Milagro limits and HAWC sensitivity for the rate-density of evaporating Primordial Black Holes

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On the sensitivity of the HAWC observatory to gamma-ray bursts

We present the sensitivity of HAWC to Gamma Ray Bursts (GRBs). HAWC is a very high-energy gamma-ray observatory currently under construction in Mexico at an altitude of 4100 m. It will observe atmospheric air showers via the water Cherenkov method. HAWC will consist of 300 large water tanks instrumented with 4 photomultipliers each. HAWC has two data acquisition (DAQ) systems. The main DAQ system reads out coincident signals in the tanks and reconstructs the direction and energy of individual atmospheric showers. The scaler DAQ counts the hits in each photomultiplier tube (PMT) in the detector and searches for a statistical excess over the noise of all PMTs. We show that HAWC has a realistic opportunity to observe the high-energy power law components of GRBs that extend at least up to 30 GeV, as it has been observed by Fermi LAT. The two DAQ systems have an energy threshold that is low enough to observe events similar to GRB 090510 and GRB 090902b with the characteristics observed by Fermi LAT. HAWC will provide information about the high-energy spectra of GRBs which in turn could help to understanding about e-pair attenuation in GRB jets, extragalactic background light absorption, as well as establishing the highest energy to which GRBs accelerate particles

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

The effect of rearing - temperature and sex on swimming performance of zebrafish (Danio rerio)

Το zebrafish είναι ένα μικρό, πολύχρωμο, τροπικό ψάρι που αποικίζει μικρές λίμνες και ρυάκια της Νοτιοανατολικής Ασίας. Τις τελευταίες δεκαετίες, αποτελεί έναν πολύ σημαντικό οργανισμό-μοντέλο σε διάφορα πεδία έρευνας όπως Νευροβιολογία, Αναπτυξιακή Βιολογία και Γενετική. Παρόλα αυτά, μόνο πρόσφατα έχουν αρχίσει να μελετώνται διάφορα βασικά στοιχεία της βιολογίας και της οικολογίας του. Η κολυμβητική ικανότητα, αποτελεί ένα πολύ σημαντικό χαρακτηριστικό για την επιβίωση των ψαριών καθώς η μέγιστη τιμή της επηρεάζει σημαντικές πτυχές της ζωής τους όπως την απόκτηση τροφής, την εύρεση ταιριού και την αποφυγή των θηρευτών. Η θερμοκρασία ανάπτυξης και το φύλο, είναι δύο παράγοντες που έχουν αποδειχθεί πολύ σημαντικοί ως προς την επίδρασή τους στην κολυμβητική επίδοση. Έτσι στην παρούσα μελέτη, εξετάστηκε η επίδραση του φύλου στην κολυμβητική ικανότητα, σε zebrafish από διαφορετικές θερμοκρασίες εκτροφής. Για το σκοπό αυτό, εκτράφηκαν συνολικά 4 πληθυσμοί σε διαφορετικές θερμοκρασίες νερού (22, 25, 28 και 31οC) και στη συνέχεια αφού εγκλιματίστηκαν όλοι σε μία κοινή θερμοκρασία (26,5οC), υποβλήθηκαν σε ασκήσεις κολύμβησης με σκοπό την εύρεση της μέγιστης κρίσιμης σχετικής ταχύτητας (RUcrit) για κάθε περίπτωση. Επίσης, επειδή η συσσώρευση του γαλακτικού οξέος στους μύες καθορίζει σε μεγάλο βαθμό την ικανότητα κολύμβησης, η εργασία πλαισιώθηκε από τον προσδιορισμό της συγκέντρωσης του γαλακτικού οξέος στους μύες πριν και μετά από εξουθενωτική άσκηση. Η θερμοκρασία ανάπτυξης φαίνεται να επιδρά στην κολυμβητική ικανότητα μόνο στην περίπτωση των αρσενικών ατόμων, με τα άτομα των 22 οC να εμφανίζουν στατιστικά χαμηλότερη επίδοση από τα άτομα των 31οC. Τα αποτελέσματα εμφάνισαν στατιστικά σημαντικές διαφορές ανάμεσα σε αρσενικά και θηλυκά που αναπτύχθηκαν στους 31οC, με τα αρσενικά να επιτυγχάνουν καλύτερη επίδοση. Η διαφορά αυτή δεν μπορεί να εξηγηθεί από μεταβολικής σκοπιάς, καθώς με βάση τα αποτελέσματα της συγκέντρωσης του γαλακτικού οξέος στους μύες, τα θηλυκά φαίνονται ικανά για μεγαλύτερες επιδόσεις. Έτσι, η διαφοροποίηση της κολυμβητικής ικανότητας μπορεί τελικά να αποδοθεί είτε στην άμεση επίδραση του επιπλέον όγκου των αβγών που έχουν τα θηλυκά και το σχετικό εμπόδιο στην κίνηση που αυτός ο όγκος προκαλεί (λόγω μεγαλύτερης διατομής ή/και μικρότερης αναλογίας μυϊκής μάζας/μάζα σώματος), ή στην έμμεση επίδραση αυτού στις ιδιότητες συστολής (contractile properties) του μυϊκού ιστού. Ενδιαφέρουσες προεκτάσεις στο θέμα αυτό, θα ήταν η σύγκριση κολυμβητικών επιδόσεων μεταξύ θηλυκών ατόμων πριν και μετά την ωοτοκία, η μελέτη της επίδρασης της ωοτοκίας στην ποσότητα και το μέγεθος των μυϊκών ινών και στη σχετική κατανομή της μυϊκής μάζας στο σώμα των θηλυκών και τέλος να εξετασθεί αν υπάρχει διαφορετική επίδραση της θερμοκρασίας ανάπτυξης στην οντογένεση των μυών ανάμεσα στα αρσενικά και τα θηλυκά άτομα.Zebrafish is a small, colourful, tropical fish inhabiting small ponds and slow moving streams in Southeast Asia. For the past few decades, it has been a very important model-organism in research fields such as Neurobiology, Developmental Biology and Genetics. Even though, only recently did the researchers start to examine the basic aspects of its biology and ecology. It is widely known that swimming performance is a very important characteristic for fish survival, as it can affect food capture, mating success and the escape from predators. Developmental temperature and sex are two well known factors that strongly affect swimming capacity of fish. Therefore, in the present study, the effect of sex in the swimming performance of zebrafish reared in different temperatures was examined. For this purpose, 4 populations were reared in different water temperatures (22, 25, 28 and 31οC) and after being acclimatized in a common temperature (26.5οC) for over a month, they were subjected to swimming exercises in order to evaluate the maximum relative critical velocity (RUcrit) in each case. Moreover, as the accumulation of the lactate in fish muscles defines at a great extend their exercise ability, the muscle lactate concentrations before and after exhaustive exercise were also measured. Rearing temperature seems to affect swimming capacity only in the case of male zebrafish, as the fish that were reared in 22οC showed statistically significant lower performance than the ones reared in 31οC. Furthermore, the results showed statistically significant differences between males and females that were reared in 31οC, where the males turned out to be faster swimmers. This differentiation cannot be explained from a metabolic aspect, because as the measurements of the muscle lactate concentrations revealed, the females seem capable of higher performances. Therefore, the observed difference in swimming capacity is probably due to the added mass of eggs and its associated drag (due to larger girth and/or lower muscle power to body mass ratio), or the changes in the contractile properties of the muscles. In order to shed more light in this subject, future work could include comparing swimming performances of female zebrafish before and right after spawning, studying the effect of pregnancy on quantity and size of muscle fibres and the relative distribution of muscle tissue in fish body and examining if the temperature affects differently the ontogeny of muscle in males and females

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease

Verification of the Optical System of the 9.7-m Prototype Schwarzschild-Couder Telescope

International audienceFor the first time in the history of ground-based $\gamma$-ray astronomy, the on-axis performance of the dual mirror, aspheric, aplanatic Schwarzschild-Couder optical system has been demonstrated in a $9.7$-m aperture imaging atmospheric Cherenkov telescope. The novel design of the prototype Schwarzschild-Couder Telescope (pSCT) is motivated by the need of the next-generation Cherenkov Telescope Array (CTA) observatory to have the ability to perform wide ($\geq 8^{\circ}$) field-of-view observations simultaneously with superior imaging of atmospheric cascades (resolution of $0.067^{\circ}$ per pixel or better). The pSCT design, if implemented in the CTA installation, has the potential to improve significantly both the $\gamma$-ray angular resolution and the off-axis sensitivity of the observatory, reaching nearly the theoretical limit of the technique and thereby making a major impact on the CTA observatory sky survey programs, follow-up observations of multi-messenger transients with poorly known initial localization, as well as on the spatially resolved spectroscopic studies of extended $\gamma$-ray sources. This contribution reports on the initial alignment procedures and point-spread-function results for the challenging segmented aspheric primary and secondary mirrors of the pSCT