Albert E. Sobel

Bio: Albert E. Sobel is an academic researcher from Jewish Hospital. The author has contributed to research in topics: Vitamin & Calcification. The author has an hindex of 30, co-authored 95 publications receiving 3496 citations.

Local factors in the mechanism of calcification

Abstract: The fact that normal mineralization takes place at specific sites in the body indicates that a “local factor(s)” present in the calcifying matrix favors the process which gives mineralized tissues their characteristic hardness. The nature and operation of the “local factor(s)” may be regarded as the key problem in studies involving the understanding of the mineralizing process. The present approach to understanding the “local factor(s)” stemmed from physicochemical concepts of phase rule and solubility product. An attempt was made to determine from the composition and degree of mineralization whether the “local factor(s)” operates within these principles or in some way modifies the conditions so that the simple physicochemical principles do not apply. From both the agreements and the discrepancies between these concepts and the experimental results, further studies were designed to obtain insight into the minimal system required for the process of mineralization.

Intrinsically Disordered Proteins

Abstract: Proteins can exist in a trinity of structures: the ordered state, the molten globule, and the random coil. The five following examples suggest that native protein structure can correspond to any of the three states (not just the ordered state) and that protein function can arise from any of the three states and their transitions. (1) In a process that likely mimics infection, fd phage converts from the ordered into the disordered molten globular state. (2) Nucleosome hyperacetylation is crucial to DNA replication and transcription; this chemical modification greatly increases the net negative charge of the nucleosome core particle. We propose that the increased charge imbalance promotes its conversion to a much less rigid form. (3) Clusterin contains an ordered domain and also a native molten globular region. The molten globular domain likely functions as a proteinaceous detergent for cell remodeling and removal of apoptotic debris. (4) In a critical signaling event, a helix in calcineurin becomes bound and surrounded by calmodulin, thereby turning on calcineurin's serine/threonine phosphatase activity. Locating the calcineurin helix within a region of disorder is essential for enabling calmodulin to surround its target upon binding. (5) Calsequestrin regulates calcium levels in the sarcoplasmic reticulum by binding approximately 50 ions/molecule. Disordered polyanion tails at the carboxy terminus bind many of these calcium ions, perhaps without adopting a unique structure. In addition to these examples, we will discuss 16 more proteins with native disorder. These disordered regions include molecular recognition domains, protein folding inhibitors, flexible linkers, entropic springs, entropic clocks, and entropic bristles. Motivated by such examples of intrinsic disorder, we are studying the relationships between amino acid sequence and order/disorder, and from this information we are predicting intrinsic order/disorder from amino acid sequence. The sequence-structure relationships indicate that disorder is an encoded property, and the predictions strongly suggest that proteins in nature are much richer in intrinsic disorder than are those in the Protein Data Bank. Recent predictions on 29 genomes indicate that proteins from eucaryotes apparently have more intrinsic disorder than those from either bacteria or archaea, with typically > 30% of eucaryotic proteins having disordered regions of length > or = 50 consecutive residues.

Regulation and function of ascorbate peroxidase isoenzymes

Abstract: Even under optimal conditions, many metabolic processes, including the chloroplastic, mitochondrial, and plasma membrane-linked electron transport systems of higher plants, produce active oxygen species (AOS). Furthermore, the imposition of biotic and abiotic stress conditions can give rise to excess concentrations of AOS, resulting in oxidative damage at the cellular level. Therefore, antioxidants and antioxidant enzymes function to interrupt the cascades of uncontrolled oxidation in each organelle. Ascorbate peroxidase (APX) exists as isoenzymes and plays an important role in the metabolism of H(2)O(2) in higher plants. APX is also found in eukaryotic algae. The characterization of APX isoenzymes and the sequence analysis of their clones have led to a number of investigations that have yielded interesting and novel information on these enzymes. Interestingly, APX isoenzymes of chloroplasts in higher plants are encoded by only one gene, and their mRNAs are generated by alternative splicing of the gene's two 3'-terminal exons. Manipulation of the expression of the enzymes involved in the AOS-scavenging systems by gene-transfer technology has provided a powerful tool for increasing the present understanding of the potential of the defence network against oxidative damage caused by environmental stresses. Transgenic plants expressing E. coli catalase to chloroplasts with increased tolerance to oxidative stress indicate that AOS-scavenging enzymes, especially chloroplastic APX isoenzymes are sensitive under oxidative stress conditions. It is clear that a high level of endogenous ascorbate is essential effectively to maintain the antioxidant system that protects plants from oxidative damage due to biotic and abiotic stresses.

Chapter III Chemical Analysis of Microbial Cells

Abstract: Publisher Summary This chapter discusses the chemical analysis of microbial cells. The preparation of material for analysis is discussed, because changes in the chemical composition of cells may occur as a result of the washing and storage conditions used. Wet- and dry-weight determinations of bacterial samples and assay of total cell numbers are described, because analytical results must refer to one or other of these values. Selection of an analytical procedure is a subjective process, because the number of suitable methods is large and each will have different merits and defects. Primary considerations are sensitivity, specificity, reproducibility, and absolute accuracy. Automatic methods for performing biochemical analyses, already widely accepted in hospitals and in industry, are beginning to make their way into the research laboratory. All automatic analyzers developed so far may be classified as either “continuous-flow” or “discrete” types. All of them use colorimetric methods exclusively and contain some form of automatic colorimeter for final read-out. The first and best-known is the Technicon “AutoAnalyzer,” which is of the continuous-flow type.

Label-Free, Single-Molecule Detection with Optical Microcavities

Abstract: Current single-molecule detection techniques require labeling the target molecule. We report a highly specific and sensitive optical sensor based on an ultrahigh quality (Q) factor (Q > 10^8) whispering-gallery microcavity. The silica surface is functionalized to bind the target molecule; binding is detected by a resonant wavelength shift. Single-molecule detection is confirmed by observation of single-molecule binding events that shift the resonant frequency, as well as by the statistics for these shifts over many binding events. These shifts result from a thermo-optic mechanism. Additionally, label-free, single-molecule detection of interleukin-2 was demonstrated in serum. These experiments demonstrate a dynamic range of 10^(12) in concentration, establishing the microcavity as a sensitive and versatile detector.