Microscopic description for the emergence of collective dissipation in extended quantum systems

Practical implementations of quantum technology are limited by unavoidable effects of decoherence and dissipation. With achieved experimental control for individual atoms and photons, more complex platforms composed by several units can be assembled enabling distinctive forms of dissipation and decoherence, in independent heat baths or collectively into a common bath, with dramatic consequences for the preservation of quantum coherence. The cross-over between these two regimes has been widely attributed in the literature to the system units being farther apart than the bath's correlation length. Starting from a microscopic model of a structured environment (a crystal) sensed by two bosonic probes, here we show the failure of such conceptual relation, and identify the exact physical mechanism underlying this cross-over, displaying a sharp contrast between dephasing and dissipative baths. Depending on the frequency of the system and, crucially, on its orientation with respect to the crystal axes, collective dissipation becomes possible for very large distances between probes, opening new avenues to deal with decoherence in phononic baths

Highly scab-resistant transgenic apple lines achieved by introgression of HcrVf2 controlled by different native promoter lengths

Apple scab, caused by the ascomycete Venturia inaequalis, is the most damaging fungal disease of commercial apple orchards. Functional scab resistance genes are present in some wild Malus species. The HcrVf2 gene, derived from the Vf-region of the wild apple Malus floribunda 821 and encoding a receptor-like protein, has proved to confer scab resistance in a transgenic susceptible cultivar. In order to minimize nonplant DNA in genetically modified apple and to go a step toward the development of cisgenic apples, we have studied the capability of the HcrVf2 gene to confer apple scab resistance when it is controlled by its own promoter. Three promoter deletion constructs containing 115, 288, and 779bp of the 5′ untranslated region and the HcrVf2 gene were used to transform the scab susceptible apple cvs. ‘Gala' and ‘Elstar.' The influence of the promoter length on both the HcrVf2 expression level and the response to V. inaequalis was analyzed in different transgenic lines. Promoter length was found to influence both the constitutive transcription levels of HcrVf2 in transgenic lines and the resistance level. Highly scab resistant ‘Elstar' and ‘Gala' plants were obtained, proving that the HcrVf2 gene controlled by its native promoter is effective in conferring resistance to V. inaequalis similarly as Vf introgressed in apple cvs. through classical breedin

In Silico Identification of MYB and bHLH Families Reveals Candidate Transcription Factors for Secondary Metabolic Pathways in Cannabis sativa L

Plant secondary metabolic pathways are finely regulated by the activity of transcription factors, among which members of the bHLH and MYB subfamilies play a main role. Cannabis sativa L. is a unique officinal plant species with over 600 synthesized phytochemicals having diverse scale-up industrial and pharmaceutical usage. Despite comprehensive knowledge of cannabinoids\u2019 metabolic pathways, very little is known about their regulation, while the literature on flavonoids\u2019 metabolic pathways is still scarce. In this study, we provide the first genome-wide analysis of bHLH and MYB families in C. sativa reference cultivar CBDRx and identification of candidate coding sequences for these transcription factors. Cannabis sativa bHLHs and MYBs were then classified into functional subfamilies through comparative phylogenetic analysis with A. thaliana transcription factors. Analyses of gene structure and motif distribution confirmed that CsbHLHs and CsMYBs belonging to the same evolutionary clade share common features at both gene and amino acidic level. Candidate regulatory genes for key metabolic pathways leading to flavonoid and cannabinoid synthesis in Cannabis were also retrieved. Furthermore, a candidate gene approach was used to identify structural enzyme-coding genes for flavonoid and cannabinoid synthesis. Taken as a whole, this work represents a valuable resource of candidate genes for further investigation of the C. sativa cannabinoid and flavonoid metabolic pathways for genomic studies and breeding programs

Identification of proteins associated with ligand-activated estrogen receptor alpha in human breast cancer cell nuclei by tandem affinity purification and nanoLC-MS/MS.

Estrogen receptor a (ER-a) is a key mediator of estrogen actions in breast cancer (BC) cells. Understanding the effects of ligand-activated ER-a in target cells requires identification of the molecular partners acting in concert with this nuclear receptor to transduce the hormonal signal. We applied tandem affinity purification (TAP), glycerol gradient centrifugation and MS analysis to isolate and identify proteins interacting with ligand-activated ER-a in MCF-7 cell nuclei. This led to the identification of 264 ER-associated proteins, whose functions highlight the hinge role of ER-a in the coordination of multiple hormone-regulated nuclear processes in BC cells

Quantitative expression profiling of highly degraded RNA from formalin-fixed, paraffin-embedded breast tumor biopsies by oligonucleotide microarrays.

Microarray-based gene expression profiling is well suited for parallel quantitative analysis of large numbers of RNAs, but its application to cancer biopsies, particularly formalin-fixed, paraffin-embedded (FFPE) archived tissues, is limited by the poor quality of the RNA recovered. This represents a serious drawback, as FFPE tumor tissue banks are available with clinical and prognostic annotations, which could be exploited for molecular profiling studies, provided that reliable analytical technologies are found. We applied and evaluated here a microarray-based cDNA-mediated annealing, selection, extension and ligation (DASL) assay for analysis of 502 mRNAs in highly degraded total RNA extracted from cultured cells or FFPE breast cancer (MT) biopsies. The study included quantitative and qualitative comparison of data obtained by analysis of the same RNAs with genome-wide oligonucleotide microarrays vs DASL arrays and, by DASL, before and after extensive in vitro RNA fragmentation. The DASL-based expression profiling assay applied to RNA extracted from MCF-7 cells, before or after 24 h stimulation with a mitogenic dose of 17b-estradiol, consistently allowed to detect hormone-induced gene expression changes following extensive RNA degradation in vitro. Comparable results where obtained with tumor RNA extracted from FFPE MT biopsies (6 to 19 years old). The method proved itself sensitive, reproducible and accurate, when compared to results obtained by microarray analysis of RNA extracted from snap-frozen tissue of the same tumor

Modeling acquired resistance to the second-generation androgen receptor antagonist enzalutamide in the TRAMP model of prostate cancer

Enzalutamide (MDV3100) is a potent second-generation androgen receptor antagonist approved for the treatment of castration-resistant prostate cancer (CRPC) in chemotherapy-naïve as well as in patients previously exposed to chemotherapy. However, resistance to enzalutamide and enzalutamide withdrawal syndrome have been reported. Thus, reliable and integrated preclinical models are required to elucidate the mechanisms of resistance and to assess therapeutic settings that may delay or prevent the onset of resistance. In this study, the prostate cancer multistage murine model TRAMP and TRAMP-derived cells have been used to extensively characterize in vitro and in vivo the response and resistance to enzalutamide. The therapeutic profile as well as the resistance onset were characterized and a multiscale stochastic mathematical model was proposed to link the in vitro and in vivo evolution of prostate cancer. The model showed that all therapeutic strategies that use enzalutamide result in the onset of resistance. The model also showed that combination therapies can delay the onset of resistance to enzalutamide, and in the best scenario, can eliminate the disease. These results set the basis for the exploitation of this "TRAMP-based platform" to test novel therapeutic approaches and build further mathematical models of combination therapies to treat prostate cancer and CRPC.Significance: Merging mathematical modeling with experimental data, this study presents the "TRAMP-based platform" as a novel experimental tool to study the in vitro and in vivo evolution of prostate cancer resistance to enzalutamide

Direct regulation of microRNA biogenesis and expression by estrogen receptor beta in hormone-responsive breast cancer.

Estrogen effects on mammary epithelial and breast cancer (BC) cells are mediated by the nuclear receptors ERα and ERβ, transcription factors that display functional antagonism with each other, with ERβ acting as oncosuppressor and interfering with the effects of ERα on cell proliferation, tumor promotion and progression. Indeed, hormone-responsive, ERα+ BC cells often lack ERβ, which when present associates with a less aggressive clinical phenotype of the disease. Recent evidences point to a significant role of microRNAs (miRNAs) in BC, where specific miRNA expression profiles associate with distinct clinical and biological phenotypes of the lesion. Considering the possibility that ERβ might influence BC cell behavior via miRNAs, we compared miRNome expression in ERβ+ vs ERβ- hormone-responsive BC cells and found a widespread effect of this ER subtype on the expression pattern of these non-coding RNAs. More importantly, the expression pattern of 67 miRNAs, including 10 regulated by ERβ in BC cells, clearly distinguishes ERβ+, node-negative, from ERβ-, metastatic, mammary tumors. Molecular dissection of miRNA biogenesis revealed multiple mechanisms for direct regulation of this process by ERβ+ in BC cell nuclei. In particular, ERβ downregulates miR-30a by binding to two specific sites proximal to the gene and thereby inhibiting pri-miR synthesis. On the other hand, the receptor promotes miR-23b, -27b and 24-1 accumulation in the cell by binding in close proximity of the corresponding gene cluster and preventing in situ the inhibitory effects of ERα on pri-miR maturation by the p68/DDX5-Drosha microprocessor complex. These results indicate that cell autonomous regulation of miRNA expression is part of the mechanism of action of ERβ in BC cells and could contribute to establishment or maintenance of a less aggressive tumor phenotype mediated by this nuclear receptor

The Peach v2.0 release: High-resolution linkage mapping and deep resequencing improve chromosome-scale assembly and contiguity

Background: The availability of the peach genome sequence has fostered relevant research in peach and related Prunus species enabling the identification of genes underlying important horticultural traits as well as the development of advanced tools for genetic and genomic analyses. The first release of the peach genome (Peach v1.0) represented a high-quality WGS (Whole Genome Shotgun) chromosome-scale assembly with high contiguity (contig L50 214.2 kb), large portions of mapped sequences (96%) and high base accuracy (99.96%). The aim of this work was to improve the quality of the first assembly by increasing the portion of mapped and oriented sequences, correcting misassemblies and improving the contiguity and base accuracy using high-throughput linkage mapping and deep resequencing approaches. Results: Four linkage maps with 3,576 molecular markers were used to improve the portion of mapped and oriented sequences (from 96.0% and 85.6% of Peach v1.0 to 99.2% and 98.2% of v2.0, respectively) and enabled a more detailed identification of discernible misassemblies (10.4 Mb in total). The deep resequencing approach fixed 859 homozygous SNPs (Single Nucleotide Polymorphisms) and 1347 homozygous indels. Moreover, the assembled NGS contigs enabled the closing of 212 gaps with an improvement in the contig L50 of 19.2%. Conclusions: The improved high quality peach genome assembly (Peach v2.0) represents a valuable tool for the analysis of the genetic diversity, domestication, and as a vehicle for genetic improvement of peach and related Prunus species. Moreover, the important phylogenetic position of peach and the absence of recent whole genome duplication (WGD) events make peach a pivotal species for comparative genomics studies aiming at elucidating plant speciation and diversification processes

Backgrounding steers on temperate grasses mixed with vetch and/or using energy supplementation

Objective The aim was to evaluate backgrounding beef steers on oat + ryegrass pastures mixed with vetch and/or using energy supplementation. Methods A randomized block design with three treatments and three replications was used. The treatments were: grass + supplement (oat + ryegrass + supplementation), legume + supplement (oat + ryegrass + vetch + supplementation) and grass + legume (oat + ryegrass + vetch). A continuous grazing system with a variable stocking rate was used. Twenty-seven intact crossbred steers (1/4 Marchigiana, 1/4 Aberdeen Angus and 2/4 Nellore) aged 7 months old and average weight of 190 kg were used. Steers were supplemented at 1% of the body weight of ground corn. The experiment lasted 84 days, between May and August 2014. Behavioral assessments were performed two times per experimental period, for 24 hours. Results The forage mass was different between treatments, being greater for steers fed without legume. The accumulation rate, forage allowance, and stocking rate did not differ between treatments due to the adequate adjustment of forage allowance. The final weight of animals, as well as the dry matter intake (kg/d), did not differ between treatments. However, forage intake was higher for non-supplemented animals in relation to supplemented steers. Supplement intake did not alter the total digestible nutrient intake due to pasture quality. Animals fed grass + supplement had higher live weight gain per area than those fed grass + legume. Animals without supplementation spent more time in grazing. Conclusion Feeding behavior was not altered by mixing with vetch or supplementation. Non-supplemented animals started the grazing peak earlier and spent more time in grazing than those supplemented; however, the average daily gain was similar between treatments. The live weight gain per hectare was 47% higher in pastures in which the animals received supplementation compared with those mixed with vetch, a consequence of the substitutive effect