Boyle, Glauber, and Newton: The Redintegration Experiment with Saltpeter.

In 1661, Robert Boyle published his Essay on Nitre. In this famous essay, the author of The Sceptical Chymist (1661) introduces and promotes his new Corpuscular Philosophy. Central to this paper was the so-called redintegration or reconstitution experiment with saltpeter. However, this article shows that Boyle borrowed this experiment from Johann Rudolph Glauber, who had given it an alchemical interpretation. By contrast, opening the way to modern chemistry, Boyle gave it a new interpretation within the conceptual framework of his own Mechanical Philosophy. The redintegration experiment is not only important for the history of chemistry. It is very likely that the experiment also inspired Newton in his views on the composition of white light.

Co-Expression Network Analysis Identifies miRNA⁻mRNA Networks Potentially Regulating Milk Traits and Blood Metabolites.

MicroRNAs (miRNA) regulate mRNA networks to coordinate cellular functions. In this study, we constructed gene co-expression networks to detect miRNA modules (clusters of miRNAs with similar expression patterns) and miRNA⁻mRNA pairs associated with blood (triacylglyceride and nonesterified fatty acids) and milk (milk yield, fat, protein, and lactose) components and milk fatty acid traits following dietary supplementation of cows' diets with 5% linseed oil (LSO) (n = 6 cows) or 5% safflower oil (SFO) (n = 6 cows) for 28 days. Using miRNA transcriptome data from mammary tissues of cows for co-expression network analysis, we identified three consensus modules: blue, brown, and turquoise, composed of 70, 34, and 86 miRNA members, respectively. The hub miRNAs (miRNAs with the most connections with other miRNAs) were miR-30d, miR-484 and miR-16b for blue, brown, and turquoise modules, respectively. Cell cycle arrest, and p53 signaling and transforming growth factor⁻beta (TGF-ß) signaling pathways were the common gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched for target genes of the three modules. Protein percent (p = 0.03) correlated with the turquoise module in LSO treatment while protein yield (p = 0.003) and milk yield (p = 7 × 10-04) correlated with the turquoise model, protein and milk yields and lactose percent (p < 0.05) correlated with the blue module and fat percent (p = 0.04) correlated with the brown module in SFO treatment. Several fatty acids correlated (p < 0.05) with the blue (CLA:9,11) and brown (C4:0, C12:0, C22:0, C18:1n9c and CLA:10,12) modules in LSO treatment and with the turquoise (C14:0, C18:3n3 and CLA:9,11), blue (C14:0 and C23:0) and brown (C6:0, C16:0, C22:0, C22:6n3 and CLA:10,12) modules in SFO treatment. Correlation of miRNA and mRNA data from the same animals identified the following miRNA⁻mRNA pairs: miR-183/RHBDD2 (p = 0.003), miR-484/EIF1AD (p = 0.011) and miR-130a/SBSPON (p = 0.004) with lowest p-values for the blue, brown, and turquoise modules, respectively. Milk yield, protein yield, and protein percentage correlated (p < 0.05) with 28, 31 and 5 miRNA⁻mRNA pairs, respectively. Our results suggest that, the blue, brown, and turquoise modules miRNAs, hub miRNAs, miRNA⁻mRNA networks, cell cycle arrest GO term, p53 signaling and TGF-ß signaling pathways have considerable influence on milk and blood phenotypes following dietary supplementation of dairy cows' diets with 5% LSO or 5% SFO.

Transcriptome adaptation of the bovine mammary gland to diets rich in unsaturated fatty acids shows greater impact of linseed oil over safflower oil on gene expression and metabolic pathways.

BACKGROUND: Nutritional strategies can decrease saturated fatty acids (SFAs) and increase health beneficial fatty acids (FAs) in bovine milk. The pathways/genes involved in these processes are not properly defined. Next-generation RNA-sequencing was used to investigate the bovine mammary gland transcriptome following supplemental feeding with 5% linseed oil (LSO) or 5% safflower oil (SFO). Holstein cows in mid-lactation were fed a control diet for 28 days (control period) followed by supplementation with 5% LSO (12 cows) or 5% SFO (12 cows) for 28 days (treatment period). Milk and mammary gland biopsies were sampled on days-14 (control period), +7 and +28 (treatment period). Milk was used to measure fat(FP)/protein(PP) percentages and individual FAs while RNA was subjected to sequencing. RESULTS: Milk FP was decreased by 30.38% (LSO) or 32.42% (SFO) while PP was unaffected (LSO) or increased (SFO). Several beneficial FAs were increased by LSO (C18:1n11t, CLA:10t12c, CLA:9c11t, C20:3n3, C20:5n3, C22:5n3) and SFO (C18:1n11t, CLA:10t12c, C20:1c11, C20:2, C20:3n3) while several SFAs (C4:0, C6:0, C8:0, C14:0, C16:0, C17:0, C24:0) were decreased by both treatments (P < 0.05). 1006 (460 up- and 546 down-regulated) and 199 (127 up- and 72 down-regulated) genes were significantly differentially regulated (DE) by LSO and SFO, respectively. Top regulated genes (≥ 2 fold change) by both treatments (FBP2, UCP2, TIEG2, ANGPTL4, ALDH1L2) are potential candidate genes for milk fat traits. Involvement of SCP2, PDK4, NQO1, F2RL1, DBI, CPT1A, CNTFR, CALB1, ACADVL, SPTLC3, PIK3CG, PIGZ, ADORA2B, TRIB3, HPGD, IGFBP2 and TXN in FA/lipid metabolism in dairy cows is being reported for the first time. Functional analysis indicated similar and different top enriched functions for DE genes. DE genes were predicted to significantly decrease synthesis of FA/lipid by both treatments and FA metabolism by LSO. Top canonical pathways associated with DE genes of both treatments might be involved in lipid/cholesterol metabolism. CONCLUSION: This study shows that rich α-linolenic acid LSO has a greater impact on mammary gland transcriptome by affecting more genes, pathways and processes as compared to SFO, rich in linoleic acid. Our study suggest that decrease in milk SFAs was due to down-regulation of genes in the FA/lipid synthesis and lipid metabolism pathways while increase in PUFAs was due to increased availability of ruminal biohydrogenation metabolites that were up taken and incorporated into milk or used as substrate for the synthesis of PUFAs.

Deep sequencing shows microRNA involvement in bovine mammary gland adaptation to diets supplemented with linseed oil or safflower oil.

BACKGROUND: Bovine milk fat composition is responsive to dietary manipulation providing an avenue to modify the content of fatty acids and especially some specific unsaturated fatty acid (USFA) isomers of benefit to human health. MicroRNAs (miRNAs) regulate gene expression but their specific roles in bovine mammary gland lipogenesis are unclear. The objective of this study was to determine the expression pattern of miRNAs following mammary gland adaptation to dietary supplementation with 5 % linseed or safflower oil using next generation RNA-sequencing. METHODS: Twenty-four Canadian Holstein dairy cows (twelve per treatment) in mid lactation were fed a control diet (total mixed ration of corn:grass silages) for 28 days followed by a treatment period (control diet supplemented with 5 % linseed or safflower oil) of 28 days. Milk samples were collected weekly for fat and individual fatty acid determination. RNA from mammary gland biopsies harvested on day-14 (control period) and on days +7 and +28 (treatment period) from six randomly selected cows per treatment was subjected to small RNA sequencing. RESULTS: Milk fat percentage decreased significantly (P < 0.001) during treatment with the two diets as compared to the control period. The individual saturated fatty acids C4:0, C6:0, C8:0, C14:0 and C16:0 decreased significantly (P < 0.05) while five USFAs (C14:1, C18:1n11t, C20:3n3, C20:5n3 and CLA:t10c12) increased remarkably (P < 0.05) in response to both treatments. Analysis of 361 million sequence reads generated 321 known bovine miRNAs and 176 novel miRNAs. The expression of fourteen and twenty-two miRNAs was affected (P < 0.05) by linseed and safflower oil treatments, respectively. Seven miRNAs including six up-regulated (bta-miR-199c, miR-199a-3p, miR-98, miR-378, miR-148b and miR-21-5p) and one down-regulated (bta-miR-200a) were found to be regulated (P < 0.05) by both treatments, and thus considered core differentially expressed (DE) miRNAs. The gene targets of core DE miRNAs have functions related to gene expression and general cellular metabolism (P < 0.05) and are enriched in four pathways of lipid metabolism (3-phosphoinositide biosynthesis, 3-phosphoinositide degradation, D-myo-inisitol-5-phosphate metabolism and the superpathway of inositol phosphate compounds). CONCLUSION: Our results suggest that DE miRNAs in this study might be important regulators of bovine mammary lipogenesis and metabolism. The novel miRNAs identified in this study will further enrich the bovine miRNome repertoire and contribute to understanding mammary gland biology.

Identification of 'carbon hot-spots' and quantification of GHG intensities in the biodiesel supply chain using hybrid LCA and structural path analysis.

It is expected that biodiesel production in the EU will remain the dominant contributor as part of a 10% minimum binding target for biofuel in transportation fuel by 2020 within the 20% renewable energy target in the overall EU energy mix. Life cycle assessments (LCA) of biodiesel to evaluate its environmental impacts have, however, remained questionable, mainly because of the adoption of a traditional process analysis approach resulting in system boundary truncation and because of issues regarding the impacts of land use change and N(2)O emissions from fertilizer application. In this study, a hybrid LCA methodology is used to evaluate the life cycle CO(2) equivalent emissions of rape methyl ester (RME) biodiesel. The methodology uses input-output analysis to estimate upstream indirect emissions in order to complement traditional process LCA in a hybrid framework. It was estimated that traditional LCA accounted for 2.7 kg CO(2)-eq per kg of RME or 36.6% of total life cycle emissions of the RME supply chin. Further to the inclusion of upstream indirect impacts in the LCA system (which accounted for 23% of the total life cycle emissions), emissions due to direct land use change (6%) and indirect land use change (16.5%) and N(2)O emissions from fertilizer applications (17.9%) were also calculated. Structural path analysis is used to decompose upstream indirect emissions paths of the biodiesel supply chain in order to identify, quantify, and rank high carbon emissions paths or 'hot-spots' in the biodiesel supply chain. It was shown, for instance, that inputs from the 'Other Chemical Products' sector (identified as phosphoric acid, H(3)PO(4)) into the biodiesel production process represented the highest carbon emission path (or hot-spot) with 5.35% of total upstream indirect emissions of the RME biodiesel supply chain.

Pediatric training in family practice: a core curriculum.

Official residency guidelines for pediatric training of family practice residents focus on the number of months of block time on pediatric rotations and the percentage of pediatric patients in the resident's model practice. These guidelines do not ensure competence in pediatrics. Family practice residencies need a competency-based curriculum derived from actual pediatric experience in family practice. Such a curriculum should define specific knowledge, skills, and attitudes required, define the family physician's role in handling each issue or condition, be used on a daily basis, and form a basis for evaluation of residents and curriculum. This paper describes the development and implementation of such a pediatric core curriculum at the University of Colorado Family Practice Residency.

Mathematical model of muscular fatigue. I. Metabolite level changes during exercises of different intensities.

To quantify muscular fatigue we study by a mathematical modelization the changes of the levels of ATP and various metabolites, and of the oxygen uptake with the intensity of a requested muscular exercise. The proposed model is consistent with the main phenomena experimentally observed during exercises; it allows also one to extrapolate these experimental results to any condition and to simulate exercise-complete and/or incomplete recovery cycles. The lactate kinetics allows one particularly to justify the empirical optimization of rest rhythms during exercises of long duration. Equations are solved using a 4th order Runge-Kutta method; computations are performed on an IRIS 80 CII computer.

A compound carbon thermometer for the temperature range 0.3-100 K.

A compound carbon thermometer consisting of an abreast connection of a carbon Speer resistor and a carbon Allen-Bradley resistor was tested in the temperature interval 0.3-100 K, an interval which generally requires two independent resistors to be covered. The characteristics, sensitivity, and analytical handling of the resistance versus temperature data are discussed and compared with the corresponding behavior of other thermometers. The satisfactory performance of the compound carbon device contributes to the extension of wide-range thermometry to 0.3 K.

Tissue lipoprotein lipase in the hyperthyroid rat. Effect of growth and aging.

The hydrolysis of lipoprotein triglycerides is catalyzed by lipoprotein lipase (LPL), an enzyme found in many tissues. We have examined tissue LPL activity (LPLA) in rats with experimentally-induced hyperthyroidism. In younger, lighter rats, hyperthyroidism was accompanied by a decrease in LPL in adipose tissue whereas heart and diaphragm muscle LPL activities were increased. These changes are consistent with the hypothesis that the hypercatabolism and increased beta-adrenergic activity of hyperthyroidism result in characteristic changes in tissue LPLA. In older, heavier hyperthyroid animals, however, adipose tissue LPLA was increased and heart and diaphragmatic LPLA were similar to control activities. Propranolol feeding abolished the thyroxine-induced increase in adipose tissue LPLA. In euthyroid animals of similar size the response of muscle LPLA to short-term starvation was also attenuated. These changes in tissue LPLA may provide a mechanism for shunting triglyceride fatty acids away from adipose tissue for utilization by muscle in the hyperthyroid state. During growth and aging, these adaptations are modified.