Science and philosophy in early modern Europe: The historiographical significance of the work of Charles B. Schmitt

In his many contributions to the history of science and the history of philosophy, the late Charles Schmitt demonstrated the interdependence of these two spheres of thought in early modern Europe. Schmitt was particularly insistent on a large and positive role for Aristotelian philosophy in the development of early modern science.     

Ablation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathy

Cyclase-associated proteins are highly conserved proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium-regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2’s role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physiological functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects.     

A kinesin-mediated mechanism that couples centrosomes to nuclei

The M-type kinesin isoform, Kif9, has recently been implicated in maintaining a physical connection between the centrosome and nucleus in Dictyostelium discoideum. However, the mechanism by which Kif9 functions to link these two organelles remains obscure. Here we demonstrate that the Kif9 protein is localized to the nuclear envelope and is concentrated in the region underlying the centrosome point of attachment. Nuclear anchorage appears mediated through a specialized transmembrane domain located in the carboxyl terminus. Kif9 interacts with microtubules in in vitro binding assays and effects an endwise depolymerization of the polymer. These results suggest a model whereby Kif9 is anchored to the nucleus and generates a pulling force that reels the centrosome up against the nucleus. This is a novel activity for a kinesin motor, one important for progression of cells into mitosis and to ensure centrosome-nuclear parity in a multinuclear environment.     

Presumptive identification of aminoglycoside antibiotics by the pH susceptibility disc agar-diffusion method.

Using the pH (buffered) sensitivity discs for the agar-diffusion bioassay of aminoglycoside antibiotics, characteristic response curves were obtained. Since the nature of the activities observed are structure-related, this method can serve as a useful aid for primary identification of members of this class of antibiotics.     

In vivo inhibition of the tyrosinase of hamster melanoma with sodium diethyldithiocarbamate.

In vivo inhibition of the DOPA-oxydase activity of the soluble tyrosinase fraction of melanotic hamster melanoma is found after i.p. administration of diethyldithiocarbamate, with considerable increase in the content of SH-groups which probably play the role of free radical scavengers.     

Adrenergic reinnervation of the denervated rat urinary bladder.

In rats undergoing unilateral extirpation of the pelvic ganglion, the adrenergic innervation disappeared on the ipsilateral side of the urinary bladder. It had reappeared after 6--9 weeks.     

Absence of dopamine sensitive adenylate cyclase in the A10 region, the origin of mesolimbic dopamine neurones.

Dopamine (DA) failed to stimulate the adenylate cyclase of the mesolimbic A10 DA nerve cell body area, in contrast to tis activating effect in the nigrostriatal A9 DA cell body area. The enzyme was stimulated by GMPPNP (a GTP analog) and NaF. This indicates the absence in the A 10 cell area of DA receptors with functional coupling on adenylate cyclase, in contrast to the A9 cell area where such DA receptors are believed to be located on afferent axon terminals.     

Isoelectric focusing study of radiation damage to dry conalbumin.

The effect of gamma-rays on iron-free conalbumin was studied by isoelectric focusing technique. The results obtained can be interpreted on the basis of radiation-induced conformational changes of the macromolecules through a cleavage of disulphide bridges. Treatments with reagents acting on disulphide bridges lead to isoelectric focusing patterns that confirm this hypothesis.