Deletion of Betaine-Homocysteine S -Methyltransferase in Mice Perturbs Choline and 1-Carbon Metabolism, Resulting in Fatty Liver and Hepatocellular Carcinomas

Betaine-homocysteine S-methyltransferase (BHMT) uses betaine to catalyze the conversion of homocysteine (Hcy) to methionine. There are common genetic polymorphisms in the BHMT gene in humans that can alter its enzymatic activity. We generated the first Bhmt−/− mouse to model the functional effects of mutations that result in reduced BHMT activity. Deletion of Bhmt resulted in a 6-fold increase (p < 0.01) in hepatic and an 8-fold increase (p < 0.01) in plasma total Hcy concentrations. Deletion of Bhmt resulted in a 43% reduction in hepatic S-adenosylmethionine (AdoMet) (p < 0.01) and a 3-fold increase in hepatic S-adenosylhomocysteine (AdoHcy) (p < 0.01) concentrations, resulting in a 75% reduction in methylation potential (AdoMet:AdoHcy) (p < 0.01). Bhmt−/− mice accumulated betaine in most tissues, including a 21-fold increase in the liver concentration compared with wild type (WT) (p < 0.01). These mice had lower concentrations of choline, phosphocholine, glycerophosphocholine, phosphatidylcholine, and sphingomyelin in several tissues. At 5 weeks of age, Bhmt−/− mice had 36% lower total hepatic phospholipid concentrations and a 6-fold increase in hepatic triacyglycerol concentrations compared with WT (p < 0.01), which was due to a decrease in the secretion of very low density lipoproteins. At 1 year of age, 64% of Bhmt−/− mice had visible hepatic tumors. Histopathological analysis revealed that Bhmt−/− mice developed hepatocellular carcinoma or carcinoma precursors. These results indicate that BHMT has an important role in Hcy, choline, and one-carbon homeostasis. A lack of Bhmt also affects susceptibility to fatty liver and hepatocellular carcinoma. We suggest that functional polymorphisms in BHMT that significantly reduce activity may have similar effects in humans

Correlated Strength in Nuclear Spectral Function

We have carried out an (e,e'p) experiment at high momentum transfer and in parallel kinematics to measure the strength of the nuclear spectral function S(k,E) at high nucleon momenta k and large removal energies E. This strength is related to the presence of short-range and tensor correlations, and was known hitherto only indirectly and with considerable uncertainty from the lack of strength in the independent-particle region. This experiment confirms by direct measurement the correlated strength predicted by theory.Comment: 4 pages, 2 figures, accepted by Phys. Rev. Let

The classification of bulimic eating disorders: a community-based cluster analysis study

Published online by Cambridge University Press 09 Jul 2009There is controversy over how best to classify eating disorders in which there is recurrent binge eating. Many patients with recurrent binge eating do not meet diagnostic criteria for either of the two established eating disorders, anorexia nervosa or bulimia nervosa. The present study was designed to derive an empirically based, and clinically meaningful, diagnostic scheme by identifying subgroups from among those with recurrent binge eating, testing the validity of these subgroups and comparing their predictive validity with that of the DSM-IV scheme. A general population sample of 250 young women with recurrent binge eating was recruited using a two-stage design. Four subgroups among the sample were identified using a Ward's cluster analysis. The first subgroup had either objective or subjective bulimic episodes and vomiting or laxative misuse; the second had objective bulimic episodes and low levels of vomiting or laxative misuse; the third had subjective bulimic episodes and low levels of vomiting or laxative misuse; and the fourth was heterogeneous in character. This cluster solution was robust to replication. It had good descriptive and predictive validity and partial construct validity. The results support the concept of bulimia nervosa and its division into purging and non-purging subtypes. They also suggest a possible new binge eating syndrome. Binge eating disorder, listed as an example of Eating Disorder Not Otherwise Specified within DSM-IV, did not emerge from the cluster analysis.P. J. Hay, C. G. Fairburn and H. A. Dol

Obesity: A Biobehavioral Point of View

Excerpt: If you ask an overweight person, “Why are you fat?’, you will, almost invariably, get the answer, “Because 1 eat too much.” You will get this answer in spite of the fact that of thirteen studies, six find no significant differences in the caloric intake of obese versus nonobese subjects, five report that the obese eat significantly less than the nonobese, and only two report that they eat significantly more

Longitudinal-Transverse Separations of Structure Functions at Low Q2Q^{2} for Hydrogen and Deuterium

We report on a study of the longitudinal to transverse cross section ratio, $R=\sigma_L/\sigma_T$, at low values of $x$ and $Q^{2}$, as determined from inclusive inelastic electron-hydrogen and electron-deuterium scattering data from Jefferson Lab Hall C spanning the four-momentum transfer range 0.06 $< Q^{2} < 2.8$ GeV$^{2}$. Even at the lowest values of $Q^{2}$, $R$ remains nearly constant and does not disappear with decreasing $Q^{2}$, as expected. We find a nearly identical behaviour for hydrogen and deuterium.Comment: 4 pages, 2 gigure

First measurements of the ^16O(e,e'pn)^14N reaction

This paper reports on the first measurement of the ^16O(e,e'pn)^14N reaction. Data were measured in kinematics centred on a super-parallel geometry at energy and momentum transfers of 215 MeV and 316 MeV/c. The experimental resolution was sufficient to distinguish groups of states in the residual nucleus but not good enough to separate individual states. The data show a strong dependence on missing momentum and this dependence appears to be different for two groups of states in the residual nucleus. Theoretical calculations of the reaction using the Pavia code do not reproduce the shape or the magnitude of the data.Comment: 10 pages, 11 figures, 2 tables, Accepted for publication in EPJ

A Measurement of the Electric Form Factor of the Neutron through d⃗(e⃗,e′n)p\vec{d}(\vec{e},e'n)p at Q2=0.5Q^2 = 0.5 (GeV/c)2^2

We report the first measurement of the neutron electric form factor $G_E^n$ via $\vec{d}(\vec{e},e'n)p$ using a solid polarized target. $G_E^n$ was determined from the beam-target asymmetry in the scattering of longitudinally polarized electrons from polarized deuterated ammonia, $^{15}$ND$_3$. The measurement was performed in Hall C at Thomas Jefferson National Accelerator Facility (TJNAF) in quasi free kinematics with the target polarization perpendicular to the momentum transfer. The electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle segmented detector. We find $G_E^n = 0.04632\pm0.00616 (stat.) \pm0.00341 (syst.)$ at $Q^2 = 0.495$ (GeV/c)$^2$.Comment: Latex2e 5 pages, 3 figure

Measurement of Nuclear Transparency for the A(e,e' pi^+) Reaction

We have measured the nuclear transparency of the A(e,e' pi^+) process in ^{2}H,^{12}C, ^{27}Al, ^{63}Cu and ^{197}Au targets. These measurements were performed at the Jefferson Laboratory over a four momentum transfer squared range Q^2 = 1.1 - 4.7 (GeV/c)^2. The nuclear transparency was extracted as the super-ratio of $(\sigma_A/\sigma_H)$ from data to a model of pion-electroproduction from nuclei without pi-N final state interactions. The Q^2 and atomic number dependence of the nuclear transparency both show deviations from traditional nuclear physics expectations, and are consistent with calculations that include the quantum chromodynamical phenomenon of color transparency.Comment: 5 pages, 3 figs Changes to figure 2 and 3 (error band updated and theory curves updated

Study of the A(e,e'π+\pi^+) Reaction on 1^1H, 2^2H, 12^{12}C, 27^{27}Al, 63^{63}Cu and 197^{197}Au

Cross sections for the p($e,e'\pi^{+}$)n process on $^1$H, $^2$H, $^{12}$C, $^{27}$Al, $^{63}$Cu and $^{197}$Au targets were measured at the Thomas Jefferson National Accelerator Facility (Jefferson Lab) in order to extract the nuclear transparencies. Data were taken for four-momentum transfers ranging from $Q^2$=1.1 to 4.8 GeV$^2$ for a fixed center of mass energy of $W$=2.14 GeV. The ratio of $\sigma_L$ and $\sigma_T$ was extracted from the measured cross sections for $^1$H, $^2$H, $^{12}$C and $^{63}$Cu targets at $Q^2$ = 2.15 and 4.0 GeV$^2$ allowing for additional studies of the reaction mechanism. The experimental setup and the analysis of the data are described in detail including systematic studies needed to obtain the results. The results for the nuclear transparency and the differential cross sections as a function of the pion momentum at the different values of $Q^2$ are presented. Global features of the data are discussed and the data are compared with the results of model calculations for the p($e,e'\pi^{+}$)n reaction from nuclear targets.Comment: 28 pages, 19 figures, submited to PR

Scaling of the F_2 structure function in nuclei and quark distributions at x>1

We present new data on electron scattering from a range of nuclei taken in Hall C at Jefferson Lab. For heavy nuclei, we observe a rapid falloff in the cross section for $x>1$, which is sensitive to short range contributions to the nuclear wave-function, and in deep inelastic scattering corresponds to probing extremely high momentum quarks. This result agrees with higher energy muon scattering measurements, but is in sharp contrast to neutrino scattering measurements which suggested a dramatic enhancement in the distribution of the `super-fast' quarks probed at x>1. The falloff at x>1 is noticeably stronger in ^2H and ^3He, but nearly identical for all heavier nuclei.Comment: 5 pages, 4 figures, to be submitted to physical revie