On the motivations for Merleau-Ponty’s ontological research

This paper attempts to clarify Merleau-Ponty’s later work by tracing a hitherto overlooked set of concerns that were of key consequence for the formulation of his ontological research. I argue that his ontology can be understood as a response to a set of problems originating in reflections on the intersubjective use of language in dialogue, undertaken in the early 1950s. His study of dialogue disclosed a structure of meaning-formation and pointed towards a theory of truth (both recurring ontological topics) that post-Phenomenology premises could not account for. A study of dialogue shows that speakers’ positions are interchangeable, that speaking subjects are active and passive in varying degrees, and that the intentional roles of subjects and objects are liable to shift or ‘transgress’ themselves. These observations anticipate the concepts of ‘reversibility’ and ‘narcissism’, his later view of activity and passivity, and his later view of intentionality, and sharpened the need to adopt an intersubjective focus in ontological research

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A Propaedeutic to Dialogue: "On The Oneness Of The Hermeneutical Horizon(s)" & "On The Importance Of Getting Things Straight"

S. Geniusas: Although Gadamer’s hermeneutics has suffered attacks from a number of philosophical perspectives, the profusion of criticisms seldom constitutes new challenges and for the most part is a reiteration of two seemingly opposite claims. On the one hand, we often hear that Gadamer’s hermeneutics is merely a disguised brand of the “philosophy of the subject” which under the pretext of openness reduces the Other to the self. On the other hand, it is just as often claimed that Gadamer’s writings fall into the category of the “hermeneutics of the fundamental questions” and therefore they cannot account for the selfhood of the self. Taking as its focus the theme of the oneness of the hermeneutical horizon(s), this paper argues that this theme carries no hegemonic or essentialist connotations. Rather, a careful analysis, which accentuates the negative and the dialectical elements of the oneness of horizons and the fact that this theme is for Gadamer both a presupposition and an achievement, reveals the shortcomings of both critiques. In the final analysis, the oneness of the horizon(s) is the dialogue that we ourselves are. Special attention is granted to Richard Kearney’s critique of Gadamer, to Gadamer’s critique of the incommensurabilist stance, and to the relevance of Gadamer’s hermeneutics in the context of today’s socio-political concerns. G. B. Madison: This essay is a companion piece to S. Geniusas’ “On the Oneness of the Hermeneutical Horizon(s)” and seeks to correct some of the serious misunderstandings of the philosophical hermeneutics of Hans-Georg Gadamer that one often encounters in the literature. It seeks above all to show how Gadamer’s commitment to philosophical universalism is ideally suited to enabling philosophy to confront the ethical challenges posed by the phenomenon of globalization

Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations

International audiencePurpose:CACNA1C encodes the alpha-1-subunit of a voltage-dependent L-type calcium channel expressed in human heart and brain. Heterozygous variants in CACNA1C have previously been reported in association with Timothy syndrome and long QT syndrome. Several case reports have suggested that CACNA1C variation may also be associated with a primarily neurological phenotype.Methods:We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.Results:Fourteen individuals have de novo, nontruncating variants and present variably with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy. Functional studies of a subgroup of missense variants via patch clamp experiments demonstrated differential effects on channel function in vitro, including loss of function (p.Leu1408Val), neutral effect (p.Leu614Arg), and gain of function (p.Leu657Phe, p.Leu614Pro). The remaining 11 individuals from eight families have truncating variants in CACNA1C. The majority of these individuals have expressive language deficits, and half have autism.Conclusion:We expand the phenotype associated with CACNA1C variants to include neurodevelopmental abnormalities and epilepsy, in the absence of classic features of Timothy syndrome or long QT syndrome

Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain

Purpose We characterize the clinical and molecular phenotypes of six unrelated individuals with intellectual disability and autism spectrum disorder who carry heterozygous missense variants of the PRKAR1B gene, which encodes the R1 beta subunit of the cyclic AMP-dependent protein kinase A (PKA). Methods Variants of PRKAR1B were identified by single- or trio-exome analysis. We contacted the families and physicians of the six individuals to collect phenotypic information, performed in vitro analyses of the identified PRKAR1B-variants, and investigated PRKAR1B expression during embryonic development. Results Recent studies of large patient cohorts with neurodevelopmental disorders found significant enrichment of de novo missense variants in PRKAR1B. In our cohort, de novo origin of the PRKAR1B variants could be confirmed in five of six individuals, and four carried the same heterozygous de novo variant c.1003C>T (p.Arg335Trp; NM_001164760). Global developmental delay, autism spectrum disorder, and apraxia/dyspraxia have been reported in all six, and reduced pain sensitivity was found in three individuals carrying the c.1003C>T variant. PRKAR1B expression in the brain was demonstrated during human embryonal development. Additionally, in vitro analyses revealed altered basal PKA activity in cells transfected with variant-harboring PRKAR1B expression constructs. Conclusion Our study provides strong evidence for a PRKAR1B-related neurodevelopmental disorder