The stimulation of the initiation of DNA synthesis by fibroblast growth factor in swiss 3T3 cells: Interactions with hormones during the pre-replicative phase

Fibroblast Growth Factor (FGF) stimulates quiescent Swiss 3T3 cells to initiate DNA synthesis and divide. Cells begin to enter the S-phase after a lag of 13–15 hr, and the rate of initiation of DNA synthesis in the population can be quantified by a first order rate constant, k. A subsaturating concentration of FGF may establish the lag phase, while the value of k is dependent on the FGF concentration present during the second half of the lag phase. Insulin and hydrocortisone enhance the effect of FGF by increasing k without changing the lag phase, and they can act when added at any time after FGF. Prostaglandin E₁ (PGE₁) causes a decrease in k and a lengthening of the lag phase, and acts only when added during the first 8 hr. None of these agents stimulate DNA synthesis in the absence of FGF. These results show that the stimulation of growth by FGF follows the same basic pattern as was previously shown with Prostaglandin F_2α (PGF_2α). However, since hydrocortisone inhibits stimulation by PGF_2α when added during the first 4 hr of the lag phase, there are clearly differences in some events stimulated by the two growth factors.     

Further evidence for masculinization of female rats by males located caudally in utero

The morphology and behavior of female rodents is partially masculinized as a result of residence near males in the same uterine horn (Clemens effect). Two hypothetical mechanisms have been proposed to account for this effect. In the first hypothesis (“contiguity”) androgens secreted by males in utero are proposed to diffuse across the amniotic membrane, reaching adjacent fetuses. In the second hypothesis (“caudal male”) androgens are transported via the cervical-to-ovarian blood flow and may diffuse directly between closely apposed uterine veins and arteries. This study was designed to test directly which of these mechanisms appears more influential in masculinizing the morphology of female rats. Pregnant Sprague-Dawley rats were decapitated early on Day 22 of gestation and pups were Caesarean delivered. Their anogenital distance and body weight were recorded, location in utero coded by means of footpad tatooing, and each litter fostered to a maternal female. Measurements were taken again when the animals were weaned. Statistical analysis revealed that the presence of one or more males caudal to a female in the uterine horn has a more critical influence on that female's morphology than contiguity per se. Such a mechanism may result in partial masculinization of dimorphic behaviors later in life.     

Characterisation of Tn501, a transposon determining resistance to mercuric ions

Summary The transposon encoding resistance to mercuric ions, Tn501, is 5.2 (±0.1)×10⁶ daltons and is bounded by small inverted repeats. The restriction sites for the restriction endonucleases EcoRI, HindIII and SalGI have been mapped on the element.     

Water metabolism in free-ranging pine voles (Microtus pinetorum)

Rates of body water turnover in free-ranging pine voles exceeded those reported for a large number of similarly sized mammals. Concentrations of urine obtained from free-ranging pine voles were significantly lower than values published for other free-ranging mammals and also for laboratory-maintained members of this species. Rates of body water turnover in this species were not correlated with seasonal changes in soil temperatures.     

Cardiac overexpression of metallothionein rescues cold exposure-induced myocardial contractile dysfunction through attenuation of cardiac fibrosis despite cardiomyocyte mechanical anomalies

Cold exposure is associated with an increased prevalence of cardiovascular disease although the mechanism is unknown. Metallothionein, a heavy-metal-scavenging antioxidant, protects against cardiac anomalies. This study was designed to examine the impact of metallothionein on cold exposure-induced myocardial dysfunction, intracellular Ca(2+) derangement, fibrosis, endoplasmic reticulum (ER) stress, and apoptosis. Echocardiography, cardiomyocyte function, and Masson trichrome staining were evaluated in Friend virus B (FVB) and cardiac-specific metallothionein transgenic mice after cold exposure (3 months, 4 °C). Cold exposure increased plasma levels of norepinephrine, endothelin-1, and TGF-β; reduced plasma NO levels and cardiac antioxidant capacity; enlarged ventricular end-systolic diameter; compromised fractional shortening; promoted reactive oxygen species (ROS) production and apoptosis; and suppressed the ER stress markers Bip, calregulin, and phospho-eIF2α, accompanied by cardiac fibrosis and elevated levels of matrix metalloproteinases and Smad-2/3 in FVB mice. Cold exposure-induced echocardiographic, histological, ER stress, ROS, apoptotic, and fibrotic signaling changes (but not plasma markers) were greatly improved by metallothionein. In vitro metallothionein induction by zinc chloride ablated H(2)O(2)- but not TGF-β-induced cell proliferation in fibroblasts. In summary, our data suggest that metallothionein protects against cold exposure-induced cardiac anomalies possibly through attenuation of myocardial fibrosis.