More than 15 million people have been affected by coronavirus disease 2019 (COVID‐19) and it has caused 640 016 deaths as of July 26, 2020. Currently, no effective treatment option is available for COVID‐19 patients. Though many drugs have been proposed, none of them has shown particular efficacy in clinical trials. In this article, the relationship between the Adrenergic system and the renin‐angiotensin‐aldosterone system (RAAS) is focused in COVID‐19 and a vicious circle consisting of the Adrenergic system‐RAAS‐Angiotensin converting (...) enzyme 2 (ACE2)‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) (which is referred to as the “ARAS loop”) is proposed. Hyperactivation of the ARAS loop may be the underlying pathophysiological mechanism in COVID‐19, and beta‐adrenergic blockers are proposed as a potential treatment option. Beta‐adrenergic blockers may decrease the SARS‐CoV‐2 cellular entry by decreasing ACE2 receptors expression and cluster of differentiation 147 (CD147) in various cells in the body. Beta‐adrenergic blockers may decrease the morbidity and mortality in COVID‐19 patients by preventing or reducing acute respiratory distress syndrome (ARDS) and other complications. Retrospective and prospective clinical trials should be conducted to check the validity of the hypothesis. Also see the video abstract here https://youtu.be/uLoy7do5ROo. (shrink)

Noradrenergic pathways are involved in mediating the central and peripheral effects of physiological arousal. The aim of the present study was to investigate the role of noradrenergic transmission in moral decision-making. We studied the effects in healthy volunteers of propranolol (a noradrenergic beta-adrenoceptor antagonist) on moral judgement in a set of moral dilemmas pitting utilitarian outcomes (e.g., saving five lives) against highly aversive harmful actions (e.g., killing an innocent person) in a double-blind, placebo-controlled, parallel group design. Propranolol (40 mg (...) orally) significantly reduced heart rate, but had no effect on self-reported mood. Importantly, propranolol made participants more likely to judge harmful actions as morally unacceptable, but only in dilemmas where harms were ‘up close and personal’. In addition, longer response times for such personal dilemmas were only found for the placebo group. Finally, judgments in personal dilemmas by the propranolol group were more decisive. These findings indicate that noradrenergic pathways play a role in responses to moral dilemmas, in line with recent work implicating emotion in moral decision-making. However, contrary to current theorising, these findings also suggest that aversion to harming is not driven by emotional arousal. Our findings are also of significant practical interest given that propranolol is a widely used drug in different settings, and is currently being considered as a potential treatment for post-traumatic stress disorder in military and rescue service personnel. (shrink)

Members of the transforming growth factor beta (TGFβ) family are pleiotropic cytokines with key roles in tissue morphogenesis and growth. TGFβ1, TGFβ2 and TGFβ3 are abundant in mammalian reproductive tissues, where development and cyclic remodelling continue in post‐natal and adult life. Potential roles for TGFβ have been identified in gonad and secondary sex organ development, spermatogenesis and ovarian function, immunoregulation of pregnancy, embryo implantation and placental development. However, better tools must now be employed to map more precisely essential functions (...) and the regulatory networks governing their activity. Gene ablation and transgenic models are expected to provide novel insights into distinct physiological activities for each TGFβ isoform in normal reproductive function and reproductive pathologies. It is also necessary to consider the mechanisms controlling TGFβ activation from latent precursor forms, and receptor and binding protein expression. Smad intracellular signalling circuitry and modulation by environmental stimuli through cross‐talk with other signal transduction pathways will further constrain TGFβ action. This review examines existing evidence for TGFβ1, TGFβ2 and TGFβ3 regulation of male and female reproductive biology, and highlights prospects for future research. BioEssays 24:904–914, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Psychotropic and other drugs can alter brain mechanisms regulating the formation, storage, and retrieval of different types of memory. These include “off label” uses of existing drugs and new drugs designed specifically to target the neural bases of memory. This paper discusses the use of beta-adrenergic antagonists to prevent or erase non-conscious pathological emotional memories in the amygdala. It also discusses the use of novel psychopharmacological agents to enhance long term semantic and short term working memory by altering (...) storage and retrieval mechanisms in the hippocampus and prefrontal cortex. Although intervention in the brain to alter memory as therapy or enhancement holds considerable promise, the long term effects of experimental drugs on the brain and memory are not known. More studies are needed to adequately assess the potential benefits and risks of these interventions. (shrink)

Insulin is well known for its essential role in carbohydrate metabolism: insulin deficiency results in the development of diabetes mellitus. It has been known for many years that people with diabetes mellitus are predisposed to develop thrombotic diseases including myocardial infarction. It was thought that the thrombus formation was the consequence of impaired carbohydrate metabolism. In recent years, it has become apparent that insulin is capable of ameliorating several pathophysiological events, leading to the inhibition and dissolution of the formed thrombus (...) in the system. These insulin‐induced events include inhibition of platelet aggregation by prompting the synthesis of NO in platelet and prostacyclin in endothelial cells. Furthermore, insulin upregulates prostacyclin receptors and downregulates α2 adrenergic receptor in platelets, thereby amplifying the inhibition of platelet aggregation. Insulin also releases tissue plasminogen activator, a potent thrombolytic enzyme, from the platelet membrane which dissolves the formed thrombus leading to the resumption of normal blood circulation. In effect, insulin could be an essential tool in the control of thrombotic disorders. BioEssays 26:91–98, 2004. © 2003 Wiley Periodicals, Inc. (shrink)

The T lymphocyte receptor for antigen, which operates in conjunction with gene products of the major histocompatibility complex (MHC), is a molecular complex comprised of five polypeptide chains. Both the 49 kDa alpha and 43 kDa beta chains are immunoglobulin‐like and thus contain variable domains responsible for ligand binding. In contrast, the 20–25 kDa T3 gamma, delta and epsilon chains are monomorphic structures presumably involved in transmembrane signalling. The alpha and beta subunits are disulfide bonded to each (...) other and held in noncovalent association with the T3 chains. T3‐Ti receptor crosslinking leads to conformational modification of a second T lineage specific molecule, termed the 50 kDa T11 structure which in turn leads to protein kinase C activation, elevation in intracytoplasmic free calcium and Na+/H+ antiport stimulation. (shrink)

A better understanding of how schistosomes exploit host nutrients, neuro‐endocrine hormones and signalling pathways for growth, development and maturation may provide new insights for improved interventions in the control of schistosomiasis. This paper describes recent advances in the identification and characterisation of schistosome tyrosine kinase and signalling pathways. It discusses the potential intervention value of insulin signalling, which may play an important role in glucose uptake and carbohydrate metabolism in schistosomes, providing the nutrients essential for parasite growth, development and, notably, (...) female fecundity. Significant progress has also been made in the characterisation of other schistosome growth factor receptors, such as transforming growth factor beta receptor and epidermal growth factor receptor, and in our understanding of their roles in the host‐parasite molecular dialogue and parasite development. The use of parasite signal transduction components as novel vaccine or drug targets may prove invaluable in prevention, treatment and control strategies to combat schistosomiasis. (shrink)

Adenosine 5′-triphosphate (ATP) was identified in 1970 as the transmitter responsible for non-adrenergic, non-cholinergic neurotransmission in the gut and bladder and the term ‘purinergic’ was coined. Purinergic cotransmission was proposed in 1976 and ATP is now recognized as a cotransmitter in all nerves in the peripheral and central nervous systems. P1 (adenosine) and P2 (ATP) receptors were distinguished in 1978. Cloning of these receptors in the early 1990s was a turning point in the acceptance of the purinergic signalling hypothesis. (...) There are both short-term purinergic signalling in neurotransmission, neuromodulation and secretion and long-term (trophic) purinergic signalling of cell proliferation, differentiation and death in development and regeneration. Much is known about the mechanisms of ATP release and its breakdown by ectonucleotidases. Recently, there has been emphasis on purinergic pathophysiology, including neurodegenerative and neuropsychiatric disorders. Purinergic therapeutic strategies are being developed for treatment of gut, kidney, bladder, lung, skeletal and reproductive system disorders, pain and cancer. (shrink)

The present review highlights an association between autism, Alzheimer disease , and fragile X syndrome . We propose a conceptual framework involving the amyloid-beta peptide , Abeta precursor protein , and fragile X mental retardation protein based on experimental evidence. The anabolic effect of the secreted alpha form of the amyloid-beta precursor protein may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPalpha levels associate with more severe (...) symptoms of autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 . Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPalpha level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPalpha and production of insoluble Abeta would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism. (shrink)

Apoptotic pathways have always been regarded as a key‐player in preserving tissue and organ homeostasis. Excessive activation or resistance to activation of cell death signaling may indeed be responsible for several mechanisms of disease, including malignancy and chronic degenerative diseases. Therefore, targeting apoptotic factors gained more and more attention in the scientific community and novel strategies emerged aimed at selectively blocking or stimulating cell death signaling. This is also the case for the TMEM219 death receptor, which is activated by (...) a circulating ligand, the Insulin‐like growth factor binding protein 3 (IGFBP3) and induces a caspase‐8‐dependent apoptosis of the target cells. Interestingly, stimulation of the IGFBP3/TMEM219 axis exerts an anti‐proliferative effect, while blockade of the TMEM219 deleterious signal protects TMEM219‐expressing cells of the endocrine pancreas, lung, and intestine from damage and death. Here, we summarize the most updated reports on the role of the IGFBP3/TMEM219 apoptotic axis in disease conditions, including intestinal disorders and diabetes, and we describe the advancements in designing and testing novel TMEM219‐based targeting approaches in emerging potential clinical applications. (shrink)

Name der Zeitschrift: Byzantinische Zeitschrift Jahrgang: 107 Heft: 1 Seiten: 37-50.

The book provides an analysis of the ungraspable. In sensible reality, we often speak of the “untouchable,” the “invisible,” the “inaudible,” and the “untastable.” In the abstract realm, we speak of the “non-conceptual,” the “ineffable,” the “unsayable.” These are the modalities of the ungraspable that are explored in this study.

Estrogen receptor α (ERα) is a ligand‐dependent transcription factor that regulates the expression of estrogen‐responsive genes. Approximately 70% of patients with breast cancer are ERα positive. Estrogen stimulates cancer cell proliferation and contributes to tumor progression. Endocrine therapies, which suppress the ERα signaling pathway, significantly improve the prognosis of patients with breast cancer. However, the development of de novo or acquired endocrine therapy resistance remains a barrier to breast cancer treatment. Therefore, understanding the regulatory mechanisms of ERα is essential (...) to overcome the resistance to treatment. This review focuses on the regulation of ERα expression, including copy number variation, epigenetic regulation, transcriptional regulation, and stability, as well as functions from the point of view post‐translational modifications. (shrink)

The beta thymosins are a highly conserved family of strongly polar 5 kDa polypeptides that are widely distributed among vertebrate classes; most are now known to bind to monomeric actin and inhibit its polymerization. One beta thymosin, beta four, (Tβ4) is the predominant form in mammalian cells, present at up to 0.5 mM. Many species are known to produce at least two beta thymosin isoforms, in some cases in the same cell. Their expression can be separately (...) regulated. When present outside the cell, the N‐terminal tetrapeptide of beta four appears to affect cell cycle regulation; beta thymosins or smaller fragments derived from them may have additional regulatory functions. We suggest that many developmental changes in beta thymosin levels within cells and tissues may be related to changes in G‐actin pool size. (shrink)

Alpha-beta pruning is a technique for pruning trees in artificial intelligence game-playing. This note draws an analogy between the technique, which is, in essence, an application of many-valued logic to the cut-off of the evaluation of conditionals in computer programs (for efficiency).

The Protein Ontology provides terms for and supports annotation of species-specific protein complexes in an ontology framework that relates them both to their components and to species-independent families of complexes. Comprehensive curation of experimentally known forms and annotations thereof is expected to expose discrepancies, differences, and gaps in our knowledge. We have annotated the early events of innate immune signaling mediated by Toll-Like Receptor 3 and 4 complexes in human, mouse, and chicken. The resulting ontology and annotation data set (...) has allowed us to identify species-specific gaps in experimental data and possible functional differences between species, and to employ inferred structural and functional relationships to suggest plausible resolutions of these discrepancies and gaps. (shrink)

Neurosteroid 17 beta-estradiol (E2) is a steroid synthesized de novo in the nervous system that might influence neuronal activity and behavior. Nevertheless, the impact of E2 on the functioning of those neural systems in which it is slightly synthesized is less questioned. The vestibulo-ocular reflex (VOR) adaptation, may provide an ideal arena for investigating this issue. Indeed, E2 modulates cerebellar parallel fiber-Purkinje cell synaptic plasticity that underlies encoding of VOR adaptation. Moreover, aromatase expression in the cerebellum of adult rodents (...) is maintained at very low levels and localized to Purkinje cells. The significance of age-related maintenance of low levels of aromatase expression in the cerebellum on behavior, however, has yet to be explored. Our aim in this study was to determine whether E2 synthesis exerts an effective and persistent modulation of VOR adaptation in adult male rats. To answer this question, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in VOR adaptation using an oral dose (2.5 mg/kg) of the aromatase inhibitor Letrozole in peri-pubertal and post-pubertal male rats. We found that Letrozole acutely impaired gain increases and decreases in VOR adaptation without altering basal ocular-motor performance and that these effects were similar in peri-pubertal and post-pubertal rats. Thus, in adult male rats neurosteroid E2 effectively modulates VOR adaptation in both of the periods studied. These findings imply that the adult cerebellum uses E2 synthesis for modulating motor memory formation and suggest that low and extremely localized E2 production may play a role in adaptive phenomena. (shrink)

As it is well known, mobile phones have become a basic gadget for any individual that usually stores sensitive information. This mainly motivates the increase in the number of attacks aimed at jeopardizing smartphones, being an extreme concern above all on Android OS, which is the most popular platform in the market. Consequently, a strong effort has been devoted for mitigating mentioned incidents in recent years, even though few researchers have addressed the application of visualization techniques for the analysis of (...) malware. Within this field, the present work proposes the extension of a new technique called Hybrid Unsupervised Exploratory Plots to visualize Android malware datasets. More precisely, the novel Beta-Hebbian Learning (BHL) method is applied for the first time and validated under the frame of Hybrid Unsupervised Exploratory Plots, in conjunction with clustering methods. The informative visualization achieved provides a picture of the structure of the malware families, allowing subsequent analysis of their organization. To validate the Hybrid Unsupervised Exploratory Plot extension and its tuning, the popular Android Malware Genome dataset has been used in the experimental setting. Promising results have been obtained, suggesting that BHL applied in combination with clustering techniques in Hybrid Unsupervised Exploratory Plots are a viable resource for the visualization of malware families. (shrink)

We propose that the primary cause of schizophrenia is a pathological extension of synaptic pruning involving local connectivity that unfolds ordinarily during adolescence. Computer simulations suggest that this pathology provides reasonable accounts of a range of symptoms in schizophrenia, and is consistent with recent postmortem and genetic studies. NMDA-receptors play a regulatory role in maintaining and/or eliminating cortical synapses, and therefore may play a pathophysiological role.

Stroke remains one of the leading causes of various disabilities, including debilitating motor and language impairments. Though various treatments exist, post-stroke impairments frequently become chronic, dramatically reducing daily life quality, and requiring specific rehabilitation. A critical goal of chronic stroke rehabilitation is to induce, usually through behavioral training, experience-dependent plasticity processes in order to promote functional recovery. However, the efficiency of such interventions is typically modest, and very little is known regarding the neural dynamics underpinning recovery processes and possible biomarkers (...) of their efficiency. Some studies have emphasized specific alterations of excitatory–inhibitory balance within distributed neural networks as an important recovery correlate. Neural processes sensitive to these alterations, such as task-dependent oscillatory activity in beta as well as alpha bands, may be candidate biomarkers of chronic stroke functional recovery. In this review, we discuss the results of studies on motor and language recovery with a focus on oscillatory processes centered around the beta band and their modulations during functional recovery in chronic stroke. The discussion is based on a framework where task-dependent modulations of beta and alpha oscillatory activity, generated by the deep cortical excitatory–inhibitory microcircuits, serve as a neural mechanism of domain-general top-down control processes. We discuss the findings, their limitations, and possible directions for future research. (shrink)

The majority of G protein-coupled receptors (GPCRs) self-assemble in the form dimeric/oligomeric complexes along the plasma membrane. Due to the molecular interactions they participate, GPCRs can potentially provide the framework for discriminating a wide variety of intercellular signals, as based on some kind of combinatorial receptor codes. GPCRs can in fact transduce signals from the external milieu by modifying the activity of such intracellular proteins as adenylyl cyclases, phospholipases and ion channels via interactions with specific G-proteins. However, in spite (...) of the number of cell functions they can actually control, both GPCRs and their associated signal transduction pathways are extremely well conserved, for only a few alleles with null or minor functional alterations have so far been found. This would seem to suggest that, beside a mechanism for DNA repairing, there must be another level of quality control that may help maintaining GPCRs rather stable throughout evolution. We propose here receptor oligomerization to be a basic molecular mechanism controlling GPCRs redundancy in many different cell types, and the plasma membrane as the first hierarchical cell structure at which selective categorical sensing may occur. Categorical sensing can be seen as the cellular capacity for identifying and ordering complex patterns of mixed signals out of a contextual matrix, i.e., the recognition of meaningful patterns out of ubiquitous signals. In this context, redundancy and degeneracy may appear as the required feature to integrate the cell system into functional units of progressively higher hierarchical levels. (shrink)

Nine leading scholars of ancient philosophy from Europe, the UK, and North America offer a systematic study of Book Beta of Aristotle's Metaphysics. The work takes the form of a series of aporiai or 'difficulties' which Aristotle presents as necessary points of engagement for those who wish to attain wisdom. The topics include causation, substance, constitution, properties, predicates, and generally the ontology of both the perishable and the imperishable world. Each contributor discusses one or two of these aporiai in (...) sequence: the result is a discursive commentary on this seminal text of Western philosophy. (shrink)

This paper aims to enhance security in IoT device networks through a visual tool that utilizes three projection techniques, including Beta Hebbian Learning (BHL), t-distributed Stochastic Neighbor Embedding (t-SNE) and ISOMAP, in order to facilitate the identification of network attacks by human experts. This work research begins with the creation of a testing environment with IoT devices and web clients, simulating attacks over Message Queuing Telemetry Transport (MQTT) for recording all relevant traffic information. The unsupervised algorithms chosen provide a (...) set of projections that enable human experts to visually identify most attacks in real-time, making it a powerful tool that can be implemented in IoT environments easily. (shrink)

The Protein Ontology (PRO) is designed as a formal and principled Open Biomedical Ontologies (OBO) Foundry ontology for proteins. The components of PRO extend from a classification of proteins on the basis of evolutionary relationships at the homeomorphic level to the representation of the multiple protein forms of a gene, including those resulting from alternative splicing, cleavage and/or posttranslational modifications. Focusing specifically on the TGF-beta signaling proteins, we describe the building, curation, usage and dissemination of PRO. PRO provides a (...) framework for the formal representation of protein classes and protein forms in the OBO Foundry. It is designed to enable data retrieval and integration and machine reasoning at the molecular level of proteins, thereby facilitating cross-species comparisons, pathway analysis, disease modeling and the generation of new hypotheses. (shrink)

Progress in solving the structure of insulin bound to its receptor has been slow and stepwise, but a milestone has now been reached with a refined structure of a complex of insulin with a “microreceptor” that contains the primary binding site. The insulin receptor is a dimeric allosteric enzyme that belongs to the family of receptor tyrosine kinases. The insulin binding process is complex and exhibits negative cooperativity. Biochemical evidence suggested that insulin, through two distinct binding sites, (...) crosslinks two receptor sites located on each α subunit. The structure of the unliganded receptor ectodomain showed a symmetrical folded‐over conformation with an antiparallel disposition. Further work resolved the detailed structure of receptor site 1, both without and with insulin. Recently, a missing piece in the puzzle was added: the C‐terminal portion of insulin's B‐chain known to be critical for binding and negative cooperativity. Here I discuss these findings and their implications. (shrink)

In three recent articles it was shown that β‐catenin is crucial for the establishment and the maintenance of the overall polarity and especially for the character ‘posterior’ in planarians. If the transcription of the β‐catenin gene was silenced by RNA interference, the overall polarity is lost, and in regenerating fragments a posterior blastema displays anterior characters by forming eyes and anterior ganglia. An attempt is made to integrate these new data, well‐known older observations, and observations from other regenerating systems into (...) an outline of a model that will clarify our current understanding as well as highlight areas still to be developed. (shrink)

How different neural crest derivatives differentiate in distinct embryonic locations in the vertebrate embryo is an intriguing issue. Many attempts have been made to understand the underlying mechanism of specific pathway choices made by migrating neural crest cells. In this speculative review we suggest a new mechanism for the regulation of neural crest cell migration patterns in avian and mammalian embryos, based on recent progress in understanding the expression and activity of receptor tyrosine kinases during embryogenesis. Distinct subpopulations of (...) crest‐derived cells express specific receptor tyrosine kinases while residing in a migration staging area. We postulate that the differential expression of receptor tyrosine kinases by specific subpopulations of neural crest cells allows them to respond to localized growth factor ligand activity in the embryo. Thus, the migration pathway taken by neural crest subpopulations is determined by their receptor tyrosine kinase response to the differential localization of their cognate ligand. (shrink)

Plasma membranes are subject to continuous deformations. Strikingly, some of these transient membrane undulations yield membrane‐associated signaling hubs that differ in composition and function, depending on membrane geometry and the availability of co‐factors. Here, recent advancements on this ubiquitous type of receptor‐independent signaling are reviewed, with a special focus on emerging concepts and technical challenges associated with studying these elusive signaling sites.

Christians working cross-culturally to bring about change in other societies desire to conduct their interventions ethically. What seems ethical and endorsed by God from the donor's point of view, however, may not be perceived as ethical in terms of the cultural values of the receptors. The nature of this problem is discussed and guidelines suggested to assist us in recognizing and overcoming the problem. The primary guideline in the application of the Golden Rule in terms of the culturally conditioned perception (...) of the receptors. (shrink)

Let ${\beta(\mathbb{N})}$ denote the Stone–Čech compactification of the set ${\mathbb{N}}$ of natural numbers (with the discrete topology), and let ${\mathbb{N}^\ast}$ denote the remainder ${\beta(\mathbb{N})-\mathbb{N}}$ . We show that, interpreting modal diamond as the closure in a topological space, the modal logic of ${\mathbb{N}^\ast}$ is S4 and that the modal logic of ${\beta(\mathbb{N})}$ is S4.1.2.

Phi Beta Kappa Romanell Lectures, given at Michigan State University, February 2008.

Sex steroids, through their receptors, have potent effects on the signal pathways involved in osteogenic or myogenic differentiation. However, a considerable segment of those signal pathways has a prominent role in epithelial neoplastic transformation. The capability to intervene locally has focused on specific ligands for the receptors. Nevertheless, many signals are mapped to interactions of steroid receptor motifs with heterologous regulatory proteins. Some of those proteins interact with the glucocorticoid receptor and other factors essential to cell fate. Interactions (...) of steroid receptor domain motifs with heterologous proteins affect specific target pathways; consequently, manipulation of specified protein modules complexed with steroid receptors may be a next major step for enhancing molecular targeted therapeutics. In the future, intervention at specific sections of receptor primary sequence may prove therapeutically more efficient in targeting pathways of choice than ligand selectivity can be. (shrink)

Beta integrals for several non-integer values of the exponents were calculated by Leonhard Euler in 1730, when he was trying to find the general term for the factorial function by means of an algebraic expression. Nevertheless, 70 years before, Pietro Mengoli (1626–1686) had computed such integrals for natural and half-integer exponents in his Geometriae Speciosae Elementa (1659) and Circolo(1672) and displayed the results in triangular tables. In particular, his new arithmetic–algebraic method allowed him to compute the quadrature of the (...) circle. The aim of this article is to show how Mengoli calculated the values of these integrals as well as how he analysed the relation between these values and the exponents inside the integrals. This analysis provides new insights into Mengoli’s view of his algorithmic computation of quadratures. (shrink)

Meeting humans is an everyday experience for most companion dogs, and their behavior in these situations and its genetic background is of major interest. Previous research in our laboratory reported that in German shepherd dogs the lack of G allele, and in Border collies the lack of A allele, of the oxytocin receptor gene (OXTR) 19208A/G single nucleotide polymorphism (SNP) was linked to increased friendliness, which suggests that although broad traits are affected by genetic variability, the specific links between (...) alleles and behavioural variables might be breed-specific. In the current study, we found that Siberian huskies with the A allele approached a friendly unfamiliar woman less frequently in a greeting test, which indicates that certain polymorphisms are related to human directed behaviour, but that the relationship patterns between polymorphisms and behavioural phenotypes differ between populations. This finding was further supported by our next investigation. According to primate studies, endogenous opioid peptide (e.g. endorphins) receptor genes have also been implicated in social relationships. Therefore, we examined the rs21912990 of the OPRM1 gene. Firstly, we found that the allele frequencies of Siberian huskies and gray wolves were similar, but differed from that of Border collies and German shepherd dogs, which might reflect their genetic relationship. Secondly, we detected significant associations between the OPRM1 SNP and greeting behaviour among German shepherd dogs and a trend in Border collies, but we could not detect an association in Siberian huskies. Although our results with OXTR and OPRM1 gene variants should be regarded as preliminary due to the relatively low sample size, they suggest that (1) OXTR and OPRM1 gene variants in dogs affect human-directed social behaviour and (2) their effects differ between breeds. (shrink)