Establishing operant conflict tests for the translational study of anxiety in mice

Rationale In conflict-based anxiety tests, rodents decide between actions with simultaneous rewarding and aversive outcomes. In humans, computerised operant conflict tests have identified response choice, latency, and vigour as distinct behavioural components. Animal operant conflict tests for measurement of these components would facilitate translational study. Objectives In C57BL/6 mice, two operant conflict tests for measurement of response choice, latency, and vigour were established, and effects of chlordiazepoxide (CDZ) thereon investigated. Methods Mice were moderately diet-restricted to increase sucrose reward salience. A 1-lever test required responding under medium-effort reward/threat conditions of variable ratio 2–10 resulting in sucrose at p = 0.7 and footshock at p = 0.3. A 2-lever test mandated a choice between low-effort reward/threat with a fixed-ratio (FR) 2 lever yielding sucrose at p = 0.7 and footshock at p = 0.3 versus high-effort reward/no threat with a FR 20 lever yielding sucrose at p = 1. Results In the 1-lever test, CDZ (7.5 or 15 mg/kg i.p.) reduced post-trial pause (response latency) following either sucrose or footshock and reduced inter-response interval (increased response vigour) after footshock. In the 2-lever test, mice favoured the FR2 lever and particularly at post-reward trials. CDZ increased choice of FR2 and FR20 responding after footshock, reduced response latency overall, and increased response vigour at the FR2 lever and after footshock specifically. Conclusions Mouse operant conflict tests, especially 2-lever choice, allow for the translational study of distinct anxiety components. CDZ influences each component by ameliorating the impact of both previous punishment and potential future punishment

Sledding injuries: is safety in this winter pastime overlooked? A three-year survey in South-Tyrol

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Sledding is a popular traditional pastime in northern countries. However it is only rarely thought as a potentially dangerous activity even though serious injuries and deaths do occur. The purpose of this study was to calculate the incidence, the severity and the pattern of sleddingrelated injuries in our area, in order to set up possible preventive measures. Results: In three consecutive winter seasons (Dec.–Apr.,2002–2005). 356 patients (182 males, 174 females, mean age 26.9 years, range 2 to 81) were referred directly to our ED after a sledding injury. One patient (male, age 21 years) was transferred from a community hospital and died on the following day. Two patients (males, age 47 and 28 years) were declared dead on the scene. In the majority of the cases the accident was due to a fall and collision with the ground or a standing object. The number of injuries showed a progressive increase during the observed seasons and all deadly accidents were observed in the last season. Injuries were divided into three severity classes: minor (ISS ≤ 3), intermediate (ISS ≥ 4 < 15), severe (ISS ≥ 15). Minor and intermediate injuries were equally distributed between males and females, whereas all severe and deadly accidents occurre

Novel alterations in corneal neuroimmune phenotypes in mice with central nervous system tauopathy

BACKGROUND: Tauopathy in the central nervous system (CNS) is a histopathological hallmark of frontotemporal dementia (FTD) and Alzheimer's disease (AD). Although AD is accompanied by various ocular changes, the effects of tauopathy on the integrity of the cornea, which is densely innervated by the peripheral nervous system and is populated by resident dendritic cells, is still unknown. The aim of this study was to investigate if neuroimmune interactions in the cornea are affected by CNS tauopathy. METHODS: Corneas from wild type (WT) and transgenic rTg4510 mice that express the P301L tau mutation were examined at 2, 6, 8, and 11 months. Clinical assessment of the anterior segment of the eye was performed using spectral domain optical coherence tomography. The density of the corneal epithelial sensory nerves and the number and field area of resident epithelial dendritic cells were assessed using immunofluorescence. The immunological activation state of corneal and splenic dendritic cells was examined using flow cytometry and compared between the two genotypes at 9 months of age. RESULTS: Compared to age-matched WT mice, rTg4510 mice had a significantly lower density of corneal nerve axons at both 8 and 11 months of age. Corneal nerves in rTg4510 mice also displayed a higher percentage of beaded nerve axons and a lower density of epithelial dendritic cells compared to WT mice. From 6 months of age, the size of the corneal dendritic cells was significantly smaller in rTg4510 compared to WT mice. Phenotypic characterization by flow cytometry demonstrated an activated state of dendritic cells (CD86+ and CD45+ CD11b+CD11c+) in the corneas of rTg4510 compared to WT mice, with no distinct changes in the spleen monocytes/dendritic cells. At 2 months of age, there were no significant differences in the neural or immune structures between the two genotypes. CONCLUSIONS: Corneal sensory nerves and epithelial dendritic cells were altered in the rTg4510 mouse model of tauopathy, with temporal changes observed with aging. The activation of corneal dendritic cells prior to the gradual loss of neighboring sensory nerves suggests an early involvement of corneal immune cells in tau-associated pathology originating in the CNS

The Bell Beaker rock sanctuary Pigloner Kopf (South Tyrol, Italy): Burnt offerings and local metallurgy in the Eastern Alps

The archaeological site Pigloner Kopf (Vadena/Pfatten, South Tyrol, Italy) has revealed unexpected elements related to the local Bell Beaker culture, like the local production of shaft-hole axes, typologically linked to the Balkans and the Danube region. The site also shows the oldest evidence of ritual burnt offerings in the Eastern Alps. The mostly burnt animal bones, cereals, flint tools and fragments of pottery could be interpreted as the remains of a rock sanctuary with burnt offerings. The site can be considered as a prototype of the alpine places of worship and mountain sanctuaries. These burning rituals were practised from the beginning of the Bronze Age until the late Roman Empire. The aim of the paper is to present the results of the study of materials and their analyses, focussing on the metallurgical industry, composed mostly by objects produced with local copper, such as 10 miniaturised shaft-hole axes, 7 awls and a pin and also by imported objects like a dagger blade and spiral ornaments. The deposition of copper tools in hoards in association with burnt offerings suggest a ritual interpretation of the site, dated to the late Copper Age with Bell Beaker elements in lithics and pottery

Smelting slags from Copper and Bronze Age archaeological sites in Trentino and Alto Adige

More than 100 Ltvalitic metalluraicul slags from prehistoric copper production sites in d~e Easrern Alp; wcre <.;J~alY7.ed by ch\ue8mical and minerulogrcal techniques, The im-estigated sarnples include the oldest hnds ot metullurgical .ictivity in Trentino und ;\lco _-\dige and yidd iniormarion t'or rhe interpretation of tbc introduction .ind development ot merallurgical tecb niqucs in tbc E"lstcrn A.lps, 'I'lie slags fllLlnd in most drcn;;lcological sites are distinct into rwo groups having ditterer.t minerulogjcal, chemical, and tcxtural fcatures, ,,11le! thev are inrcrpreted as derived lrom two di Fferent steps oF the copper smelring process tr01T1 sulphides. Cooling rates derived rrorn the Invulitc te:-:rUi.-CS arc consistent with this interorc.ution

Analisi di scorie di estrazione del rame provenienti da siti dell\u2019Et\ue0 del Bronzo dell\u2019Alto Adige

Sono state analizzate, attraverso tecniche chimiche e mineralogiche, pi\uf9 di 100 scorie metallurgiche provenienti da 12 siti preistorici di produzione del rame situati nelle Alpi Orientali. I campioni studiati includono le scorie dovute ad attivit\ue0 metallurgica pi\uf9 vecchie rinvenute in Trentino e Alto Adige, e danno informazioni per l\u2019interpretazione dell\u2019introduzione e dello sviluppo delle tecniche metallurgiche nelle Alpi Orientali. Le scorie trovate nella maggior parte dei siti sono distinte in due gruppi con propriet\ue0 mineralogiche, chimiche e tessiturali differenti e sono interpretate come derivanti da due differenti metodi di raffreddamento dello stesso processo di smelting da solfuri. Le velocit\ue0 di raffreddamento derivate dalla tessitura dei cristalli di fayalite sono consistenti con questa interpretazione