Multiregional origins of the domesticated tetraploid wheats

We used genotyping-by-sequencing (GBS) to investigate the evolutionary history of domesticated tetraploid wheats. With a panel of 189 wild and domesticated wheats, we identified 1,172,469 single nucleotide polymorphisms (SNPs) with a read depth ≥3. Principal component analyses (PCAs) separated the Triticum turgidum and Triticum timopheevii accessions, as well as wild T. turgidum from the domesticated emmers and the naked wheats, showing that SNP typing by GBS is capable of providing robust information on the genetic relationships between wheat species and subspecies. The PCAs and a neighbour-joining analysis suggested that domesticated tetraploid wheats have closest affinity with wild emmers from the northern Fertile Crescent, consistent with the results of previous genetic studies on the origins of domesticated wheat. However, a more detailed examination of admixture and allele sharing between domesticates and different wild populations, along with genome-wide association studies (GWAS), showed that the domesticated tetraploid wheats have also received a substantial genetic input from wild emmers from the southern Levant. Taking account of archaeological evidence that tetraploid wheats were first cultivated in the southern Levant, we suggest that a pre-domesticated crop spread from this region to southeast Turkey and became mixed with a wild emmer population from the northern Fertile Crescent. Fixation of the domestication traits in this mixed population would account for the allele sharing and GWAS results that we report. We also propose that feralization of the component of the pre-domesticated population that did not acquire domestication traits has resulted in the modern wild population from southeast Turkey displaying features of both the domesticates and wild emmer from the southern Levant, and hence appearing to be the sole progenitor of domesticated tetraploids when the phylogenetic relationships are studied by methods that assume a treelike pattern of evolution.This work was supported by: TAB, 339941, European Research Council; TAB, NE/M010805/1, Natural Environment Research Councilinfo:eu-repo/semantics/publishedVersio

Running marathons in high school: A 5-year review of injury in a structured training program

Objective: The aim in this study was to quantify the number, nature, and severity of injuries sustained by male and female high school students who took part in a running training program that culminated in the completion of a half or full marathon. Design: This study is a retrospective clinical audit. Methods: Injury reports from high school students (grades 9 – 12) who participated in a half or full marathon 30-week progressive training program comprising four training days per week (three running days and one cross-training day) were reviewed. The number of runners completing a marathon, together with the number, nature, severity of injuries, and treatment types, as reported to the program physiotherapist, were the main outcome measures. Results: Program completion was 96% (n = 448/469). Of all participants, 186 (39.6 %) were injured, with 14 withdrawing from the program due to injury. For those who completed a marathon, 172 (38 %) reported 205 musculoskeletal injuries (age of injured runners: 16.3 ± 1.1 years; 88 girls (51.2 %) and 84 boys (48.8 %)). More than half (n = 113, 55.1 %) of the reported injuries were soft tissue injuries. Most injuries were localized to the lower leg (n = 88, 42.9 %) and were of a minor nature (n = 181, 90 %), requiring only 1–2 treatments. Conclusions: There was a low number of relatively minor injuries for high school participants taking part in a graduated and supervised marathon training program. The injury definition was conservative (i.e., any attendance to physiotherapist) and the relative severity of injuries was minor (i.e., requiring 1 – 2 treatment sessions). Overall, these results do not support a need to restrict high school students from taking part in marathon running, though continued emphasis on graduated program development and close supervision of young participants is recommended

Abetalipoproteinemia Due to a Novel Splicing Variant in MTTP in 3 Siblings

Abetalipoproteinemia (ABL) is a rare recessive condition caused by biallelic loss-of-function mutations in the MTTP gene encoding the microsomal triglyceride transfer protein large subunit. ABL is characterized by absence of apolipoprotein B–containing lipoproteins and deficiencies in fat-soluble vitamins leading to multisystem involvement of which neurological complications are the most serious. We present 3 siblings with ABL who were born to non-consanguineous parents of Filipino and Chinese background. Identical twin boys with long-standing failure to thrive and malabsorption were diagnosed at age 2 years. ABL therapy with vitamins and a specialized diet was initiated, replacing total parenteral nutrition at age 3 years. Their younger sister was diagnosed from a blood sample taken at birth; treatment was instituted shortly thereafter. We observed in the twins reversal and in their sister prevention of ABL systemic features following early implementation of fat restriction and high doses of oral fat-soluble vitamins. A targeted sequencing panel found that each affected sibling is homozygous for a novel MTTP intron 13 -2A\u3eG splice acceptor site mutation, predicted to abolish splicing of intron 13. This variant brings to more than 60 the number of reported pathogenic mutations, which are summarized in this article. The twin boys and their sister are now doing well at 11 and 4 years of age, respectively. This experience underscores the importance of early initiation of targeted specialized dietary and fat-soluble vitamin replacements in ABL

Rocaglates as dual-targeting agents for experimental cerebral malaria

Cerebral malaria (CM) is a severe and rapidly progressing complication of infection by Plasmodium parasites that is associated with high rates of mortality and morbidity. Treatment options are currently few, and intervention with artemisinin (Art) has limited efficacy, a problem that is compounded by the emergence of resistance to Art in Plasmodium parasites. Rocaglates are a class of natural products derived from plants of the Aglaia genus that have been shown to interfere with eukaryotic initiation factor 4A (eIF4A), ultimately blocking initiation of protein synthesis. Here, we show that the rocaglate CR-1-31B perturbs association of Plasmodium falciparum eIF4A (PfeIF4A) with RNA. CR-1-31B shows potent prophylactic and therapeutic antiplasmodial activity in vivo in mouse models of infection with Plasmodium berghei (CM) and Plasmodium chabaudi (blood-stage malaria), and can also block replication of different clinical isolates of P. falciparum in human erythrocytes infected ex vivo, including drug-resistant P. falciparum isolates. In vivo, a single dosing of CR-1-31B in P. berghei-infected animals is sufficient to provide protection against lethality. CR-1-31B is shown to dampen expression of the early proinflammatory response in myeloid cells in vitro and dampens the inflammatory response in vivo in P. berghei-infected mice. The dual activity of CR-1-31B as an antiplasmodial and as an inhibitor of the inflammatory response in myeloid cells should prove extremely valuable for therapeutic intervention in human cases of CM.We thank Susan Gauthier, Genevieve Perreault, and Patrick Senechal for technical assistance. This work was supported by a research grant (to P.G.) from the Canadian Institutes of Health Research (CIHR) (Foundation Grant). J.P. and P.G. are supported by a James McGill Professorship salary award. D.L. is supported by fellowships from the Fonds de recherche sante Quebec, the CIHR Neuroinflammation training program. J.P. is supported by CIHR Research Grant FDN-148366. M.S. is supported by a CIHR Foundation grant. J.A.P. is supported by NIH Grant R35 GM118173. Work at the Boston University Center for Molecular Discovery is supported by Grant R24 GM111625. K.C.K. was supported by a CIHR Foundation Grant and the Canada Research Chair program. (Canadian Institutes of Health Research (CIHR); James McGill Professorship salary award; Fonds de recherche sante Quebec; CIHR Neuroinflammation training program; FDN-148366 - CIHR Research Grant; CIHR Foundation grant; R35 GM118173 - NIH; Canada Research Chair program; R24 GM111625

Effects of Three Modest Levels of Proximal Loading on Marathon Pace Running Economy

International Journal of Exercise Science 13(7): 1120-1131, 2020. This study examined the effect of modest increases in proximal body mass on running economy expressed as metabolic cost (MC). External loads of 1.6 (L), 2.4 (M), and 3.2 kg (H) were added to the anterior and posterior torso region of male (n = 18) and female (n = 18) runners using a double-layered compression garment with gel inserts. MC was evaluated using stoichiometry equations of data collected via indirect calorimetry. Data was collected during four, 5-min running bouts at marathon pace for the 3 load levels and an unloaded state (CON). When data from both sexes were combined, MC for CON (13.2 ± 2.7) was lower (p \u3c 0.05) versus L (13.5 ± 2.6), M (13.6 ± 2.6), and H (13.7 ± 2.6 kcal/min), but L did not differ from CON when data was analyzed for each sex. Male runners exhibited stepped increases in MC across loads and a weak-moderate relationship (r = 0.37; p \u3c 0.01) between percentage change in absolute MC and increased percent body mass. A prediction model for MC (∆% kcal/min = 0.98(∆% body mass) – 0.91; SEE = ± 2.5%) was developed. For female runners, L increased MC by ~3.5% above CON, but no differentiation was found among L, M, and H, limiting the development of a prediction equation for females. Modest increases in body mass can produce detectable and potentially important levels of running economy impairment, but the relationship between changes in body mass and RE are complex, particularly in regards to sex

Visual-olfactory integration in the human disease vector mosquito, Aedes aegypti

Mosquitoes rely on the integration of multiple sensory cues, including olfactory, visual, and thermal stimuli, to detect, identify, and locate their hosts [1, 2, 3, 4]. Although we increasingly know more about the role of chemosensory behaviors in mediating mosquito-host interactions [1], the role of visual cues is comparatively less studied [3], and how the combination of olfactory and visual information is integrated in the mosquito brain remains unknown. In the present study, we used a tethered-flight light-emitting diode (LED) arena, which allowed for quantitative control over the stimuli, and a control theoretic model to show that CO_2 modulates mosquito steering responses toward vertical bars. To gain insight into the neural basis of this olfactory and visual coupling, we conducted two-photon microscopy experiments in a new GCaMP6s-expressing mosquito line. Imaging revealed that neuropil regions within the lobula exhibited strong responses to objects, such as a bar, but showed little response to a large-field motion. Approximately 20% of the lobula neuropil we imaged were modulated when CO2 preceded the presentation of a moving bar. By contrast, responses in the antennal (olfactory) lobe were not modulated by visual stimuli presented before or after an olfactory stimulus. Together, our results suggest that asymmetric coupling between these sensory systems provides enhanced steering responses to discrete objects

Deletion of the Stress Response Gene \u3ci\u3eDDR48\u3c/i\u3e From \u3ci\u3eHistoplasma capsulatum\u3c/i\u3e Increases Sensitivity to Oxidative Stress, Increases Susceptibility to Antifungals, and Decreases Fitness In Macrophages

The stress response gene DDR48 has been characterized in Saccharomyces cerevisiae and Candida albicans to be involved in combating various cellular stressors, from oxidative agents to antifungal compounds. Surprisingly, the biological function of DDR48 has yet to be identified, though it is likely an important part of the stress response. To gain insight into its function, we characterized DDR48 in the dimorphic fungal pathogen Histoplasma capsulatum. Transcriptional analyses showed preferential expression of DDR48 in the mycelial phase. Induction of DDR48 in Histoplasma yeasts developed after treatment with various cellular stress compounds. We generated a ddr48∆ deletion mutant to further characterize DDR48 function. Loss of DDR48 alters the transcriptional profile of the oxidative stress response and membrane synthesis pathways. Treatment with ROS or antifungal compounds reduced survival of ddr48∆ yeasts compared to controls, consistent with an aberrant cellular stress response. In addition, we infected RAW 264.7 macrophages with DDR48-expressing and ddr48∆ yeasts and observed a 50% decrease in recovery of ddr48∆ yeasts compared to wild-type yeasts. Loss of DDR48 function results in numerous negative effects in Histoplasma yeasts, highlighting its role as a key player in the global sensing and response to cellular stress by fungi

The Role of Glutamate and GABA in Autism Spectrum Disorders: Pilot Results from a Proton Magnetic Resonance Spectroscopy Study

Objectives: To measure the levels of glutamate, a major excitatory neurotransmitter; glutamine, a metabolite of glutamate; and γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter; in a pilot study of proton magnetic resonance spectroscopy (1H-MRS) findings in adolescents with Autism Spectrum Disorders (ASD). Methods: The subjects were assessed with the Autism Diagnostic Observation Schedule (ADOS), the Reading the Mind in the Eyes test (RMET) and the Social Responsiveness Scale (SRS). 1H-MRS measures of the anterior cingulate cortex were conducted using a Philips 3.0 T scanner. Results: To date, we have completed the data analysis on 18 subjects, 8 with ASD and 10 healthy control (HC) subjects. There was no significant difference between the combined glutamate + glutamine concentrations as measured by 1H-MRS (ASD = 12.0 ± 0.9 IU, HC = 11.6 ± 0.8 IU, p = 0.37). However, there was a higher than average glutamine level in the ASD group compared to healthy controls (ASD = 2.4 ± 0.2 IU, HC = 1.9 ± 0.3 IU, p = 0.01). This was accompanied by a trend toward lower GABA/Cr levels in the ASD group (ASD = 0.073 ± 0.010, HC = 0.082 ± 0.010, p = 0.06). Glutamine levels in the ACC were correlated positively with deficits of social cognition across groups (higher SRS, lower RMET scores). Those with higher glutamine levels made more errors when identifying emotions in the RMET task (r(10) = -0.77, p = 0.009), and also had more clinically significant scores on the SRS (r(10) = 0.87, p = 0.001). Conclusions: Our results present evidence that glutamine levels measured within the ACC region are higher for adolescent males with ASD than age-matched HC males, and signal that GABA levels may also be decreased in this region. These changes are correlated with deficits in social cognition

Impact of vascular screening interventions on perceived threat, efficacy beliefs and behavioural intentions: A systematic narrative review

Health-related behaviours contribute to the global burden of cardiovascular disease (CVD). Cardiovascular imaging can be used to screen asymptomatic individuals for increased risk of CVD to enable earlier interventions to promote health-related behaviours to prevent or reduce CVD risk. Some theories of behaviour and behaviour change assume that engagement in a given behaviour is a function of individual threat appraisals, beliefs regarding the performance of behaviour, self-efficacy for performing the desired behaviour and/or dispositions to act (e.g. behavioural intentions). To date, little is known about the impact of cardiovascular imaging interventions on these constructs. This article summarises evidence related to perceived threat, efficacy beliefs, and behavioural intentions after CVD screening. We identified 10 studies (2 RCTs and 8 non-randomised studies, n = 2498) through a combination of screening citations from published systematic reviews and meta-analyses and searching electronic databases. Of these, 7 measured behavioural intentions and perceived susceptibility and 3 measured efficacy beliefs. Findings showed largely encouraging effects of screening interventions on bolstering self-efficacy beliefs and strengthening behavioural intentions. Imaging results that suggest the presence of coronary or carotid artery disease also increased perceived susceptibility to CVD. However, the review also identified some gaps in the literature, such as a lack of guiding theoretical frameworks and assessments of critical determinants of health-related behaviours. By carefully considering the key issues highlighted in this review, we can make significant strides towards reducing CVD risks and improving population health

py4DSTEM: a software package for multimodal analysis of four-dimensional scanning transmission electron microscopy datasets

Scanning transmission electron microscopy (STEM) allows for imaging, diffraction, and spectroscopy of materials on length scales ranging from microns to atoms. By using a high-speed, direct electron detector, it is now possible to record a full 2D image of the diffracted electron beam at each probe position, typically a 2D grid of probe positions. These 4D-STEM datasets are rich in information, including signatures of the local structure, orientation, deformation, electromagnetic fields and other sample-dependent properties. However, extracting this information requires complex analysis pipelines, from data wrangling to calibration to analysis to visualization, all while maintaining robustness against imaging distortions and artifacts. In this paper, we present py4DSTEM, an analysis toolkit for measuring material properties from 4D-STEM datasets, written in the Python language and released with an open source license. We describe the algorithmic steps for dataset calibration and various 4D-STEM property measurements in detail, and present results from several experimental datasets. We have also implemented a simple and universal file format appropriate for electron microscopy data in py4DSTEM, which uses the open source HDF5 standard. We hope this tool will benefit the research community, helps to move the developing standards for data and computational methods in electron microscopy, and invite the community to contribute to this ongoing, fully open-source project