Cell Sheet Comprised of Mesenchymal Stromal Cells Overexpressing Stem Cell Factor Promotes Epicardium Activation and Heart Function Improvement in a Rat Model of Myocardium Infarction

Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF. In a rat model of myocardium infarction, we show that transplantation of SCF producing cell sheet induced activation of the epicardium and promoted the accumulation of c-kit positive cells in ischemic muscle. Morphometry showed the reduction of infarct size (16%) and a left ventricle expansion index (0.12) in the treatment group compared to controls (24–28%; 0.17–0.32). The ratio of viable myocardium was more than 1.5-fold higher, reaching 49% compared to the control (28%) or unmodified cell sheet group (30%). Finally, by day 30 after myocardium infarction, SCF-producing cell sheet transplantation increased left ventricle ejection fraction from 37% in the control sham-operated group to 53%. Our results suggest that, combining the genetic modification of MSCs and their assembly into a multilayered construct, we can provide prolonged pleiotropic effects to the damaged heart, induce endogenous regenerative processes, and improve cardiac function.     

Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin

Glycoprotein 330 (gp330) is a member of a family of endocytic receptors related to the low density lipoprotein receptor. gp330 has previously been shown to bind a number of ligands in common with its family member, the low density lipoprotein receptor-related protein (LRP). To identify ligands specific for gp330 and relevant to its localization on epithelia such as in the mammary gland, gp330-Sepharose affinity chromatography was performed. As a result, a 70-kDa protein was selected from human milk and identified by protein sequencing to be apolipoprotein J/clusterin (apoJ). Solid-phase binding assays confirmed that gp330 bound to apoJ with high affinity (Kd = 14.2 nM). Similarly, gp330 bound to apoJ transferred to nitrocellulose after SDS-polyacrylamide gel electrophoresis. LRP, however, showed no binding to apoJ in either type of assay. The binding of gp330 to apoJ could be competitively inhibited with excess apoJ as well as with the gp330 ligands apolipoprotein E, lipoprotein lipase, and the receptor-associated protein, a 39-kDa protein that acts to antagonize binding of all known ligands for gp330 and LRP. Several cultured cell lines that express gp330 and ones that do not express the receptor were examined for their ability to bind and internalize 125I-apoJ. Only cells that expressed gp330 endocytosed and degraded radiolabeled apoJ. Furthermore, F9 cells treated with retinoic acid and dibutyryl cyclic AMP to increase expression levels of gp330 displayed an increased capacity to internalize and degrade apoJ. Cellular internalization and degradation of radiolabeled apoJ could be inhibited with unlabeled apoJ, receptor-associated protein, and gp330 antibodies. The results indicate that gp330 but not LRP can bind to apoJ in vitro and that gp330 expressed by cells can mediate apoJ endocytosis leading to lysosomal degradation.     

Congratulations to Vladimir Viktorovich Baulin

Soil Mechanics and Foundation Engineering -     

Laboratory studies in cross-species lung transplantation

The lack of sufficient suitable human donor lungs for the many patients requiring pulmonary transplantation as life-saving therapy for end-stage lung diseases has generated extensive interest in cross-species lung transplantation. Ethical concerns and those of animal rights advocates have prompted studies of nonprimate species as potential solid organ donors for humans. This paper provides an overview of some of the laboratory studies of cross-species pulmonary transplantation performed over the past 20 years and focuses, in particular, on more recent work (from our laboratory and others) in the area of porcine-to-primate pulmonary xenotransplantation.     

The standard impact factor as an evaluation tool of science fields and scientific journals

The standard impact factor for particular fields of science (Ig) and the relative impact factor K for scientific journals are introduced. The technique of calculation of standard impact factor (Ig) for a field is an inherent part of a method which allows a cross-field evaluation of scientific journals. This method for evaluating scientific journals elaborated in 1988 was aimed at the analysis of Russian journals covered by the SCI database, it was also used for chemical journals (more that 300) and for journals in the Life sciences (more than 1000). The results are discussed.     

Quantum-mechanical reaction rate constants from centroid molecular dynamics simulations: Barrier crossing in an asymmetrical double-well

Quantum-mechanical reaction rate constants were calculated from centroid molecular dynamics (CMD) simulations, for the case of barrier crossing in an asymmetrical double-well potential bilinearly coupled to a harmonic bath. The calculation is based on a recently proposed formulation of the reaction rate constant in terms of the position—flux correlation function, which can be approximated via CMD in a well-defined manner. The predictions of CMD and various simplified versions of it are compared to exact results, which were obtained via the quasi-adiabatic propagator path integral (QUAPI) method, and/or path integral quantum transition state theory (PI-QTST). The predictions based on CMD are found to be in good agreement with both.     

Generalized Bose–Lin Codes, a Class of Codes Detecting Asymmetric Errors

Bose and Lin introduced a class of systematic codes for detection of binary asymmetric errors. In this note, we describe a generalization to q-ary asymmetric error detecting codes. For these codes, the possible undetectable errors are characterized and the undetectable errors of minimum weight are determined     

Towards a Dual-Tip STM Application in Mesoscopic Electron Transport

A new design for a dual-tip scanning tunneling microscope (STM) is presented. The design is a variation on the mechanically controllable break-junction with two electron beam-induced deposition nano-tips. The new design enables one to scan surfaces simultaneously with two probes having a nano-gap separation. By collecting the lateral current flowing between the tips, the transconductance map can then be compared with the STM images for local characterizations of the electron transport. Since the lateral beam carries the property of the density of states of the surface at momentum space, the dispersion of the electronic structure should give an orientation and position dependence of the local transconductance current. In addition, the reduced terminal separation, on the order of the characteristic mesoscopic length scales, is likely to be sensitive to a variety of typically observed interactions and interference effects.