The role of calcium oscillations in the phenotype selection in endothelial cells

Angiogenesis is an important process in the formation and maintenance of tissues which is driven by a complex system of intracellular and intercellular signaling mechanisms. Endothelial cells taking part in early angiogenesis must select their phenotype as either a tip cells (leading, migratory) or a stalk cells (following). Recent experiments have demonstrated that rapid calcium oscillations within active cells characterize this phenotype selection process and that these oscillations play a necessary role in governing phenotype selection and eventual vessel architecture. In this work, we develop a mathematical model capable of describing these oscillations and their role in phenotype selection then use it to improve our understanding of the biological mechanisms at play. We developed a model based on two previously published and experimentally validated mathematical models of calcium and angiogenesis then use our resulting model to simulate various multi-cell scenarios. We are able to capture essential calcium oscillation dynamics and intercellular communication between neighboring cells. The results of our model show that although the late DLL4 (a transmembrane protein that activates Notch pathway) levels of a cell are connected with its initial IP3 (Inositol 1,4,5-trisphosphate) level, cell-to-cell communication determines its eventual phenotype.

Click chemistry–enabled CRISPR screening reveals GSK3 as a regulator of PLD signaling

Enzymes that produce second messengers are highly regulated. Revealing the mechanisms underlying such regulation is critical to understanding both how cells achieve specific signaling outcomes and return to homeostasis following a particular stimulus. Pooled genome-wide CRISPR screens are powerful unbiased approaches to elucidate regulatory networks, their principal limitation being the choice of phenotype selection. Here, we merge advances in bioorthogonal fluorescent labeling and CRISPR screening technologies to discover regulators of phospholipase D (PLD) signaling, which generates the potent lipid second messenger phosphatidic acid. Our results reveal glycogen synthase kinase 3 as a positive regulator of protein kinase C and PLD signaling. More generally, this work demonstrates how bioorthogonal, activity-based fluorescent tagging can expand the power of CRISPR screening to uncover mechanisms regulating specific enzyme-driven signaling pathways in mammalian cells.

The interplay of spatial scale and landscape transformation modulates the abundance and intraspecific variation in the ecomorphological traits of a phyllostomid bat

Land use intensification imposes selective pressures that systematically change the frequency of wild population phenotypes. Growing evidence is biased towards the comparison of populations from discrete categories of land uses, ignoring the role of landscape emerging properties on the phenotype selection of wild fauna. Across the largest urban–rural gradient of the Colombian Orinoquia, we measured ecomorphological traits of 216 individuals of the flat-faced fruit-eating bat Artibeus planirostris. We did this to evaluate the scale of effect at which landscape transformation better predicts changes in phenotype and abundance of an urban-tolerant species. Forest percentage at 1.25 km was the main predictor affecting negatively bat abundance and positively its wing aspect ratio and body mass. Landscape variables affected forearm length at all spatial scales, this effect appeared to be sex-dependent, and the most important predictor, forest percentage at 0.5 km, had a negative effect on this trait. Our results indicate that landscape elements and spatial scale interact to shape ecomorphological traits and the abundance of A. planirostris. Interestingly, the scale of effect coincided at 1.25 km among all biological responses, suggesting that species’ abundance can be linked to the variation on phenotype under different environmental filters across landscape scenarios.

Two emerging international orders? China and the United States

If it continues, deglobalization may lead not to atomization but two overlapping international orders: a liberal one (LIO) led by the United States, and an authoritarian–capitalist one (ACIO) led by China. This equilibrium could emerge because a central purpose of international orders is to preserve the domestic regimes of their Great Power sponsors. The United States and China have markedly different domestic regimes, and so as China continues to grow in power and influence, tension over the content of international order should continue to grow. I borrow from Darwinian evolution the notion of ‘niche construction’: just as organisms alter phenotype selection by manipulating their natural environments, states can alter the ‘selection’ of domestic regimes by shaping their international environments. Modes of international niche construction include foreign regime promotion, interdependence, transnational interaction and multilateral institutions. The liberal democratic niche constructed by the United States and its allies after the Second World War preserved democracy for many decades. Today, China is attempting through various means to build a niche that will eliminate the liberal bias in international institutions and safeguard its own Market-Leninist regime. The resulting ACIO would select for autocracy and hence be partially separate from the LIO, which selects for liberal democracy.

The interplay of spatial scale and landscape transformation moderates the abundance and intraspecific variation in the ecomorphological traits of a phyllostomid bat

Land-use intensification imposes selective pressures that systematically change the frequency of wild population phenotypes. Growing evidence is biased towards the comparison of populations from discrete categories of land uses, ignoring the role of landscape emerging properties on the phenotype selection of wild fauna. Across the largest urban-rural gradient of the Colombian Orinoquia, we measured ecomorphological traits of 216 individuals of the Flat-faced Fruit-eating Bat Artibeus planirostris, to evaluate the scale of effect at which landscape transformation better predicts changes in phenotype and abundance of an urban-tolerant species. Forest percentage at 1.25 km was the main predictor affecting abundance, wing aspect ratio, and body mass of this phyllostomid; but the direction of the effect differed between abundance and ecomorphological traits. Although landscape factors explained changes in the forearm length at all spatial scales, the effect was sex-dependent and the most important predictor was forest percentage at 0.5 km. Our results indicate that landscape elements and spatial scale interact to shape ecomorphological traits and the abundance of A. planirostris. Interestingly, the scale of effect was congruent among all biological responses. A pattern that likely arises since species' abundance can reflect the variation on phenotype under different environmental filters across landscape scenarios.

When the microbiome defines the host phenotype: selection on vertical transmission in varying environments

The microbiome can contribute to variation in fitness-related traits of their hosts, and thus to host evolution. Hosts are therefore expected to be under selection to control their microbiome, for instance through controlling microbe transmission from parents to offspring. Current models have mostly focused on microbes that either increase or decrease fitness. In that case, host-level selection is relatively straightforward, favouring either complete or no inheritance. In natural systems, however, vertical transmission fidelity varies widely, and microbiome composition is often shaped by a combination of vertical and horizontal transmission modes. We propose that such mixed transmission could optimize host fitness under fluctuating environments. Using a general model, we illustrate that decreasing vertical transmission fidelity increases the amount of microbiome variation, and thus potentially phenotypic variation, across hosts. Whether or not this is advantageous depends on environmental conditions, how much the microbiome changes during host development, and the contribution of other factors to trait variation. We discuss how environmentally-dependent microbial effects can favor intermediate transmission, review examples from natural systems, and suggest research avenues to empirically test our predictions. Overall, we show that imperfect transmission may be adaptive by allowing individuals to ensure phenotypic variability in their offspring in contexts where varying environments mean that this strategy increases long-term fitness.

Biological features of pigs of different productivity types in early ontogenesis

The morphogenetic period is the most important period of ontogenesis, the period of the highest activity of genes that provide the fundamental foundation and development of the main systems of the body. Breeding changes always begin with genetic changes that change the course of development and are realized in the phenotype. Thus, at the level of the phenotype selection plays an important role. The path from gene to trait is a major problem in developmental biology. The study was carried out on fetuses, embryos and newborn piglets of large white, Landrace and Mirgorod breed. The animal organism is an integral structure, where all organs, systems and tissues are interdependent and interconnected. Correlations preserve the organism as an integral structure. The study of biological patterns of development is of great practical importance in pig breeding. Their knowledge allows not only to improve existing breeds, breed types, but also allows to create new breeds and manage productivity. The directed development of the organism is influenced by the controlling factors of heredity in interaction with the environment. The intensity of metabolism is associated with its development and the formation of productive qualities. The type of animal can be the main factor in the assessment that determines the productivity of the animal. The type of animal includes its general appearance by which the productivity of the animal is determined. Meat, greasy and versatile types can be clearly distinguished. The main indicators that characterize the features of the morphogenetic period of ontogenesis are the following: live weight, height, development of the physique, internal organs, skeleton and muscle tissue. The role of blood in the body is very diverse. The main indicators for studying the properties of blood, its total amount, composition (the number of erythrocytes and leukocytes, the content of hemoglobin, protein, its fractions) are also relevant. In fetuses of Landrace and Large White breeds, along with high fertility, a greater number of blood cells and a high concentration of protein in the plasma of blood elements were revealed in comparison with fetuses and newborns of Mirgorod breed.

The Value of Phenotypes in Knee Osteoarthritis Research

Background: Over the past decade, phenotypes have been used to help categorize knee osteoarthritis patients relative to being subject to disease, disease progression, and treatment response. A review of potential phenotype selection is now appropriate. The appeal of using phenotypes is that they most rely on simple physical examination, clinically routine imaging, and demographics. The purpose of this review is to describe the panoply of phenotypes that can be potentially used in osteoarthritis research. Methods: A search of PubMed was used singularly to review the literature on knee osteoarthritis phenotypes. Results: Four phenotype assembly groups were based on physical features and noninvasive imaging. Demographics included metabolic syndrome (dyslipidemia, hypertension, obesity, and diabetes). Mechanical characteristics included joint morphology, alignment, the effect of injury, and past and present history. Associated musculoskeletal disorder characteristics included multiple joint involvement, spine disorders, neuromuscular diseases, and osteoporosis. With the knee as an organ, tissue characteristics were used to focus on synovium, meniscus, articular cartilage, patella fat pad, bone sclerosis, bone cysts, and location of pain. Discussion: Many of these phenotype clusters require further validation studies. There is special emphasis on knee osteoarthritis phenotypes due to its predominance in osteoarthritic disorders and the variety of tissues in that joint. More research will be required to determine the most productive phenotypes for future studies. Conclusion: The selection and assignment of phenotypes will take on an increasing role in osteoarthritis research in the future.