386 research outputs found
The crystallization of asymmetric patchy models for globular proteins in solution
Asymmetric patchy particle models have recently been shown to describe the
crystallization of small globular proteins with near quantitative accuracy.
Here, we investigate how asymmetry in patch geometry and bond energy generally
impact the phase diagram and nucleation dynamics of this family of soft matter
models. We find the role of the geometry asymmetry to be weak, but the energy
asymmetry to markedly interfere with the crystallization thermodynamics and
kinetics. These results provide a rationale for the success and occasional
failure of George and Wilson's proposal for protein crystallization conditions
as well as physical guidance for developing more effective protein
crystallization strategies.Comment: 10 pages, 8 figure
Stability for the Surface Diffusion Flow
We study the global existence and stability of surface diffusion flow (the
normal velocity is given by the Laplacian of the mean curvature) of smooth
boundaries of subsets of the --dimensional flat torus. More precisely, we
show that if a smooth set is ``close enough'' to a strictly stable critical set
for the Area functional under a volume constraint, then the surface diffusion
flow of its boundary hypersurface exists for all time and asymptotically
converges to the boundary of a ``translated'' of the critical set. This result
was obtained in dimension by Acerbi, Fusco, Julin and Morini (extending
previous results for spheres of Escher, Mayer and Simonett and Elliott and
Garcke in dimension ). Our work generalizes such conclusion to any
dimension . For sake of clarity, we show all the details in
dimension and we list the necessary modifications to the quantities
involved in the proof in the general --dimensional case, in the last
section
Ordered structure of the transcription network inherited from the yeast whole-genome duplication
<p>Abstract</p> <p>Background</p> <p>Gene duplication, a major evolutionary path to genomic innovation, can occur at the scale of an entire genome. One such "whole-genome duplication" (WGD) event among the Ascomycota fungi gave rise to genes with distinct biological properties compared to small-scale duplications.</p> <p>Results</p> <p>We studied the evolution of transcriptional interactions of whole-genome duplicates, to understand how they are wired into the yeast regulatory system. Our work combines network analysis and modeling of the large-scale structure of the interactions stemming from the WGD.</p> <p>Conclusions</p> <p>The results uncover the WGD as a major source for the evolution of a complex interconnected block of transcriptional pathways. The inheritance of interactions among WGD duplicates follows elementary "duplication subgraphs", relating ancestral interactions with newly formed ones. Duplication subgraphs are correlated with their neighbours and give rise to higher order circuits with two elementary properties: newly formed transcriptional pathways remain connected (paths are not broken), and are preferentially cross-connected with ancestral ones. The result is a coherent and connected "WGD-network", where duplication subgraphs are arranged in an astonishingly ordered configuration.</p
Bizonal cardiac engineered tissues with differential maturation features in a mid-throughput multimodal bioreactor
Functional three-dimensional (3D) engineered cardiac tissue (ECT) models are essential for effective drug screening and biological studies. Application of physiological cues mimicking those typical of the native myocardium is known to promote the cardiac maturation and functionality in vitro. Commercially available bioreactors can apply one physical force type at a time and often in a restricted loading range. To overcome these limitations, a millimetric-scalemicroscope-integrated bioreactor was developed to deliver multiple biophysical stimuli to ECTs. In this study, we showed that the single application of auxotonic loading (passive) generated a bizonal ECT with a unique cardiac maturation pattern. Throughout the statically cultured constructs and in the ECT region exposed to high passive loading, cardiomyocytes predominantly displayed a round morphology and poor contractility ability. The ECT region with a low passive mechanical stimulation instead showed both rat- and human-origin cardiac cell maturation and organization, as well as increased ECT functionality
Sex-Specific Incompatibility Generates Locus-Specific Rates of Introgression Between Species
Disruption of interactions among ensembles of epistatic loci has been shown to contribute to reproductive isolation among various animal and plant species. Under the BatesonâDobzhanskyâMuller model, such interspecific incompatibility arises as a by-product of genetic divergence in each species, and the OrrâTurelli model indicates that the number of loci involved in incompatible interactions may âsnowballâ over time. We address the combined effect of multiple incompatibility loci on the rate of introgression at neutral marker loci across the genome. Our analysis extends previous work by accommodating sex specificity: differences between the sexes in the expression of incompatibility, in rates of crossing over between neutral markers and incompatibility loci, and in transmission of markers or incompatibility factors. We show that the evolutionary process at neutral markers in a genome subject to incompatibility selection is well approximated by a purely neutral process with migration rates appropriately scaled to reflect the influence of selection targeted to incompatibility factors. We confirm that in the absence of sex specificity and functional epistasis among incompatibility factors, the barrier to introgression induced by multiple incompatibility factors corresponds to the product of the barriers induced by the factors individually. A new finding is that barriers to introgression due to sex-specific incompatibility depart in general from multiplicativity. Our partitioning of variation in relative reproductive rate suggests that such departures derive from associations between sex and incompatibility and between sex and neutral markers. Concordant sex-specific incompatibility (for example, greater impairment of male hybrids or longer map lengths in females) induces lower barriers (higher rates of introgression) than expected under multiplicativity, and discordant sex-specific incompatibility induces higher barriers
Multimodality Imaging in Cardiomyopathies with Hypertrophic Phenotypes
Multimodality imaging is a comprehensive strategy to investigate left ventricular hypertrophy (LVH), providing morphologic, functional, and often clinical information to clinicians. Hypertrophic cardiomyopathy (HCM) is defined by an increased LV wall thickness not only explainable by abnormal loading conditions. In the context of HCM, multimodality imaging, by different imaging techniques, such as echocardiography, cardiac magnetic resonance, cardiac computer tomography, and cardiac nuclear imaging, provides essential information for diagnosis, sudden cardiac death stratification, and management. Furthermore, it is essential to uncover the specific cause of HCM, such as Fabry disease and cardiac amyloidosis, which can benefit of specific treatments. This review aims to elucidate the current role of multimodality imaging in adult patients with HCM
Suppression of Lung Adenocarcinoma Progression by Nkx2-1
Despite the high prevalence and poor outcome of patients with
metastatic lung cancer the mechanisms of tumour progression and
metastasis remain largely uncharacterized. Here we modelled
human lung adenocarcinoma, which frequently harbours activating
point mutations in KRAS and inactivation of the p53 pathway,
using conditional alleles in mice. Lentiviral-mediated somatic
activation of oncogenic Kras and deletion of p53 in the lung epithelial
cells of Kras[superscript LSL-G12D/+];p53[superscript flox/flox] mice initiates lung adenocarcinoma
development4. Although tumours are initiated synchronously
by defined genetic alterations, only a subset becomes malignant,
indicating that disease progression requires additional alterations.
Identification of the lentiviral integration sites allowed us to distinguish
metastatic from non-metastatic tumours and determine the
gene expression alterations that distinguish these tumour types.
Cross-species analysis identified the NK2-related homeobox transcription
factor Nkx2-1 (also called Ttf-1 or Titf1) as a candidate
suppressor of malignant progression. In this mouse model, Nkx2-1
negativity is pathognomonic of high-grade poorly differentiated
tumours. Gain- and loss-of-function experiments in cells derived
from metastatic and non-metastatic tumours demonstrated that
Nkx2-1 controls tumour differentiation and limitsmetastatic potential
in vivo. Interrogation of Nkx2-1-regulated genes, analysis of
tumours at defined developmental stages, and functional complementation
experiments indicate that Nkx2-1 constrains tumours in
part by repressing the embryonically restricted chromatin regulator
Hmga2. Whereas focal amplification of NKX2-1 in a fraction of
human lung adenocarcinomas has focused attention on its oncogenic
function, our data specifically link Nkx2-1 downregulation
to loss of differentiation, enhanced tumour seeding ability and
increased metastatic proclivity. Thus, the oncogenic and suppressive
functions ofNkx2-1 in the sametumourNational Institutes of Health (U.S.) (grant U01-CA84306 )National Institutes of Health (U.S.) (grant K99-CA151968)Howard Hughes Medical InstituteLudwig Center for Molecular OncologyNational Cancer Institute (U.S.) (Cancer Center Support (core) grant P30-CA14051
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