Current theories suggest that the brain is the sole source of mental illness. However, affective disorders, and major depressive disorder (MDD) in particular, may be better conceptualized as brain-body disorders that involve peripheral systems as well. This perspective emphasizes the embodied, multifaceted physiology of well-being, and suggests that afferent signals from the body may contribute to cognitive and emotional states. In this review, we focus on evidence from preclinical and clinical studies suggesting that afferent thermosensory signals contribute to well-being and (...) depression. Although thermoregulatory systems have traditionally been conceptualized as serving primarily homeostatic functions, increasing evidence suggests neural pathways responsible for regulating body temperature may be linked more closely with emotional states than previously recognized, an affective warmth hypothesis. Human studies indicate that increasing physical warmth activates brain circuits associated with cognitive and affective functions, promotes interpersonal warmth and prosocial behavior, and has antidepressant effects. Consistent with these effects, preclinical studies in rodents demonstrate that physical warmth activates brain serotonergic neurons implicated in antidepressant-like effects. Together, these studies suggest that (1) thermosensory pathways interact with brain systems that control affective function, (2) these pathways are dysregulated in affective disorders, and (3) activating warm thermosensory pathways promotes a sense of well-being and has therapeutic potential in the treatment of affective disorders. (shrink)

The transfer of the capital to a new site on Brazil's central plateau had a particular significance in the eyes of those who conceived the idea. Its primary aim was to create a nucleus from which to promote the development of the vast and almost deserted interior regions, abandoning Rio de Janeiro which was, for various reasons, no longer judged capable of fulfilling its role as the seat of national political life. As the Brasilia project was realized, thanks to (...) the inspiration of President Kubitschek, it was hoped that it would contribute to the solution of urgent problems stemming from the country's development. Its basic function was to stimulate this development, no longer seen only as the development of the coastal regions but also of the interior, the sertão, that is the “great desert” of the Goiás, the Mato-Grosso and of Amazonia. (shrink)

Mitotic recombination is a repair process which is known to repair double strand breaks and to fill double‐strand gaps by copying a homologous sequence. Meiotic recombination is a process of heteroduplex formation which sometimes generates crossovers. Evidence is presented that the later stages of meiotic recombination have some characteristics of mitotic repair recombination, leading to the conclusion that mismatch repair may be a recombinogenic repair process. The evidence suggests that the recombinational repair process generates hetero‐duplex bubbles which can move. Some (...) bubbles become crossovers. Others cease to exist, perhaps because topoisomerase activity breaks them down. (shrink)

Implanting deep brain stimulation (DBS) electrodes in patients with Parkinson’s disease often results in the appearance of a non-infectious, delayed-onset edema that disappears over time. However, the time window between the DBS electrode and DBS stimulating device implant is often used to record local field potentials (LFPs) which are used both to better understand basal ganglia pathophysiology and to improve DBS therapy. In this work, we investigated whether the presence of post-surgery edema correlates with the quality of LFP recordings in (...) eight patients with advanced Parkinson’s disease implanted with subthalamic DBS electrodes. The magnetic resonance scans of the brain after 8.5 ± 1.5 days from the implantation surgery were segmented and the peri-electrode edema volume was calculated for both brain hemispheres. We found a correlation (ρ = −0.81, p < 0.0218, Spearman’s correlation coefficient) between left side local field potentials of the low beta band (11–20 Hz) and the edema volume of the same side. No other significant differences between the hemispheres were found. Despite the limited sample size, our results suggest that the effect on LFPs may be related to the edema localization, thus indicating a mechanism involving brain networks instead of a simple change in the electrode-tissue interface. (shrink)

The amygdala is a hub in brain networks that supports social life and fear processing. Compared with other apes, humans have a relatively larger lateral nucleus of the amygdala, which is consistent with both the self-domestication and the cooperative breeding hypotheses of human evolution. Here, we take a comparative approach to the evolutionary origin of the relatively larger lateral amygdala nucleus in humans. We carry out phylogenetic analysis on a sample of 17 mammalian species for which (...) we acquired single amygdala nuclei volumetric data. Our results indicate that there has been convergent evolution toward larger lateral amygdala nuclei in both domesticated and cooperatively breeding mammals. These results suggest that changes in processing fearful stimuli to reduce fear-induced aggression, which are necessary for domesticated and cooperatively breeding species alike, tap into the same neurobiological proximate mechanism. However, humans show changes not only in processing fearful stimuli but also in proactive prosociality. Since cooperative breeding, but not domestication, is also associated with increased proactive prosociality, a prominent role of the former during human evolution is more parsimonious, whereas self-domestication may have been involved as an additional stepping stone. (shrink)

The repeatedly noted absence of case-reports of individuals with schizophrenia and congenital/early developed blindness has led several authors to argue that the latter can confer protective effects against the former. In this work, we present a number of relevant case-reports from different syndromes that show comorbidity of congenital and early blindness with schizophrenia. On the basis of these reports, we argue that a distinction between different types of blindness in terms of the origin of the visual deficit, cortical or peripheral, (...) is crucial for understanding the observed patterns of comorbidity. We discuss the genetic underpinnings and the brain structures involved in schizophrenia and blindness, with insights from language processing, laying emphasis on the three structures that particularly stand out: the occipital cortex, the lateral geniculate nucleus and the pulvinar. Last, we build on previous literature on the nature of the protective effects in order to offer novel insights into the nature of the protection mechanism from the perspective of the brain structures involved in each type of blindness. (shrink)

Initial evaluation structures (IESs) currently proposed as the earliest detectors of affective stimuli (e.g., amygdala, orbitofrontal cortex, or insula) are high-order structures (a) whose response latency cannot account for the first visual cortex emotion-related response (~80 ms), and (b) lack the necessary infrastructure to locally analyze the visual features that define emotional stimuli. Several thalamic structures accomplish both criteria. The lateral geniculate nucleus (LGN), a first-order thalamic nucleus that actively processes visual information, with the complement of the (...) thalamic reticular nucleus (TRN) are proposed as core IESs. This LGN–TRN tandem could be supported by the pulvinar, a second-order thalamic structure, and by other extrathalamic nuclei. The visual thalamus, scarcely explored in affective neurosciences, seems crucial in early emotional evaluation. (shrink)

Previous research on the neural basis of cognitive control processes has mainly focused on cortical areas, while the role of subcortical structures in cognitive control is less clear. Models of basal ganglia function as well as clinical studies in neurodegenerative diseases suggest that the striatum (putamen and caudate nucleus) modulates the inhibition of interfering responses and thereby contributes to an important aspect of cognitive control, namely response interference control. To further investigate the putative role of the striatum in the (...) control of response interference, 23 patients with stroke-induced lesions of the striatum and 32 age-matched neurologically healthy controls performed a unimanual version of the Simon task. In the Simon task, the correspondence between stimulus location and response location is manipulated so that control over response interference can be inferred from the reaction time costs in incongruent trials. Results showed that stroke patients responded overall slower and more erroneous than controls. The difference in response times (RTs) between incongruent and congruent trials (known as the Simon effect) was smaller in the ipsilesional/-lateral hemifield, but did not differ significantly between groups. However, in contrast to controls, stroke patients exhibited an abnormally stable Simon effect across the reaction time distribution indicating a reduced efficiency of the inhibition process. Thus, in stroke patients unilateral lesions of the striatum did not significantly impair the general ability to control response interference, but led to less efficient selective inhibition of interfering responses. (shrink)

Considerable evidence from preclinical and clinical investigations implicates disturbances of brain dopamine (DA) function in the pathophysiology of several psychiatric and neurologic disorders. We describe a neural model that may help organize theseindependent experimental observations. Cortical regions classically associated with the limbic system interact with infracortical structures, including the nucleus accumbens, ventral pallidum, and dorsomedial nucleus of the thalamus. In our model, overactivity in forebrain DA systems results in the loss of lateral inhibitory interactions in the (...) class='Hi'>nucleus accumbens, causing disinhibition of pallidothalamic efferents; this in turn causes rapid changes and a loss of focused corticothalamic activity in cortical regions controlling cognitive and emotional processes. These effects might be manifested clinically by some symptoms of psychoses. Underactivity of forebrain DA results in excess lateral inhibition in the nucleus accumbens, causing tonic inhibition of pallidothalamic efferents; this perpetuates tonic corticothalamic activity and prevents the initiation of new activity in other critical cortical regions. These effects might be manifested clinically by some symptoms of depression. This model parallels existing explanations for the etiology of several movement disorders, and may lead to testable inferences regarding the neural substrates of specific psychopathologies. (shrink)

IntroductionParkinson’s disease patients have a significantly higher risk of developing dementia in later disease stages, leading to severe impairments in quality of life and self-functioning. Questions remain on how deep brain stimulation affects cognition, and whether we can individualize therapy and reduce the risk for adverse cognitive effects. Our aim in this systematic review is to assess the current knowledge in the field and determine if the findings could influence clinical practice.MethodsWe have conducted a systematic review according to PRISMA guidelines (...) through MEDLINE and Embase databases, with studies being selected for inclusion via a set inclusion and exclusion criteria.ResultsSixty-seven studies were included in this systematic review according to the selected criteria. This includes 6 meta-analyses, 18 randomized controlled trials, 17 controlled clinical trials, and 26 observational studies with no control arms. The total number of PD patients encompassed in the studies cited in this review is 3677, not including the meta-analyses.ConclusionCognitive function in PD patients can deteriorate, in most cases mildly, but still impactful to the quality of life. The strongest evidence is present for deterioration in verbal fluency, while inconclusive evidence is still present for executive function, memory, attention and processing speed. Global cognition does not appear to be significantly impacted by DBS, especially if cognitive screening is performed prior to the procedure, as lower baseline cognitive function is connected to poor outcomes. Further randomized controlled studies are required to increase the level of evidence, especially in the case of globus pallidus internus DBS, pedunculopontine nucleus DBS, and the ventral intermediate nucleus of thalamus DBS, and more long-term studies are required for all respective targets. (shrink)

The discovery, made in Oxford, that crude penicillin could cure systemic and life‐threatening bacterial infections was followed by attempts to purify penicillin, to determine its structure and then to produce it by total chemical synthesis. The β‐lactam structure of the molecule, first proposed in October 1943, was a source of controversy until 1945. However, no useful chemical synthesis was achieved and fermentation became the commercial source of the antibiotic.In 1953, one of the products of a Cephalosporium sp. from Sardinia was (...) shown to be a new and hydrophilic penicillin (penicillin N). This was contaminated with a substance having the same side‐chain but a characteristic absorption spectrum. The latter, cephalosporin C, showed antibacterial activity but was not inactivated by a penicillinase. The determination of its β‐lactam structure and isolation of its nucleus enabled pharmaceutical companies to produce many semisynthetic cephalosporins.A new tripeptide was later found to be an intermediate in the biosynthesis of both penicillin N and cephalosporin C, and this was followed by the complete elucidation of the biosynthetic pathways leading to these compounds and to benzylpenicillin. (shrink)

Tenth-century Islamic alchemy attributed different roles to the figure of Hermes, all of which were retained in later alchemy. The playful changing of perspectives, in which Harmis al-Harāmisa perpetually changed his connotation, allowed for a complex game played at the border between science and literature. In the process, he turned from representing the venerable author of the early alchemical texts - master over ancient wisdom and scientific 'subject' - into an 'object' of research, into an allegory of the nucleus (...) of the Great Work, and into a mysterious image of the secret that he himself had handed over to men. (shrink)

The genetic code appeared on Earth at the origin of life, and the codes of culture arrived almost four billion years later. For a long time it has been assumed that these are the only codes that exist in Nature, and if that were true we would have to conclude that codes are extraordinary exceptions that appeared only at the beginning and at the end of the history of life. In reality, various other organic codes have been discovered in the (...) past few decades and it is likely that more will come to light in the future. The existence of many organic codes in Nature is therefore an experimental fact, but also more than that. It is one of those facts that have extraordinary implications. In this book it is shown that the genetic code was a precondition for the origin of the first cells, the signal transduction codes divided the first cells into three primary kingdoms (Archaea, Bacteria and Eukarya), the splicing codes were instrumental to the origin of the eukaryotic nucleus, the histone code provided a new regulation system in eukaryotic genomes, and the cytoskeleton codes allowed the Eukarya to perform internal movements, including those of mitosis and meiosis. It is shown, furthermore, that organic codes had a key role in multicellular life, in particular in the origin of animals, the origin of mind and the origin of language. The great events of macroevolution, in other words, were associated with the appearance of new organic codes, and we can easily understand why. The reason is that a new code brings into existence something that has never existed before because it creates arbitrary associations, relationships that are not determined by physical necessity. Another outstanding implication is the fact that codes involve meaning and we need therefore to introduce in biology, with the standard methods of science, not only the concept of biological information but also that of biological meaning. The research on biological codes, in conclusion, is bringing to light new mechanisms in evolution and new fundamental concepts in science. This research is the field of Code Biology, the study of all codes of life, from the genetic code to the codes of culture, from the origin of life to the origin of man. (shrink)

We examined amygdala subregion volumes in patients with a first episode of major depression and in healthy subjects. Covariate-adjusted linear regression was performed to compare the MD and healthy groups, and adjustments for age, gender, and total estimated intracranial volume showed no differences in amygdala subregion volumes between the healthy and MD groups. Within the MD group, we examined the association between amygdala subregion volume and the 17-item Hamilton Rating Scale for Depression score and the HAMD subscale score, and found (...) no association in the left amygdala. In the right amygdala, however, there was an inverse linear association between the HAMD total and the HAMD core and lateral nucleus and anterior-amygdaloid-regions. Furthermore, an inverse linear association was seen between the HAMD psychic and the lateral nucleus, anterior-amygdaloid-regions, transition, and whole amygdala. The findings of this study suggest that the severity of MD and some symptoms of MD are associated with right amygdala volume. There have been few reports on the relationship between MD and amygdala subregional volume, and further research is needed to accumulate more data for further validation. (shrink)

Increasingly, functional and evolutionary research has highlighted the important contribution emotion processing makes to complex human social cognition. As such, it may be asked whether neural structures involved in emotion processing, commonly referred to as limbic structures, have been impacted in human brain evolution. To address this question, we performed an extensive evolutionary analysis of multiple limbic structures using modern phylogenetic tools. For this analysis, we combined new volumetric data for the hominoid (human and ape) amygdala and 4 amygdaloid nuclei, (...) hippocampus, and striatum, collected using stereological methods in complete histological series, with previously published datasets on the amygdala, orbital and medial frontal cortex, and insula, as well as a non-limbic structure, the dorsal frontal cortex, for contrast. We performed a parallel analysis using large published datasets including many anthropoid species (human, ape, and monkey), but fewer hominoids, for the amygdala and 2 amygdaloid subdivisions, hippocampus, schizocortex, striatum, and septal nuclei. To address evolutionary change, we compared observed human values to values predicted from regressions run through a) nonhuman hominoids and b) nonhuman anthropoids, assessing phylogenetic influence using phylogenetic generalized least squares regression.Compared with other hominoids, the volumes of the hippocampus, the lateral nucleus of the amygdala, and the orbital frontal cortex were, respectively, 50%, 37%, and 11% greater in humans than predicted for an ape of human hemisphere volume, while the medial and dorsal frontal cortex were, respectively, 26% and 29% significantly smaller. Compared with other anthropoids, only human values for the striatum fell significantly below predicted values. Overall, the data present support for the idea that regions involved in emotion processing are not necessarily conserved or regressive, but may even be enhanced in recent human evolution. (shrink)

Both the concept of a Darwinian tree of life (TOL) and the possibility of its accurate reconstruction have been much criticized. Criticisms mostly revolve around the extensive occurrence of lateral gene transfer (LGT), instances of uptake of complete organisms to become organelles (with the associated subsequent gene transfer to the nucleus), as well as the implications of more subtle aspects of the biological species concept. Here we argue that none of these criticisms are sufficient to abandon the valuable (...) TOL concept and the biological realities it captures. Especially important is the need to conceptually distinguish between organismal trees and gene trees, which necessitates incorporating insights of widely occurring LGT into modern evolutionary theory. We demonstrate that all criticisms, while based on important new findings, do not invalidate the TOL. After considering the implications of these new insights, we find that the contours of evolution are best represented by a TOL. (shrink)

Erwin Schrödinger and Werner Heisenberg were the originators of two approaches, known respectively as “wave mechanics” and “matrix mechanics”, to what is now called “quantum mechanics” or “quantum theory”. The two approaches appear to be extremely different, both in their technical forms, and in their philosophical underpinnings. Heisenberg arrived at his theory by effectively renouncing the idea of trying to represent a physical system, such as a hydrogen Bohr's atom model for example, as a structure in space—time, but instead, following (...) the lead of Einstein's 1905 theory of relativity, representing only empirically observable properties, such as the transition amplitudes between the stationary states of the atom. These amplitudes can be arranged in square arrays of numbers. In Heisenberg's scheme these arrays, and other like them, are combined according to certain rules that were later recognized by Max Born to be the rules of matrix multiplication. The whole scheme is abstract and mathematical, and avoids using any space—time picture of what is going on at the atomic level. Schrödinger, on the other hand, represented the electron in an atom by a cloudlike wave surrounding the nucleus. This is a space—time structure that, superficially at least, is more in line with the classical physical theories of the eighteenth and nineteenth centuries. -/- Niels Bohr invited Schrödinger to come to Copenhagen to present his ideas, and to discuss this subject with himself, Heisenberg, and others. Schrödinger arrived in Copenhagen on October 1st, 1926, and was immediately intensively engaged by Bohr and the others in a “debate” that lasted for days. Eventually, Schrödinger become ill, and was confined in Bohr's home to a bed, upon which Bohr sat, continuing the discussion. Schrödinger finally exclaimed “If all the quantum jumping is here to stay, then I am sorry that I ever became involved in quantum mechanics”. Bohr replied, “But we are glad that you did!”. (shrink)

Directional deep brain stimulation contacts provide greater spatial flexibility for therapy than traditional ring-shaped electrodes, but little is known about longitudinal changes of impedance and orientation. We measured monopolar and bipolar impedance of DBS contacts in 31 patients who underwent unilateral subthalamic nucleus deep brain stimulation as part of a randomized study. At different follow-up visits, patients were assigned new stimulation configurations and impedance was measured. Additionally, we measured the orientation of the directional lead during surgery, immediately after surgery, (...) and 1 year later. Here we contrast impedances in directional versus ring contacts with respect to local anatomy, active stimulation contact, and over time. Directional contacts display larger impedances than ring contacts. Impedances generally increase slightly over the first year of therapy, save for a transient decrease immediately post-surgery under general anesthesia during pulse generator placement. Local impedances decrease at active stimulation sites, and contacts in closest proximity to internal capsule display higher impedances than other anatomic sites. DBS leads rotate slightly in the immediate postoperative period but otherwise remain stable over the following year. These data provide useful information for setting clinical stimulation parameters over time. (shrink)

The thesis of this paper is that Husserl, in his later ethics, reinterprets the philosophical content that discloses itself in the Kantian conception of a “fact of practical reason”. From 1917/18 on, Husserl increasingly ceases to pursue his initial idea of a scientific ethics. The reason for this move lies precisely in the phenomenological analysis of “Gemütsakte”, through which two main features of the fact of practical reason impose themselves more and more on Husserls thought: the personal concernment/obligation and the (...) primacy of the practical with the coeval call for universal validity. Husserl recognizes that the form of ethical facticity or entanglement cannot be grasped by a science of evidence, which speaks objectively and non-personally of acts of willing, valuing or preferring. Husserl thus gets to a reinterpretation of the fact of practical reason as the philosophical nucleus of his ethics, which is now a personal and affective ethics. He bestows a texture on this fact, however not as he would have thought in the first place: not as evident laws of a material apriori of “Gemüt”. In the person and her ethical experience as absolute affection Husserl rather discovers that which is per se not objectifiable and not to be made rationally evident. By this, Husserl captures and phenomenologically explains the non-objectifiable source of obligation and the possibility of complying with it. (shrink)

Anxious temperament (AT) in human and non-human primates is a trait-like phenotype evident early in life that is characterized by increased behavioural and physiological reactivity to mildly threatening stimuli1–4. Studies in children demonstrate that AT is an important risk factor for the later development of anxiety disorders, depression and comorbid substance abuse5. Despite its importance as an early predictor of psychopathology, little is known about the factors that predispose vulnerable children to develop AT and the brain systems that underlie its (...) expression. To characterize the neural circuitry associated with AT and the extent to which the function of this circuit is heritable, we studied a large sample of rhesus monkeys phenotyped for AT. Using 238 young monkeys from a multigenerational single-family pedigree, we simultaneously assessed brain metabolic activity and AT while monkeys were exposed to the relevant ethological condition that elicits the phenotype. High-resolution 18F-labelled deoxyglucose positron-emission tomography (FDG–PET) was selected as the imaging modality because it provides semi-quantitative indices of absolute glucose metabolic rate, allows for simultaneous measurement of behaviour and brain activity, and has a time course suited for assessing temperament-associated sustained brain responses. Here we demonstrate that the central nucleus region of the amygdala and the anterior hippocampus are key components of the neural circuit predictive of AT. We also show significant heritability of the AT phenotype by using quantitative genetic analysis. Additionally, using voxelwise analyses, we reveal significant heritability of metabolic activity in AT-associated hippocampal regions. However, activity in the amygdala region predictive of AT is not significantly heritable. Furthermore, the heritabilities of the hippocampal and amygdala regions significantly differ from each other. Even though these structures are closely linked, the results suggest differential influences of genes and environment on how these brain regions mediate AT and the ongoing risk of developing anxiety and depression. Anxiety disorders are among the most common forms of psychopathology6, and frequently begin during childhood and adolescence. Although all children experience acute anxiety, children with AT display extreme behavioural and physiological reactivity to novel stimuli, and in the presence of strangers inhibit their locomotor activity and vocalizations3.. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:TragedyA Lesson in SurvivalChristopher Perricone (bio)Tragedy and Its Historical Context"Tragedy" in the strict sense of the word refers to an ancient Greek literary genre, a form of drama for the most part performed publicly in the theater. As is well known, the word "tragedy" literally means "goat song." The belief among scholars is that early singers of tragedy wore goatskin costumes in imitation of satyrs. Also, as is well (...) known, Aristotle defines "tragedy" in the strict sense of the word as "the imitation of an action that is serious and also having magnitude, complete in itself; in language with pleasurable accessories, each kind brought in separately in the parts of the work; in a dramatic, not in a narrative form; with incidents arousing pity and fear, wherewith to accomplish its catharsis of such emotions."1 Of course, when one thinks of tragedy in the strict sense the names that come to mind are Aeschylus, Sophocles, and Euripides. It is arguable that these men not only set the stage for and developed the idea of tragedy in the strict sense, but they also laid the foundations of tragedy for centuries to come.After the Greeks, not surprisingly, tragedy evolves. The strict sense of the term as a point of reference, origin, or nucleus, remains—that is, after the Greeks, tragedy still retains that sense of "an imitation of an action that is serious." However, when one considers what later goes by the name of tragedy, one is hard-pressed, without resorting to Procrustean measures, to fit with any precision those later works of tragedy into the original Greek mold. After the Greeks, Seneca composes tragedies, as do Marlowe, Shakespeare, Corneille, Racine, Goethe, Schiller, Ibsen, Chekov, Lorca, Anouilh, Miller, et al. Even the sense of "serious" is not exactly the same: is the seriousness of Hedda Gabler's or Willie Loman's fate at all comparable to the fates of [End Page 70] Medea or Oedipus? The former cases surely seem serious in some domestic sense, whereas the latter clearly are intended to imply seriousness on a much grander and perhaps cosmic scale.The reason I mention all this is that "tragedy," both in what I call the strict and nuclear ancient Greek sense of the term (which does not imply that tragedy is clearly and distinctly defined, even in ancient Greece) and in the looser, derived sense of the word, has a long and compelling history. Tragedy is a form of drama to which we continually return. It is a genre that seems intrinsic not only to our very idea of theater but also to the very nature of art itself. Although one may debate the plausibility of writing tragedies in a disillusioned and nonheroic age, nevertheless one can hardly imagine the theater existing without tragedy. One way or another, it seems tragedies, whether in the strict or loose sense, will always be performed, and not merely out of nostalgia. Indeed, given the compelling nature of tragedy, it seems no accident that among the giants of literature, the tragedians are significantly represented. The compelling nature of tragedy is nicely expressed by the literary critic F. L. Lucas, and his statements should be considered a complement to Aristotle:Tragedy, then, is a representation of human unhappiness, which pleases us notwithstanding, by the truth with which it is seen and the fineness with which it is communicated—"l'amertume poignante et fortifiante de tout ce qui est vrai." ["The invigorating and poignant bitterness of whatever is true"; my translation.] The world of everyday seems often a purposeless chaos, a mangy tiger without even the fearful symmetry of Blake's vision; but the world of tragedy we can face, for we feel mind behind it and the symmetry is there. Tragedy, in fine, is man's answer to this universe that crushes him so pitilessly. Destiny scowls upon him; his answer is to sit down and paint her where she stands.2It is not only true that tragedy as practice and performance has a long and rich history; the study of tragedy has an equally long and rich history. The idea of tragedy has attracted, tantalized, frustrated, and exercised... (shrink)

The analysis of the data so far available indicates that eukaryotic chromosome with splicing characteristics appeared quite early in evolution possibly parallel and not sequential to the prokaryotic system. The endosymbiotic origin of the eukaryotic cell involved a primitive undifferentiated unicellular eukaryote and a photosynthetic or non-photosynthetic microbe. Certain regulatory genes of extra-cellular organelles were transferred later through molecular hybridization to the nucleus. The evolution of multicellularity and sexual reproduction led to the origin of innumerable eukaryotic forms in the (...) late precambrian period. This new concept of the author can account for the evolution of complex eukaryotic chromosome and harmonious functioning of extra-cellular organelles with the nucleus. The concept also explains the sudden spurt of innumerable eukaryotic fossils at the early palaeozoic era. (shrink)

The paper propose an assemble of (un)conventional explanatory hypotheses regarding insufficiently known aspects of the genesis and evolution of the human language. The causes and mechanisms that justify the hypothesis of an original linguistic nucleus generating ethnic dialects later on have been studied here. These aspects, regarded from the interdisciplinary perspective of such sciences as semiotics and linguistics, neurology and biophotonics, psychosociology, logic and philosophy, are sustaining that the human language (word) history presupposes: an “iconicity phase” (naturalist theory), permitting (...) an essentially motivated communication, and an “arbitrary phase” (conventionalist theory). The “Babel language” myth, for which the “power of the word” means an archetype of reference, has been selected as a symbolic frame in order to describe the stages through which the human language passes on its way from Nature (“language of living“) to Culture (“language of spiritual meanings“). (shrink)

Chapter One distinguishes the early, individualistic, writings from the later, more socially conscious ones. The metaphysical language of impermeable surfaces and levels, and rigid hierarchies, is consonant in James's writing with the assumption of what Dewey calls an individual/society split. ;Chapter Two focuses upon the relational self from the Principles of Psychology. The central pair of terms is that of strength/fragility, in which a self is revealed that is both functionally efficacious through activities of emphasis, selection, and negation, and permeable (...) to context. ;Chapter Three discusses the "social organism" and the "intellectual republic" from The Will to Believe and Other Essays in Popular Philosophy. James uses more socially conscious metaphors, and discusses the public and the private; "inner" and "outer" tolerance; and the "personal contribution," "X," which must be added to the "world," "M." ;Chapter Four discusses the "nucleus" of relations from Essays in Radical Empiricism. The personal aspect of social experience falls within the realm of "co-conscious relations" and the public falls within the sphere of the "conterminous." The strong side of the self, from Chapter Two; the private, or personal; inner tolerance; and the personal contribution, "X," from Chapter Three, belong to the sphere of co-conscious relations, as discussed in Chapter Four, just as the fragile side, the public; outer tolerance; and the world, "M," all belong to the sphere of conterminous relations. ;Chapter Five discusses the metaphor of Papini's corridor from Pragmatism. The adjoining rooms can be seen to symbolize the sphere of co-conscious relations, and the corridor of conterminous ones. The metaphysics of background and foreground points to an instrumentalist interpretation of the self, which represents a complete departure from James's early individualism. (shrink)

As is well known, Roman Ingarden and Edith Stein had a deep intellectual relationship and friendship, which began during their stay in Göttingen and Freiburg. The time spent together during this period and the correspondence that they maintained over the following years allowed them to be in close contact with their respective philosophies and to influence each other. This article aims at illustrating the affinities between Ingarden’s description of soul in § 78 of Controversy over the Existence of the World (...) and the analysis of soul and psyche developed by Stein between 1916 and 1922. Furthermore, it aims at presenting the hypothesis that this analysis influenced the formal anthropology elaborated by the Polish philosopher many years later. Both the depiction of the soul as a personal nucleus that manifests itself in human lived experiences and the description of this manifestation through the notion of “force” are theoretical elements that are essential in Ingarden’s mature ontology of man and that already played a crucial role in Stein’s early writings. Both thinkers, within several years of one another, elaborated an anthropological view that does not have the life of consciousness as a primary guideline, but that brings to light the ontological relevance of the unitary psychic source of human dispositions, of human character, and of consciousness itself. (shrink)

BackgroundIn Parkinson's disease, the side of motor symptoms onset may influence disease progression, with a faster motor symptom progression in patients with left side lateralization. Moreover, worse neuropsychological outcomes after subthalamic nucleus deep brain stimulation have been described in patients with predominantly left-sided motor symptoms. The objective of this study was to evaluate if the body side of motor symptoms onset may predict motor outcome of bilateral STN-DBS.MethodsThis retrospective study included all consecutive PD patients treated with bilateral STN-DBS at (...) Grenoble University Hospital from 1993 to 2015. Demographic, clinical and neuroimaging data were collected before and 1 year after surgery. The predictive factors of motor outcome at one-year follow-up, measured by the percentage change in the MDS-UPDRS-III score, were evaluated through univariate and multivariate linear regression analysis.ResultsA total of 233 patients were included with one-year follow-up after surgery [143 males ; 121 right body onset; 112 left body onset; mean age at surgery, 55.31 ± 8.44 years; mean disease duration, 11.61 ± 3.87]. Multivariate linear regression analysis showed that the left side of motor symptoms onset did not predict motor outcome.ConclusionsIn this retrospective study, the body side of motor symptoms onset did not significantly influence the one-year motor outcome in a large cohort of PD patients treated with bilateral STN-DBS. (shrink)

The segregation of damaged components at cell division determines the survival and aging of cells. In cells that divide asymmetrically, such as Saccharomyces cerevisiae, aggregated proteins are retained by the mother cell. Yet, where and how aggregation occurs is not known. Recent work by Zhou and collaborators shows that the birth of protein aggregates, under specific stress conditions, requires active translation, and occurs mainly at the endoplasmic reticulum. Later, aggregates move to the mitochondrial surface through fis1‐dependent association. During replicative aging, (...) aggregate association with the mother‐cell mitochondria contributes to the asymmetric segregation of aggregates, because mitochondria in the daughter cell do not carry aggregates. With increasing age of mother cells, aggregates lose their connection to the mitochondria, and segregation is less asymmetric. Relating these findings to other mechanisms of aggregate segregation in different organisms, we postulate that fusion between aggregates and their tethering to organelles such as the vacuole, nucleus, ER, or mitochondria are common principles that establish asymmetric segregation during stress resistance and aging. (shrink)

The discovery that hypocretins are involved in narcolepsy, a disorder associated with excessive daytime sleepiness, cataplexy and unusually rapid transitions to rapid‐eye‐movement sleep, opens a new field of investigation in the area of sleep control physiology. Hypocretin‐1 and ‐2 (also called orexin‐A and ‐B) are newly discovered neuropeptides processed from a common precursor, preprohypocretin. Hypocretin‐containing cells are located exclusively in the lateral hypothalamus, with widespread projections to the entire neuroaxis. Two known receptors, Hcrtr1 and Hcrtr2, have been reported. The (...) functional significance of the hypocretin system is rapidly emerging in both animals and humans. Hypocretin abnormalities cause narcolepsy in dogs, human and mice. The role of the hypocretin system in normal sleep regulation is more uncertain. We believe hypocretin cells drive cholinergic and monoaminergic activity across the sleep cycle. Input from the suprachiasmatic nucleus to hypocretin‐containing neurons may explain the occurrence of clock‐dependent alertness. Other functions are suggested by pharmacological and neurochemical experiments. These include regulation of food intake, neuroendocrine function, autonomic nervous system activity and energy balance. BioEssays 23:397–408, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

BackgroundThe preferable position of Deep Brain Stimulation electrodes is proposed to be located in the dorsolateral subthalamic nucleus to improve general motor performance. The optimal DBS electrode localization for the post-operative improvement of balance and gait is unknown.MethodsIn this single-center, retrospective analyses, 66 Parkinson’s disease patients were assessed pre- and post-operatively by using MDS-UPDRS, freezing of gait score, Giladi’s gait and falls questionnaire and Berg balance scale. The clinical outcome was related to the DBS electrode coordinates in x, y, (...) z plane as revealed by image-based reconstruction. Binomial generalized linear mixed models with fixed-effect variables electrode asymmetry, parkinsonian subtype, medication, age class and clinical DBS induced changes were analyzed.ResultsSubthalamic nucleus-deep brain stimulation improved all motor, balance and FoG scores in MED OFF condition, however there were heterogeneous results in MED ON condition. DBS electrode reconstructed coordinates impacted the responsiveness of axial symptoms. FoG and balance responders showed slightly more medially located STN electrode coordinates and less medio-lateral asymmetry of the electrode reconstructed coordinates across hemispheres compared to non-responders.ConclusionDeep brain stimulation electrode reconstructed coordinates, particularly electrode asymmetry on the medio-lateral axis affected the post-operative responsiveness of balance and FoG symptoms in PD patients. (shrink)

A particularly heartening feature of intellectual life in Ireland is the concentration in University College, Dublin of a nucleus of scholars who can well lay the foundations of a sorely–needed department of Christian Latin. In addition to Professor O’Meara, the College can boast Dr. Ludwig Bieler, whose erudition in palaeography and mediaeval Latinity alike has achieved such notable results for Hiberno–Latin, and Dr. James Shiel, an expert in the manuscripts of Boethius and indeed in the later Roman philosophical tradition. (...) If such a department of Christian Latin could be established, the repercussions could be important both in these islands and in America. One hopes that Professor O’Meara’s efforts in this direction will meet with encouragement and appreciation in proportion to the urgency of the project. (shrink)

For all these reasons, it is helpful to have a volume such as the one under review, which gives the historical and textual background for Crisis. Ably edited by Reinhold N. Smid, who has been associated with the Husserl Archives at Cologne for many years, the volume contains papers from the period 1934-37, just before Husserl's death in 1938. Crisis itself was published in its present form only posthumously in 1954, but its first two parts appeared in the journal Philosophia, (...) published in Belgrade, in 1936. The idea of composing this work came to Husserl after he gave two lectures in Prague on 14-15 November 1935. The lectures provided the nucleus for Crisis, and the typescript for them is published in thirty-three pages of this volume. It is interesting to note that the title for the typescript is "Psychology in the Crisis of European Science." Although psychology is extensively treated in Crisis, the issue of that science is not one of the themes that commentators usually discuss. It is helpful to see how central psychology was in Husserl's later thought. The point is that he must distinguish the philosophical study of man from the empirical psychological study if he is to avoid taking philosophy as merely a partial science and if he is not to betray the special mode of being of transcendental subjectivity. The study of man must not be carried out according to the "objectivist" methods of modern science. (shrink)

Aggleton & Brown propose that familiarity-based recognition depends on a perirhinal-medial dorsal thalamic system. However, connections between these structures are sparse or absent. In contrast, the perirhinal cortex is connected to midline/intralaminar nuclei. In a human, a lesion in this thalamic domain, sparing the medial dorsal nucleus, impaired familiarity-based recognition while sparing recollective-based recognition. It is thus more likely that the intralaminar/midline nuclei are involved in recognition.

Aggressive behavior is instinctively driven behavior that helps animals to survive and reproduce and is closely related to multiple behavioral and physiological processes. The dorsal raphe nucleus (DRN) is an evolutionarily conserved midbrain structure that regulates aggressive behavior by integrating diverse brain inputs. The DRN consists predominantly of serotonergic (5‐HT:5‐hydroxytryptamine) neurons and decreased 5‐HT activity was classically thought to increase aggression. However, recent studies challenge this 5‐HT deficiency model, revealing a more complex role for the DRN 5‐HT system in (...) aggression. Furthermore, emerging evidence has shown that non‐5‐HT populations in the DRN and specific neural circuits contribute to the escalation of aggressive behavior. This review argues that the DRN serves as a multifaceted modulator of aggression, acting not only via 5‐HT but also via other neurotransmitters and neural pathways, as well as different subsets of 5‐HT neurons. In addition, we discuss the contribution of DRN neurons in the behavioral and physiological aspects implicated in aggressive behavior, such as arousal, reward, and impulsivity, to further our understanding of DRN‐mediated aggression modulation. (shrink)

A review of research with chicks, songbirds, rodents, and nonhuman primates indicates that the brain is lateralized for a number of behavioral functions. These findings can be understood in terms of three hypothetical brain processes derived from a brain model based on general systems theory: hemispheric activation, interhemispheric inhibition, and interhemispheric coupling.Left-hemisphere activation occurs in songbirds and nonhuman primates in response to salient auditory or visual input, or when a communicative output is required. The right hemisphere is activated in rats (...) when spatial performance is required, and in chicks when they are placed in an emotion-provoking situation. In rats and chicks interhemispheric activation and inhibition occur when there is an affective component in the environment (novelty, aversive conditioning) or when an emotional response is emitted (copulation, attack, killing). An interhemispheric coupling (correlation) found in rats and rabbits implies that the hemispheres are two major components in a control system with a negative feedback loop. Early-experience variables in rats can induce laterality in a symmetric brain or facilitate its development in an already biased brain.It is predicted that functional lateralization, when present, will be similar across species: the left hemisphere will tend to be involved in communicative functions while the right hemisphere will respond to spatial and affective information; both hemispheres will often interact via activation-inhibition mechanisms when affective or emotional processes are involved. Homologous brain areas and their connecting callosal fibers must be intact at birth and must remain intact throughout development for lateralization to reach its maximum level. Injury to any portion of this unit will result in hemispheric redundancy rather than specialization. One major function of early experience is to provide stimulation during development, which acts to enhance the growth and development of the corpus callosum, thereby giving rise to a more specialized brain. (shrink)

Parkinson´s disease (PD) is a neurodegenerative disorder characterized by motor symptoms following dopaminergic depletion in the substantia nigra. Besides motor impairments however, several non-motor detriments can have the potential to considerably impact subjectively perceived quality of life in patients. Particularly emotion recognition of facial expressions has been shown to be affected in PD, and especially the perception of negative emotions like fear, anger or disgust is impaired. While emotion processing generally refers to automatic implicit as well as conscious explicit processing, (...) the focus of most previous studies in PD was on explicit recognition of emotions only, while largely ignoring implicit processing deficits. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is widely accepted as therapeutic measure in the treatment of PD and has been shown to advantageously influence motor problems. Among various concomitant non-motor effects of STN-DBS, modulation of facial emotion recognition under subthalamic stimulation has been investigated in previous studies with rather heterogeneous results. While there seems to be consensus regarding the processing of disgust which significantly deteriorates under STN stimulation, findings concerning emotions like fear or happiness report heterogeneous data and seem to depend on various experimental settings and measurements. In the present review, we summarized previous investigations focusing on STN-DBS influence on recognition of facial emotional expressions in patients suffering from PD. In a first step, we provide a synopsis of disturbances and problems in facial emotion processing observed in patients with PD. Secondly, we present findings of STN-DBS influence on facial emotion recognition and especially highlight different impacts of stimulation on implicit and explicit emotional processing. (shrink)

BackgroundThe cognitive outcomes induced by subthalamic nucleus deep brain stimulation (STN-DBS) remain unclear, especially in PD patients with mild cognitive impairment (MCI). This study explored the cognitive effects of STN-DBS in PD patients with MCI.MethodsThis was a retrospective cohort study that included 126 PD patients who underwent STN-DBS; all patients completed cognitive and motor assessments before and at least 6 months after surgery. Cognitive changes were mainly evaluated by the Montreal cognitive assessment (MoCA) scale and the seven specific MoCA (...) domains, including visuospatial/executive function, naming, attention, language, abstract, delayed recall, and orientation. Motor improvement was evaluated by the UPDRS-III. Cognitive changes and motor improvements were compared between PD-MCI and normal cognitive (NC) patients. Logistic regression analyses were performed to explore predictors of post-operative cognitive change.ResultsAt the time of surgery, 61.90% of the included PD patients had MCI. Compared with the PD-MCI group, the PD-NC group had a significantly higher proportion of cases with post-operative cognitive decline during follow-up of up to 36 months (mean 17.34 ± 10.61 months), mainly including in global cognitive function, visuospatial/executive function and attention. Covariate-adjusted binary logistic regression analyses showed that pre-operative global cognitive status was an independent variable for post-operative cognitive decline. We also found that pre-operative cognitive specific function could predict its own decline after STN-DBS, except for the naming and orientation domains.ConclusionPD-MCI patients are at a lower risk of cognitive decline after STN-DBS compared with PD-NC patients. (shrink)

Bosbach and Riečan states on residuated lattices both are generalizations of probability measures on Boolean algebras. Just from the observation that both of them can be defined by using the canonical structure of the standard MV-algebra on the unit interval [0, 1], generalized Riečan states and two types of generalized Bosbach states on residuated lattices were recently introduced by Georgescu and Mureşan through replacing the standard MV-algebra with arbitrary residuated lattices as codomains. In the present paper, the Glivenko theorem is (...) first extended to residuated lattices with a nucleus, which gives several necessary and sufficient conditions for the underlying nucleus to be a residuated lattice homomorphism. Then it is proved that every generalized Bosbach state (of type I, or of type II) compatible with the nucleus on a nucleus-based-Glivenko residuated lattice is uniquely determined by its restriction on the nucleus image of the underlying residuated lattice, and every relatively generalized Riečan state compatible with the double relative negation on an arbitrary residuated lattice is uniquely determined by its restriction on the double relative negation image of the residuated lattice. Our results indicate that many-valued probability theory compatible with nuclei on residuated lattices reduces in essence to probability theory on algebras of fixpoints of the underlying nuclei. (shrink)

'David Pole, in his The Later Philosophy of Wittgenstein, makes an admirable attempt to clarify the central points of Wittgenstein's philosophy in a straightforward manner. He approaches it from the outside with sympathy and good sense. And since he combines a clear head with a fluent style of writing – a combination that is rare among the initiated – his book will prove an excellent introduction for those who need a succinct account of Wittgenstein's later philosophy without any mystical overtones.' (...) - The Economist 'There is now a real need for a commentary on what must in frankness be admitted to be an exceedingly difficult corpus of philosophy. Mr Pole's little book is a response to that need; if small in bulk, it is rich in ideas... and all students of Wittgenstein will turn to it with gratitude.' - Sunday Times. (shrink)

The present article is based on a interview with a Japanese experienced caregiver who specializes in patients with amyotrophic lateral sclerosis, which generally leads to the locked-in syndrome. Professional caregivers for ALS patients with ventilator experience two particular temporalities in their practice. First, they must monitor the patient continuously during a seven-hour stay. Because a single problem in the ventilator can have fatal consequences, the care of an ALS patient with a ventilator requires long periods of sustained concentration. Second, (...) trying to understand the signs of a patient with a ventilator sometimes requires three hours to go through ten alphabets. In addition to the huge effort that such communication requires, caregivers must complete the meaning of the signs with their imagination: the ten alphabets are not sufficient to understand what the patient really wants to say. This imaginative capacity, however, is based on a long relationship, which started when the patient was still able to speak and move. That is why, as this article will show, even when a patient has entered total LIS, the caregiver can continue to realize his or her wishes. (shrink)

The origin of the eukaryotic cell nucleus and the selective forces that drove its evolution remain unknown and are a matter of controversy. Autogenous models state that both the nucleus and endoplasmic reticulum (ER) derived from the invagination of the plasma membrane, but most of them do not advance clear selective forces for this process. Alternative models proposing an endosymbiotic origin of the nucleus fail to provide a pathway fully compatible with our knowledge of cell biology. We (...) propose here an evolutionary scenario that reconciles both an ancestral endosymbiotic origin of the eukaryotic nucleus (endosymbiosis of a methanogenic archaeon within a fermentative myxobacterium) with an autogenous generation of the contemporary nuclear membrane and ER from the bacterial membrane. We specifically state two selective forces that operated sequentially during its evolution: (1) metabolic compartmentation to avoid deleterious co‐existence of anabolic (autotrophic synthesis by the methanogen) and catabolic (fermentation by the myxobacterium) pathways in the cell, and (2) avoidance of aberrant protein synthesis due to intron spreading in the ancient archaeal genome following mitochondrial acquisition and loss of methanogenesis. BioEssays 28: 525–533, 2006. © 2006 Wiley Periodicals, Inc. (shrink)