ALBERT

Description: Mutations in lamin A/C result in a range of tissue-specific disorders collectively called laminopathies. Of these, Emery–Dreifuss and Limb-Girdle muscular dystrophy 1B mainly affect striated muscle. A useful model for understanding both laminopathies and lamin A/C function is the Lmna –/– mouse. We found that skeletal muscle growth and muscle satellite (stem) cell proliferation were both reduced in Lmna –/– mice. Lamins A and C associate with lamina-associated polypeptide 2 alpha (Lap2α) and the retinoblastoma gene product, pRb, to regulate cell cycle exit. We found Lap2α to be upregulated in Lmna –/– myoblasts (MBs). To specifically test the contribution of elevated Lap2α to the phenotype of Lmna –/– mice, we generated Lmna –/– Lap2α –/– mice. Lifespan and body mass were increased in Lmna –/– Lap2α –/– mice compared with Lmna –/– . Importantly, the satellite cell proliferation defect was rescued, resulting in improved myogenesis. Lmna –/– MBs also exhibited increased levels of Smad2/3, which were abnormally distributed in the cell and failed to respond to TGFβ1 stimulation as in control cells. However, using SIS3 to inhibit signaling via Smad3 reduced cell death and augmented MB fusion. Together, our results show that perturbed Lap2α/pRb and Smad2/3 signaling are important regulatory pathways mediating defective muscle growth in Lmna –/– mice, and that inhibition of either pathway alone or in combination can ameliorate this deleterious phenotype.

Description: This article surveys efforts on text mining of the pharmacogenomics literature, mainly from the period 2008 to 2011. Pharmacogenomics (or pharmacogenetics) is the field that studies how human genetic variation impacts drug response. Therefore, publications span the intersection of research in genotypes, phenotypes and pharmacology, a topic that has increasingly become a focus of active research in recent years. This survey covers efforts dealing with the automatic recognition of relevant named entities (e.g. genes, gene variants and proteins, diseases and other pathological phenomena, drugs and other chemicals relevant for medical treatment), as well as various forms of relations between them. A wide range of text genres is considered, such as scientific publications (abstracts, as well as full texts), patent texts and clinical narratives. We also discuss infrastructure and resources needed for advanced text analytics, e.g. document corpora annotated with corresponding semantic metadata (gold standards and training data), biomedical terminologies and ontologies providing domain-specific background knowledge at different levels of formality and specificity, software architectures for building complex and scalable text analytics pipelines and Web services grounded to them, as well as comprehensive ways to disseminate and interact with the typically huge amounts of semiformal knowledge structures extracted by text mining tools. Finally, we consider some of the novel applications that have already been developed in the field of pharmacogenomic text mining and point out perspectives for future research.

Description: In a world of diminishing water reservoirs and a rising demand for food, the practice and development of water stress indicators and sensors are in rapid progress. The heat dissipation method, originally established by Granier, is herein applied and modified to enable sap flow measurements in date palm trees in the southern Arava desert of Israel. A long and tough sensor was constructed to withstand insertion into the date palm's hard exterior stem. This stem is wide and fibrous, surrounded by an even tougher external non-conducting layer of dead leaf bases. Furthermore, being a monocot species, water flow does not necessarily occur through the outer part of the palm's stem, as in most trees. Therefore, it is highly important to investigate the variations of the sap flux densities and determine the preferable location for sap flow sensing within the stem. Once installed into fully grown date palm trees stationed on weighing lysimeters, sap flow as measured by the modified sensors was compared with the actual transpiration. Sap flow was found to be well correlated with transpiration, especially when using a recent calibration equation rather than the original Granier equation. Furthermore, inducing the axial variability of the sap flux densities was found to be highly important for accurate assessments of transpiration by sap flow measurements. The sensors indicated no transpiration at night, a high increase of transpiration from 06:00 to 09:00, maximum transpiration at 12:00, followed by a moderate reduction until 08:00; when transpiration ceased. These results were reinforced by the lysimeters' output. Reduced sap flux densities were detected at the stem's mantle when compared with its center. These results were reinforced by mechanistic measurements of the stem's specific hydraulic conductivity. Variance on the vertical axis was also observed, indicating an accelerated flow towards the upper parts of the tree and raising a hypothesis concerning dehydrating mechanisms of the date palm tree. Finally, the sensors indicated reduction in flow almost immediately after irrigation of field-grown trees was withheld, at a time when no climatic or phenological conditions could have led to reduction in transpiration.

Description: Motivation: Correlated events of gains and losses enable inference of co-evolution relations. The reconstruction of the co-evolutionary interactions network in prokaryotic species may elucidate functional associations among genes. Results: We developed a novel probabilistic methodology for the detection of co-evolutionary interactions between pairs of genes. Using this method we inferred the co-evolutionary network among 4593 Clusters of Orthologous Genes (COGs). The number of co-evolutionary interactions substantially differed among COGs. Over 40% were found to co-evolve with at least one partner. We partitioned the network of co-evolutionary relations into clusters and uncovered multiple modular assemblies of genes with clearly defined functions. Finally, we measured the extent to which co-evolutionary relations coincide with other cellular relations such as genomic proximity, gene fusion propensity, co-expression, protein–protein interactions and metabolic connections. Our results show that co-evolutionary relations only partially overlap with these other types of networks. Our results suggest that the inferred co-evolutionary network in prokaryotes is highly informative towards revealing functional relations among genes, often showing signals that cannot be extracted from other network types. Availability and implementation: Available under GPL license as open source. Contact: talp@post.tau.ac.il . Supplementary information: Supplementary data are available at Bioinformatics online.

Description: The purpose of this article is to describe connections between the loop space of the 2-sphere and Artin's braid groups. The current article exploits Lie algebras associated with Vassiliev invariants in the work of Kohno ( Linear representations of braid groups and classical Yang-Baxter equations , Cont. Math. 78 (1988), 339–369 and Vassiliev invariants and de Rham complex on the space of knots , Symplectic Geometry and Quantization, Contemp. Math. 179 (1994), Am. Math. Soc. Providence, RI, 123–138), and provides connections between these various topics. Two consequences are as follows: the homotopy groups of spheres are identified as ‘natural’ sub-quotients of free products of pure braid groups, and an axiomatization of certain simplicial groups arising from braid groups is shown to characterize the homotopy types of connected CW -complexes.

Description: Thermal dissipation probes (TDPs) were calibrated in three diffuse porous fruit trees and one ornamental species in the field by comparison with heat pulse probes (nectarine and persimmon), in a greenhouse on lysimeters (apple and persimmon) and in the laboratory by pushing water through cut branches (apple, Peltophorum and nectarine). Two operational methods were used: continuous (constant thermal dissipation, CTD) and discontinuous, or transient, heating (transient thermal dissipation, TTD). Correction for the radial distribution of sap flux density was with an analytical function derived from a linear decrease in flux density with depth, as measured with a multi-depth ‘Tmax’ heat pulse system. When analyzed with previous calibration factors, the measured sap flow was 〈50% of actual value. The underestimations were consistent, and calibrations for each species in the field, greenhouse and laboratory gave approximately the same factors. Reasonable values of tree water use were obtained with the new calibration factors. Evidence is provided that even though the xylem was diffuse porous, the underestimations were caused by contact of the probes with inactive xylem along their length. The average portion of probe in contact with inactive xylem, measured in stained branches following laboratory calibrations, was 0.2–0.24. Using the measured fractions to correct temperature differentials between heated and unheated probes for CTD and TTD, based on Clearwater et al. (in Potential errors in measurement of nonuniform sap flow using heat dissipation probes. Tree Physiol 1999;19:681–687) almost completely compensated for the underestimations. Calibrations are given for each species both before and after corrections of temperature differentials, along with a multispecies calibration. These results should be an important step in reconciling many reports of different calibration factors for TDP probes.

Description: The SIRT6 deacetylase is a key regulator of mammalian genome stability, metabolism and lifespan. Previous studies indicated that SIRT6 exhibits poor deacetylase activity in vitro . Here, we explored the specific conditions that allow SIRT6 to function as a significant deacetylase. We show that SIRT6 associates with the nucleosome and deacetylates histones H3 and H4 when they are packaged as nucleosomes, but not as free histones. In contrast, SIRT1 shows the opposite characteristics. Thus, our results show that SIRT6 activity is nucleosome dependent, and suggest that its binding to the nucleosome might convert it into an active structure.

Description: We present the results of 45 transit observations obtained for the transiting exoplanet HAT-P-32b. The transits have been observed using several telescopes mainly throughout the YETI (Young Exoplanet Transit Initiative) network. In 25 cases, complete transit light curves with a timing precision better than 1.4 min have been obtained. These light curves have been used to refine the system properties, namely inclination i , planet-to-star radius ratio R p / R s , and the ratio between the semimajor axis and the stellar radius a / R s . First analyses by Hartman et al. suggests the existence of a second planet in the system, thus we tried to find an additional body using the transit timing variation (TTV) technique. Taking also the literature data points into account, we can explain all mid-transit times by refining the linear ephemeris by 21 ms. Thus, we can exclude TTV amplitudes of more than ~1.5 min.

Description: We measured velocities of 862 individual red giant stars in seven isolated dwarf galaxies in the Local Group: NGC 6822, IC 1613, VV 124 (UGC 4879), the Pegasus dwarf irregular galaxy (DDO 216), Leo A, Cetus and Aquarius (DDO 210). We also computed velocity dispersions, taking into account the measurement uncertainties on individual stars. None of the isolated galaxies is denser than the densest Local Group satellite galaxy. Furthermore, the isolated dwarf galaxies have no obvious distinction in the velocity dispersion–half-light radius plane from the satellite galaxies of the Milky Way and M31. The similarity of the isolated and satellite galaxies’ dynamics and structural parameters imposes limitations on environmental solutions to the ‘too big to fail’ problem, wherein there are fewer dense dwarf satellite galaxies than would be expected from cold dark matter simulations. This data set also has many other applications for dwarf galaxy evolution, including the transformation of dwarf irregular into dwarf spheroidal galaxies. We intend to explore these issues in future work.