KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype.

To characterise the genetics of splenic marginal zone lymphoma (SMZL), we performed whole exome sequencing of 16 cases and identified novel recurrent inactivating mutations in Kruppel-like factor 2 (KLF2), a gene whose deficiency was previously shown to cause splenic marginal zone hyperplasia in mice. KLF2 mutation was found in 40 (42%) of 96 SMZLs, but rarely in other B-cell lymphomas. The majority of KLF2 mutations were frameshift indels or nonsense changes, with missense mutations clustered in the C-terminal zinc finger domains. Functional assays showed that these mutations inactivated the ability of KLF2 to suppress NF-κB activation by TLR, BCR, BAFFR and TNFR signalling. Further extensive investigations revealed common and distinct genetic changes between SMZL with and without KLF2 mutation. IGHV1-2 rearrangement and 7q deletion were primarily seen in SMZL with KLF2 mutation, while MYD88 and TP53 mutations were nearly exclusively found in those without KLF2 mutation. NOTCH2, TRAF3, TNFAIP3 and CARD11 mutations were observed in SMZL both with and without KLF2 mutation. Taken together, KLF2 mutation is the most common genetic change in SMZL and identifies a subset with a distinct genotype characterised by multi-genetic changes. These different genetic changes may deregulate various signalling pathways and generate cooperative oncogenic properties, thereby contributing to lymphomagenesis.

Differential monocular vs. binocular pupil responses from melanopsin-based photoreception in patients with anterior ischemic optic neuropathy.

We examined the effect of anterior ischemic optic neuropathy (AION) on the activity of intrinsically photosensitive retinal ganglion cells (ipRGCs) using the pupil as proxy. Eighteen patients with AION (10 unilateral, 8 bilateral) and 29 age-matched control subjects underwent chromatic pupillometry. Red and blue light stimuli increasing in 0.5 log steps were presented to each eye independently under conditions of dark and light adaptation. The recorded pupil contraction was plotted against stimulus intensity to generate scotopic and photopic response curves for assessment of synaptically-mediated ipRGC activity. Bright blue light stimuli presented monocularly and binocularly were used for melanopsin activation. The post-stimulus pupil size (PSPS) at the 6th second following stimulus offset was the marker of intrinsic ipRGC activity. Finally, questionnaires were administered to assess the influence of ipRGCs on sleep. The pupil response and PSPS to all monocularly-presented light stimuli were impaired in AION eyes, indicating ipRGC dysfunction. To binocular light stimulation, the PSPS of AION patients was similar to that of controls. There was no difference in the sleep habits of the two groups. Thus after ischemic injury to one or both optic nerves, the summated intrinsic ipRGC activity is preserved when both eyes receive adequate light exposure.

Zone indécise. Périphéries urbaines et voyage de proximité dans la littérature contemporaine

Depuis les années 1980, les périphéries urbaines sont très fortement investies par les écrivains. Six d'entre eux sont étudiés dans ce livre: François Bon, François Maspero, Jacques Réda, Jean Rolin, Denis Tillinac et Philippe Vasset. Ils "voyagent" sur le pourtour parisien, parfois plus loin, là où, dit-on, la ville est moins ville que la ville, dans des espaces qui souffriraient d'un déficit d'urbanité. Ce faisant, ils en éprouvent la consistance paysagère, compliquent l'opposition facile entre Paris et sa banlieue, apparaissent, de fait, comme les agents d'une requalification symbolique de la ville contemporaine. La démarche de l'auteur se situe ici au confluent d'un corpus particulier, circonscrit dans le temps - les textes retenus ont paru entre 1990 et 2007 - et d'une question de grande ampleur historique, culturelle et esthétique: le paysage. Tout en plaçant les oeuvres commentées dans la lumière où elles trouvent leur relief spécifique, sa réflexion, associant ponctuellement l'analyse littéraire à d'autres disciplines (géographie, sociologie, philosophie), apporte, sur un champ peu exploré de la littérature vivante, un éclairage neuf et original qui s'adresse aux spécialistes du contemporain, ou de l'extrême contemporain, mais aussi à tous les lecteurs intéressés par les pratiques et les savoirs de la ville.

The Sottunga-Jurmo shear zone : structure and deformation history of a crustal-scale ductile shear zone in SW Finland

The aim of this study is to gain a better understanding of the structure and the deformation history of a NW-SE trending regional, crustal-scale shear structure in the Åland archipelago, SW Finland, called the Sottunga-Jurmo shear zone (SJSZ). Approaches involving e.g. structural geology, geochronology, geochemistry and metamorphic petrology were utilised in order to reconstruct the overall deformation history of the study area. The study therefore describes several features of the shear zone including structures, kinematics and lithologies within the study area, the ages of the different deformation phases (ductile to brittle) within the shear zone, as well as some geothermobarometric results. The results indicate that the SJSZ outlines a major crustal discontinuity between the extensively migmatized rocks NE of the shear zone and the unmigmatised, amphibolite facies rocks SW of the zone. The main SJSZ shows overall dextral lateral kinematics with a SW-side up vertical component and deformation partitioning into pure shear and simple shear dominated deformation styles that was intensified toward later stages of the deformation history. The deformation partitioning resulted in complex folding and refolding against the SW margin of the SJSZ, including conical and sheath folds, and in a formation of several minor strike-slip shear zones both parallel and conjugate to the main SJSZ in order to accommodate the regional transpressive stresses. Different deformation phases within the study area were dated by SIMS (zircon U-Pb), ID-TIMS (titanite U-Pb) and 40Ar/39Ar (pseudotachylyte wholerock) methods. The first deformation phase within the ca. 1.88 Ga rocks of the study area is dated at ca. 1.85 Ga, and the shear zone was reactivated twice within the ductile regime (at ca. 1.83 Ga and 1.79 Ga), during which the strain was successively increasingly partitioned into the main SJSZ and the minor shear zones. The age determinations suggest that the orogenic processes within the study area did not occur in a temporal continuum; instead, the metamorphic zircon rims and titanites show distinct, 10-20 Ma long breaks in deformation between phases of active deformation. The results of this study further imply slow cooling of the rocks through 600-700ºC so that at 1.79 Ga, 2 the temperature was still at least 600ºC. The highest recorded metamorphic pressures are 6.4-7.1 kbar. At the late stages or soon after the last ductile phase (ca. 1.79 Ga), relatively high-T mylonites and ultramylonites were formed, witnessing extreme deformation partitioning and high strain rates. After the rocks reached lower amphibolite facies to amphibolite-greenschist facies transitional conditions (ca. 500-550ºC), they cooled rapidly, probably due to crustal uplift and exhumation. The shear zone was reactivated at least once within the semi-brittle to brittle regime between ca. 1.79 Ga and 1.58 Ga, as evidenced by cataclasites and pseudotachylytes. In summary, the results of this study suggest that the Sottunga-Jurmo shear zone (and the South Finland shear zone) defines a major crustal discontinuity, and played a central role in accommodating the regional stresses during and after the Svecofennian orogeny.

An active zone characterized by slow normal faults, the northwestern margin of the València trough (NE Iberia): a review

The northwestern margin of the Valencia trough is an area of low strain characterized by slow normal faults and low to moderate seismicity. Since the mid 1990s this area has been the subject of a number of studies on active tectonic which have proposed different approaches to the location of active faults and to the calculation of the parameters that describe their seismic cycle. Fifty-six active faults have been found and a classification has been made in accordance with their characteristics: a) faults with clear evidence of large paleo-, historic or instrumental earthquakes (2/56); b) faults with evidence of accumulated activity during the Plio-Quaternary and with associated instrumental seismicity (7/56); c) faults with evidence of accumulated activity during the Plio-Quaternary and without associated instrumental seismicity (17/56); d) faults with associated instrumental seismicity and without evidence of accumulated activity during the Plio-Quaternary (30/56), and e) faults without evidence of activity or inactive faults. The parameters that describe the seismic cycle of these faults have been evaluated by different methods that use the geological data obtained for each fault except when paleoseismological studies were available. This classification can be applied to other areas with low slip faults because of the simplicity of the approaches adopted. This study reviews the different approaches proposed and describes the active faults located, highlighting the need a) to better understand active faults in slow strain zones through paleoseismological studies, and b) to include them in seismic hazard studies.