Escherichia coli molecular chaperone GroEL and co-chaperone GroES are well known to assist the folding/refolding of a diverse range of substrate proteins. Despite this, there have been relatively few reports of the GroEL/GroES molecular chaperone system being used as a biotechnology tool for protein folding/refolding. In this paper, a solution-phase protein folding bioreactor is described that involves the complete GroEL/GroES system. The main features of this bioreactor are the use of a stirred-cell concentrator fitted with a 100 kDa molecular weight cutoff membrane and an attached buffer reservoir. This bioreactor system was used successfully for assisted-batch refolding of guanidinium chloride (Gu-HCl) unfolded mitochondrial malate dehydrogenase (mMDH). We believe that protein folding bioreactor systems of this type could have wide potential utility for the folding/refolding of unfolded protein substrates.

Animals↗

PubMedDate not supplied

Retrovirus-mediated transfer and expression of drug resistance genes in human haematopoietic progenitor cells.

Patients with certain genetic disorders can be cured by bone marrow transplantation. However, as prospective donors do not exist for most patients with potentially curable genetic abnormalities, an alternative treatment for such patients involves the transfer of cloned genes into the patient's haematopoietic stem cells followed by re-infusion of the treated cells. Retroviral vectors provide an efficient means for transferring genes into mammalian cells and have been used to transfer genes into mouse haematopoietic cells. We have now produced amphotropic retroviral vectors containing either the bacterial gene for neomycin resistance or a mutant dihydrofolate reductase gene that confers resistance to methotrexate and have used these vectors to infect and confer drug resistance to human haematopoietic progenitor cells in vitro. Transfer could be demonstrated in the absence of helper virus by using an amphotropic retrovirus packaging cell line, PA12 (ref. 9). These studies are an important step towards the eventual application of retrovirus-mediated gene transfer to human gene therapy and for molecular approaches to the study of human haematopoiesis.

Bone Marrow Cells↗

PubMedDate not supplied

Mental retardation facilities as part of the public health services of the community.

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Community Mental Health Services↗

PubMedDate not supplied

Physiological evidence that the vestibular system participates in autonomic and respiratory control.

Electrical or natural stimulation of the vestibular system results in changes in blood pressure and respiratory motor output. An increase in excitatory drive on the sympathetic nervous system occurs during nose-up vestibular stimulation in cats; this response is appropriate to offset orthostatic hypotension that could result from nose-up body rotations during movements such as vertical climbing. In addition, transection of the vestibular nerves in anesthetized or awake cats compromises the ability to correct decreases in blood pressure that result from nose-up body tilt. The vestibular system also has influences on respiratory muscles; these effects are appropriate to participate in making adjustments in the activity of respiratory muscles that are necessary to offset mechanical constraints on these muscles that occur during changes in body position. These data thus suggest that the influences of the vestibular system on the autonomic and respiratory systems serve to maintain homeostasis during movement.

Animals↗