Statistical Mechanics of Torque Induced Denaturation of DNA

A unifying theory of the denaturation transition of DNA, driven by temperature T or induced by an external mechanical torque Gamma is presented. Our model couples the hydrogen-bond opening and the untwisting of the helicoidal molecular structure. We show that denaturation corresponds to a first-order phase transition from B-DNA to d-DNA phases and that the coexistence region is naturally parametrized by the degree of supercoiling sigma. The denaturation free energy, the temperature dependence of the twist angle, the phase diagram in the T,Gamma plane and isotherms in the sigma, Gamma plane are calculated and show a good agreement with experimental data.Comment: 5 pages, 3 figures, model improve

The Spitzer Spectroscopic Survey of S-type Stars

S-type AGB stars are thought to be in the transitional phase between M-type and C-type AGB stars. Because of their peculiar chemical composition, one may expect a strong influence of the stellar C/O ratio on the molecular chemistry and the mineralogy of the circumstellar dust. In this paper, we present a large sample of 87 intrinsic galactic S-type AGB stars, observed at infrared wavelengths with the Spitzer Space Telescope, and supplemented with ground-based optical data. On the one hand, we derive the stellar parameters from the optical spectroscopy and photometry, using a grid of model atmospheres. On the other, we decompose the infrared spectra to quantify the flux-contributions from the different dust species. Finally, we compare the independently determined stellar parameters and dust properties. For the stars without significant dust emission, we detect a strict relation between the presence of SiS absorption in the Spitzer spectra and the C/O ratio of the stellar atmosphere. These absorption bands can thus be used as an additional diagnostic for the C/O ratio. For stars with significant dust emission, we define three groups, based on the relative contribution of certain dust species to the infrared flux. We find a strong link between group-membership and C/O ratio. We show that these groups can be explained by assuming that the dust-condensation can be cut short before silicates are produced, while the remaining free atoms and molecules can then form the observed magnesium sulfides or the carriers of the unidentified 13 and 20 micron features. Finally, we present the detection of emission features attributed to molecules and dust characteristic to C-type stars, such as molecular SiS, hydrocarbons and magnesium sulfide grains. We show that we often detect magnesium sulfides together with molecular SiS and we propose that it is formed by a reaction of SiS molecules with Mg.Comment: Accepted for publication in A&

Expression of Msx1 and Dlx1 during Dumbo rat head development: Correlation with morphological features

The Dumbo rat possesses some characteristics that evoke several human syndromes, such as Treacher-Collins: shortness of the maxillary, zygomatic and mandibular bones, and low position of the ears. Knowing that many homeobox genes are candidates in craniofacial development, we investigated the involvement of the Msx1 and Dlx1 genes in the Dumbo phenotype with the aim of understanding their possible role in abnormal craniofacial morphogenesis and examining the possibility of using Dumbo rat as an experimental model for understanding abnormal craniofacial development. We studied the expression of these genes during craniofacial morphogenesis by RT-PCR method. We used Dumbo embryos at E12 and E14 and included the Wistar strain as a control. Semi-quantitative PCR analysis demonstrated that Msx1 and Dlx1 are expressed differently between Dumbo and Wistar rats, indicating that their low expression may underly the Dumbo phenotype

Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used

BACKGROUND:The GOLD multidimensional classification of COPD severity combines the exacerbation risk with the symptom experience, for which 3 different questionnaires are permitted. This study investigated differences in physical activity (PA) in the different GOLD quadrants and patient's distribution in relation to the questionnaire used. METHODS:136 COPD patients (58±21% FEV1 predicted, 34F/102M) completed COPD assessment test (CAT), clinical COPD questionnaire (CCQ) and modified Medical Research Council (mMRC) questionnaire. Exacerbation history, spirometry and 6MWD were collected. PA was objectively measured for 2 periods of 1 week, 6 months apart, in 5 European centres; to minimise seasonal and clinical variation the average of these two periods was used for analysis. RESULTS:GOLD quadrants C+D had reduced PA compared with A+B (3824 [2976] vs. 5508 [4671] steps.d-1, p<0.0001). The choice of questionnaire yielded different patient distributions (agreement mMRC-CAT κ = 0.57; CCQ-mMRC κ = 0.71; CCQ-CAT κ = 0.72) with different clinical characteristics. PA was notably lower in patients with an mMRC score ≥2 (3430 [2537] vs. 5443 [3776] steps.d-1, p <0.001) in both the low and high risk quadrants. CONCLUSIONS:Using different questionnaires changes the patient distribution and results in different clinical characteristics. Therefore, standardization of the questionnaire used for classification is critical to allow comparison of different studies using this as an entry criterion. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov NCT01388218

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

The Changing Face of Winter: Lessons and Questions From the Laurentian Great Lakes

Among its many impacts, climate warming is leading to increasing winter air temperatures, decreasing ice cover extent, and changing winter precipitation patterns over the Laurentian Great Lakes and their watershed. Understanding and predicting the consequences of these changes is impeded by a shortage of winter-period studies on most aspects of Great Lake limnology. In this review, we summarize what is known about the Great Lakes during their 3–6 months of winter and identify key open questions about the physics, chemistry, and biology of the Laurentian Great Lakes and other large, seasonally frozen lakes. Existing studies show that winter conditions have important effects on physical, biogeochemical, and biological processes, not only during winter but in subsequent seasons as well. Ice cover, the extent of which fluctuates dramatically among years and the five lakes, emerges as a key variable that controls many aspects of the functioning of the Great Lakes ecosystem. Studies on the properties and formation of Great Lakes ice, its effect on vertical and horizontal mixing, light conditions, and biota, along with winter measurements of fundamental state and rate parameters in the lakes and their watersheds are needed to close the winter knowledge gap. Overcoming the formidable logistical challenges of winter research on these large and dynamic ecosystems may require investment in new, specialized research infrastructure. Perhaps more importantly, it will demand broader recognition of the value of such work and collaboration between physicists, geochemists, and biologists working on the world\u27s seasonally freezing lakes and seas

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Bmp4 Is Essential for the Formation of the Vestibular Apparatus that Detects Angular Head Movements

Angular head movements in vertebrates are detected by the three semicircular canals of the inner ear and their associated sensory tissues, the cristae. Bone morphogenetic protein 4 (Bmp4), a member of the Transforming growth factor family (TGF-β), is conservatively expressed in the developing cristae in several species, including zebrafish, frog, chicken, and mouse. Using mouse models in which Bmp4 is conditionally deleted within the inner ear, as well as chicken models in which Bmp signaling is knocked down specifically in the cristae, we show that Bmp4 is essential for the formation of all three cristae and their associated canals. Our results indicate that Bmp4 does not mediate the formation of sensory hair and supporting cells within the cristae by directly regulating genes required for prosensory development in the inner ear such as Serrate1 (Jagged1 in mouse), Fgf10, and Sox2. Instead, Bmp4 most likely mediates crista formation by regulating Lmo4 and Msx1 in the sensory region and Gata3, p75Ngfr, and Lmo4 in the non-sensory region of the crista, the septum cruciatum. In the canals, Bmp2 and Dlx5 are regulated by Bmp4, either directly or indirectly. Mechanisms involved in the formation of sensory organs of the vertebrate inner ear are thought to be analogous to those regulating sensory bristle formation in Drosophila. Our results suggest that, in comparison to sensory bristles, crista formation within the inner ear requires an additional step of sensory and non-sensory fate specification