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Floral transition under drought conditions is accelerated by enabling ABA-dependent up-regulation of the florigen genes. Modulation of the transition to flowering plays an important role in the adaptation to drought. The drought-escape (DE) response allows plants to adaptively shorten their life cycle to make seeds before severe stress leads to death. However, the molecular basis of the DE response is unknown. A screen of different Arabidopsis (Arabidopsis thaliana) flowering time mutants under DE-triggering conditions revealed the central role of the flower-promoting gene GIGANTEA (GI) and the florigen genes FLOWERING LOCUS T (FT) and TWIN SISTER OF FT (TSF) in the DE response. Further screens showed that the phytohormone abscisic acid is required for the DE response, positively regulating flowering under long-day conditions. Drought stress promotes the transcriptional up-regulation of the florigens in an abscisic acid- and photoperiod-dependent manner, so that early flowering only occurs under long days. Along with the florigens, the floral integrator SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 is also up-regulated in a similar fashion and contributes to the activation of TSF. The DE response was recovered under short days in the absence of the floral repressor SHORT VEGETATIVE PHASE or in GI-overexpressing plants. Our data reveal a key role for GI in connecting photoperiodic cues and environmental stress independently from the central FT/TSF activator CONSTANS. This mechanism explains how environmental cues may act upon the florigen genes in a photoperiodically controlled manner, thus enabling plastic flowering responses.

IntroductionThe virtual environment with realistically rendered fear-inducing stimuli is enough to conduct VR exposure therapy (VRE), although the total control over the virtual environment also enables presentation of stimuli, contexts, and tasks not possible in in vivo exposure therapy (i.e. flight etc.)30 randomized controlled trials revealing high efficacy and effect sizes comparable of VRE-CBT to in vivo exposure therapy. Aerophobia is a very frequent limitation and affect 25% of the population and 30% of the subjects who fly make habitual use of anxiolytics.ObjectivesThe aims of this study is to show that conducting VR exposure in CBT for simple phobia (flight phobia) is effective and is an efficacious treatment for fear and anxiety,Vs other treatments.MethodsParticipants (n = 39; age between 19 and 60 years) in the active arms received individual CBT VR exposure for six sessions and outcome was assessed with questionnaires: MSPS;Rathus Assertiveness Scale (RAS); HAM-A; QMAV; QSAV – (Flying fear); QoL INDEX and a behaviour avoidance test (really take the plane). Wilcoxon tests was using for the statistical analysis.Results36 subjects managed to take the plane at the end of treatment and the results obtained showed a significant difference between “before treatment (T0) and after (T1)” with the exception of the Rathus test. All the SF-36 scales show a significant difference between “before-after”. 3 subjects was dropped outConclusionsUsing VR can be advantageous over standard CBT as a potential solution for treatment avoidance and as an efficient, cost-effective and practical medium of exposure.DisclosureNo significant relationships.

The tumor-suppressor p53 can induce various biological responses. Yet, it is not clear whether it is p53 in vivo promoter selectivity that triggers different transcription programs leading to different outcomes. Our analysis of genome-wide chromatin occupancy by p53 using chromatin immunoprecipitation (ChIP)-seq revealed ‘p53 default program’, that is, the pattern of major p53-bound sites that is similar upon p53 activation by nutlin3a, reactivation of p53 and induction of tumor cell apoptosis (RITA) or 5-fluorouracil in breast cancer cells, despite different biological outcomes. Parallel analysis of gene expression allowed identification of 280 novel p53 target genes, including p53-repressed AURKA . We identified Sp1 as one of the p53 modulators, which confer specificity to p53-mediated transcriptional response upon RITA. Further, we found that STAT3 antagonizes p53-mediated repression of a subset of genes, including AURKA .

Objective: To analyze the effect of the juice obtained from two varieties of sweet orange (Citrus sinensis L. Osbeck), Moro (a blood orange) and Navelina (a blond orange), on fat accumulation in mice fed a standard or a high-fat diet (HFD). Methods: Obesity was induced in male C57/Bl6 mice by feeding a HFD. Moro and Navelina juices were provided instead of water. The effect of an anthocyanin-enriched extract from Moro oranges or purified cyanidin-3-glucoside (C3G) was also analyzed. Body weight and food intake were measured regularly over a 12-week period. The adipose pads were weighted and analyzed histologically; total RNA was also isolated for microarray analysis. Results: Dietary supplementation of Moro juice, but not Navelina juice significantly reduced body weight gain and fat accumulation regardless of the increased energy intake because of sugar content. Furthermore, mice drinking Moro juice were resistant to HFD-induced obesity with no alterations in food intake. Only the anthocyanin extract, but not the purified C3G, slightly affected fat accumulation. High-throughput gene expression analysis of fat tissues confirmed that Moro juice could entirely rescue the high fat-induced transcriptional reprogramming. Conclusion: Moro juice anti-obesity effect on fat accumulation cannot be explained only by its anthocyanin content. Our findings suggest that multiple components present in the Moro orange juice might act synergistically to inhibit fat accumulation.

BackgroundTo determine whether granulocyte colony-stimulating factor (G-CSF) improves clinical outcomes after large ST-elevation myocardial infarction (STEMI) when administered early in patients with left ventricular (LV) dysfunction after successful percutaneous coronary intervention (PCI).MethodsSTEM-AMI OUTCOME was designed as a prospective, multicentre, nationwide, randomised, open-label, phase III trial (ClinicalTrials.gov ID: NCT01969890) to demonstrate the efficacy and safety of early G-CSF administration in reducing 2-year cardiac mortality and morbidity in patients with STEMI with LV ejection fraction ≤45% after PCI. The primary outcome was a composite of all-cause death, recurrence of myocardial infarction and hospitalisation for heart failure. Due to low recruitment and event rates, the study was discontinued and did not achieve adequate statistical power to verify the hypothesis.ResultsPatients were randomly allocated to G-CSF (n=260) or standard of care (SOC; n=261). No difference was found in the composite primary outcome between study groups (HR 1.20; 95% CI 0.63 to 2.28). The 2-year mortality was 2.31% in the G-CSF and 2.68% in the control group (HR 0.88; 95% CI 0.29 to 2.60). Adverse events did not differ between the G-CSF (n=65) and SOC groups (n=58; OR 1.17; 95% CI 0.78 to 1.75). In post hoc analyses on the intervention group, we observed a trend towards fewer composite primary outcomes in patients with low bone marrow (BM) cell mobilisation (n=108) versus those with high mobilisation (n=152, with peak leucocyte count >50×109/L; HR 2.86; 95% CI 0.96 to 8.56). Primary outcomes were lower in patients with severe LV systolic dysfunction at discharge treated with G-CSF than in controls (interaction β±SE, −0.08±0.04; p=0.034).ConclusionsAlthough inconclusive, this is the largest trial in the field of cell-based cardiac repair after STEMI providing evidence of the tolerability and long-term safety of G-CSF treatment. The results prompt further studies to understand which patient can benefit most from BM cell mobilisation.Trial registration number NCT01969890.

Fluorinated polyurethanes characterized by a segmented structure, containing hard segments based on 4,4′-methylenebis (phenylisocyanate) (MDI), chain-extender 1,4 n -butandiol (BDO), and soft blocks like perfluoropolyether (PFPE), and poly- ε -caprolactone (PCL) were synthesized keeping constant the equivalent ratio among reagents, but varying the experimental conditions. Copolymers show a complex micro- and macrostrucrture with different morphology and calorimetry, similar tensile properties and undistinguishable, but strongly upgraded surface properties. The morphology should be governed by the different fluorine content of the polymeric chains along with the hard segment structure; tensile properties are little influenced by the morphology. All these characteristics are interpreted in terms of polymerization procedure which results to be a key parameter for ruling the composition of the different polymeric chains, due to a very limited mutual solubility of the reagents. Surprisingly, a beneficial effect of the catalyst dibutyltindilaurate for the increase of the reaction kinetics among segregated phases in the reaction mass was observed.

The tumour suppressor p53 is a transcription factor that controls cellular stress responses. Here, we dissected the transcriptional programmes triggered upon restoration of p53 in Myc-driven lymphomas, based on the integrated analysis of p53 genomic occupancy and gene regulation. p53 binding sites were identified at promoters and enhancers, both characterized by the pre-existence of active chromatin marks. Only a small fraction of these sites showed the 20 base-pair p53 consensus motif, suggesting that p53 recruitment to genomic DNA was primarily mediated through protein-protein interactions in a chromatin context. p53 also targeted distal sites devoid of activation marks, at which binding was prevalently driven by sequence recognition. In all instances, the relevant motif was the canonical unsplit consensus element, with no clear evidence for p53 recruitment by split motifs. At promoters, p53 binding to the consensus motif was associated with gene induction, but not repression, indicating that the latter was most likely indirect. Altogether, our data highlight key features of genome recognition by p53 and provide unprecedented insight into the pathways associated with p53 reactivation and tumour regression, paving the way for their therapeutic application.

Purpose of Review The portion of the population comprised by those aged 65 years and older is the fastest growing age group. With the aging of Americans, so goes the age of a surgeon’s patients. It is also well established that with aging, the incidence of various diseases also increases. Thus, more surgical care will be consumed by the elderly. The cost of care however will be greater for geriatric patients when compared to younger patients due to the greater incidence of comorbidities in the elderly. The surgical community will need to develop new protocols for the perioperative care of these frail patients in order to provide safe care with acceptable morbidity and mortality rates. Recent Findings Over the past 5 years, there have been notable changes in the surgical management of geriatric patients. Increased evidence in several surgical specialties supports that minimally invasive techniques for traditional open procedures improve outcomes. Additional knowledge regarding the effect of aging on organ function has led to improved stratification and preoperative preparation of patients prior to surgery. An example of this is the establishment of specific triage criteria for geriatric trauma patients. These changes have resulted in reduced morbidity and mortality rates. Summary The elderly form a large portion of surgical patients, and this portion will continue to grow as life expectancy improves. Surgeons must adapt to this changing environment to provide optimal care to geriatric patients.

The surface modification of cellulose opens the way towards almost infinite new applications, making it suitable for functional and sustainable materials. Additionally, it also represents a possibility for up-grading traditional products. In this work, we report about the photo-induced grafting onto cellulose substrates of a highly fluorinated acrylic monomer, characterized by a long perfluoropolyether chain. Grafting changed the surface composition, as assessed by XPS measurements: the values of F/C atomic ratio were close to that of the pure monomer at the most external surface (~13 Å depth). Surface energy was therefore dramatically reduced. This led to interesting modifications of the paper characteristics. The wettability by different liquids was decreased and the stain resistance improved. Moreover, anti-adhesion properties were imparted to the paper sheet. At the same time the bulk properties of the modified fibre network, such as its tensile strength and the burst resistance, were unchanged.

RationaleIn rodents, acute haloperidol treatment induces psychomotor impairments known as catalepsy, which models akinesia in humans and is characterized as an animal model of acute Parkinsonism, whereas sub-chronic haloperidol reduces exploratory behavior, which resembles bradykinesia. Haloperidol-induced catalepsy in rats can be ameliorated by playback of 50-kHz ultrasonic vocalizations (USV), an emotionally and motivationally relevant appetitive auditory stimulus, representing an animal model of paradoxical kinesia. In a condition like PD where patients suffer from chronic motor impairments, it is paramount to assess the long-term symptom relief in an animal model of Parkinsonism.ObjectivesWe investigated whether 50-kHz USV playback ameliorates psychomotor deficits induced by haloperidol in a sub-chronic dosing regimen.MethodsIn phase 1, distance traveled and number of rearing behavior were assessed in an activity chamber in order to investigate whether sub-chronic haloperidol treatment induced psychomotor impairments. In phase 2, we investigated whether 50-kHz USV playback could overcome these impairments by assessing exploratory behaviors and approach behavior towards the sound source in the 50-kHz USV radial maze playback paradigm.ResultsSub-chronic haloperidol treatment led to psychomotor deficits since the distance traveled and number of rearing behavior were reduced as compared to saline control group or baseline. These psychomotor impairments were ameliorated during playback of 50-kHz USV, with haloperidol treated rats showing a clear social approach behavior towards the sound source exclusively during playback.ConclusionsThis study provides evidence that 50-kHz USV playback induces paradoxical kinesia in rats exhibiting motor deficits after sub-chronic haloperidol, as we previously showed after acute haloperidol treatment.