COPII-coated vesicles are the primary mediators of ER-to-Golgi trafficking. Sar1, one of the five core COPII components, is a highly conserved small GTPase, which, upon GTP binding, recruits the other COPII proteins to the ER membrane. It has been hypothesized that the changes in the kinetics of SAR1 GTPase may allow for the secretion of large cargoes.
View Article and Find Full Text PDFThe coat protein complex II (COPII) is essential for the transport of large cargo, such as 300-nm procollagen I (PC1) molecules, from the endoplasmic reticulum (ER) to the Golgi. Previous work has shown that the CUL3-KLHL12 complex increases the size of COPII vesicles at ER exit sites to more than 300 nm in diameter and accelerates the secretion of PC1. However, the role of large COPII vesicles as PC1 transport carriers was not unambiguously demonstrated.
View Article and Find Full Text PDFThe ubiquitin ligase CUL3 is an essential regulator of neural crest specification whose aberrant activation has been linked to autism, schizophrenia, and hypertension. CUL3 exerts its roles by pairing with ∼90 distinct substrate adaptors, yet how the different CUL3-complexes are activated is poorly understood. Here, we show that CUL3 and its adaptor KLHL12 require two calcium-binding proteins, PEF1 and ALG2, for recognition of their substrate SEC31.
View Article and Find Full Text PDFMyxococcus xanthus is a bacterial micro-predator known for hunting other microbes in a wolf pack-like manner. Outer membrane vesicles (OMVs) are produced in large quantities by M. xanthus and have a highly organized structure in the extracellular milieu, sometimes occurring in chains that link neighboring cells within a biofilm.
View Article and Find Full Text PDFThe overwhelming majority of bacteria live in slime embedded microbial communities termed biofilms, which are typically adherent to a surface. However, when several Staphylococcus epidermidis strains were cultivated in static liquid cultures, macroscopic aggregates were seen floating within the broth and also sedimented at the test tube bottom. Light- and electron microscopy revealed that early-stage aggregates consisted of bacteria and extracellular matrix, organized in sheet-like structures.
View Article and Find Full Text PDFThe social soil bacterium, Myxococcus xanthus, displays a variety of complex and highly coordinated behaviours, including social motility, predatory rippling and fruiting body formation. Here we show that M. xanthus cells produce a network of outer membrane extensions in the form of outer membrane vesicle chains and membrane tubes that interconnect cells.
View Article and Find Full Text PDFOral Surg Oral Med Oral Pathol Oral Radiol
January 2013
Objective: Bacterial biofilms play a role in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). The purpose of this preliminary study was to test the hypothesis that the extracellular filaments observed in biofilms associated with BRONJ contain electrically conductive nanowires.
Study Design: Bone samples of patients affected by BRONJ were evaluated for conductive nanowires by scanning electron microscopy (SEM) and conductive probe atomic force microscopy (CP-AFM).
Oral Surg Oral Med Oral Pathol Oral Radiol
October 2012
Objective: Recently, specific in vitro bisphosphonate concentrations have been established for reaching a toxic threshold that could result in the induction of bisphosphonate-related osteonecrosis of the jaw (BRONJ), but these data have not been validated in vivo. The purpose of this study was to quantify the concentration of bisphosphonates (BPs) in the diseased jaw bone of patients experiencing BRONJ.
Study Design: We hypothesized that if the average natural nitrogen content of mammalian bone is known, the excess of nitrogen in the jaw bone of BRONJ patients is likely to reflect the concentration of amino-BP.
Packaging of proteins from the endoplasmic reticulum into COPII vesicles is essential for secretion. In cells, most COPII vesicles are approximately 60-80 nm in diameter, yet some must increase their size to accommodate 300-400 nm procollagen fibres or chylomicrons. Impaired COPII function results in collagen deposition defects, cranio-lenticulo-sutural dysplasia, or chylomicron retention disease, but mechanisms to enlarge COPII coats have remained elusive.
View Article and Find Full Text PDFAlmost nothing is known about the mechanisms of dissimilatory metal reduction by Gram-positive bacteria, although they may be the dominant species in some environments. Thermincola potens strain JR was isolated from the anode of a microbial fuel cell inoculated with anaerobic digester sludge and operated at 55 °C. Preliminary characterization revealed that T.
View Article and Find Full Text PDFBackground: Biofilm-induced inflammatory osteolytic oral infections, such as periodontitis and peri-implantitis, have complex etiology and pathogenesis. A significant obstacle to research has been the lack of appropriate animal models where the inflammatory response to biofilms can be investigated. The aim of this study is to develop a novel animal model to study the host response to Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans)-biofilm colonizing titanium implants.
View Article and Find Full Text PDFOphthalmic Plast Reconstr Surg
March 2011
Purpose: To demonstrate the presence of bacterial biofilms on a dacryocystorhinostomy silicone stent and a Jones tube.
Methods: One dacryocystorhinostomy silicone stent and one Jones tube were removed from 2 patients who presented with an infection of their respective nasolacrimal system. Cultures were obtained, and the implants were processed for scanning electron microscopy and confocal laser scanning microscopy, advanced microscopic methods that are applicable for detection of uncultivable biofilm organisms.
Microbial biofilms have been observed and described in bone specimens of patients with bisphosphonate (BP)-associated osteonecrosis of the jaw (BONJ) and investigators are more recently suggesting that this condition essentially represents an osteomyelitis of the jaw clinically, with greater susceptibility in some patients on BP therapy. This article explains the role of microbial biofilms in BONJ and also discusses associated factors in the disease pathogenesis, which include BP effects on bone remodeling, anti-angiogenesis, matrix necrosis, microcracks, soft tissue toxicity, and inflammation and wound healing. Recent findings suggest a key role for microbial biofilms in the pathogenesis of BONJ; this has important therapeutic implications because biofilm organisms represent a clinical target for prevention and treatment efforts aimed at reducing the significant morbidity and costs associated with this condition.
View Article and Find Full Text PDFBackground: The authors report their observations with respect to microbial biofilms in osteomyelitis of the jaw (OMJ), compare these findings with those for osteonecrosis of the jaw (ONJ) secondary to bisphosphonate therapy and discuss recent findings that the pathogenesis of ONJ may represent a biofilm-mediated infectious disease in the context of bisphosphonate therapy.
Methods: In 2004, a program was established at the University of Southern California, Los Angeles, to evaluate, treat and monitor patients who have OMJ and ONJ. Twenty people from this cohort of study patients who were scheduled to undergo surgical debridement or sequestrectomy and who met the authors' inclusion criteria gave informed consent for the study.
A light and electron microscope examination of the resected root tip of a failing endodontically re-treated lower molar was examined. The tooth had been initially treated 10 years ago and then re-treated 2 years ago. The resected root tip was sectioned axially, and thin sections were examined through the entire length of the specimen.
View Article and Find Full Text PDFBackground: Periodontitis is a classic example of biofilm-mediated diseases.
Methods: The authors reviewed selected publications in English-language peer-reviewed journals with respect to microbial biofilms, focusing on representative works that provided a historical to a contemporary perspective on periodontal oral biofilms in the larger context of biofilm microbiology.
Results: Developments in advanced microscopy and molecular microbiology have allowed scientists to examine and characterize microbial biofilm-mediated diseases, such as periodontitis, more accurately than in the past.
Objective: The objective of this study was to evaluate the effect of a dental water jet on plaque biofilm removal using scanning electron microscopy (SEM).
Methodology: Eight teeth with advanced aggressive periodontal disease were extracted. Ten thin slices were cut from four teeth.
Purpose: Biofilm theory has emerged to explain the etiology of the chronic infections that have come to constitute between 65% to 80% of the microbial diseases treated by physicians in the developed world. The purpose of this article is to report for the first time the observation of multispecies microbial biofilms on affected bone in patients with osteonecrosis of the jaws (ONJ) secondary to bisphosphonate therapy.
Patients And Methods: A program has been established at the University of Southern California to monitor and evaluate patients with ONJ as a multidisciplinary collaboration between the School of Dentistry, Center for Biofilms, Center for Craniofacial Molecular Biology and the Keck School of Medicine.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
April 2008
Background: Toxic epidermal necrolysis (TEN) is a rare and potentially fatal adverse dermatologic reaction, often secondary to drug intake.
Methods And Results: We report a case of an adult male who developed TEN that was complicated by a sepsis-induced coma lasting a period of 3 months. Although the patient eventually recovered, severe oral mucosal involvement during the course of disease resulted in frenum-like fibrotic bands that connected movable oral mucosa (tongue and lips) to attached oral mucosa (gingiva).
Objective: Microbial biofilms are communities of sessile microorganisms formed by cells that are attached irreversibly to a substratum or interface or to each other and embedded in a hydrated matrix of extracellular polymeric substances. Microbial biofilms have been implicated in >80% of human infections such as periodontitis, urethritis, endocarditis, and device-associated infections. Thus far, intraamniotic infection has been attributed to planktonic (free-floating) bacteria.
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