The identification of additional subunits of the cGMP-gated cation channel suggests exciting questions about their regulatory roles and about structure/functional relationships. How do the different subunits interact? How is the complex assembled into the plasma membrane? Divalent cations have been implicated in the regulation of adaptation. One often overlooked cation is magnesium. Could this ion play a role in phototransduction?

René Descartes’ conception of the human will has important implications for his conception of human beings as rational and moral agents. Specifically, the will plays a significant role in his views on what control we have over our beliefs; what kind of freedom we enjoy; how our emotions affect our actions, and how we can moderate our emotions. I explore these issues in three contexts that arise throughout Descartes’ corpus, from his earliest significant work, Rules for the Direction of the (...) Mind (the Regulae, 1619-1628), to his last published work, The Passions of the Soul (1649). I begin with the question of why Descartes construes judgment as an operation of the will in the Meditations. This is a change in view from the Regulae. I argue that to understand this change, we need to consider his conceptions of error and activity in the Regulae. I trace the development in his philosophical views about error and activity from the Regulae to the Meditations and show that these commitments underpin his mature theory of judgment. I then turn to Descartes’ conception of freedom in the Fourth Meditation. Descartes’ conception of the will, I argue, figures centrally in his conception of freedom. I show that Descartes holds that freedom is compatible with determination and consists in the power of the will to determine itself. I show, further, that Descartes’ later correspondence helps to clarify and unify his characterization of freedom in the Fourth Meditation: freedom is proportional to the ease of self-determination. Lastly, I consider Descartes’ conception of the relationship between the will and the passions of the soul (the passions). I begin by addressing how the passions affect the will, and I argue for a “bifurcated” approach to the function of the passions. This interpretation holds that the passions affect the will differently depending on what kind of volition results—volitions involved in action or volitions involved in judgment. I then discuss several ways in which Descartes conceives of the passions as problematic. I conclude by exploring three means Descartes prescribes for controlling them: habituation, indirect control, and the regulation of desire. (shrink)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

Justice in the bible -- Plato's The Republic -- Aristotle's Nicomachean ethics -- Justice in Islamic law -- Saint Thomas Aquinas' summa theologica -- Confucius in china -- The conquest of America -- Machiavelli: "the end justifies the means" -- Jiirgen Habermas' theory of diskursethik -- John Rawls' Justice as fairness -- Ronald Dworkin's Taking rights seriously -- Robert N Ozick's Anarchy, state, and utopia -- Justice as "efficiency" -- Justice and "desert" -- Precedents -- Wojciech sadurski -- Marx's justice (...) as a "critique" -- Alasdair macintyre -- "Feminist" justice. (shrink)

Volume 19, Issue 10, October 2019, Page 3-7.

Definición del derecho natural -- Definición del derecho de gentes -- Diferencia de otras ciencias -- Del derecho público -- De la política -- Necesidad y utilidad del derecho natural y de gentes -- Origen y antiguedad de este derecho -- Formación de esta ciencia -- Progresos y escritores principales. Hugo Grotius -- John Selden -- Thomas Hobbes -- Samuel Pufendorf -- Christian Thomasius -- Johann Gottlieb Heineccius -- Christian Wolff -- Emer de Vattel -- Jean-Jacques Burlamaqui. Fortunato Bartolomeo De (...) Felice -- Otros escritores en com un -- Montesquieu -- Simon-Nicolas-Henri Linguet -- Jean-Jacques Rousseau -- Escritos modernos detestables -- Vicios y defectos de muchos modernos -- Modo para conocer los autores sospechosos -- Autores católicos con que se refutan -- Precaución para establecer las reglas del derecho natural -- Falsa preocupaci on de buscar un primer principio -- Métodos que se proponen -- No son necesarios -- Del método escolástico -- Universidades en que se enseña este derecho. (shrink)

There is a need for empirically based research on social and ethical challenges related to informed consent processes, particularly in studies focusing on adolescent sexual and reproductive health. In a pilot study of a school-based pregnancy prevention intervention in rural Zambia, the majority of the guardians who were asked to consent to their daughters’ participation, refused. In this paper we explore the reasons behind the low participation in the pilot with particular attention to challenges related to the community engagement and (...) informed consent process. The pilot was implemented in two schools and examined the acceptability of a package of interventions including economic support to families to keep their girls in school, pocket money for girls, youth club meetings on reproductive health, and community meetings to sensitize the community. Focus group discussions were conducted with girls who participated in the pilot, boys in their class and with parents. Individual semi-structured interviews were conducted with teachers, peer educators and community health workers involved in the coordination of the intervention as well as with religious and traditional leaders. Data were analyzed through thematic analysis. The findings indicate that inadequate use of recognized community communication channels during the community engagement process and dissemination of information about the pilot resulted in limited understanding of the pilot concept by the community. This surfaced through uncertainty and fear that the intervention may result in loss of control over daughters, worries about why money was provided unconditionally to girls, and suspicion of links to satanism. The sense of insecurity appeared to be exacerbated by low literacy levels, poverty, fear of loss of bride wealth, perceived disregard for local perceptions of social status, and scanty trust in the actors implementing the pilot. Inadequate use of locally appropriate channels in the dissemination of information created room for interpretation and facilitated development of mistrust, undermining the conditions for community engagement and actual informed consent. A key lesson learnt is the importance of taking seriously the complexity of local values and structures that may impact people’s capability to consent or not consent to a study in an informed manner. (shrink)

In euthanasia and/or assisted suicide of persons with dementia, the controversy has mostly focused on decisionally incapable persons with very advanced dementia for whom the procedure must be based on a written advance euthanasia directive. This focus on advance euthanasia directive-based EAS has been accompanied by scant attention to the issue of decision-making capacity assessment of persons with dementia who are being evaluated for concurrent request EAS. We build on a previous analysis of concurrent request EAS cases from the Netherlands, (...) which showed that many such cases involve persons with significant cognitive impairment. We use illustrative cases to describe the difficulty of determining decisional capacity in persons whose stage of dementia falls between severely impaired and mildly impaired. We show that the Dutch practice of capacity assessment in such dementia cases is difficult to reconcile with the widely accepted functional model of capacity—a model explicitly endorsed by the Dutch euthanasia review committees. We discuss why such deviations from the standard functional model might be occurring, as well as their ethical implications for dementia EAS policy and practice. (shrink)

All contemporary frameworks of mental capacity stipulate that we must begin from the presumption that an adult has capacity. This presumption is crucial, as it manifests respect for autonomy and guards against prejudice and paternalism on the part of the evaluator.Given its ubiquity, we might presume that we all understand the presumption’s meaning and application in the same way. Evidence demonstrates that this is not the case and that this has led to harm in vulnerable persons. There is thus strong (...) reason to question our presumptions about the presumption of capacity.We distinguish between two main ways of understanding and applying the presumption of capacity, and advocate for the one that we argue mitigates risk of harm. Our proposed interpretation offers many advantages in that it is consonant with actual practice of capacity evaluations, precludes confused and abusive avoidance of needed evaluations, and preserves the respect for autonomy motivating the presumption in the first place. (shrink)

Proceedings of a forum held in Austin, Tex., on Mother's Day, 1996.

Presenting evidence from the social brain, we argue that neural reuse is a dynamic, socially organized process that is influenced ontogenetically and evolutionarily by the cultural transmission of mental techniques, values, and modes of thought. Anderson's theory should be broadened to accommodate cultural effects on the functioning of architecturally similar neural systems, and the implications of these differences for reuse.

Challenges to Legal Theory offers the reader a fascinating journey though a variety of multi-disciplinary topics, ranging from law and literature, and law and religion, to legal philosophy and constitutional law. The collection reflects some of the challenges that the field of legal theory currently faces. It is compiled by a selection of international and Spanish scholars, whose essays are made available in English translation for the first time. The volume is based on a collection of essays, published in Spanish, (...) in honour of Professor José Iturmendi Morales, of Complutense University, Madrid, and brings the rich scholarship of pre-eminent Spanish scholars of law and legal theory to an international audience. (shrink)

Analyses of environmental DNAs have provided tantalizing evidence for “rozellida” or “cryptomycota”, a clade of mostly undescribed and deeply diverging aquatic fungi. Here, we put cryptomycota into perspective through consideration of Rozella, the only clade member growing in culture. This is timely on account of the publication in Nature of the first images of uncultured cryptomycota from environmental filtrates, where molecular probes revealed non‐motile cyst‐like structures and motile spores, all lacking typical fungal chitinous cell walls. Current studies of Rozella can (...) complement these fragmentary observations from environmental samples. Rozella has a fungal‐specific chitin synthase and its resting sporangia have walls that appear to contain chitin. Cryptomycota, including Rozella, lack a cell wall when absorbing food but like some other fungi, they may have lost their “dinner jacket” through convergence. Rather than evolutionary intermediates, the cryptomycota may be strange, divergent fungi that evolved from an ancestor with a nearly complete suite of classical fungal‐specific characters. (shrink)

We applaud Ray and Cooper (2024) for emphasizing environmental health as a bioethics issue. As a team of interdisciplinary pediatric researchers and providers who are part of an institutional clima...

«Claros del bosque» es uno de los libros esenciales de la trayectoria filosófica de María Zambrano en el que vemos, por primera vez, en marcha su «razón poética». Nadie mejor que la propia autora para presentarnos el significado de esta obra: “«Claros del bosque» dentro de mi pensamiento vertido en lo impreso, salvo alguna excepción, aparece como algo inédito salido de ese escribir irreprimible que brota por sí mismo y que ha ido a parar a cuadernos y hojas que nadie (...) conoce, ni yo misma, reacia que soy a releerme. Tenía que suceder por fuerza. Mas creo que el carácter de ofrenda de «Claros del bosque» a la persona a quien va dedicado en su tránsito tiene que ver en ello, acentuando así el carácter de ofrenda que todo lo que he publicado tiene desde siempre. Nada es de extrañar que la razón discursiva apenas aparezca. Con anterioridad esbocé una ‘Crítica de la razón discursiva’ que no podría prometerme que salga de ese estado. Creo, pues, que como libro es el que más responde a esa ‘idea’ hace tiempo formulada de que ‘pensar es ante todo –como raíz, como acto–– descifrar lo que se siente’, entendiendo por sentir el ‘sentir originario’, expresión usada por mí desde hace años. Y también que ‘el hombre es el ser que padece su propia trascendencia’ en un incesante proceso de unificación entre pasividad y conocimiento, entre ser y vida. Vida verdadera, sorprendida tan sólo en algunos claros que se abren en la espesura inicial entre cielo y tierra. Y en el remoto horizonte donde cielo y tierra, ser y vida, vida y muerte se anegan”. (shrink)

This study explores the perceptions of Norwegian nurses who have received assisted dying requests from terminally ill patients. Assisted dying is illegal in Norway, while in some countries, it is an option. Nurses caring for terminally ill patients may experience ethical challenges by receiving requests for euthanasia and assisted suicide. We applied a qualitative research design with a phenomenological hermeneutic approach using open individual interviews. A total of 15 registered nurses employed in pulmonary and oncology wards of three university hospitals (...) and home care in one municipality were recruited. Four themes emerged from the analysis: (1) unprepared for the request; (2) meeting direct, indirect, and nonverbal requests; (3) working in a gray zone, and (4) feeling alone and powerless. The study found that nurses were unsure how to handle such requests due to professional uncertainty about assisted dying. Working in an environment where the topic is taboo made nurses morally uncertain, and some perceived this as moral distress. The hospital chaplain played a significant role in providing support to these nurses. (shrink)

AimWhite matter changes in individuals at ultra-high risk for psychosis (UHR) may be involved in the transition to psychosis. Sleep-wake disturbances commonly precede the first psychotic episode and predict development of psychosis. We examined associations between white matter microstructure and sleep-wake disturbances in UHR individuals compared to healthy controls (HC), as well as explored the confounding effect of medication, substance use, and level of psychopathology.MethodsSixty-four UHR individuals and 35 HC underwent clinical interviews and diffusion weighted imaging. Group differences on global (...) and callosal mean fractional anisotropy (FA) was tested using general linear modeling. Sleep-wake disturbances were evaluated using the subjective measures disturbed sleep index (DSI) and disturbed awakening index (AWI) from the Karolinska Sleep Questionnaire, supported by objective sleep measures from one-night actigraphy. The primary analyses comprised partial correlation analyses between global FA/callosal FA and sleep-wake measures. Secondary analyses investigated multivariate patterns of covariance between measures of sleep-wake disturbances and FA in 48 white matter regions of interest using partial least square correlations.ResultsUltra-high risk for psychosis individuals displayed lower global FA (F = 14.56, p < 0.001) and lower callosal FA (F = 11.34, p = 0.001) compared to HC. Subjective sleep-wake disturbances were significantly higher among the UHR individuals (DSI: F = 27.59, p < 0.001, AWI: F = 36.42, p < 0.001). Lower callosal FA was correlated with increased wake after sleep onset (r = −0.34, p = 0.011) and increased sleep fragmentation index (r = −0.31, p = 0.019) in UHR individuals. Multivariate analyses identified a pattern of covariance in regional FA which were associated with DSI and AWI in UHR individuals (p = 0.028), but not in HC. Substance use, sleep medication and antipsychotic medication did not significantly confound these associations. The association with objective sleep-wake measures was sustained when controlling for level of depressive and UHR symptoms, but symptom level confounded the covariation between FA and subjective sleep-wake measures in the multivariate analyses.ConclusionCompromised callosal microstructure in UHR individuals was related to objectively observed disruptions in sleep-wake functioning. Lower FA in ventrally located regions was associated with subjectively measured sleep-wake disturbances and was partly explained by psychopathology. These findings call for further investigation of sleep disturbances as a potential treatment target. (shrink)

Peter Abelard (1079–1142 ce) was the most wide‐ranging philosopher of the twelfth century. He quickly established himself as a leading teacher of logic in and near Paris shortly after 1100. After his affair with Heloise, and his subsequent castration, Abelard became a monk, but he returned to teaching in the Paris schools until 1140, when his work was condemned by a Church Council at Sens. His logical writings were based around discussion of the “Old Logic”: Porphyry's Isagoge, aristotle'S Categories and (...) On Interpretation and boethius'S textbook on topical inference. They comprise a freestanding Dialectica (“Logic”; probably c.1116), a set of commentaries (known as the Logica [Ingredientibus], c. 1119) and a later (c. 1125) commentary on the Isagoge (Logica Nostrorum Petititoni Sociorum or Glossulae). In a work Abelard called his Theologia, issued in three main versions (between 1120 and c.1134), he attempted a logical analysis of trinitarian relations and explored the philosophical problems surrounding God's claims to omnipotence and omniscience. The Collationes (“Debates,” also known as “Dialogue between a Christian, a Philosopher and a Jew”; probably c.1130) present a rational investigation into the nature of the highest good, in which the Christian and the Philosopher (who seems to be modeled on a philosopher of pagan antiquity) are remarkably in agreement. The unfinished Scito teipsum (“Know thyself,” also known as the “Ethics”; c.1138) analyses moral action. (shrink)

l presente texto propone un recorrido por la obra de Gilbert Simondon a partir de una pregunta acerca de la piel y el contacto. Su conceptualización del límite y de la relación en La individuación a la luz de las nociones de forma y de información permite trazar líneas conceptuales para pensar el contacto en un diálogo con prácticas corporales y artísticas del campo de las técnicas somáticas y de la danza. La lectura de Simondon en diálogo con experiencias sensibles (...) permite entender algunos de los conceptos centrales de su obra y conceptualizaciones originales que se elaboran en el cruce. (shrink)

Dentro de la tradición de la hermenéutica filosófica y, más específicamente, de la ontología hermenéutica del filósofo alemán H.G. Gadamer, "Interpretar y argumentar" constituye una indagación en el modelo de racionalidad propio ...