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.

Task complexity, the Cognition Hypothesis and second language learning and performance

In this paper we describe a taxonomy of task demands which distinguishes between Task Complexity, Task Condition and Task Difficulty. We then describe three theoretical claims and predictions of the Cognition Hypothesis (Robinson 2001, 2003b, 2005a) concerning the effects of task complexity on: (a) language production; (b) interaction and uptake of information available in the input to tasks; and (c) individual differences-task interactions. Finally we summarize the findings of the empirical studies in this special issue which all address one or more of these predictions and point to some directions for continuing, future research into the effects of task complexity on learning and performance.

The spreading of the introduced seaweed Caulerpa taxifolia (Vahl) C. Agardh in the Mediterranean Sea: testing the boat transportation hypothesis

The Spreading of the Introduced Seaweed Caulerpa taxifolia (Vahl) C. Agardh in the Mediterranean Sea: Testing the Boat Transportation Hypothesis

Minimal requirements for parameters to be used for the development of predictive models for microbial source tracking. The example of the pair somatic coliphages and phages infecting Bacteroides

Several methods and approaches for measuring parameters to determine fecal sources of pollution in water have been developed in recent years. No single microbial or chemical parameter has proved sufficient to determine the source of fecal pollution. Combinations of parameters involving at least one discriminating indicator and one universal fecal indicator offer the most promising solutions for qualitative and quantitative analyses. The universal (nondiscriminating) fecal indicator provides quantitative information regarding the fecal load. The discriminating indicator contributes to the identification of a specific source. The relative values of the parameters derived from both kinds of indicators could provide information regarding the contribution to the total fecal load from each origin. It is also essential that both parameters characteristically persist in the environment for similar periods. Numerical analysis, such as inductive learning methods, could be used to select the most suitable and the lowest number of parameters to develop predictive models. These combinations of parameters provide information on factors affecting the models, such as dilution, specific types of animal source, persistence of microbial tracers, and complex mixtures from different sources. The combined use of the enumeration of somatic coliphages and the enumeration of Bacteroides-phages using different host specific strains (one from humans and another from pigs), both selected using the suggested approach, provides a feasible model for quantitative and qualitative analyses of fecal source identification.

Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism.

Several observations support the hypothesis that differences in synaptic and regional cerebral plasticity between the sexes account for the high ratio of males to females in autism. First, males are more susceptible than females to perturbations in genes involved in synaptic plasticity. Second, sex-related differences in non-autistic brain structure and function are observed in highly variable regions, namely, the heteromodal associative cortices, and overlap with structural particularities and enhanced activity of perceptual associative regions in autistic individuals. Finally, functional cortical reallocations following brain lesions in non-autistic adults (for example, traumatic brain injury, multiple sclerosis) are sex-dependent. Interactions between genetic sex and hormones may therefore result in higher synaptic and consecutively regional plasticity in perceptual brain areas in males than in females. The onset of autism may largely involve mutations altering synaptic plasticity that create a plastic reaction affecting the most variable and sexually dimorphic brain regions. The sex ratio bias in autism may arise because males have a lower threshold than females for the development of this plastic reaction following a genetic or environmental event.

More evidence concerning the aspect hypothesis: The acquisition of English progressive aspect by Catalan-Spanish instructed learners

A robust finding of studies investigating the Aspect Hypothesis is that learners at early stages of acquisition show a strong preference for using the progressive aspect as associated with activity verbs. As they advance in their acquisition of the second or foreign language, learners move from this prototypical association to associations traditionally considered to be more peripheral (e.g.-ing with accomplishments or achievements). Within this framework, the goal of this paper is to provide further evidence from groups of learners with different proficiency levels with regard to the acquisition of progressive aspect by tutored learners of English who are bilingual Catalan-Spanish. This is done by eliciting data by means of two different task types and by looking at both tokens and types. Our results are consistent with previous research according to which-ing morphology is closely associated with durative lexical aspect, although not necessarily with activity predicates. The study also shows that the type of task has an influence on the frequency and the distribution of learners" progressive forms.

Central serous chorioretinopathy: Recent findings and new physiopathology hypothesis.

Central serous chorioretinopathy (CSCR) is a major cause of vision threat among middle-aged male individuals. Multimodal imaging led to the description of a wide range of CSCR manifestations, and highlighted the contribution of the choroid and pigment epithelium in CSCR pathogenesis. However, the exact molecular mechanisms of CSCR have remained uncertain. The aim of this review is to recapitulate the clinical understanding of CSCR, with an emphasis on the most recent findings on epidemiology, risk factors, clinical and imaging diagnosis, and treatments options. It also gives an overview of the novel mineralocorticoid pathway hypothesis, from animal data to clinical evidences of the biological efficacy of oral mineralocorticoid antagonists in acute and chronic CSCR patients. In rodents, activation of the mineralocorticoid pathway in ocular cells either by intravitreous injection of its specific ligand, aldosterone, or by over-expression of the receptor specifically in the vascular endothelium, induced ocular phenotypes carrying many features of acute CSCR. Molecular mechanisms include expression of the calcium-dependent potassium channel (KCa2.3) in the endothelium of choroidal vessels, inducing subsequent vasodilation. Inappropriate or over-activation of the mineralocorticoid receptor in ocular cells and other tissues (such as brain, vessels) could link CSCR with the known co-morbidities observed in CSCR patients, including hypertension, coronary disease and psychological stress.

History of offending behavior in first episode psychosis patients : a marker of specific clinical needs and a call for early detection strategies among young offenders

Plusieurs études suggèrent que les patients qui présentent un premier épisode psychotique et un passé délictueux présenteraient une clinique spécifique et nécessiteraient une prise en charge adaptée. A partir d'une cohorte de patients suivis pour un premier épisode psychotique dans la région de Melbourne {The Early Psychosis Prevention and Intervention Centre), nous avons analysé la prévalence d'actes délictueux dans leur passé (1), les caractéristiques cliniques à leur admission (2), l'évolution à court terme des patients ayant commis des délits par rapport aux autres patients (3). Nous avons également cherché à déterminer si des délits plus graves (atteinte à l'intégrité d'une personne) étaient corrélés à des caractéristiques cliniques particulières. Sur les 649 patients dont les données ont pu être analysées entre 1998 et 2000, 29% avaient un passé délictueux. Ils étaient en majorité des hommes et présentaient des difficultés sociales et scolaires plus importantes que les autres patients. Ils avaient également recours de manière plus régulière à des substances illicites et commis plus souvent des tentatives de suicide. Le tableau clinique qu'ils présentaient à leur admission dans le programme de soins était plus complexe et l'évolution globalement plus défavorable après 18 mois de traitement. Nous avons relevé aussi que la durée de psychose non traitée était plus longue que celle des autres patients. Enfin, les délits avec atteinte à l'intégrité d'une autre personne étaient plus fréquents en présence d'un insight faible et nécessitaient un plus grand nombre d'hospitalisation. Ces résultats confirment le besoin d'une recherche approfondie dans ce champ de la clinique et de stratégies de prévention et de soins plus spécifiques. Une détection précoce chez les jeunes hommes qui commettent des actes délictueux serait particulièrement importante puisque notre étude suggère que certains d'entre eux seraient dans une phase débutante et non reconnue d'un épisode psychotique. Une intervention plus rapide et adaptée pourrait avoir des conséquences positives à plusieurs niveaux.

Diagonal ear lobe crease and atherosclerosis: a review of the medical literature and dental implications

In Spain a significant number of individuals die from atherosclerotic disease of the coronary and carotid arteries without having classic risk factors and prodromal symptoms. The diagonal ear lobe crease (DELC) has been characterized in the medical literature as a surrogate marker which can identify high risk patients having occult atherosclerosis. This topic however has not been examined in either the medical or dental literature emanating from Spain. The majority of clinical, angiography and postmortem reports support the premise that DELC is a valuable extravascular physical sign able to distinguish some patients at risk of succumbing to atherosclerosis of the coronary arteries. A minority of studies have however failed to support this hypothesis. More recently reports using B mode ultrasound have also linked DELC to atherosclerosis of the carotid artery and another report has related DELC to the presence of calcified carotid artery atheromas on panoramic radiographs. DELC is readily visible during head and neck cancer screening examinations. In conjunction with the patient"s medical history, vital signs, and panoramic radiograph, the DELC may assist in atherosclerotic risk assessment

Steroid hormones interrelationships in the metabolic syndrome: an introduction to the ponderostat hypothesis

Sexual dimorphism in the metabolic syndrome. The clairvoyant early implication of sex hormones in the characterization of the metabolic syndrome (MS) was detected early, and in accordance with the well-known sex-related main patterns of fat deposition in obesity: gynoid and android. The differences point to a direct implication of androgens and estrogens in the development, properties and maintenance of obesity and, by extension, to the cumulus of diseases grouped in the MS. For a long time, the key issue of the MS, i.e. the metabolic event explaining (and justifying) most of the derangements of the MS, has been considered to be insulin resistance (...)

Lipid mobilization and gluconeogenesis in plants: Do glyoxylate cycle enzyme activities constitute a real cycle? A hypothesis

Glyoxysomes are specialized peroxisomes present in various plant organs such as germinating cotyledons or senescing leaves. They are the site of beta-oxidation and of the glyoxylate cycle. These consecutive pathways are essential to the maintenance of gluconeogenesis initiated by the degradation of reserve or structural lipids. In contrast to mitochondrial beta-oxidation, which is prevalent in animal cells, glyoxysomal beta-oxidation and the glyoxylate cycle have no direct access to the mitochondrial respiratory chain because of the impermeability of the glyoxysomal membrane to the reduced cofactors. The necessity of NAD(+) regeneration can conceivably be fulfilled by membrane redox chains and/or by transmembrane shuttles. Experimental evidence based on the active metabolic roles of higher plant glyoxysomes and yeast peroxisomes suggests the coexistence of two mechanisms, namely a reductase/peroxidase membrane redox chain and a malate/aspartate shuttle susceptible to transfer electrons to the mitochondrial ATP generating system. Such a model interconnects beta-oxidation, the glyoxylate cycle, the respiratory chain and gluconeogenesis in such a way that glyoxysomal malate dehydrogenase is an essential and exclusive component of beta-oxidation (NAD(+) regeneration). Consequently, the classical view of the glyoxylate cycle is superseded by a tentative reactional scheme deprived of cyclic character.