Quality control and integration of genotypes from two calling pipelines for whole genome sequence data in the Alzheimer's disease sequencing project

The Alzheimer's Disease Sequencing Project (ADSP) performed whole genome sequencing (WGS) of 584 subjects from 111 multiplex families at three sequencing centers. Genotype calling of single nucleotide variants (SNVs) and insertion-deletion variants (indels) was performed centrally using GATK-HaplotypeCaller and Atlas V2. The ADSP Quality Control (QC) Working Group applied QC protocols to project-level variant call format files (VCFs) from each pipeline, and developed and implemented a novel protocol, termed “consensus calling,” to combine genotype calls from both pipelines into a single high-quality set. QC was applied to autosomal bi-allelic SNVs and indels, and included pipeline-recommended QC filters, variant-level QC, and sample-level QC. Low-quality variants or genotypes were excluded, and sample outliers were noted. Quality was assessed by examining Mendelian inconsistencies (MIs) among 67 parent-offspring pairs, and MIs were used to establish additional genotype-specific filters for GATK calls. After QC, 578 subjects remained. Pipeline-specific QC excluded ~12.0% of GATK and 14.5% of Atlas SNVs. Between pipelines, ~91% of SNV genotypes across all QCed variants were concordant; 4.23% and 4.56% of genotypes were exclusive to Atlas or GATK, respectively; the remaining ~0.01% of discordant genotypes were excluded. For indels, variant-level QC excluded ~36.8% of GATK and 35.3% of Atlas indels. Between pipelines, ~55.6% of indel genotypes were concordant; while 10.3% and 28.3% were exclusive to Atlas or GATK, respectively; and ~0.29% of discordant genotypes were. The final WGS consensus dataset contains 27,896,774 SNVs and 3,133,926 indels and is publicly available.     

An application of scissored-pair control moment gyroscopes in a design of wearable balance assistance device for the elderly

Impaired balance control ability and degraded functional mobility increases the risk of falling in elderly people. The elderly show more postural sway when standing compared with young people. A sway fall occurs when the center of gravity moves outside the limit of stability. In order to reduce the fall risk from the excessive sway, this study presents the design of wearable balance assistance device for the elderly. Scissored-pair control moment gyroscopes were selected as a torque actuator. A two-axis inclination sensor was used to detect the inclined angle of the wearer’s body. The direction of sway was calculated from the detected inclined angle. The designed device weighs 8.2 kg with a height of 32 cm × width of 40 cm × depth of 22 cm. A multi-segment model of a standing human was used to investigate the device’s performance for balance recovery. According to the simulations, balance recovery in any direction was successfully accomplished with the appropriate initial angle. The relationship between the effective initial angle and detected inclined angle was subsequently established. The stability provided by activation of the device was able to limit the unstable user’s sway boundary. The designed device shows promise for use as a balance assistance device for the elderly.     

Comparison of the human-exosuit interaction using ankle moment and ankle positive power inspired walking assistance

Previous ankle exoskeleton assistance techniques that were able to demonstrate metabolic reductions can be categorized into those that delivered moment profiles similar to the biological ankle moment throughout the stance phase, and others that delivered positive power only during push off. Both assistance techniques and a powered-off condition were compared in treadmill walking (1.5 m s⁻¹) with a soft exosuit. We hypothesized that both techniques can result in a similar metabolic reduction when providing a similar level of average positive exosuit power at each ankle (0.12 W kg⁻¹) and hip (0.02 W kg⁻¹) while the underlying global center-of-mass and local joint biomechanics would be different. We found a similar net metabolic rate reduction of 15% relative to walking with the suit powered-off for both techniques. The ankle moment inspired technique showed larger magnitudes of reductions for biological moment and power at the hip and the ankle. The ankle power inspired technique might benefit from higher biological efficiency, when reducing positive instead of negative power at the knee and when almost keeping the isometric function of the plantarflexors before push-off. Changes at the ankle caused energetic reductions at the knee, hip and the center-of-mass. A major contribution to metabolic reduction might be based on them. As the lower limb biomechanics that led to these reductions were different, we believe that humans alter their gait to maximize their energetic benefit based on the exosuit assistance. For further insights on mechanisms that lead to metabolic reduction, joint mechanics and muscle-tendon dynamics must be analyzed in combination.     

Correlations of pelvis state to foot placement do not imply within-step active control

Experimental studies of human walking have shown that within an individual step, variations in the center of mass (CoM) state can predict corresponding variations in the next foot placement. This has been interpreted by some to indicate the existence of active control in which the nervous system uses the CoM state at or near mid-stance to regulate subsequent foot placement. However, the passive dynamics of the moving body and/or moving limbs also contribute (perhaps strongly) to foot placement, and thus to its variation. The extent to which correlations of CoM state to foot placement reflect the effects of within-step active control, those of passive dynamics, or some combination of both, remains an important and still open question. Here, we used an open-loop-stable 2D walking model to show that this predictive ability cannot by itself be taken as evidence of within-step active control. In our simulations, we too find high correlations between the CoM state and subsequent foot placement, but these correlations are entirely due to passive dynamics as our system has no active control, either within a step or between steps. This demonstrates that any inferences made from such correlations about within-step active control require additional supporting evidence beyond the correlations themselves. Thus, these within-step predictive correlations leave unresolved the relative importance of within-step active control as compared to passive dynamics, meaning that such methods should be used to characterize control in human walking only with caution.     

韩国与中国东北地区松鼠线粒体DNA控制区的序列变异

为了研究松鼠东北亚种(Sciurus vulgaris manchuricusThomas)不同种群的序列变异水平并进一步确定分类地位,我们分析了韩国5个地点和中国东北2个地点的松鼠标本的线粒体DNA控制区的全序列(1 058 bp)。39个韩国松鼠标本显示出21种单倍型,这些单倍型间的平均Tamura-Nei距离为1·0%; 24个中国松鼠标本显示21种单倍型,单倍型间的平均Tamura-Nei距离为1·4% (1 058 bp的全序列中发生变异的位点有119个,占11·2%)。韩国松鼠和中国松鼠间的平均距离为1·3%。并且韩国和中国松鼠的所有42个单倍型形成了一个单系分支,Fst值为0·04,表明在两个国家的松鼠间没有发生遗传分化。因此,序列分析的分子生物学的结果支持现行的分类,即来自韩国的朝鲜亚种(S·v·coreae)是中国北部地区松鼠东北亚种(S·v·manchuricus)的同物异名。这还需要进一步对北朝鲜和中国东北其它地区更多标本的分子和形态学分析来验证这一结论。     

Sustainable management of grassland ecosystems for controlling Asian dusts and desertification in Asian continent and a suggestion of Eco-Village study in China

Asian dusts, yellow sand, or dust and sand storms (DSS) in Asian continent are the end products of desertification, which became a regional environmental problem being aggravated by time. It is closely related to an issue of sustainability in the region. As the desertification is caused not only by natural factors, such as the climate change, strong wind, and low precipitation, but also by rapidly increasing human activities, such as overgrazing, misuse of water resources, and irrational land use, it is urgent to make efforts to combat desertification in Asian continent including China. In this regard, it is necessary to consider socio-economic aspects as well as ecological aspects and, consequently, the project for the construction of a Demonstration Model Village for eco-environmental rehabilitation should be paid to a special attention. The authors deal with this regional issue in consideration of three Es, which are represented by ecology, economy, and environment in providing the perspectives in sound approach to the issue. As an approach to the issue of Asian dusts and desertification in Asian continent, this Eco-Village study provides one way forward.     

Dictyocaulus viviparus bulk tank milk seropositivity is correlated with meteorological variables

Control of infections with Dictyocaulus viviparus is difficult due to its volatile epidemiology. In the absence of predictive models, ‘vigilance and treatment’ is today’s mainstay for control. In order to evaluate the potential of predictive model development to support a more preventative approach, this longitudinal study aimed at understanding the influence of weather factors on D. viviparus bulk tank milk antibody ELISA results. Bulk tank milk samples were analysed with a Major Sperm Protein-based ELISA (expressed as an optical density ratio) twice monthly on 717 Flemish dairy farms during the grazing season (April–October) in 2018. Meteorological data of the sampled farms were obtained at 1 km spatial scale using the ALARO-SURFEX climate model. A mixed effects model showed that the bulk tank milk optical density ratio was significantly associated with the month of sampling, evapotranspiration, temperature and its quadratic term, the number of hot days and the number of rainy days in the 7–8 weeks prior to sampling. There were significant farm effects involved. The model’s accuracy to predict bulk tank milk optical density ratio infection status was 80%, while optical density ratios were generally overestimated by 38%. Inclusion of the previous (2-week-old) optical density ratio values increased accuracy to 86% and reduced the mean square error. We conclude that meteorological parameters have a predictive value for bulk tank milk optical density ratio results, while further research should evaluate model improvements through the addition of herd management factors as well as confirm the predictive power through external validation in additional farms and years.     

Under pressure from above: Overgrazing decreases mycorrhizal colonization of both preferred and unpreferred grasses in the Patagonian steppe

Arbuscular mycorrhizal fungi (AMF) are related to plant community dynamics and ecosystem functioning. Overgrazing can negatively affect plant performance, and consequently unbalance the association with AMF. We studied the grazing effect on AMF colonization for preferred (Bromus pictus and Poa ligularis) and unpreferred grasses (Pappostipa speciosa and Pappostipa humilis) by sheep in the Patagonian steppe. For each species, AMF colonization in ungrazed, moderate and intense grazing sites was quantified. In ungrazed areas, B. pictus showed the highest extent of AMF colonization. Mycorrhizal colonization was higher during the active season, and largely reduced by intense grazing conditions. The decrease of AMF colonization was maximal for the most preferred species, but also significant for the unpreferred species. Our results suggest that overgrazing could reduce mycorrhizal benefits for the plant by reduction of AMF colonization, which can be a good indicator of ecosystem functioning, eventually revealing an increasing degree of environmental degradation.     

Murine Norovirus 1 (MNV1) Replication Induces Translational Control of the Host by Regulating eIF4E Activity during Infection

Protein synthesis is a tightly controlled process responding to several stimuli, including viral infection. As obligate intracellular parasites, viruses depend on the translation machinery of the host and can manipulate it by affecting the availability and function of specific eukaryotic initiation factors (eIFs). Human norovirus is a member of the Caliciviridae family and is responsible for gastroenteritis outbreaks. Previous studies on feline calicivirus and murine norovirus 1 (MNV1) demonstrated that the viral protein, genome-linked (VPg), acts to direct translation by hijacking the host protein synthesis machinery. Here we report that MNV1 infection modulates the MAPK pathway to activate eIF4E phosphorylation. Our results show that the activation of p38 and Mnk during MNV1 infection is important for MNV1 replication. Furthermore, phosphorylated eIF4E relocates to the polysomes, and this contributes to changes in the translational state of specific host mRNAs. We propose that global translational control of the host by eIF4E phosphorylation is a key component of the host-pathogen interaction.     

An immune response profile model for immunogenicity quantitation

We propose an analytical model, which can simultaneously depict many fundamental characteristics of the immunogenicity of various vaccines. This model, the Immune Response (IR) profile, conveniently expresses the mathematical relation between pre- and post-vaccination titers. A vaccine's IR profile is antigen-specific, dose-dependent and post-vaccination interval-dependent. The maximal capability for serological response to a vaccine can be determined using this model irrespective of the dose administered, the post-vaccination assay interval, or the live or killed state of the vaccine. The IR profile obtained from analysis of booster vaccine responses in a limited number of seropositive study subjects can be used to predict maximal antibody titers which are expected after vaccination and can predict the geometric mean post-vaccination antibody titer of a cohort of subjects undergoing primary immunization. Using this model, it is anticipated that the immunoregulation implied by the IR profile may also prove to be correlated with cellular subpopulations and idiotypic antibody functions. Although derived from influenza vaccines analyses, the model successfully describes immune response characteristics following natural infection with malaria and following diphtheria and rubella vaccine administration.