Different Allele Frequency between Males and Females of a SNP of the Human Beta T Cell Receptor

We studied a single nucleotide polymorphism (SNP) located in the human beta T-cell receptor, in association studies and different allele frequency in the two sexes. Here we report a new series of 200 subjects (100 males and 100 females) in a restricted age range, 20-30 years. We found the following results: in males 57/100 (57%) were heterozygous, 26/100 (26%) were homozygous for the two digestion fragments and 17/100 (17%) were homozygous for the 603bp fragment. Females were 44/100 (44%) heterozygous, 24/100 (24%) homozygous for the two digestion fragments and 32/100 (32%) homozygous for the 603bp fragment. The allele frequency was significantly different according to chi square analysis (X square statistic (df = 2) = 7.412; p = 0.025). Our study shows that in females, but not in males , there is a significant increase of CC homozygous status and a proportionate decrease of heterozygous status compared with Hardy-Weinberg expectations. This study could explain the controversial results obtained by association studies between this SNP (rs1800907) and autoimmune diseases made in the ninety and uncorfirmed in more recent papers. Moreover it could be a starting point to search for other autosomical DNAs diffences between the two sexes

Discovery of unexpected sphingolipids in almonds and pistachios with an innovative use of triple quadrupole tandem mass spectrometry

The densely packed storage of valuable nutrients (carbohydrates, lipids, proteins, micronutrients) in the endosperm of nuts and seeds makes the study of their complex composition a topic of great importance. Ceramides in the total lipid extract of some ground almonds and pistachios were searched with a systematic innovative discovery precursor ion scan in a triple quadrupole tandem mass spectrometry, where iso-energetic collision activated dissociation was performed. Five descriptors were used to search components with different C18 long chain bases containing different structural motifs (d18:0, d18:1, d18:2, t18:0, t18:1). The presence of hexoside unit was screened with a specific neutral loss experiment under iso-energetic collision activated dissociation conditions. The discovery scans highlighted the presence of two specific hexosyl-ceramides with a modified sphingosine component (d18:2) and C16:0 or C16:0 hydroxy-fatty acids. The hexosyl-ceramide with the non-hydroxylated fatty acid seemed specific of pistachios and was undetected in almonds. The fast and comprehensive mass spectrometric method used here can be useful to screen lipid extracts of several more seeds of nutraceutical interest, searching for unusual and/or specific sphingosides with chemically decorated long chain bases

Unambiguous Characterization of p-Cresyl Sulfate, a Protein-Bound Uremic Toxin, as Biomarker of Heart and Kidney Disease

p-Cresyl sulfate is one of the bound uremic toxins whose level increases in the sera of patients with the severity of chronic kidney disease and is therefore used as a standard for clinical investigations. Our first attempts to obtain p-cresyl sulfate led exclusively to the product of sulfonation of the aromatic ring instead of sulfation on the OH moiety. Nevertheless, this initial discouraging result allowed us to handle both p-cresyl sulfate and 2-hydroxy-5-methylbenzenesulfonic acid obtained by different synthetic pathways. Interestingly, the comparison between the two isomers pointed out that the two molecules show the same fragmentation pattern and are indistinguishable by mass spectrometry. They cannot be separated on several commercially available columns. The only difference between the two compounds is a 10-fold higher ionization yield under negative ion electrospray ionization. NMR spectral studies definitely confirmed the different molecular structures. We present here an unambiguous biomimetic synthetic route for p-cresyl sulfate and the spectroscopic characterization of both the compounds by nuclear magnetic resonance and mass spectrometry

Feedback cooling of the normal modes of a massive electromechanical system to submillikelvin temperature

We apply a feedback cooling technique to simultaneously cool the three electromechanical normal modes of the ton-scale resonant-bar gravitational wave detector AURIGA. The measuring system is based on a dc Superconducting Quantum Interference Device (SQUID) amplifier, and the feedback cooling is applied electronically to the input circuit of the SQUID. Starting from a bath temperature of 4.2 K, we achieve a minimum temperature of 0.17 mK for the coolest normal mode. The same technique, implemented in a dedicated experiment at subkelvin bath temperature and with a quantum limited SQUID, could allow to approach the quantum ground state of a kilogram-scale mechanical resonator.Comment: 4 pages, 4 figure

T-cell receptor polymorphism in primary biliary cirrhosis

T-cell receptor (TCR) plays a key role in immune regulation and polymorphisms of its genes have been found in association with several autoimmune diseases. No data are available for primary biliary cirrhosis, an autoimmune liver disease the natural history of which is highly variable. We studied a TCR constant beta-2 chain polymorphism in 70 patients affected by primary biliary cirrhosis and in 70 healthy controls. The DNA chains of patients and controls were amplified by means of polymerase chain reaction using primers designed around a Bgl II polymorphic restriction site and digested for restriction fragment length polymorphism analysis. We found a slight increase of the heterozygous genotype in patients compared with controls (49 vs 40%), which became higher if only patients with early disease were considered (60 vs 40%). Heterozygous patients had less severe disease as indicated by a lower Mayo score (5.1 +/- 1.2 vs 5.7 +/- 1.2 in non-heterozygous). Our data suggest that TCR constant beta-2 polymorphism does not play a key role in modulating the multifactorial etiopathogenesis of primary biliary cirrhosis

IGEC2: A 17-month search for gravitational wave bursts in 2005-2007

We present here the results of a 515 days long run of the IGEC2 observatory, consisting of the four resonant mass detectors ALLEGRO, AURIGA, EXPLORER and NAUTILUS. The reported results are related to the fourfold observation time from Nov. 6 2005 until Apr. 14 2007, when Allegro ceased its operation. This period overlapped with the first long term observations performed by the LIGO interferometric detectors. The IGEC observations aim at the identification of gravitational wave candidates with high confidence, keeping the false alarm rate at the level of 1 per century, and high duty cycle, namely 57% with all four sites and 94% with at least three sites in simultaneous observation. The network data analysis is based on time coincidence searches over at least three detectors: the four 3-fold searches and the 4-fold one are combined in a logical OR. We exchanged data with the usual blind procedure, by applying a unique confidential time offset to the events in each set of data. The accidental background was investigated by performing sets of 10^8 coincidence analyses per each detector configuration on off-source data, obtained by shifting the time series of each detector. The thresholds of the five searches were tuned so as to control the overall false alarm rate to 1/century. When the confidential time shifts was disclosed, no gravitational wave candidate was found in the on-source data. As an additional output of this search, we make available to other observatories the list of triple coincidence found below search thresholds, corresponding to a false alarm rate of 1/month.Comment: 10 pages, 8 figures Accepted for publication on Phys. Rev.

Results of the IGEC-2 search for gravitational wave bursts during 2005

The network of resonant bar detectors of gravitational waves resumed coordinated observations within the International Gravitational Event Collaboration (IGEC-2). Four detectors are taking part in this collaboration: ALLEGRO, AURIGA, EXPLORER and NAUTILUS. We present here the results of the search for gravitational wave bursts over 6 months during 2005, when IGEC-2 was the only gravitational wave observatory in operation. The network data analysis implemented is based on a time coincidence search among AURIGA, EXPLORER and NAUTILUS, keeping the data from ALLEGRO for follow-up studies. With respect to the previous IGEC 1997-2000 observations, the amplitude sensitivity of the detectors to bursts improved by a factor about 3 and the sensitivity bandwidths are wider, so that the data analysis was tuned considering a larger class of detectable waveforms. Thanks to the higher duty cycles of the single detectors, we decided to focus the analysis on three-fold observation, so to ensure the identification of any single candidate of gravitational waves (gw) with high statistical confidence. The achieved false detection rate is as low as 1 per century. No candidates were found.Comment: 10 pages, to be submitted to Phys. Rev.

Nonequilibrium steady state fluctuations in actively cooled resonators

We analyze heat and work fluctuations in the gravitational wave detector AURIGA, modeled as a macroscopic electromechanical oscillator in contact with a thermostat and cooled by an active feedback system. The oscillator is driven to a steady state by the feedback cooling, equivalent to a viscous force. The experimentally measured fluctuations are in agreement with our theoretical analysis based on a stochastically driven Langevin system. The asymmetry of the fluctuations of the absorbed heat characterizes the oscillator's nonequilibrium steady state and reveals the extent to which a feedback cooled system departs from equilibrium in a statistical mechanics perspective.Comment: to be published in Phys. Rev. Let

Dual detectors of gravitational waves

In a "Dual" gravitational wave (GW) detector a wide band sensitivity is obtained by measuring the differential displacement, driven by the GW, of the facing surfaces of two nested massive bodies mechanically resonating at different frequencies. A "selective readout" scheme, capable of specifically selecting the signal contributed by the vibrational modes sensitive to the gravitational waves, could then reduce the thermal noise contribution from the not sensitive modes. In a dual detector the sensitivity improvement in the displacement transduction could be pursued by means of mechanical amplification systems. This solution is innovative for the resonant GW detectors and we report about preliminary theoretical and experimental study

Chromosome 7 monosomy and deletions in myeloproliferative diseases

We studied deletion and monosomy of chromosome 7 in 150 patients with myeloproliferative diseases. We found 8/150 patients with monosomy 7 by cytogenetics and 4/150 with deletions of the long arm of chromosome 7 by restriction fragment length polymorphism (RFLP) analysis performed with Southern and polymerase chain reaction. To overcome limitation of RFLP analysis, we restricted loss of heterozygosity study with microsatellites to 45 patients, observing deletion 7q31.1 in 7/45 patients. In all patients with molecular alterations the deletion was observed only in myeloid cells, while the monosomy was detected in both myeloid precursor and lymphocytes. This finding suggests a CD34-totipotent stem cell origin for the monosomy and a colony forming unit - granulocyte, erythrocyte, monocyte, megakaryocytes (CFU-GEMM) stem cell origin for the deletions