Bruce Springsteen: Voice of the Working Class

This paper explores the notion of Bruce Springsteen as the voice of the working class. It touches on Springsteen’s background and he development of his working class identity. It then goes onto discuss how Springsteen’s working class identity is portrayed in his writing in a generalized fashion to represent a large portion of working class people. He does this through storytelling and the creation of characters. Springsteen also looks to represent common emotions rather than specific circumstances. Specific examples from Springsteen’s writing are given. The paper also examines how Springsteen has advocated for the working class people both through his music and other means. Overall, the central idea is that Springsteen has used his platform and experiences to speak for the working class people in such a way that they cannot be ignored

Modeling Gene Expression with Differential Equations

Gene expression is the process by which the information stored in DNA is convertedinto a functional gene product, such as protein. The two main functions that makeup the process of gene expression are transcription and translation. Transcriptionand translation are controlled by the number of mRNA and protein in the cell. Geneexpression can be represented as a system of first order differential equations for the rateof change of mRNA and proteins. These equations involve transcription, translation,degradation and feedback loops. In this paper, I investigate a system of first orderdifferential equations to model gene expression proposed by Hunt, Laplace, Miller andPham in their technical report, “A Continuous Model of Gene Expression”, as wellas past models that inspired theirs. I solve the model by Hunt et al. for variousequilibrium points and analyze those points through eigenvalues and bifurcations to understand the biological relevance

Synthesis and pharmacological profiling of analogues of benzyl quinolone carboxylic acid (BQCA) as allosteric modulators of the M1 muscarinic receptor

Established therapy in Alzheimer’s disease involves potentiation of the endogenous orthosteric ligand, acetylcholine, at the M1 muscarinic receptors found in higher concentrations in the cortex and hippocampus. Adverse effects, due to indiscriminate activation of other muscarinic receptor subtypes, are common. M1 muscarinic positive allosteric modulators/allosteric agonists such as BQCA offer an attractive solution, being exquisitely M1-selective over other muscarinic subtypes. A common difficulty with allosteric ligands is interpreting SAR, based on composite potency values derived in the presence of fixed concentration of agonist. In reality these values encompass multiple pharmacological parameters, each potentially and differentially sensitive to structural modification of the ligand. We report novel BQCA analogues which appear to augment ligand affinity for the receptor (pKB), intrinsic efficacy (τB), and both binding (α) and functional (β) cooperativity with acetylcholine. Ultimately, development of such enriched SAR surrounding allosteric modulators will provide insight into their mode of action

Soil chemical properties affect the reaction of forest soil bacteria to drought and rewetting stress

Reaction of soil bacteria to drought and rewetting stress may depend on soil chemical properties. The objectives of this study were to test the reaction of different bacterial phyla to drought and rewetting stress and to assess the influence of different soil chemical properties on the reaction of soil bacteria to this kind of stress. The soil samples were taken at ten forest sites and measured for pH and the contents of organic C (C(org)) and total N (N(t)), Zn, Cu, and Pb. The samples were kept without water addition at 20 – 30 °C for 8 weeks and subsequently rewetted to achieve moisture equal to 50 – 60 % of their maximum water-holding capacity. Prior to the drought period and 24 h after the rewetting, the structure of soil bacterial communities was determined using pyrosequencing of 16S rRNA genes. The drought and rewetting stress altered bacterial community structure. Gram-positive bacterial phyla, Actinobacteria and Firmicutes, increased in relative proportion after the stress, whereas the Gram-negative bacteria in most cases decreased. The largest decrease in relative abundance was for Gammaproteobacteria and Bacteroidetes. For several phyla the reaction to drought and rewetting stress depended on the chemical properties of soils. Soil pH was the most important soil property influencing the reaction of a number of soil bacterial groups (including all classes of Proteobacteria, Bacteroidetes, Acidobacteria, and others) to drought and rewetting stress. For several bacterial phyla the reaction to the stress depended also on the contents of N(t) and C(org) in soil. The effect of heavy metal pollution was also noticeable, although weaker compared to other chemical soil properties. We conclude that soil chemical properties should be considered when assessing the effect of stressing factors on soil bacterial communities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13213-014-1002-0) contains supplementary material, which is available to authorized users

Mechanistic insights into allosteric structure-function relationships at the M1 muscarinic acetylcholine receptor

Background: Selective and potent positive allosteric modulators (PAMs) of the M1 mAChR have been recently described. Results: Use of structural analogues and mutagenic mapping identified the mechanistic basis for increased PAM activity. Conclusion: Combined analytical, structure-function, and modeling approaches uncover allosteric mechanisms at the M1 mAChR. Significance: New chemical space can be explored in the development of tailored M1 mAChR PAMs

Heart transcriptome of the bank vole (Myodes glareolus): towards understanding the evolutionary variation in metabolic rate

Longer reads and higher sequence yield per run provided by the 454 Titanium technology in comparison to earlier generations of pyrosequencing proved beneficial for the quality of assembly. An almost full representation of genes known to be expressed in the mouse heart was identified. Usage of the extensive genomic resources available for the house mouse, a moderately (20-40 mln years) divergent relative of the voles, enabled a comprehensive assessment of the transcript completeness. Transcript sequences generated in the present study allowed the identification of candidate SNPs associated with divergence of selection lines and constitute a valuable permanent resource forming a foundation for RNAseq experiments aiming at detection of adaptive changes both at the level of gene expression and sequence variants, that would facilitate studies of the genetic basis of evolutionary divergence

Tetra­chlorido(2,3-di-2-pyridylpyrazine-κ2 N 1,N 2)platinum(IV)

In the title complex, [PtCl4(C14H10N4)], the PtIV atom is six-coordinated in an octa­hedral configuration by two N atoms from one 2,3-di-2-pyridylpyrazine ligand and four terminal Cl atoms. Inter­molecular C—H⋯Cl and C—H⋯N hydrogen bonds stabilize the crystal structure

Evolution of major histocompatibility complex class I and class II genes in the brown bear

International audienceBackground: Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae . Results: We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (d N ) exceeded the rate of synonymous substitutions (d S ) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca. Conclusions: Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South - north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia

No evidence for the effect of MHC on male mating success in the brown bear

Mate choice is thought to contribute to the maintenance of the spectacularly high polymorphism of the Major Histocompatibility Complex (MHC) genes, along with balancing selection from parasites, but the relative contribution of the former mechanism is debated. Here, we investigated the association between male MHC genotype and mating success in the brown bear. We analysed fragments of sequences coding for the peptide-binding region of the highly polymorphic MHC class I and class II DRB genes, while controlling for genome-wide effects using a panel of 18 microsatellite markers. Male mating success did not depend on the number of alleles shared with the female or amino-acid distance between potential mates at either locus. Furthermore, we found no indication of female mating preferences for MHC similarity being contingent on the number of alleles the females carried. Finally, we found no significant association between the number of MHC alleles a male carried and his mating success. Thus, our results provided no support for the role of mate choice in shaping MHC polymorphism in the brown bear