SUMO is a pervasive regulator of meiosis

Protein modification by SUMO helps orchestrate the elaborate events of meiosis to faithfully produce haploid gametes. To date, only a handful of meiotic SUMO targets have been identified. Here, we delineate a multidimensional SUMO-modified meiotic proteome in budding yeast, identifying 2747 conjugation sites in 775 targets, and defining their relative levels and dynamics. Modified sites cluster in disordered regions and only a minority match consensus motifs. Target identities and modification dynamics imply that SUMOylation regulates all levels of chromosome organization and each step of meiotic prophase I. Execution-point analysis confirms these inferences, revealing functions for SUMO in S-phase, the initiation of recombination, chromosome synapsis and crossing over. K15-linked SUMO chains become prominent as chromosomes synapse and recombine, consistent with roles in these processes. SUMO also modifies ubiquitin, forming hybrid oligomers with potential to modulate ubiquitin signaling. We conclude that SUMO plays diverse and unanticipated roles in regulating meiotic chromosome metabolism

X-ray and optical monitoring of the peculiar source 4U 1700+24/V934 Her

(Abridged) We report on ASCA and BeppoSAX observations of the X-ray source 4U 1700+24 and on (quasi-)simultaneous spectroscopy of its optical counterpart, V934 Her, from the Loiano 1.5-meter telescope. Archival ROSAT and RXTE data as well as the RXTE ASM light curve of 4U 1700+24 are also analyzed along with a 1985 EXOSAT pointing. The optical spectra are typical of a M2 III star; a revised distance to the object of ~400 pc is inferred. While these spectra do not show either any change between the two epochs or any peculiar feature, the X-ray spectra reveal a complex and long-term variable shape, with a clear soft excess. The X-ray spectral properties of the source are best described by a thermal Comptonization spectrum plus a soft energy(<1 keV) excess, which can be modeled with a blackbody emission with kT_BB ~ 1 keV; the latter component is not detected at the lowest source flux levels. The ratio between the two components varies substantially with the source flux. The X-ray emission from the object appears to become harder as its luminosity increases, and the RXTE data acquired during an outburst occurred during Fall 1997 display a hard tail detected up to 100 keV. Apart from erratic shot-noise variability on timescales of tens to thousands of seconds, no significant pulsations or QPOs are found from the timing analysis of the X-ray light curves. With the new distance determination, the 2-10 keV X-ray luminosity range spanned in the considered observations lies between ~2x10^32 and ~1x10^34 erg/s. All this allows us to suggest a scenario consisting of a wide binary system in which a neutron star accretes matter from the wind of an M giant.Comment: 14 pages, 5 figures, to be published on Astronomy & Astrophysics, Main Journa

Earliest rock fabric formed in the Solar System preserved in a chondrule rim

Rock fabrics – the preferred orientation of grains – provide a window into the history of rock formation, deformation and compaction. Chondritic meteorites are among the oldest materials in the Solar System1 and their fabrics should record a range of processes occurring in the nebula and in asteroids, but due to abundant fine-grained material these samples have largely resisted traditional in situ fabric analysis. Here we use high resolution electron backscatter diffraction to map the orientation of sub-micrometre grains in the Allende CV carbonaceous chondrite: the matrix material that is interstitial to the mm-sized spherical chondrules that give chondrites their name, and fine-grained rims which surround those chondrules. Although Allende matrix exhibits a bulk uniaxial fabric relating to a significant compressive event in the parent asteroid, we find that fine-grained rims preserve a spherically symmetric fabric centred on the chondrule. We define a method that quantitatively relates fabric intensity to net compression, and reconstruct an initial porosity for the rims of 70-80% - a value very close to model estimates for the earliest uncompacted aggregates2,3. We conclude that the chondrule rim textures formed in a nebula setting and may therefore be the first rock fabric to have formed in the Solar System

Conditional Loss of ErbB3 Delays Mammary Gland Hyperplasia Induced by Mutant PIK3CA without Affecting Mammary Tumor Latency, Gene Expression, or Signaling

Mutations in PIK3CA, the gene encoding the p110α catalytic subunit of phosphatidylinositol-3 kinase (PI3K), have been shown to transform mammary epithelial cells (MECs). Studies suggest this transforming activity requires binding of mutant p110α via p85 to phosphorylated YXXM motifs in activated receptor tyrosine kinases (RTKs) or adaptors. Using transgenic mice, we examined if ErbB3, a potent activator of PI3K, is required for mutant PIK3CA-mediated transformation of MECs. Conditional loss of ErbB3 in mammary epithelium resulted in a delay of PIK3CAH1047R-dependent mammary gland hyperplasia, but tumor latency, gene expression and PI3K signaling were unaffected. In ErbB3-deficient tumors, mutant PI3K remained associated with several tyrosyl phosphoproteins, potentially explaining the dispensability of ErbB3 for tumorigenicity and PI3K activity. Similarly, inhibition of ErbB RTKs with lapatinib did not affect PI3K signaling in PIK3CAH1047R-expressing tumors. However, the p110α-specific inhibitor BYL719, in combination with lapatinib impaired mammary tumor growth and PI3K signaling more potently than BYL719 alone. Further, co-inhibition of p110α and ErbB3 potently suppressed proliferation and PI3K signaling in human breast cancer cells harboring PIK3CAH1047R. These data suggest that PIK3CAH1047R-driven tumor growth and PI3K signaling can occur independently of ErbB RTKs. However, simultaneous blockade of p110α and ErbB RTKs results in superior inhibition of PI3K and mammary tumor growth, suggesting a rational therapeutic combination against breast cancers harboring PIK3CA activating mutations

Application of hierarchical Bayesian unmixing models in river sediment source apportionment

1 .pdf copy (1 Pag.) of the abstract published by the Organization. © Author(s) 2016. CC Attribution 3.0 License.In this contribution, key components of the model are evaluated in the context of common experimental designs for sediment fingerprinting studies namely simple, nested and distributed catchment sampling programmes. Illustrative examples using geochemical and compound specific stable isotope datasets are presented and used to discuss best practice with specific attention to (1) the tracer selection process, (2) incorporation of fixed effects relating to sample timeframe and sediment type in the modelling process, (3) deriving and using informative priors in sediment fingerprinting context and (4) transparency of the process and replication of model results by other users.Peer reviewe

Chromatin Remodeling Pathways in Smooth Muscle Cell Differentiation, and Evidence for an Integral Role for p300

Phenotypic alteration of vascular smooth muscle cells (SMC) in response to injury or inflammation is an essential component of vascular disease. Evidence suggests that this process is dependent on epigenetic regulatory processes. P300, a histone acetyltransferase (HAT), activates crucial muscle-specific promoters in terminal (non-SMC) myocyte differentiation, and may be essential to SMC modulation as well.We performed a subanalysis examining transcriptional time-course microarray data obtained using the A404 model of SMC differentiation. Numerous chromatin remodeling genes (up to 62% of such genes on our array platform) showed significant regulation during differentiation. Members of several chromatin-remodeling families demonstrated involvement, including factors instrumental in histone modification, chromatin assembly-disassembly and DNA silencing, suggesting complex, multi-level systemic epigenetic regulation. Further, trichostatin A, a histone deacetylase inhibitor, accelerated expression of SMC differentiation markers in this model. Ontology analysis indicated a high degree of p300 involvement in SMC differentiation, with 60.7% of the known p300 interactome showing significant expression changes. Knockdown of p300 expression accelerated SMC differentiation in A404 cells and human SMCs, while inhibition of p300 HAT activity blunted SMC differentiation. The results suggest a central but complex role for p300 in SMC phenotypic modulation.Our results support the hypothesis that chromatin remodeling is important for SMC phenotypic switching, and detail wide-ranging involvement of several epigenetic modification families. Additionally, the transcriptional coactivator p300 may be partially degraded during SMC differentiation, leaving an activated subpopulation with increased HAT activity and SMC differentiation-gene specificity

Placental transfusion: a review

Recently there have been a number of studies and presentations on the importance of providing a placental transfusion to the newborn. Early cord clamping is an avoidable, unphysiologic intervention that prevents the natural process of placental transfusion. However, placental transfusion, although simple in concept, is affected by multiple factors, is not always straightforward to implement, and can be performed using different methods, making this basic procedure important to discuss. Here, we review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking and cut-umbilical cord milking, and the evidence in term and preterm newborns supporting this practice. We will also review several factors that influence placental transfusion, and discuss perceived risks versus benefits of this procedure. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution

Differential Impact of Tetratricopeptide Repeat Proteins on the Steroid Hormone Receptors

Tetratricopeptide repeat (TPR) motif containing co-chaperones of the chaperone Hsp90 are considered control modules that govern activity and specificity of this central folding platform. Steroid receptors are paradigm clients of Hsp90. The influence of some TPR proteins on selected receptors has been described, but a comprehensive analysis of the effects of TPR proteins on all steroid receptors has not been accomplished yet.We compared the influence of the TPR proteins FK506 binding proteins 51 and 52, protein phosphatase-5, C-terminus of Hsp70 interacting protein, cyclophillin 40, hepatitis-virus-B X-associated protein-2, and tetratricopeptide repeat protein-2 on all six steroid hormone receptors in a homogeneous mammalian cell system. To be able to assess each cofactor's effect on the transcriptional activity of on each steroid receptor we employed transient transfection in a reporter gene assay. In addition, we evaluated the interactions of the TPR proteins with the receptors and components of the Hsp90 chaperone heterocomplex by coimmunoprecipitation. In the functional assays, corticosteroid and progesterone receptors displayed the most sensitive and distinct reaction to the TPR proteins. Androgen receptor's activity was moderately impaired by most cofactors, whereas the Estrogen receptors' activity was impaired by most cofactors only to a minor degree. Second, interaction studies revealed that the strongly receptor-interacting co-chaperones were all among the inhibitory proteins. Intriguingly, the TPR-proteins also differentially co-precipitated the heterochaperone complex components Hsp90, Hsp70, and p23, pointing to differences in their modes of action.The results of this comprehensive study provide important insight into chaperoning of diverse client proteins via the combinatorial action of (co)-chaperones. The differential effects of the TPR proteins on steroid receptors bear on all physiological processes related to steroid hormone activity

Linking soil microbial community structure to potential carbon mineralization: A continental scale assessment of reduced tillage

Potential carbon mineralization (Cmin) is a commonly used indicator of soil health, with greater Cmin values interpreted as healthier soil. While Cmin values are typically greater in agricultural soils managed with minimal physical disturbance, the mechanisms driving the increases remain poorly understood. This study assessed bacterial and archaeal community structure and potential microbial drivers of Cmin in soils maintained under various degrees of physical disturbance. Potential carbon mineralization, 16S rRNA sequences, and soil characterization data were collected as part of the North American Project to Evaluate Soil Health Measurements (NAPESHM). Results showed that type of cropping system, intensity of physical disturbance, and soil pH influenced microbial sensitivity to physical disturbance. Furthermore, 28% of amplicon sequence variants (ASVs), which were important in modeling Cmin, were enriched under soils managed with minimal physical disturbance. Sequences identified as enriched under minimal disturbance and important for modeling Cmin, were linked to organisms which could produce extracellular polymeric substances and contained metabolic strategies suited for tolerating environmental stressors. Understanding how physical disturbance shapes microbial communities across climates and inherent soil properties and drives changes in Cmin provides the context necessary to evaluate management impacts on standardized measures of soil microbial activity