The first high-density sequence characterized SNP-based linkage map of olive (Olea europaea L. subsp. europaea) developed using genotyping by sequencing

A number of linkage maps have been previously developed in olive; however, these are mostly composed of markers that have not been characterized at the sequence level, supplemented with smaller numbers of microsatellite markers. In this investigation, we sought to develop a saturated linkage mapping resource for olive composed entirely of sequence characterized markers. We employed genotyping by sequencing to develop a map of a F2 population derived from the selfing of the cultivar Koroneiki. The linkage map contained a total of 23 linkage groups comprised of 1,597 tagged SNP markers in 636 mapping bins spanning a genetic distance of 1189.7 cM. An additional 6,658 segregating SNPs were associated with the 23 linkage groups identified but their marker order was not determined in this investigation. The SNP markers sequences were submitted to NCBI database. The linkage map produced will be an invaluable resource for the study of tree habit and vigour traits segregating in the progeny, and will assist to anchor and orientate sequencing scaffolds from future genome sequencing efforts

Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals

Despite multiple sexual exposure to HIV-1 virus, some individuals remain HIV-1 seronegative (exposed seronegative, ESN). The mechanisms underlying this resistance remain still unclear, although a multifactorial pathogenesis can be hypothesised. Although several genetic factors have been related to HIV-1 resistance, the homozigosity for a mutation in CCR5 gene (the 32 bp deletion, i.e. CCR5-Delta32 allele) is presently considered the most relevant one. In the present study we analysed the genotype at CCR5 locus of 30 Italian ESN individuals (case group) who referred multiple unprotected heterosexual intercourse with HIV-1 seropositive partner(s), for at least two years. One hundred and twenty HIV-1 infected patients and 120 individuals representative of the general population were included as control groups. Twenty percent of ESN individuals had heterozygous CCR5-Delta 32 genotype, compared to 7.5% of HIV-1 seropositive and 10% of individuals from the general population, respectively. None of the analysed individuals had CCR5-Delta 32 homozygous genotype. Sequence analysis of the entire open reading frame of CCR5 was performed in all ESN subjects and no polymorphisms or mutations were identified. Moreover, we determined the distribution of C77G variant in CD45 gene, which has been previously related to HIV-1 infection susceptibility. The frequency of the C77G variant showed no significant difference between ESN subjects and the two control groups. In conclusion, our data show a significantly higher frequency of CCR5-Delta 32 heterozygous genotype (p = 0.04) among the Italian heterosexual ESN individuals compared to HIV-1 seropositive patients, suggesting a partial protective role of CCR5-Delta 32 heterozygosity in this cohort

Polymorphism of Beta2-Adrenoceptor and Regular Use of Formoterol in Asthma: Preliminary Results

Polymorphism at codon 16 of the beta2-adrenoceptor (beta2-AR) affects the responsiveness to salmeterol in asthmatics. Data concerning formoterol are more controversial in the literature. The aim of this study was to verify whether homozygous for arginine-16 (ArgArg16) and homozygous for glycine-16 (GlyGly16) genotypes differently influence the long-term responsiveness to formoterol. Twenty-nine patients with mild-to-moderate asthma, in stable clinical conditions, underwent genotyping at codon 16 of the beta2-AR by RFLP-PCR assay. The effects of a 4-week monotherapy with formoterol (12 μg BID) were tested on the peak expiratory flow (PEF) variability and the forced expiratory volume in 1 sec (FEV1) slope of the dose-response curve to salbutamol. Variability in PEF significantly increased during the 4-week treatment period in 14 patients with GlyGly16, but not in 15 patients with ArgArg16 and ArgGly16 (P=0.032). The FEV1 slope of the dose-response curve to salbutamol decreased after the 4-week treatment period in GlyGly16, but not in pooled ArgArg16 and ArgGly16 patients. This study provides preliminary evidence that tolerance to formoterol develops more frequently in asthmatics with GlyGly16 genotype. If confirmed in a larger population, this finding might be useful in choosing the bronchodilator therapy on the basis of genetic polymorphism of the beta2-AR

Wigner-function theory and decoherence of the quantum-injected optical parametric amplifier

Recent experimental results demonstrated the generation of a quantum superpositon (MQS), involving a number of photons in excess of 5x10^4, which showed a high resilience to losses. In order to perform a complete analysis on the effects of de-coherence on this multiphoton fields, obtained through the Quantum Injected Optical Parametric Amplifier (QIOPA), we invesigate theoretically the evolution of the Wigner functions associated to these states in lossy conditions. Recognizing the presence of negative regions in the W-representation as an evidence of non-classicality, we focus our analysis on this feature. A close comparison with the MQS based on coherent states allows to identify differences and analogies.Comment: 29 pages, 25 figure

Aortic centres should represent the standard of care for acute aortic syndrome

Background Existing evidence suggests that patients affected by acute aortic syndromes (AAS) may benefit from treatment at dedicated specialized aortic centres. The purpose of the present study was to perform a meta-analysis to evaluate the impact aortic service configuration has in clinical outcomes in AAS patients. Methods The design was a quantitative and qualitative review of observational studies. We searched PubMed/ MEDLINE, EMBASE, and Cochrane Library from inception to the end of December 2017 to identify eligible articles. Areas of interest included hospital and surgeon volume activity, presence of a multidisciplinary thoracic aortic surgery program, and a dedicated on-call aortic team. Participants were patients undergoing repair for AAS, and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were adopted for synthesizing hospital/30-day mortality. Results A total of 79,131 adult patients from a total of 30 studies were obtained. No randomized studies were identified. Pooled unadjusted ORs showed that patients treated in high-volume centres or by high-volume surgeons were associated with lower mortality rates (OR 0.51; 95% CI 0.46-0.56, and OR 0.41, 95% CI 0.25-0.66, respectively). Pooled adjusted estimates for both high-volume centres and surgeons confirmed these survival benefits (adjusted OR, 0.56; 95% CI 0.45-0.70, respectively). Patients treated in centres that introduced a specific multidisciplinary aortic program and a dedicated on-call aortic team also showed a significant reduction in mortality (OR 0.31; 95% CI 0.19-0.5, and OR 0.37; 95% CI 0.15-0.87, respectively). Conclusions We found that specialist aortic care improves outcomes and decreases mortality in patients affected by AAS

Deletion of Murine SMN Exon 7 Directed to Skeletal Muscle Leads to Severe Muscular Dystrophy

Spinal muscular atrophy (SMA) is characterized by degeneration of motor neurons of the spinal cord associated with muscle paralysis and caused by mutations of the survival motor neuron gene (SMN). To determine whether SMN gene defect in skeletal muscle might have a role in SMA pathogenesis, deletion of murine SMN exon 7, the most frequent mutation found in SMA, has been restricted to skeletal muscle by using the Cre-loxP system. Mutant mice display ongoing muscle necrosis with a dystrophic phenotype leading to muscle paralysis and death. The dystrophic phenotype is associated with elevated levels of creatine kinase activity, Evans blue dye uptake into muscle fibers, reduced amount of dystrophin and upregulation of utrophin expression suggesting a destabilization of the sarcolemma components. The mutant mice will be a valuable model for elucidating the underlying mechanism. Moreover, our results suggest a primary involvement of skeletal muscle in human SMA, which may contribute to motor defect in addition to muscle denervation caused by the motor neuron degeneration. These data may have important implications for the development of therapeutic strategies in SMA

Establishing a Reference Baseline for Midday Stem Water Potential in Olive and Its Use for Plant-Based Irrigation Management

12 páginas.- 7 figuras.- 4 tablas.- 55 referencias.-Midday stem water potential (SWP) is rapidly becoming adopted as a standard tool for plant-based irrigation management in many woody perennial crops. A reference or “baseline” SWP has been used in some crops (almond, prune, grape, and walnut) to account for the climatic influence of air vapor pressure deficit (VPD) on SWP under non-limiting soil moisture conditions. The baseline can be determined empirically for field trees maintained under such non-limiting conditions, but such conditions are difficult to achieve for an entire season. We present the results of an alternative survey-based approach, using a large set of SWP and VPD data collected over multiple years, from irrigation experiments in olive orchards located in multiple countries [Spain, United States (California), Italy, and Argentina]. The relation of SWP to midday VPD across the entire data set was consistent with an upper limit SWP which declined with VPD, with the upper limit being similar to that found in Prunus. A best fit linear regression estimate for this upper limit (baseline) was found by selecting the maximum R2 and minimum probability for various upper fractions of the SWP/VPD relation. In addition to being surprisingly similar to the Prunus baseline, the olive baseline was also similar (within 0.1 MPa) to a recently published mechanistic olive soil-plant-atmosphere-continuum (SPAC) model for “super high density” orchard systems. Despite similarities in the baseline, the overall physiological range of SWP exhibited by olive extends to about −8 MPa, compared to about −4 MPa for economically producing almond. This may indicate that, despite species differences in physiological responses to low water availability (drought), there may be convergent adaptations/acclimations across species to high levels of water availability. Similar to its use in other crops, the olive baseline will enable more accurate and reproducible plant-based irrigation management for both full and deficit irrigation practices, and we present tentative SWP guidelines for this purpose. Copyright © 2021 Shackel, Moriana, Marino, Corell, Pérez-López, Martin-Palomo, Caruso, Marra, Agüero Alcaras, Milliron, Rosecrance, Fulton and Searles.In addition to the authors institutions, this research was supported by the Olive Oil Commission of California and the California Olive Committee.Peer reviewe

Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors.

It is generally assumed that recurrent mutations within a given cancer driver gene elicit similar drug responses. Cancer genome studies have identified recurrent but divergent missense mutations affecting the substrate-recognition domain of the ubiquitin ligase adaptor SPOP in endometrial and prostate cancers. The therapeutic implications of these mutations remain incompletely understood. Here we analyzed changes in the ubiquitin landscape induced by endometrial cancer-associated SPOP mutations and identified BRD2, BRD3 and BRD4 proteins (BETs) as SPOP-CUL3 substrates that are preferentially degraded by endometrial cancer-associated SPOP mutants. The resulting reduction of BET protein levels sensitized cancer cells to BET inhibitors. Conversely, prostate cancer-specific SPOP mutations resulted in impaired degradation of BETs, promoting their resistance to pharmacologic inhibition. These results uncover an oncogenomics paradox, whereby mutations mapping to the same domain evoke opposing drug susceptibilities. Specifically, we provide a molecular rationale for the use of BET inhibitors to treat patients with endometrial but not prostate cancer who harbor SPOP mutations