A microvolume molecular filter

A microvolume polymer membrane filter based on Amicon hollow fibers in described which permits separation of low molecular weight compounds from proteins, and can be used for desalting volumes of 100 microliter or less, or to separate cellular protein debris from perfusates during release studies. The filter has the advantage of being reusable and having almost no void volume.     

A molecular view of cardiogenesis

Cardiac development involves a complex integration of subcellular processes into multicellular and, finally, whole organ effects. Until recently it has been difficult to investigate the genetic control of this organ level differentiation of the heart. The proliferation of molecular biology methodologies has provided mechanisms to directly investigate the control of these processes. This article focuses on molecular lines of research on two key areas in cardiac development: the regulation of expression of sarcomeric contractile and regulatory proteins, and atrial natriuretic factor. Molecular approaches are described which have allowed investigators to begin to determine the tissue and stage-specific expression of genes, to locate those genes in the genome, determine their sequences, and to directly investigate the mechanisms controlling their expression.     

A robust neural network filter for electricity demand prediction

This paper is concerned with one-day-ahead hourly predictions of electricity demand for Puget Power, a local electricity utility for the Seattle area. Standard modelling techniques, including neural networks, will fail when the assumptions of the model are violated. It is demonstrated that typical modelling assumptions such as no outliers or level shifts are incorrect for electric power demand time series. A filter which removes or lessens the significance of outliers and level shifts is demonstrated. This filter produces ‘clean data’ which is used as the basis for future robust predictions. The robust predictions are shown to be better than non-robust counterparts on electricity load data. The outliers identified by the filter are shown to correspond with suspicious data. Finally, the estimated level shifts are in agreement with the belief that load growth is taking place year to year.     

A selective de-heparinizer filter made of new cross-linked polymers of a poly-amido-amine structure

Riassunto Dae polimeri reticolati di nuova sintesi, contenenti gruppi amminici terziari, sono in grado di assorbire selettivamente eparina dal sangue. Essi non sono emolitici e non interferiscono con i fattori della coagulazione.

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Acknowledgment. This work was supported by the Programma Speciale Technologie Biomediche of the Italian National Council of Researches.     

Cellular and molecular pathogenesis of type 1A diabetes

Type 1A diabetes is an organ-specific autoimmune disease resulting from destruction of insulin-producing pancreatic beta-cells. The main susceptibility genes code for polymorphic HLA molecules and in particular alleles of class II MHC genes (DR, DQ and DP). Polymorphisms of individual genes outside the MHC also contribute to diabetes risk but recent evidence suggests that there are additional non-HLA genes determining susceptibility linked to the MHC. It is now possible using genetic and autoantibody assays to predict the development of type 1A diabetes in the majority of individuals, and trials of diabetes prevention are underway.     

A low molecular weight glycosaminoglycan from the human aorta

Summary A low mol.wt, dialyzable glycosaminoglycan was isolated from human aorta and was found to be homogeneous on 2 dimensional electrophoresis. As judged by its electrophoretic mobilities and its hydrolysis by chondroitin sulfatase ABC, it was concluded that this hitherto unknown glycosaminoglycan is an oversulfated chondroitin sulfate.This study was supported by grants from the National Institutes of Health (GM-10374, HL-13262), U.S. Public Health Service.     

Modulation of phospholipase A2 activity generated by molecular evolution

Snake venom oligomeric neurotoxins offer several unique examples of modulation of phospholipase A2 (PLA2) activity generated by molecular evolution. This phenomenon was found in evolutionary younger snakes and is probably common for representatives of the genus Vipera. At present, the best-studied example is the heterodimeric neurotoxin vipoxin from the venom of the southeast European snake Vipera ammodytes meridionalis. It is a complex between a basic strongly toxic PLA2 and an acidic and catalytically inactive PLA2-like component (Inh). This is the first reported example of a high degree of structural homology (62%) between an enzyme and its natural protein inhibitor. The inhibitor is a product of the divergent evolution of the unstable PLA2 in order to stabilize it and to preserve the pharmacological activity/toxicity for a long time. Inh reduces both the catalytic activity and toxicity of PLA2. Vipoxin also illustrates evolution of the catalytic into a inhibitory function. Vipoxin analogues have been found in the venom of viperid snakes inhabiting diverse regions of the world. An attempt is made to explain modulation of the toxic function by the three-dimensional structure of vipoxin.     

A new plot to estimate protein molecular weight by density gradient ultracentrifugation

Summary A plot of the logarithm of the molecular weight against the logarithm of the sedimenting distance is proposed for estimation of protein molecular weight. The proteins are separated in acrylamide-containing linear density gradients, polymerized and stained after centrifugation.     

A new small molecular tracer for permeability studies with the electron microscope

Résumé Le gluconate de fer a la propriété de suivre les molécules d'un poids moléculaire de } 500. Il traverse avec elles l'endothélium des vaisseaux sanguins et l'épithélium de la vessie en passant par les joints ou, pour une faible part, entre les vésicles.

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We are most grateful for the skilful assistance of Mr.B. R. Dixon and the partial support of the Australian Research Grants Committee.     

Retrovirus molecular conjugates

Retrovirus-derived vectors are currently the preferred vectors used for human gene therapy protocols. Serious safety concerns persist, however, which are specifically related to the formation of a replication-competent virus, and no synthesis method currently employed precludes its formation with certainty. For many cell types, a low transduction efficiency results in insufficient therapeutic benefit. We describe the development of a molecular conjugate system, which permits transient chemical modification of a retrovirus with polylysine. This modification not only introduces additional safety features over standard unmodified retrovirus vectors, but also provides enhanced transduction efficiency.     

A peripheral high molecular weight glycoprotein located at the surface of human platelets

Summary A high molecular weight glycoprotein solubilised during platelet membrane isolation appeared to be a peripheral component of the human platelet surface and was susceptible to the action of neuraminidase when added to washed platelet suspensions.Part of this work was performed at The Nuffield Institute of Comparative Medicine, Zoological Society of London, Regents Park, London (England).     

A low molecular weight tracer molecule for immunocytochemistry. Identification of cytoplasmic actin

Summary Anti actin Fab-fragments were tagged to a small electron dense tracer molecule; ferrocene monocarboxylic acid (230 daltons). The conjugate stains actin filaments, which were found mainly in the core of microvilli.     

Progress in molecular parasitology

Substantial progress has been made in the last ten years in understanding the structural and functional organization of parasitic protozoa and helminths and the complex physiological relationships that exist between these organisms and their hosts. By employing the new powerful techniques of biochemistry, molecular biology and immunology the genomic organization in parasites, the molecular basis of parasite's variation in surface antigens and the biosynthesis, processing, transport and membrane anchoring of these and other surface proteins were extensively investigated. Significant advances have also been made in our knowledge of the specific and often peculiar strategies of intermediary metabolism, cell compartmentation, the role of oxygen for parasites and the mechanisms of antiparasitic drug action. Further major fields of interest are currently the complex processes which enables parasites to evade the host's immune defense system and other mechanisms which have resulted in the specific adaptations which enabled parasites to survive within their host environments. Various approaches in molecular and biochemical parasitology and in immunoparasitology have been proven to be of high potential for serodiagnosis, immunoprophylaxis and drug design.