Adult Phenotype Research Articles

Relatively lower BMI-adjusted calf circumference is associated with metabolically unhealthy phenotype in non-obese adults: a cross-sectional study

BackgroundMetabolically unhealthy non-obese (MUNO) individuals are at higher risk of cardiovascular diseases, while not receiving sufficient attention. This study was conducted to explore the association between BMI-adjusted CC and MUNO in non-obese US adults using the NHANES database.MethodsA total of 9,628 non-obese US adults (48.01% female and 51.99% male) were included in this cross-sectional study. The metabolically unhealthy phenotype was defined as ≥ 2 components of metabolic abnormalities. BMI-adjusted CC and BMI-adjusted skeletal muscle mass (SMM) were divided into quartiles. Weighted multiple logistic regression model was used to evaluate the study aims. The relation between BMI-adjusted CC and BMI-adjusted SMM was tested by Spearman correlation.ResultsIn the multivariate analysis, compared with the lowest quartile of BMI-adjusted CC and BMI-adjusted SMM, OR (95%CI) of the highest quartile was 0.30 (0.25, 0.35) (P < 0.001, P for trend < 0.001) and 0.39 (0.29, 0.53) (P < 0.001, P for trend < 0.001), respectively. BMI-adjusted CC was positively correlated with BMI-adjusted SMM for all participants (r = 0.48). A weak non-linear association was observed in BMI-adjusted CC and MUNO (P = 0.047). Similar results were observed in sex- and BMI-specific subgroup and sensitivity analysis.ConclusionBMI-adjusted CC was inversely associated with MUNO, suggesting more attention should be paid to monitoring BMI-adjusted CC for the public to ease the disease burden, especially for people without obesity.

Adult Phenotype of CHD2-Associated Disorders.

Pathogenic CHD2 variants are associated with neurodevelopmental disorders and developmental and epileptic encephalopathy. While pediatric CHD2 phenotypes have been readily explored, adult phenotypes are not well understood. We aimed to investigate the phenotypic spectrum of adult patients with CHD2 variants. Patients 18 years or older with likely pathogenic or pathogenic (LP/P) CHD2 variants were included. We used standardized tools to evaluate current seizures, medication use, sleep, gastrointestinal symptoms, pain response, gait, social communication disorder, and adaptive behavioral skills of patients. In this prospective study, 14 unrelated adult patients (age range: 18-45 years, median: 21 years) with LP/P CHD2 variants were described. Eleven novel variants were identified. No genotype-phenotype correlations were identified. 79% of adults still have ongoing seizures. Photosensitivity was present in 64% of adult patients. Autism spectrum disorder was diagnosed in 71% of patients. Only 29% were able to read and understand material at a sixth-grade level or higher. Behavioral issues were reported in 100% of adult patients, and 71% had internalizing features, such as anxiety. Self-injurious behaviors were present in 50%. Only 43% could ambulate independently. Additional characteristics included reflux (36%), constipation (71%), and abnormal pain responsiveness (43%). 1 patient presented with nonepileptic breath-holding spells leading to cyanosis. No patient could perform all basic activities of daily living independently, all the time. Higher seizure severity was associated with worse nonseizure outcomes (p = 0.04). Most adults with CHD2 continue to have seizures, and seizure severity is associated with worse comorbidities such as maladaptive behaviors, gait, gastrointestinal, sleep, and abnormal pain responsiveness. Longevity has not been systematically studied in this group of patients. Here we describe a group of adult patients (up to 45 years of age) and the natural history of this condition. These data may provide prognostic insights for families of pediatric patients and help identify key points to be addressed in future precision trials for patients with CHD2 variants.

Polygenic Risk Scores and Extreme Coronary Artery Calcium Phenotypes (CAC=0 and CAC≥1000) in Adults ≥75 Years Old: The ARIC Study.

Coronary artery calcium (CAC) is heterogeneous in older age and is incompletely explained by traditional atherosclerotic cardiovascular disease risk factors. The extremes of subclinical atherosclerosis burden are strongly associated with either a low or high 10-year risk of incident atherosclerotic cardiovascular disease, respectively. However, the genetic underpinnings of differences in arterial aging remain unclear. We sought to determine the independent association of 2 polygenic scores for coronary heart disease (CHD) with CAC in adults ≥75 years of age. There were 1865 ARIC (Atherosclerosis Risk in Communities) participants who underwent genetic testing at visit 1 (1987-1989) and CAC scans at visit 7 (2018-2019). In the primary analysis, an externally derived multi-ancestry polygenic CHD risk score was calculated for both White and Black participants. Results were confirmed using a separate ARIC-derived polygenic CHD risk score, including ≥6 million variants computed for White participants. We used multivariable logistic regression models to assess the association of polygenic CHD risk with CAC, after adjusting for baseline, time-averaged lifestyle, traditional risk factors, and local ancestry principal components. In the primary analysis, the average age was 80.6 years old, 61.6% were women, and the median CAC score was 246 (189 participants with CAC=0, 364 participants with CAC≥1000). Compared with persons below the 20th percentile of polygenic CHD risk, persons with polygenic-CHD risk above the 80th percentile had 82% lower odds of having CAC=0 (odds ratio, 0.18 [95% CI, 0.09-0.37]) and had >4-fold higher odds of CAC≥1000 (odds ratio, 4.77 [95% CI, 2.88-7.88]). On a continuous scale, each SD increment increase in the polygenic risk score was associated with a 78% higher CAC score. Results were nearly identical using a second confirmatory polygenic CHD risk score in White participants. Polygenic CHD risk is robustly associated with a lower prevalence of CAC=0 and a higher prevalence of CAC≥1000 in adults ≥75 years of age, beyond lifestyle and traditional risk factors. These results suggest a heritable contribution to distinct healthy and unhealthy arterial aging phenotypes that persist throughout the life course.

Occupational and Hobby Exposures Associated with Myositis Phenotypes in a National Myositis Patient Registry.

To investigate occupational and hobby exposures to silica, solvents, and heavy metals and odds of idiopathic inflammatory myositis (IIM) phenotypes, dermatomyositis (DM) and polymyositis (PM) versus inclusion body myositis (IBM), lung disease plus fever or arthritis (LD+), and systemic autoimmune rheumatic disease-overlap myositis (OM). The sample included 1390 patients (598 DM, 409 PM, and 383 IBM) ages ≥18 years from a national registry. Of these, 218 (16%) were identified with LD+, i.e., self-reported lung disease with fever and/or arthritis, and 166 (12%) with OM. Questionnaire data on jobs, hobbies, and exposures before diagnosis were evaluated using a rules-based protocol and expert assessment of silica dust, solvents, and heavy metals exposure. We calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) and explored joint effects with smoking. High silica exposure was associated with an increased odds of having DM (OR=2.02; 95%CI 1.18-3.46, compared to no exposure; p-trend=0.004), LD+ (1.75; 1.10-2.78; p-trend=0.005, versus no LD), and OM (2.07; 1.19-3.61; p-trend=0.020). Moderate to high heavy metals exposure was associated with greater odds of having LD+ (1.49; 1.00-2.14; p-trend=0.026) and OM (1.59; 0.99-2.55, p-trend=0.051). Greater odds of LD+ were seen among smokers with moderate to high silica exposure versus non-smokers with low or no exposure (high-certainty assessment, 2.53; 1.31-4.90; p-interaction=0.061). These findings, based on a systematic exposure assessment, suggest that occupational and hobby exposures to silica and heavy metals contribute to adult IIM phenotypes, including DM, OM, and LD+, a possible marker for anti-synthetase or other autoantibody-associated lung disease.

Identifying and Estimating Frailty Phenotypes by Vocal Biomarkers: Cross-Sectional Study.

Researchers have developed a variety of indices to assess frailty. Recent research indicates that the human voice reflects frailty status. Frailty phenotypes are seldom discussed in the literature on the aging voice. This study aims to examine potential phenotypes of frail older adults and determine their correlation with vocal biomarkers. Participants aged ≥60 years who visited the geriatric outpatient clinic of a teaching hospital in central Taiwan between 2020 and 2021 were recruited. We identified 4 frailty phenotypes: energy-based frailty, sarcopenia-based frailty, hybrid-based frailty-energy, and hybrid-based frailty-sarcopenia. Participants were asked to pronounce a sustained vowel "/a/" for approximately 1 second. The speech signals were digitized and analyzed. Four voice parameters-the average number of zero crossings (A1), variations in local peaks and valleys (A2), variations in first and second formant frequencies (A3), and spectral energy ratio (A4)-were used for analyzing changes in voice. Logistic regression was used to elucidate the prediction model. Among 277 older adults, an increase in A1 values was associated with a lower likelihood of energy-based frailty (odds ratio [OR] 0.81, 95% CI 0.68-0.96), whereas an increase in A2 values resulted in a higher likelihood of sarcopenia-based frailty (OR 1.34, 95% CI 1.18-1.52). Respondents with larger A3 and A4 values had a higher likelihood of hybrid-based frailty-sarcopenia (OR 1.03, 95% CI 1.002-1.06) and hybrid-based frailty-energy (OR 1.43, 95% CI 1.02-2.01), respectively. Vocal biomarkers might be potentially useful in estimating frailty phenotypes. Clinicians can use 2 crucial acoustic parameters, namely A1 and A2, to diagnose a frailty phenotype that is associated with insufficient energy or reduced muscle function. The assessment of A3 and A4 involves a complex frailty phenotype.

NompC regulates locomotion and touch sensation in Bactrocera dorsalis.

No mechanoreceptor potential C (NompC) is a major mechanotransduction channel with an important role in sensing of external mechanical stimuli by insects, which help these organisms to avoid injury and adapt to environmental changes. To explore the biological functions of NompC in Bactrocera dorsalis, a notorious agricultural pest, we successfully generated NompC knockout strains using clustered regularly interspaced small palindromic repeats (CRISPR) / CRISPR-associated nuclease 9 (Cas9) technology. BdorNompC knockout led to an adult lethal phenotype, with approximately 100% mortality at 3 d after eclosion. Morphological observation revealed that the legs and wings of BdorNompC knockout insects were deformed, while behavioral assays showed that the locomotion was impaired in both adults and larvae, relative to that of the wild-type strain. Moreover, BdorNompC knockout reduced gentle-touch response in larvae. These results suggest that BdorNompC is critical for B. dorsalis survival, and that this mechanosensation channel represents a potential new target for pest control agents. Our findings also represent novel evidence indicating that insect NompC is involved in modulating adult wing and leg morphology.

Sex specific gut-microbiota signatures of resilient and comorbid gut-brain phenotypes induced by early life stress

BackgroundAlterations in gut-brain axis communication pathways and the gut microbiota ecosystem caused by early life stress have been extensively described as critical players in the pathophysiology of stress-induced disorders. However, the extent to which stress-induced gut microbiota alterations manifest in early life and contribute to the sex-specific susceptibility to distinct gut-brain phenotypes in adulthood has yet to be defined. MethodsMale and female Sprague-Dawley rat offspring underwent maternal separation (3h/day from postnatal day 2–12). Faecal samples were collected before weaning for gut microbiota 16S rRNA sequencing and metabolomic analysis. Visceral pain sensitivity and negative valence behaviours were assessed in adulthood using colorectal distension and the forced swim test respectively. Behavioural data were processed in a two-step cluster analysis to identify groupings within the dataset. Multi-omics analysis was carried out to investigate if the microbial signatures following early life stress were already defined according to the membership of the adult behavioural phenotypes. ResultsMaternal separation resulted in increased visceral hypersensitivity while showing a trend for a sex-dependent increase in negative valence behaviour in adulthood. The cluster analysis revealed four clusters within the dataset representing distinct pathophysiological domains reminiscent of the behavioural consequences of early-life stress: 1. resilient, 2. pain, 3. immobile and 4. comorbid. The early life gut microbiota of each of these clusters show distinct alterations in terms of diversity, genus level differential abundance, and functional modules. Multi-omic integrations points towards a role for different metabolic pathways underlying each cluster-specific phenotype. ConclusionOur study is the first to identify distinct phenotypes defined by susceptibility or resilience to gut-brain dysfunction induced by early life stress. The gut microbiota in early life shows sex-dependent alterations in each cluster that precede specific behavioural phenotypes in adulthood. Future research is warranted to determine the causal relationship between early-life stress-induced changes in the gut microbiota and to understand the trajectory leading to the manifestation of different behavioural phenotypes in adulthood.

Central and Peripheral Sensitivity to Thyroid Hormones Correlate to Metabolically Obesity Phenotypes in Chinese Euthyroid Adults: A Cross-Sectional Study.

Thyroid hormones impact lipid metabolism and glucose homoeostasis through both central and peripheral regulation; however, little research has delved into the association between thyroid hormone sensitivity and metabolically obese phenotypes. We aimed to investigate the correlation between indices of central and peripheral sensitivity to thyroid hormones and metabolically obese phenotypes in euthyroid Chinese adults. This cross-sectional study included 20,084 euthyroid individuals. Central thyroid hormone sensitivity was assessed using the thyroid feedback quantile-based index (TFQI), parametric thyroid feedback quantile-based index (PTFQI), thyroid-stimulating hormone index (TSHI), and thyrotropin thyroxine resistance index (TT4RI), while peripheral thyroid hormone sensitivity was measured by FT3/FT4. Metabolically obesity phenotypes included metabolically healthy non-obesity (MHNO), unhealthy non-obesity (MUNO), metabolically healthy obesity (MHO), and unhealthy obesity (MUO). Multinomial logistic regression and restricted cubic spline analyses were conducted to investigate the association between thyroid hormone sensitivity indices and metabolically obese phenotypes risk. Subgroup analysis was also performed to examine this association stratified by sex and age. Mediation analysis was performed to estimate direct and indirect effects of BMI. Prevalence of MHNO, MUNO, MHO and MUO was 66.1% (n=13,273), 21.3% (n=4271), 5.3% (n=1055), and 7.4% (n=1485) respectively. After adjustment for potential confounders, the odds ratios (ORs) (95% CI) for MUNO and MUO were increased with all elevated thyroid hormones sensitivity indices (per SD increase) [MUNO: TFQI 1.14(1.09-1.19), PTFQI 1.18(1.23-1.23); TSHI 1.26(1.19-1.33), TT4RI 1.41, (1.31-1.53), FT3/FT4 1.20(1.14-1.25) and [MUO: TFQI 1.20(1.11-1.31), PTFQI 1.26(1.16-1.37), TSHI 1.39 (1.26-1.54), TT4RI 1.70(1.48-1.95), FT3/FT4 1.26 (1.16-1.37)] (p value<0.001), and only TSHI and TT4RI (per SD increase) significantly increased the risk of MHO (TSHI: OR=1.12, 95% CI 1.01-1.24; TT4RI: OR=1.25, 95%CI 1.08-1.4) (p value<0.05). Non-linear relationships were observed between central thyroid hormones sensitivity indices and MUNO and MUO(p for nonlinearity<0.05). Conversely, a linear relationship between FT3/FT4 and metabolically obese phenotypes was noted in all subjects (p for nonlinearity>0.05). Besides, subgroup analysis indicated that this association remained consistent among sex and age (p for interaction>0.05). The proportions mediated by BMI on the association of TFQI, PTFQI, TSHI, TT4RI, FT3/FT4 and risk of metabolically unhealthy conditions were 13.73%, 25.38%, 22.75%, 17.94% and 62.28%, respectively. In euthyroid adults, central and peripheral sensitivity to thyroid hormones indices are positively associated with metabolically obese phenotypes risk, especially MUNO and MUO phenotypes.

Nasal allergen challenge with Blomia tropicalis in children and adolescents.

Local allergic rhinitis (LAR) is a well-defined phenotype in adults, but still there is little data available on children. This scarcity of data can be partly attributed to the lack of standardized protocols for Nasal Allergen Challenges (NAC) in this demographic. 20 controls (control group) and 24 patients (rhinitis group) with allergic rhinitis diagnosis sensitized to Blomia tropicalis (Bt) underwent the NAC with Bt. The acoustic rhinometry was performed after instillation of increasing concentrations of Bt (5,000 BU/mL). The median reduction in the volume of the nasal cavity in its first five centimeters (V5) by the conclusion of the NAC in the rhinitis group was markedly higher than that observed in the control group, at -22.9% (range: -21.1% to -26.2%) compared to -7.7% (ranging: -4.8% to +12.8%). Our research demonstrates the efficacy and safety of the NAC protocol utilizing Bt in distinguishing allergic from non-allergic children.

Maternal exercise opportunity before, during, and after pregnancy alters maternal care behavior and offspring development and survival, but has few effects on offspring physical activity or body composition

Early-life experiences, especially during critical periods of development and growth, can have long-lasting effects on adult phenotypes. Parents are a crucial part of the offspring early-life environment, particularly in mammals (e.g., via pregnancy), and parental behaviors (e.g., maternal exercise) can modify the early-life environment experienced by offspring. Such changes might be beneficial or detrimental, depending on how they affect offspring development and growth or interact with other key parental behaviors (e.g., nursing).We used mice from a long-term artificial selection experiment for high voluntary wheel-running behavior to determine whether maternal exercise opportunity affected (1) maternal physical activity, (2) maternal care behavior, or (3) offspring physical activity and body composition. Eighty prospective dams (40 from 4 selectively bred High Runner [HR] lines and 40 from 4 non-selected Control [CON] lines) were housed with continuous wheel access starting two weeks prior to breeding and ending 10 days postpartum, after which dams were housed without wheels until offspring weaning (21 days postpartum). An additional 100 dams (50 HR, 50 CON) were housed without wheels.Prospective dams from HR lines ran more revolutions/day (mainly by running faster) than those from CON lines when individually housed and in the days leading up to, but not after, birth. During postpartum days 1-5, HR and CON dams with wheels tended to exhibit less maternal behavior than those without (PWheel = 0.0672). During post-partum days 6-10, HR dams with wheels continued to exhibit less maternal behavior than those without, whereas CON dams with wheels exhibited more than those without (PLinetype*Wheel = 0.0218). The proportion of dams giving birth did not differ among groups. However, CON dams with wheels were less likely to have litter death between birth and weaning than those without wheels, whereas the opposite was true for HR dams (PLinetype*Wheel = 0.0447). Both HR and CON dams with wheels had litters with a higher proportion of females at weaning than those without wheels (PWheel = 0.0129).Maternal wheel access had few statistically significant effects on offspring, but may have resulted in developmental delays (e.g., delayed eye opening and decreased lean mass at weaning and sexual maturity). Additionally, maternal wheel access and sex may have interacted to affect wheel-running distance (PSex*Wheel = 0.0683) and duration (PSex*Wheel = 0.0926); female offspring from dams with wheels ran fewer revolutions per day, by running fewer minutes per day, than from dams without wheels, whereas males ran more. However, maternal exercise had no statistically significant effects on offspring food consumption (mass-adjusted), home-cage activity, open-field behavior, the reproductive characteristics of offspring, their adult body composition, nor relative organ masses; nor did maternal wheel access have statistically significant effects on grand-offspring food consumption, body composition or voluntary exercise behavior.Overall, our results provide some support for maternal exercise opportunity altering maternal care behavior. Altered maternal care could explain the observed trends in offspring survival, development, and voluntary exercise behavior. However, these effects did not have apparent long-lasting impacts on offspring or grand-offspring body composition or reproductive characteristics.

A supergene affects androgen concentrations during early development in a bird with alternative reproductive morphs

Species with alternative reproductive tactics typically show pronounced phenotypic variation between and within sexes. In some species, this variation culminates in discrete reproductive morphs that are genetically determined, facilitating studies on how genetic variation translates into phenotypic variation. In ruffs (Calidris pugnax), an autosomal inversion polymorphism underlies three reproductive morphs (Independents, Satellites and Faeders), which differ in circulating steroid concentrations in adults. Yet, it remains unknown whether morph differences in steroid concentrations already arise before adulthood. We examined variation in circulating testosterone, androstenedione and progesterone concentrations between morphs and sexes in ruff chicks and juveniles and compared the differences to those in adults. Since measured hormone concentrations only provide momentary states and show high within- and between-individual variation, we took repeated measurements to compare means, variances and skewness between groups. We found clear differences between morphs but not the sexes in early life. Between morphs, androgen concentrations in young ruffs differed in variance and skewness, but not in their means. For testosterone, Independents had a higher variance than Satellites/Faeders, whereas for androstenedione, we observed the opposite pattern. For progesterone, we did not detect clear differences between groups. Skewness values mirrored differences in morph variances. Compared to adults, premature ruffs had lower androgen concentrations. In both life stages, we detected morph-specific associations between androgen concentrations: androstenedione concentrations increased with testosterone concentrations more in Satellites/Faeders than in Independents. These observed morph differences during early life are consistent with a supergene-mediated regulation of androgen variation that underlies the diversification of adult behavioural phenotypes.

Sex differences in paediatric onset hypertrophic cardiomyopathy

Abstract Background Hypertrophic Cardiomyopathy (HCM) is a heterogeneous disease characterised by age related incomplete penetrance and variable long term outcomes. Sex differences have been described in both the clinical phenotype and natural history of adults with the disease, which have been attributed to both biological (eg sex hormone effect) and non-biological (eg societal and cultural effects) factors. It is unknown if similar sex differences exist in childhood-onset HCM. Purpose This study aimed to investigate the influence of biological sex on the clinical characteristics and outcomes of children with HCM. Methods Retrospective cohort study from an international registry of patients diagnosed under the age of 18 years with HCM. Patients with syndromic disease (RASopathy syndromes, inborn errors of metabolism, neuromuscular disease) were excluded. Sex differences in baseline characteristics and clinical outcomes were described. Primary outcomes were all-cause mortality or cardiac transplantation, Major Arrhythmic Cardiac Event (MACE) and heart failure event (defined as heart failure death or cardiac transplantation) Results Of 1262 patients, 851 (67.4%) were male (median age 11 yrs (IQR 7.4, 14.4) vs 11.1 (IQR 6.9, 14.0) in females, p=0.0312). Female patients were more likely to have a sarcomeric variant identified (n=208, 85.6% vs 388 (79.4%), p=0.041) despite equivalent genetic testing utilisation between sexes. Female patients were more likely to have severe heart failure symptoms (NYHA 3 or 4) (n=19, 6.1% vs n=20, 2.5% p value 0.030) but there was no difference in the proportion on medical therapy (male n=328, 39.7%, female n=167, 41.8, p value 0.476). The clinical phenotype in terms of degree of hypertrophy, left atrial size and left ventricular outflow tract gradient did not differ by sex. Over a median follow up of 5.2 years (IQR 2.4, 9.9) all-cause mortality or cardiac transplantation did not vary by sex but females were more likely to experience a heart failure event (females 0.6/100,000 pt years (95% CI 0.39-0.92) vs males 0.32/100,000 pt years (95% CI 0.21 – 0.50), hazard ratio 1.89, p value 0.0467). The incidence of MACE did not differ by sex but there was a trend towards higher implantable cardioverter defibrillator implantation in females (n=123, 30.7% vs n=210, 25.4%, p value 0.051). Conclusions For the first time, this study has shown sex differences in paediatric-onset hypertrophic cardiomyopathy. Despite no difference in baseline clinical phenotype, young female patients are more likely to experience heart failure symptoms and heart failure events over follow up. Further studies are required to explore the underlying mechanisms for these observed differences.Table summarising outcomes by sexSurvival free from heart failure

Larval growth rate is not a major determinant of adult wing shape and eyespot size in the seasonally polyphenic butterfly Melanitis leda.

Insects often show adaptive phenotypic plasticity where environmental cues during early stages are used to produce a phenotype that matches the environment experienced by adults. Many tropical satyrine butterflies (Nymphalidae: Satyrinae) are seasonally polyphenic and produce distinct wet- and dry-season form adults, providing tight environment-phenotype matching in seasonal environments. In studied Mycalesina butterflies, dry-season forms can be induced in the laboratory by growing larvae at low temperatures or on poor food quality. Since both these factors also tend to reduce larval growth rate, larval growth rate may be an internal cue that translates the environmental cues into the expression of phenotypes. If this is the case, we predict that slower-growing larvae would be more likely to develop a dry-season phenotype. We performed the first experimental study on seasonal polyphenism of a butterfly in the tribe Melanitini. We measured both larval growth rate and adult phenotype (eyespot size and wing shape) of common evening brown butterflies (Melanitis leda), reared at various temperatures and on various host-plant species. We constructed provisional reaction norms, and tested the hypothesis that growth rate mediates between external cues and adult phenotype. Reaction norms were similar to those found in Mycalesina butterflies. We found that both among and within treatments, larvae with lower growth rates (low temperature, particular host plants) were more likely to develop dry-season phenotypes (small eyespots, falcate wing tips). However, among temperature treatments, similar growth rates could lead to very different wing phenotypes, and within treatments the relationships were weak. Moreover, males and females responded differently, and eyespot size and wing shape were not strongly correlated with each other. Overall, larval growth rate seems to be weakly related to eyespot size and wing shape, indicating that seasonal plasticity in M. leda is primarily mediated by other mechanisms.

Body compositions phenotypes of older adults with COPD.

Changes in nutritional status are important extrapulmonary manifestations of the chronic obstructive pulmonary disease (COPD). The study aimed to assess the prevalence of different body composition phenotypes in older patients with COPD and to investigate the relationship between these phenotypes and the severity of the disease, as well as physical performance of the subjects. The study included 124 subjects aged ≥60 with COPD. In all of them body composition analysis and muscle strength measurement were performed. Additionally, data from patients' medical records were analyzed. Study sample was divided into four groups based on the phenotypic body composition: normal phenotype (N), sarcopenia, obesity and sarcopenic obesity (SO). Incidence of sarcopenia was significantly higher in patients with severe or very severe COPD based on GOLD in comparison with subjects with mild or moderate obstruction (p = 0.043). Participants with sarcopenia, obesity and SO had lower results of the 6-min walk test than subjects with N (225.77 m, 275.33 m, 350.67 m, 403.56 m, respectively). Moreover, sarcopenia and SO had lower results than obesity (p = 0.001, p = 0.041, respectively). Sarcopenia is common in patients with advanced COPD. Sarcopenia and SO are associated with poorer physical performance. All older people with COPD should routinely have their body composition assessed, instead of simply measuring of body weight or body mass index (BMI).

Morphological Study of Left-Right Head Asymmetry in Doubledaya bucculenta (Coleoptera: Erotylidae: Languriinae).

Left-right asymmetry in paired organs is well documented across various species, including the claws of fiddler crabs and snail-eating snakes' dentition. However, the mechanisms underlying these asymmetries remain largely elusive. This study investigates Doubledaya bucculenta (Coleoptera: Erotylidae), a lizard beetle species known for pronounced left-sided asymmetry in adult female mandible and gena. Given that insect mouthparts comprise multiple functionally significant appendages, we aimed to clarify the degree of asymmetry extending beyond the mandibles and genae. Phenotypic morphology was assessed through trait measurement and asymmetry index calculations. Our detailed morphometric analyses revealed left-longer asymmetry not only in mandibles and genae but also in maxillae and labium. Notably, the degree of asymmetry in other mouthparts was generally less pronounced compared to that in outer mandibles, suggesting a potential influence of left mandible development on other mouthparts. Additionally, male mandibles exhibited region-specific asymmetry, potentially indicative of constrained evolutionary adaptations. This study enhances a comprehensive understanding of adult phenotype morphology and offers insights into the developmental basis of asymmetrical mouthparts.

The Association of the Oral Microbiota with Cognitive Functioning in Adolescence.

Background: A growing body of research supports the role of the microbial communities residing in the digestive system in the host's cognitive functioning. Most of these studies have been focused on the gut microbiome and its association with clinical phenotypes in middle-aged and older adults. There is an insufficiency of population-based research exploring the association of normative cognitive functioning with the microbiome particularly with the oral microbiota. Methods: In this study, using metagenomics and metabolomics, we characterized the salivary microbiome diversity in a sample of 51 males of Hispanic and African American origin aged 12-18 years and explored the associations between the microbiome and the youths' cognitive performance captured with the Kaufman Assessment Battery for Children II (KABC-II). Results: Several bacterial species of the oral microbiota and related metabolic pathways were associated with cognitive function. In particular, we found negative associations between indicators of general intelligence and the relative abundance of Bacteroidetes and Lachnospiraceae and positive associations with Bifidobacteriaceae and Prevotella histicola sp. Among metabolic pathways, the super pathways related to bacterial cell division and GABA metabolism were linked to cognitive function. Conclusions: The results of our work are consistent with the literature reporting on the association between microbiota and cognitive function and support further population work to elucidate the potential for a healthy oral microbiome to improve cognitive health.

A phenome-wide association study of polygenic scores for selected childhood cancer: Results from the UK Biobank

The aim of this study was to scan phenotypes in adulthood associated with polygenic risk scores (PRS) for childhood cancers with well-articulated genetic architectures: acute lymphoblastic leukemia (ALL), Ewing sarcoma, and neuroblastoma to examine genetic pleiotropy. Furthermore, we aimed to determine which single nucleotide polymorphisms (SNPs) could drive associations. Per-SNP summary statistics were extracted for PRS calculation. Participants with white British ancestry were exclusively included for analyses. SNPs were queried from the UK biobank genotype imputation data. Records from the cancer registry, death registry, and inpatient diagnoses were abstracted for phenome-wide scans. Firth logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) alongside corresponding p-values, adjusting for age at recruitment and sex. A total of 244,332 unrelated white British participants were included. We observed a significant association between ALL-PRS and ALL (OR: 1.20e+24, 95% CI: 9.08e+14-1.60e+33). In addition, we observed a significant association between high-risk neuroblastoma PRS and nonrheumatic aortic valve disorders (OR: 43.9, 95% CI: 7.42-260). There were no significant phenotype associations with Ewing sarcoma and neuroblastoma PRS. Regarding individual SNPs, rs17607816 increased the risk of ALL (OR: 6.40, 95% CI: 3.26-12.57). For high-risk neuroblastoma, rs80059929 elevated the risk of atrioventricular block (OR: 3.04, 95% CI: 1.85-4.99). Our findings suggest that individuals with genetic susceptibility to ALL may face a lifelong risk for developing ALL, along with a genetic pleiotropic association between high-risk neuroblastoma and circulatory diseases.

Neurological manifestations in adult patients with the m.3243A>G variant in mitochondrial DNA

BackgroundThe m.3243A>G variant in mitochondrial DNA (mtDNA) is the most common cause of the MELAS (Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes) syndrome usually commencing in childhood or adolescence. In...

Age- and size-related changes in hind limb muscles in two baboon species (Papio anubis and P. papio).

Body size has an impact on all biological functions and analyzing how body size impacts functional traits such as locomotion is critical. Body size does not only vary across species but also during ontogeny. Indeed, juvenile animals are often at a competitive disadvantage due to their smaller absolute size. Consequently, understanding size- and age-related changes in the locomotor system is critical for our understanding of adult phenotypes. Here, we address this question by exploring growth of the hind limb muscles in two species of closely related baboons that differ in their ecology, the olive baboon, Papio Anubis, the Guinea baboon, and Papio papio. To do so, we dissected 40 P. anubis and 10 P. papio and measured the mass and physiological cross-sectional area (PCSA) of the hind limb muscles. Our results showed no sexual differences in size- or age-related growth patterns, but did show differences between species. Whereas the scaling of muscle mass and PCSA was largely isometric in P. anubis, allometric scaling was more common in P. papio. Despite these differences between species, the knee extensors and external rotators at the knee scaled with positive allometry in both species highlighting their important role during adult locomotion. Although life-history data for P. papio are scarce, we suggest that differences between species may be associated with differences in adult body size and age of locomotor independence between species.

Tiny but Mighty: Vipera ammodytes meridionalis (Eastern Long-Nosed Viper) Ontogenetic Venom Variations in Procoagulant Potency and the Impact on Antivenom Efficacies.

The Eastern Long-Nosed Viper (Vipera ammodytes meridionalis) is considered one of the most venomous snakes in Europe. However, it is unknown whether ontogenetic variation in venom effects occurs in this subspecies and how this may impact antivenom efficacy. In this study, we compared the procoagulant activities of V. a. meridionalis venom on human plasma between neonate and adult venom phenotypes. We also examined the efficacy of three antivenoms-Viperfav, ViperaTAb, and Inoserp Europe-across our neonate and adult venom samples. While both neonate and adult V. a. meridionalis venoms produced procoagulant effects, the effects produced by neonate venom were more potent. Consistent with this, neonate venom was a stronger activator of blood-clotting zymogens, converting them into their active forms, with a rank order of Factor X >> Factor VII > Factor XII. Conversely, the less potent adult venom had a rank order of FXII marginally more activated than Factor VII, and both much more so than Factor X. This adds to the growing body of evidence that activation of factors besides FII (prothrombin) and FX are significant variables in reptile venom-induced coagulopathy. Although all three examined antivenoms displayed effective neutralization of both neonate and adult V. a. meridionalis venoms, they generally showed higher efficacy on adult venom than on neonate venom. The ranking of antivenom efficacy against neonate venom, from the most effective to the least effective, were Viperfav, Inoserp Europe, ViperaTAb; for adult venom, the ranking was Inoserp Europe, Viperfav, ViperaTAb. Our data reveal ontogenetic variation in V. a meridionalis, but this difference may not be of clinical concern as antivenom was effective at neutralizing both adult and neonate venom phenotypes. Regardless, our results highlight a previously undocumented ontogenetic shift, likely driven by the documented difference in prey preference observed for this species across age classes.