Functional Aspects Research Articles

Polycatenanes Formed of Self‐Assembled Metal‐Organic Cages

AbstractPoly‐[n]‐catenanes (PCs) self‐assembled of three‐dimensional (3D) metal organic cages (MOCs) (hereafter referred to as PCs‐MOCs) are a relatively new class of mechanically interlocked molecules (MIMs) that combine the properties of MOCs and polymers. The synthesis of PCs‐MOCs is challenging because of the difficulties associated with interlocking MOCs, the occurrence of multiple weak supramolecular electrostatic interactions between cages, and the importance of solvent templating effects. The high density of mechanical bonds interlocking the MOCs endows the MOCs with mechanical and physical properties such as enhanced stability, responsive dynamic behavior and low solubility, which can unlock new functional properties. In this Minireview, we highlight the benefit of interlocking MOCs in the formation of PCs‐MOCs structures as well as the synthetic approaches exploited in their preparation, from thermodynamic to kinetic methods, both in the solution and solid‐states. Examples of PCs‐MOCs self‐assembled from various types of nanosized cages (i.e., tetrahedral, trigonal prismatic, octahedral and icosahedral) are described in this article, providing an overview of the research carried out in this area. The focus is on the structure–property relationship with examples of functional applications such as electron conductivity, X‐ray attenuation, gas adsorption and molecular sensing. We believe that the structural and functional aspects of the reviewed PCs‐MOCs will attract chemists in this research field with great potential as new functional materials in nanotechnological disciplines such as gas adsorption, sensing and photophysical properties such as X‐ray attenuation or electron conductivity.

Concerning structure-functional features of the leaf apparatus of some stone crops varieties belonging to <i>Prunus</i> (Rosaceae Juss.) genus

For the Rosaceae family (Rosaceae Juss.), which is part of the group of families with the highest species abundance, one of the largest genera is the Prunus genus, which, according to the Catalog of Life, includes 395 species, 16 subspecies, 55 variations. Various sources for this genus indicate from 250 to 400 species of trees and shrubs widely distributed in the northern temperate zone, subtropical and tropical regions, from forests to deserts, in altitude ranges from sea level to alpine zones. In the Samara Oblast, among 67 species of woody Rosaceae, there are 30 native and 36 introduced species (adventitious and wild). The genus is most widespread in the temperate zone of the Northern Hemisphere, is widely represented in North America, Europe and Northern Asia, and includes a number of cultivated species of global economic importance. The active involvement of interspecific hybridization between representatives of the Prunus genus is considered by experts as a determining factor in the evolutionary development of its species diversity, which manifested itself in the appearance of a number of hybridogenic species that were able to overcome successfully the effects of abiotic stressors in the process of expanding ranges, the formation of cultigenic species of stone crops and their varietal diversity. In recent decades, the characteristics of leaves have gained special place in the research programs of plant ecologists as significant indicators of various aspects of growth, reproduction and functions of the plant organism, water use, nutrients, adaptation to environmental changes, including projected climatic changes. Leaf indicators are the most accessible for study throughout almost the entire growing season, they can be evaluated quickly enough, without involving expensive equipment, the screening procedure for leaf apparatus indicators is well standardized. The combined efforts of researchers led to the creation of large and complete databases of leaf apparatus features for various plant species. For the leaves of 15 varieties of stone crops (cherry Olechka, Chernookaya, Kalinka, Nyusha, Pervinka; apricot Samara, Yantar Povolzhya; Russian plum Dolgozhdannaya, Konservnaya, Velikansha, Naryadnaya, Kompotnaya, Lunnaya; domestic plum Dachnaya, Doch Eurasii) quantitative indicators determined for samples selected in July 2020, 2021 and 2022 are analyzed. In order to visualize the possible features of the leaf apparatus in groups of varieties of various fruit crops, the construction of dot diagrams with a limited area of location for each group of points was used. This technique made it possible to identify both the presence of separate groups of points corresponding to one indicator of the leaves of individual stone fruits, and the overlap of the corresponding ranges of other indicators of values. Probably, this picture is a reflection of a certain ecological and physiological heterogeneity in groups of stone fruit varieties, which are cultigenic hybrids of complex origin.

Chronic β3 adrenergic agonist treatment improves brain microvascular endothelial function and cognition in aged mice.

Microvascular endothelial dysfunction, characterized by impaired neurovascular coupling, reduced glucose uptake, blood-brain barrier disruption, and microvascular rarefaction, plays a critical role in the pathogenesis of age-related vascular cognitive impairment (VCI). Emerging evidence points to non-cell autonomous mechanisms mediated by adverse circulating milieu (an increased ratio of pro-geronic to anti-geronic circulating factors) in the pathogenesis of endothelial dysfunction leading to impaired cerebral blood flow and cognitive decline in the aging population. In particular, age-related adipose dysfunction contributes, at least in part, to an unfavorable systemic milieu characterized by chronic hyperglycemia, hyperinsulinemia, dyslipidemia, and altered adipokine profile, which together contribute to microvascular endothelial dysfunction. Hence, in the present study, we aimed to test whether thermogenic stimulation, an intervention known to improve adipose and systemic metabolism by increasing cellular energy expenditure, could mitigate brain endothelial dysfunction and improve cognition in the aging population. Eighteen-month-old old C57BL/6J mice were treated with saline or CL (β3-adrenergic agonist) for 6 weeks followed by functional analysis to assess endothelial function and cognition. CL treatment improved neurovascular coupling responses and rescued brain glucose uptake in aged animals. In addition, CL treatment also attenuated blood-brain barrier leakage and associated neuroinflammation in the cortex of aged animals. More importantly, these beneficial changes in microvascular function translated to improved cognitive performance in radial arm water maze and Y-maze tests. Our results suggest that β3-adrenergic agonist treatment improves multiple aspects of brain microvascular endothelial function and can be potentially repurposed for treating age-associated cognitive decline.

A Controlled Clinical Trial on the Effects of Aquatic Exercise on Cognitive Functions in Community-Dwelling Older Adults.

Several therapies have been developed to reduce cognitive decline associated with aging. Aquatic exercises, which are widely used to enhance functional capacity, may play a role in stimulating cognitive functions. This study investigated the effects of a 3-month aquatic exercise program on cognitive functions in community-dwelling older adults. In this prospective, single-blinded, controlled clinical trial, 31 participants were allocated to either the experimental (aquatic exercises) or control (no-exercise) group. The intervention program consisted of exercises conducted twice a week in a 1.2 m deep indoor pool. The main outcome measures were cognitive functions, assessed using Raven's Progressive Matrices test and the Wisconsin Card Sorting Test. A repeated-measures analysis of variance was used to assess the impact of the exercise program. The effect sizes (η2p) were reported when a level of significance was achieved (p < 0.05). Compared with the control group, the participants who underwent aquatic exercises showed positive outcomes in Raven's Progressive Matrices test (p = 0.046; η2p = 0.131) and the Wisconsin Card Sorting Test (p = 0.001, η2p = 0.589). Complementary analyses of the Wisconsin Card Sorting Test indicated that the benefits of the aquatic exercise were observed in terms of the number of trials (p = 0.001, η2p = 0.478), number of errors (p = 0.001, η2p = 0.458), and number of non-perseverative errors (p = 0.001, η2p = 0.302). The results indicate that a period of three months of aquatic exercise was beneficial for stimulating specific aspects of the cognitive function of community-dwelling older individuals. Aquatic exercise should be prescribed to this population.

SWI/SNF Complex Connects Signaling and Epigenetic State in Cells of Nervous System.

SWI/SNF protein complexes are evolutionarily conserved epigenetic regulators described in all eukaryotes. In metameric animals, the complexes are involved in all processes occurring in the nervous system, from neurogenesis to higher brain functions. On the one hand, the range of roles is wide because the SWI/SNF complexes act universally by mobilizing the nucleosomes in a chromatin template at multiple loci throughout the genome. On the other hand, the complexes mediate the action of multiple signaling pathways that control most aspects of neural tissue development and function. The issues are discussed to provide insight into the molecular basis of the multifaceted role of SWI/SNFs in cell cycle regulation, DNA repair, activation of immediate-early genes, neurogenesis, and brain and connectome formation. An overview is additionally provided for the molecular basis of nervous system pathologies associated with the SWI/SNF complexes and their contribution to neuroinflammation and neurodegeneration. Finally, we discuss the idea that SWI/SNFs act as an integration platform to connect multiple signaling and genetic programs.

Crop functional structure predicts the provision of Nature´s material Contribution to People in diversified agroforestry

Applying concepts from natural ecosystem ecology, particularly through diversified cropping systems that integrate woody crops with other crops, can enhance agrobiodiversity and significantly contribute to multifunctional agriculture. The ecological and, more recently, the agronomic literature have indicated that functional trait aspects of diversity offer a more comprehensive explanation for ecosystem functions compared to species richness alone. In this study, we apply the trait-based approach during experimental agroforest succession in subtropical Southern Brazil to investigate the main factors of crop functional structure, differentiating the effects of functional diversity (FD) from functional identity (CWM - community weighted mean), on Nature's Contributions to People (NCP). The experiment was designed varying crop FD, based on leaf nitrogen concentration, while maintaining crop species richness constant across all treatments. To assess FD and CWM, we measured six crop traits; maximum plant height, leaf area, specific leaf area, leaf nitrogen content, leaf dry-matter content, and stem-specific density. Additionally, we evaluated four material NCP (green manure, forage, germplasm, and food) based on data collected during the initial four years of the experiment (2017–2020). To analyze the data, we employed principal component analysis to reduce the number of variables and subsequently fitted linear mixed-effect models. Our findings provide support for the hypothesis that crop functional structure, particularly in relation to leaf traits (leaf area and leaf nitrogen content) and vegetative height, significantly influences material outputs and predicts above-ground biomass production that can be utilized as green manure and animal feed in agroforestry and silvopastoral systems. Both FD and CWM were important drivers of NCPs, showing that both niche complementarity and selection effects contribute to explain agroecosystem functioning. By utilizing functional traits, we reached valuable insights for generating agronomical recommendations and enhancing cropping system diversification through effective trait-based management.

Selection with two alleles of X-linkage and its application to the fitness component analysis of OdsH in Drosophila.

In organisms with the XY sex-determination system, there is an imbalance in the inheritance and transmission of the X chromosome between males and females. Unlike an autosomal allele, an X-linked recessive allele in a female will have phenotypic effects on its male counterpart. Thus, genes located on the X chromosome are of particular interest to researchers in molecular evolution and genetics. Here we present a model for selection with two alleles of X-linkage to understand fitness components associated with genes on the X chromosome. We apply this model to the fitness analysis of an X-linked gene, OdsH (16D), in the fruit fly Drosophila melanogaster. The function of OdsH is involved in sperm production and the gene is rapidly evolving under positive selection. Using site-directed gene targeting, we generated functional and defective OdsH variants tagged with the eye-color marker gene white. We compare the allele frequency changes of the two OdsH variants, each directly competing against a wild-type OdsH allele in concurrent but separate experimental populations. After twenty generations, the two genetically modified OdsH variants displayed a 40% difference in allele frequencies, with the functional OdsH variant demonstrating an advantage over the defective variant. Using maximum likelihood estimation (MLE), we determined the fitness components associated with the OdsH alleles in males and females. Our analysis revealed functional aspects of the fitness determinants associated with OdsH, and that sex-specific fertility and viability consequences both contribute to selection on an X-linked gene.

Adverse Effects of Nicotine on Human Sperm Nuclear Proteins.

The effects of smoking on human health have long been documented. However, only a few studies have highlighted the direct effects of nicotine on sperm function. Nicotine, as a chemical compound found in tobacco, has been shown to modulate different aspects of spermatogenesis and sperm functions. Nicotine can lead to a reduction in the number of sperm, their motility and functionality. It can change the molecular expressions involved in sperm function, including genes encoding sperm nuclear proteins. The most important nuclear proteins that play a critical role in sperm function are known as H2B histone family, member W, testis-specific (H2BFWT), transition protein 1 (TNP1), transition protein 2 (TNP2), protamine-1 (PRM1), and protamine-2 (PRM2). These proteins are involved in sperm chromatin condensation, which in turn affects fertilization and embryonic development. Any alteration in the expression of these genes due to nicotine exposure/usage may lead to adverse implications in couples' fertility and the health of future generations. Since research in this area is still relatively new, it underscores the importance of understanding the potential side effects of environmental factors such as nicotine on reproductive health.

The multifaceted effects of flavonoids on neuroplasticity.

There has been a significant increase in the incidence of multiple neurodegenerative and terminal diseases in the human population with life expectancy increasing in the current times. This highlights the urgent need for a more comprehensive understanding of how different aspects of lifestyle, in particular diet, may affect neural functioning and consequently cognitive performance as well as in enhancing overall health. Flavonoids, found in a variety of fruits, vegetables, and derived beverages, provide a new avenue of research that shows a promising influence on different aspects of brain function. However, despite the promising evidence, most bioactive compounds lack strong clinical research efficacy. In the current scoping review, we highlight the effects of Flavonoids on cognition and neural plasticity across vertebrates and invertebrates with special emphasis on the studies conducted in the pond snail, Lymnaea stagnalis, which has emerged to be a functionally dynamic model for studies on learning and memory. In conclusion, we suggest future research directions and discuss the social, cultural, and ethnic dependencies of bioactive compounds that influence how these compounds are used and accepted globally. Bridging the gap between preclinical and clinical studies about the effects of bioactive natural compounds on brain health will surely lead to lifestyle choices such as dietary Flavonoids being used complementarily rather than as replacements to classical drugs bringing about a healthier future.

Advances in mass spectrometry imaging for plant metabolomics-Expanding the analytical toolbox.

Mass spectrometry imaging (MSI) has become increasingly popular in plant science due to its ability to characterize complex chemical, spatial, and temporal aspects of plant metabolism. Over the past decade, as the emerging and unique features of various MSI techniques have continued to support new discoveries in studies of plant metabolism closely associated with various aspects of plant function and physiology, spatial metabolomics based on MSI techniques has positioned it at the forefront of plant metabolic studies, providing the opportunity for far higher resolution than was previously available. Despite these efforts, profound challenges at the levels of spatial resolution, sensitivity, quantitative ability, chemical confidence, isomer discrimination, and spatial multi-omics integration, undoubtedly remain. In this Perspective, we provide a contemporary overview of the emergent MSI techniques widely used in the plant sciences, with particular emphasis on recent advances in methodological breakthroughs. Having established the detailed context of MSI, we outline both the golden opportunities and key challenges currently facing plant metabolomics, presenting our vision as to how the enormous potential of MSI technologies will contribute to progress in plant science in the coming years.

Serum Amylase Levels in T2DM Patients: Surrogate Biomarker of Cardiometabolic Status

Abstract Introduction: Diabetes mellitus with hyperglycaemia is a chronic metabolic disorder. The endocrinal function of the pancreas is altered in diabetes mellitus. There is a close anatomic and functional relationship between the exocrine and endocrine portions of the pancreas. The current study was conducted to evaluate the blood glucose and serum amylase levels in type 2 diabetic patients as they represent the two functional aspects of the gland. The aim of the study was to determine the serum amylase and serum lipase in type 2 diabetic patients and to compare and correlate these parameters with those of age- and sex-matched healthy controls. Methodology: Already diagnosed 300 type 2 diabetes mellitus patients have been included in our study as cases and 50 healthy individuals attending the outpatient department have been included as controls. Fasting venous samples have been collected from cases and controls and analysed for blood glucose, lipid profile, renal function test, liver function test, serum amylase and lipase. The results were analysed using Student’s t-test and correlation coefficient. Results: Low levels of serum amylase were observed in type 2 diabetic patients and the values were statistically significant with P &lt; 0.005. The levels of total cholesterol, triglyceride and low-density lipoprotein cholesterol were compared among both the groups and values were significantly higher in cases compared to the controls with P &lt; 0.05, &lt;0.001 and &lt;0.05, respectively. The high-density lipoprotein (HDL) levels were found to be lower in cases with the P &lt; 0.001. Conclusion: In our study, it was observed that, as the blood glucose levels are higher in type 2 diabetic patients, the serum amylase levels were lower significantly. There was a positive correlation between the HDL and serum amylase values, which signifies the role of amylase as an additional and surrogate biomarker for monitoring cardiometabolic status.

Association between dietary (poly)phenol intake and the ATHLOS Healthy Ageing Scale in the Polish arm of the HAPIEE study.

Inverse association between (poly)phenol intake and age-related disorders has been demonstrated; however, little is known whether they affect comprehensively assessed healthy aging. The aim of this study was to evaluate the associations between the intake of (poly)phenol (including selected classes and subclasses) and healthy aging scores related to biopsychosocial aspects of health and functioning. A cross-sectional study was performed using data on 9774 randomly selected citizens of Krakow (Poland) who were 45-69years of age. Dietary (poly)phenol intake was evaluated using a food frequency questionnaire and matching food consumption data with the Phenol-Explorer database. The healthy aging scores were estimated from the ATHLOS Healthy Ageing Scale (HAS) developed by the Ageing Trajectories of Health-Longitudinal Opportunities and Synergies (ATHLOS) consortium. Beta coefficients were calculated using multivariable linear regression models. In multivariable adjusted models, there were significant positive associations between the ATHLOS HAS score and intake of total (poly)phenols (b per increase of 100mg/day = 0.081; 95% CI, 0.050; 0.112) and among main classes of (poly)phenols with phenolic acids (b = 0.139; 95% CI, 0.098; 0.180). Intake of remaining classes of (poly)phenols (flavonoids, lignans, stilbenes, and others) was not related to the ATHLOS HAS score. Among individual classes studied, hydroxycinnamic acids, flavonols, flavones, and dihydrochalcones were associated with better healthy aging. The findings suggest the beneficial effect of total dietary (poly)phenol and some classes and subclasses of (poly)phenol intake in terms of healthy aging in Poland. These findings should be confirmed in other settings and with prospective data.

Association between dietary (poly)phenol intake and the ATHLOS Healthy Ageing Scale in the Polish arm of the HAPIEE study.

Inverse association between (poly)phenol intake and age-related disorders has been demonstrated; however, little is known whether they affect comprehensively assessed healthy aging. The aim of this study was to evaluate the associations between the intake of (poly)phenol (including selected classes and subclasses) and healthy aging scores related to biopsychosocial aspects of health and functioning. A cross-sectional study was performed using data on 9774 randomly selected citizens of Krakow (Poland) who were 45-69years of age. Dietary (poly)phenol intake was evaluated using a food frequency questionnaire and matching food consumption data with the Phenol-Explorer database. The healthy aging scores were estimated from the ATHLOS Healthy Ageing Scale (HAS) developed by the Ageing Trajectories of Health-Longitudinal Opportunities and Synergies (ATHLOS) consortium. Beta coefficients were calculated using multivariable linear regression models. In multivariable adjusted models, there were significant positive associations between the ATHLOS HAS score and intake of total (poly)phenols (b per increase of 100mg/day = 0.081; 95% CI, 0.050; 0.112) and among main classes of (poly)phenols with phenolic acids (b = 0.139; 95% CI, 0.098; 0.180). Intake of remaining classes of (poly)phenols (flavonoids, lignans, stilbenes, and others) was not related to the ATHLOS HAS score. Among individual classes studied, hydroxycinnamic acids, flavonols, flavones, and dihydrochalcones were associated with better healthy aging. The findings suggest the beneficial effect of total dietary (poly)phenol and some classes and subclasses of (poly)phenol intake in terms of healthy aging in Poland. These findings should be confirmed in other settings and with prospective data.

ENHANCING EMOTIONAL VOCABULARY FOR PSYCHOLOGICAL LITERACY

Various aspects of language development, comprehension and neurological functioning contribute to reflective psychological attitudes and indicate the importance of language in understanding human behaviour. In this perspective we focus our attention on the role of emotional language in shaping psychological literacy. Our research mostly relies on the findings of the Theory of Constructed Emotion (TCE) and EmotionFocused Therapy (EFT) that confirmed the importance of emotional vocabulary in the process of forming the effective understanding of the emotions and creating new conscious experiences. Due to the development of affective neuroscience, emotional vocabulary is presented as a necessary tool for psychological studies of personality, emotions and mood that aim to increase empirical evidence on the ways how emotions are organised in the mind. Special attention is given to the phenomenon of blended emotions that refer to the simultaneous experience of two or more emotions. We show that the awareness of the complexity of emotional experience is directly related to finding words that capture combinations of a variety of emotions. Keywords: emotional vocabulary; psychological literacy; emotion awareness; emotional psychology

The relationship between personality and cognition in older adults with and without early-onset depression.

It is well established that personality traits impact cognition, as certain personality factors are associated with performance in specific cognitive domains. However, the findings on the relationships between the Big Five traits and cognition are mixed. Additionally, few studies have explored these relationships in older adults with a history of depression. The present study aimed to (a) evaluate the impact of the Big Five personality traits in older adults with and without a lifetime history of depression; and (b) test the hypotheses that higher trait neuroticism would correlate negatively with cognitive performance, while openness to experience would correlate positively with cognition. The sample consisted of 138 participants between the ages of 55 and 78 (M = 65.56, SD = 6.36). Sixty-two participants met criteria for current or remitted Major Depressive Disorder, while 76 had no history of depression or other mental health disorders. Participants underwent comprehensive neuropsychological testing. Personality was assessed using the NEO Personality Inventory-Revised (NEO-PI-R), while depression status was determined using the Structured Clinical Interview for DSM-5 (SCID-5). Following a series of Pearson correlations of cognitive variables and the five personality factors, linear regression models were estimated for each significant correlation. Demographic variables (i.e., age, education and sex) were entered in block 1, depression status (never vs. ever) was entered in block 2, and the personality factor score, or sub-facet was entered in block 3. Neuroticism was not associated with cognitive performance on any outcome measure. The facets Openness to Feelings and Openness to Values were positively related to phonemic fluency. Further Openness to Values was positively related to cognitive flexibility. Our results suggest that older people who are (a) more capable of identifying and understanding their feelings and the feelings of others, and (b) who are more willing to re-examine social, political, and religious values perform stronger on tasks measuring verbal fluency and cognitive flexibility, which are aspects of executive functioning. Interventions that aim to enhance open mindedness in older adults may have a parallel impact on improving executive functioning, though this would need to be examined prospectively.

Spatial selectivity of ATase inhibition in mouse models of Charcot-Marie-Tooth disease

Abstract The endoplasmic reticulum acetylation machinery has emerged as a new branch of the larger endoplasmic reticulum quality control system. It regulates the selection of correctly folded polypeptides as well as reticulophagy-mediated removal of toxic protein aggregates with the former being a particularly important aspect of the proteostatic functions of endoplasmic reticulum acetylation. Essential to this function is the Nε-lysine acetyltransferase activity of acetyltransferase 1 and acetyltransferase 2, which regulates the induction of endoplasmic reticulum-specific autophagy though the acetylation of the autophagy-related protein 9A. Here, we used three mouse models of Charcot-Marie-Tooth disease, peripheral myelin protein 22/Tr-J, C3-peripheral myelin protein 22, and myelin protein zero/ttrr, to study spatial and translational selectivity of endoplasmic reticulum acetyltransferase inhibitors. The results show that inhibition of the endoplasmic reticulum acetyltransferases selectively targets misfolding/pro-aggregating events occurring in the lumen of the organelle. Therefore, they establish acetyltransferase 1 and acetyltransferase 2 as the first proven targets for disease-causing proteotoxic states that initiate within the lumen of the endoplasmic reticulum/secretory pathway.

Spatial selectivity of ATase inhibition in mouse models of Charcot-Marie-Tooth disease.

The endoplasmic reticulum acetylation machinery has emerged as a new branch of the larger endoplasmic reticulum quality control system. It regulates the selection of correctly folded polypeptides as well as reticulophagy-mediated removal of toxic protein aggregates with the former being a particularly important aspect of the proteostatic functions of endoplasmic reticulum acetylation. Essential to this function is the Nε-lysine acetyltransferase activity of acetyltransferase 1 and acetyltransferase 2, which regulates the induction of endoplasmic reticulum-specific autophagy through the acetylation of the autophagy-related protein 9A. Here, we used three mouse models of Charcot-Marie-Tooth disease, peripheral myelin protein 22/Tr-J, C3-peripheral myelin protein 22 and myelin protein zero/ttrr, to study spatial and translational selectivity of endoplasmic reticulum acetyltransferase inhibitors. The results show that inhibition of the endoplasmic reticulum acetyltransferases selectively targets misfolding/pro-aggregating events occurring in the lumen of the organelle. Therefore, they establish acetyltransferase 1 and acetyltransferase 2 as the first proven targets for disease-causing proteotoxic states that initiate within the lumen of the endoplasmic reticulum/secretory pathway.

Coarse-Grained Modeling of Liquid-Liquid Phase Separation in Cells: Challenges and Opportunities.

Liquid-liquid phase separation (LLPS) within cells gives rise to membraneless organelles, which play pivotal roles in numerous cellular functions. A comprehensive understanding of the functional aspects of intrinsically disordered protein (IDP) condensates necessitates elucidating their inherent structures and establishing correlations with biological functions. Coarse-grained (CG) molecular dynamics (MD) simulations present a promising avenue for gaining insights into LLPS mechanisms of biomacromolecules. Essential to this endeavor is the development of tailored CG force fields for MD simulations, incorporating the full spectrum of biomolecules involved in the formation of condensates and accounting for real-time biochemical reactions coupled to the LLPS. Moreover, developing accurate theoretical frameworks and establishing links between condensate structure and its function are imperative for a thorough comprehension of LLPS of biological systems.

Genotype-specific expression of uncle fester suggests a role in allorecognition education in a basal chordate.

Histocompatibility is the ability to discriminate between self and non-self tissues, and has been described in species throughout the metazoa. Despite its universal presence, histocompatibility genes utilized by different phyla are unique- those found in sponges, cnidarians, ascidians and vertebrates are not orthologous. Thus, the origins of these sophisticated recognition systems, and any potential functional commonalities between them are not understood. We are studying histocompatibility in the botryllid ascidians, members of the chordate subphylum, Tunicata, which provide a powerful model to understand both the origins and functional aspects of this process. Histocompatibility in the botryllids occurs at the tips of an extracorporeal vasculature that come into contact when two individuals grow into proximity. If compatible, the vessels will fuse, forming a parabiosis between the two individuals. If incompatible, the two vessels will reject- an inflammatory reaction that results in melanin scar formation at the point of contact, blocking anastomosis. Compatibility is determined by a single, highly polymorphic locus called the fuhc with the following rules: individuals that share one or both fuhc alleles will fuse, while those who share neither will reject. The fuhc locus encodes at least six proteins with known roles in allorecognition. One of these genes, called uncle fester, is necessary and sufficient to initiate the rejection response. Here we report the existence of genotype-specific expression levels of uncle fester, differing by up to 8-fold at the mRNA-level, and that these expression levels are constant and maintained for the lifetime of an individual. We also found that these differences had functional consequences: the expression level of uncle fester correlated with the speed and severity of the rejection response. These findings support previous conclusions that uncle fester levels modulate the rejection response, and may be responsible for controlling the variation observed in the timing and intensity of the reaction. The maintenance of genotype specific expression of uncle fester is also evidence of an education process reminiscent of that which occurs in mammalian Natural Killer (NK) cells. In turn, this suggests that while histocompatibility receptors and ligands evolve via convergent evolution, they may utilize conserved intracellular machinery to interpret binding events at the cell surface.

Optogenetics in pancreatic islets: Actuators and effects.

The Islets of Langerhans reside within the endocrine pancreas as highly vascularised micro-organs that are responsible for the secretion of key hormones, such as insulin and glucagon. Islet function relies on a range of dynamic molecular processes that include calcium (Ca2+) waves, hormone pulses, and complex interactions between islet cell types. Dysfunction of these processes results in poor maintenance of blood glucose homeostasis and is a hallmark of diabetes. Very recently, the development of optogenetic methods that rely on light-sensitive molecular actuators has allowed perturbing islet function with near physiological spatio-temporal acuity. These actuators harness natural photoreceptor proteins and their engineered variants to manipulate mouse and human cells that are not normally light-responsive. Until recently, optogenetics in islet biology has primarily focused on hormone production and secretion; however, studies on further aspects of islet function, including paracrine regulation between islet cell types and dynamics within intracellular signaling pathways are emerging. Here, we discuss the applicability of optogenetics to islets cells and comprehensively review seminal as well as recent work on optogenetic actuators and their effects in islet function and diabetes mellitus (DM).