Direct electrochemistry of proteins. Investigations of yeast cytochrome c mutants and their complexes with cytochrome b5.

Direct electrochemistry of site-specific mutants of yeast iso-1-cytochrome c (cyt c) and their complexes with bovine cytochrome b5 (cyt b5) has been investigated at edge-plane pyrolytic graphite (EPG) and bis(4-pyridyl)-disulphide-modified gold electrodes. Structure/function relationships have been investigated with the particular aim of clarifying the factors controlling the interactions of proteins at electrode/electrolyte interfaces and the determinants for direct electrochemistry in ternary protein/protein/electrode adducts, e.g. cyt c/cyt b5/EPG. Investigations of the cyt c mutants alone revealed a variety of electrochemical responses: all the mutants show similar voltammetric reversibility at modified gold electrodes, whereas at EPG electrodes the reversibility follows the order: Asn52Ile-Cys102Thr greater than Cys102Thr greater than Asn52Ala-Cys102Thr. Mid-point potentials follow the order: Arg13Ile (+60 +/- 5 mV vs. standard calomel electrode) greater than Cys102Thr (+40 +/- 5 mV) greater than Lys27Gln (+30 +/- 5 mV) approximately Lys72Asp (+30 +/- 5 mV) greater than Asn52Ala-Cys102Thr (+15 +/- 5 mV) greater than Asn52Ile-Cys102Thr (-10 +/- 5 mV). The structural basis for these differences is briefly discussed. When these mutants are bound to cyt b5, the differences in electrochemical response are greatly enhanced in the ternary cyt c/cyt b5/EPG adducts. A minimal analysis of these differences supports a model of multiple overlapping binding and recognition domains on cyt c which may be finely tuned to allow ternary complex formation so that a single-site variation could modify or abolish direct electrochemistry in the ternary adduct.     

Co-ordinating interneurones of the locust which convey two patterns of motor commands: their connexions with ventilatory motoneurones.

1. The interneurones which make widespread connexions with flight motoneurones also synapse upon ventilatory motoneurones so that in all 50 motoneurones receive synapses. They influence three aspects of ventilation; (a) the closing and opening movements of the thoracic spiracles, (b) some aspects of abdominal pumping movements and (c) the recruitment of some motoneurones controlling head pumping. 2. The two closer motoneurones of a particular thoracic spiracle receive the same excitatory synaptic inputs (EPSPs) during expiration. The EPSPs match those in appropriate flight motoneurones. 3. The closer motoneurones of each thoracic spiracle whose somata are in the pro-, meso- or metathoracic ganglia all receive the same excitatory synaptic inputs. These inputs are an adequate explanation of the pattern of spikes in the closer motoneurones. Both the slow ventilatory and fast rhythms of synaptic potentials are expressed as spikes; the slow as the overall expiratory burst of spikes and the fast as the groups of spikes within that burst. This establishes a ventilatory function for the interneurones. All thoracic closer motoneurones therefore receive the same excitatory commands which will tend to synchronize the movements of each spiracle. 4. Spiracular opener motoneurones are inhibited during expiration, their IPSPs matching the EPSPs in flight or closer motoneurones. Therefore the interneurones have reciprocal effects on the antagonistic motoneurones of the spiracles. 5. The interneurones synapse upon some motoneurones which control the pumping movements of the abdomen and which have their somata in the metathoracic or first unfused abdominal ganglion. Motoneurones in four separate ganglia therefore receive inputs from these interneurones. 6. The interneurones also synapse upon motoneurones which control an auxiliary form of ventilation, head pumping.     

Isotype switching in human B lymphocyte malignancies occurs by DNA deletion: evidence for nonspecific switch recombination

The mechanism and specificity of isotype switching operative in human B lymphocytes was investigated by a determination of immunophenotype and immunoglobulin heavy and light chain gene status in a panel of human Ig-, IgM, IgG, and IgA B cell malignancies. Regardless of specific tumor type or switched immunophenotype, isotype switching was accompanied by the rearrangement of the expressed CH gene downstream of VDJH, with concomitant deletion of upstream CH genes in all cases. On the allelically excluded chromosome, 25% of the IgG or IgA tumors have retained C mu, and 75% have deleted C mu. The 5' recombination breakpoints for both productive and excluded alleles lie within or near S mu, 3' of the enhancer. No correlation between the extent of allelically excluded CH deletions and the isotype produced by the tumor was observed. Excluded chromosome deletion endpoints were found 5', equal to, or 3' of productive chromosome deletion endpoints. Furthermore, we have identified at least one IgM+ tumor that has undergone abortive CH gene deletions and have observed several unanticipated switch region deletions and potential translocations. The data suggest that isotype switching in human B cells occurs by a nonsubclass- and nonclass-specific switch recombinase.     

3H-Haloperidol binding to tissue receptors: influence of some drugs and antipsychotic potency

The drug concentrations which inhibited 50% of ³H-haloperidol specific binding (the IC₅₀) by striatal receptors of fluphenazine dihydrochloride, 7-hydroxy fluphenazine, chlorpromazine hydrochloride, 7-hydroxy chlorpromazine, pericyazine, and nomifensine were measured: 2.7 nM, 3.3nM, 6.3nM, 4.7nM, 360nM.Fluphenazine sulphoxide and the glucuronide of 7-hydroxychlorpromazine were inactive in competing for binding sites. The IC₅₀ of fluphenazine dihydrochloride, chlorpromazine, and pericyazine followed in the same ranking order as their daily clinical doses as antipsychotics.     

BOOK REVIEWS

Book reviewed in this article:
North America: The Fort Belknap Assiniboine of Montana: a Study in Culture Change. D avid R odnick .
North America: Adventure on Red River. Report on the Exploration of the Headwaters of the Red River by Captain Randolph B. Marcy and Captain G. B. McClellan. G rant F oreman (ed.).
North America: Red Cloud's Folk: a History of the Oglala Sioux Indians. G eorge E. H yde .     

Decline of height with age in adults in a general population sample: estimating maximum height and distinguishing birth cohort effects from actual loss of stature with aging

The decline in stature with age among adults is well documented. Although part of this represents a birth cohort effect, actual height declines among older individuals are known to contribute to the effect. In this study we used longitudinal changes in the heights of adults in a general population sample to determine the rate of decline in height over time in individuals of different ages. This allowed an estimation of the age at which decline in height begins, a value close to age 40 in both sexes. It also allowed derivation of equations from which the maximum height of subjects can be estimated on the basis of their sex, current height, and age. These equations should prove useful when examining the effect of aging per se on physiological measurements that are height dependent. The data also allow one to compare the magnitude of the effect of year of birth with that of the actual decline in height seen among the elderly. We estimate that approximately 60% of the smaller stature of older male subjects and 45% of the smaller stature of older female subjects is a birth cohort effect deriving from the secular trend toward greater stature; the remainder is a result of an actual decrement in height after the age of 40.