Concurrence of Danish Dementia and Cataract: Insights from the Interactions of Dementia Associated Peptides with Eye Lens α-Crystallin

Familial Danish Dementia (FDD) is an autosomal disease, which is distinguished by gradual loss of vision, deafness, progressive ataxia and dementia. Cataract is the first manifestation of the disease. In this article, we demonstrate a specific correlation between the poisoning of the chaperone activity of the rat eye lens α-crystallins, loss of lens transparency in organ culture by the pathogenic form of the Danish dementia peptide, i.e. the reduced Danish dementia peptide (redADan peptide), by a combination of ex vivo, in vitro, biophysical and biochemical techniques. The interaction of redADan peptide and lens crystallins are very specific when compared with another chaperone, HSP-70, underscoring the specificity of the pathogenic form of Danish dementia peptide, redADan, for the early onset of cataract in this disease

Drosophila Dynein Intermediate Chain Gene, Dic61B, Is Required for Spermatogenesis

This study reports the identification and characterization of a novel gene, Dic61B, required for male fertility in Drosophila. Complementation mapping of a novel male sterile mutation, ms21, isolated in our lab revealed it to be allelic to CG7051 at 61B1 cytogenetic region, since two piggyBac insertion alleles, CG7051c05439 and CG7051f07138 failed to complement. CG7051 putatively encodes a Dynein intermediate chain. All three mutants, ms21, CG7051c05439 and CG7051f07138, exhibited absolute recessive male sterility with abnormally coiled sperm axonemes causing faulty sperm individualization as revealed by Phalloidin staining in Don Juan-GFP background. Sequencing of PCR amplicons uncovered two point mutations in ms21 allele and confirmed the piggyBac insertions in CG7051c05439 and CG7051f07138 alleles to be in 5′UTR and 4th exon of CG7051 respectively, excision of which reverted the male sterility. In situ hybridization to polytene chromosomes demonstrated CG7051 to be a single copy gene. RT-PCR of testis RNA revealed defective splicing of the CG7051 transcripts in mutants. Interestingly, expression of cytoplasmic dynein intermediate chain, α, β, γ tubulins and α-spectrin was normal in mutants while ultra structural studies revealed defects in the assembly of sperm axonemes. Bioinformatics further highlighted the homology of CG7051 to axonemal dynein intermediate chain of various organisms, including DNAI1 of humans, mutations in which lead to male sterility due to immotile sperms. Based on these observations we conclude that CG7051 encodes a novel axonemal dynein intermediate chain essential for male fertility in Drosophila and rename it as Dic61B. This is the first axonemal Dic gene of Drosophila to be characterized at molecular level and shown to be required for spermatogenesis

Particle identification studies with a full-size 4-GEM prototype for the ALICE TPC upgrade

A large Time Projection Chamber is the main device for tracking and charged-particle identification in the ALICE experiment at the CERN LHC. After the second long shutdown in 2019/20, the LHC will deliver Pb beams colliding at an interaction rate of about 50 kHz, which is about a factor of 50 above the present readout rate of the TPC. This will result in a significant improvement on the sensitivity to rare probes that are considered key observables to characterize the QCD matter created in such collisions. In order to make full use of this luminosity, the currently used gated Multi-Wire Proportional Chambers will be replaced. The upgrade relies on continuously operated readout detectors employing Gas Electron Multiplier technology to retain the performance in terms of particle identification via the measurement of the specific energy loss by ionization d$E$/d$x$. A full-size readout chamber prototype was assembled in 2014 featuring a stack of four GEM foils as an amplification stage. The performance of the prototype was evaluated in a test beam campaign at the CERN PS. The d$E$/d$x$ resolution complies with both the performance of the currently operated MWPC-based readout chambers and the challenging requirements of the ALICE TPC upgrade program. Detailed simulations of the readout system are able to reproduce the data.Comment: Submitted to NIM

The upgrade of the ALICE TPC with GEMs and continuous readout

The upgrade of the ALICE TPC will allow the experiment to cope with the high interaction rates foreseen for the forthcoming Run 3 and Run 4 at the CERN LHC. In this article, we describe the design of new readout chambers and front-end electronics, which are driven by the goals of the experiment. Gas Electron Multiplier (GEM) detectors arranged in stacks containing four GEMs each, and continuous readout electronics based on the SAMPA chip, an ALICE development, are replacing the previous elements. The construction of these new elements, together with their associated quality control procedures, is explained in detail. Finally, the readout chamber and front-end electronics cards replacement, together with the commissioning of the detector prior to installation in the experimental cavern, are presented. After a nine-year period of R&D, construction, and assembly, the upgrade of the TPC was completed in 2020.publishedVersio

Different experimental approaches in modelling cataractogenesis: An overview of selenite-induced nuclear cataract in rats

Cataract, the opacification of eye lens, is the leading cause of blindness worldwide. At present, the only remedy is surgical removal of the cataractous lens and substitution with a lens made of synthetic polymers. However, besides significant costs of operation and possible complications, an artificial lens just does not have the overall optical qualities of a normal one. Hence it remains a significant public health problem, and biochemical solutions or pharmacological interventions that will maintain the transparency of the lens are highly required. Naturally, there is a persistent demand for suitable biological models. The ocular lens would appear to be an ideal organ for maintaining culture conditions because of lacking blood vessels and nerves. The lens in vivo obtains its nutrients and eliminates waste products via diffusion with the surrounding fluids. Lens opacification observed in vivo can be mimicked in vitro by addition of the cataractogenic agent sodium selenite (Na2SeO3) to the culture medium. Moreover, since an overdose of sodium selenite induces also cataract in young rats, it became an extremely rapid and convenient model of nuclear cataract in vivo. The main focus of this review will be on selenium (Se) and its salt sodium selenite, their toxicological characteristics and safety data in relevance of modelling cataractogenesis, either under in vivo or in vitro conditions. The studies revealing the mechanisms of lens opacification induced by selenite are highlighted, the representatives from screening for potential anti-cataract agents are listed

Measurement of the Lifetime and Λ Separation Energy of _{Λ}^{3}H

The most precise measurements to date of the _{Λ}^{3}H lifetime τ and Λ separation energy B_{Λ} are obtained using the data sample of Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV collected by ALICE at the LHC. The _{Λ}^{3}H is reconstructed via its charged two-body mesonic decay channel (_{Λ}^{3}H→^{3}He+π^{-} and the charge-conjugate process). The measured values τ=[253±11(stat)±6(syst)]  ps and B_{Λ}=[102±63(stat)±67(syst)]  keV are compatible with predictions from effective field theories and confirm that the _{Λ}^{3}H structure is consistent with a weakly bound system

f0(980) production in inelastic pp collisions at s = 5.02 TeV

The measurement of the production of f0(980) in inelastic pp collisions at sqrt(s) = 5.02 TeV is presented. This is the first reported measurement of inclusive f0(980) yield at LHC energies. The production is measured at midrapidity, |y| pi+pi- hadronic decay channel using the ALICE detector. The pT-differential yields are compared to those of pions, protons and ϕ mesons as well as to predictions from the HERWIG 7.2 QCD-inspired Monte Carlo event generator and calculations from a coalescence model that uses the AMPT model as an input. The ratio of the pT-integrated yield of f0(980) relative to pions is compared to measurements in e+e- and pp collisions at lower energies and predictions from statistical hadronisation models and HERWIG 7.2. A mild collision energy dependence of the f0(980) to pion production is observed in pp collisions from SPS to LHC energies. All considered models underpredict the pT-integrated 2f0(980)/(pi+ + pi-) ratio. The prediction from the canonical statistical hadronisation model assuming a zero total strangeness content of f0(980) is consistent with the data within 1.9σ and is the closest to the data. The results provide an essential reference for future measurements of the particle yield and nuclear modification in p–Pb and Pb–Pb collisions, which have been proposed to be instrumental to probe the elusive nature and quark composition of the f0(980) scalar meson

Measurement of the non-prompt D-meson fraction as a function of multiplicity in proton-proton collisions at s \sqrt{s} = 13 TeV

The fractions of non-prompt (i.e. originating from beauty-hadron decays) D0 and D+ mesons with respect to the inclusive yield are measured as a function of the charged-particle multiplicity in proton-proton collisions at a centre-of-mass energy of √s = 13 TeV with the ALICE detector at the LHC. The results are reported in intervals of transverse momentum (pT) and integrated in the range 1 < pT < 24 GeV/c. The fraction of non-prompt D0 and D+ mesons is found to increase slightly as a function of pT in all the measured multiplicity intervals, while no significant dependence on the charged- particle multiplicity is observed. In order to investigate the production and hadronisation mechanisms of charm and beauty quarks, the results are compared to PYTHIA 8 as well as EPOS 3 and EPOS 4 Monte Carlo simulations, and to calculations based on the colour glass condensate including three-pomeron fusion

Observation of flow angle and flow magnitude fluctuations in Pb-Pb collisions at sNN=5.02TeV at the CERN Large Hadron Collider

This Letter reports on the first measurements of transverse momentum dependent flow angle n and flow magnitude vn fluctuations determined using new four-particle correlators. The measurements are performed for various centralities in Pb–Pb collisions at a center-of-mass energy per nucleon pair of √s NN = 5.02 TeV with ALICE at the CERN Large Hadron Collider. Both flow angle and flow magnitude fluctuations are observed in the presented centrality ranges and are strongest in the most central collisions and for a transverse momentum pT > 2 GeV/c. Comparison with theoretical models, including iEBE-VISHNU, MUSIC, and AMPT, show that the measurements exhibit unique sensitivities to the initial state of heavy-ion collisions