Allelic Variants of HLA-C Upstream Region, PSORS1C3, MICA, TNFA and Genes Involved in Epidermal Homeostasis and Barrier Function Influence the Clinical Response to Anti-IL-12/IL-23 Treatment of Patients with Psoriasis

Several biologic therapies have been developed to treat moderate-to-severe psoriasis, with patients exhibiting different clinical benefits, possibly due to the heterogeneity of pathogenic processes underlying their conditions. Ustekinumab targets the IL-12/IL-23-p40 subunit and inhibits type-1 and type-17 T-cell responses. Although ustekinumab is effective as both short- and long-term treatment, therapeutic response varies considerably among patients. Ustekinumab biosimilars will be commercialized in the very next future, likely broadening the use of this drug in the treatment of psoriasis patients. Our pharmacogenomic study evaluated the influence of 417 single-nucleotide polymorphisms (SNPs) in psoriasis-risk alleles on the clinical response to ustekinumab in a cohort of 152 patients affected by moderate-to-severe plaque-type psoriasis. Differences in SNP pattern characterizing HLA-Cw6(+) or HLA-Cw6(-) patients, showing high or low responses to ustekinumab, were also analysed. We identified twelve SNPs in HLA-C upstream region (rs12189871, rs4406273, rs9348862 and rs9368670), PSORS1C3 (rs1265181), MICA (rs2523497), LCE3A-B intergenic region (rs12030223, rs6701730), CDSN (rs1042127, rs4713436), CCHCR1 (rs2073719) and in TNFA (rs1800610) genes associated with excellent response to ustekinumab. We also found that HLA-Cw6(+) and HLA-Cw6(-) patients carried out distinct patterns of SNPs associated with different clinical responses. The assessment of HLA-C alleles, together with other genetic variants, could be helpful for defining patients who better benefit from anti-IL-12/IL-23 therapy

Evaluation of Variability in the Sweet Orange Germplasm through Next Generation Clonal Fingerprinting

The great phenotypic variability characterizing the sweet orange [Citrus sinensis(L.) Osbeck] germplasm arises from spontaneous bud mutations, causing a diversification into major groups (common, Navel and blood oranges). A huge divergence also occurred within each varietal group. The genetic basis of such variability, also including nutritional and qualitative traits (ripening time, colour, fruit shape, acidity, sugars), is currently uncharacterized, and therefore not exploitable. With the aim of describing the somatic mutation events in the sweet orange group a deep-sequencing of 20 Italian and foreign accessions was performed by Illumina platform, allowing the identification of single nucleotide polymorphisms (SNPs), structural variants (SVs) and large deletions, specific to each varietal group or clone-specific. A subset of SNPs used for the design of two 384 SNP - GoldenGate Assays allowed to genotype 225 CREA sweet orange accessions. The developed markers represent the first reliable molecular tools able to unambiguously fingerprint each somatic mutant. Moreover, they might be used to associate mutations with phenotypic traits, and are a powerful tool for traceability. By using the GoldenGate assay, we have been able to fingerprint several blood orange clones starting from DNAs isolated from leaves or juice. These tools will potentially provide the consumer with a guarantee on the quality and origin of juices, avoiding eventual frauds

Negative emotions in migraineurs dreams : the increased prevalence of oneiric fear and anguish, unrelated to mood disorders

BACKGROUND: Migraineurs brain has shown some functional peculiarities that reflect not only in phonophobia, and photophobia, but also in mood and sleep. Dreaming is a universal mental state characterized by hallucinatory features in which imagery, emotion, motor skills, and memory are created de novo. We evaluated dream contents and associated emotions in migraineurs. MATERIALS AND METHODS: 412 subjects: 219 controls; and 148 migraineurs (66 with aura, MA; 82 without aura, MO), and 45 tension type headache patients (TTH). A semistructured retrospective self-reported questionnaire was used to evaluate dreams. The Generalized Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire (PHQ-9) were administered to evaluate anxiety and depression. RESULTS: Migraineurs showed increased levels of anxiety (P = 0.0002 for MA versus controls, P = 0.004 for MO versus controls). Fear and anguish during dreaming were more frequently reported by migraine patients compared to controls, independently by anxiety and depression scores. DISCUSSION: The brain of migraineurs seems to dream with some peculiar features, all with a negative connotation, as fear and anguish. It may be due to the recorded negative sensations induced by recurrent migraine pain, but it may just reflect a peculiar attitude of the mesolimbic structures of migraineurs brain, activated in both dreaming and migraine attacks

Multi-Objective and Financial Portfolio Optimization of Carrier-Sense Multiple Access Protocols with Cooperative Diversity

8th International Workshop on Multiple Access Communications (MACOM2015), Helsinki, Finland.This paper presents a trade-off design and optimization of a class of wireless carrier-sense multiple access protocols where collision-free transmissions are assisted by the potential cooperative retransmissions of inactive terminals with a correct copy of the original transmission. Terminals are enabled with a decode-and-forward relaying protocol. The analysis is focused on asymmetrical settings, where terminals experience different channel and queuing statistics. This work is based on multi-objective and financial portfolio optimization tools. Each packet transmission is thus regarded not only as a network resource, but also as a financial asset with different values of return and risk (or variance of the return). The objective of this financial optimization is to find the transmission policy that simultaneously maximizes return and minimizes risk in the network. The work is focused on the characterization of the boundaries (envelope) of different types of trade-off performance regions: the conventional throughput region, sum-throughput vs. fairness, sum-throughput vs. power, and return vs. risk regions. Fairness is evaluated by means of the Gini-index, which is a metric commonly used in economics to measure income inequality. Transmit power is directly linked to the global transmission rate. The protocol is shown to outperform non-cooperative solutions under different network conditions that are here discussed

A chromosome-scale assembly reveals chromosomal aberrations and exchanges generating genetic diversity in Coffea arabica germplasm

In order to better understand the mechanisms generating genetic diversity in the recent allotetraploid species Coffea arabica, here we present a chromosome-level assembly obtained with long read technology. Two genomic compartments with different structural and functional properties are identified in the two homoeologous genomes. The resequencing data from a large set of accessions reveals low intraspecific diversity in the center of origin of the species. Across a limited number of genomic regions, diversity increases in some cultivated genotypes to levels similar to those observed within one of the progenitor species, Coffea canephora, presumably as a consequence of introgressions deriving from the so-called Timor hybrid. It also reveals that, in addition to few, early-occurring exchanges between homoeologous chromosomes, there are numerous recent chromosomal aberrations including aneuploidies, deletions, duplications and exchanges. These events are still polymorphic in the germplasm and could represent a fundamental source of genetic variation in such a lowly variable species

Minimal fluoroscopic approaches and factors associated with radiation dose when high-definition mapping is used for supraventricular tachycardia ablation: insight from the CHARISMA registry

Abstract Funding Acknowledgements Type of funding sources: None. Background Limited data exist on factors associated with radiation exposure during ablation procedures when a high definition mapping technology is used. Purpose To report factors associated with radiation exposure and data on feasibility and safety of a minimal fluoroscopic approach using the Rhythmia mapping system in supraventricular tachycardia (SVT) ablation procedures. Methods Consecutive patients indicated for arrhythmia ablation were enrolled in the CHARISMA study at 12 centers. We included in this analysis consecutive right-side procedures performed through a minimal fluoroscopy approach with the Rhythmia mapping system were analyzed. A 3D geometry of chambers of interest was reconstructed on the basis of the electroanatomic information taken from the mapping system. Fluoroscopy was used only if deemed necessary. The effective dose (ED) was calculated using accepted formula. For our purpose high dose exposure was defined as an ED greater than the median value of ED of the population exposed to radiation. Results This analysis included 325 patients (mean age = 56 ± 17 years, 57% male) undergoing SVT procedures (152 AVNRT, 116 AFL, 41 AP and 16 AT). During the study, 27481 seconds of fluoroscopy was used (84.6 ± 224 seconds per procedure), resulting in a mean equivalent ED of 1.1 ± 3.7 mSv per patient. The mean reconstructed RA volume was 99 ± 54 ml in a mean mapping time of 12.2 ± 7 min. The mean number of radiofrequency ablations (RFC) to terminate each arrhythmia was 9.4 ± 9 (mean RFC delivery time equal to 6.7 ± 6 min). 192 procedures (59.1%) were completed without any use of fluoroscopy; during the remaining 133 procedures (39.9%), 206.6 ± 313.4 seconds of fluoroscopy was used (median ED = 1.2 mSv). In a minority of the cases (n = 25, 7.7%) the fluoroscopy time was higher than 5 minutes (median ED = 6.5 mSv), whereas radiologic exposure time greater than 1 minute occurred in ninety cases (27.7%, median ED = 2.1 mSv). On multivariate logistic analysis adjusted for baseline confounders the RFC application time (OR = 1.0014, 95%CI: 1.0007 to 1.0022; p = 0.0001) was independently associated to an ED greater than 1.2 mSv, whereas female gender had an inverse association (0.54, 0.29 to 0.98; p = 0.0435). Acute success was reached in 97.8% of the cases. During a mean of 290.7 ± 169.6 days follow-up, no major adverse events related to the procedure were reported. Overall, the recurrence rate of the primary arrhythmia during follow-up was 2.5%. Conclusions In our experience, arrhythmias ablation through minimal fluoroscopy approach with the use of a novel ablation technology is safe, feasible, and effective in common right atrial arrhythmias. High-dose exposure occurred in a very limited number of cases, without any reduction of the safety and acute and long-term effectiveness profile

A chromosome-anchored eggplant genome sequence reveals key events in Solanaceae evolution

With approximately 450 species, spiny Solanum species constitute the largest monophyletic group in the Solanaceae family, but a high-quality genome assembly from this group is presently missing. We obtained a chromosome-anchored genome assembly of eggplant (Solanum melongena), containing 34,916 genes, confirming that the diploid gene number in the Solanaceae is around 35,000. Comparative genomic studies with tomato (S. lycopersicum), potato (S. tuberosum) and pepper (Capsicum annuum) highlighted the rapid evolution of miRNA:mRNA regulatory pairs and R-type defense genes in the Solanaceae, and provided a genomic basis for the lack of steroidal glycoalkaloid compounds in the Capsicum genus. Using parsimony methods, we reconstructed the putative chromosomal complements of the key founders of the main Solanaceae clades and the rearrangements that led to the karyotypes of extant species and their ancestors. From 10% to 15% of the genes present in the four genomes were syntenic paralogs (ohnologs) generated by the pre-γ, γ and T paleopolyploidy events, and were enriched in transcription factors. Our data suggest that the basic gene network controlling fruit ripening is conserved in different Solanaceae clades, and that climacteric fruit ripening involves a differential regulation of relatively few components of this network, including CNR and ethylene biosynthetic genes