Miracle-dz/UniFAR-FTUs huggingface dataset:
Heparin inhibits BMP‐2 osteogenic bioactivity by binding to both BMP‐2 and BMP receptor

Heparin demonstrates several kinds of biological activities by binding to various extracellular molecules and plays pivotal roles in bone metabolism. However, the role of heparin in the biological activity of bone morphogenetic protein (BMP) remains unclear. In the present study, we examined whether heparin has the effects on osteoblast differentiation induced by BMP‐2 in vitro and also elucidated the precise mechanism by which heparin regulates bone metabolism induced by this molecule. Our results showed that heparin inhibited alkaline phosphatase (ALP) activity and mineralization in osteoblastic cells cultured with BMP‐2. Heparin was found to suppress the mRNA expressions of osterix, Runx2, ALP and osteocalcin, as well as phosphorylation of Smad1/5/8 and p38 MAPK. Further, heparin bound to both BMP‐2 and BMP receptor (BMPR). These results suggest that heparin suppresses BMP‐2‐BMPR binding, and inhibits BMP‐2 osteogenic activity in vitro. J. Cell. Physiol. 216: 844–850, 2008, © 2008 Wiley‐Liss, Inc.
The role of local ecology during hybridization at the initial stages of ecological speciation in a marine snail

Hybrid zones of ecologically divergent populations are ideal systems to study the interaction between natural selection and gene flow during the initial stages of speciation. Here, we perform an amplified fragment length polymorphism (AFLP) genome scan in parallel hybrid zones between divergent ecotypes of the marine snail Littorina saxatilis, which is considered a model case for the study of ecological speciation. Ridged‐Banded (RB) and Smooth‐Unbanded (SU) ecotypes are adapted to different shore levels and microhabitats, although they present a sympatric distribution at the mid‐shore where they meet and mate (partially assortatively). We used shell morphology, outlier and nonoutlier AFLP loci from RB, SU and hybrid specimens captured in sympatry to determine the level of phenotypic and genetic introgression. We found different levels of introgression at parallel hybrid zones and nonoutlier loci showed more gene flow with greater phenotypic introgression. These results were independent from the phylogeography of the studied populations, but not from the local ecological conditions. Genetic variation at outlier loci was highly correlated with phenotypic variation. In addition, we used the relationship between genetic and phenotypic variation to estimate the heritability of morphological traits and to identify potential Quantitative Trait Loci to be confirmed in future crosses. These results suggest that ecology (exogenous selection) plays an important role in this hybrid zone. Thus, ecologically based divergent natural selection is responsible, simultaneously, for both ecotype divergence and hybridization. On the other hand, genetic introgression occurs only at neutral loci (nonoutliers). In the future, genome‐wide studies and controlled crosses would give more valuable information about this process of speciation in the face of gene flow.
Investigating the production of sexual resting structures in a plant pathogen reveals unexpected self‐fertility and genotype‐by‐environment effects

The sexual stage of pathogens governs recombination patterns and often also provides means of surviving the off‐season. Despite its importance for evolutionary potential and between‐season epidemiology, sexual systems have not been carefully investigated for many important pathogens, and what generates variation in successful sexual reproduction of pathogens remains unexplored. We surveyed the sexually produced resting structures (chasmothecia) across 86 natural populations of fungal pathogen Podosphaera plantaginis (Ascomycota) naturally infecting Plantago lanceolata in the Åland archipelago, southwestern Finland. For this pathosystem, these resting structures are a key life‐history stage, as more than half of the local pathogen populations go extinct every winter. We uncovered substantial variation in the level of chasmothecia produced among populations, ranging from complete absence to presence on all infected leaves. We found that chasmothecia developed within clonal isolates (single‐strain cultures). Additionally, these clonal isolates all contained both MAT1‐1‐1 and MAT1‐2‐1 genes that characterize mating types in Ascomycetes. Hence, contrary to expectations, we conclude that this species is capable of haploid selfing. In controlled inoculations, we discovered that pathogen genotypes varied in their tendency to produce chasmothecia. Production of chasmothecia was also affected by ambient temperature (E) and by the interaction between temperature and pathogen genotype (G × E). These G, E and G × E effects found both at a European scale and within the Åland archipelago may partly explain the high variability observed among populations in chasmothecia levels. Consequently, they may be key drivers of the evolutionary potential and epidemiology of this highly dynamic pathosystem.
Konzeptualisierung und Operationalisierung sozialer Ungleichheit im Kinder- und Jugendgesundheitssurvey

Poverty and social disadvantages are often accompanied by long-lasting social and psychosocial strain on the well-being and health of children and adolescents. From a health policy point of view the rising poverty quotas among young people indicate a high need for action. The status of empirical research is insufficient, so that it is difficult to plan and undertake political measures. The National Health Survey for Children and Adolescents will provide data permitting differentiated analysis of relations between poverty, social inequality and health in the adolescent generation. To get a first impression of possible analyses, the present article demonstrates which information on the living situation will be ascertained in the National Health Survey for Children and Adolescents, and which theoretical and methodological considerations have been playing a role.
Role of the hemopexin domain of matrix metalloproteinases in cell migration

The biological functions of matrix metalloproteinases (MMPs) extend beyond extracellular matrix degradation. Non‐proteolytic activities of MMPs are just beginning to be understood. Herein, we evaluated the role of proMMPs in cell migration. Employing a Transwell chamber migration assay, we demonstrated that transfection of COS‐1 cells with various proMMP cDNAs resulted in enhancement of cell migration. Latent MMP‐2 and MMP‐9 enhanced cell migration to a greater extent than latent MMP‐1, ‐3, ‐11 and ‐28. To examine if proteolytic activity is required for MMP‐enhanced cell migration, three experimental approaches, including fluorogenic substrate degradation assay, transfection of cells with catalytically inactive mutant MMP cDNAs, and addition of hydroxamic acid‐derived MMP inhibitors, were employed. We demonstrated that the proteolytic activities of MMPs are not required for MMP‐induced cell migration. To explore the mechanism underlying MMP‐enhanced cell migration, structure‐function relationship of MMP‐9 on cell migration was evaluated. By using a domain swapping approach, we demonstrated that the hemopexin domain of proMMP‐9 plays an important role in cell migration when examined by a transwell chamber assay and by a phagokinetic migration assay. TIMP‐1, which interacts with the hemopexin domain of proMMP‐9, inhibited cell migration, whereas TIMP‐2 had no effect. Employing small molecular inhibitors, MAPK and PI3K pathways were found to be involved in MMP‐9‐mediated cell migration. In conclusion, we demonstrated that MMPs utilize a non‐proteolytic mechanism to enhance epithelial cell migration. We propose that hemopexin homodimer formation is required for the full cell migratory function of proMMP‐9. J. Cell. Physiol. 217: 643–651, 2008. © 2008 Wiley‐Liss, Inc.
Multiple Kv1.5 targeting to membrane surface microdomains

Surface expression of voltage‐dependent K+ channels (Kv) has a pivotal role in leukocyte physiology. Although little is known about the physiological role of lipid rafts, these microdomains concentrate signaling molecules and their ion channel substrates. Kv1.3 associates with Kv1.5 to form functional channels in macrophages. Different isoform stoichiometries lead to distinct heteromeric channels which may be further modulated by targeting the complex to different membrane surface microdomains. Kv1.3 targets to lipid rafts, whereas Kv1.5 localization is under debate. With this in mind, we wanted to study whether heterotetrameric Kv1.5‐containing channels target to lipid rafts. While in transfected HEK‐293 cells, homo‐ and heterotetrameric channels targeted to rafts, Kv1.5 did not target to rafts in macrophages. Therefore, Kv1.3/Kv1.5 hybrid channels are mostly concentrated in non‐raft microdomains. However, LPS‐induced activation, which increases the Kv1.3/Kv1.5 ratio and caveolin, targeted Kv1.5 back to lipid rafts. Moreover, Kv1.5 did not localize to low‐buoyancy fractions in L6E9 skeletal myoblasts, which also coexpress both channels, heart membranes or cardiomyocyes. Coexpression of a Cav3DGV‐mutant confined Kv1.5 to Cav3DGV‐vesicles of HEK cells. Contrarily, coexpression of Kvβ2. 1 impaired the Kv1.5 targeting to raft microdomains in HEK cells. Our results indicate that Kv1.5 partnership interactions are underlying mechanisms governing channel targeting to lipid rafts. J. Cell. Physiol. 217: 667–673, 2008. © 2008 Wiley‐Liss, Inc.
Nursing Care of the Person With Sporadic Creutzfeldt-Jakob Disease

Creutzfeldt-Jakob disease is a rare, rapidly progressive, fatal neurodegenerative prion disease that manifests clinically with neuromuscular symptoms and profound dementia. Because of the rapid course and terminal prognosis, the affected person is referred to palliative and hospice care soon after receiving the diagnosis. This article provides an overview of familial, sporadic, and acquired forms of Creutzfeldt-Jakob disease. There is also an in-depth explanation of the sporadic form's pathogenesis, diagnosis, clinical features, disease course, infection control guidelines, and treatment, as well as a full discussion of the challenging nursing care issues from diagnosis to death.
Predicting hydration free energies of amphetamine-type stimulants with a customized molecular model

Amphetamine-type stimulants (ATS) are a group of incitation and psychedelic drugs affecting the central nervous system. Physicochemical data for these compounds are essential for understanding the stimulating mechanism, for assessing their environmental impacts, and for developing new drug detection methods. However, experimental data are scarce due to tight regulation of such illicit drugs, yet conventional methods to estimate their properties are often unreliable. Here we introduce a tailor-made multiscale procedure for predicting the hydration free energies and the solvation structures of ATS molecules by a combination of first principles calculations and the classical density functional theory. We demonstrate that the multiscale procedure performs well for a training set with similar molecular characteristics and yields good agreement with a testing set not used in the training. The theoretical predictions serve as a benchmark for the missing experimental data and, importantly, provide microscopic insights into manipulating the hydrophobicity of ATS compounds by chemical modifications.
How traits shape trees: new approaches for detecting character state‐dependent lineage diversification

Biologists have long sought to understand the processes underlying disparities in clade size across the tree of life and the extent to which such clade size differences can be attributed to the evolution of particular traits. The association of certain character states with species‐rich clades suggests that trait evolution can lead to increased diversification, but such a pattern could also arise due other processes, such as directional trait evolution. Recent advances in phylogenetic comparative methods have provided new statistical approaches for distinguishing between these intertwined and potentially confounded macroevolutionary processes. Here, we review the historical development of methods for detecting state‐dependent diversification and explore what new methods have revealed about classic examples of traits that affect diversification, including evolutionary dead ends, key innovations and geographic traits. Applications of these methods thus far collectively suggest that trait diversity commonly arises through the complex interplay between transition, speciation and extinction rates and that long hypothesized evolutionary dead ends and key innovations are instead often cases of directional trends in trait evolution.
Evidence that microgynes of Myrmica rubra ants are social parasites that attack old host colonies

Ant microgynes are miniaturized queen forms found together with normal queens (macrogynes) in species occurring across the ant phylogeny. Their role is not yet fully understood: in some cases, they seem to be nonparasitic alternative reproductive morphs, in others incipient social parasites, and thus potential models for studying the evolution of social parasitism. Whether they are regarded as parasitic or not has traditionally been based on genetic differentiation from syntopic macrogynes and/or the queen/worker ratio of their offspring rather than measuring fitness traits. We confirmed previously reported genetic differentiation between microgynes and macrogynes of Myrmica rubra in a population studied for the first time. Further, we measured virulence and infectivity of M. rubra microgynes in a controlled laboratory experiment. Nests headed only by macrogynes (controls), only by microgynes, and naturally and artificially mixed nests were kept under identical conditions. We found reduction in worker numbers of both naturally and artificially mixed macrogyne/microgyne nests compared with controls, and strong reduction but also surprising variation in fitness of nests headed only by microgynes. Microgyne nests produced workers, males and microgynes. Microgynes did not themselves reproduce in artificially mixed nests, but reproduced most in naturally mixed nests that had lost their macrogyne queen. This, together with higher mortality of field‐collected macrogyne queens from naturally infested colonies and greater estimated relative age of macrogyne queens in naturally infected nests, suggests that they preferentially exploit older host colonies. We conclude that M. rubra microgynes are intraspecific social parasites specialized on exploiting old host colonies.
Multilevel selection theory and evidence: a critique of Gardner, 2015

Gardner (2015) recently developed a model of a ‘Genetical Theory of Multilevel Selection, which is a thoughtfully developed, but flawed model. The model's flaws appear to be symptomatic of common misunderstandings of the multi level selection (MLS) literature and the recent quantitative genetic literature. I use Gardner's model as a guide for highlighting how the MLS literature can address the misconceptions found in his model, and the kin selection literature in general. I discuss research on the efficacy of group selection, the roll of indirect genetic effects in affecting the response to selection and the heritability of group‐level traits. I also discuss why the Price multilevel partition should not be used to partition MLS, and why contextual analysis and, by association, direct fitness are appropriate for partitioning MLS. Finally, I discuss conceptual issues around questions concerning the level at which fitness is measured, the units of selection, and I present a brief outline of a model of selection in class‐structured populations. I argue that the results derived from the MLS research tradition can inform kin selection research and models, and provide insights that will allow researchers to avoid conceptual flaws such as those seen in the Gardner model.
Ratings of perceived exertion in an incremental test in elderly women

Although the rating of perceived exertion (RPE) is used in the evaluation and prescription of physical activity for the elderly, some subjects might find it hard tounderstand the Borg scale. This study aimed to verify whether elderly women could notice, associate, and report changes in physical effort using the perceived exertion scale in response to a stress test. We also aimed to verify the possibility of predicting a respiratory compensation point (RCP) using the Borg scale. Twenty six elderly women took a stress test on a treadmill, with ergospirometry and ECG monitoring and RPE in a ramp protocol. Based on the RPEs for different exercise intensities (low, moderate, high), we assessed the women's perception, association, and report of changes in physical effort. Eight subjects (30.77%) did not notice, associate or report changes in effort using RPE. For those who did, the percentage of maximum workload at the moment of RPE 13 (69.92 ± 10,30) and 14 (78.90 ± 11,00) did not differ significantly from the one at the moment of RCP (75.45 ± 9.65). We conclude that some elderly women may have difficulties noticing, associating and reporting changes in physical effort using the Borg scale. However, for those who do not have any difficulty, RPE 13 and 14 coincide with the RCP.
Beyond the wing planform: morphological differentiation between migratory and nonmigratory dragonfly species

Migration is a significant trait of the animal kingdom that can impose a strong selective pressure on several structures to overcome the amount of energy that the organism invests in this particular behaviour. Wing linear dimensions and planform have been a traditional focus in the study of flying migratory species; however, other traits could also influence aerodynamic performance. We studied the differences in several flight‐related traits of migratory and nonmigratory Libellulid species in a phylogenetic context to assess their response to migratory behaviour. Wings were compared by linear measurements, shape, surface corrugations and microtrichia number. Thorax size and pilosity were also compared. Migratory species have larger and smoother wings, a larger anal lobe that is reached through an expansion of the discoidal region, and longer and denser thoracic pilosity. These differences might favour gliding as an energy‐saving displacement strategy. Most of the changes were identified in the hind wings. No differences were observed for the thorax linear dimensions, wetted aspect ratio, some wing corrugations or the wing microtrichiae number. Similar changes in the hind wing are present in clades where migration evolved. Our results emphasize that adaptations to migration through flight may extend to characteristics beyond the wing planform and that some wing characteristics in libellulids converge in response to migratory habits, whereas other closely related structures remain virtually unchanged. Additionally, we concluded that despite a close functional association and similar selective pressures on a structure, significant differences in the magnitude of the response may be present in its components.
Plastic and evolutionary responses to heat stress in a temperate dung fly: negative correlation between basal and induced heat tolerance?

Extreme weather events such as heat waves are becoming more frequent and intense. Populations can cope with elevated heat stress by evolving higher basal heat tolerance (evolutionary response) and/or stronger induced heat tolerance (plastic response). However, there is ongoing debate about whether basal and induced heat tolerance are negatively correlated and whether adaptive potential in heat tolerance is sufficient under ongoing climate warming. To evaluate the evolutionary potential of basal and induced heat tolerance, we performed experimental evolution on a temperate source population of the dung fly Sepsis punctum. Offspring of flies adapted to three thermal selection regimes (Hot, Cold and Reference) were subjected to acute heat stress after having been exposed to either a hot‐acclimation or non‐acclimation pretreatment. As different traits may respond differently to temperature stress, several physiological and life history traits were assessed. Condition dependence of the response was evaluated by exposing juveniles to different levels of developmental (food restriction/rearing density) stress. Heat knockdown times were highest, whereas acclimation effects were lowest in the Hot selection regime, indicating a negative association between basal and induced heat tolerance. However, survival, adult longevity, fecundity and fertility did not show such a pattern. Acclimation had positive effects in heat‐shocked flies, but in the absence of heat stress hot‐acclimated flies had reduced life spans relative to non‐acclimated ones, thereby revealing a potential cost of acclimation. Moreover, body size positively affected heat tolerance and unstressed individuals were less prone to heat stress than stressed flies, offering support for energetic costs associated with heat tolerance. Overall, our results indicate that heat tolerance of temperate insects can evolve under rising temperatures, but this response could be limited by a negative relationship between basal and induced thermotolerance, and may involve some but not other fitness‐related traits.
Response to Recommendations for Blood Pressure Measurement in Human and Experimental Animals; Part 1: Blood Pressure Measurement in Humans and Miscuffing: A Problem With New Guidelines: Addendum

Since the recommendations for blood pressure measurement in humans were published,1 questions have been raised regarding the recommendations for cuff sizes in subjects with obese arms and how the width of the cuffs should relate to the length.2 In the 1993 recommendations,3 the largest recommended bladder width was 20 cm, whereas in the latest version it is 16 cm (Table). View this table: 1993 and 2005 Recommendations for Cuff Sizes in Obese and Overweight Subjects The 2005 document stated that, “the ‘ideal’ cuff should have a bladder length that is 80%, and a width that is at least 40% of arm circumference (a length to width ratio of 2:1). A recent study comparing intra-arterial and auscultatory blood pressure concluded that the error is minimized with a cuff width of 46% of the arm circumference. ” The study that examined this issue was published by Marks and Groch,4 who measured blood pressure directly from the radial artery and indirectly from the brachial artery in 50 subjects who were in an intensive care unit and had intra-arterial lines as part of their routine care. The average arm circumference of these patients was 29.7 cm, and the published figure show that the highest circumference was 37 cm. Thus, only 2 of their 50 patients had arm circumferences in the 35 to 44 cm range, and none had circumferences …
The LENS Neurofeedback with Animals

SUMMARY Background. A customary route for research in the life sciences is to begin with animal studies, and only after thorough evaluation, attempt the same procedure with humans. In this pilot clinical outcomes study, the inverse procedure is followed. Encouraging results in the areas of CNS regulation led clinicians to explore whether the method is equally effective with animals who suffered the same problems as humans. The qualities studied included aggressiveness, mood instability, hypervigilance, inability to learn from experience. Species studies over about three years consisted of horses, dogs, and cats. Method. All animals were treated on the Low Energy Neurofeedback System (LENS) using the I-330 C2, the mini-C2, or the GP plus EEG processor with a laptop computer. Unlike with human subjects, it was impossible to use “eyes-closed” condition, so blink artifact was impossible to rule out. Animals stood in stalls, tied to hitching posts (horses), or on the floor or in their owner's lap (dogs and cat.