Many targets of the Wnt/β-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a “transcriptional switch,” repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to contribute to (...) the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood. In this mini-review, we discuss several recent reports that address the prevalence and molecular mechanisms of the Wnt transcription switch, including the finding of Wnt-dependent ubiquitination/inactivation of TLEs. Together, these findings highlight the growing complexity of the regulation of gene expression by the Wnt pathway. Wnt targets are regulated by a “switch” where TLE co-repressors are displaced from TCFs by β-catenin, leading to activation of transcription. Recent reports challenge this view and suggest that additional processes, including exchange of specific TCF proteins and Wnt-dependent ubiquitination of TLEs, play important roles in the Wnt transcriptional switch. (shrink)

The major challenge in complex disease genetics is to understand the fundamental features of this complexity and why functional alterations at multiple independent genes conspire to lead to an abnormal phenotype. We hypothesize that the various genes involved are all functionally united through gene regulatory networks (GRN), and that mutant phenotypes arise from the consequent perturbation of one or more rate‐limiting steps that affect the function of the entire GRN. Understanding a complex phenotype thus entails unraveling the details of each (...) GRN, namely, the transcription factors that bind to cis regulatory elements affected by sequence variants altering transcription of specific genes, and their mutual feedback relationships. These GRNs can be identified through their rate‐limiting steps and are best uncovered by genomic analyses of rare, extreme phenotype families, thus providing a coherent molecular basis to complex traits and disorders. (shrink)

Study on the fundamentals of Vaiśeṣika school in six systems of Hindu philosophy.

On educational thoughts of Rabindranath Tagore, 1861-1941, Bengali litterateur and Mahatma Gandhi, 1869-1948, Indian statesman and nationalist.

Study of Nītimañjarī, work on Hindu ethics by Dyādviveda, 15th cent.

Study on concept of perfection (guṇa) in the schools of Indic philosophy.

Social, cultural and contemporary study of Jainism and Jaina literature.

Transcript of papers on culture, philosophy, doctrines and other facets Buddhism; presented at a conference held in March, 2006 at Jai Narain Vyas University, organized by Bauddha Adhyayana Kendra.

On Sankhya philosophy; Sanskrit text with Hindi translation.

Study on the concept of jiva in Śaktiviśiṣṭādvaitavedānta philosophy and also in Indic philosophy.

Study of Śrīkarabhāṣya, Viraśaiva commentary by Śrīpatipaṇḍita, 14th century on Brahmasūtra of Bādarāyaṇa, basic work on Vedanta philosophy; includes complete text of Śrīkarabhāṣya.

On Ambedkar's philosophy and views, and Indian philosophy on dalits; includes quotation extracted from Buddhist scriptures and literature.

If stem cell-based therapies are developed, we will likely confront a difficult problem of justice: for biological reasons alone, the new therapies might benefit only a limited range of patients. In fact, they might benefit primarily white Americans, thereby exacerbating long-standing differences in health and health care.

We report on the deliberations of an interdisciplinary group of experts in science, law, and philosophy who convened to discuss novel ethical and policy challenges in stem cell research. In this report we discuss the ethical and policy implications of safety concerns in the transition from basic laboratory research to clinical applications of cell-based therapies derived from stem cells. Although many features of this transition from lab to clinic are common to other therapies, three aspects of stem cell biology pose (...) unique challenges. First, tension regarding the use of human embryos may complicate the scientific development of safe and effective cell lines. Second, because human stem cells were not developed in the laboratory until 1998, few safety questions relating to human applications have been addressed in animal research. Third, preclinical and clinical testing of biologic agents, particularly those as inherently complex as mammalian cells, present formidable challenges, such as the need to develop suitable standardized assays and the difficulty of selecting appropriate patient populations for early phase trials. We recommend that scientists, policy makers, and the public discuss these issues responsibly, and further, that a national advisory committee to oversee human trials of cell therapies be established. **NB we did not reccommend a NAC, we think it might be appropriate**. (shrink)

Biography of Aurobindo Ghose, 1872-1950, Indian philosopher and writer.

Biography of Aurobindo Ghose, 1872-1950, Indian philosopher.

Study on the view of Aurobindo Ghose on philosophy of education.

Life and works of Aurobindo Ghose, 1872-1950, Indic philosopher.

This paper focuses on the phenomenology of timeless awareness.

Il existe plusieurs faisceaux de présomption qui témoigneraient de relation entre les Polynésiens et les Amérindiens d’Amérique du Sud : il est aujourd’hui admis que les Polynésiens ont atteint l’Amérique du Sud. Si la patate douce est un indice d’anciens contacts entre la Polynésie et l’Amérique du Sud, des archéologues ont aussi trouvé sur la façade pacifique de l’Amérique du Chili des ossements de poulets polynésiens. Quelles seraient les étoiles que les Polynésiens pourraient avoir suivies pour se pourvoir en patate (...) douce en Amérique du Sud et plus précisément au Chili, sous les latitudes où les chercheurs ont trouvé des poules polynésiennes? L’ethnoastronomie tentera de répondre à la question de l’itinéraire de la patate douce, en soulevant l’hypothèse du rôle des étoiles comme repère spatial. There are several bundles of presumption that would testify of relationship between Polynesians and Native Americans from South America: it is now accepted that the Polynesians have reached South America. If sweet potato is a sign of ancient contacts between Polynesia and South America, archaeologists have also found on the Pacific Ocean facade in Chile the bones of Polynesian chickens. What would be the stars possibly followed by the Polynesians to get sweet potato in South America and Chile, under the latitudes where researchers have found Polynesian chickens? The ethnoastronomy will attempt to respond to the issue of the route of the sweet potato, by raising the hypothesis of the role of the stars as spatial coordinate system. (shrink)

Study on the aspect of consciousness in Indic philosophy with special reference to the works of Vasubandhu, Śaṅkarācārya, and Aurobindo Ghose, 1872-1950, philosophers.

On philosophical and historical perspectives of education : with special reference to Sri Aurobindo, 1872-1950, Indian philosopher and John Dewey, 1859-1952, an American philosopher and educational reformer.