Targeting VIP and PACAP receptor signalling: new therapeutic strategies in multiple sclerosis

MS (multiple sclerosis) is a chronic autoimmune and neurodegenerative pathology of the CNS (central nervous system) affecting approx. 2.5 million people worldwide. Current and emerging DMDs (disease-modifying drugs) predominantly target the immune system. These therapeutic agents slow progression and reduce severity at early stages of MS, but show little activity on the neurodegenerative component of the disease. As the latter determines permanent disability, there is a critical need to pursue alternative modalities. VIP (vasoactive intestinal peptide) and PACAP (pituitary adenylate cyclase-activating peptide) have potent anti-inflammatory and neuroprotective actions, and have shown significant activity in animal inflammatory disease models including the EAE (experimental autoimmune encephalomyelitis) MS model. Thus, their receptors have become candidate targets for inflammatory diseases. Here, we will discuss the immunomodulatory and neuroprotective actions of VIP and PACAP and their signalling pathways, and then extensively review the structure–activity relationship data and biophysical interaction studies of these peptides with their cognate receptors

Observational constraints to boxy/peanut bulge formation time

Boxy/peanut bulges are considered to be part of the same stellar structure as bars and both could be linked through the buckling instability. The Milky Way is our closest example. The goal of this letter is determining if the mass assembly of the different components leaves an imprint in their stellar populations allowing to estimate the time of bar formation and its evolution. To this aim we use integral field spectroscopy to derive the stellar age distributions, SADs, along the bar and disc of NGC 6032. The analysis shows clearly different SADs for the different bar areas. There is an underlying old (>=12 Gyr) stellar population for the whole galaxy. The bulge shows star formation happening at all times. The inner bar structure shows stars of ages older than 6 Gyrs with a deficit of younger populations. The outer bar region presents a SAD similar to that of the disc. To interpret our results, we use a generic numerical simulation of a barred galaxy. Thus, we constrain, for the first time, the epoch of bar formation, the buckling instability period and the posterior growth from disc material. We establish that the bar of NGC 6032 is old, formed around 10 Gyr ago while the buckling phase possibly happened around 8 Gyr ago. All these results point towards bars being long-lasting even in the presence of gas.Comment: Accepted for publication in MNRAS Letter

Prospects for a Dark Matter annihilation signal towards the Sagittarius dwarf galaxy with ground based Cherenkov telescopes

Dwarf galaxies are widely believed to be among the best targets for indirect dark matter searches using high-energy gamma rays; and indeed gamma-ray emission from these objects has long been a subject of detailed study for ground-based atmospheric Cherenkov telescopes. Here, we update current exclusion limits obtained on the closest dwarf, the Sagittarius dwarf galaxy, in light of recent realistic dark matter halo models. The constraints on the velocity-weighted annihilation cross section of the dark matter particle are of a few 10$^{-23}$ cm$^{3}$s$^{-1}$ in the TeV energy range for a 50 h exposure. The limits are extrapolated to the sensitivities of future Cherenkov Telescope Arrays. For 200 h of observation time, the sensitivity at 95% C.L. reaches 10$^{-25}$ cm$^{3}$s$^{-1}$. Possible astrophysical backgrounds from gamma-ray sources dissembled in Sagittarius dwarf are studied. It is shown that with long-enough observation times, gamma-ray background from millisecond pulsars in a globular cluster contained within Sagittarius dwarf may limit the sensitivity to dark matter annihilations.Comment: 12 pages, 5 figures, 2 tables, accepted for publication in Ap

Effect of pretreatment with low-frequency ultrasound on quality parameters in gulupa (Passiflora edulis sims) pulp

The Gulupa (Passiflora edulis f. edulis Sims) is an expression of South America’s tropics’ biodiversity, and a source of B vitamins and amino acids. It is a climacteric export fruit for which it is necessary to incorporate emerging technologies for its conservation and transport. This work investigated the effect of ultrasound on gulupa pulp and verified the stability of the characters of interest in the shelf life of 20 days. Six treatments and a control sample were used, evaluated in triplicate, and varied in frequency (30 and 40 kHz) with an exposure time of 10, 20, and 30 min. A statistical analysis of unidirectional variances and Dunnett’s test was used. It was found that the ultrasound treatments did not affect the pH or the titratable acidity. Soluble solid results presented a significant increase (p < 0.05) (from 13.4 to 14.8% w/v) in the antioxidant capacity (from 1.13 to 1.54 µmol Trolox Equivalent (TE)/g by the ABTS•+ (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) Cationic Radical Assay and from 3.3 to 3.7 µmol TE/g by the DPPH· (2,2-diphenyl-1-picrilhydrazil) Radical Scavenging Assay). During the shelf life, ascorbic acid was the parameter that varied most (p < 0.05). It decreased from 42.7 to 21.6 mg ascorbic acid/100 g of pulp in the control sample. However, a smaller decrease was observed (23.8–24.5 mg ascorbic acid/100 g of pulp) in the 40 kHz treatments. The smallest global color difference (∆E) for the control was found in the 40 kHz treatment at 30 min through the entire shelf life (day 0 to 20). Ultrasound treatment offers a new strategy to improve and extend the shelf life of chilled gulupa pulp

Design and development of a multiplex microsatellite panel for the genetic characterisation and diversity assessment of domestic turkey (Meleagris gallopavo gallopavo)

Domestic turkey production generally utilises only a few genetically improved lines, and local breeds are severely endangered as a result. Furthermore, the genetic resources of domestic turkeys have not been properly investigated, which could, ultimately, lead to the extinction of local breeds and negatively affect their corresponding genetic diversity and environmental adaptation. Although, several microsatellite markers have been designed for mapping and quantitative trait locus analysis, there is no standard panel of markers for genetic characterisation or genetic diversity assessment. Accordingly, the present study aimed to develop a set of polymorphic microsatellite markers that could be used for international turkey population studies. Thirty-nine microsatellites were selected based on polymorphism, DNA sequence and chromosome position, as well as on amplification efficiency, success rate and the absence of nonspecific amplification. The markers were screened using 105 DNA samples from local turkey breeds from Mexico, the United States, Italy, Brazil, Egypt and Spain. A total of 401 alleles were identified, with a mean number of alleles per marker of 10.28 \ub1 4.25. All microsatellites were polymorphic, with at least four alleles and no more than 19 alleles. Furthermore, allelic richness ranged from 3.810 to 17.985, mean heterozygosity ranged from 0.452 \ub1 0.229 to 0.667 \ub1 0.265, polymorphic information content values ranged from 0.213 (MNT264) to 0.850 (RHT0024) and the mean Fis value was 0.322. Overall, the panel was highly polymorphic and exhibited moderate Hardy\u2013Weinberg disequilibrium, thereby indicating its value as a tool for biodiversity and population structure studies that could play an important role in promoting the conservation of local turkey breeds.Highlights Important genetic resources reside within indigenous turkey populations. These are linked to historic heritage production values and breeds. It is important to preserve this heritage and genetic diversity, which threatens to be lost as production systems focus on production characteristics. Microsatellite markers, even though, they are now replaced by single nucleotide polymorphism automatic genotyping platforms in many fields of genetics, remain a viable alternative thanks to their cheapness and simplicity of study which makes them particularly useful when the population to be studied lacks information of the prior genetic structure

The AMS-02 RICH Imager Prototype - In-Beam Tests with 20 GeV/c per Nucleon Ions -

A prototype of the AMS Cherenkov imager (RICH) has been tested at CERN by means of a low intensity 20 GeV/c per nucleon ion beam obtained by fragmentation of a primary beam of Pb ions. Data have been collected with a single beam setting, over the range of nuclear charges 2<Z<~45 in various beam conditions and using different radiators. The charge Z and velocity beta resolutions have been measured.Comment: 4 pages, contribution to the ICRC 200

Telomere Length Shows No Association with BRCA1 and BRCA2 Mutation Status

This study aimed to determine whether telomere length (TL) is a marker of cancer risk or genetic status amongst two cohorts of BRCA1 and BRCA2 mutation carriers and controls. The first group was a prospective set of 665 male BRCA1/2 mutation carriers and controls (mean age 53 years), all healthy at time of enrolment and blood donation, 21 of whom have developed prostate cancer whilst on study. The second group consisted of 283 female BRCA1/2 mutation carriers and controls (mean age 48 years), half of whom had been diagnosed with breast cancer prior to enrolment. TL was quantified by qPCR from DNA extracted from peripheral blood lymphocytes. Weighted and unweighted Cox regressions and linear regression analyses were used to assess whether TL was associated with BRCA1/2 mutation status or cancer risk. We found no evidence for association between developing cancer or being a BRCA1 or BRCA2 mutation carrier and telomere length. It is the first study investigating TL in a cohort of genetically predisposed males and although TL and BRCA status was previously studied in females our results don't support the previous finding of association between hereditary breast cancer and shorter TL

Quantum computations on a topologically encoded qubit

The construction of a quantum computer remains a fundamental scientific and technological challenge, in particular due to unavoidable noise. Quantum states and operations can be protected from errors using protocols for fault-tolerant quantum computing (FTQC). Here we present a step towards this by implementing a quantum error correcting code, encoding one qubit in entangled states distributed over 7 trapped-ion qubits. We demonstrate the capability of the code to detect one bit flip, phase flip or a combined error of both, regardless on which of the qubits they occur. Furthermore, we apply combinations of the entire set of logical single-qubit Clifford gates on the encoded qubit to explore its computational capabilities. The implemented 7-qubit code is the first realization of a complete Calderbank-Shor-Steane (CSS) code and constitutes a central building block for FTQC schemes based on concatenated elementary quantum codes. It also represents the smallest fully functional instance of the color code, opening a route towards topological FTQC

A broad spectrum of genomic changes in latinamerican patients with EXT1/EXT2-CDG

Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). In contrast, solitary osteochondroma (SO) is a non-hereditary condition. EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. We present the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO). Sixty-three percent of all MO cases presented severe phenotype and two malignant transformations to chondrosarcoma (7%). We found the mutant allele in 78% of MO patients. Ten mutations were novel. The disease-causing mutations remained unknown in 22% of the MO patients and in all SO patients. No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. Neither EXT1 nor EXT2 protein could be detected in this sample. This is the first Latin American research program on EXT1/EXT2-CDG.Fil: Delgado, M. A.. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Martinez Domenech, G.. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Sarrión, P.. Universidad de Barcelona; EspañaFil: Urreizti, R.. Universidad de Barcelona; EspañaFil: Zecchini, L.. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Robledo, H. H.. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Segura, F.. Universidad Nacional de Córdoba; ArgentinaFil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Balcells, S.. Universidad de Barcelona; EspañaFil: Grinberg, D.. Universidad de Barcelona; EspañaFil: Asteggiano, Carla Gabriela. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Est.de Las Metabolopatias Congenitas. Cátedra de Clinica Pediatrica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

The Ring Imaging Cherenkov detector (RICH) of the AMS experiment

The Alpha Magnetic Spectrometer (AMS) experiment to be installed on the International Space Station (ISS) will be equipped with a proximity focusing Ring Imaging Cherenkov (RICH) detector for measuring the electric charge and velocity of the charged cosmic particles. A RICH prototype consisting of 96 photomultiplier units, including a piece of the conical reflector, was built and its performance evaluated with ion beam data. Preliminary results of the in-beam tests performed with ion fragments resulting from collisions of a 158 GeV/c/nuc primary beam of Indium ions (CERN SPS) on a Pb target are reported. The collected data included tests to the final front-end electronics and to different aerogel radiators. Cherenkov rings for a large range of charged nuclei and with reflected photons were observed. The data analysis confirms the design goals. Charge separation up to Fe and velocity resolution of the order of 0.1% for singly charged particles are obtained.Comment: 29th International Conference on Cosmic Rays (Pune, India