ABSTRACT
Horse domestication revolutionized warfare and accelerated travel, trade, and the geographic expansion of languages. Here, we present the largest DNA time series for a non-human organism to date, including genome-scale data from 149 ancient animals and 129 ancient genomes (≥1-fold coverage), 87 of which are new. This extensive dataset allows us to assess the modern legacy of past equestrian civilizations. We find that two extinct horse lineages existed during early domestication, one at the far western (Iberia) and the other at the far eastern range (Siberia) of Eurasia. None of these contributed significantly to modern diversity. We show that the influence of Persian-related horse lineages increased following the Islamic conquests in Europe and Asia. Multiple alleles associated with elite-racing, including at the MSTN "speed gene," only rose in popularity within the last millennium. Finally, the development of modern breeding impacted genetic diversity more dramatically than the previous millennia of human management.
Subject(s)
Horses/genetics , Animals , Asia , Biological Evolution , Breeding/history , DNA, Ancient/analysis , Domestication , Equidae/genetics , Europe , Female , Genetic Variation/genetics , Genome/genetics , History, Ancient , Male , PhylogenyABSTRACT
During the Early Bronze Age, populations of the western Eurasian steppe expanded across an immense area of northern Eurasia. Combined archaeological and genetic evidence supports widespread Early Bronze Age population movements out of the Pontic-Caspian steppe that resulted in gene flow across vast distances, linking populations of Yamnaya pastoralists in Scandinavia with pastoral populations (known as the Afanasievo) far to the east in the Altai Mountains1,2 and Mongolia3. Although some models hold that this expansion was the outcome of a newly mobile pastoral economy characterized by horse traction, bulk wagon transport4-6 and regular dietary dependence on meat and milk5, hard evidence for these economic features has not been found. Here we draw on proteomic analysis of dental calculus from individuals from the western Eurasian steppe to demonstrate a major transition in dairying at the start of the Bronze Age. The rapid onset of ubiquitous dairying at a point in time when steppe populations are known to have begun dispersing offers critical insight into a key catalyst of steppe mobility. The identification of horse milk proteins also indicates horse domestication by the Early Bronze Age, which provides support for its role in steppe dispersals. Our results point to a potential epicentre for horse domestication in the Pontic-Caspian steppe by the third millennium BC, and offer strong support for the notion that the novel exploitation of secondary animal products was a key driver of the expansions of Eurasian steppe pastoralists by the Early Bronze Age.
Subject(s)
Dairying/history , Human Migration , Proteome , Animals , Archaeology , Asia , Dental Calculus/metabolism , Domestication , Europe , Gene Flow , Grassland , History, Ancient , Horses , Humans , MilkABSTRACT
We are a group of archaeologists, anthropologists, curators and geneticists representing diverse global communities and 31 countries. All of us met in a virtual workshop dedicated to ethics in ancient DNA research held in November 2020. There was widespread agreement that globally applicable ethical guidelines are needed, but that recent recommendations grounded in discussion about research on human remains from North America are not always generalizable worldwide. Here we propose the following globally applicable guidelines, taking into consideration diverse contexts. These hold that: (1) researchers must ensure that all regulations were followed in the places where they work and from which the human remains derived; (2) researchers must prepare a detailed plan prior to beginning any study; (3) researchers must minimize damage to human remains; (4) researchers must ensure that data are made available following publication to allow critical re-examination of scientific findings; and (5) researchers must engage with other stakeholders from the beginning of a study and ensure respect and sensitivity to stakeholder perspectives. We commit to adhering to these guidelines and expect they will promote a high ethical standard in DNA research on human remains going forward.
Subject(s)
Cadaver , DNA, Ancient/analysis , Guidelines as Topic , Human Genetics/ethics , Internationality , Molecular Biology/ethics , American Indian or Alaska Native , Anthropology/ethics , Archaeology/ethics , Community-Institutional Relations , Humans , Indigenous Peoples , Stakeholder Participation , TranslationsABSTRACT
BACKGROUND: Fundamental motor skills (FMS) and physical fitness (FIT) play important roles in child development and provide a foundation for lifelong participation in physical activity (PA). Unfortunately, many children have suboptimal levels of PA, FMS, and FIT. The Active Learning Norwegian Preschool(er)s (ACTNOW) study investigated the effects of a staff-led PA intervention on FMS, FIT, and PA in 3-5-year-old children. METHODS: Preschools in Western Norway having ≥ six 3-4-year-old children were invited (n = 56). Of these, 46 agreed to participate and were cluster-randomized into an intervention (n = 23 preschools [381 children, 3.8 yrs., 55% boys]) or a control group (n = 23 [438, 3.7 yrs., 52% boys]). Intervention preschools participated in an 18-month PA intervention involving a 7-month staff professional development between 2019 and 2022, amounting to 50 h, including face-to-face seminars, webinars, and digital lectures. Primary outcomes in ACTNOW were cognition variables, whereas this study investigated effects on secondary outcomes. FMS was measured through 9 items covering locomotor, object control, and balance skills. FIT was assessed as motor fitness (4 × 10 shuttle-run test) and upper and lower muscular strength (handgrip and standing long jump). PA was measured with accelerometers (ActiGraph GT3X +). All measures took place at baseline, 7-, and 18-month follow-up. Effects were analysed using a repeated measures linear mixed model with child and preschool as random effects and with adjustment for baseline scores. RESULTS: Participants in the intervention preschools showed positive, significant effects for object control skills at 7 months (standardized effect size (ES) = 0.17) and locomotor skills at 18 months (ES = 0.21) relative to controls. A negative effect was found for handgrip strength (ES = -0.16) at 7 months. No effects were found for balance skills, standing long jump, or motor fitness. During preschool hours, sedentary time decreased (ES = -0.18), and light (ES = 0.14) and moderate-to-vigorous PA (ES = 0.16) increased at 7 months, whereas light PA decreased at 18 months (ES = -0.15), for intervention vs control. No effects were found for other intensities or full day PA. CONCLUSIONS: The ACTNOW intervention improved some FMS outcomes and increased PA short-term. Further research is needed to investigate how to improve effectiveness of staff-led PA interventions and achieve sustainable improvements in children's PA, FMS, and FIT. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT04048967 , registered August 7, 2019. FUNDING: ACTNOW was supported by the Research Council of Norway (grant number 287903), the County Governor of Sogn og Fjordane, the Sparebanken Sogn og Fjordane Foundation, and the Western Norway University of Applied Sciences.
Subject(s)
Exercise , Motor Skills , Physical Fitness , Humans , Male , Female , Norway , Child, Preschool , Health Promotion/methods , Child Development , Staff Development/methods , Hand StrengthABSTRACT
Background: After-hours telemedicine services for emergency care are thought to offer a solution for patients who live at a distance from traditional face-to-face emergency services. This study evaluates such a service in a Health Maintenance Organization, focusing on the differences between central and peripheral populations. Methods: In this cross-sectional database study, we collected data regarding the encounter and patient characteristics, including prescriptions, referrals for further evaluation in a traditional emergency department (ED), and the distance from a traditional ED. Other outcome measures included health care utilization after the encounter such as primary care physician (PCP) encounters, additional telemedicine encounters, ED visits, and hospitalization. Results: In total, 45,411 patient visits were analyzed. Medication was prescribed in 25% of the encounters, and a referral to an ED was given in 22%. In total, 17.7% of the patients visited an ED within 24 h of the index encounter. In total, 64.8% of patients visited a PCP in the following 30 days. No further care was needed in 32.4% of the encounters. In multivariable logistic regression, the odds of using the service were lower for low socio-economic status groups and inhabitants of the periphery than the central areas. A weak reverse correlation was observed in Jewish sectors regarding distance from traditional ED, whereas no correlation was found in the Arab sector. Conclusion: It is commonly believed that telemedicine overcomes geographical barriers. The results of this research do not support this hypothesis.
ABSTRACT
This article is told as a story about how a project, Strong culture, healthier lifestyles, took steps towards decolonisation as an evolving methodological journey with Country. The story is primarily about how our methodology moved from a Western model of 'doing' research, to the research team being part of the research process, as team members with Country and the participating local community members: a methodology of partnership. First, we provide a general overview of the initial project to set up how we came to understand its disconnection to community and Country. Second, we unpack the storying approach as methodology that is bound with the local Country: Yuin on the South Coast of New South Wales, Australia. Third, using the storying approach, we reflect through Country and the community to discover ways forward in Aboriginal and non-Aboriginal knowledge partnerships. We share our story in an attempt to limit colonial practice (decolonisation) and replace it with a re-culturalising approach; the re-connecting of Country as a source of interconnectedness into the research process. Country includes all the living communities of nature, and we explore how this relationship in the human element (community) impacted and developed our methodology of partnership.
Subject(s)
Australian Aboriginal and Torres Strait Islander Peoples , Health Services, Indigenous , Humans , Australia , New South Wales , Health Knowledge, Attitudes, PracticeABSTRACT
Chronic respiratory morbidity is unfortunately common in childhood, particularly in those born very prematurely or with congenital anomalies affecting pulmonary development and those with sickle cell disease. Our research group, therefore, has focused on the early origins of chronic respiratory disease. This has included assessing antenatal diagnostic techniques and potentially therapeutic interventions in infants with congenital diaphragmatic hernia. Undertaking physiological studies, we have increased the understanding of the premature baby's response to resuscitation and evaluated interventions in the delivery suite. Mechanical ventilation modes have been optimised and randomised controlled trials (RCTs) with short- and long-term outcomes undertaken. Our studies highlighted respiratory syncytial virus lower respiratory tract infections (LRTIs) and other respiratory viral LRTIs had an adverse impact on respiratory outcomes of prematurely born infants, who we demonstrated have a functional and genetic predisposition to respiratory viral LRTIs. We have described the long-term respiratory outcomes for children with sickle cell disease and importantly identified influencing factors. In conclusion, it is essential to undertake long term follow up of infants at high risk of chronic respiratory morbidity if effective preventative strategies are to be developed.
Subject(s)
Anemia, Sickle Cell , Respiration Disorders , Respiratory Syncytial Virus Infections , Respiratory Tract Infections , Child , Humans , Infant , Lung , Respiratory Syncytial Virus Infections/complications , Respiratory Syncytial Virus Infections/therapy , Respiratory Syncytial Virus Infections/genetics , Respiratory Tract Infections/complications , Respiratory Tract Infections/diagnosis , Hernias, Diaphragmatic, Congenital/complications , Hernias, Diaphragmatic, Congenital/diagnosis , Hernias, Diaphragmatic, Congenital/therapyABSTRACT
Physical activity (PA) is important for children's development of fundamental motor skills (FMS) and physical fitness (FIT) but evidence regarding which intensities are associated with these outcomes in early childhood is limited. The aim of this study was to determine the cross-sectional multivariate PA intensity signatures associated with FMS and FIT in children aged 3-5 years. We used a sample of 952 Norwegian preschoolers (4.3 years, 51% boys) who provided data on PA (ActiGraph GT3X+), at least one FMS (locomotor, object control and/or balance skills) or FIT (speed agility, standing long jump, and/or handgrip strength) outcome, body mass index, and socioeconomic status in 2019-2020. We created 17 PA intensity variables (0-99 to ≥15000 counts per minute) from the vertical axis and used multivariate pattern analysis for analyses. The PA intensity spectrum (including sedentary time) was significantly associated with all outcomes. Associations for PA intensities were positive (negative for sedentary time), strongest for moderate and vigorous intensities, and were significant across sex and age groups. Our findings show that the PA intensity spectrum is associated with FMS and FIT in young children and that promotion of PA, in particular moderate- and vigorous-intensity activity, from an early age benefits children's physical development.
Subject(s)
Hand Strength , Motor Skills , Male , Humans , Child, Preschool , Female , Cross-Sectional Studies , Accelerometry , Exercise , Physical FitnessABSTRACT
PURPOSE: South Africa has long endured a high prevalence of mental disorders at the national level, and its unique social and historical context could be a contributor to an increased risk of mental health problems. Our current understanding is limited regarding the relative importance of various social determinants to mental health challenges in South Africa, and how existing racial inequities may be explained by these determinants. METHODS: This study attempted to elucidate potential social determinants of mental health in South Africa using data from the nationally representative South African National Health and Nutrition Examination Survey (SANHANES-1). The main outcome of interest was psychological distress, measured with the Kessler-10 scale. Hierarchical linear regression models included covariates for demographic and socioeconomic factors, count of traumatic events, and a series of stress-related constructs. Analyses were conducted on two populations: the entire sample (n = 15,981), and the African subpopulation (n = 10,723). RESULTS: Regression models on the entire sample indicated racial disparities in psychological distress, with Africans experiencing higher distress than White and Coloured individuals. Results within the African sub-population indicated geo-spatial disparities, with Africans in formal urban settings experiencing higher psychological distress than those living in formal and informal rural locales. Across both samples, results indicated a cumulative association between count of stressors and traumatic events and distress. CONCLUSION: We found racial disparities across several mental health-related domains. Africans had greater exposure to traumatic events, social stressors, and psychological distress. This research is a necessary foundation for public health interventions and policy change to effectively reduce inequities in psychological distress.
Subject(s)
Apartheid , Psychological Distress , Cross-Sectional Studies , Humans , Nutrition Surveys , South Africa/epidemiologyABSTRACT
Non-communicable diseases (NCDs) constitute a significant public health challenge and pose a great burden on health and social systems throughout the world. The Asia-Pacific region is in a vulnerable position as the prevalence of NCDs will inevitably increase with rapid socioeconomic transitions; yet it is ill prepared for this public health challenge as Asian children are among the most physically inactive in the world. Aligned with the WHO's global strategy to control NCDs via preventive measures and health promotion policies, representatives from the Asia-Pacific region came together to develop consensus statement on integrated 24-hour activity guidelines for children and adolescents. These guidelines apply to children and adolescents, aged 5-18 years, in the Asia-Pacific region, regardless of gender, cultural background or socioeconomic status. These guidelines aim to provide the latest evidence-based recommendations, taking a holistic approach to lifestyle activities and adopting a practical perspective by framing these activities within a 24-hour period. Eating and dietary elements were incorporated as they closely influence the energy balance of the movement behaviours and vice versa. By investing in the younger generations through advocacy for healthier lifestyles, we aim to reduce the burden of NCDs in the Asia-Pacific region.
Subject(s)
Life Style , Sedentary Behavior , Adolescent , Asia , Child , Consensus , Health Promotion , HumansABSTRACT
For vehicles to operate in unmapped areas with some degree of autonomy, it would be useful to aggregate and store processed sensor data so that it can be used later. In this paper, a tool that records and optimizes the placement of costmap data on a persistent map is presented. The optimization takes several factors into account, including local vehicle odometry, GPS signals when available, local map consistency, deformation of map regions, and proprioceptive GPS offset error. Results illustrating the creation of maps from previously unseen regions (a 100 m × 880 m test track and a 1.2 km dirt trail) are presented, with and without GPS signals available during the creation of the maps. Finally, two examples of the use of these maps are given. First, a path is planned along roads that have been seen exactly once during the mapping phase. Secondly, the map is used for vehicle localization in the absence of GPS signals.
ABSTRACT
Importance: Effective treatment of acute kidney injury (AKI) is predicated on timely diagnosis; however, the lag in the increase in serum creatinine levels after kidney injury may delay therapy initiation. Objective: To determine the derivation and validation of predictive models for AKI after cardiac surgery. Design, Setting, and Participants: Multivariable prediction models were derived based on a retrospective observational cohort of adult patients undergoing cardiac surgery between January 2000 and December 2019 from a US academic medical center (n = 58â¯526) and subsequently validated on an external cohort from 3 US community hospitals (n = 4734). The date of final follow-up was January 15, 2020. Exposures: Perioperative change in serum creatinine and postoperative blood urea nitrogen, serum sodium, potassium, bicarbonate, and albumin from the first metabolic panel after cardiac surgery. Main Outcomes and Measures: Area under the receiver-operating characteristic curve (AUC) and calibration measures for moderate to severe AKI, per Kidney Disease: Improving Global Outcomes (KDIGO), and AKI requiring dialysis prediction models within 72 hours and 14 days following surgery. Results: In a derivation cohort of 58â¯526 patients (median [IQR] age, 66 [56-74] years; 39â¯173 [67%] men; 51â¯503 [91%] White participants), the rates of moderate to severe AKI and AKIrequiring dialysis were 2674 (4.6%) and 868 (1.48%) within 72 hours and 3156 (5.4%) and 1018 (1.74%) within 14 days after surgery. The median (IQR) interval to first metabolic panel from conclusion of the surgical procedure was 10 (7-12) hours. In the derivation cohort, the metabolic panel-based models had excellent predictive discrimination for moderate to severe AKI within 72 hours (AUC, 0.876 [95% CI, 0.869-0.883]) and 14 days (AUC, 0.854 [95% CI, 0.850-0.861]) after the surgical procedure and for AKI requiring dialysis within 72 hours (AUC, 0.916 [95% CI, 0.907-0.926]) and 14 days (AUC, 0.900 [95% CI, 0.889-0.909]) after the surgical procedure. In the validation cohort of 4734 patients (median [IQR] age, 67 (60-74) years; 3361 [71%] men; 3977 [87%] White participants), the models for moderate to severe AKI after the surgical procedure showed AUCs of 0.860 (95% CI, 0.838-0.882) within 72 hours and 0.842 (95% CI, 0.820-0.865) within 14 days and the models for AKI requiring dialysis and 14 days had an AUC of 0.879 (95% CI, 0.840-0.918) within 72 hours and 0.873 (95% CI, 0.836-0.910) within 14 days after the surgical procedure. Calibration assessed by Spiegelhalter z test showed P >.05 indicating adequate calibration for both validation and derivation models. Conclusions and Relevance: Among patients undergoing cardiac surgery, a prediction model based on perioperative basic metabolic panel laboratory values demonstrated good predictive accuracy for moderate to severe acute kidney injury within 72 hours and 14 days after the surgical procedure. Further research is needed to determine whether use of the risk prediction tool improves clinical outcomes.
Subject(s)
Acute Kidney Injury/etiology , Cardiac Surgical Procedures/adverse effects , Models, Statistical , Postoperative Complications/etiology , Acute Kidney Injury/blood , Acute Kidney Injury/epidemiology , Acute Kidney Injury/therapy , Area Under Curve , Humans , Postoperative Complications/blood , Postoperative Complications/epidemiology , Predictive Value of Tests , ROC Curve , Renal Dialysis , Retrospective Studies , Risk Assessment/methodsABSTRACT
OBJECTIVES: To evaluate whether intrauterine growth restriction (IUGR) adds further neurodevelopmental risk to that posed by very preterm birth alone in terms of alterations in brain growth and poorer toddlerhood outcomes. STUDY DESIGN: Participants were 314 infants of very preterm birth enrolled in the Evaluation of Preterm Imaging Study (e-Prime) who were subsequently followed up in toddlerhood. IUGR was identified postnatally from discharge records (n = 49) and defined according to prenatal evaluation of growth restriction confirmed by birth weight <10th percentile for gestational age and/or alterations in fetal Doppler. Appropriate for gestational age (AGA; n = 265) was defined as birth weight >10th percentile for gestational age at delivery. Infants underwent magnetic resonance imaging at term-equivalent age (median = 42 weeks); T2-weighted images were obtained for voxelwise gray matter volumes. Follow-up assessments were conducted at corrected median age of 22 months using the Bayley Scales of Infant and Toddler Development III and the Modified-Checklist for Autism in Toddlers. RESULTS: Infants of very preterm birth with IUGR displayed a relative volumetric decrease in gray matter in limbic regions and a relative increase in frontoinsular, temporal-parietal, and frontal areas compared with peers of very preterm birth who were AGA. At follow-up, toddlers born very preterm with IUGR had significantly lower cognitive (effect size = 0.42) and motor (effect size = 0.41) scores and were more likely to have a positive Modified-Checklist for Autism in Toddlers screening for autism (OR = 2.12) compared with peers of very preterm birth who were AGA. CONCLUSIONS: IUGR might confer a neurodevelopmental risk that is greater than that posed by very preterm alone, in terms of both alterations in brain growth and poorer toddlerhood outcomes.
Subject(s)
Autism Spectrum Disorder/diagnosis , Brain/pathology , Fetal Growth Retardation/diagnostic imaging , Adult , Brain/diagnostic imaging , Female , Fetal Growth Retardation/pathology , Humans , Infant , Infant, Extremely Premature , Infant, Newborn , Longitudinal Studies , Magnetic Resonance Imaging/methods , Male , PregnancyABSTRACT
Magnetic resonance imaging (MRI) in pregnancy is commonly undertaken in the left lateral tilt (LLT) position to prevent inferior vena cava (IVC) compression and supine hypotensive events, although this may be suboptimal for image quality. The supine position may also have an adverse effect on fetal well-being. The spinal venous plexus may provide an alternative pathway for venous return in the presence of IVC compression. This study assesses morphology and blood flow of the IVC and spinal venous plexus for pregnant women in LLT and supine positions to ascertain the effect of maternal position on venous return during MRI. Eighty-two pregnant women underwent phase contrast MRI (PC-MRI) of the IVC and spinal venous plexus in the supine position; 25 were also imaged in the LLT position. Differences in life monitoring, IVC, spinal venous plexus and total venous return between the two positions were assessed. A linear regression assessed the relationship between flow in the IVC and the spinal venous plexus in the supine position. Increasing gestational age and the right-sided position of the uterus on IVC and spinal venous plexus venous return were also evaluated. Hypotension symptoms were similar in supine (10%) and LLT (8%) positioning. Supine positioning decreased IVC height (p < 0.004) and flow (p = 0.045) but flow in the spinal venous plexus increased (p < 0.001) compared with the LLT position. Total venous return showed no difference (p = 0.989) between the two positions. Additional measurements of flow in the aorta also showed no significant difference between the two groups (p = 0.866). Reduced IVC flow in the supine position was associated with increasing gestational age (p = 0.004) and degree of right-sided uterine position (p = 0.004). Women in the left lateral decubitus position who then rotated supine had greater flow in the IVC (p = 0.008) and spinal venous plexus (p = 0.029) than those who started supine. For the majority of women, the spinal venous plexus acts as a complementary venous return system for pregnant women in the supine position, maintaining vascular homeostasis. Further study is needed to assess the effects on the health of the fetus.
Subject(s)
Magnetic Resonance Imaging/methods , Patient Positioning , Pregnancy/physiology , Vena Cava, Inferior/physiology , Female , Humans , Pregnant Women , Regional Blood Flow , Spine/blood supply , Supine PositionABSTRACT
We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost 400,000 polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of Western and Far Eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, â¼8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a â¼24,000-year-old Siberian. By â¼6,000-5,000 years ago, farmers throughout much of Europe had more hunter-gatherer ancestry than their predecessors, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but also from a population of Near Eastern ancestry. Western and Eastern Europe came into contact â¼4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced â¼75% of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least â¼3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for a steppe origin of at least some of the Indo-European languages of Europe.
Subject(s)
Cultural Evolution/history , Grassland , Human Migration/history , Language/history , Europe/ethnology , Genome, Human/genetics , History, Ancient , Humans , Male , Polymorphism, Genetic/genetics , Population Dynamics , RussiaABSTRACT
Ancient DNA makes it possible to observe natural selection directly by analysing samples from populations before, during and after adaptation events. Here we report a genome-wide scan for selection using ancient DNA, capitalizing on the largest ancient DNA data set yet assembled: 230 West Eurasians who lived between 6500 and 300 bc, including 163 with newly reported data. The new samples include, to our knowledge, the first genome-wide ancient DNA from Anatolian Neolithic farmers, whose genetic material we obtained by extracting from petrous bones, and who we show were members of the population that was the source of Europe's first farmers. We also report a transect of the steppe region in Samara between 5600 and 300 bc, which allows us to identify admixture into the steppe from at least two external sources. We detect selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height.
Subject(s)
Genome, Human/genetics , Selection, Genetic/genetics , Agriculture/history , Asia/ethnology , Body Height/genetics , Bone and Bones , DNA/genetics , DNA/isolation & purification , Diet/history , Europe/ethnology , Genetics, Population , Haplotypes/genetics , History, Ancient , Humans , Immunity/genetics , Male , Multifactorial Inheritance/genetics , Pigmentation/genetics , Sequence Analysis, DNAABSTRACT
We report [18F]nifene binding to α4ß2* nicotinic acetylcholinergic receptors (nAChRs) in Parkinson's disease (PD). The study used transgenic Hualpha-Syn(A53T) PD mouse model of α-synucleinopathy for PET/CT studies in vivo and autoradiography in vitro. Additionally, postmortem human PD brain sections comprising of anterior cingulate were used in vitro to assess translation to human studies. Because the small size of mice brain poses challenges for PET imaging, improved methods for radiosynthesis of [18F]nifene and simplified PET/CT procedures in mice were developed by comparing intravenous (IV) and intraperitoneal (IP) administered [18F]nifene. An optimal PET/CT imaging time of 30-60 min post injection of [18F]nifene was established to provide thalamus to cerebellum ratio of 2.5 (with IV) and 2 (with IP). Transgenic Hualpha-Syn(A53T) mice brain slices exhibited 20-35% decrease while in vivo a 20-30% decrease of [18F]nifene was observed. Lewy bodies and α-synuclein aggregates were confirmed in human PD brain sections which lowered the [18F]nifene binding by more than 50% in anterior cingulate. Thus [18F]nifene offers a valuable tool for PET imaging studies of PD.
Subject(s)
Parkinson Disease/diagnostic imaging , Pyridines/analysis , Pyrroles/analysis , Receptors, Nicotinic/analysis , Synucleinopathies/diagnostic imaging , Animals , Brain/diagnostic imaging , Disease Models, Animal , Female , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Transgenic , Positron Emission Tomography Computed Tomography/methodsABSTRACT
The use of polydiacetylene (PDA) vesicles in sensing systems are wide-spread due to the interesting optical properties of this stimuli-responsive material; however, agglutination based sensing with PDA have been relatively underutilized. To demonstrate the means for rapidly generating an agglutination probe based on peptide-displaying polydiacetylene vesicles, we implement here the use of a biotin mimetic peptide functionalized to a diacetylene amphiphile for proof-of-concept detection of a multivalent target, specifically streptavidin. Tuning of the vesicle composition revealed a distinct limit in the surface density of peptide amphiphile that could be displayed for this particular peptide sequence. A wide operational detection range was demonstrated, and the result also revealed an effective agglutination response of the PDA-based probe to streptavidin suggesting possible use of future formulations in profiling other multivalent targets.
ABSTRACT
INTRODUCTION: Eccentric exercise can reverse age-related decreases in muscle strength and mass; however, no data exist describing its effects on postural sway. As the ankle may be more important for postural sway than hip and knee joints, and with older adults prone to periods of inactivity, the effects of two 6-week seated isokinetic eccentric exercise programmes, and an 8-week detraining period, were examined in 27 older adults (67.1 ± 6.0 years). METHODS: Neuromuscular parameters were measured before and after training and detraining periods with subjects assigned to ECC (twice-weekly eccentric-only hip and knee extensor contractions) or ECCPF (identical training with additional eccentric-only plantarflexor contractions) training programmes. RESULTS: Significant (P < 0.05) increases in mobility (decreased timed-up-and-go time [- 7.7 to - 12.0%]), eccentric strength (39.4-58.8%) and vastus lateralis thickness (9.8-9.9%) occurred after both training programmes, with low-to-moderate weekly rate of perceived exertion (3.3-4.5/10) reported. No significant change in any postural sway metric occurred after either training programme. After 8 weeks of detraining, mobility (- 8.2 to - 11.3%), eccentric strength (30.5-50.4%) and vastus lateralis thickness (6.1-7.1%) remained significantly greater than baseline in both groups. CONCLUSION: Despite improvements in functional mobility, muscle strength and size, lower-limb eccentric training targeting hip, knee and ankle extensor muscle groups was not sufficient to influence static balance. Nonetheless, as the beneficial functional and structural adaptations were largely maintained through an 8-week detraining period, these findings have important implications for clinical exercise prescription as the exercise modality, low perceived training intensity, and adaptive profile are well suited to the needs of older adults.
Subject(s)
Exercise Therapy/methods , Movement , Muscle Strength , Postural Balance , Aged , Aged, 80 and over , Female , Humans , Male , Middle AgedABSTRACT
The primary aim of this research was to generate insight into observable mentally tough behaviours, or MTb, across different contexts (e.g., training and competition) in an Australian football (AF) environment. A second aim of this research was to explore the utility of MTb as a distinct concept, and identify common behavioural qualities associated with MTb that separate it from other similar constructs. In total, 10 experienced full-time football operations staff were interviewed using a semi-structured interview guide, with inductive thematic analysis employed to analyse the data. Five main themes relating to MTb were identified: adaptive development, consistent training conduct, composed performance actions, responsible and accountable, and team supportive. Overall, the findings of the research provided preliminary support for the proposition that there exists a collection of MTb that are displayed more frequently by athletes considered to possess high levels of mental toughness compared to athletes who are perceived to have low levels of this psychological capacity. We propose a collection of necessary and sufficient behavioural qualities and a working definition of MTb to further our understanding of potential strategies to develop MT.