Comparative chromosome band mapping in primates byin situ suppression hybridization of band specific DNA microlibraries

A DNA-library established from microdissected bands 8q23 to 8q24.1 of normal human chromosomes 8 (Lüdecke et al., 1989) was used as a probe for chromosomal in situ suppression (CISS-) hybridization to metaphase chromosomes of man and primates including Hylobates lar and Macaca fuscata. Comparative band mapping as first applied in this study shows the specific visualization of a single subchromosomal region in all three species and thus demonstrates that synteny of the bulk sequences of a specific human chromosome subregion has been conserved for more than 20 million years

PP2A inhibition overcomes acquired resistance to HER2 targeted therapy

Background: HER2 targeted therapies including trastuzumab and more recently lapatinib have significantly improved the prognosis for HER2 positive breast cancer patients. However, resistance to these agents is a significant clinical problem. Although several mechanisms have been proposed for resistance to trastuzumab, the mechanisms of lapatinib resistance remain largely unknown. In this study we generated new models of acquired resistance to HER2 targeted therapy and investigated mechanisms of resistance using phospho-proteomic profiling. Results: Long-term continuous exposure of SKBR3 cells to low dose lapatinib established a cell line, SKBR3-L, which is resistant to both lapatinib and trastuzumab. Phospho-proteomic profiling and immunoblotting revealed significant alterations in phospho-proteins involved in key signaling pathways and molecular events. In particular, phosphorylation of eukaryotic elongation factor 2 (eEF2), which inactivates eEF2, was significantly decreased in SKBR3-L cells compared to the parental SKBR3 cells. SKBR3-L cells exhibited significantly increased activity of protein phosphatase 2A (PP2A), a phosphatase that dephosphorylates eEF2. SKBR3-L cells showed increased sensitivity to PP2A inhibition, with okadaic acid, compared to SKBR3 cells. PP2A inhibition significantly enhanced response to lapatinib in both the SKBR3 and SKBR3-L cells. Furthermore, treatment of SKBR3 parental cells with the PP2A activator, FTY720, decreased sensitivity to lapatinib. The alteration in eEF2 phosphorylation, PP2A activity and sensitivity to okadaic acid were also observed in a second HER2 positive cell line model of acquired lapatinib resistance, HCC1954-L. Conclusions: Our data suggests that decreased eEF2 phosphorylation, mediated by increased PP2A activity, contributes to resistance to HER2 inhibition and may provide novel targets for therapeutic intervention in HER2 positive breast cancer which is resistant to HER2 targeted therapies

Feeding restriction impairs milk yield and physicochemical properties rendering it less suitable for sale

Feed shortages are relatively frequent in subtropical pasture-based dairy production systems. The effect of feed restriction on milk yield and physical-chemical traits was evaluated in this study. The experiment was carried out in Brazil’s south region. Treatments consisted of control and restricted diet. Six multiparous and six primiparous cows, with 499 ± 47.20 kg body weight (BW), at mid-lactation (188 ± 124 days in milk), producing 19.35 ± 4.10 kg of milk were assigned to two groups, balanced for parity, each group receiving a different sequence of the dietary treatments for 56 days, in a crossover design. Diet nominated as control included 8 kg DM 100 kg BW–1 of Bermuda grass var. Tifton pasture (Cynodon dactylon (L.) Pers.), 5.00 kg of concentrate and 2.50 kg of Tifton hay per day. The restriction diet consisted of 50 % of the quantity offered in the control diet. Milk production and physicochemical composition were evaluated. Feed restriction reduced milk production by 40 %, body condition score by 5 %, milk magnesium by 14.3 %, lactose by 1.7 %, titratable acidity by 10 % and stability to the ethanol test by 9 % and it tended to increase (7 %) milk potassium content. No changes were found for the remaining characteristics. Since feed restriction is quite frequent in Brazil’s extensive dairy production systems, our concern is that besides decreased milk production, changes can occur in the physiochemical attributes of the milk, mainly a reduction in the stability to the ethanol test, which may increase the volume of milk rejected by the industry

Heavy Quarks and Heavy Quarkonia as Tests of Thermalization

We present here a brief summary of new results on heavy quarks and heavy quarkonia from the PHENIX experiment as presented at the "Quark Gluon Plasma Thermalization" Workshop in Vienna, Austria in August 2005, directly following the International Quark Matter Conference in Hungary.Comment: 8 pages, 5 figures, Quark Gluon Plasma Thermalization Workshop (Vienna August 2005) Proceeding

Single Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s) = 200 GeV

The invariant differential cross section for inclusive electron production in p+p collisions at sqrt(s) = 200 GeV has been measured by the PHENIX experiment at the Relativistic Heavy Ion Collider over the transverse momentum range $0.4 <= p_T <= 5.0 GeV/c at midrapidity (eta <= 0.35). The contribution to the inclusive electron spectrum from semileptonic decays of hadrons carrying heavy flavor, i.e. charm quarks or, at high p_T, bottom quarks, is determined via three independent methods. The resulting electron spectrum from heavy flavor decays is compared to recent leading and next-to-leading order perturbative QCD calculations. The total cross section of charm quark-antiquark pair production is determined as sigma_(c c^bar) = 0.92 +/- 0.15 (stat.) +- 0.54 (sys.) mb.Comment: 329 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Nuclear Modification of Electron Spectra and Implications for Heavy Quark Energy Loss in Au+Au Collisions at sqrt(s_NN)=200 GeV

The PHENIX experiment has measured mid-rapidity transverse momentum spectra (0.4 < p_T < 5.0 GeV/c) of electrons as a function of centrality in Au+Au collisions at sqrt(s_NN)=200 GeV. Contributions from photon conversions and from light hadron decays, mainly Dalitz decays of pi^0 and eta mesons, were removed. The resulting non-photonic electron spectra are primarily due to the semi-leptonic decays of hadrons carrying heavy quarks. Nuclear modification factors were determined by comparison to non-photonic electrons in p+p collisions. A significant suppression of electrons at high p_T is observed in central Au+Au collisions, indicating substantial energy loss of heavy quarks.Comment: 330 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Measurement of Transverse Single-Spin Asymmetries for Mid-rapidity Production of Neutral Pions and Charged Hadrons in Polarized p+p Collisions at sqrt(s) = 200 GeV

The transverse single-spin asymmetries of neutral pions and non-identified charged hadrons have been measured at mid-rapidity in polarized proton-proton collisions at sqrt(s) = 200 GeV. The data cover a transverse momentum (p_T) range 0.5-5.0 GeV/c for charged hadrons and 1.0-5.0 GeV/c for neutral pions, at a Feynman-x (x_F) value of approximately zero. The asymmetries seen in this previously unexplored kinematic region are consistent with zero within statistical errors of a few percent. In addition, the inclusive charged hadron cross section at mid-rapidity from 0.5 < p_T < 7.0 GeV/c is presented and compared to NLO pQCD calculations. Successful description of the unpolarized cross section above ~2 GeV/c using NLO pQCD suggests that pQCD is applicable in the interpretation of the asymmetry results in the relevant kinematic range.Comment: 331 authors, 6 pages text, 2 figures, 3 tables. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration

Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (p_T), elliptic flow, two-particle correlations, non-statistical fluctuations, and suppression of particle production at high p_T. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted to Nuclear Physics A as a regular article; v3 has minor changes in response to referee comments. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix