BiP maintains the permeability barrier of the ER membrane by sealing the lumenal end of the translocon pore before and early in translocation

Secretory proteins are cotranslationally translocated across the mammalian ER membrane through an aqueous pore in the translocon while the permeability barrier is maintained by a tight ribosome-membrane junction. The lumenal end of the pore is also blocked early in translocation. Extraction of soluble lumenal proteins from microsomes and reconstitution with purified proteins demonstrate, by fluorescence collisional quenching, that BiP seals the lumenal end of this pore. BiP also seals translocons that are assembled but are not engaged in translocation. These ribosome-free translocons have smaller pores (9-15 A diameter versus 40-60 A in functioning translocons) and are generated when ribosomes dissociate from functioning translocons with large pores. BiP therefore maintains the permeability barrier by sealing both nontranslocating and newly targeted translocons.     

The Australian brushtail possum (Trichosurus vulpecula) gonadotrophin alpha-subunit: analysis of cDNA sequence and pattern of expression

Substantial evidence has accumulated to suggest that in the near future implementation of the veto-cell-suppressor concept in the treatment of kidney allograft recipients might lead to the establishment of life-long specific allograft tolerance in the absence of further immunosuppressive therapy. Veto suppression prevents the generation of antigen-specific T-helper and cytotoxic T lymphocytes in vitro provided that the T-lymphocyte precursors specifically recognize antigenic peptides associated with the major histocompatibility complex molecules class II and class I, respectively, expressed on the surface of the veto-active cell. Data from a large number of experimental and clinical studies strongly indicate that veto-active cells function in vivo and are capable of preventing allograft rejection. Thus, donor-cell-mediated veto activity is the most likely explanation for the well-known graft tolerizing effect of pretransplant donor blood transfusions in kidney graft recipients. A prerequisite for a veto-active environment in vivo is the establishment of lymphoid microchimerism, in which veto-active donor and recipient cells mutually downregulate potential alloaggression.     

The min K channel underlies the cardiac potassium current IKs and mediates species-specific responses to protein kinase C

A clone encoding the guinea pig (gp) min K potassium channel was isolated and expressed in Xenopus oocytes. The currents, gpIsK, exhibit many of the electrophysiological and pharmacological properties characteristic of gpIKs, the slow component of the delayed rectifier potassium conductance in guinea pig cardiac myocytes. Depolarizing commands evoke outward potassium currents that activate slowly, with time constants on the order of seconds. The currents are blocked by the class III antiarrhythmic compound clofilium but not by the sotalol derivative E4031 or low concentrations of lanthanum. Like IKs in guinea pig myocytes, gpIsK is modulated by stimulation of protein kinase A and protein kinase C (PKC). In contrast to rat and mouse IsK, which are decreased upon stimulation of PKC, myocyte IK and gpIsK in oocytes are increased after PKC stimulation. Substitution of an asparagine residue at position 102 by serine (N102S), the residue found in the analogous position of the mouse and rat min K proteins, results in decreased gpIsK in response to PKC stimulation. These results support the hypothesis that the min K protein underlies the slow component of the delayed rectifier potassium current in ventricular myocytes and account for the species-specific responses to stimulation of PKC.     

Respiration and the generation of rhythmic outputs in insects

In insects gas exchange may be: 1) entirely passive, when metabolic rate is low; 2) enhanced automatically by muscle contractions that produce movements, e.g., wing movements in flight; or 3) produced by ventilatory movements, particularly of the abdomen. In terrestrial insects such as locusts and cockroaches ventilatory movements are governed by a dominant oscillator in the metathoracic or anterior abdominal ganglion. The dominant oscillator overrides local oscillators in the abdominal ganglia and thus sets the rhythm for the entire abdomen, and it also controls spiracle opening and closing in several thoracic and abdominal segments. This ventilatory control mechanism appears to be different from that generating metachronal rhythms such as occur in the ventilatory and locomotory movements of aquatic arthropods. There are now several examples of rhythms, both ventilatory and locomotory, that can be generated by the central nervous system in the absence of phasic sensory feedback, but the mechanism of rhythm production is not known. Studies of ganglionic output suggest that neuronal oscillators can produce a range of frequencies and that some oscillators may be employed in more than one function or behavior. The mechanisms by which central oscillators are coupled to the output motorneurons are also not known; large phase changes suggest that in some cases different coupling interneurons are active. Intracellular recordings from identified neurons have begun to clarify the important roles of interneurons in the production of motor patterns.