Conformations of deoxydinucleoside phosphates containing pyrimidine-pyrimidine photodimers

Conformational analysis of deoxydinucleoside monophosphates with the sequences TpT and CpC have been carried out with the incorporation of both cyclobutane type pyrimidine dimers and 6-4 photoadducts using the methods of molecular mechanics energy minimization. The effect of flexibility with respect to sugar geometries and glycosidic torsions have been studied and the relative energies of a large variety of structures have been compared. The salient features obtained from these calculations have been compared with the crystallographic and spectroscopic data on pyrimidine dimer incorporated deoxydinucleoside monophosphates. Effects of "inserting" the energetically favourable conformations of such structures into B-DNA helices have been discussed in terms of the distortions in helical structures.     

Mathematical model of the simple cells in the visual cortex

A mathematical model for the spatial computations performed by simple cells in the mammalian visual cortex is derived. The construction uses as organizing principles the experimentally observed simple cell linearity and rotational symmetry breaking, together with the constraint that simple cell inputs must effectively be ganglion cell outputs. This leads to a closed form expression for the simple cellkernel in terms of Jacobi-functions. Using a-function identity, it is also shown how Gabor sampling arises as an approximation to this exact kernel for most cells. In addition, the model provides a natural mechanism for introducing the type of nonlinearity observed in some simple cells. The cell's responses to a variety of visual stimuli are calculated using the exact kernel and compared to single cell recordings. In all cases, the model's predictions are in agreement with available experimental data.Work supported by the National Science Foundation, grant PHYS86-20266Work supported by the Department of Energy, contract DE-AC02-76ERO2220     

Astrocyte death in organotypic cultures of fetal spinal cord from rats with unilateral micromelia

Growth and differentiation of neurons and glia in spinal cord explants of 16 days old rat fetuses with teratogen-induced left-sided micromelia were studied. Progressive destruction of astrocytes that differentiate in interstitial zone of cultures was observed in 37% of explants of the left side, while the development was normal in cultures of the right side. Possible mechanisms leading to destruction of astrocytes in cultures of spinal cord regions that innervate anomalous limbs are discussed.     

The transformation of the mammalian genome and the teratogenic activity of chloridin

Susceptibility to the effect of teratogen chloridine of three generations produced from transgenic rats with human growth hormone gene was investigated. The offsprings were shown to reveal elevated teratogenic injury as compared with intact animals.     

Dynamic changes in optic fiber terminal arbors lead to retinotopic map formation: an in vivo confocal microscopic study

Dynamic remodeling of retinal ganglion cell terminal arbors has been proposed to contribute to formation of the topographically ordered retinotectal projection. To test this directly, the growth of individual terminal arbors was observed in live X. laevis tadpoles using a confocal microscope to visualize their complex three-dimensional structure. During initial development, nasal and temporal retinal arbors covered overlapping tectal areas. Despite subsequent remodeling, the dimensions and positions of the temporal arbors remained relatively stable. In contrast, the nasal arbors grew caudally, as they extended caudal branches and retracted rostral branches. These results suggest that differences in the remodeling of the nasal and temporal arbors lead to the emergence of retino-topography along the rostrocaudal axis of the tectum. All the terminal arbors were dynamic, including those with stable dimensions, suggesting that continual remodeling of arbors may be a universal feature of neuronal projections.     

A morphometric analysis of individual cell death in bronchial carcinoids

Abstract. The incidence and morphometric characteristics of individual dead cells have been measured in 51 cases of broncho-pulmonary carcinoid tumours. In both typical and atypical carcinoids, these dead cells were distinguished by nuclei that were significantly smaller and less regular than those of 'intact' tumour parenchymal cells. The proportion of dead to all tumour cells was not significantly different for typical and atypical carcinoids (17 and 13%, respectively). For 33 of these tumours, their ploidy status had also been established. In diploid tumours, the proportion of dead cells was 18% and in aneuploid tumours 12%. The prognosis of patients with atypical carcinoids was significantly worse and such tumours were more commonly aneuploid. Thus the incidence of individual cell death does not appear to be positively associated with poor prognosis in this series. The association between 'necrosis' and poor prognosis commented on in the literature may relate more to a different form of cell death, expressed histopathologically as gross coagulative necrosis, the incidence of which is significantly higher among the atypical, aneuploid tumours.     

Isolation and characterization of a variant myoblast cell line that is temperature sensitive for differentiation.

A new variant rat myogenic cell line, ts485, was isolated by subcloning the cell line ts3b2 (H. T. Nguyen, R. M. Medford, and B. Nadal-Ginard, Cell 34:281-293, 1983). Unlike the progenitor cell line, ts485 was thermosensitive for differentiation. Experiments with conditioned medium suggested that diffusible extracellular factors were not involved in dictating the differential phenotypes of ts485 cells cultured at the permissive and nonpermissive temperatures. Temperature shift experiments performed on cultures of ts485 cells indicated that the temperature-sensitive lesion was in a factor active during the growth phase and required to trigger a cascade of events leading to terminal differentiation.     

Biochemical correlates of fatigue. A brief review

Muscle fatigue, defined as a decreased force generating capacity, develops gradually during exercise and is distinct from exhaustion, which occurs when the required force or exercise intensity can no longer be maintained. We have reviewed several biochemical and ionic changes reported to occur in exercising muscle, and analysed the possible effects these changes may have on the electrical and contractile properties of the muscle. There is no evidence that substrate depletion can account for the decreased force generating capacity, but this factor may be important for the rate of energy turnover and be a major determinant for endurance. Increased concentration of inorganic phosphate and hydrogen ions will depress the force generating capacity, but since fatigue can develop gradually without accumulation of these ions they can only be important when aerobic ATP production is insufficient to support the contractions. Evidence is presented showing that a disturbed balance of K+ alone might cause depolarisation block at high stimulation frequencies, but extracellular K+ accumulation does not increase gradually during prolonged dynamic or static exercise, and is therefore not closely related to fatigue. The repeated release of Ca2+ from the sarcoplasmic reticulum (SR) during muscular activity is suggested of Ca2+ by the mitochondria, increasing with stimulation frequency and duration and possibly also deteriorating mitochondrial function. We therefore speculate that decreased Ca2+ availability for release from SR might contribute to a gradual decline in force generating capacity during all types of exercise.