Comparative genomic analysis reveals independent expansion of a lineage-specific gene family in vertebrates: The class II cytokine receptors and their ligands in mammals and fish

BACKGROUND: The high degree of sequence conservation between coding regions in fish and mammals can be exploited to identify genes in mammalian genomes by comparison with the sequence of similar genes in fish. Conversely, experimentally characterized mammalian genes may be used to annotate fish genomes. However, gene families that escape this principle include the rapidly diverging cytokines that regulate the immune system, and their receptors. A classic example is the class II helical cytokines (HCII) including type I, type II and lambda interferons, IL10 related cytokines (IL10, IL19, IL20, IL22, IL24 and IL26) and their receptors (HCRII). Despite the report of a near complete pufferfish (Takifugu rubripes) genome sequence, these genes remain undescribed in fish. RESULTS: We have used an original strategy based both on conserved amino acid sequence and gene structure to identify HCII and HCRII in the genome of another pufferfish, Tetraodon nigroviridis that is amenable to laboratory experiments. The 15 genes that were identified are highly divergent and include a single interferon molecule, three IL10 related cytokines and their potential receptors together with two Tissue Factor (TF). Some of these genes form tandem clusters on the Tetraodon genome. Their expression pattern was determined in different tissues. Most importantly, Tetraodon interferon was identified and we show that the recombinant protein can induce antiviral MX gene expression in Tetraodon primary kidney cells. Similar results were obtained in Zebrafish which has 7 MX genes. CONCLUSION: We propose a scheme for the evolution of HCII and their receptors during the radiation of bony vertebrates and suggest that the diversification that played an important role in the fine-tuning of the ancestral mechanism for host defense against infections probably followed different pathways in amniotes and fish

Gaia Data Release 2: Calibration and mitigation of electronic offset effects in the data

The European Space Agency Gaia satellite was launched into orbit around L2 in December 2013. This ambitious mission has strict requirements on residual systematic errors resulting from instrumental corrections in order to meet a design goal of sub-10 microarcsecond astrometry. During the design and build phase of the science instruments, various critical calibrations were studied in detail to ensure that this goal could be met in orbit. In particular, it was determined that the video-chain offsets on the analogue side of the analogue-to-digital conversion electronics exhibited instabilities that could not be mitigated fully by modifications to the flight hardware. We provide a detailed description of the behaviour of the electronic offset levels on microsecond timescales, identifying various systematic effects that are known collectively as offset non-uniformities. The effects manifest themselves as transient perturbations on the gross zero-point electronic offset level that is routinely monitored as part of the overall calibration process. Using in-orbit special calibration sequences along with simple parametric models, we show how the effects can be calibrated, and how these calibrations are applied to the science data. While the calibration part of the process is relatively straightforward, the application of the calibrations during science data processing requires a detailed on-ground reconstruction of the readout timing of each charge-coupled device (CCD) sample on each device in order to predict correctly the highly time-dependent nature of the corrections. We demonstrate the effectiveness of our offset non-uniformity models in mitigating the effects in Gaia data. We demonstrate for all CCDs and operating instrument and modes on board Gaia that the video-chain noise-limited performance is recovered in the vast majority of science samples

Systematisation of spatial uncertainties for comparison between a MR and a CT-based radiotherapy workflow for prostate treatments

<p>Abstract</p> <p>Background</p> <p>In the present work we compared the spatial uncertainties associated with a MR-based workflow for external radiotherapy of prostate cancer to a standard CT-based workflow. The MR-based workflow relies on target definition and patient positioning based on MR imaging. A solution for patient transport between the MR scanner and the treatment units has been developed. For the CT-based workflow, the target is defined on a MR series but then transferred to a CT study through image registration before treatment planning, and a patient positioning using portal imaging and fiducial markers.</p> <p>Methods</p> <p>An "open bore" 1.5T MRI scanner, Siemens Espree, has been installed in the radiotherapy department in near proximity to a treatment unit to enable patient transport between the two installations, and hence use the MRI for patient positioning. The spatial uncertainty caused by the transport was added to the uncertainty originating from the target definition process, estimated through a review of the scientific literature. The uncertainty in the CT-based workflow was estimated through a literature review.</p> <p>Results</p> <p>The systematic uncertainties, affecting all treatment fractions, are reduced from 3-4 mm (1Sd) with a CT based workflow to 2-3 mm with a MR based workflow. The main contributing factor to this improvement is the exclusion of registration between MR and CT in the planning phase of the treatment.</p> <p>Conclusion</p> <p>Treatment planning directly on MR images reduce the spatial uncertainty for prostate treatments.</p

Multiple Sclerosis Decreases Explicit Counterfactual Processing and Risk Taking in Decision Making

Deficits in decision making (DM) are commonly associated with prefrontal cortical damage, but may occur with multiple sclerosis (MS). There are no data concerning the impact of MS on tasks evaluating DM under explicit risk, where different emotional and cognitive components can be distinguished.Methods: We assessed 72 relapsing-remitting MS (RRMS) patients with mild to moderate disease and 38 healthy controls in two DM tasks involving risk with explicit rules: (1) The Wheel of Fortune (WOF), which probes the anticipated affects of decisions outcomes on future choices; and (2) The Cambridge Gamble Task (CGT) which measures risk taking. Participants also underwent a neuropsychological and emotional assessment, and skin conductance responses (SCRs) were recorded.Results: In the WOF, RRMS patients showed deficits in integrating positive counterfactual information (p <0.005) and greater risk aversion (p <0.001). They reported less negative affect than controls (disappointment: p = 0.007; regret: p = 0.01), although their implicit emotional reactions as measured by post-choice SCRs did not differ. In the CGT, RRMS patients differed from controls in quality of DM (p = 0.01) and deliberation time (p = 0.0002), the latter difference being correlated with attention scores. Such changes did not result in overall decreases in performance (total gains).Conclusions: The quality of DM under risk was modified by MS in both tasks. The reduction in the expression of disappointment coexisted with an increased risk aversion in the WOF and alexithymia features. These concomitant emotional alterations may have implications for better understanding the components of explicit DM and for the clinical support of MS patients

Holoprosencephaly

Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia and growth hormone deficiency are frequent. To date, seven genes have been positively implicated in HPE: Sonic hedgehog (SHH), ZIC2, SIX3, TGIF, PTCH, GLI2 and TDGF1. A molecular diagnosis can be performed by gene sequencing and allele quantification for the four main genes SHH, ZIC2, SIX3 and TGIF. Major rearrangements of the subtelomeres can also be identified by multiplex ligation-dependent probe amplification (MLPA). Nevertheless, in about 70% of cases, the molecular basis of the disease remains unknown, suggesting the existence of several other candidate genes or environmental factors. Consequently, a "multiple-hit hypothesis" of genetic and/or environmental factors (like maternal diabetes) has been proposed to account for the extreme clinical variability. In a practical approach, prenatal diagnosis is based on ultrasound and magnetic resonance imaging (MRI) rather than on molecular diagnosis. Treatment is symptomatic and supportive, and requires a multidisciplinary management. Child outcome depends on the HPE severity and the medical and neurological complications associated. Severely affected children have a very poor prognosis. Mildly affected children may exhibit few symptoms and may live a normal life