Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination

RAG1 binding to TCR gene elements is dictated by transcriptional control elements and by transcription itself; these findings provide direct confirmation of the long-held accessibility model

Reading Scepticism Historically. Scepticism, Acatalepsia and the Fall of Adam in Francis Bacon

The first part of this paper will provide a reconstruction of Francis Bacon’s interpretation of Academic scepticism, Pyrrhonism, and Dogmatism, and its sources throughout his large corpus. It shall also analyze Bacon’s approach against the background of his intellectual milieu, looking particularly at Renaissance readings of scepticism as developed by Guillaume Salluste du Bartas, Pierre de la Primaudaye, Fulke Greville, and John Davies. It shall show that although Bacon made more references to Academic than to Pyrrhonian Scepticism, like most of his contemporaries, he often misrepresented and mixed the doctrinal components of both currents. The second part of the paper shall offer a complete chronological survey of Bacon’s assessment of scepticism throughout his writings. Following the lead of previous studies by other scholars, I shall support the view that, while he approved of the state of doubt and the suspension of judgment as a provisional necessary stage in the pursuit of knowledge, he rejected the notion of acatalepsia. To this received reading, I shall add the suggestion that Bacon’s criticism of acatalepsia ultimately depends on his view of the historical conditions that surround human nature. I deal with this last point in the third part of the paper, where I shall argue that Bacon’s evaluation of scepticism relied on his adoption of a Protestant and Augustinian view of human nature that informed his overall interpretation of the history of humanity and nature, including the sceptical schools

Identification of CD4−CD8− Double-Negative Natural Killer T Cell Precursors in the Thymus

BACKGROUND: It is well known that CD1d-restricted Valpha14 invariant natural killer T (NKT) cells are derived from cells in the CD4(+)CD8(+) double-positive (DP) population in the thymus. However, the developmental progression of NKT cells in the earlier stages remains unclear, and the possible existence of NKT cell presursors in the earlier stages than DP stage remains to be tested. PRINCIPAL FINDINGS: Here, we demonstrate that NKT cell precursors that express invariant Valpha14-Jalpha18 transcripts but devoid of surface expression of the invariant Valpha14 receptor are present in the late CD4(-)CD8(-) double-negative (DN)4 stage and have the potential to generate mature NKT cells in both in vivo and in vitro experimental conditions. Moreover, the DN4 population in CD1d knock-out (CD1dKO) mice was similar to those with an NKT cell potential in wild-type (WT) C57BL/6 (B6) mice, but failed to develop into NKT cells in vitro. However, these precursors could develop into NKT cells when co-cultured with normal thymocytes or in an in vivo experimental setting, indicating that functional NKT cell precursors are present in CD1dKO mice. CONCLUSIONS: Together, these results demonstrate that thymic DN4 fraction contains NKT cell precursors. Our findings provide new insights into the early development of NKT cells prior to surface expression of the invariant Valpha14 antigen receptor and suggest the possible alternative developmental pathway of NKT cells

Relationship between karstification and burial dolomitization in Permian platform carbonates (Lower Khuff - Oman)

Large breccia fabrics associated with karst constitute an important structure in massive limestone successions. The dimensions and shapes of breccia structures are controlled by the initial fracture pattern of the limestone and preferential pathways of the karstifying fluids, but subsequently breccia fabrics can also govern the migration of later fluids. Therefore, breccias are highly relevant features to capture for reservoir characterisation. Outcrop analogues for Lower Khuff units in the Middle East present in the Central Oman Mountains reveal brecciated fabrics up to 10’s of meters in diameter. These brecciated units are closely associated with dolomite bodies of late diagenetic origin. Based on an integrated set of data, the breccias are interpreted as collapsed karst cavities either formed by meteoric or hypogenic fluids. The exact origin of the fluids could not be constrained due to an overprint by later dolomitizing fluids. Based on the composition of the clasts and matrix in the breccias, two dolomitization events are interpreted to have affected the succession, one prior to (early diagenetic [ED] dolomite) and one after brecciation (late diagenetic [DT2] dolomite). Dolomite of shallow burial origin (ED dolomite) was only observed as clasts within breccia and is much more frequent than late diagenetic (medium to deep burial) dolomite clasts. Thus, the timing of the brecciation and collapse is assumed to postdate shallow burial early diagenetic dolomitization. Late diagenetic replacive dolomite (DT2 dolomite) forms 90% of the matrix in the breccia fabrics with the exception of a small area that was not affected by dolomitization, but is rarely present as clasts. Stable isotope measurements [δ18O: − 2.5‰ to − 6‰ VPDB and δ13C: 2.9‰ to 4.8‰ VPDB] suggest a burial origin for the late diagenetic dolomite potentially with the participation of hydrothermal fluids. The dolomitized matrix indicates a migration of late dolomitizing fluids subsequent to or postdating the collapse of the karstic cavities. Thus, early karstification processes seem to have played a big role in controlling subsequent loci of late dolomitization in the Oman Mountains, and potentially in other similar settings elsewhere

Numerical Modelling Of The V-J Combinations Of The T Cell Receptor TRA/TRD Locus

T-Cell antigen Receptor (TR) repertoire is generated through rearrangements of V and J genes encoding α and β chains. The quantification and frequency for every V-J combination during ontogeny and development of the immune system remain to be precisely established. We have addressed this issue by building a model able to account for Vα-Jα gene rearrangements during thymus development of mice. So we developed a numerical model on the whole TRA/TRD locus, based on experimental data, to estimate how Vα and Jα genes become accessible to rearrangements. The progressive opening of the locus to V-J gene recombinations is modeled through windows of accessibility of different sizes and with different speeds of progression. Furthermore, the possibility of successive secondary V-J rearrangements was included in the modelling. The model points out some unbalanced V-J associations resulting from a preferential access to gene rearrangements and from a non-uniform partition of the accessibility of the J genes, depending on their location in the locus. The model shows that 3 to 4 successive rearrangements are sufficient to explain the use of all the V and J genes of the locus. Finally, the model provides information on both the kinetics of rearrangements and frequencies of each V-J associations. The model accounts for the essential features of the observed rearrangements on the TRA/TRD locus and may provide a reference for the repertoire of the V-J combinatorial diversity

Political Economy of Civil Society

This chapter explores the role of civil society in relation to the economy and the polity by focusing on three distinct yet related dimensions: (1) the conceptual history of civil society in relation to political economy; (2) the theory underpinning a political economy of civil society; (3) the implications of a political economy of civil society for policy-making. The main argument is that there is a fundamental difference between ancient and medieval conceptions, which emphasise natural sociability, and modern accounts that accentuate a violent ‘state of nature’. As a result, civil society either reflects the fundamental embeddedness of economic and political processes in social relations or is an artificial construct. The chapter develops a typology of four modern models, provides a theory of the political economy of civil society and outlines a series of policy ideas

Bentham y el derecho natural clásico

Esta interesante obra se apoya sobre el bien fundado principio de que "el mejor modo para explicitar y explicar la filosofía jurídica de Bentham es el arrojará, en primer lugar, la luz de su filosofía general" (p.32). Las grandes líneas de esta filosofía general se encuentran en el volumen VIII de la antigua edición de las obras de Bentham

Bentham y el derecho natural clásico

Esta interesante obra se apoya sobre el bien fundado principio de que "el mejor modo para explicitar y explicar la filosofía jurídica de Bentham es el arrojará, en primer lugar, la luz de su filosofía general" (p.32). Las grandes líneas de esta filosofía general se encuentran en el volumen VIII de la antigua edición de las obras de Bentham

Simulation thermique de l'évolution diagénétique des kérogènes : étude par résonance paramagnétique électronique

Dans cet article sont exposés les résultats obtenus en résonance paramagnétique électronique (RPE) sur des séries chauffées en laboratoire, d'échantillons de kérogènes, illustrant les trois lignées évolutives. L'évolution de ces kérgènes est caractérisée par la susceptibilité paramagnétique, la largeur et la forme de la raie RPE et le facteur de décomposition spectrale g. Ces résultats sont, d'une part comparés à ceux obtenus (sur les mêmes échantillons) en microscopie électronique à haute résolution, en spectroscopie infra-rouge, en analyse thermique et élémentaire, d'autre part confrontés aux données RPE de kérogènes différents précédemment étudiés. Enfin, le modèle d'évolution d'un carbonisat proposé par la microscopie électronique est ici complété