Diet-Independent Remodeling of Cellular Membranes Precedes Seasonally Changing Body Temperature in a Hibernator

Polyunsaturated fatty acids (PUFA) have a multitude of health effects. Their incorporation into membrane phospholipids (PL) is generally believed to depend directly on dietary influx. PL influence transmembrane protein activity and thus can compensate temperature effects; e.g. PL n-6 PUFA are thought to stabilize heart function at low body temperature (Tb), whereas long chain (>C18) n-3 PUFA may boost oxidative capacity. We found substantial remodeling of membranes in free-living alpine marmots which was largely independent of direct dietary supply. Organ PL n-6 PUFA and n-6 to n-3 ratios were highest at onset and end of hibernation after rapid increases during a brief transitional period prior to hibernation. In contrast, longer chain PL n-3 PUFA content was low at end of summer but maximal at end of hibernation. After termination of hibernation in spring, these changes in PL composition were rapidly reversed. Our results demonstrate selective trafficking of PUFA within the body, probably governed by a circannual endogenous rhythm, as hibernating marmots were in winter burrows isolated for seven months from food and external cues signaling the approaching spring. High concentrations of PL n-6 PUFA throughout hibernation are in line with their hypothesized function of boosting SERCA 2a activity at low Tb. Furthermore, we found increasing rate of rewarming from torpor during winter indicating increasing oxidative capacity that could be explained by the accumulation of long-chain PL n-3 PUFA. It may serve to minimize the time necessary for rewarming despite the increasing temperature range to be covered, because rewarming is a period of highest metabolic rate and hence production of reactive oxygen species. Considering the importance of PUFA for health our results may have important biomedical implications, as seasonal changes of Tb and associated remodeling of membranes are not restricted to hibernators but presumably common among endothermic organisms

Next-to-leading order QCD corrections to Higgs boson production in association with a photon via weak-boson fusion at the LHC

Higgs boson production in association with a hard central photon and two forward tagging jets is expected to provide valuable information on Higgs boson couplings in a range where it is difficult to disentangle weak-boson fusion processes from large QCD backgrounds. We present next-to-leading order QCD corrections to Higgs production in association with a photon via weak-boson fusion at a hadron collider in the form of a flexible parton-level Monte Carlo program. The QCD corrections to integrated cross sections are found to be small for experimentally relevant selection cuts, while the shape of kinematic distributions can be distorted by up to 20% in some regions of phase space. Residual scale uncertainties at next-to-leading order are at the few-percent level.Comment: 17 pages, 7 figures, 1 tabl

A Novel Tandem Mass Spectrometry Method for Rapid Confirmation of Medium- and Very Long-Chain acyl-CoA Dehydrogenase Deficiency in Newborns

BACKGROUND:Newborn screening for medium- and very long-chain acyl-CoA dehydrogenase (MCAD and VLCAD, respectively) deficiency, using acylcarnitine profiling with tandem mass spectrometry, has increased the number of patients with fatty acid oxidation disorders due to the identification of additional milder, and so far silent, phenotypes. However, especially for VLCADD, the acylcarnitine profile can not constitute the sole parameter in order to reliably confirm disease. Therefore, we developed a new liquid chromatography tandem mass spectrometry (LC-MS/MS) method to rapidly determine both MCAD- and/or VLCAD-activity in human lymphocytes in order to confirm diagnosis. METHODOLOGY:LC-MS/MS was used to measure MCAD- or VLCAD-catalyzed production of enoyl-CoA and hydroxyacyl-CoA, in human lymphocytes. PRINCIPAL FINDINGS:VLCAD activity in controls was 6.95+/-0.42 mU/mg (range 1.95 to 11.91 mU/mg). Residual VLCAD activity of 4 patients with confirmed VLCAD-deficiency was between 0.3 and 1.1%. Heterozygous ACADVL mutation carriers showed residual VLCAD activities of 23.7 to 54.2%. MCAD activity in controls was 2.38+/-0.18 mU/mg. In total, 28 patients with suspected MCAD-deficiency were assayed. Nearly all patients with residual MCAD activities below 2.5% were homozygous 985A>G carriers. MCAD-deficient patients with one other than the 985A>G mutation had higher MCAD residual activities, ranging from 5.7 to 13.9%. All patients with the 199T>C mutation had residual activities above 10%. CONCLUSIONS:Our newly developed LC-MS/MS method is able to provide ample sensitivity to correctly and rapidly determine MCAD and VLCAD residual activity in human lymphocytes. Importantly, based on measured MCAD residual activities in correlation with genotype, new insights were obtained on the expected clinical phenotype

Physics Opportunities of e+e- Linear Colliders

We describe the anticipated experimental program of an e+e- linear collider in the energy range 500 GeV -- 1.5 TeV. We begin with a description of current collider designs and the expected experimental environment. We then discuss precision studies of the W boson and top quark. Finally, we review the range of models proposed to explain the physics of electroweak symmetry breaking and show, for each case, the central role that the linear collider experiments will play in elucidating this physics. (to appear in Annual Reviews of Nuclear and Particle Science)Comment: 93 pages, latex + 23 figures; typos corrections + 1 reference adde

Modified CAGE as a Screening Tool for Mechanical Fall Risk Assessment: A Pilot Survey

Modified CAGE as a Screening Tool for Mechanical Fall Risk Assessment: A Pilot Survey Marna Rayl Greenberg DO, MPH, Michael C Nguyen MD, Bernadette G Porter BA,Robert DBarraco, MD MPH, Brian Stello MD, Arnold Goldberg MD, Clare M Lenhart, PhD MPH,Anita Kurt PhD, RN, Bryan G Kane, MD Background: Falls in the elderly cause serious injury. The literature does not hold answers to patient perceptions about their personal fall risk, their comfort level in discussing their fall history, or a home safety plan with their healthcare provider. Existing risk-assessing tools may be prohibitive in the Emergency Department due to their length and complexity. Objective: We piloted a modified CAGE screen (Fig1) to identify adults at risk for falls. Methods: At a community health event, a convenience sample ofparticipants (50 years or older) was surveyed. The survey included demographics, the Falls Efficacy Scale (FES), the modified CAGEand questions about fall risk.The FES is a validated, but longer, survey metric for comparison. A modified CAGE score greater than or equal to 1 was considered positive. Analysis included descriptive statistics and modified CAGE groups were compared by gender, fall risk and history with chi-square. Results: One hundred sevensubjects (66.4%female, 32.7% male) with a mean age of 66 (SD7.9)participated; 98 (91.6%)were Caucasian. Twenty (18.7%) lived alone,43 (40.2%) had a cat or dog, and 91 (85%) had stairs at home. Six (5.6%) reported using assistive devices, 2 (1.9%) at-risk alcohol use; 9 (8.4%)taking blood thinners, 50 (46.7%) taking blood pressure medications, and 22 (20.6%) one or more medications that could make them drowsy. Thirty-threesubjects(30.8%) reported having fallen in the past year; only13 (39.4% of those fallen)sought treatment. Collectively, these variables resulted in a mean risk of falling score of 2.49 (SD=1.36) out of 9. Eleven (31.4%)femalesand27 (38.0%)malesrecorded ≥1 positive responses on the modified CAGE.A modified CAGE positive responsewas significantly greater among those with past-year falls (51.5%) than those without (29.7%), p=0.031.A positive modified CAGE screen was also associated with a higher mean FES score (10.82 v7.83, p More females than males reported past year falls (36.6% vs. 17.1%, p=0.04) yet no difference in fall risk was noted between genders (4.44 vs. 4.26, p=0.506). The proportion of modified CAGE positive participants did not vary between females and males (38% vs. 31%, p=0.505). Of those whoscreened positive on the modified CAGE, 36 (92.3%) reported comfort in speaking to their healthcare provider about their fall risk and 26 (66.7%) in having a home safety evaluation. Conclusions: In this pilot, a positive modified CAGE is associated with both higher FES scores and a willingness to discuss fall risk with a health care provider. The modifiedCAGE may be a usefulbrief screening tool to detect fall risk in adults. Further studies to determine the extent of its utility in an Emergency Department should be considered

Gender Differences in Emergency Department (ED) Patient Mechanical Fall Risk and Openness to Communication with Providers

Gender Differences in Emergency Department (ED) Patient Mechanical Fall Risk and Openness to Communication with Providers Bryan G Kane, MD, Michael C Nguyen MD, Robert D Barraco, MD MPH, Brian Stello MD, Arnold Goldberg MD, Clare M Lenhart, PhD MPH, Bernadette G Porter BA ,Anita Kurt PhD, RN, Marna Rayl Greenberg DO, MPH Objectives: The CDC reports that among older adults (≥65), falls are the leading cause of injury-related death and rates of fall-related fractures among older women are more than twice those for men. We set out to determine ED patient perceptions (analyzed by gender) about their personal fall risk compared to their actual risk and their comfort level in discussing their fall history or a home safety plan with their healthcare provider. Methods: After IRB approval, a convenience sample of ED patients (50 years or older) was surveyed at a suburban Level 1 Trauma center with an annual ED census of approximately 75,000. The survey included demographics, the Falls Efficacy Scale (FES), and questions about fall risk. The FES is a validated survey measuring concern of falling. Analysis included descriptive statistics and assessment of fall risk and fear of falling by gender using chi-square and t-tests as indicated. Significance was set at 0.05. Results: Of the 150 surveys collected, 149 indicated gender and were included in this analysis. Fifty-five percent of the sample was female (n=82); 45% (n=67) were male. Most (98%) were Caucasian and 22% reported living alone. There was not a difference in the mean age of female participants 69.79 years (SD=12.08) vs. males 68.06 (SD=10.36; p=0.355). See Table 1 for distribution of reported fall risk factors between genders. Collectively, these variables resulted in a mean risk of falling score of 3.37(SD=1.62) out of 9. On average, female participants had a significantly higher objective risk of falling than did male participants (3.65 vs. 3.02 p=0.018). Similarly, females also reported greater fear of falling than did males (FES score 12.33 vs. 9.62; p=0.005). Significantly more females (41.5%) than males (23.9%, p=0.037) reported having fallen in the past year. Of the 50 participants reporting past-year falls, only 19 (12 female and 7 male, p=0.793) sought treatment. The correlation between actual fall risk and fear of falling were greater among females (p The majority of patients (76.4%) were willing to speak to a provider about their fall risk. No significant difference was noted in willingness to discuss this topic with a provider based on gender (p=0.619), objective fall risk (p=0.145) or FES score (p=0.986). Similarly, many respondents indicated a willing to discuss a home safety evaluation with a provider (58.1%) and responses did not vary significantly by gender (p=.140), objective fall risk (p=0.168) or FES score (p=.584). Conclusion: In this study, female ED patients reported a greater fear of falling, had a significantly higher objective risk of falling, and had a higher correlation between their perceived risk and actual risk of falling than did males. The majority of both genders were amenable to discussing their fall risk and a home safety evaluation with their provider

The Genomic Signature of Crop-Wild Introgression in Maize

The evolutionary significance of hybridization and subsequent introgression has long been appreciated, but evaluation of the genome-wide effects of these phenomena has only recently become possible. Crop-wild study systems represent ideal opportunities to examine evolution through hybridization. For example, maize and the conspecific wild teosinte Zea mays ssp. mexicana, (hereafter, mexicana) are known to hybridize in the fields of highland Mexico. Despite widespread evidence of gene flow, maize and mexicana maintain distinct morphologies and have done so in sympatry for thousands of years. Neither the genomic extent nor the evolutionary importance of introgression between these taxa is understood. In this study we assessed patterns of genome-wide introgression based on 39,029 single nucleotide polymorphisms genotyped in 189 individuals from nine sympatric maize-mexicana populations and reference allopatric populations. While portions of the maize and mexicana genomes were particularly resistant to introgression (notably near known cross-incompatibility and domestication loci), we detected widespread evidence for introgression in both directions of gene flow. Through further characterization of these regions and preliminary growth chamber experiments, we found evidence suggestive of the incorporation of adaptive mexicana alleles into maize during its expansion to the highlands of central Mexico. In contrast, very little evidence was found for adaptive introgression from maize to mexicana. The methods we have applied here can be replicated widely, and such analyses have the potential to greatly informing our understanding of evolution through introgressive hybridization. Crop species, due to their exceptional genomic resources and frequent histories of spread into sympatry with relatives, should be particularly influential in these studies

Black holes in supergravity and integrability

Stationary black holes of massless supergravity theories are described by certain geodesic curves on the target space that is obtained after dimensional reduction over time. When the target space is a symmetric coset space we make use of the group-theoretical structure to prove that the second order geodesic equations are integrable in the sense of Liouville, by explicitly constructing the correct amount of Hamiltonians in involution. This implies that the Hamilton-Jacobi formalism can be applied, which proves that all such black hole solutions, including non-extremal solutions, possess a description in terms of a (fake) superpotential. Furthermore, we improve the existing integration method by the construction of a Lax integration algorithm that integrates the second order equations in one step instead of the usual two step procedure. We illustrate this technology with a specific example.Comment: 44 pages, small typos correcte

An effective theory for jet propagation in dense QCD matter: jet broadening and medium-induced bremsstrahlung

Two effects, jet broadening and gluon bremsstrahlung induced by the propagation of a highly energetic quark in dense QCD matter, are reconsidered from effective theory point of view. We modify the standard Soft Collinear Effective Theory (SCET) Lagrangian to include Glauber modes, which are needed to implement the interactions between the medium and the collinear fields. We derive the Feynman rules for this Lagrangian and show that it is invariant under soft and collinear gauge transformations. We find that the newly constructed theory SCET$_{\rm G}$ recovers exactly the general result for the transverse momentum broadening of jets. In the limit where the radiated gluons are significantly less energetic than the parent quark, we obtain a jet energy-loss kernel identical to the one discussed in the reaction operator approach to parton propagation in matter. In the framework of SCET$_{\rm G}$ we present results for the fully-differential bremsstrahlung spectrum for both the incoherent and the Landau-Pomeranchunk-Migdal suppressed regimes beyond the soft-gluon approximation. Gauge invariance of the physics results is demonstrated explicitly by performing the calculations in both the light-cone and covariant $R_{\xi}$ gauges. We also show how the process-dependent medium-induced radiative corrections factorize from the jet production cross section on the example of the quark jets considered here.Comment: 52 pages, 15 pdf figures, as published in JHE

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available