The " Mendelian Gene " and the " Molecular Gene " : Two Relevant Concepts of Genetic Units

International audienceWe focus here on two prevalent meanings of the word gene in research articles. On one hand, the gene, named here “molecular gene”, is a stretch of DNA that is transcribed and codes for an RNA or a polypeptide with a known or presumed function (as in “gene network'), whose exact spatial delimitation on the chromosome remains a matter of debate, especially in cases with alternative splicing, antisense transcripts, etc. On the other hand, the gene, called here “Mendelian gene”, is a segregating genetic unit which is detected through phenotypic differences associated with different alleles at the same locus (as in “gene flow”). We show that the “Mendelian gene” concept is still extensively used today in biology research and is sometimes confused with the “molecular gene”. We try here to clarify the distinction between both concepts. Efforts to delineate the beginning and the end of the DNA sequence corresponding to the “Mendelian gene” and the “molecular gene” reveal that both entities do not always match. We argue that both concepts are part of two relevant frameworks for explaining the biological world

Nori 1-motives

Let EHM be Nori's category of effective homological mixed motives. In this paper, we consider the thick abelian subcategory EHM_1 generated by the i-th relative homology of pairs of varieties for i = 0,1. We show that EHM_1 is naturally equivalent to the abelian category M_1 of Deligne 1-motives with torsion; this is our main theorem. Along the way, we obtain several interesting results. Firstly, we realize M_1 as the universal abelian category obtained, using Nori's formalism, from the Betti representation of an explicit diagram of curves. Secondly, we obtain a conceptual proof of a theorem of Vologodsky on realizations of 1-motives. Thirdly, we verify a conjecture of Deligne on extensions of 1-motives in the category of mixed realizations for those extensions that are effective in Nori's sense

Numerical Assessment of Morphological and Hydraulic Properties of Moss, Lichen and Peat from a Permafrost Peatland

Due to its insulating and draining role, assessing ground vegetation cover properties is important for high-resolution hydrological modeling of permafrost regions. In this study, morphological and effective hydraulic properties of Western Siberian Lowland ground vegetation samples (lichens, Sphagnum mosses, peat) are numerically studied based on tomography scans. Porosity is estimated through a void voxels counting algorithm, showing the existence of representative elementary volumes (REVs) of porosity for most samples. Then, two methods are used to estimate hydraulic conductivity depending on the sample's homogeneity. For homogeneous samples, direct numerical simulations of a single-phase flow are performed, leading to a definition of hydraulic conductivity related to a REV, which is larger than those obtained for porosity. For heterogeneous samples, no adequate REV may be defined. To bypass this issue, a pore network representation is created from computerized scans. Morphological and hydraulic properties are then estimated through this simplified representation. Both methods converged on similar results for porosity. Some discrepancies are observed for a specific surface area. Hydraulic conductivity fluctuates by 2 orders of magnitude, depending on the method used. Porosity values are in line with previous values found in the literature, showing that arctic cryptogamic cover can be considered an open and well-connected porous medium (over 99 % of overall porosity is open porosity). Meanwhile, digitally estimated hydraulic conductivity is higher compared to previously obtained results based on field and laboratory experiments. However, the uncertainty is less than in experimental studies available in the literature. Therefore, biological and sampling artifacts are predominant over numerical biases. This could be related to compressibility effects occurring during field or laboratory measurements. These numerical methods lay a solid foundation for interpreting the homogeneity of any type of sample and processing some quantitative properties' assessment, either with image processing or with a pore network model. The main observed limitation is the input data quality (e.g., the tomographic scans' resolution) and its pre-processing scheme. Thus, some supplementary studies are compulsory for assessing syn-sampling and syn-measurement perturbations in experimentally estimated, effective hydraulic properties of such a biological porous medium.</p

Exploring T and S parameters in Vector Meson Dominance Models of Strong Electroweak Symmetry Breaking

We revisit the electroweak precision tests for Higgsless models of strong EWSB. We use the Vector Meson Dominance approach and express S and T via couplings characterizing vector and axial spin-1 resonances of the strong sector. These couplings are constrained by the elastic unitarity and by requiring a good UV behavior of various formfactors. We pay particular attention to the one-loop contribution of resonances to T (beyond the chiral log), and to how it can improve the fit. We also make contact with the recent studies of Conformal Technicolor. We explain why the second Weinberg sum rule never converges in these models, and formulate a condition necessary for preserving the custodial symmetry in the IR.Comment: 35 pages, 7 figures; v3: refs added, to appear in JHE

One-Loop Calculation of the Oblique S Parameter in Higgsless Electroweak Models

We present a one-loop calculation of the oblique S parameter within Higgsless models of electroweak symmetry breaking and analyze the phenomenological implications of the available electroweak precision data. We use the most general effective Lagrangian with at most two derivatives, implementing the chiral symmetry breaking SU(2)_L x SU(2)_R -> SU(2)_{L+R} with Goldstones, gauge bosons and one multiplet of vector and axial-vector massive resonance states. Using the dispersive representation of Peskin and Takeuchi and imposing the short-distance constraints dictated by the operator product expansion, we obtain S at the NLO in terms of a few resonance parameters. In asymptotically-free gauge theories, the final result only depends on the vector-resonance mass and requires M_V > 1.8 TeV (3.8 TeV) to satisfy the experimental limits at the 3 \sigma (1\sigma) level; the axial state is always heavier, we obtain M_A > 2.5 TeV (6.6 TeV) at 3\sigma (1\sigma). In strongly-coupled models, such as walking or conformal technicolour, where the second Weinberg sum rule does not apply, the vector and axial couplings are not determined by the short-distance constraints; but one can still derive a lower bound on S, provided the hierarchy M_V < M_A remains valid. Even in this less constrained situation, we find that in order to satisfy the experimental limits at 3\sigma one needs M_{V,A} > 1.8 TeV.Comment: 34 pages, 9 figures. Version published in JHEP. Some references and sentences have been added to facilitate the discussio

Persistent Amyloidosis following Suppression of Aβ Production in a Transgenic Model of Alzheimer Disease

BACKGROUND: The proteases (secretases) that cleave amyloid-β (Aβ) peptide from the amyloid precursor protein (APP) have been the focus of considerable investigation in the development of treatments for Alzheimer disease. The prediction has been that reducing Aβ production in the brain, even after the onset of clinical symptoms and the development of associated pathology, will facilitate the repair of damaged tissue and removal of amyloid lesions. However, no long-term studies using animal models of amyloid pathology have yet been performed to test this hypothesis. METHODS AND FINDINGS: We have generated a transgenic mouse model that genetically mimics the arrest of Aβ production expected from treatment with secretase inhibitors. These mice overexpress mutant APP from a vector that can be regulated by doxycycline. Under normal conditions, high-level expression of APP quickly induces fulminant amyloid pathology. We show that doxycycline administration inhibits transgenic APP expression by greater than 95% and reduces Aβ production to levels found in nontransgenic mice. Suppression of transgenic Aβ synthesis in this model abruptly halts the progression of amyloid pathology. However, formation and disaggregation of amyloid deposits appear to be in disequilibrium as the plaques require far longer to disperse than to assemble. Mice in which APP synthesis was suppressed for as long as 6 mo after the formation of Aβ deposits retain a considerable amyloid load, with little sign of active clearance. CONCLUSION: This study demonstrates that amyloid lesions in transgenic mice are highly stable structures in vivo that are slow to disaggregate. Our findings suggest that arresting Aβ production in patients with Alzheimer disease should halt the progression of pathology, but that early treatment may be imperative, as it appears that amyloid deposits, once formed, will require additional intervention to clear

Modifier Effects between Regulatory and Protein-Coding Variation

Genome-wide associations have shown a lot of promise in dissecting the genetics of complex traits in humans with single variants, yet a large fraction of the genetic effects is still unaccounted for. Analyzing genetic interactions between variants (epistasis) is one of the potential ways forward. We investigated the abundance and functional impact of a specific type of epistasis, namely the interaction between regulatory and protein-coding variants. Using genotype and gene expression data from the 210 unrelated individuals of the original four HapMap populations, we have explored the combined effects of regulatory and protein-coding single nucleotide polymorphisms (SNPs). We predict that about 18% (1,502 out of 8,233 nsSNPs) of protein-coding variants are differentially expressed among individuals and demonstrate that regulatory variants can modify the functional effect of a coding variant in cis. Furthermore, we show that such interactions in cis can affect the expression of downstream targets of the gene containing the protein-coding SNP. In this way, a cis interaction between regulatory and protein-coding variants has a trans impact on gene expression. Given the abundance of both types of variants in human populations, we propose that joint consideration of regulatory and protein-coding variants may reveal additional genetic effects underlying complex traits and disease and may shed light on causes of differential penetrance of known disease variants