Cardiac Restricted Overexpression of Membrane Type-1 Matrix Metalloproteinase Causes Adverse Myocardial Remodeling following Myocardial Infarction

The membrane type-1 matrix metalloproteinase (MT1-MMP) is a unique member of the MMP family, but induction patterns and consequences of MT1-MMP overexpression (MT1-MMPexp), in a left ventricular (LV) remodeling process such as myocardial infarction (MI), have not been explored. MT1-MMP promoter activity (murine luciferase reporter) increased 20-fold at 3 days and 50-fold at 14 days post-MI. MI was then induced in mice with cardiac restricted MT1-MMPexp (n = 58) and wild type (WT, n = 60). Post-MI survival was reduced (67% versus 46%, p < 0.05), and LV ejection fraction was lower in the post-MI MT1-MMPexp mice compared with WT (41 ± 2 versus 32 ± 2%,p < 0.05). In the post-MI MT1-MMPexp mice, LV myocardial MMP activity, as assessed by radiotracer uptake, and MT1-MMP-specific proteolytic activity using a specific fluorogenic assay were both increased by 2-fold. LV collagen content was increased by nearly 2-fold in the post-MI MT1-MMPexp compared with WT. Using a validated fluorogenic construct, it was discovered that MT1-MMP proteolytically processed the pro-fibrotic molecule, latency-associated transforming growth factor-1 binding protein (LTBP-1), and MT1-MMP-specific LTBP-1 proteolytic activity was increased by 4-fold in the post-MI MT1-MMPexp group. Early and persistent MT1-MMP promoter activity occurred post-MI, and increased myocardial MT1-MMP levels resulted in poor survival, worsening of LV function, and significant fibrosis. A molecular mechanism for the adverse LV matrix remodeling with MT1-MMP induction is increased processing of pro-fibrotic signaling molecules. Thus, a proteolytically diverse portfolio exists for MT1-MMP within the myocardium and likely plays a mechanistic role in adverse LV remodeling.     

Inhibition of myeloid differentiation by inhibitors of ADP-ribosylation

Inhibitors of ADP-ribosylation inhibited the myeloid differentiation of murine myelomonocytic leukemia, WEHI-3BD+ cells induced by granulocyte colony-stimulating factor. Benzamide, at 2.0 mM, inhibited 50% of the WEHI-3BD+ cell differentiation but had no significant effect on the proliferation. However, benzylaminododecylguanine hydrochloride and p-methoxylbenzylaminodecamethylene guanidine sulfate at 2.0 and 2.2 microM, respectively, inhibited 50% of proliferation but had no effect at all on differentiation. The differential effects of inhibitors provide a model to study the role of ADP-ribosylation in myeloid differentiation.     

Stimulation of the protein synthetic process by adenosine 3':5'-monophosphate and hexose phosphates in gel-filtered rabbit reticulocyte lysates.

The addition of 0.167 to 4.0 mM cAMP to gel-filtered rabbit reticulocyte lysates stimulates the initial rate and the extent of polypeptide synthesis. The stimulation is at the initiation step of polypeptide synthesis as measured by the (i) increased dipeptide, methionyl-valine, accumulation in the presence of the specific initiation inhibitor, pactamycin, and (ii) increased formation of the 40 S and 80 S initiation complex when gel-filtered lysates are incubated with [35S]Met-tRNAFMet. Furthermore, a synergistic stimulation of protein synthesis is observed when cAMP and hexose phosphates (which alone elicit a 1.8-fold stimulation of protein synthesis) are added simultaneously to gel-filtered rabbit reticulocyte lysates. These results indicate that cAMP and hexose phosphates are both essential to maintain the high rate of initiation.     

THE PRIMARY ROOT EPIDERMIS OF PANICUM VIRGATUM L. I. ONTOGENY AND FINE STRUCTURE OF THE EPIDERMAL CYTOPLASMIC INCLUSIONS

The ontogeny of large, globular, epidermal cytoplasmic inclusions (ECI) in P. virgatum roots was studied at the ultrastructural level. These ECI were seen to originate in meristematic cells as small electron translucent vesicles. Subsequently, the ECI, which appeared to be temporary storage sites, were seen to enlarge and increase in density by accumulating masses of a granular matrix as well as some small vesicular inclusions. In the zone of elongation, as the epidermal cells matured, the ECI within each cell gradually fused and the contents were lost. The pattern of the ontogeny of the ECI in the growing epidermal cells was consistent with the presence of cells of different physiologies in the zone of cell elongation of these roots.     

Structure and function of the head in flabelligerid polychaetes

The functional anatomy of the head of Flabelliderma commensalis is described and compared to other flabelligerid polychaetes. Prostomial parts include the dorsal lip, the palps, two pairs of nuchal organs, four eyes and the prostomial lobe and ridge. The eyes are inverse pigment cup types with the medial portions of the sensory cells expanded to form a clear lens-like body. Peristomial parts include the median and ventral lips, the branchial membrane and the branchiae. The derivation of the nephridiopore is unknown. The spiraled branchiae of Coppingeria and the gill books of Diplocirrus are newly described variations in branchial structure. The head is retractable in some species and the anterior setigers are modified to form a protective setal cage. Two methods are employed for feeding: one for host fecal pellets and the other for detrital materials. Chemoreception, respiration, feeding and cleaning rely on a complex pattern of ciliary currents.