross-flow air heater system. Five wood pellet fuels were investigated from different sources and the influence on particle mass and size distribution was determined. The influence of burner excess air on gaseous and particulate emissions was determined. The optimum excess air for minimum emissions and maximum thermal efficiency for the pellet burner was higher at 42% than for the oil burner at 23%. The thermal efficiency of the pellet heater was determined to be slightly less than that of the oil heater. The main reason for this was operation of the heater at higher excess air levels with pellets. The hydrocarbon and particulate carbon fraction emissions were lower for the pellet burner but the CO and NOx emissions were higher. Composition differences between different pellet manufacturers, due to the use of different wood sources, were significant and this produced significant variation in the stoichiometric A/F, which without oxygen feedback control, resulted in different excess air levels for the same pellet feed rate. This resulted in a significant influence of pellet composition on emissions due to excess air variations. Particulate mass and number emissions were low for the biomass pellet burner and similar to the oil burner, provided both burners were at their optimum excess air operational condition. Particulate emissions increased dramatically if the excess air was reduced to 23%

Fluoromycobacteriophages for rapid, specific, and sensitive antibiotic susceptibility testing of Mycobacterium tuberculosis

Rapid antibiotic susceptibility testing of Mycobacterium tuberculosis is of paramount importance as multiple- and extensively- drug resistant strains of M. tuberculosis emerge and spread. We describe here a virus-based assay in which fluoromycobacteriophages are used to deliver a GFP or ZsYellow fluorescent marker gene to M. tuberculosis, which can then be monitored by fluorescent detection approaches including fluorescent microscopy and flow cytometry. Pre-clinical evaluations show that addition of either Rifampicin or Streptomycin at the time of phage addition obliterates fluorescence in susceptible cells but not in isogenic resistant bacteria enabling drug sensitivity determination in less than 24 hours. Detection requires no substrate addition, fewer than 100 cells can be identified, and resistant bacteria can be detected within mixed populations. Fluorescence withstands fixation by paraformaldehyde providing enhanced biosafety for testing MDR-TB and XDR-TB infections. © 2009 Piuri et al

A Minimal Model of Metabolism Based Chemotaxis

Since the pioneering work by Julius Adler in the 1960's, bacterial chemotaxis has been predominantly studied as metabolism-independent. All available simulation models of bacterial chemotaxis endorse this assumption. Recent studies have shown, however, that many metabolism-dependent chemotactic patterns occur in bacteria. We hereby present the simplest artificial protocell model capable of performing metabolism-based chemotaxis. The model serves as a proof of concept to show how even the simplest metabolism can sustain chemotactic patterns of varying sophistication. It also reproduces a set of phenomena that have recently attracted attention on bacterial chemotaxis and provides insights about alternative mechanisms that could instantiate them. We conclude that relaxing the metabolism-independent assumption provides important theoretical advances, forces us to rethink some established pre-conceptions and may help us better understand unexplored and poorly understood aspects of bacterial chemotaxis

Kondo Problem and Related One-Dimensional Quantum Systems: Bethe Ansatz Solution and Boundary Conformal Field Theory

We review some exact results on Kondo impurity systems derived from Bethe-ansatz solutions and boundary conformal field theory with particular emphasis on universal aspects of the phenomenon. The finite-size spectra characterizing the low-energy fixed point are computed from the Bethe-ansatz solutions of various models related to the Kondo problem. Using the finite-size scaling argument, we investigate their exact critical properties. We also discuss that a universal relation between the Kondo effect and the impurity effect in one-dimensional quantum systems usefully expedites our understanding of these different phenomena.Comment: 6 pages, no figure