KATANA : a charge-sensitive trigger/veto array for the SπS\pi RIT TPC

KATANA — the Krak´ow Array for Triggering with Amplitude discrimiNAtion, has been built and used as a trigger and veto detector for the SπRIT TPC at RIKEN. Its construction allows operating in magnetic field, providing fast response for ionizing particles and giving the approximate multiplicity and charge information on forward emitted reaction products. Depending on this information, trigger and veto signals are generated. Multi-Pixel Photon Counters were used as light sensors for plastic scintillators. Custom designed front-end and peripheral electronics will be presented as well

KATANA : a charge-sensitive triggering/veto system for the Sπ\piRIT experiment

KATANA — the Kraków Array for Triggering with Amplitude discrimiNAtion, has been built and used as a trigger and Veto detector for the S$\pi$RIT TPC at RIKEN. Its construction allows for operation in magnetic field and provides a fast response for ionizing particles giving the approximate forward multiplicity and charge information. Depending on this information, trigger and veto signals are generated. The Multi-Pixel Photon Counters were used as light sensors for plastic scintillators. Performance of the detector is presented

KATANA - a charge-sensitive triggering system for the Sπ\piRIT experiment

KATANA - the Krakow Array for Triggering with Amplitude discrimiNAtion - has been built and used as a trigger and veto detector for the S$\pi$RIT TPC at RIKEN. Its construction allows operating in magnetic field and providing fast response for ionizing particles, giving the approximate forward multiplicity and charge information. Depending on this information, trigger and veto signals are generated. The article presents performance of the detector and details of its construction. A simple phenomenological parametrization of the number of emitted scintillation photons in plastic scintillator is proposed. The effect of the light output deterioration in the plastic scintillator due to the in-beam irradiation is discussed.Comment: 14 pages, 11 figure

Quantitative reduction of RyR1 protein caused by a single-allele frameshift mutation in RYR1 ex36 impairs the strength of adult skeletal muscle fibres

Here we characterized a mouse model knocked-in for a frameshift mutation in RYR1 exon 36 (p.Gln1970fsX16) that is isogenic to that identified in one parent of a severely affected patient with recessively inherited multiminicore disease. This individual carrying the RYR1 frameshifting mutation complained of mild muscle weakness and fatigability. Analysis of the RyR1 protein content in a muscle biopsy from this individual showed a content of only 20% of that present in a control individual. The biochemical and physiological characteristics of skeletal muscles from RyR1Q1970fsX16 heterozygous mice recapitulates that of the heterozygous parent. RyR1 protein content in the muscles of mutant mice reached 38% and 58% of that present in total muscle homogenates of fast and slow muscles from wild-type (WT) littermates. The decrease of RyR1 protein content in total homogenates is not accompanied by a decrease of Cav1.1 content, whereby the Cav1.1/RyR1 stoichiometry ratio in skeletal muscles from RyR1Q1970fsX16 heterozygous mice is lower compared to that from WT mice. Electron microscopy (EM) revealed a 36% reduction in the number/area of calcium release units accompanied by a 2.5-fold increase of dyads (triads that have lost one junctional sarcoplasmic reticulum element); both results suggest a reduction of the RyR1 arrays. Compared to WT, muscle strength and depolarization-induced calcium transients in RyR1Q1970fsX16 heterozygous mice muscles were decreased by 20% and 15%, respectively. The RyR1Q1970fsX16 mouse model provides mechanistic insight concerning the phenotype of the parent carrying the RYR1 ex36 mutation and suggests that in skeletal muscle fibres there is a functional reserve of RyR1

Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma

Abstract: Psychiatric diseases have a strong heritable component known to not be restricted to DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in germ cells. Initial evidence suggested that sperm RNA is causally linked to the transmission of symptoms induced by traumatic experiences. Here, we show that alterations in long RNA in sperm contribute to the inheritance of specific trauma symptoms. Injection of long RNA fraction from sperm of males exposed to postnatal trauma recapitulates the effects on food intake, glucose response to insulin and risk-taking in adulthood whereas the small RNA fraction alters body weight and behavioural despair. Alterations in long RNA are maintained after fertilization, suggesting a direct link between sperm and embryo RNA

Inhibitory Kcnip2 neurons of the spinal dorsal horn control behavioral sensitivity to environmental cold

Proper sensing of ambient temperature is of utmost importance for the survival of euthermic animals, including humans. While considerable progress has been made in our understanding of temperature sensors and transduction mechanisms, the higher-order neural circuits processing such information are still only incompletely understood. Using intersectional genetics in combination with circuit tracing and functional neuron manipulation, we identified Kcnip2-expressing inhibitory (Kcnip2GlyT2) interneurons of the mouse spinal dorsal horn as critical elements of a neural circuit that tunes sensitivity to cold. Diphtheria toxin-mediated ablation of these neurons increased cold sensitivity without affecting responses to other somatosensory modalities, while their chemogenetic activation reduced cold and also heat sensitivity. We also show that Kcnip2GlyT2 neurons become activated preferentially upon exposure to cold temperatures and subsequently inhibit spinal nociceptive output neurons that project to the lateral parabrachial nucleus. Our results thus identify a hitherto unknown spinal circuit that tunes cold sensitivity. Keywords: circuit; cold; cold allodynia; cold analgesia; cooling; dre recombinase; interneuron; intersectional gene targeting; kcnip2; pai

c-Maf-positive spinal cord neurons are critical elements of a dorsal horn circuit for mechanical hypersensitivity in neuropathy

Corticospinal tract (CST) neurons innervate the deep spinal dorsal horn to sustain chronic neuropathic pain. The majority of neurons targeted by the CST are interneurons expressing the transcription factor c-Maf. Here, we used intersectional genetics to decipher the function of these neurons in dorsal horn sensory circuits. We find that excitatory c-Maf (c-Maf$^{EX}$) neurons receive sensory input mainly from myelinated fibers and target deep dorsal horn parabrachial projection neurons and superficial dorsal horn neurons, thereby connecting non-nociceptive input to nociceptive output structures. Silencing c-Maf$^{EX}$ neurons has little effect in healthy mice but alleviates mechanical hypersensitivity in neuropathic mice. c-Maf$^{EX}$ neurons also receive input from inhibitory c-Maf and parvalbumin neurons, and compromising inhibition by these neurons caused mechanical hypersensitivity and spontaneous aversive behaviors reminiscent of c-Maf$^{EX}$ neuron activation. Our study identifies c-Maf$^{EX}$ neurons as normally silent second-order nociceptors that become engaged in pathological pain signaling upon loss of inhibitory control

Characterization of serum biomarkers and antibody responses against Prevotella spp. in preclinical and new-onset phase of rheumatic diseases

IntroductionThe characterization of the influence of the microbiota on the development and drug responses during rheumatic diseases has intensified in recent years. The role of specific bacteria during disease development has become a central research question. Notably, several lines of evidence point to distinct microbes, e.g., Prevotella copri (P. copri) being targeted by antibodies in clinical phases of rheumatic diseases.MethodsIn the present study, we compiled a broad collection of human serum samples from individuals at risk of developing RA, chronic RA patients as well as patients with new-onset of rheumatic diseases. We evaluated the presence of inflammatory biomarkers in our serum collection as well as serum antibody responses against novel, genetically distinct isolates of P. copri and several oral pathobionts.ResultsOur analysis revealed the presence of increased levels of inflammatory markers already in pre-clinical and new onset rheumatoid arthritis. However, antibody reactivity against the microbes did not differ between patient groups. Yet, we observed high variability between the different P. copri strains. We found total serum IgG levels to slightly correlate with IgG antibody responses against P. copri, but no relation between the latter and presence or prevalence of P. copri in the intestine.DiscussionIn conclusion, our work underlined the importance of strain-level characterization and its consideration during further investigations of host-microbiota interactions and the development of microbiome-based therapeutic approaches for treating rheumatic diseases

Results from the first use of low radioactivity argon in a dark matter search

Liquid argon is a bright scintillator with potent particle identification properties, making it an attractive target for direct-detection dark matter searches. The DarkSide-50 dark matter search here reports the first WIMP search results obtained using a target of low-radioactivity argon. DarkSide-50 is a dark matter detector, using two-phase liquid argon time projection chamber, located at the Laboratori Nazionali del Gran Sasso. The underground argon is shown to contain Ar-39 at a level reduced by a factor (1.4 +- 0.2) x 10^3 relative to atmospheric argon. We report a background-free null result from (2616 +- 43) kg d of data, accumulated over 70.9 live-days. When combined with our previous search using an atmospheric argon, the 90 % C.L. upper limit on the WIMP-nucleon spin-independent cross section based on zero events found in the WIMP search regions, is 2.0 x 10^-44 cm^2 (8.6 x 10^-44 cm^2, 8.0 x 10^-43 cm^2) for a WIMP mass of 100 GeV/c^2 (1 TeV/c^2 , 10 TeV/c^2).Comment: Accepted by Phys. Rev.

The first search for bosonic super-WIMPs with masses up to 1 MeV/c2^2 with GERDA

We present the first search for bosonic super-WIMPs as keV-scale dark matter candidates performed with the GERDA experiment. GERDA is a neutrinoless double-beta decay experiment which operates high-purity germanium detectors enriched in $^{76}$Ge in an ultra-low background environment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN in Italy. Searches were performed for pseudoscalar and vector particles in the mass region from 60 keV/c$^2$ to 1 MeV/c$^2$. No evidence for a dark matter signal was observed, and the most stringent constraints on the couplings of super-WIMPs with masses above 120 keV/c$^2$ have been set. As an example, at a mass of 150 keV/c$^2$ the most stringent direct limits on the dimensionless couplings of axion-like particles and dark photons to electrons of $g_{ae} < 3 \cdot 10^{-12}$ and ${\alpha'}/{\alpha} < 6.5 \cdot 10^{-24}$ at 90% credible interval, respectively, were obtained.Comment: 6 pages, 3 figures, submitted to Physical Review Letters, added list of authors, updated ref. [21