Phenotypic Composition Research Articles

Possible Epigenetic Origin of a Recurrent Gynandromorph Pattern in Megachile Wild Bees.

Simple SummaryGynandromorphs, i.e., individuals with a mix of male and female body parts, are known for many species of insects and other animals with separate sexes. This anomaly is generally regarded as the result of localized genetic mutations in sex-determining genes. We analyzed the specific mix of male and female characters in naturally occurring gynandromorphs of 21 species of the wild bee genus Megachile and found a recurrent pattern. Based on the regularity of this pattern, and the current knowledge on sex determination and sex differentiation in the relatively closely-related honey bee, we argue that the origin of these composite phenotypes is possibly epigenetic, rather than genetic, i.e., produced by some defects in the maintenance of the regulatory signals that control sex differentiation at the level of single cell lineages, rather than triggered by genetic mutations.Gynandromorphs, i.e., individuals with a mix of male and female traits, are common in the wild bees of the genus Megachile (Hymenoptera, Apoidea). We described new transverse gynandromorphs in Megachile pilidens Alfkeen, 1924 and analyze the spatial distribution of body parts with male vs. female phenotype hitherto recorded in the transverse gynandromorphs of the genus Megachile. We identified 10 different arrangements, nine of which are minor variants of a very general pattern, with a combination of male and female traits largely shared by the gynandromorphs recorded in 20 out of 21 Megachile species in our dataset. Based on the recurrence of the same gynandromorph pattern, the current knowledge on sex determination and sex differentiation in the honey bee, and the results of recent gene-knockdown experiments in these insects, we suggest that these composite phenotypes are possibly epigenetic, rather than genetic, mosaics, with individual body parts of either male or female phenotype according to the locally expressed product of the alternative splicing of sex-determining gene transcripts.

The ecological causes and consequences of hard and soft selection.

Interactions between natural selection and population dynamics are central to both evolutionary-ecology and biological responses to anthropogenic change. Natural selection is often thought to incur a demographic cost that, at least temporarily, reduces population growth. However, hard and soft selection clarify that the influence of natural selection on population dynamics depends on ecological context. Under hard selection, an individual's fitness is independent of the population's phenotypic composition, and substantial population declines can occur when phenotypes are mismatched with the environment. In contrast, under soft selection, an individual's fitness is influenced by its phenotype relative to other interacting conspecifics. Soft selection generally influences which, but not how many, individuals survive and reproduce, resulting in little effect on population growth. Despite these important differences, the distinction between hard and soft selection is rarely considered in ecology. Here, we review and synthesize literature on hard and soft selection, explore their ecological causes and implications and highlight their conservation relevance to climate change, inbreeding depression, outbreeding depression and harvest. Overall, these concepts emphasise that natural selection and evolution may often have negligible or counterintuitive effects on population growth-underappreciated outcomes that have major implications in a rapidly changing world.

Phenology-mediated effects of phenotype on the probability of social polygyny and its fitness consequences in a migratory passerine

Why females engage in social polygyny remains an unresolved question in species where the resources provided by males maximize female fitness. In these systems, the ability of males to access several females, as well as the willingness of females to mate with an already mated male, and the benefits of this choice, may be constrained by the socio-ecological factors experienced at the local scale. Here, we used a 19-year dataset from an individual-monitored population of pied flycatchers (Ficedula hypoleuca) to establish local networks of breeding pairs. Then, we examined whether the probability of becoming socially polygynous and of mating with an already mated male (thus becoming a secondary female) is influenced by morphological and sexual traits as proxies of individual quality relative to the neighbours. We also evaluated whether social polygyny is adaptive for females by examining the effect of females’ mating status (polygamously-mated vs monogamously-mated) on direct (number of recruits in a given season) and indirect (lifetime number of fledglings produced by these recruits) fitness benefits. The phenotypic quality of individuals, by influencing their breeding asynchrony relative to their neighbours, mediated the probability of being involved in a polygynous event. Individuals in middle-age (2–3 years), with large wings and, in the case of males, with conspicuous sexual traits, started to breed earlier than their neighbours. By breeding locally early, males increased their chances of becoming polygynous, while females reduced their chances of mating with an already mated male. Our results suggest that secondary females may compensate the fitness costs, if any, of sharing a mate, since their number of descendants did not differ from monogamous females. We emphasize the need of accounting for local breeding settings (ecological, social, spatial, and temporal) and the phenotypic composition of neighbours to understand individual mating decisions.

Shell banding and colour polymorphism of introduced snailCepaea hortensis (Gastropoda, Pulmonata, Helicidae)from some parts of Eastern Europe

The phenotypic composition of C. hortensis colonies was studied in Western Ukraine (more than 30 thousand adults from 23 settlements and 5 administrative regions) and the Moscow region of Russia (more than 500 adults and juveniles from two colonies in Moscow and Vidnoe). Most Western Ukrainian colonies were characterized by the absence of pink shells, the high frequencies of unbanded shells (70% or more), as well as the white ground colour in all banded shells. It is supposed that the latter feature makes it possible to reliably identify the colonies formed by the descendants of the primary introduction of C. hortensis into Western Ukraine, which occurred in the 20th century, from later and independent repeated introductions of this species. Unlike Western Ukraine, snails with yellow banded and pink shells were found in both colonies from the Moscow region. Pink banded shells were registered only in Moscow as well as in two colonies from Lviv. In two of the three colonies mentioned, part of the pink unbanded (Moscow) or all pink shells (Lviv) had a dark lip.

Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response

The heterogeneity of breast cancer plays a major role in drug response and resistance and has been extensively characterized at the genomic level. Here, a single-cell breast cancer mass cytometry (BCMC) panel is optimized to identify cell phenotypes and their oncogenic signalling states in a biobank of patient-derived tumour xenograft (PDTX) models representing the diversity of human breast cancer. The BCMC panel identifies 13 cellular phenotypes (11 human and 2 murine), associated with both breast cancer subtypes and specific genomic features. Pre-treatment cellular phenotypic composition is a determinant of response to anticancer therapies. Single-cell profiling also reveals drug-induced cellular phenotypic dynamics, unravelling previously unnoticed intra-tumour response diversity. The comprehensive view of the landscapes of cellular phenotypic heterogeneity in PDTXs uncovered by the BCMC panel, which is mirrored in primary human tumours, has profound implications for understanding and predicting therapy response and resistance.

Integrated Genome-Wide Analysis of MicroRNA Expression Quantitative Trait Loci in Pig Longissimus Dorsi Muscle.

Determining mechanisms regulating complex traits in pigs is essential to improve the production efficiency of this globally important protein source. MicroRNAs (miRNAs) are a class of non-coding RNAs known to post-transcriptionally regulate gene expression affecting numerous phenotypes, including those important to the pig industry. To facilitate a more comprehensive understanding of the regulatory mechanisms controlling growth, carcass composition, and meat quality phenotypes in pigs, we integrated miRNA and gene expression data from longissimus dorsi muscle samples with genotypic and phenotypic data from the same animals. We identified 23 miRNA expression Quantitative Trait Loci (miR-eQTL) at the genome-wide level and examined their potential effects on these important production phenotypes through miRNA target prediction, correlation, and colocalization analyses. One miR-eQTL miRNA, miR-874, has target genes that colocalize with phenotypic QTL for 12 production traits across the genome including backfat thickness, dressing percentage, muscle pH at 24 h post-mortem, and cook yield. The results of our study reveal genomic regions underlying variation in miRNA expression and identify miRNAs and genes for future validation of their regulatory effects on traits of economic importance to the global pig industry.

Group phenotypic composition in cancer.

Although individual cancer cells are generally considered the Darwinian units of selection in malignant populations, they frequently act as members of groups where fitness of the group cannot be reduced to the average fitness of individual group members. A growing body of studies reveals limitations of reductionist approaches to explaining biological and clinical observations. For example, induction of angiogenesis, inhibition of the immune system, and niche engineering through environmental acidification and/or remodeling of extracellular matrix cannot be achieved by single tumor cells and require collective actions of groups of cells. Success or failure of such group activities depends on the phenotypic makeup of the individual group members. Conversely, these group activities affect the fitness of individual members of the group, ultimately affecting the composition of the group. This phenomenon, where phenotypic makeup of individual group members impacts the fitness of both members and groups, has been captured in the term ‘group phenotypic composition’ (GPC). We provide examples where considerations of GPC could help in understanding the evolution and clinical progression of cancers and argue that use of the GPC framework can facilitate new insights into cancer biology and assist with the development of new therapeutic strategies.

HIF-1α and Pro-Inflammatory Signaling Improves the Immunomodulatory Activity of MSC-Derived Extracellular Vesicles.

Despite the strong evidence for the immunomodulatory activity of mesenchymal stromal cells (MSCs), clinical trials have so far failed to clearly show benefit, likely reflecting methodological shortcomings and lack of standardization. MSC-mediated tissue repair is commonly believed to occur in a paracrine manner, and it has been stated that extracellular vesicles (EVs) secreted by MSCs (EVMSC) are able to recapitulate the immunosuppressive properties of parental cells. As a next step, clinical trials to corroborate preclinical studies should be performed. However, effective dose in large mammals, including humans, is quite high and EVs industrial production is hindered by the proliferative senescence that affects MSCs during massive cell expansion. We generated a genetically modified MSC cell line overexpressing hypoxia-inducible factor 1-alpha and telomerase to increase the therapeutic potency of EVMSC and facilitate their large-scale production. We also developed a cytokine-based preconditioning culture medium to prime the immunomodulatory response of secreted EVs (EVMSC-T-HIFc). We tested the efficacy of this system in vitro and in a delayed-type hypersensitivity mouse model. MSC-T with an HIF-1α-GFP lentiviral vector (MSC-T-HIF) can be effectively expanded to obtain large amounts of EVs without major changes in cell phenotype and EVs composition. EVMSC-T-HIFc suppressed the proliferation of activated T-cells more effectively than did EVs from unmodified MSC in vitro, and significantly blunted the ear-swelling response in vivo by inhibiting cell infiltration and improving tissue integrity. We have developed a long-lived EV source that secretes high quantities of immunosuppressive EVs, facilitating a more standard and cost-effective therapeutic product.

Augmenting Tendon-to-Bone Repair with Functionally Graded Scaffolds.

Tendon-to-bone repair often fails because the functionally graded attachment is not regenerated during the healing process. Biomimetic scaffolds that recapitulate the unique features of the native tendon-to-bone attachment hold great promise for enhancing the healing process. Among various types of scaffolds that are developed and evaluated for tendon-to-bone repair, those with gradations (in either a stratified or a continuous fashion) in composition, structure, mechanical properties, and cell phenotype have gained the most attention. In this progress report, the recent efforts in the rational design and fabrication of functionally graded scaffolds based upon electrospun nanofiber mats and inverse opal structures, as well as the evaluation of their applications in augmenting tendon-to-bone repair, are reviewed. This report concludes with perspectives on the necessary future steps for clinical translation of the scaffolds.

New Frontiers of Body Composition in Sport.

The body composition phenotype of an athlete displays the complex interaction among genotype, physiological and metabolic demands of a sport, diet, and physical training. Observational studies dominate the literature and describe the sport-specific physique characteristics (size, shape, and composition) of adult athletes by gender and levels of competition. Limited data reveal how body composition measurements can benefit an athlete. Thus, the objective is to identify purposeful measurements of body composition, notably fat and lean muscle masses, and determine their impact on the health and performance of athletes. Areas of interest include relationships among total and regional body composition measurements, muscle function, sport-specific performance, risk of injury, return to sport after injury, and identification of activity-induced fluid shifts. Discussion includes the application of specific uses of dual X-ray absorptiometry and bioelectrical impedance including an emphasis on the need to minimize measurement errors and standardize protocols, and highlights opportunities for future research. This focus on functional body composition can benefit the health and optimize the performance of an athlete.

Spatial patterns in phage-Rhizobium coevolutionary interactions across regions of common bean domestication

Bacteriophages play significant roles in the composition, diversity, and evolution of bacterial communities. Despite their importance, it remains unclear how phage diversity and phage-host interactions are spatially structured. Local adaptation may play a key role. Nitrogen-fixing symbiotic bacteria, known as rhizobia, have been shown to locally adapt to domesticated common bean at its Mesoamerican and Andean sites of origin. This may affect phage-rhizobium interactions. However, knowledge about the diversity and coevolution of phages with their respective Rhizobium populations is lacking. Here, through the study of four phage-Rhizobium communities in Mexico and Argentina, we show that both phage and host diversity is spatially structured. Cross-infection experiments demonstrated that phage infection rates were higher overall in sympatric rhizobia than in allopatric rhizobia except for one Argentinean community, indicating phage local adaptation and host maladaptation. Phage-host interactions were shaped by the genetic identity and geographic origin of both the phage and the host. The phages ranged from specialists to generalists, revealing a nested network of interactions. Our results suggest a key role of local adaptation to resident host bacterial communities in shaping the phage genetic and phenotypic composition, following a similar spatial pattern of diversity and coevolution to that in the host.

Pulmonary administration of a CSF-1R inhibitor alters the balance of tumor-associated macrophages and supports first-line chemotherapy in a lung cancer model

Lung cancers remain the leading cause of cancer-related death in both men and women. Infiltrating immune cells in the tumor microenvironment (TME) play a critical role in the formation, progression, and the response of solid tumors to therapy, including in lung cancers. Clinical studies have established that tumor-associated macrophages (TAMs) and their phenotypical composition are critical immune infiltrates in the lung TME, with the abundance of the M2-like phenotype negatively correlating with patient survival. Colony-Stimulating Factor 1 (CSF-1) receptor (CSF-1R) is a type III protein tyrosine kinase receptor that plays an important role in the recruitment and differentiation of monocytes into tumor-promoting M2-like TAMs and their survival. In this work we evaluated the therapeutic potential of PLX 3397 (PLX), a small molecule CSF-1R inhibitor (CSF-1Ri), upon local lung administration in an immune-competent mouse model of lung cancer. The efficacy of local lung delivered PLX as single therapy was investigated first. As assessed by immunofluorescence of sections of lung tumor nodules, a statistically significant reduction in M2-like TAMs and an increase in M1-like TAMs was observed, thus leading to a shift in the (M1/M2) balance. Those changes in abundance of immune infiltrates correlated with a significant decrease in tumor burden when compared to control. When combined with systemically administered cisplatin (CIS) PLX treatment provided further benefits, leading to a significant decrease in tumor burden when compared to either PLX or CIS treatments alone, as measured by bioluminescence intensity (BLI) in vivo (thoracic area) and ex vivo (lung tissue). This combination therapy led to the most pronounced increase in M1/M2 ratio, followed by a significant decrease in M2-like TAMs with the CIS therapy. This work is clinically relevant as it demonstrates the potential of local lung administration of PLX to support standard of care chemotherapy for lung cancer management. This is important as the pulmonary route of administration is a plausible strategy for reducing the total dose of CSF-1Ris as the tissue of interest (lungs) can be locally targeted. Because the major off-target effect of CSF-1Ris is liver toxicity, reducing systemic concentration will support translation of those therapies, especially in combination with standard of care chemotherapy that has significant off-target toxicity and patient attrition itself. This work is scientifically relevant as we demonstrate for the first time that local administration of a CSF-1Ri to the lungs leads to a shift in the balance of TAMs in the TME of a model of lung tumor, adding to the sparse literature of CSF-1Ris related to lung cancers.

Using Composite Phenotypes to Reveal Hidden Physiological Heterogeneity in High-Altitude Acclimatization in a Chinese Han Longitudinal Cohort

Altitude acclimatization is a human physiological process of adjusting to the decreased oxygen availability. Since several physiological processes are involved and their correlations are complicated, the analyses of single traits are insufficient in revealing the complex mechanism of high-altitude acclimatization. In this study, we examined these physiological responses as the composite phenotypes that are represented by a linear combination of physiological traits. We developed a strategy that combines both spectral clustering and partial least squares path modeling (PLSPM) to define composite phenotypes based on a cohort study of 883 Chinese Han males. In addition, we captured 14 composite phenotypes from 28 physiological traits of high-altitude acclimatization. Using these composite phenotypes, we applied k-means clustering to reveal hidden population physiological heterogeneity in high-altitude acclimatization. Furthermore, we employed multivariate linear regression to systematically model (Models 1 and 2) oxygen saturation (SpO2) changes in high-altitude acclimatization and evaluated model fitness performance. Composite phenotypes based on Model 2 fit better than single trait-based Model 1 in all measurement indices. This new strategy of using composite phenotypes may be potentially employed as a general strategy for complex traits research such as genetic loci discovery and analyses of phenomics.

Cardiometabolic Profile of Different Body Composition Phenotypes in Children.

Cardiometabolic profiles of different body composition phenotypes are poorly characterized in young children, where it is well established that high adiposity is unfavorable, but the role of lean mass is unclear. We hypothesized that higher lean mass attenuates cardiometabolic risk in children with high fat mass. In 6-year-old children (n = 377) from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) prospective birth cohort, whole-body composition was measured by quantitative magnetic resonance, a novel validated technology. Based on fat mass index (FMI) and lean mass index (LMI), 4 body composition phenotypes were derived: low FMI-low LMI (LF-LL), low FMI-high LMI (LF-HL), high FMI-low LMI (HF-LL), high FMI-high LMI (HF-HL). Body mass index (BMI) z-score, fasting plasma glucose, insulin resistance, metabolic syndrome risk score, fatty liver index, and blood pressure. Compared with the LF-HL group, children in both high FMI groups had increased BMI z-score (HF-HL: 1.43 units 95% CI [1.11,1.76]; HF-LL: 0.61 units [0.25,0.96]) and metabolic syndrome risk score (HF-HL: 1.64 [0.77,2.50]; HF-LL: 1.28 [0.34,2.21]). The HF-HL group also had increased fatty liver index (1.15 [0.54,1.77]). Girls in HF-HL group had lower fasting plasma glucose (-0.29 mmol/L [-0.55,-0.04]) and diastolic blood pressure (-3.22 mmHg [-6.03,-0.41]) than girls in the HF-LL group. No similar associations were observed in boys. In a multi-ethnic Asian cohort, lean mass seemed to protect against some cardiometabolic risk markers linked with adiposity, but only in girls. The FMI seemed more important than lean mass index in relation to cardiometabolic profiles of young children.

Variation of gut microbiota caused by an imbalance diet is detrimental to bugs' survival

Diet is an important factor in shaping and influencing both an insect's phenotype and gut bacterial community, which commonly establishes diversely symbiotic interactions with the host. Efforts to leverage the connection between diet, insects, and gut microbiome primarily focus on how diet alters insect's phenotype or gut microbial composition and relatively few studies have illuminated the link between the diet-induced insect phenotypic difference and variation of gut microbiota. Mirids bugs, Adelphocoris suturalis, are plant sap-feeding omnivores that sometimes complementarily prey on other insects, like aphids (the dietary regime is referred to hereafter as balanced diet). In this study, we found that an imbalanced diet (exclusive ingestion of aphids) induced significantly higher mortality in A. suturalis (86.66%). Further gut microbial community analysis showed that the dietary difference significantly changed both the abundance and composition of the bug's gut microbiome. Most notably, an abundance of entomopathogenic Serratia bacteria in the A. suturalis gut was positively correlated with the proportion of aphids in A. suturalis diet, and Serratia marcescens was found to transfer into the hemocoels of carnivorous bugs. Injection of S. marcescens to the hemocoels further confirmed its detrimental effect to the bugs. Collectively, our study suggests that the diet-altered variation of gut microbiota may be detrimental to host insect, advancing the knowledge of omnivorous insects' strategy in forage allocation of different foods.

Body composition and breast cancer risk and treatment: mechanisms and impact.

The purpose of this review is to clarify the association of body composition with breast cancer risk and treatment, including physiological mechanisms, and to elucidate strategies for overcoming unfavorable body composition changes that relate to breast cancer progression. We have summarized updated knowledge regarding the mechanism of the negative association of altered body composition with breast cancer risk and treatment. We also review strategies for reversing unfavorable body composition based on the latest clinical trial results. Body composition changes in patients with breast cancer typically occur during menopause or as a result of chemotherapy or endocrine therapy. Dysfunction of visceral adipose tissue (VAT) in the setting of obesity underlies insulin resistance and chronic inflammation, which can lead to breast cancer development and progression. Insulin resistance and chronic inflammation are also observed in patients with breast cancer who have sarcopenia or sarcopenic obesity. Nutritional support and a personalized exercise program are the fundamental interventions for reversing unfavorable body composition. Other interventions that have been explored in specific situations include metformin, testosterone, emerging agents that directly target the adipocyte microenvironment, and bariatric surgery. A better understanding of the biology of body composition phenotypes is key to determining the best intervention program for patients with breast cancer.

Body composition phenotypes in rheumatoid arthritis

Objective. To study body composition phenotypes, the frequency of osteoporosis (OP), sarcopenia (SP), and obesity in postmenopausal women with rheumatoid arthritis (RA). Material and methods. 99 women (aged 40-75 years) with RA were enrolled in the study. All patients were interviewed using a special questionnaire. Anthropometric measurements and muscle strength determination were also peiformed. Bone mineral density and body composition were assessed with dual energy X-ray absorptiometry. Results. The frequency of OP was 31.3 % and the confirmed SP was 21.2 %. Isolated osteopenic phenotype was found in 14.1 %, osteosarcopenia - in 6.1 %, isolated sarcopenic phenotype - in 2.0 %, and phenotypes with obesity (osteopenic obesity, osteosarcopenic obesity and isolated obesity) - in 70.7 % of patients. Only 7.1 % of women had healthy phenotype. Conclusion. Patients with RA had combined phenotypes of body composition more often than isolated ones. Phenotypes with obesity determined by densitometry were the most common.

Shell colour and banding polymorphism in <i>Cepaea nemoralis</i>(Gastropoda, Pulmonata, Helicidae) from the Moscow region

The shell colour and banding were analyzed in more than 2000 specimens of Cepaea nemoralis collected in 11 localities in Moscow and the Moscow region. In the colonies studied, snails with pink shells usually predominate, most often represented by the phenotype 00000 (complete absence of the spiral bands). In most cases, yellow unbanded shells were absent or represented by single specimens. Brown shells, almost exclusively unbanded, were found only in 5 sites. On the example of colonies from Zagoryanski and Buch (Berlin), as well as Sheremetievski and Dolgoprudnyi, the phenotypic composition of newly formed colonies and colonies that could have been their origins was compared. A decrease in phenotypic diversity of newly formed colonies was noted.

Characterisation of body size phenotypes in a middle-aged Maltese population.

Obesity is increasingly recognised as being a heterogeneous disease. Some obese individuals may present a metabolically healthy profile (metabolically healthy obese (MHO)), while some normal weight individuals exhibit an adverse cardiometabolic phenotype (metabolically unhealthy normal weight individuals (MUHNW)). The objectives of the present study were to examine the prevalence and associated characteristics of the different body composition phenotypes within a Maltese cohort. This was a cross-sectional analysis involving 521 individuals aged 41 ± 5 years. The metabolically unhealthy state was defined as the presence of ≥2 metabolic syndrome components (NCEP-ATPIII parameters), while individuals with ≤1 cardiometabolic abnormalities were classified as metabolically healthy. Overall, 70 % of the studied population was overweight or obese and 30⋅7 % had ≥2 cardiometabolic abnormalities. The prevalence of MHO and MUHNW was 10⋅7 and 2⋅1 %, respectively. Individuals with the healthy phenotype were more likely to consume alcohol, participate in regular physical activity and less likely to be smokers. While the MHO phenotype had similar values for waist, hip and neck circumferences, waist-hip ratio and insulin resistance when compared with MUHNW individuals, there was a lower proportion of MHO subjects having a high fasting plasma glucose, hypertriglyceridaemia or low HDL-C when compared with the unhealthy lean individuals. A high prevalence of the metabolically unhealthy phenotype was observed in this relatively young population which may result in significant future cardiovascular disease burden if timely assessment and management of modifiable risk factors are not implemented. Furthermore, the present study suggests that the MHO phenotype is not totally benign as previously thought.

Assessment of the population and subpopulation composition of lymphocytes and their relationship in patients with sensorineural hearing loss

Phenotyping of blood lymphocytes (CD3+, CD4+, CD8+, CD9+, CD16+, CD20+, CD21+, CD23+, CD25+, CD95+) was performed by indirect immunofluorescence. Individuals with sensorineural hearing loss were found to have hyperactivation in both T- and B-cell links immunity. The revealed changes indicate a violation of immunoregulation through factors of intercellular cooperation, and the established relationships between populations and subpopulations of lymphocytes indicate increased activity components of the immune system, their important role in the implementation of the immune response in persons with sensorineural hearing loss.