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The macromorphological characteristics and frequency of endocranial abnormal blood vessel impressions (ABVI) and periosteal appositions of dura mater (PADM), and their association with sex, age-at-death and scurvy-like lesions were studied. The possible etiologies of these lesions were discussed. A total of 144 adult skulls excavated from an early modern (16th-19th c. CE) cemetery at the Czysty Square in Wrocław (Poland) were examined, most of which were intact. The endocranial surface was inspected with an endoscope for the presence, location, and severity of ABVI and PADM. Frequencies of ABVI and PADM were grouped by sex and age-at-death. A little more than a half (53.5 %) of the examined skulls were affected by ABVI and/or PADM. PADM were more frequent in females. However, both alteration types occurred with similar frequencies across all age-at-death categories. The high frequency of ABVI and PADM suggests that meningeal infections and/or hemorrhage among inhabitants of early modern Wrocław, especially in females, were common. The paper emphasizes the need for using an endoscope in standard anthropological analysis of intact skulls, as it allows for a nondestructive inspection of the endocranial surface. The endoscope did not allow for an accurate examination of the middle cranial fossa. Comparative studies with other historical populations are necessary to better understand the possible etiologies of macromorphological and demographic characteristics of ABVI and PADM. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2009.12.002 Byline: Jamy C. Peng (1), Anton Valouev (2), Tomek Swigut (1), Junmei Zhang (5), Yingming Zhao (6), Arend Sidow (2)(3), Joanna Wysocka (1)(4) Keywords: STEMCELL; DEVBIO; PROTEINS Abstract: Polycomb Repressive Complex 2 (PRC2) regulates key developmental genes in embryonic stem (ES) cells and during development. Here we show that Jarid2/Jumonji, a protein enriched in pluripotent cells and a founding member of the Jumonji C (JmjC) domain protein family, is a PRC2 subunit in ES cells. Genome-wide ChIP-seq analyses of Jarid2, Ezh2, and Suz12 binding reveal that Jarid2 and PRC2 occupy the same genomic regions. We further show that Jarid2 promotes PRC2 recruitment to the target genes while inhibiting PRC2 histone methyltransferase activity, suggesting that it acts as a 'molecular rheostat' that finely calibrates PRC2 functions at developmental genes. Using Xenopus laevis as a model we demonstrate that Jarid2 knockdown impairs the induction of gastrulation genes in blastula embryos and results in failure of differentiation. Our findings illuminate a mechanism of histone methylation regulation in pluripotent cells and during early cell-fate transitions. Author Affiliation: (1) Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA (2) Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA (3) Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA (4) Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA (5) Protein Chemistry Technology Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA (6) Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA Article History: Received 3 June 2009; Revised 17 August 2009; Accepted 1 December 2009 Article Note: (miscellaneous) Published: December 24, 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2007.09.026 Byline: Tomek Swigut (1), Joanna Wysocka (1) Abstract: Methylation of lysine 27 on histone H3 (H3K27me) by the Polycomb complex (PRC2) proteins is associated with gene silencing in many developmental processes. A cluster of recent papers () identify the JmjC-domain proteins UTX and JMJD3 as H3K27-specific demethylases that remove this methyl mark, enabling the activation of genes involved in animal body patterning and the inflammatory response. Author Affiliation: (1) Department of Chemical and Systems Biology and Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA

A study revealed that LSD1, a nuclear amine oxidase homolog, is a bona fide histone H3 lysine 4 demethylase. Results suggest that LSD1's specificity and activity is in fact regulated by associated protein cofactors.

A common component of MLL1, MLL2, and hSet1 human proteins H3 K4 methyltransferase complexes, the WD40-repeat protein WDR5, directly associates with histone H3 di- and trimethylated at K4 and with H3-K4-dimethlylated nucleosomes is demonstrated. Results show that a WD40-repeat protein acts as a modification and suggest a mechanism for reading and writing an epigenetic mark for gene activation.

A stable complex containing MLL1 and MOF proteins is immunoaffinity purified from a human cell line that stably expresses an epitope-tagged WDR5 subunit. Results indicate an activator-based mechanism for joint MLL1 and MOF recruitment and targeted methylation and acetylation along with a molecular explanation for the closely correlated distribution of Histone-H3 lysine-K4 methylation and H4 K16 acetylation on active genes.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2010.06.013 Byline: Edward J. Grow (1)(2), Joanna Wysocka (2)(3) Abstract: The MLL1 (mixed lineage leukemia 1) protein, which is often disrupted in leukemia, both activates and represses Hox genes during hematopoiesis. Now, demonstrate that the cyclophilin CyP33 underpins this regulatory switch by altering the state of MLL1 through cis-trans proline isomerization in the linker region between MLL1's third PHD finger and bromodomain. Author Affiliation: (1) Department of Genetics, Stanford University, Stanford, CA 94305, USA (2) Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA (3) Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2009.04.008 Byline: Tomek Swigut (1), Joanna Wysocka (1)(2) Abstract: The memory of somatic cell gene expression is reset in the germline in a process that is accompanied by dramatic changes in chromatin modifications. In this issue, show that the histone demethylase Lsd1/Spr-5 may participate in this resetting process in the worm, thereby preventing a decline in germ cell epigenetic stability and viability over ensuing generations. Author Affiliation: (1) Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA (2) Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA

Abstract Various bee products were found to be efficient corrosion inhibitors of aluminium in different environments. In particular, bee pollen was found to be highly effective in alkaline electrolytes, yet its highly complex composition and possible synergistic interactions hinder determination of the compounds acting as active corrosion inhibitors. The main purpose of the following work is to investigate the effect of solvents used for pollen extraction process on the corrosion inhibition of AA5754 alloy in alkaline environment. Both infrared and mass spectroscopies as well as chromatographic analysis were used to determine differences in the composition of each obtained extract. The inhibition efficiency (IE %) of each extract was determined by using the potentiodynamic polarization and impedance studies. The highest IE % , exceeding 90% at 10 gL-1, was recorded for the water/ethanol extract. Most importantly, it has been found that the dichloromethane extract containing less polar compounds enhanced the corrosion rate at low bee pollen concentrations, and offered lower inhibition efficiency at the concentrations above 10 gL-1. The adsorption isotherms were drawn based on dynamic impedance spectroscopy in galvanostatic mode (g-DEIS), while the measurements carried out at elevated temperatures allowed the construction of Arrhenius plots and, consequently, the confirmation of the physical mechanism of adsorption. Graphical abstract Image 1089025 [ABSTRACT FROM AUTHOR]

Abstract The efficiency of AA5754 aluminium alloy corrosion inhibition achieved with maleic, malic, succinic, tartaric, citric, tricarballylic acids and serine in alkaline environment (pH 11) was examined. Selected corrosion inhibitors are characterized by different numbers and distribution of carbonyl and hydroxyl groups within their molecules. We have proposed and verified a novel approach for determining the adsorption isotherms based on the impedance measurements in galvanostatic mode (g-DEIS), allowing to distinguish subtle changes in the adsorption dynamics. It was shown that g-DEIS precisely determines the inhibitor concentration required for the full coverage of aluminium surface with the adsorbed inhibitor monolayer. Our approach was then cross-verified with the ellipsometry, cyclic polarization and classic EIS measurements, while the SEM and XPS analyses served to determine changes in the surface topography and chemistry. We have demonstrated that the investigated compounds significantly decelerate the corrosion rate of AA5754 at low inhibitor concentrations. Inhibition efficiency exceeds 99% at 6.9 mM for tricarballylic, 8.1 mM for citric and 12.0 mM for tartaric acid. The inhibition efficiency was primarily dependent on the high number of carbonyl groups in the molecule, while the inhibition provided by monocarboxylic amino acid (serine) was negligible, reaching 60% at 20 mM. The plotted isotherms fitted the Langmuir adsorption model, with similar values of Gibbs free energy for each studied inhibitor. The adsorption of carboxylic acids onto the surface of aluminium occurred via ligand exchange mechanism. On the basis of electrochemical and XPS studies, we claim that the role played by hydroxyl groups is secondary, while their presence slightly worsens the corrosion resistance of aluminium. Graphical abstract Image [ABSTRACT FROM AUTHOR]

A novel approach is proposed for constructing the adsorption isotherm in corrosion studies, based on a well-known interaction between citric acid and aluminium in alkaline electrolytes. Our approach utilizes the instantaneous impedance measurements via Dynamic Electrochemical Impedance Spectroscopy in galvanostatic mode (g-DEIS). Unlike other common tools, g-DEIS delivers exact information about the concentration required for full surface coverage with adsorbed inhibitor. A significantly larger data set enables observation of multi-stage mechanism of adsorption and complex interaction between citric acid and the metal surface. The obtained impedance results displayed a high convergence with other electrochemical, XPS and SEM studies carried out for verification purposes. It was shown that citric acid exhibits critical concentration with respect to the inhibition efficiency. Chemistry of the adsorbed layer was altered and secondary increase in the corrosion rate was observed in the excess of citric acid, a feature typical for surfactants. Furthermore, authors compared different aluminium alloys with respect to their corrosion resistance mediated by citric acid. The conclusion was reached that regardless of corrosion resistance, the kinetics and mechanism of passive layer formation in Al alloys depends only slightly on alloying additives. AA7020 alloy was an exception because of a specific interaction between zinc and citric acid. [ABSTRACT FROM AUTHOR]

The most common method of determination of cavitation erosion resistance as well as the magnitude of erosion-corrosion synergistic interaction is based on the weight loss measurements. Nondestructive characterization of installations elements is in most cases impossible to perform. Also, such a measurement does not include local types of failure or alteration of operating conditions. There is an urge to elaborate a method for monitoring of cavitation erosion-corrosion damage. The authors used dynamic impedance technique to study change of electric parameters of various engineering alloys under synergistic interaction of cavitation erosion and corrosion in 3% NaCl solution. Monitoring of electric parameters offers a very good resemblance to failure level identified with weight loss function and microscopic analysis. It was possible to distinguish different stages of material degradation by means of instantaneous impedance measurements. Instantaneous value of charge transfer resistance provides information about synergistic influence of mechanical erosion on corrosion. [ABSTRACT FROM AUTHOR]

Transcriptional enhancers are the primary determinants of tissue-specific gene expression. Although the majority of our current knowledge of enhancer elements comes from detailed analyses of individual loci, recent progress in epigenomics has led to the development of methods for comprehensive and conservation-independent annotation of cell type-specific enhancers. Here, we discuss the advantages and limitations of different genomic approaches to enhancer mapping and summarize observations that have been afforded by the genome-wide views of enhancer landscapes, with a focus on development. We propose that enhancers serve as information integration hubs, at which instructions encoded by the genome are read in the context of a specific cellular state, signaling milieu and chromatin environment, allowing for exquisitely precise spatiotemporal control of gene expression during embryogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Background: After surgery and anthracycline adjuvant treatment, about 60% of early advanced breast cancer patients develop recurrence. These differences in treatment outcome indicate the need to identify markers for risk of recurrence. The aim of this study was the retrospective analysis of relationship between tumour features (topoisomerase IIα (TOPOIIα), human epidermal growth factor receptor 2 (HER2), hormone receptors, cytokeratin (CK)5/6 expression and proliferation rate) and disease-free survival (DFS) of breast cancer patients treated with anthracyclines in adjuvant setting. Material and methods: The study was performed in the group of 172 patients (mean age: 52.8 years, T1–T2, N1–N2, M0). HER2, TOPOIIα, estrogen receptor (ER) and progesterone receptor (PgR) expression and proliferation rate were studied immunohistochemically. HER2 overexpression was confirmed by fluorescence in situ hybridisation (FISH). These data were correlated with 5-year DFS. Results: In univariate analysis, lower TOPOIIα expression (median value ≤ 11.9%) and tumour grade G1 + G2 were favourable prognostic factors. All tumours were classified into four subtypes: (1) lower TOPOIIα expression and G1 + G2, (2) lower TOPOIIα expression and G3, (3) higher TOPOIIα expression and G3, and (4) higher TOPOIIα expression and G1 + G2. In Cox multivariate regression analysis, tumour subtype distinguished by TOPOIIα expression and grade was independent prognostic factor for DFS. All patients (n = 52) with TOPOIIα lower expression and G1 + G2 tumours, survived 5 years without any evidence of disease. Conclusion: The results suggest that lower TOPOIIα expression and lower tumour grade are favourable prognostic factors for early advanced breast cancer patients after adjuvant anthracycline chemotherapy. [Copyright &y& Elsevier]

PHD fingers and bromodomains are found in close proximity to each other in many chromatin-associated proteins and can functionally synergize. Recently, it has been demonstrated that the PHD finger of the KAP1 co-repressor functions as an E3 SUMO ligase for the adjacent bromodomain. This PHD-mediated SUMOylation stabilizes the association of the bromodomain with the chromatin modifiers SETDB1 and the nucleosome remodeling and deacetylation (NuRD) complex, thereby promoting establishment of the silent gene expression state. [Copyright &y& Elsevier]

When herpes simplex virus (HSV) infects human cells, it is able to enter two modes of infection: lytic and latent. A key activator of lytic infection is a virion protein called VP16, which, upon infection of a permissive cell, forms a transcriptional regulatory complex with two cellular proteins – the POU-domain transcription factor Oct-1 and the cell-proliferation factor HCF-1 – to activate transcription of the first set of expressed viral genes. This regulatory complex, called the VP16-induced complex, reveals mechanisms of combinatorial control of transcription. The activities of Oct-1 and HCF-1 – two important regulators of cellular gene expression and proliferation – illuminate strategies by which HSV might coexist with its host. [Copyright &y& Elsevier]

Abstract: Allelic frequencies of 15 short tandem repeat (STR) markers (AmpFISTR® Identifiler™) were analyzed using AmpFlSTR® Identifiler™ PCR Amplification Kit in Belarusian (N =176) and Slovak (N =164) individuals. No deviation from Hardy–Weinberg equilibrium was found for all loci. These results were compared with data available for northern Poland and Belarusian minority residing in northeastern Poland [Z. Szczerkowska, E. Kapińska, J. Wysocka, L. Cybulska, Northern Polish population data and forensic usefulness of 15 autosomal STR loci, Forensic Sci. Int. 144 (2004) 69–71; W. Pepinski, A. Niemcunowicz-Janica, M. Skawrowska, E. Koc-Zorawska, J. Janica, I. Soltyszewski, Allele distribution of 15 STR loci in a population sample of Belarusian minority residing in the northeastern Poland, Forensic Sci. Int. 139 (2004) 265–267]. Statistically significant differences were observed between Belarusian [K. Rębała, J. Wysocka, E. Kapińska, L. Cybulska, A.I. Mikulich, I.S. Tsybovsky, Z. Szczerkowska, Belarusian population genetic database for 15 autosomal STR loci, Forensic Sci. Int. (2007), doi:10.1016/j.forsciint.2007.02.002] and Slovak populations and other compared populations. The values of heterozygosity, polymorphic information content (PIC), power of discrimination (PD), power of exclusion (PE), paternity index (PI) and matching probability (pM) were calculated. The results demonstrated the forensic usefulness of the analyzed loci. [Copyright &y& Elsevier]

Abstract: Allele frequencies of 15 short tandem repeat loci included in the AmpFlSTR Identifiler kit (Applied Biosystems) were obtained from a sample set of unrelated individuals living in Belarus (n =176). For all loci, no deviation from Hardy–Weinberg equilibrium was found. Results were compared with data available for the Belarusian minority residing in northeastern Poland and for other Slavic populations. Statistically significant differences were observed between Belarusians and all compared populations. The values of heterozygosity, polymorphic information content (PIC), power of discrimination (PD), power of exclusion (PE), paternity index (PI) and matching probability (pM) were calculated. [Copyright &y& Elsevier]

Abstract: We have investigated four X-chromosomal STR loci (a tetranucleotide repeat marker HPRTB, DXS7423 and trinucleotide repeat systems DXS101, DXS8377) in population samples of unrelated Belarusian and Slovak males (N =180 and 116, respectively). Markers were amplified in a multiplex PCR reaction with primers labeled with fluorescent dyes 5-FAM and 5-JOE (dye set F). The separation and detection of PCR products were performed by capillary electrophoresis on a 3130 Genetic Analyzer (Applied Biosystems), using positive controls (K562 and NA9947A) and the GeneScan-500 ROX internal lane standard. Allele designation was based on comparison with the constructed allelic ladder. We performed statistical analysis estimating power of discrimination for males (PDmale). Our data was compared with European populations from Poland and Germany. The obtained data are useful in forensic practice and they contribute to creation of national X-STR databases in Belarus and Slovakia. [Copyright &y& Elsevier]

Abstract: Experimental diastereoselectivities of the direct solvent-less (neat) aldol reactions of tropinone (8-methyl-8-azabicyclo[3.2.1]octan-3-one) and granatanone (pseudopelletierine, 9-methyl-9-azabicyclo[3.3.1]nonan-3-one) in the presence of catalytic amounts of water are most accurately reproduced by thermodynamic distributions of isomeric products calculated in the gas phase at the B3LYP/6-31g(d) level of theory. Less than 30% systematic errors, on average, exist in the predicted anti/syn-diastereomeric ratio (dr) for the solvent-less reaction of tropinone with several aromatic aldehydes. The CPCM-B3LYP/6-31g(d) method reproduces the anti/syn-diastereomeric ratio of the aqueous aldol reaction of tropinone with several aromatic aldehydes with reasonable deviation (0–88%), excellent (0–10)% agreement was found for the reactions of tropinone and granatanone with benzaldehyde. Qualitatively satisfactory agreement was also found for dr values in different solvents (DMF, THF, and Et3N). The density functional theory (DFT) results support the notion of the thermodynamic control of the reaction. [Copyright &y& Elsevier]

Inappropriate activation of the p53 transcription factor contributes to numerous developmental syndromes characterized by distinct constellations of phenotypes. How p53 drives exquisitely specific sets of symptoms in diverse syndromes, however, remains enigmatic. Here, we deconvolute the basis of p53-driven developmental syndromes by leveraging an array of mouse strains to modulate the spatial expression pattern, temporal profile, and magnitude of p53 activation during embryogenesis. We demonstrate that inappropriate p53 activation in the neural crest, facial ectoderm, anterior heart field, and endothelium induces distinct spectra of phenotypes. Moreover, altering the timing and degree of p53 hyperactivation substantially affects the phenotypic outcomes. Phenotypes are associated with p53-driven cell-cycle arrest or apoptosis, depending on the cell type, with gene expression programs, rather than extent of mitochondrial priming, largely governing the specific response. Together, our findings provide a critical framework for decoding the role of p53 as a mediator of diverse developmental syndromes. • Inappropriate p53 activation during embryogenesis triggers developmental defects • Spectrum of defects depends on degree and spatiotemporal pattern of p53 activation • p53 activation drives apoptosis and cell-cycle arrest in a context-dependent manner • Gene expression rather than mitochondrial priming dictates apoptotic responses Various developmental syndromes are associated with increased p53 activity. Bowen et al. generate a panel of mouse models to define how different spatial expression patterns, temporal profiles, and magnitudes of p53 activation during embryogenesis drive distinct spectra of developmental phenotypes. [ABSTRACT FROM AUTHOR]

Summary Somatic progenitors sustain tissue self-renewal while suppressing premature differentiation. Protein arginine methyltransferases (PRMTs) affect many processes; however, their role in progenitor function is incompletely understood. PRMT1 was found to be the most highly expressed PRMT in epidermal progenitors and the most downregulated PRMT during differentiation. In targeted mouse knockouts and in long-term regenerated human mosaic epidermis in vivo , epidermal PRMT1 loss abolished progenitor self-renewal and led to premature differentiation. Mass spectrometry of the PRMT1 protein interactome identified the CSNK1a1 kinase, which also proved essential for progenitor maintenance. CSNK1a1 directly bound and phosphorylated PRMT1 to control its genomic targeting to PRMT1-sustained proliferation genes as well as PRMT1-suppressed differentiation genes. Among the latter were GRHL3, whose derepression was required for the premature differentiation seen with PRMT1 and CSNK1a1 loss. Maintenance of the progenitors thus requires cooperation by PRMT1 and CSNK1a1 to sustain proliferation gene expression and suppress premature differentiation driven by GRHL3. [ABSTRACT FROM AUTHOR]

Summary Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric cancer with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone-3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using bromodomain inhibition or CDK7 blockade. Targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition, and DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade. Identification of super-enhancers in DIPG provides insights toward the cell of origin, highlighting oligodendroglial lineage genes, and reveals unexpected mechanisms mediating tumor viability and invasion, including potassium channel function and EPH receptor signaling. The findings presented demonstrate transcriptional vulnerabilities and elucidate previously unknown mechanisms of DIPG pathobiology. [ABSTRACT FROM AUTHOR]