252 research outputs found
Correlation between nucleotide composition and folding energy of coding sequences with special attention to wobble bases
Background: The secondary structure and complexity of mRNA influences its
accessibility to regulatory molecules (proteins, micro-RNAs), its stability and
its level of expression. The mobile elements of the RNA sequence, the wobble
bases, are expected to regulate the formation of structures encompassing coding
sequences.
Results: The sequence/folding energy (FE) relationship was studied by
statistical, bioinformatic methods in 90 CDS containing 26,370 codons. I found
that the FE (dG) associated with coding sequences is significant and negative
(407 kcal/1000 bases, mean +/- S.E.M.) indicating that these sequences are able
to form structures. However, the FE has only a small free component, less than
10% of the total. The contribution of the 1st and 3rd codon bases to the FE is
larger than the contribution of the 2nd (central) bases. It is possible to
achieve a ~ 4-fold change in FE by altering the wobble bases in synonymous
codons. The sequence/FE relationship can be described with a simple algorithm,
and the total FE can be predicted solely from the sequence composition of the
nucleic acid. The contributions of different synonymous codons to the FE are
additive and one codon cannot replace another. The accumulated contributions of
synonymous codons of an amino acid to the total folding energy of an mRNA is
strongly correlated to the relative amount of that amino acid in the translated
protein.
Conclusion: Synonymous codons are not interchangable with regard to their
role in determining the mRNA FE and the relative amounts of amino acids in the
translated protein, even if they are indistinguishable in respect of amino acid
coding.Comment: 14 pages including 6 figures and 1 tabl
A-type K(+) channels impede supralinear summation of clustered glutamatergic inputs in layer 3 neocortical pyramidal neurons
A-type K+ channels restrain the spread of incoming signals in tufted and apical dendrites of pyramidal neurons resulting in strong compartmentalization. However, the exact subunit composition and functional significance of K+ channels expressed in small diameter proximal dendrites remain poorly understood. We focus on A-type K+ channels expressed in basal and oblique dendrites of cortical layer 3 pyramidal neurons, in ex vivo brain slices from young adult mice. Blocking putative Kv4 subunits with phrixotoxin-2 enhances depolarizing potentials elicited by uncaging RuBi-glutamate at single dendritic spines. A concentration of 4-aminopyridine reported to block Kv1 has no effect on such responses. 4-aminopyridine and phrixotoxin-2 increase supralinear summation of glutamatergic potentials evoked by synchronous activation of clustered spines. The effect of 4-aminopyridine on glutamate responses is simulated in a computational model where the dendritic A-type conductance is distributed homogeneously or in a linear density gradient. Thus, putative Kv4-containing channels depress excitatory inputs at single synapses. The additional recruitment of Kv1 subunits might require the synchronous activation of multiple inputs to regulate the gain of signal integration
The Proteomic Code: a molecular recognition code for proteins
<p>Abstract</p> <p>Background</p> <p>The Proteomic Code is a set of rules by which information in genetic material is transferred into the physico-chemical properties of amino acids. It determines how individual amino acids interact with each other during folding and in specific protein-protein interactions. The Proteomic Code is part of the redundant Genetic Code.</p> <p>Review</p> <p>The 25-year-old history of this concept is reviewed from the first independent suggestions by Biro and Mekler, through the works of Blalock, Root-Bernstein, Siemion, Miller and others, followed by the discovery of a Common Periodic Table of Codons and Nucleic Acids in 2003 and culminating in the recent conceptualization of partial complementary coding of interacting amino acids as well as the theory of the nucleic acid-assisted protein folding.</p> <p>Methods and conclusions</p> <p>A novel cloning method for the design and production of specific, high-affinity-reacting proteins (SHARP) is presented. This method is based on the concept of proteomic codes and is suitable for large-scale, industrial production of specifically interacting peptides.</p
How do anthropogenic contaminants (ACs) affect behaviour? Multi-level analysis of the effects of copper on boldness in hermit crabs
The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes
Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease
Evolution of sex-specific pace-of-life syndromes: genetic architecture and physiological mechanisms
Sex differences in life history, physiology, and behavior are nearly ubiquitous across taxa, owing to sex-specific selection that arises from different reproductive strategies of the sexes. The pace-of-life syndrome (POLS) hypothesis predicts that most variation in such traits among individuals, populations, and species falls along a slow-fast pace-of-life continuum. As a result of their different reproductive roles and environment, the sexes also commonly differ in pace-of-life, with important consequences for the evolution of POLS. Here, we outline mechanisms for how males and females can evolve differences in POLS traits and in how such traits can covary differently despite constraints resulting from a shared genome. We review the current knowledge of the genetic basis of POLS traits and suggest candidate genes and pathways for future studies. Pleiotropic effects may govern many of the genetic correlations, but little is still known about the mechanisms involved in trade-offs between current and future reproduction and their integration with behavioral variation. We highlight the importance of metabolic and hormonal pathways in mediating sex differences in POLS traits; however, there is still a shortage of studies that test for sex specificity in molecular effects and their evolutionary causes. Considering whether and how sexual dimorphism evolves in POLS traits provides a more holistic framework to understand how behavioral variation is integrated with life histories and physiology, and we call for studies that focus on examining the sex-specific genetic architecture of this integration
First measurement of the |t|-dependence of coherent J/Ï photonuclear production
The first measurement of the cross section for coherent J/Ï photoproduction as a function of |t|, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral PbâPb collisions at a centre-of-mass energy per nucleon pair sNN=5.02TeV with the J/Ï produced in the central rapidity region |y|<0.8, which corresponds to the small Bjorken-x range (0.3â1.4)Ă10â3.
The measured |t|-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent BalitskyâKovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken-x.publishedVersio
First measurement of coherent Ï0 photoproduction in ultra-peripheral XeâXe collisions at âsNN = 5.44 TeV
The first measurement of the coherent photoproduction of Ï0 vector mesons in ultra-peripheral XeâXe collisions at sNN=5.44 TeV is presented. This result, together with previous HERA Îłp data and ÎłâPb measurements from ALICE, describes the atomic number (A) dependence of this process, which is particularly sensitive to nuclear shadowing effects and to the approach to the black-disc limit of QCD at a semi-hard scale. The cross section of the Xe+XeâÏ0+Xe+Xe process, measured at midrapidity through the decay channel Ï0âÏ+Ïâ, is found to be dÏ/dy=131.5±5.6(stat.)â16.9+17.5(syst.) mb. The ratio of the continuum to resonant contributions for the production of pion pairs is also measured. In addition, the fraction of events accompanied by electromagnetic dissociation of either one or both colliding nuclei is reported. The dependence on A of cross section for the coherent Ï0 photoproduction at a centre-of-mass energy per nucleon of the ÎłA system of WÎłA,n=65 GeV is found to be consistent with a power-law behaviour Ï(ÎłAâÏ0A)âAα with a slope α=0.96±0.02(syst.). This slope signals important shadowing effects, but it is still far from the behaviour expected in the black-disc limit.publishedVersio
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