The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis

https://zenodo.org/record/1258475/files/article.pdf

Electron transfers in chemistry and biology

It has become increasingly difficult to find an area of cell biology in which lipids do not have important, if not key, roles as signalling and regulatory molecules. The rapidly expanding field of bioactive lipids is exemplified by many sphingolipids, such as ceramide, sphingosine, sphingosine-1-phosphate (S1P), ceramide-1-phosphate and lyso-sphingomyelin, which have roles in the regulation of cell growth, death, senescence, adhesion, migration, inflammation, angiogenesis and intracellular trafficking. Deciphering the mechanisms of these varied cell functions necessitates an understanding of the complex pathways of sphingolipid metabolism and the mechanisms that regulate lipid generation and lipid action.

Principles of bioactive lipid signalling: lessons from sphingolipids

The murine monoclonal antibody mumAb4D5, directed against human epidermal growth factor receptor 2 (p185HER2), specifically inhibits proliferation of human tumor cells overexpressing p185HER2. However, the efficacy of mumAb4D5 in human cancer therapy is likely to be limited by a human anti-mouse antibody response and lack of effector functions. A "humanized" antibody, humAb4D5-1, containing only the antigen binding loops from mumAb4D5 and human variable region framework residues plus IgG1 constant domains was constructed. Light- and heavy-chain variable regions were simultaneously humanized in one step by "gene conversion mutagenesis" using 311-mer and 361-mer preassembled oligonucleotides, respectively. The humAb4D5-1 variant does not block the proliferation of human breast carcinoma SK-BR-3 cells, which overexpress p185HER2, despite tight antigen binding (Kd = 25 nM). One of seven additional humanized variants designed by molecular modeling (humAb4D5-8) binds the p185HER2 antigen 250-fold and 3-fold more tightly than humAb4D5-1 and mumAb4D5, respectively. In addition, humAb4D5-8 has potency comparable to the murine antibody in blocking SK-BR-3 cell proliferation. Furthermore, humAb4D5-8 is much more efficient in supporting antibody-dependent cellular cytotoxicity against SK-BR-3 cells than mumAb4D5, but it does not efficiently kill WI-38 cells, which express p185HER2 at lower levels.

https://www.pnas.org/content/pnas/89/10/4285.full.pdf

Humanization of an anti-p185HER2 antibody for human cancer therapy.

Sonic Hedgehog Mediates the Polarizing Activity of the ZPA

Measurements of the true affinity constant in solution of antigen-antibody complexes by enzyme-linked immunosorbent assay.

We review firstly the specificities of the different types of dentin present in mammalian teeth. The outer layers include the mantle dentin, the Tomes' granular and the hyaline Hopewell-Smith's layers. Circumpulpal dentin forming the bulk of the tooth, comprises intertubular and peritubular dentin. In addition to physiological primary and secondary dentin formation, reactionary dentin is produced in response to pathological events. Secondly, we evaluate the role of odontoblasts in dentin formation, their implication in the synthesis and secretion of type I collagen fibrils and non-collagenous molecules. Thirdly, we study the composition and functions of dentin extracellular matrix (ECM) molecules implicated in dentinogenesis. As structural proteins they are mineralization promoters or inhibitors. They are also signaling molecules. Three different forms of dentinogenesis are identified: i) matrix vesicles are implicated in early dentin formation, ii) collagen and some proteoglycans are involved in the formation of predentin, further transformed into intertubular dentin, iii) the distal secretion of some non-collagenous ECM molecules and some serum proteins contribute to the formation of peritubular dentin.

/pdf/dentin-structure-composition-and-mineralization-xjyavemgiq.pdf

Dentin: structure, composition and mineralization.

The objective of this review is to summarize our understanding of the role of host matrix metalloproteinases (MMPs) in the caries process and to discuss new therapeutic avenues. MMPs hydrolyze components of the extracellular matrix and play a central role in many biological and pathological processes. MMPs have been suggested to play an important role in the destruction of dentin organic matrix following demineralization by bacterial acids and, therefore, in the control or progression of carious decay. Host-derived MMPs can originate both from saliva and from dentin. They may be activated by an acidic pH brought about by lactate release from cariogenic bacteria. Once activated, they are able to digest demineralized dentin matrix after pH neutralization by salivary buffers. Furthermore, the degradation of SIBLINGs (Small Integrin-binding Ligand N-linked Glycoproteins) by the caries process may potentially enhance the release of MMPs and their activation. This review also explores the different available MMP inhibitors, natural or synthetic, and suggests that MMP inhibition by several inhibitors, particularly by natural substances, could provide a potential therapeutic pathway to limit caries progression in dentin.

The Role of Matrix Metalloproteinases (MMPs) in Human Caries

In vitro and in vivo studies have clearly identified that some components of restorative composite resins, adhesives, and resin-modified glass ionomer cements are toxic. The mechanisms of cytotoxicity are related firstly to the short-term release of free monomers occurring during the monomer–polymer conversion. Secondly, long-term release of leachable substances is generated by erosion and degradation over time. In addition, ion release and proliferation of bacteria located at the interface between the restorative material and dental tissues are also implicated in the tissue response. Molecular mechanisms involve glutathione depletion and reactive oxygen species (ROS) production as key factors leading to pulp or gingival cell apoptosis. Experimental animal approaches substantiate the occurrence of allergic reactions. There is a large gap between the results published by research laboratories and clinical reports.

In vitro and in vivo studies on the toxicity of dental resin components: a review

Hydrogen peroxide (H2O2) is a powerful oxidising agent. It gives rise to agents known to be effective bleaching agents. The mechanisms of bleaching involve the degradation of the extracellular matrix and oxidation of chromophores located within enamel and dentin. However, H2O2 produces also local undesirable effects on tooth structures and oral mucosa. In clinical conditions, the daily low-level doses used to produce tooth whitening never generate general acute and sub-acute toxic effects. Genotoxicity and carcinogenicity only occur at concentrations that are never reached during dental treatments. Some transient adverse effects have been reported on the oral mucosa and the digestive tract if the product is swallowed. Local effects may occur on the oral mucosa and dental tissues during whitening, namely, pulp sensitivity, cervical resorption, release of selected components of dental restorative materials, and alteration of the enamel surface. Most of the local effects are dependent of the technique and concentration of the product so far used, but as the results of bleaching obtained are not stable, repeated treatments add to the adverse effects. The informed decision to administer or not and the control of bleaching effects should stand in the hand of dental surgeons and certainly not as it appears at present, as cosmetics sold without any restriction despite the potential health hazards of peroxides.

Michel Goldberg

Papers

Measurements of the true affinity constant in solution of antigen-antibody complexes by enzyme-linked immunosorbent assay.

Dentin: structure, composition and mineralization.

The Role of Matrix Metalloproteinases (MMPs) in Human Caries

In vitro and in vivo studies on the toxicity of dental resin components: a review

Undesirable and adverse effects of tooth-whitening products: a review.