A QTL on chromosome 3q23 influences processing speed in humans

Processing speed is a psychological construct that refers to the speed with which an individual can perform any cognitive operation. Processing speed correlates strongly with general cognitive ability, declines sharply with age, and is impaired across a number of neurological and psychiatric disorders. Thus, identifying genes that influence processing speed will likely improve understanding of the genetics of intelligence, biological aging, and the etiologies of numerous disorders. Previous genetics studies of processing speed have relied on simple phenotypes (e.g., mean reaction time) derived from single tasks. This strategy assumes, erroneously, that processing speed is a unitary construct. In the present study, we aimed to characterize the genetic architecture of processing speed by using a multi-dimensional model applied to a battery of cognitive tasks. Linkage and QTL-specific association analyses were performed on the factors from this model. The randomly ascertained sample comprised 1291 Mexican-American individuals from extended pedigrees. We found that performance on all three distinct processing-speed factors (Psychomotor Speed; Sequencing and Shifting and Verbal Fluency) were moderately and significantly heritable. We identified a genome-wide significant QTL on chromosome 3q23 for Psychomotor Speed (LOD = 4.83). Within this locus, we identified a plausible and interesting candidate gene for Psychomotor Speed (Z = 2.90, p = 1.86×10−03)

Analysis of Chimpanzee History Based on Genome Sequence Alignments

Population geneticists often study small numbers of carefully chosen loci, but it has become possible to obtain orders of magnitude for more data from overlaps of genome sequences. Here, we generate tens of millions of base pairs of multiple sequence alignments from combinations of three western chimpanzees, three central chimpanzees, an eastern chimpanzee, a bonobo, a human, an orangutan, and a macaque. Analysis provides a more precise understanding of demographic history than was previously available. We show that bonobos and common chimpanzees were separated ∼1,290,000 years ago, western and other common chimpanzees ∼510,000 years ago, and eastern and central chimpanzees at least 50,000 years ago. We infer that the central chimpanzee population size increased by at least a factor of 4 since its separation from western chimpanzees, while the western chimpanzee effective population size decreased. Surprisingly, in about one percent of the genome, the genetic relationships between humans, chimpanzees, and bonobos appear to be different from the species relationships. We used PCR-based resequencing to confirm 11 regions where chimpanzees and bonobos are not most closely related. Study of such loci should provide information about the period of time 5–7 million years ago when the ancestors of humans separated from those of the chimpanzees

PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth.

BackgroundProgesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms.ResultsWe demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/AKT activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/AKT activation. Mutation of Y180F strongly attenuated subcutaneous xenograft tumor growth in NOD-SCID gamma mice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells.ConclusionsAltogether, these results indicate that mutational manipulation of PGRMC1 phosphorylation status exerts broad pleiotropic effects relevant to cancer and other cell biology

The sleep EEG spectrum is a sexually dimorphic marker of general intelligence

The shape of the EEG spectrum in sleep relies on genetic and anatomical factors and forms an individual “EEG fingerprint”. Spectral components of EEG were shown to be connected to mental ability both in sleep and wakefulness. EEG sleep spindle correlates of intelligence, however, exhibit a sexual dimorphism, with a more pronounced association to intelligence in females than males. In a sample of 151 healthy individuals, we investigated how intelligence is related to spectral components of full-night sleep EEG, while controlling for the effects of age. A positive linear association between intelligence and REM anterior beta power was found in females but not males. Transient, spindle-like “REM beta tufts” are described in the EEG of healthy subjects, which may reflect the functioning of a recently described cingular-prefrontal emotion and motor regulation network. REM sleep frontal high delta power was a negative correlate of intelligence. NREM alpha and sigma spectral power correlations with intelligence did not unequivocally remain significant after multiple comparisons correction, but exhibited a similar sexual dimorphism. These results suggest that the neural oscillatory correlates of intelligence in sleep are sexually dimorphic, and they are not restricted to either sleep spindles or NREM sleep

Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R) in cancer cachexia

<p>Abstract</p> <p>Background</p> <p>At present pathogenic mechanisms of cancer cachexia are poorly understood. Previous evidence in animal models implicates the melanocortin-4 receptor gene (<it>MC4R</it>) in the development of cancer cachexia. In humans, <it>MC4R </it>mutations that lead to an impaired receptor function are associated with obesity; in contrast, the most frequent polymorphism (Val103Ile, rs2229616; heterozygote frequency approximately 2%) was shown to be negatively associated with obesity. We tested if cancer patients that are homo-/heterozygous for the Val103Ile polymorphism are more likely to develop cachexia and/or a loss of appetite than non-carriers of the 103Ile-allele.</p> <p>Methods</p> <p>BMI (body mass index in kg/m²) of 509 patients (295 males) with malignant neoplasms was determined; additionally patients were asked about premorbid/pretherapeutical changes of appetite and weight loss. Cachexia was defined as a weight loss of at least 5% prior to initiation of therapy; to fulfil this criterion this weight loss had to occur independently of other plausible reasons; in single cases weight loss was the initial reason for seeing a physician. The average age in years (± SD) was 59.0 ± 14.5 (males: 58.8 ± 14.0, females 59.2 ± 14.0). Blood samples were taken for genotyping of the Val103Ile by PCR- RFLP.</p> <p>Results</p> <p>Most of the patients suffered from lymphoma, leukaemia and gastrointestinal tumours. 107 of the patients (21%) fulfilled our criteria for cancer cachexia. We did not detect association between the Val103Ile polymorphism and cancer cachexia. However, if we exploratively excluded the patients with early leucaemic stages, we detected a trend towards the opposite effect (p < 0.05); heterozygotes for the 103Ile-allele developed cancer cachexia less frequently in comparison to the rest of the study group. Changes of appetite were not associated with the 103Ile-allele carrier status (p > 0.39).</p> <p>Conclusion</p> <p>Heterozygotes for the 103Ile-allele are not more prone to develop cancer cachexia than patients without this allele; possibly, Ile103 carriers might be more resistant to cancer cachexia in patients with solid tumors. Further studies of the melanocortinergic system in cachexia of patients with solid tumors are warranted.</p

High grade B-cell gastric lymphoma with complete pathologic remission after eradication of helicobacter pylori infection: Report of a case and review of the literature

<p>Abstract</p> <p>Background</p> <p>Treatment of primary gastric diffuse large B-cell lymphoma is still controversial. The treatment of localized disease was based on surgery alone, or followed by chemotherapy and/or radiotherapy. High-grade gastric lymphomas are generally believed to be <it>Helicobacter pylori </it>(HP)-independent growing tumors. However a few cases of regression of high-grade gastric lymphomas after the cure of <it>Helicobacter pylori </it>infection had been described.</p> <p>Case presentation</p> <p>We report here a case with primary diffuse large B-cell lymphoma that showed a complete pathologic remission after HP eradication and we reviewed the literature. A computerized literature reach through Medline, Cancerlit and Embase were performed, applying the words: high grade gastric lymphoma, or diffuse large B cell, MALT gastric lymphoma, DLBCLL (MALT) lymphoma and Helicobacter. Articles and abstracts were also identified by back-referencing from original and relevant papers. Selected for the present review were papers published in English before January 2007.</p> <p>Conclusion</p> <p>Forty two cases of primary high grade gastric lymphoma that regressed with anti HP treatment were found. There were anedoctal cases reported and patients belonging to prospective studies; four trials studied the effect of eradication of <it>Helicobacter pylori</it> as first line therapy in high grade gastric lymphoma: 22 of a total of 38 enrolled patients obtained complete remission. Depth of gastric wall infiltration and clinical stage were important factors to predict the response to antibiotic therapy. Our case and the review of the literature show that high-grade transformation is not necessarily associated with the loss HP dependence. In early stage, for high-grade B-cell HP-positive gastric lymphomas, given the limited toxicity of anti-HP therapy, this treatment may be considered as one of the first line treatment options.</p

Precision measurement of the top quark mass from dilepton events at CDF II

We report a measurement of the top quark mass, M_t, in the dilepton decay channel of $t\bar{t}\to b\ell'^{+}\nu_{\ell'}\bar{b}\ell^{-}\bar{\nu}_{\ell}$ using an integrated luminosity of 1.0 fb^{-1} of p\bar{p} collisions collected with the CDF II detector. We apply a method that convolutes a leading-order matrix element with detector resolution functions to form event-by-event likelihoods; we have enhanced the leading-order description to describe the effects of initial-state radiation. The joint likelihood is the product of the likelihoods from 78 candidate events in this sample, which yields a measurement of M_{t} = 164.5 \pm 3.9(\textrm{stat.}) \pm 3.9(\textrm{syst.}) \mathrm{GeV}/c^2, the most precise measurement of M_t in the dilepton channel.Comment: 7 pages, 2 figures, version includes changes made prior to publication by journa

Cross Section Measurements of High-pTp_T Dilepton Final-State Processes Using a Global Fitting Method

We present a new method for studying high-$p_T$ dilepton events ($e^{\pm}e^{\mp}$, $\mu^{\pm}\mu^{\mp}$, $e^{\pm}\mu^{\mp}$) and simultaneously extracting the production cross sections of $p\bar{p} \to t\bar{t}$, $p\bar{p} \to W^+W^-$, and p\bar{p} \to \ztt at a center-of-mass energy of $\sqrt{s} = 1.96$ TeV. We perform a likelihood fit to the dilepton data in a parameter space defined by the missing transverse energy and the number of jets in the event. Our results, which use $360 {\rm pb^{-1}}$ of data recorded with the CDF II detector at the Fermilab Tevatron Collider, are $\sigma(t\bar{t}) = 8.5_{-2.2}^{+2.7}$ pb, $\sigma(W^+W^-) = 16.3^{+5.2}_{-4.4}$ pb, and \sigma(\ztt) =291^{+50}_{-46} pb.Comment: 20 pages, 2 figures, to be submitted to PRD-R

Measurement of the Ratios of Branching Fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) and B(Bs -> Ds pi) / B(Bd -> Dd pi)

Using 355 pb^-1 of data collected by the CDF II detector in \ppbar collisions at sqrt{s} = 1.96 TeV at the Fermilab Tevatron, we study the fully reconstructed hadronic decays B -> D pi and B -> D pi pi pi. We present the first measurement of the ratio of branching fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) = 1.05 pm 0.10 (stat) pm 0.22 (syst). We also update our measurement of B(Bs -> Ds pi) / B(Bd -> Dd pi) to 1.13 pm 0.08 (stat) pm 0.23 (syst) improving the statistical uncertainty by more than a factor of two. We find B(Bs -> Ds pi) = [3.8 pm 0.3 (stat) pm 1.3 (syst)] \times 10^{-3} and B(Bs -> Ds pi pi pi) = [8.4 pm 0.8 (stat) pm 3.2 (syst)] \times 10^{-3}.Comment: 7 pages, 2 figure

Measurement of the Lambda_b Lifetime in Lambda_b --> J/psi Lambda0 in p-pbar Collisions at sqrt(s)=1.96 TeV

We report a measurement of the Lambda_b lifetime in the exclusive decay Lambda_b --> J/psi Lambda0 in p-pbar collisions at sqrt(s) = 1.96 TeV using an integrated luminosity of 1.0 fb^{-1} of data collected by the CDF II detector at the Fermilab Tevatron. Using fully reconstructed decays, we measure tau(Lambda_b) = 1.593 ^{+0.083}_{-0.078} (stat.) +- 0.033 (syst.) ps. This is the single most precise measurement of tau(Lambda_b) and is 3.2 sigma higher than the current world average.Comment: 7 Pages, 2 Figures, 1 Table. Submitted to Phys. Rev. Let