DNA methylation and gene expression regulation associated with vascularization in Sorghum bicolor.

Plant secondary cell walls constitute the majority of plant biomass. They are predominantly found in xylem cells, which are derived from vascular initials during vascularization. Little is known about these processes in grass species despite their emerging importance as biomass feedstocks.

Clinical Actionability of Comprehensive Genomic Profiling for Management of Rare or Refractory Cancers.

Background: The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important.

Methods: A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors.

The Genomic Landscape of Renal Oncocytoma Identifies a Metabolic Barrier to Tumorigenesis.

Oncocytomas are predominantly benign neoplasms possessing pathogenic mitochondrial mutations and accumulation of respiration-defective mitochondria, characteristics of unknown significance. Using exome and transcriptome sequencing, we identified two main subtypes of renal oncocytoma. Type 1 is diploid with CCND1 rearrangements, whereas type 2 is aneuploid with recurrent loss of chromosome 1, X or Y, and/or 14 and 21, which may proceed to more aggressive eosinophilic chromophobe renal cell carcinoma (ChRCC).

Whole-genome sequencing analysis of phenotypic heterogeneity and anticipation in Li-Fraumeni cancer predisposition syndrome.

The Li-Fraumeni syndrome (LFS) and its variant form (LFL) is a familial predisposition to multiple forms of childhood, adolescent, and adult cancers associated with germ-line mutation in the TP53 tumor suppressor gene. Individual disparities in tumor patterns are compounded by acceleration of cancer onset with successive generations. It has been suggested that this apparent anticipation pattern may result from germ-line genomic instability in TP53 mutation carriers, causing increased DNA copy-number variations (CNVs) with successive generations.

Single temperature for Monte Carlo optimization on complex landscapes.

We propose a new strategy for Monte Carlo (MC) optimization on rugged multidimensional landscapes. The strategy is based on querying the statistical properties of the landscape in order to find the temperature at which the mean first passage time across the current region of the landscape is minimized. Thus, in contrast to other algorithms such as simulated annealing, we explicitly match the temperature schedule to the statistics of landscape irregularities.

Statistical mechanics of nucleosome ordering by chromatin-structure-induced two-body interactions.

One-dimensional arrays of nucleosomes (DNA-bound histone octamers separated by stretches of linker DNA) fold into higher-order chromatin structures which ultimately make up eukaryotic chromosomes. Chromatin structure formation leads to 10-11 base pair (bp) discretization of linker lengths caused by the smaller free energy cost of packaging nucleosomes into regular chromatin fibers if their rotational setting (defined by the DNA helical twist) is conserved. We describe nucleosome positions along the fiber using a thermodynamic model of finite-size particles with both intrinsic histone-DNA interactions and an effective two-body potential.

Chromatin remodelers clear nucleosomes from intrinsically unfavorable sites to establish nucleosome-depleted regions at promoters.

Most promoters in yeast contain a nucleosome-depleted region (NDR), but the mechanisms by which NDRs are established and maintained in vivo are currently unclear. We have examined how genome-wide nucleosome placement is altered in the absence of two distinct types of nucleosome remodeling activity. In mutants of both SNF2, which encodes the ATPase component of the Swi/Snf remodeling complex, and ASF1, which encodes a histone chaperone, distinct sets of gene promoters carry excess nucleosomes in their NDRs relative to wild-type.

High-throughput sequencing reveals a simple model of nucleosome energetics.

We use genome-wide nucleosome maps to study sequence specificity of intrinsic histone-DNA interactions. In contrast with previous approaches, we employ an analogy between a classical one-dimensional fluid of finite-size particles in an arbitrary external potential and arrays of DNA-bound histone octamers. We derive an analytical solution to infer free energies of nucleosome formation directly from nucleosome occupancies measured in high-throughput experiments.

Genomic studies and computational predictions of nucleosome positions and formation energies.

Chromatin is a complex of DNA, RNA, and proteins whose primary function is to package genomic DNA into the tight confines of a cell nucleus. A fundamental repeating unit of chromatin is the nucleosome, an octamer of histone proteins around which 147 base pairs of DNA are wound in almost two turns of a left-handed superhelix. Chromatin is a dynamic structure that exerts profound influence on regulation of gene expression and other cellular functions.

Power spectrum scale invariance quantifies limbic dysregulation in trait anxious adults using fMRI: adapting methods optimized for characterizing autonomic dysregulation to neural dynamic time series.

In a well-regulated control system, excitatory and inhibitory components work closely together with minimum lag; in response to inputs of finite duration, outputs should show rapid rise and, following the input's termination, immediate return to baseline. The efficiency of this response can be quantified using the power spectrum density's scaling parameter beta, a measure of self-similarity, applied to the first derivative of the raw signal. In this study, we adapted power spectrum density methods, previously used to quantify autonomic dysregulation (heart rate variability), to neural time series obtained via functional MRI.

Chemosensory cues to conspecific emotional stress activate amygdala in humans.

Alarm substances are airborne chemical signals, released by an individual into the environment, which communicate emotional stress between conspecifics. Here we tested whether humans, like other mammals, are able to detect emotional stress in others by chemosensory cues. Sweat samples collected from individuals undergoing an acute emotional stressor, with exercise as a control, were pooled and presented to a separate group of participants (blind to condition) during four experiments.