In vitro and in vivo growth and casein gene expression of mouse mammary tumor epithelial cells in response to hormones

Cells from autochthonous mouse mammary carcinomas which display estrogen-independent growth _vivo were studied for their hormonal responses in primary culture. A culture system employing insulin-supplemented, serum-free medium and basement membrane Matrigel as a substratum was used to cultivate tumor cells. The cells did not exhibit in vitro estrogenor prolactin-dependent growth. Primary tumors still displayed a constitutional expression of α-, β-, and γ-casein mRNAs. These messages were dramatically reduced during the culture period. However, seven to eightfold increases in α- and β-casein mRNAs were inducible in the 5-day cultures by treatment with prolactin and hydrocortisone. If the hormones were present through a 2-week culture period, the levels of α-, β-, and γ-casein mRNAs in the cells were maintained and displayed in a time-dependent increase with a peak at 10–14 days. The accumulation of β-casein mRNA in vitro did not require DNA synthesis. Administration of prolactin directly into the growing tumors in vivo could also enhance β-casein mRNA levels in the tumor cells. Morphological studies of the cells cultured in the presence of prolactin and hydrocortisone did not reveal visible changes compared with those without hormonal treatment. Transplantation of tumor cells cultured in the presence or absence of hormones resulted in the development of tumors in mice at approximately the same time. The current studies suggest that the autochthonous mammary tumor cells, independent of estrogen for cell growth, were still inducible for casein gene expression in vitro and in vivo by appropriate hormones. The induction and maintenance of casein messages by a single hormonal treatment did not appear to correlate with morphology and DNA synthesis of cells in vitro or with tumor-producing capacities in vivo.     

The Administration of Cadmium for 2, 3 and 4 Months Causes a Loss of Recognition Memory,Promotes Neuronal Hypotrophy and Apoptosis in the Hippocampus of Rats

Cadmium (Cd) is a toxic metal and classified as a carcinogen whose exposure could affect the function of the central nervous system. There are studies that suggest that Cd promotes neurodegeneration in different regions of the brain, particularly in the hippocampus. It is proposed that its mechanism of toxicity maybe by an oxidative stress pathway, which modifies neuronal morphology and causes the death of neurons and consequently affecting cognitive tasks. However, this mechanism is not yet clear. The aim of the present work was to study the effect of Cd administration on recognition memory for 2, 3 and 4 months, neuronal morphology and immunoreactivity for caspase-3 and 9 in rat hippocampi. The results show that the administration of Cd decreased recognition memory. Likewise, it caused the dendritic morphology of the CA1, CA3 and dentate gyrus regions of the hippocampus to decrease with respect to the time of administration of this heavy metal. In addition, we observed a reduction in the density of dendritic spines as well as an increase in the immunoreactivity of caspase-3 and 9 in the same hippocampal regions of the animals treated with Cd. These results suggest that Cd affects the structure and function of the neurons of the hippocampus, which contribute to the deterioration of recognition memory. Our results suggest that the exposure to Cd represents a critical health problem, which if not addressed quickly, could cause much more serious problems in the quality of life of the human population, as well as in the environment in which they develop.

     

Carbon isotopic record of terrestrial ecosystems spanning the Late Miocene extinction of Oreopithecus bambolii, Baccinello Basin (Tuscany, Italy)

Oreopithecus bambolii is a Late Miocene hominoid with an extensive fossil record in the Baccinello Basin (Tuscany, Italy), and was the only western European hominoid to survive a major extinction event ca. 9.6 Ma (millions of years ago). Oreopithecus lived in the insular Tusco-Sardinian paleobioprovince, where it evolved many unique anatomical specializations that make it important for understanding the mechanisms and history of Late Miocene hominoid evolution. The eventual extinction of Oreopithecus and its associated fauna ca. 6.5 Ma has generally been attributed to interaction with species that arrived from continental Europe following tectonic collision of the Tusco-Sardinian province with mainland Italy, but palynological, paleontological, and sedimentological records indicate an environmental shift toward more variable climate across the extinction event.To explore the possibility of environmental change as a contributing factor in the extinction of Oreopithecus, we developed a stable carbon and oxygen isotope record from organic matter in paleosols from the Baccinello Basin. These data show very low temporal and spatial variability (indicating plant ecosystem stability through time and space) and provide no evidence for ecologically significant changes in floral composition spanning the extinction event, suggesting that environmental change was not an underlying cause for the extinction of Oreopithecus and its associated fauna. The carbon isotope values fall entirely within the range of isotopic variability for modern plants following the C₃ photosynthetic pathway (trees, shrubs, cool-season grasses), indicating that C₄ vegetation (warm-season grasses) was not an important component of biomass. When corrected for temporal variation in the carbon isotopic composition of atmospheric carbon dioxide, the paleosol carbon isotope values are consistent with predicted values based on modern plants and the Baccinello palynoflora, supporting the reliability of paleosol isotopic records as paleoecological proxies.     

Phenotypic noise and the cost of complexity

Experimental studies demonstrate the existence of phenotypic diversity despite constant genotype and environment. Theoretical models based on a single phenotypic character predict that during an adaptation event, phenotypic noise should be positively selected far from the fitness optimum because it increases the fitness of the genotype, and then be selected against when the population reaches the optimum. It is suggested that because of this fitness gain, phenotypic noise should promote adaptive evolution. However, it is unclear how the selective advantage of phenotypic noise is linked to the rate of evolution, and whether any advantage would hold for more realistic, multidimensional phenotypes. Indeed, complex organisms suffer a cost of complexity, where beneficial mutations become rarer as the number of phenotypic characters increases. Using a quantitative genetics approach, we first show that for a one-dimensional phenotype, phenotypic noise promotes adaptive evolution on plateaus of positive fitness, independently from the direct selective advantage on fitness. Second, we show that for multidimensional phenotypes, phenotypic noise evolves to a low-dimensional configuration, with elevated noise in the direction of the fitness optimum. Such a dimensionality reduction of the phenotypic noise promotes adaptive evolution and numerical simulations show that it reduces the cost of complexity.     

Diet and Exercise Interventions Reduce Intrahepatic Fat Content and Improve Insulin Sensitivity in Obese Older Adults

Both obesity and aging increase intrahepatic fat (IHF) content, which leads to nonalcoholic fatty liver disease (NAFLD) and metabolic abnormalities such as insulin resistance. We evaluated the effects of diet and diet in conjunction with exercise on IHF content and associated metabolic abnormalities in obese older adults. Eighteen obese (BMI ≥30 kg/m²) older (≥65 years old) adults completed a 6‐month clinical trial. Participants were randomized to diet (D group; n = 9) or diet + exercise (D+E group; n = 9). Primary outcome was IHF quantified by magnetic resonance spectroscopy (MRS). Secondary outcomes included insulin sensitivity (assessed by oral glucose tolerance), body composition (assessed by dual‐energy X‐ray absorptiometry), physical function (VO_2peak and strength), glucose, lipids, and blood pressure (BP). Body weight (D: ?9 ± 1%, D+E: ?10 ± 2%, both P < 0.05) and fat mass (D: ?13 ± 3%, D+E ?16 ± 3%, both P < 0.05) decreased in both groups but there was no difference between groups. IHF decreased to a similar extent in both groups (D: ?46 ± 11%, D+E: ?45 ± 8%, both P < 0.05), which was accompanied by comparable improvements in insulin sensitivity (D: 66 ± 25%, D+E: 68 ± 28%, both P < 0.05). The relative decreases in IHF correlated directly with relative increases in insulin sensitivity index (ISI) (r = ?0.52; P < 0.05). Improvements in VO_2peak, strength, plasma triglyceride (TG), and low‐density lipoprotein–cholesterol concentration, and diastolic BP occurred in the D+E group (all P < 0.05) but not in the D group. Diet with or without exercise results in significant decreases in IHF content accompanied by considerable improvements in insulin sensitivity in obese older adults. The addition of exercise to diet therapy improves physical function and other obesity‐ and aging‐related metabolic abnormalities.     

Dietary Enrichment with Medium Chain Triglycerides (AC-1203) Elevates Polyunsaturated Fatty Acids in the Parietal Cortex of Aged Dogs: Implications for Treating Age-Related Cognitive Decline

Dogs demonstrate an age-related cognitive decline, which may be related to a decrease in the concentration of omega-3 polyunsaturated fatty acids (n-3 PUFA) in the brain. Medium chain triglycerides (MCT) increase fatty acid oxidation, and it has been suggested that this may raise brain n-3 PUFA levels by increasing mobilization of n-3 PUFA from adipose tissue to the brain. The goal of the present study was to determine whether dietary MCT would raise n-3 PUFA concentrations in the brains of aged dogs. Eight Beagle dogs were randomized to a control diet (n = 4) or an MCT (AC-1203) enriched diet (n = 4) for 2 months. The animals were then euthanized and the parietal cortex was removed for phospholipid, cholesterol and fatty acid determinations by gas-chromatography. Dietary enrichment with MCT (AC-1203) resulted in a significant increase in brain phospholipid and total lipid concentrations (P < 0.05). In particular, n-3 PUFA within the phospholipid, unesterified fatty acid, and total lipid fractions were elevated in AC-1203 treated subjects as compared to controls (P < 0.05). Brain cholesterol concentrations did not differ significantly between the groups (P > 0.05). These results indicate that dietary enrichment with MCT, raises n-3 PUFA concentrations in the parietal cortex of aged dogs.     

Genomewide linkage scan for split-hand/foot malformation with long-bone deficiency in a large Arab family identifies two novel susceptibility loci on chromosomes 1q42.2-q43 and 6q14.1

Split-hand/foot malformation with long-bone deficiency (SHFLD) is a rare, severe limb deformity characterized by tibia aplasia with or without split-hand/split-foot deformity. Identification of genetic susceptibility loci for SHFLD has been unsuccessful because of its rare incidence, variable phenotypic expression and associated anomalies, and uncertain inheritance pattern. SHFLD is usually inherited as an autosomal dominant trait with reduced penetrance, although recessive inheritance has also been postulated. We conducted a genomewide linkage analysis, using a 10K SNP array in a large consanguineous family (UR078) from the United Arab Emirates (UAE) who had disease transmission consistent with an autosomal dominant inheritance pattern. The study identified two novel SHFLD susceptibility loci at 1q42.2-q43 (nonparametric linkage [NPL] 9.8, P=.000065) and 6q14.1 (NPL 7.12, P=.000897). These results were also supported by multipoint parametric linkage analysis. Maximum multipoint LOD scores of 3.20 and 3.78 were detected for genomic locations 1q42.2-43 and 6q14.1, respectively, with the use of an autosomal dominant mode of inheritance with reduced penetrance. Haplotype analysis with informative crossovers enabled mapping of the SHFLD loci to a region of approximately 18.38 cM (8.4 Mb) between single-nucleotide polymorphisms rs1124110 and rs535043 on 1q42.2-q43 and to a region of approximately 1.96 cM (4.1 Mb) between rs623155 and rs1547251 on 6q14.1. The study identified two novel loci for the SHFLD phenotype in this UAE family.     

Predation and disturbance interact to shape prey species diversity

Though predation, productivity (nutrient richness), spatial heterogeneity, and disturbance regimes are known to influence species diversity, interactions between these factors remain largely unknown. Predation has been shown to interact with productivity and with spatial heterogeneity, but few experimental studies have focused on how predation and disturbance interact to influence prey diversity. We used theory and experiments to investigate how these factors influence diversification of Pseudomonas fluorescens by manipulating both predation (presence or absence of Bdellovibrio bacteriovorus) and disturbance (frequency and intensity of disturbance). Our results show that in a homogeneous environment, predation is essential to promote prey species diversity. However, in most but not all treatments, elevated diversity was transitory, implying that the effect of predation on diversity was strongly influenced by disturbance. Both our experimental and theoretical results suggest that disturbance interacts with predation by modifying the interplay of resource and apparent competition among prey.     

Loss of cortical function in mice after decapitation, cervical dislocation, potassium chloride injection, and CO2 inhalation

Electroencephalograms (EEG) and visual evoked potentials (VEP) in mice were recorded to evaluate loss of cortical function during the first 30 s after euthanasia by various methods. Tracheal cannulae (for positive-pressure ventilation, PPV) and cortical surface electrodes were placed in mice anesthetized with inhaled halothane. Succinylcholine was used to block spontaneous breathing in the mice, which then underwent continuous EEG recording. Photic stimuli (1 Hz) were presented to produce VEPs superimposed on the EEG. Anesthesia was discontinued immediately before euthanasia. Compared with that obtained before euthanasia, EEG activity during the 30-s study period immediately after euthanasia was significantly decreased after cervical dislocation (at 5 to 10 s), 100% PPV-CO2 (at 10 to 15 s), decapitation (at 15 to 20 s), and cardiac arrest due to KCl injection (at 20 to 25 s) but not after administration of 70% PPV-CO2. Similarly, these euthanasia methods also reduced VEP amplitude, although 100% PPV-CO2 treatment affected VEP amplitude more than it did EEG activity. Thus, 100% PPV-CO2 treatment significantly decreased VEP beginning 5 to 10 s after administration, with near abolition of VEP by 30 s. VEP amplitude was significantly reduced at 5 to 10 s after cervical dislocation and at 10 to 15 s after decapitation but not after either KCl or 70% PPV-CO2 administration. The data demonstrate that 100% PPV-CO2, decapitation, and cervical dislocation lead to rapid disruption of cortical function as measured by 2 different methods. In comparison, 70% PPV-CO2 and cardiac arrest due to intracardiac KCl injection had less rapid effects on cortical function.