Effect of metabolic versus respiratory acid-base changes on isolated coronary artery and saphenous vein

Summary Experiments were performed on helically cut strips from coronary artery and saphenous vein to determine the relative influence of metabolic versus respiratory acid-base changes. Tensions were measured over a range of various HCO₃ ^– concentrations and pCO₂'s. The results suggest that tension is influenced by extracellular pH and is independent of pCO₂.Supported by USPHS grant No. HL24232.     

Population coding of saccadic eye movements by neurons in the superior colliculus

The deeper layers of the superior colliculus are involved in the initiation and execution of saccadic (high velocity) eye movements. A large population of coarsely tuned collicular neurons is active before each saccade. The mechanisms by which the signals that precisely control the direction and amplitude of a saccade are extracted from the activity of the population are unknown. It has been assumed that the exact trajectory of a saccade is determined by the activity of the entire population and that information is not extracted from only the most active cells in the population at a subsequent stage of neural processing. The trajectory of a saccade could be based on vector summation of the movement tendencies provided by each member of the population of active neurons or be determined by a weighted average of the vector contributions of each neuron in the active population. Here we present the results of experiments in which a small subset of the active population was reversibly deactivated with lidocaine. These results are consistent with the predictions of the latter population-averaging hypothesis and support the general idea that the direction, amplitude and velocity of saccadic eye movements are based on the responses of the entire population of cells active before a saccadic eye movement.     

A large population of 'Lyman-break' galaxies in a protocluster at redshift z approximately 4.1

The most massive galaxies and the richest clusters are believed to have emerged from regions with the largest enhancements of mass density relative to the surrounding space. Distant radio galaxies may pinpoint the locations of the ancestors of rich clusters, because they are massive systems associated with 'overdensities' of galaxies that are bright in the Lyman-alpha line of hydrogen. A powerful technique for detecting high-redshift galaxies is to search for the characteristic 'Lyman break' feature in the galaxy colour, at wavelengths just shortwards of Lyalpha, which is due to absorption of radiation from the galaxy by the intervening intergalactic medium. Here we report multicolour imaging of the most distant candidate protocluster, TN J1338-1942 at a redshift z approximately 4.1. We find a large number of objects with the characteristic colours of galaxies at that redshift, and we show that this excess is concentrated around the targeted dominant radio galaxy. Our data therefore indicate that TN J1338-1942 is indeed the most distant cluster progenitor of a rich local cluster, and that galaxy clusters began forming when the Universe was only ten per cent of its present age.     

Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer

SINCE insulin was first shown by Scott to crystallize in the presence of zinc ions in 1934, a variety of Zn-containing insulin crystals have been grown. The structures of insulin in the related rhombohedral crystals of 2Zn-insulin and 4Zn-insulin have been solved and reveal that the molecule is a hexamer, organized as three dimers, each containing a 2-fold symmetry axis and held together by Zn ions. In 2Zn-insulin the hexamer is nearly symmetrical with the two axial Zn ions and the two molecules of the dimer related closely by a local 2-fold axis. But in 4Zn-insulin the two molecules in the dimer differ remarkably, creating an asymmetric 4Zn-hexamer in which one trimer is essentially equivalent to that in 2Zn-insulin and the other is different by virtue of an additional stretch of N-terminal helix between residues B1 and B8 (refs 6, 7). We report here the structure of a new symmetrical hexamer, in which all six molecules have the B1-B8 helix seen in 4Zn-insulin. Phenol molecules, found bonding specifically to each molecule, evidently stabilize this new helical conformation.     

Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections

The major function of vascular smooth muscle cells (SMCs) is contraction to regulate blood pressure and flow. SMC contractile force requires cyclic interactions between SMC alpha-actin (encoded by ACTA2) and the beta-myosin heavy chain (encoded by MYH11). Here we show that missense mutations in ACTA2 are responsible for 14% of inherited ascending thoracic aortic aneurysms and dissections (TAAD). Structural analyses and immunofluorescence of actin filaments in SMCs derived from individuals heterozygous for ACTA2 mutations illustrate that these mutations interfere with actin filament assembly and are predicted to decrease SMC contraction. Aortic tissues from affected individuals showed aortic medial degeneration, focal areas of medial SMC hyperplasia and disarray, and stenotic arteries in the vasa vasorum due to medial SMC proliferation. These data, along with the previously reported MYH11 mutations causing familial TAAD, indicate the importance of SMC contraction in maintaining the structural integrity of the ascending aorta.     

Movement selection in advance of action in the superior colliculus.

The primate superior colliculus contains a map of saccadic eye movements. Saccades are high-velocity eye movements to selected targets in the visual field, but little is known about the neural mechanisms responsible for target selection or the related problem of choosing a particular movement from the oculomotor repertoire. Two classes of neurons have been described in the superior colliculus which show bursts of activity before the saccade: discrete bursters display a vigorous pre-saccadic burst and prelude bursters show low-frequency activity as a prelude to burst onset. We have designed experiments to test whether prelude activity is related to saccade selection. Our tasks use a cue to specify which of two physically identical visual stimuli is the goal of an impending saccade. This cue is spatially and temporally isolated from the potential targets as well as from visual cues signalling movement initiation. Our results show that prelude activity occurs shortly after information is available for correct saccade selection and, more importantly, the activity is predictive of saccade choice. The results thus suggest that the superior colliculus participates in the process of saccade selection.     

Blindness and auditory impairment caused by loss of the sodium bicarbonate cotransporter NBC3

Normal sensory transduction requires the efficient disposal of acid (H+) generated by neuronal and sensory receptor activity. Multiple highly sensitive transport mechanisms have evolved in prokaryotic and eukaryotic organisms to maintain acidity within strict limits. It is currently assumed that the multiplicity of these processes provides a biological robustness. Here we report that the visual and auditory systems have a specific requirement for H+ disposal mediated by the sodium bicarbonate cotransporter NBC3 (refs. 7,8). Mice lacking NBC3 develop blindness and auditory impairment because of degeneration of sensory receptors in the eye and inner ear as in Usher syndrome. Our results indicate that in certain sensory organs, in which the requirement to transduce specific environmental signals with speed, sensitivity and reliability is paramount, the choice of the H+ disposal mechanism used is limited.     

Renomedullary deficiency. A contributory factor in the pathogenesis of experimental renal hypertension

Summary The results indicate that renomedullary deficiency induced by renal artery clipping might contribute to the development of renal hypertension.Acknowledgments. The authors are grateful to Dr.B. B. Lozzio for constant help and encouragement. Supported by the American Heart Association grant No. 74-831.