Role of wind stress in driving SST biases in the tropical Atlantic

Coupled climate models used for long-term future climate projections and seasonal or decadal predictions share a systematic and persistent warm sea surface temperature (SST) bias in the tropical Atlantic. This study attempts to better understand the physical mechanisms responsible for the development of systematic biases in the tropical Atlantic using the so-called Transpose-CMIP protocol in a multi-model context. Six global climate models have been used to perform seasonal forecasts starting both in May and February over the period 2000-2009. In all models, the growth of SST biases is rapid. Significant biases are seen in the first month of forecast and, by six months, the root-mean-square SST bias is 80% of the climatological bias. These control experiments show that the equatorial warm SST bias is not driven by surface heat flux biases in all models, whereas in the south-eastern Atlantic the solar heat flux could explain the setup of an initial warm bias in the first few days. A set of sensitivity experiments with prescribed wind stress confirm the leading role of wind stress biases in driving the equatorial SST bias, even if the amplitude of the SST bias is model dependent. A reduced SST bias leads to a reduced precipitation bias locally, but there is no robust remote effect on West African Monsoon rainfall. Over the south-eastern part of the basin, local wind biases tend to have an impact on the local SST bias (except in the high resolution model). However, there is also a non-local effect of equatorial wind correction in two models. This can be explained by sub-surface advection of water from the equator, which is colder when the bias in equatorial wind stress is corrected. In terms of variability, it is also shown that improving the mean state in the equatorial Atlantic leads to a beneficial intensification of the Bjerknes feedback loop. In conclusion, we show a robust effect of wind stress biases on tropical mean climate and variability in multiple climate models

Immunodominant T Cell Determinants of Aquaporin-4, the Autoantigen Associated with Neuromyelitis Optica

Autoantibodies that target the water channel aquaporin-4 (AQP4) in neuromyelitis optica (NMO) are IgG1, a T cell-dependent Ig subclass. However, a role for AQP4-specific T cells in this CNS inflammatory disease is not known. To evaluate their potential role in CNS autoimmunity, we have identified and characterized T cells that respond to AQP4 in C57BL/6 and SJL/J mice, two strains that are commonly studied in models of CNS inflammatory diseases. Mice were immunized with either overlapping peptides or intact hAQP4 protein encompassing the entire 323 amino acid sequence. T cell determinants identified from examination of the AQP4 peptide (p) library were located within AQP4 p21-40, p91-110, p101-120, p166-180, p231-250 and p261-280 in C57BL/6 mice, and within p11-30, p21-40, p101-120, p126-140 and p261-280 in SJL/J mice. AQP4-specific T cells were CD4+ and MHC II-restricted. In recall responses to immunization with intact AQP4, T cells responded primarily to p21-40, indicating this region contains the immunodominant T cell epitope(s) for both strains. AQP4 p21-40-primed T cells secreted both IFN-γ and IL-17. The core immunodominant AQP4 21-40 T cell determinant was mapped to residues 24-35 in C57BL/6 mice and 23-35 in SJL/J mice. Our identification of the AQP4 T cell determinants and characterization of its immunodominant determinant should permit investigators to evaluate the role of AQP4-specific T cells in vivo and to develop AQP4-targeted murine NMO models

Identification of naturally processed AQP4 determinants.

<p>AQP4 peptides were tested for their ability to induce T cell proliferative responses in intact hAQP4-primed (A) C57BL/6 and (B) SJL/J mice. Each 20-mer AQP4 peptide is indicated by first residue. Mice were immunized subcutaneously with 100 µg recombinant intact hAQP4 in CFA. 10–12 days later, lymph node cells were cultured in vitro for recall responses to the indicated human or mouse overlapping 20-mer peptides. Data are shown as stimulation indices (SI's) of mean proliferative responses in the presence of peptide (25 µg/ml) compared to the absence of antigen (background). Standard errors (+/− SEM) are shown for proliferative responses tested in triplicate. Recall to intact hAQP4 is shown for comparison.</p

Characterization of the minimal core T cell epitope within AQP4 p21-40.

<p>AQP4 p21-40-specific T cells were restimulated with truncated peptides to determine the core of the p21-40 determinant in (A, B) p21-40 specific C57BL/6 cell lines and (C, D) p21-40 specific SJL/J primary lymph node cells. Cell lines were restimulated with irradiated syngeneic splenic APC and various concentrations of p21-40 or truncated peptides. After 48 hours (cell lines) or 72 hours (LN), cultures were pulsed with ³H-thymidine and harvested 16 hours later. Data shown represent means of triplicates +/− SEM.</p

Predicted I-A^b- and I-A^s- binding mAQP4 epitopes for T cell recognition.

<p>MetaSVMp, a quantitative binding affinity program that employs the immune epitope database (IEDB) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015050#pone.0015050-Hu1" target="_blank">[26]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015050#pone.0015050-Zhang1" target="_blank">[27]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015050#pone.0015050-Nielsen2" target="_blank">[30]</a>, was used to identify potential I-A^b- and I-A^s-binding of AQP4 determinants for T cell recognition. Inverse of 50% inhibition concentration values (1/IC₅₀) is plotted for I-A^b (A top panel) and I-A^s (B top panel). Peaks correspond to increased predicted binding affinity: strong binding, IC₅₀<500 nM; moderate binding, IC₅₀>500 nM and <5,000 nM, and non-binding, IC₅₀>5,000 nM. Peaks correspond to increased predicted binding affinity. The top 20% of all possible epitopes are shown for I-A^b (A bottom panel) and I-A^s (B bottom panel). MetaSVMp percentile ranks were acquired from the MetaMHC web-based application; tall peaks correspond to top-ranked predicted epitopes.</p

Temporosylvian arachnoid cysts in children. Part 1: Cognitive profile of children with a temporal cyst and impact of the cyst in daily life. A prospective study in 100 consecutive children

International audienceOBJECTIVE The aim of this study was to determine the cognitive profile of children with a temporal arachnoid cyst (TAC) and its impact on daily life. METHODS The authors prospectively analyzed the cognitive and psychological profiles of 100 consecutive children relative to age and cyst characteristics (side, cyst size, and cyst shape: convex or nonconvex) and their outcome 4 years later. RESULTS Mean IQs were normal but with high heterogeneity on Full Scale IQ (FSIQ; range 59–150); 29% of children had at least one Wechsler index below the norm, in particular, Processing Speed and Working Memory Indexes. Impairments were observed in language for 31% of children, as well as in verbal memory (28%), visual memory (23%), executive function (21%), and visual attention (24%). Half of the children (50%) needed rehabilitation for learning difficulties, and 26% had academic difficulties. The parental questionnaire BRIEF (Behavior Rating Inventory of Executive Function) revealed significant executive dysfunctions in daily life for 22% of the children. One-third of the patients (34%) required psychotherapy for anxiety or social disorders, with higher rates in patients with a right-sided cyst and older children. Cyst size had very little neuropsychological impact. Convex cysts were significantly associated with worse performance than nonconvex cysts on all Wechsler indexes and FSIQ, and in language, verbal memory, attention, and visuospatial skills. Children with a convex cyst had significantly more executive and behavior difficulties in daily life and more psychotherapy than other children. The effect of cyst shape was independent of Galassi type and cyst side. Children with a ruptured cyst or an incidentally discovered cyst usually had a good cognitive level. Four years later, children without initial disorders remained stable, whereas those with difficulties who did not undergo surgery needed more rehabilitation and school adaptations. CONCLUSIONS This large cohort study revealed a varied profile of children with a TAC: at initial assessment, 50% had neuropsychological difficulties and needed rehabilitation and/or psychotherapy for learning or behavior difficulties, and 50% had no difficulties, which may explain the debate about this pathology. Patients with neuropsychological difficulties had a heterogeneous profile with normal intelligence but selective cognitive and/or behavior disorders that may have a long-term impact on their quality of life, particularly those with a right-sided cyst. A neuropsychological evaluation is not always necessary for a cyst discovered incidentally, but early evaluation is essential in patients with academic, learning, or psychological disorders. When assessment shows selective disorders presumably linked to cyst location, surgery may be considered, particularly for convex cysts, as this study revealed more effects in association with cyst shape than with cyst size and significantly poorer performance with a convex cyst

Localization of identified murine AQP4 T cell epitopes.

<p>AQP4 peptides that elicited proliferative responses in (A) C57BL/6 and (B) SJL/J mice are located within putative transmembrane and cytoplasmic domains. (C) Sequences of human (hAQP4) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015050#pone.0015050-Yang1" target="_blank">[34]</a> and murine <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015050#pone.0015050-Turtzo1" target="_blank">[17]</a> AQP4 (mAQP4). Dashes represent homologous regions between the two species.</p

The ubiquitin-modifying enzyme A20 restricts the ubiquitination of RIPK3 and protects cells from necroptosis

A20 is an anti-inflammatory protein linked to multiple human diseases, however the mechanisms by which A20 prevents inflammatory disease are incompletely defined. We now find that A20 deficient T cells and fibroblasts are susceptible to caspase independent and RIPK3 dependent necroptosis. Global RIPK3 deficiency significantly rescues the survival of A20 deficient mice. A20 deficient cells exhibit exaggerated formation of RIPK1-RIPK3 complexes. RIPK3 undergoes physiological ubiquitination at lysine 5 (K5), and this ubiquitination event supports the formation of RIPK1-RIPK3 complexes. The catalytic cysteine of A20’s deubiquitinating motif is required for inhibiting RIPK3 ubiquitination and RIPK1-RIPK3 complex formation. These studies link A20 and RIPK3 ubiquitination to necroptotic cell death, and suggest new mechanisms by which A20 may prevent inflammatory disease

Temporosylvian arachnoid cysts in children. Part 2: Postoperative neuropsychological and clinical improvement

International audienceOBJECTIVE The authors’ objective was to study clinical, imaging, and neuropsychological changes in children who underwent surgery for a temporal arachnoid cyst (TAC). METHODS Thirty-four children were prospectively assessed similarly at diagnosis and postoperatively (mean 14 months) with clinic visits, images, cognitive tests, and parental questionnaires on mood/behavior and executive functions. The scores were compared pre- and postoperatively for the entire cohort and individually. The scores of 25 children were also compared with a control group of 23 healthy age-matched children. Parents were administered an outcome questionnaire on average 4 years postoperatively. RESULTS The 34 children selected for surgery had signs of raised intracranial pressure (74%) and/or selective neuropsychological disorders presumably linked to cyst location (learning difficulties in 65%, cognitive difficulties in 56%, and mood/ behavior difficulties in 47%). The majority of patients had a convex cyst (85%) and underwent microsurgical fenestration (85%). The TAC volume decreased ≥ 50% for 59% of children. On the Wechsler Intelligence Scale, the entire cohort significantly improved on Full Scale IQ and verbal and perceptual nonverbal indexes. Individually, nearly half of the children (47%) highly increased their scores (≥ 15 points) on at least one IQ index and 26% on at least two indexes. Language, working memory, episodic memory, and executive functions were also significantly improved. Improvements were more pronounced in patients with a preoperative heterogeneous profile with isolated lower scores and a left-sided cyst. Parental questionnaires showed reduction in anxiety, aggressiveness, social problems, and daily life executive disorders. Preschool-aged children improved significantly in language and verbal IQ, as did middle/high school–aged children in many domains. Individual analyses revealed improvement in 76% of cases. Cognitive scores were lower for patients preoperatively than for controls and were no longer significantly different postoperatively in verbal fluency, visual memory, and working memory. Four years later, 97% of parents described an improvement in their child, correlated with cognitive improvements. CONCLUSIONS Among children with a TAC, some have no clinical signs or neuropsychological difficulties, and others may show signs of raised intracranial pressure and/or specific neuropsychological disorders that impact daily life and require significant and long-lasting rehabilitation. In these cases, consideration may be given to surgical decompression. It is interesting to note that 76% of this surgically treated cohort improved regardless of the child’s age, particularly in patients with selective disorders and an impact on daily life. However, a larger number of children will need to be investigated before the true benefit of such treatment can be known