DNA methylation on N6-adenine in mammalian embryonic stem cells

It has been widely accepted that 5-methylcytosine is the only form of DNA methylation in mammalian genomes. Here we identify N6-methyladenine as another form of DNA modification in mouse embryonic stem cells. Alkbh1 encodes a demethylase for N6-methyladenine. An increase of N6-methyladenine levels in Alkbh1-deficient cells leads to transcriptional silencing. N6-methyladenine deposition is inversely correlated with the evolutionary age of LINE-1 transposons; its deposition is strongly enriched at young (6 million years old) L1 elements. The deposition of N6-methyladenine correlates with epigenetic silencing of such LINE-1 transposons, together with their neighbouring enhancers and genes, thereby resisting the gene activation signals during embryonic stem cell differentiation. As young full-length LINE-1 transposons are strongly enriched on the X chromosome, genes located on the X chromosome are also silenced. Thus, N6-methyladenine developed a new role in epigenetic silencing in mammalian evolution distinct from its role in gene activation in other organisms. Our results demonstrate that N6-methyladenine constitutes a crucial component of the epigenetic regulation repertoire in mammalian genomes

Search for Kaluza-Klein Graviton Emission in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV using the Missing Energy Signature

We report on a search for direct Kaluza-Klein graviton production in a data sample of 84 ${pb}^{-1}$ of \ppb collisions at $\sqrt{s}$ = 1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and one or two high energy jets. We compare the data with the predictions from a $3+1+n$-dimensional Kaluza-Klein scenario in which gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for $n$=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71 TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure

Correlation of histopathologic characteristics to protein expression and function in malignant melanoma

BACKGROUND: Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information. PATIENTS AND METHODS: Regional lymph node metastases obtained from ten patients with metastatic melanoma (stage III) were analyzed by histopathology and proteomics using mass spectrometry. Out of the ten patients, six had clinical follow-up data. The protein deep mining mass spectrometry data was related to the histopathology tumor tissue sections adjacent to the area used for deep-mining. Clinical follow-up data provided information on disease progression which could be linked to protein expression aiming to identify tissue-based specific protein markers for metastatic melanoma and prognostic factors for prediction of progression of stage III disease. RESULTS: In this feasibility study, several proteins were identified that positively correlated to tumor tissue content including IF6, ARF4, MUC18, UBC12, CSPG4, PCNA, PMEL and MAGD2. The study also identified MYC, HNF4A and TGFB1 as top upstream regulators correlating to tumor tissue content. Other proteins were inversely correlated to tumor tissue content, the most significant being; TENX, EHD2, ZA2G, AOC3, FETUA and THRB. A number of proteins were significantly related to clinical outcome, among these, HEXB, PKM and GPNMB stood out, as hallmarks of processes involved in progression from stage III to stage IV disease and poor survival. CONCLUSION: In this feasibility study, promising results show the feasibility of relating proteomics to histopathology and clinical outcome, and insight thus can be gained into the molecular processes driving the disease. The combined analysis of histological features including the sample cellular composition with protein expression of each metastasis enabled the identification of novel, differentially expressed proteins. Further studies are necessary to determine whether these putative biomarkers can be utilized in diagnostics and prognostic prediction of metastatic melanoma

Precision top-quark mass measurement in the lepton plus jets topology in p(p)over-bar collisions at root s=1.96 TeV

We report two measurements of the top-quark mass M-top using the CDF II detector at the Fermilab Tevatron in a 318 pb(-1) data sample of t (t) over bar events in the lepton+jets final state. One method uses an event-based likelihood technique resulting in M-top=173.2(-2.4)(+2.6)(stat)+/- 3.2(syst) GeV/c(2) or 173.2(-4.0)(+4.1) GeV/c(2). The second method reconstructs a top-quark mass in each event using the measured invariant mass of the hadronically decaying W boson to constrain the jet energy scale to obtain a value for M-top of 173.5(-3.6)(+3.7)(stat)+/- 1.3(syst) GeV/c(2) or 173.5(-3.8)(+3.9) GeV/c(2). We take the latter, which is more precise, as our result

Adverse effects from multi-drug therapy in leprosy: a Brazilian study.

INTRODUCTION: The WHO MDT for leprosy treatment was officially introduced in Brazil in 1991 and comprises three drugs: dapsone, rifampicin and clofazimine. There are few good studies on the frequency of side-effects attributable to MDT in Brazil. METHODS: A retrospective and descriptive study carried out in a LCP in Vitória, State of Espirito Santo, Brazil. A specific and detailed protocol about side-effects was prepared and filled in from the patient records. RESULTS: One hundred ninety four patients' records were analysed looking for side-effects attributable to MDT. Side-effects were attributed to at least one MDT component in 88 (45%) patients and 85 had side-effects due to dapsone, 24 due to rifampicin and 18 due to clofazimine. 185 episodes were identified. The suspected drug was stopped in 47 out of 88 episodes (24% patients); 46 had dapsone stopped, 5 had rifampicin stopped and no-one had clofazimine stopped. CONCLUSION: Side-effects attributed to MDT is more frequent than previously described, resulting in interruption of treatment in many patients