Laboratory studies of atomic collision processes of importance in planetary atmospheres

Progress in the following research supported under NSG 7386 is reported: (1) measurement of differential cross sections for atomic and molecular collisions relevant to analysis and modeling of data from Pioneer 11, Pioneer 12, Voyager 1, and Voyager 2; (2) analysis of measured differential cross section results to provide scattering data in forms that are easy to apply to atmospheric modeling work; (3) analysis of the data to give basic information on the molecular potentials involved in the scattering process; and (4) development and initial use of apparatus to study dissociative processes in neutral molecules

Laboratory studies of atomic collision processes of importance in planetary atmospheres

A series of differential cross sections for angular scattering and charge transfer was measured. These studies employ position-sensitive detectors (PSD's) to collect collision products scattered over a wide range of angles; and the research program includes investigation of differential cross sections for total angular scattering, charge transfer, stripping, and other collisions. All of these processes can be studied with the same basic apparatus, but minor modifications in the equipment details and in the data acquisition programs and techniques are required for each individual experiment

Association between MAPT polymorphism but not APOE promoter and elite rugby athlete status

INTRODUCTION: Incidence and outcomes of concussions have been hypothesised to be genetically influenced. The APOE Promoter G219T (rs405509) polymorphism has been associated with differential promoter activity and unfavourable outcomes after traumatic brain injury. The TT genotype is associated with a 3-fold greater risk of multiple concussions. The TT genotype of MAPT (rs10445337) has also been associated with poorer outcomes after concussion. Rugby has one of the highest incidences of concussion in sport, so it was hypothesised that APOE Promoter TT and MAPT TT genotypes would be less prevalent in elite rugby athletes because those genotypes, previously associated with increased risk, would be less compatible with achieving elite athlete status. METHODS: Participants were from the RugbyGene project, comprising elite Caucasian male rugby athletes (n = 528; mean (standard deviation) height 1.85 (0.07) m, mass 101 (14) kg, age 29 (7) yr), including 420 rugby union (RU) athletes that for some analyses were divided into forwards and backs and 108 rugby league (RL) athletes. Non-athletes were 592 Caucasian men and women (57% male, height 1.72 (0.10) m, mass 74 (14) kg, age 31 (7) yr). PCR of genomic DNA was used to determine genotypes using TaqMan probes, then groups were compared using χ2 and odds ratio (OR) statistics. RESULTS: All genotype data were in Hardy-Weinberg equilibrium. For MAPT (rs10445337), the risk genotype (TT) was underrepresented in rugby athletes (60%) compared to non-athletes (66%), CT more common in rugby athletes (34%) than non-athletes (29%) and little difference in CC genotype frequencies (χ2 = 7.092, P = 0.029; TT genotype frequency OR = 0.80, 95% confidence intervals (CI) = 0.62-1.02). There were no differences in MAPT (rs10445337) genotype frequencies between RU forwards and backs. For APOE Promoter G219T (rs405509), there were no differences in genotype frequencies between all athletes (RU and RL) and non-athletes (27% TT genotype in players and non-athletes), nor between RU forwards and backs. CONCLUSION: The MAPT (rs10445337) TT genotype is 6% less common in elite rugby athletes than non-athletes. Therefore, carrying at least one rs10445337 C allele appears to increase the probability of sustained career success in the high-risk concussion environment of elite rugby, perhaps via a greater ability to recover from concussions.Peer reviewe

Association of MMP3 but not TIMP2 gene variants with elite rugby player status and rugby code

Introduction: Achilles tendon pathology and anterior cruciate ligament rupture are multifactorial conditions for which genetic risk factors have been identified. Single nucleotide polymorphisms (SNPs) within the MMP3 (rs591058, rs679620, rs650108) and TIMP2 (rs4789932) genes have previously been associated with tendon and ligament pathologies. Although not entirely clear, prior literature indicates the risk alleles for Achilles tendon pathology as T (rs591058), G (rs679620) and A (rs650108) for MMP3. However, prior evidence regarding TIMP2 is equivocal. MMP3 is considered an essential regulator of matrix degradation and remodelling within diseased and normal musculoskeletal soft tissues. TIMP2 maintains homeostasis in the extracellular matrix in part by inhibiting MMP function. Given the high incidence and severity of tendon and ligament injuries in elite rugby athletes, we hypothesised that the aforementioned SNPs would be associated with career success. Methods: Participants from the RugbyGene project were elite Caucasian male rugby athletes (n = 566; mean (standard deviation) height 1.85 (0.07) m, mass 101 (14) kg, age 29 (7) yr), including 420 rugby union (RU) athletes that for some analyses were divided into forwards and backs and 120 rugby league (RL) athletes. Non-athletes were 589 Caucasian men and women (n = 589, 57% male, height 1.72 (0.10) m, mass 74 (14) kg, age 31 (7) yr). PCR of genomic DNA was used to determine genotypes using TaqMan probes, then groups were compared using Χ2 and odds ratio (OR) statistics. Results: As hypothesized, the MMP3 rs591058 risk genotype (TT) was less frequent in rugby athletes (28%) compared to non-athletes (33%) (Χ2 = 7.265, P = 0.026; OR = 1.18, 95% confidence intervals (CI) = 0.86-1.63). No differences were found for MMP3 rs679620, rs650108 or TIMP2 rs4789932 between rugby athletes and non-athletes. When RL athletes were compared to non-athletes, the risk genotype (TT) of MMP3 rs591058 was underrepresented in RL athletes (19%) compared to non-athletes (33%). The MMP3 rs679620 ‘protective’ allele (C) was more frequent in RL athletes (55%) compared to non-athletes (48%) (OR = 1.3, 95% CI = 0.98-1.74). However, for MMP3 rs650108 the ‘risk’ allele (A) was overrepresented in RL athletes (32%) compared to non-athletes (26%). There were no genotype differences for any gene variant between RU athletes and non-athletes. The ‘risk’ allele (T) of the MMP3 rs679629 polymorphism and the ‘protective’ allele (G) of the MMP3 rs650108 polymorphism were less common in RL (45%, 68%, respectively) than RU athletes (54%, 76%, respectively). Conclusion: We provide evidence for elite rugby athletes possessing a protective genetic profile regarding tendon and ligament injury risk. Notably, a less frequent rs591058 TT genotype in athletes suggests a lower risk of injury could therefore enhance career success in rugby. Furthermore, RL players appear to have differing genetic characteristics compared to their RU counterparts, which might reflect some differences in physiological demands between codes.Peer reviewedFinal Published versio

An Investigation into Genetic Associations with Musculoskeletal Soft Tissue Injuries in Elite Rugby – Preliminary Findings

Peer reviewe

Rotational hybridization, and control of alignment and orientation in triatomic ultralong-range Rydberg molecules

We explore the electronic structure and rovibrational properties of an ultralong-range triatomic Rydberg molecule formed by a Rydberg atom and a ground state heteronuclear diatomic molecule. We focus here on the interaction of a Rb($n,l\geqslant 3$) Rydberg atom with a KRb(N = 0) diatomic polar molecule. There is significant electronic hybridization with the Rb(n = 24, $l\geqslant 3$) degenerate manifold. The polar diatomic molecule is allowed to rotate in the electric fields generated by the Rydberg electron and core as well as an external field. We investigate the metamorphosis of the Born–Oppenheimer potential curves, essential for the binding of the molecule, with varying electric field and analyze the resulting properties such as the vibrational structure and the alignment and orientation of the polar diatomic molecule.RGF gratefully acknowledges a Mildred Dresselhaus award from the excellence cluster 'The Hamburg Center for Ultrafast Imaging Structure, Dynamics and Control of Matter at the Atomic Scale' of the Deutsche Forschungsgemeinschaft and financial support by the Spanish Ministry of Science FIS2011-24540 (MICINN), grants P11-FQM-7276 and FQM-4643 (Junta de Andalucía), and by the Andalusian research group FQM-207. We also acknowledge financial support by the Initial Training Network COHERENCE of the European Union FP7 framework. HRS and PS acknowledge ITAMP at the Harvard-Smithsonian Center for Astrophysics for support

Bone Mineral Density and Associated Genetic Variants in High-level Caucasian Marathon Runners

INTRODUCTION:Endurance runners (except those who may have low energy availability) tend to have higher total and/or loading site-specific bone mineral density (BMD) in comparison with non-athletes, most likely due to the larger volume of exercise completed. A large genetic component also contributes to BMD, although little is known about which specific genes are involved, whether particular genotypes are sensitive to mechanical loading and the impact of such an interaction on BMD. This study investigated if high-level endurance runners possess enhanced BMD associated with an “advantageous” genetic predisposition, via a potential gene-physical activity interaction.METHODS:Age- and weight-adjusted total BMD (TBMD) and leg BMD (LBMD) measured via Dual-energy X-ray absorptiometry of 67 high-level Caucasian marathon runners (males < 2 h 45 min, n = 37; females < 3 15 min, n = 30) was compared with 40 male and 26 female non-athletes. LRP5 rs3736228, TNFRSF11B rs4355801, VDR rs2228570, WNT16 rs3801387 and AXIN1 rs9921222 variants were then investigated singularly, and collectively, as a total genotype score (TGS) via multivariate analysis of variance in a subgroup of this cohort (male runners n = 19, controls n = 26; female runners n = 17, controls n = 14). RESULTS:Male runners had higher TBMD (1.34 vs 1.28 g/cm2; P=0.02) and LBMD (1.53 vs 1.42 g/cm2; P=<0.01) than non-athletes. Female runners had higher LBMD than non-athletes (1.30 vs 1.22 g/cm2; P=0.02) but not TBMD (1.23 vs 1.18 g/cm2; P=0.22). An interaction (P=0.047) was observed between VDR rs2228570 genotype and group regarding LBMD in males: ff genotype runners had 0.02 g/cm2 higher LBMD than FF or Ff runners, but the FF genotype had the highest LBMD (1.45 g/cm2) amongst non-athletes. LBMD was also 0.12 g/cm2 higher in ff runners compared to ff non-athletes, whereas FF and Ff runners had 0.09 g/cm2 higher LBMD compared to their genotype-matched controls. No other interactions or variants, individually or collectively as part of a TGS, were associated with BMD (P≥0.11). CONCLUSION:High-level female runners possess higher LBMD but not TBMD in comparison with non-athletes whereas male runners possess both higher TBMD and LBMD than non-athletes. Consistent with prior literature, we observed higher BMD in VDR rs2228570 FF genotype in non-athletes, which may be due to increased biological activity associated with the F variant. However, our preliminary data suggest that the ff genotype may be associated with enhanced LBMD in male runners via a gene-environment interaction.Peer reviewedFinal Published versio

Conditionally-live attenuated SIV upregulates global T effector memory cell frequency under replication permissive conditions.

Background: Live attenuated SIV induces potent protection against superinfection with virulent virus; however the mechanism of this vaccine effect is poorly understood. Such knowledge is important for the development of clinically acceptable vaccine modalities against HIV. Results: Using a novel, doxycycline dependent, replication-competent live-attenuated SIVmac239Δnef (SIVrtTAΔnef), we show that under replication-permissive conditions SIV-rtTAΔnef is fully viable. Twelve rhesus macaques were infected with a peak plasma vRNA on average two log10 lower than in 6 macaques infected with unconditionally replication-competent SIVΔnef. Consistent with the attenuated phenotype of the viruses the majority of animals displayed low or undetectable levels of viraemia by 42-84 days after infection. Next, comparison of circulating T cells before and after chronic infection with parental SIVΔnef revealed a profound global polarisation toward CD28-CCR7- T-effector memory 2 (TEM2) cells within CD95+CD4+ and CD95+CD8+ populations. Critically, a similar effect was seen in the CD95+ CD4+ population and to somewhat lesser extent in the CD95+ CD8+ population of SIV-rtTAΔnef chronically infected macaques that were maintained on doxycycline, but was not seen in animals from which doxycycline had been withdrawn. The proportions of gut-homing T-central memory (TCM) and TEM defined by the expression of α4β7 and CD95 and differential expression of CD28 were increased in CD4 and CD8 cells under replication competent conditions and gut-homing CD4 TCM were also significantly increased under non-permissive conditions. TEM2 polarisation was seen in the small intestines of animals under replication permissive conditions but the effect was less pronounced than in the circulation. Intracellular cytokine staining of circulating SIV-specific T cells for IL-2, IFN-γ, TNF-α and IL-17 showed that the extent of polyfunctionality in CD4 and CD8 T cells was associated with replication permissivity; however, signature patterns of cytokine combinations were not distinguishable between groups of macaques. Conclusion: Taken together our results show that the global T memory cell compartment is profoundly skewed towards a mature effector phenotype by attenuated SIV. Results with the replication-conditional mutant suggest that maintenance of this effect, that may be important in vaccine design, might require persistence of replicating virus