Recurrent rearrangements of human amylase genes create multiple independent CNV series

The human amylase gene cluster includes the human salivary (AMY1) and pancreatic amylase genes (AMY2A and AMY2B), and is a highly variable and dynamic region of the genome. Copy number variation (CNV) of AMY1 has been implicated in human dietary adaptation, and in population association with obesity, but neither of these findings has been independently replicated. Despite these functional implications, the structural genomic basis of CNV has only been defined in detail very recently. In this work, we use high-resolution analysis of copy number, and analysis of segregation in trios, to define new, independent allelic series of amylase CNVs in sub-Saharan Africans, including a series of higher-order expansions of a unit consisting of one copy each of AMY1, AMY2A, and AMY2B. We use fiber-FISH (fluorescence in situ hybridization) to define unexpected complexity in the accompanying rearrangements. These findings demonstrate recurrent involvement of the amylase gene region in genomic instability, involving at least five independent rearrangements of the pancreatic amylase genes (AMY2A and AMY2B). Structural features shared by fundamentally distinct lineages strongly suggest that the common ancestral state for the human amylase cluster contained more than one, and probably three, copies of AMY1

Spectral Mixture Kernels with Time and Phase Delay Dependencies

Spectral Mixture (SM) kernels form a powerful class of kernels for Gaussian processes, capable to discover patterns, extrapolate, and model negative covariances. Being a linear superposition of quasi-periodical Gaussian components, an SM kernel does not explicitly model dependencies between components. In this paper we investigate the benefits of modeling explicitly time and phase delay dependencies between components in an AM kernel. We analyze the presence of statistical dependencies between components using Gaussian conditionals and posterior covariance and use this framework to motivate the proposed SM kernel extension, called Spectral Mixture kernel with time and phase delay Dependencies (SMD). SMD is constructed in two steps: first, time delay and phase delay are incorporated into each base component; next, cross-convolution between a base component and the reversed complex conjugate of another base component is performed which yields a complex-valued and positive definite kernel representing correlations between base components. The number of hyper-parameters of SMD, except the time and phase delay ones, remains equal to that of the SM kernel. We perform a thorough comparative experimental analysis of SMD on synthetic and real-life data sets. Results indicate the beneficial effect of modeling time and phase delay dependencies between base components, notably for natural phenomena involving little or no influence from human activity.Comment: 28 page

Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes

The human salivary amylase genes display extensive copy number variation (CNV), and recent work has implicated this variation in adaptation to starch-rich diets, and in association with body mass index. In this work, we use paralogue ratio tests, microsatellite analysis, read depth and fibre-FISH to demonstrate that human amylase CNV is not a smooth continuum, but is instead partitioned into distinct haplotype classes. There is a fundamental structural distinction between haplotypes containing odd or even numbers of AMY1 gene units, in turn coupled to CNV in pancreatic amylase genes AMY2A and AMY2B. Most haplotypes have one copy each of AMY2A and AMY2B and contain an odd number of copies of AMY1; consequently, most individuals have an even total number of AMY1. In contrast, haplotypes carrying an even number of AMY1 genes have rearrangements leading to CNVs ofAMY2A/AMY2B. Read-depth and experimental data showthat different populations harbour different proportions of these basic haplotype classes. In Europeans, the copy numbers of AMY1 and AMY2A are correlated, so that phenotypic associations caused by variation in pancreatic amylase copy number could be detected indirectly as weak association with AMY1 copy number.We showthat the quantitative polymerase chain reaction (qPCR) assay previously applied to the high-throughput measurement of AMY1 copy number is less accurate than the measures we use and that qPCR data in other studies have been further compromised by systematic miscalibration. Our results uncover new patterns in human amylase variation and imply a potential role for AMY2 CNV in functional associations

Interference with the Host Haemostatic System by Schistosomes

Schistosomes, parasitic flatworms that cause the tropical disease schistosomiasis, are still a threat. They are responsible for 200 million infections worldwide and an estimated 280,000 deaths annually in sub-Saharan Africa alone. The adult parasites reside as pairs in the mesenteric or perivesicular veins of their human host, where they can survive for up to 30 years. The parasite is a potential activator of blood coagulation according to Virchow's triad, because it is expected to alter blood flow and endothelial function, leading to hypercoagulability. In contrast, hepatosplenic schistosomiasis patients are in a hypocoagulable and hyperfibrinolytic state, indicating that schistosomes interfere with the haemostatic system of their host. In this review, the interactions of schistosomes with primary haemostasis, secondary haemostasis, fibrinolysis, and the vascular tone will be discussed to provide insight into the reduction in coagulation observed in schistosomiasis patients.Interference with the haemostatic system by pathogens is a common mechanism and has been described for other parasitic worms, bacteria, and fungi as a mechanism to support survival and spread or enhance virulence. Insight into the mechanisms used by schistosomes to interfere with the haemostatic system will provide important insight into the maintenance of the parasitic life cycle within the host. This knowledge may reveal new potential anti-schistosome drug and vaccine targets. In addition, some of the survival mechanisms employed by schistosomes might be used by other pathogens, and therefore, these mechanisms that interfere with host haemostasis might be a broad target for drug development against blood-dwelling pathogens. Also, schistosome antithrombotic or thrombolytic molecules could form potential new drugs in the treatment of haemostatic disorders

Potential mechanisms of the fatigue-reducing effect of cognitive-behavioral therapy in cancer survivors:Three randomized controlled trials

OBJECTIVE: Fatigue is a common symptom among cancer survivors that can be successfully treated with cognitive‐behavioral therapy (CBT). Insights into the working mechanisms of CBT are currently limited. The aim of this study was to investigate whether improvements in targeted cognitive‐behavioral variables and reduced depressive symptoms mediate the fatigue‐reducing effect of CBT. METHODS: We pooled data from three randomized controlled trials that tested the efficacy of CBT to reduce severe fatigue. In all three trials, fatigue severity (checklist individual strength) decreased significantly following CBT. Assessments were conducted pre‐treatment and 6 months later. Classical mediation analysis testing a pre‐specified model was conducted and its results compared to those of causal discovery, an explorative data‐driven approach testing all possible causal associations and retaining the most likely model. RESULTS: Data from 250 cancer survivors (n = 129 CBT, n = 121 waitlist) were analyzed. Classical mediation analysis suggests that increased self‐efficacy and decreased fatigue catastrophizing, focusing on symptoms, perceived problems with activity and depressive symptoms mediate the reduction of fatigue brought by CBT. Conversely, causal discovery and post‐hoc analyses indicate that fatigue acts as mediator, not outcome, of changes in cognitions, sleep disturbance and depressive symptoms. CONCLUSIONS: Cognitions, sleep disturbance and depressive symptoms improve during CBT. When assessed pre‐ and post‐treatment, fatigue acts as a mediator, not outcome, of these improvements. It seems likely that the working mechanism of CBT is not a one‐way causal effect but a dynamic reciprocal process. Trials integrating intermittent assessments are needed to shed light on these mechanisms and inform optimization of CBT

Optical properties and one-particle spectral function in non-ideal plasmas

A basic concept to calculate physical features of non-ideal plasmas, such as optical properties, is the spectral function which is linked to the self-energy. We calculate the spectral function for a non-relativistic hydrogen plasma in $GW$-approximation. In order to go beyond $GW$ approximation, we include self-energy and vertex correction to the polarization function in lowest order. Partial compensation is observed. The relation of our approach to $GW$ and $GW\Gamma$ calculations in other fields, such as the band-structure calculations in semiconductor physics, is discussed. From the spectral function we derive the absorption coefficient due to inverse bremsstrahlung via the polarization function. As a result, a significant reduction of the absorption as compared to the Bethe-Heitler formula for bremsstrahlung is obtained.Comment: 13 pages, 7 figures, 52 references. Submitted to Contrib. Plasma Phys. Results presented at the International Workshop on Physics of Non-ideal Plasmas (PNP12), Darmstadt, sept. 4.-8. 200

Patterns and frequency of anxiety in women undergoing gynaecological surgery

Patterns and frequency of anxiety in women undergoing gynaecological surgery Aims. Within a gynaecological surgical setting to identify the patterns and frequency of anxiety pre- and postoperatively; to identify any correlation between raised anxiety levels and postoperative pain; to identify events, from the patients’ perspective, that may increase or decrease anxiety in the pre- and postoperative periods. Background. It is well documented that surgery is associated with increased anxiety, which has an adverse impact on patient outcomes. Few studies have been conducted to obtain the patient’s perspective on the experience of anxiety and the events and situations that aggravate and ameliorate it. Method. The study used a mixed method approach. The sample consisted of women undergoing planned gynaecological surgery. Anxiety was assessed using the State Trait Anxiety Inventory. Trait anxiety was measured at the time of recruitment. State anxiety was then assessed at six time points during the pre- and postoperative periods. Postoperative pain was also measured using a 10 cm visual analogue scale. Taped semi-structured telephone interviews were conducted approximately a week after discharge. Results. State anxiety rose steadily from the night before surgery to the point of leaving the ward to go to theatre. Anxiety then increased sharply prior to the anaesthetic decreasing sharply afterwards. Patients with higher levels of trait anxiety were more likely to experience higher levels of anxiety throughout their admission. Elevated levels of pre- and postoperative anxiety were associated with increased levels of postoperative pain. Telephone interviews revealed a range of events/situations that patients recalled distressing them and many were related to inadequate information. Conclusion. This study found higher rates of anxiety than previously reported and anxiety levels appeared raised before admission to hospital. This has important clinical and research implications.Relevance to clinical practice. Patients with high levels of anxiety may be identified preoperatively and interventions designed to reduce anxiety could be targeted to this vulnerable group. Patient experiences can inform the delivery of services to meet their health needs better