Physical activity and cognitive function in adults born very preterm or with very low birth weight-an individual participant data meta-analysis.

OBJECTIVE: Individuals born very preterm (<32 weeks of gestation) or with very low birthweight (<1500g) have lower cognitive function compared with term-born peers. Furthermore, some studies suggest that they are less physically active as young adults than controls, but the relationship between physical activity and cognitive function remains unclear. We performed an individual participant data meta-analysis to examine whether being born preterm/with very low birth weight is associated with physical activity in adulthood and examined if cognitive function mediates this association. STUDY DESIGN: Cohorts with data on physical activity and cognitive function in adults born very preterm/very low birth weight and term-born controls were recruited from the Research on European Children and Adults Born Preterm, and the Adults Born Preterm International Collaboration Consortia. A systematic literature search was performed in PubMed and Embase. RESULTS: Five cohorts with 1644 participants aged 22-28 years (595 very preterm/very low birth weight and 1049 controls) were included. Adults born very preterm/very low birth weight reported 1.11 (95% CI: 0.68 to 1.54) hours less moderate to vigorous physical activity per week than controls, adjusted for cohort, age and sex. The difference between individuals born very preterm/very low birth weight and controls was larger among women than among men. Neither intelligence quotient nor self-reported executive function mediated the association between very preterm/very low birth weight and moderate to vigorous physical activity. Results were essentially the same when we excluded individuals with neurosensory impairments. CONCLUSION: Adults born very preterm/very low birth weight, especially women, reported less moderate to vigorous physical activity than their term-born peers. Cognitive function did not mediate this association. Considering the risk of adverse health outcomes among individuals born preterm, physical activity could be a target for intervention.

Childhood outcomes after maternal antenatal sildenafil treatment for severe early-onset fetal growth restriction: a randomized trial (STRIDER NZAus).

In this follow-up at 2.5 years of children from the STRIDER NZAus Trial (N = 112), in which women with singleton pregnancies affected by severe early fetal growth restriction were randomized to sildenafil citrate 75 mg daily or placebo until 32 weeks, there was no difference between groups in survival without neurosensory impairment, defined as any of cerebral palsy, deafness, blindness, cognitive delay (Bayley III cognition or language score >1 SD below mean) or motor delay: 30/56[54%] vs. 34/56[61%]; aOR = 0.74, 95%CI: 0.31, 1.77. However, children exposed to sildenafil appeared to be more likely to have cognitive delay (13/45[29%] vs. 4/40[10%]; aOR = 3.71, 95% CI: 1.01, 13.63) but less likely to have emotional-behavioural difficulties (2/43[5%] vs. 8/38[21%]; aOR = 0.19, 95%CI: 0.03, 1.00). Conclusion: maternal sildenafil treatment for severe early-onset FGR was not associated with altered survival free of neurosensory impairment at 2.5 years' corrected age.

DNA methylation patterns at birth predict health outcomes in young adults born very low birthweight.

BACKGROUND: Individuals born very low birthweight (VLBW) are at increased risk of impaired cardiovascular and respiratory function in adulthood. To identify markers to predict future risk for VLBW individuals, we analyzed DNA methylation at birth and at 28 years in the New Zealand (NZ) VLBW cohort (all infants born < 1500 g in NZ in 1986) compared with age-matched, normal birthweight controls. Associations between neonatal methylation and cardiac structure and function (echocardiography), vascular function and respiratory outcomes at age 28 years were documented. RESULTS: Genomic DNA from archived newborn heel-prick blood (n = 109 VLBW, 51 controls) and from peripheral blood at ~ 28 years (n = 215 VLBW, 96 controls) was analyzed on Illumina Infinium MethylationEPIC 850 K arrays. Following quality assurance and normalization, methylation levels were compared between VLBW cases and controls at both ages by linear regression, with genome-wide significance set to p < 0.05 adjusted for false discovery rate (FDR, Benjamini-Hochberg). In neonates, methylation at over 16,400 CpG methylation sites differed between VLBW cases and controls and the canonical pathway most enriched for these CpGs was Cardiac Hypertrophy Signaling (p = 3.44E-11). The top 20 CpGs that differed most between VLBW cases and controls featured clusters in ARID3A, SPATA33, and PLCH1 and these 3 genes, along with MCF2L, TRBJ2-1 and SRC, led the list of 15,000 differentially methylated regions (DMRs) reaching FDR-adj significance. Fifteen of the 20 top CpGs in the neonate EWAS showed associations between methylation at birth and adult cardiovascular traits (particularly LnRHI). In 28-year-old adults, twelve CpGs differed between VLBW cases and controls at FDR-adjusted significance, including hypermethylation in EBF4 (four CpGs), CFI and UNC119B and hypomethylation at three CpGs in HIF3A and one in KCNQ1. DNA methylation GrimAge scores at 28 years were significantly greater in VLBW cases versus controls and weakly associated with cardiovascular traits. Four CpGs were identified where methylation differed between VLBW cases and controls in both neonates and adults, three reversing directions with age (two CpGs in EBF4, one in SNAI1 were hypomethylated in neonates, hypermethylated in adults). Of these, cg16426670 in EBF4 at birth showed associations with several cardiovascular traits in adults. CONCLUSIONS: These findings suggest that methylation patterns in VLBW neonates may be informative about future adult cardiovascular and respiratory outcomes and have value in guiding early preventative care to improve adult health.

Bedtime parenting practices and sensitivity are associated with young children's sleep.

Previous research has utilized naturalistic observations of parent-child interactions at bedtime to identify constellations of specific parenting behaviors and qualities that predict better infant nighttime sleep. Little work, however, has naturalistically examined associations between aspects of bedtime parenting and nighttime sleep among young children. The present study assessed observed parenting practices and sensitivity in the context of bedtime as predictors of 3-6-year-olds' sleep. Participants were 51 children (53% boys; 80% White, 18% biracial, 2% Black) and their families. Trained raters coded video recordings of bedtime for parenting practices (parental presence, contact, quiet activities; children's technology use) and sensitivity. Children's nighttime sleep (minutes, efficiency) was assessed across seven nights using actigraphy. Partial correlation analyses controlling for child and family demographics showed that more quiet activities, greater parenting sensitivity, and less child technology use at bedtime were associated with longer and more efficient sleep. There were also several significant interactions. Longer parental presence and contact at bedtime were associated with better sleep (minutes, efficiency) for children who experienced high but not low parenting sensitivity. Lower child technology use in combination with higher parental presence was also associated with longer and more efficient child sleep. The findings illuminate aspects of the bedtime context that may promote emotional security and reduce physiological and cognitive arousal in young children. These naturalistic observations may readily translate into intervention programming targeting improvement in young children's sleep. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Little evidence for long-term harm from antenatal corticosteroids in a population-based very low birthweight young adult cohort.

BACKGROUND: Antenatal corticosteroids (ACS) given to mothers with anticipated very preterm delivery are widely used and improve infant outcomes. Follow-up studies of the first trials of ACS have shown no adverse effects, but recently there have been concerns about possible longer-term harms. OBJECTIVES: We aimed to assess the relationship of ACS therapy to a range of physical health and welfare measures in a cohort of very low birthweight (VLBW; <1500 g) young adults. METHODS: Population-based cohort follow-up study. All VLBW infants born in New Zealand in 1986 were included in a prospective audit of retinopathy of prematurity. Perinatal data collection included information on ACS. At 26-30 years, 250 of 323 (77%) survivors participated, 58% having received ACS, with 229 assessed in one centre, including cardiovascular, metabolic, respiratory and neurocognitive measures. Differences in outcome between those receiving/not receiving ACS were summarised by the mean difference for continuous outcomes supplemented by Cohen's d as a standardised measure of effect size (ES), and risk ratios (RRI) for dichotomous outcomes, adjusted for relevant covariates using generalised linear regression methods. RESULTS: There were no or minimal adverse effects of receipt of ACS versus no receipt across a range of health and welfare outcomes, both for the full cohort (adjusted ES range d = 0.01-0.23; adjusted RR range 0.78-2.03) and for individuals with gestation <28 weeks (extremely preterm; EP), except for a small increase in rates of major depression. In EP adults, receipt of ACS was associated with a higher incidence of hypertension, but might have a small benefit for IQ. CONCLUSIONS: In this population-based VLBW cohort, we detected minimal adverse outcomes associated with exposure to ACS by the third decade of life, a similar result to the 30-year follow-up of participants in the first ACS trial. However, further follow-up is warranted.

Self-reported executive function problems in adults born very low birthweight.

BACKGROUND: Executive function difficulties are common among children born very preterm and/or very low birthweight (<1500 g; VLBW), but little is known about whether they persist into adulthood. OBJECTIVES: Examine the nature and pattern of self-reported executive functioning at 23 and 28 years of age using data from a national cohort study of adults born VLBW and a comparison group of same-age full-term (FT) born adults. Also examined were associations between executive function difficulties and socio-economic outcomes. METHODS: All infants born VLBW in New Zealand during 1986 were prospectively included in an audit of retinopathy of prematurity (n = 413), with 250 (77% of survivors) followed to median age 28 years. A comparison group of FT adults was also recruited at age 23 and followed to 28 years (n = 100). Across both adult assessments, executive functioning was assessed using the Behaviour Rating Inventory of Executive Function-Adult Version (BRIEF-A) and analysed with semi-parametric models to examine the effects of age and group on executive function. RESULTS: At 23 and 28 years, VLBW adults had increased risk of executive function impairment compared with FT adults in behaviour regulation (relative risk [CI] 2.37, 95% confidence interval (CI)1.27, 4.45), meta-cognition (RR 6.03, 95% CI 2.18, 16.78) and global functioning (RR 3.20, 95% CI 1.40, 7.28). Impaired global executive functioning was associated with lower socio-economic status (regression estimate [b] = -0.43, 95% CI -0.59, -0.27) and a reduced likelihood of home ownership by age 28 years (RR 0.98, 95% CI 0.96, 1.00), even after controlling for sex, ethnicity and parental socio-economic backgrounds for both groups. CONCLUSION(S): VLBW-born adults continue to experience more executive function difficulties in their everyday life relative to term controls at age 28 years. These difficulties were negatively associated with their socio-economic opportunities as young adults.

Preterm birth and cardiac function in adulthood.

Preterm birth affects 1 in 10 pregnancies worldwide, with increasing survival rates over the last 30 years. However, as this new generation of long-term survivors approaches middle age, recent studies have revealed increased cardiovascular risk factors and higher rates of ischaemic heart disease and heart failure. Cardiovascular imaging has identified smaller cardiac chamber size, changes in myocardial mass and impaired ventricular function, particularly under physiological stress. Accordingly, this population should be recognised as having a higher risk of heart failure as they age. In this review, we present current evidence for increased rates of heart failure and evidence of alterations in cardiac structure and function in those born preterm. We discuss potential mechanisms to explain this risk including greater frequency of co-morbidities known to be associated with heart failure. We also explore potential mechanistic links specific to the preterm-born population, including the impact of premature birth on myocardial and vascular development and the effects of perinatal haemodynamic changes and chronic lung disease on the developing heart. We highlight gaps in our knowledge and consider implications for patient management relevant to the adult physician.

Reduced Exercise Capacity in Adults Born at Very Low Birth Weight: A Population-based Cohort Study.

Rationale: Population-based data regarding the consequences of very low birth weight (VLBW) and bronchopulmonary dysplasia (BPD) on adult exercise capacity are limited. Objectives: To compare exercise capacity in a national VLBW cohort with term-born controls and explore factors contributing to the differences. Methods: At 26-30 years of age, 228 VLBW survivors and 100 controls underwent lung function tests, cardiopulmonary exercise testing, and assessment of resting cardiac structure and function using echocardiography. Data on self-reported physical activity were collected. Measurements and Main Results: Compared with controls, adults with VLBW demonstrated reduced oxygen uptake, work rate, and oxygen pulse at peak exercise (9.3%, 10.7%, and 10.8% lower, respectively) and earlier anaerobic threshold (all P < 0.0001), with all mean values within normal range. VLBW survivors showed reduced physical activity, impaired lung function (reduced FEV1, FEV1/FVC, and DlCO), altered left ventricular structure and function (reduced mass, size, stroke volume, and cardiac output), and reduced right atrial and ventricular size. Adjustment for the combination of three sets of covariates (physical activity with body mass index, lung function, and cardiac structure and function) explained most of the exercise group differences. Beyond the effects of physical activity and body mass index, lung function and cardiac structure and function contributed approximately equally. BPD with other prematurity-related perinatal factors (ventilation, antenatal steroids, extremely low birth weight, and extreme preterm) were not associated with a reduced exercise capacity. Conclusions: Exercise capacity was significantly reduced in adults with VLBW, which we speculate is from combined effects of impaired lung function, altered heart structure and function, and reduced physical activity. Perinatal factors including BPD were not associated with a reduced exercise capacity.

Right Ventricular Structure and Function in Young Adults Born Preterm at Very Low Birth Weight.

Being born preterm (PT, <37 weeks gestation) or at very low birth weight (VLBW, <1500 g) is associated with increased rates of cardiopulmonary disorders in childhood. As survivors age, late cardiac effects, including right ventricular (RV) remodelling and occult pulmonary hypertension are emerging. In this population-based study, we aimed to investigate right heart structure and function in young adults born PT at VLBW compared to normal-weight term-born controls. The New Zealand VLBW Study has followed all infants born in 1986 with birth weight <1500 g. All were born preterm from 24 to 37 weeks. A total of 229 (71% of survivors) had echocardiograms aged 26-30 years which were compared to age-matched, term-born, normal-weight controls (n = 100). Young adults born preterm at very low birth weight exhibited smaller RV dimensions compared to term-born peers. Standard echocardiographic measures of RV function did not differ, but mildly reduced function was detected by RV longitudinal strain. This difference was related to birth weight and gestational age but not lung function or left ventricular function. Echocardiographic strain imaging may be an important tool to detect differences in RV function preterm and VLBW.

Phage Commander, an Application for Rapid Gene Identification in Bacteriophage Genomes Using Multiple Programs.

The number of sequenced bacteriophage genomes is growing at an exponential rate. The majority of sequenced bacteriophage genomes are annotated by one or more of several freely available gene identification programs (Glimmer, GeneMark, RAST, Prodigal, etc.). No program has been shown to consistently outperform the others; thus, the choice of which program to use is not obvious. We present the Phage Commander application for rapid identification of bacteriophage genes using multiple gene identification programs. Phage Commander runs a bacteriophage genome sequence through nine gene identification programs (and an additional program for identification of tRNAs) and integrates the results within a single output table. Phage Commander also generates formatted output files for direct export to National Center for Biotechnology Information GenBank or genome visualization programs such as DNA Master. Users can select the threshold for which genes to export (genes identified by at least one program, genes identified by at least two programs, etc.). Phage Commander was benchmarked using eight high-quality bacteriophage genomes whose genes are backed by experimental data. Our results show that the most accurate annotations are obtained by exporting genes identified by at least two or three programs. Many groups opt to manually curate the annotations obtained from gene identification programs, and Phage Commander was designed to facilitate manual curation of genome annotations. Our benchmarking results show that manual curation does indeed produce more accurate annotations than any individual gene identification program. The authors thus recommend manually curating the output of Phage Commander to generate maximally accurate annotations. Phage Commander is currently being used in the corresponding author's bacteriophage genome annotation class and has reduced the labor cost and improved the quality of genome annotations.

Biomarkers of ageing in New Zealand VLBW young adults and controls.

BACKGROUND: There is individual variation in physiological ageing. Former very low birthweight (VLBW; birthweight < 1500 g) young adults may have less satisfactory measurements on some physiological parameters than term controls. We hypothesized that a summation score of physiological biomarkers that change with age would show VLBW adults to have a more advanced physiologic age than controls. METHODS: VLBW adults (229; 71% survivors of a national VLBW cohort) and term-born controls (100) were clinically assessed at 26-30 years. Ten measured physiological biomarkers were selected and measurements converted to z-scores using normative reference data. Between-group comparisons were tested for statistical significance for individual biomarker z-scores and a summation score. RESULTS: Nine of 10 biomarkers showed a mean z-score suggestive of older physiological age in the VLBW group versus controls. The observed mean difference in the summation score was highly significant (p < 0.001), representing a mean shift of 0.47 SD in the distribution of test scores for VLBW relative to controls. CONCLUSIONS: Utilizing a 10-biomarker score, VLBW young adults have a score indicative of poorer physiological functioning than term-born controls. Repeating these measures after an interval could provide insights into the comparative pace of ageing between VLBW and term-born adults. IMPACT: A summation score of 10 physiological biomarkers that are known to change with age shows that former very low birthweight adults have significantly poorer physiological functioning by the end of their third decade than term-born controls. This result adds to existing literature showing very preterm and very low birthweight young adults often have physiological and metabolic test results that are less satisfactory than those from term controls, despite mostly being in the normal range for age; for instance, higher systolic blood pressure. Although the pace of ageing in later years is yet to be established, the implications of this study are that preventative measures and lifestyle choices that impact on physiological ageing might have even greater importance for very preterm and very low birthweight graduates.

Cardiovascular Outcomes in Young Adulthood in a Population-Based Very Low Birth Weight Cohort.

OBJECTIVES: To assess differences in left heart structure and function, and endothelial function in a national cohort of very low birth weight (VLBW) young adults and term-born controls. STUDY DESIGN: The New Zealand VLBW study is a prospective, population-based, longitudinal cohort study which included all infants born <1500 g in 1986. The VLBW cohort (n = 229; 71% of survivors) and term-born controls (n = 100), were assessed at age 26-30 years. Measures of left heart structure and function were evaluated by echocardiography, vascular function was assessed using blood pressure, reactive hyperemia index, and arterioventricular coupling by calculating left ventricular (LV) and arterial elastance. RESULTS: Compared with controls, those born VLBW had smaller LVs, even when indexed for body surface area (mean LV mass, 89.7 ± 19.3 g/m2 vs 95.0 ± 22.3 g/m2 [P = .03]; LV end-diastolic volume, 58.3 ± 10.9 mL/m2 vs 62.4 ± 12.4 mL/m2 [P = .002]; and LV end-systolic volume, 20.8 ± 4.9 mL/m2 vs 22.6 ± 5.8 mL/m2 [P = .004]). VLBW participants had lower stroke volume (median, 37.2 mL/m2 [IQR, 33-42 mL/m2] vs median, 40.1 mL/m2 [IQR, 34-45 mL/m2]; P = .0059) and cardiac output (mean, 4.8 ± 1.2 L/min vs 5.1 ± 1.4 L/min; P = .03), but there was no difference in ejection fraction. The VLBW group had higher LV elastance (3.37 ± 0.88 mm Hg/mL vs 2.86 ± 0.75 mm Hg/mL; P < .0001) and arterial elastance (1.84 ± 0.4 vs 1.6 ± 0.4; P < .0001) and lower reactive hyperemia index (0.605 ± 0.28 vs 0.688 ± 0.31; P = .041). These measures were influenced by birth weight and sex, but we found limited associations with other perinatal factors. CONCLUSIONS: Being born preterm and VLBW is associated with differences in cardiovascular structure and function in adulthood. This population may be more vulnerable to cardiovascular pathology as they age. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN12612000995875.

Circulating Forms of B-Type Natriuretic Peptide in Very Preterm Infants.

BACKGROUND: B-type natriuretic peptide (BNP) is a cardiac hormone released with an N-terminal fragment (NTproBNP) under conditions of ventricular pressure or volume overload. BNP has been proposed for use as a biomarker of cardiac dysfunction in premature infants in the setting of hemodynamically significant patent ductus arteriosus (HsPDA) and bronchopulmonary dysplasia (BPD). In adult settings the presence of proBNP and glycosylated isoforms may affect assay interpretation. However, there are limited data on how immature preterm physiology may affect BNP or NTproBNP levels and no published data on post-translational BNP processing in premature infants. METHODS: Pooled serial plasma samples from preterm infants born at less than 30 weeks gestation were analyzed for BNP congeners using Luminex® assay and high performance liquid chromatography. Samples were grouped according to clinical status: Group 1, no HsPDA and no BPD, Group 2 HsPDA and no/mild BPD, Group 3 HsPDA and moderate/severe BPD. RESULTS: Plasma from 15 infants was analyzed, and across all three groups NTproBNP predominated with minimal amounts of other isoforms; no glycosylation was detected. CONCLUSIONS: NTproBNP appears to be the predominant isoform across each of our clinical groups in our pooled sample analysis with no evidence of significant glycosylation. This suggests NTproBNP is likely to be a robust marker in this clinical setting.

Neonatal Cardiovascular Function after Antenatal Sildenafil for Severe, Early-Onset Intrauterine Growth Restriction: A Substudy of the STRIDER-NZAus Randomized Placebo-Controlled Trial.

We evaluated the effect of antenatal sildenafil on neonatal cardiovascular function in a subgroup of 27 infants of mothers participating in the STRIDER-NZAus randomized controlled trial. In this small study, we found no association between antenatal sildenafil and neonatal cardiac dysfunction including no pulmonary hypertension in exposed or unexposed infants.

Linking Gait Dynamics to Mechanical Cost of Legged Locomotion.

For millenia, legged locomotion has been of central importance to humans for hunting, agriculture, transportation, sport, and warfare. Today, the same principal considerations of locomotor performance and economy apply to legged systems designed to serve, assist, or be worn by humans in urban and natural environments. Energy comes at a premium not only for animals, wherein suitably fast and economical gaits are selected through organic evolution, but also for legged robots that must carry sufficient energy in their batteries. Although a robot's energy is spent at many levels, from control systems to actuators, we suggest that the mechanical cost of transport is an integral energy expenditure for any legged system-and measuring this cost permits the most direct comparison between gaits of legged animals and robots. Although legged robots have matched or even improved upon total cost of transport of animals, this is typically achieved by choosing extremely slow speeds or by using regenerative mechanisms. Legged robots have not yet reached the low mechanical cost of transport achieved at speeds used by bipedal and quadrupedal animals. Here we consider approaches used to analyze gaits and discuss a framework, termed mechanical cost analysis, that can be used to evaluate the economy of legged systems. This method uses a point mass perspective to evaluate the entire stride as well as to identify individual events that accrue mechanical cost. The analysis of gait began at the turn of the last century with spatiotemporal analysis facilitated by the advent of cine film. These advances gave rise to the "gait diagram," which plots duty factors and phase separations between footfalls. This approach was supplanted in the following decades by methods using force platforms to determine forces and motions of the center of mass (CoM)-and analytical models that characterize gait according to fluctuations in potential and kinetic energy. Mechanical cost analysis draws from these approaches and provides a unified framework that interprets the spatiotemporal sequencing of leg contacts within the context of CoM dynamics to determine mechanical cost in every instance of the stride. Diverse gaits can be evaluated and compared in biological and engineered systems using mechanical cost analysis.

In-hospital morbidity and brain metrics of preterm neonates born 1998-2009.

AIMS: To describe the survival, in-hospital morbidity, brain metrics and two-year neurodevelopmental outcomes of two extremely preterm cohorts and discuss the contribution of changes in clinical practice to these outcomes. METHODS: Retrospective comparative cohort study, of two cohorts of neonates born <28 weeks gestation: 47 infants born 1998-2000 and 39 infants 2006-2009. RESULTS: Comparing historical to the contemporary cohort respectively, admission temperature (35.9 degrees C, 36.5) and CRIB (Clinical Risk Index in Babies) score (5.4, 3.1) improved. Inotrope support fell significantly (55.3%, 28.2%). High frequency ventilation days fell (8.0, 2.7). CPAP days increased significantly (32.2, 47.9). Chronic lung disease at 36 weeks corrected age fell significantly (61.7%, 38.5%). Red cell transfusions decreased in number (7.1, 4.8) and volume (96.2ml/kg, 70.4ml/kg). Retinopathy of prematurity (ROP) rates dropped significantly (66.0%, 28.2%). Survival was not significantly different. Nutritional improvements included shorter days to first enteral feed (3.4, 2.0), target protein (5.4, 4.3) and lipid levels (7.1, 4.1) with better breastfeeding rates at discharge (19.2%, 38.5%). By 36 weeks z scores for weight (-0.90, -0.39) were improved but not length (-1.94, -1.26) or head circumference (-0.72, -0.69). MRI brain metrics showed a significant improvement in bifrontal (59.2, 65.9), biparietal (73.7, 79.3) and transcerebellar diameter (50.6, 52.6) with improved neurodevelopmental outcome at two years. CONCLUSION: The contemporary cohort had better initial physiological stability, less chronic lung disease and retinopathy, improved body growth at 36 weeks and brain metrics at term equivalent. Improvement in neurodevelopment at two years has been seen and further analysis will be important to understand the impact of the changes in clinical care.

A collisional perspective on quadrupedal gait dynamics.

The analysis of terrestrial locomotion over the past half century has focused largely on strategies of mechanical energy recovery used during walking and running. In contrast, we describe the underlying mechanics of legged locomotion as a collision-like interaction that redirects the centre of mass (CoM). We introduce the collision angle, determined by the angle between the CoM force and velocity vectors, and show by computing the collision fraction, a ratio of actual to potential collision, that the quadrupedal walk and gallop employ collision-reduction strategies while the trot permits greater collisions. We provide the first experimental evidence that a collision-based approach can differentiate quadrupedal gaits and quantify interspecific differences. Furthermore, we show that this approach explains the physical basis of a commonly used locomotion metric, the mechanical cost of transport. Collision angle and collision fraction provide a unifying analysis of legged locomotion which can be applied broadly across animal size, leg number and gait.

Activation of metabotropic glutamate receptors does not alter the phosphorylation state of GluR1 AMPA receptor subunit at serine 845 in perirhinal cortical neurons.

Activation of group I and group II metabotropic glutamate receptors (mGluRs) is thought to be required for long-term depression (LTD) of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor-mediated synaptic transmission in the perirhinal cortex. However, little is known about how activation of mGluRs leads to this form of synaptic plasticity. AMPA receptor phosphorylation has been implicated in several forms of modulation of synaptic transmission. In the CA1 area of the hippocampus, N-methyl-d-aspartate (NMDA) receptor-dependent LTD is associated with the reduced phosphorylation of the GluR1 AMPA receptor subunit at serine 845 (GluR1-S845). Immunoblot analysis of perirhinal cortical neurons using GluR1 and GluR1-S845 phosphorylation state specific antibodies showed that stimulation of adenylyl cyclase (AC) with forskolin (FSK) dramatically increased PKA-mediated phosphorylation of GluR1-S845. However, selective or simultaneous application of mGluR5 agonist (S)-3,5-dihydroxyphenylglycine (CHPG) and mGluR2/3 agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV) did not produce detectable changes in GluR1-S845 phosphorylation. These results indicate that in the perirhinal cortex mGluR activation does not alter the phosphorylation state of GluR1-S845. Therefore, it is likely that the process involved in the modification of AMPA receptors in mGluR activation dependent LTD in the perirhinal cortex is mechanistically distinct from NMDA receptor-mediated LTD described in hippocampal neurons.