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Process models are among the principal artefacts used for managing design projects. However, the selection of effective modelling approaches can be difficult for design project managers, given that a plethora of tools exists for various modelling purposes. In addition to date no systematic approach for the assessment and selection of process modelling approaches is available to practitioners. This paper presents the development of criteria for benchmarking and selecting different process modelling tools. The results are based on three elements. (1) In a four-hour workshop undertaken by the Design Process SIG of the Design Society, bringing together around 20 international researchers and practitioners in design process modelling, an initial set of 58 criteria were brainstormed and consolidated during the workshop and in follow-up meetings. (2) The consolidated criteria were then compared with literature. The finalised criteria list was then validated by external experts in industry (3). The resulting list of 12 criteria provides a sound basis for practitioners to support a systematic selection of process modelling approaches. Further, it lays the foundation of a benchmarking tool, which is subject to future work.

Rats emit 50-kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50-kHz USV are elicited by the psychostimulant d-amphetamine. Exaggerated 50-kHz USV emission evoked by d-amphetamine is modulated by dopamine, noradrenaline and 5-hydroxytyrptamine receptor ligands and inhibited by the mood stabilizer lithium, the gold standard anti-manic drug for treating bipolar disorder. This indicates that exaggerated 50-kHz USV emission can serve as a reliable and valid measure for assessing mania-like elevated mood in rats with sufficient translational power for gaining a better understanding of relevant pathophysiological mechanisms and the identification of new therapeutic targets. The improved capacity to study the effects of anti-manic pharmacological interventions on a broader range of behaviours by including exaggerated 50-kHz USV emission as preclinical outcome measure complementary to locomotor hyperactivity will refine rodent models for mania. LINKED ARTICLES: This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc. ispartof: BRITISH JOURNAL OF PHARMACOLOGY vol:179 issue:17 pages:4201-4219 ispartof: location:England status: published

Communication constitutes a fundamental component of mammalian social behavior. Rats are highly social animals and emit 50-kHz ultrasonic vocalizations (USV), which function as social contact calls. Playback of 50-kHz USV leads to strong and immediate social approach responses in receiver rats, but this response is weak or even absent during repeated 50-kHz USV playback. Given the important role of 50-kHz USV in initiating social contact and coordinating social interactions, the occurrence of habituation is highly unexpected. It is not clear why a social signal characterized by significant incentive salience loses its power to change the behavior of the receiver so rapidly. Here, we show that the habituation phenomenon displayed by rats in response to repeated playback of 50-kHz USV (1) is characterized by limited generalizability because it is present in Wistar but not Sprague-Dawley rats, (2) can be overcome by amphetamine treatment, and (3) depends on the subject's internal state. ispartof: ISCIENCE vol:24 issue:5 ispartof: location:United States status: published

Angelman syndrome (AS) is a rare genetic neurodevelopmental disorder characterized by intellectual disabilities, motor and balance deficits, impaired communication, and a happy, excitable demeanor with frequent laughter. We sought to elucidate a preclinical outcome measure in male and female rats that addressed communication abnormalities of AS and other neurodevelopmental disorders in which communication is atypical and/or lack of speech is a core feature. We discovered, and herein report for the first time, excessive laughter-like 50 kHz ultrasonic emissions in the Ube3amat–/pat+ rat model of AS, which suggests an excitable, playful demeanor and elevated positive affect, similar to the demeanor of individuals with AS. Also in line with the AS phenotype, Ube3amat–/pat+ rats demonstrated aberrant social interactions with a novel partner, distinctive gait abnormalities, impaired cognition, an underlying LTP deficit, and profound reductions in brain volume. These unique, robust phenotypes provide advantages compared with currently available mouse models and will be highly valuable as outcome measures in the evaluation of therapies for AS. SIGNIFICANCE STATEMENT Angelman syndrome (AS) is a severe neurogenetic disorder for which there is no cure, despite decades of research using mouse models. This study used a recently developed rat model of AS to delineate disease-relevant outcome measures to facilitate therapeutic development. We found the rat to be a strong model of AS, offering several advantages over mouse models by exhibiting numerous AS-relevant phenotypes, including overabundant laughter-like vocalizations, reduced hippocampal LTP, and volumetric anomalies across the brain. These findings are unconfounded by detrimental motor abilities and background strain, issues plaguing mouse models. This rat model represents an important advancement in the field of AS, and the outcome metrics reported herein will be central to the therapeutic pipeline.

Sexual dimorphisms are widespread in the animal kingdom. At the behavioral level, there is evidence for sex differences in social play behavior. In rats, males typically engage more in rough-and-tumble play than females. One prominent component of the rough-and-tumble play repertoire in rats is the emission of 50-kHz ultrasonic vocalizations (USV). Such 50-kHz USV reflect the rewarding nature of play and serve as socioaffective signals. Here, we provide evidence for sexual dimorphisms within rough-and-tumble play-induced 50-kHz USV in juvenile rats. Specifically, females displayed reduced 50-kHz USV emission during playful interactions. This reduction was associated with changes in 50-kHz USV emission rates and subtype profiles during specific rough-and-tumble components, i.e., pinning, wrestling, and chasing, as well as differences in acoustic parameters. Interestingly, sex differences were modulated by Cacna1c, a gene strongly implicated in major neuropsychiatric disorders, often characterized by prominent sex biases, most notably autism. Specifically, Cacna1c haploinsufficiency affected the emission of 50-kHz USV during rough-and-tumble play in female rats and we provide evidence supporting the notion that such effects of Cacna1c haploinsufficiency are driven by male-typical features of 50-kHz USV emission. This is in line with the hypermasculinized social play repertoire previously observed in juvenile Cacna1c haploinsufficient females. ispartof: DEVELOPMENTAL PSYCHOBIOLOGY vol:63 issue:2 pages:262-276 ispartof: location:United States status: published

Considering animal welfare, animals should be kept in animal-appropriate and stress-free housing conditions in all circumstances. To assure such conditions, not only basic needs must be met, but also possibilities must be provided that allow animals in captive care to express all species-typical behaviors. Rack housing systems for snakes have become increasingly popular and are widely used; however, from an animal welfare perspective, they are no alternative to furnished terrariums. In this study, we therefore evaluated two types of housing systems for ball pythons (Python regius) by considering the welfare aspect animal behavior. In Part 1 of the study, ball pythons (n= 35) were housed individually in a conventional rack system. The pythons were provided with a hiding place and a water bowl, temperature control was automatic, and the lighting in the room served as indirect illumination. In Part 2 of the study, the same ball pythons, after at least 8 weeks, were housed individually in furnished terrariums. The size of each terrarium was correlated with the body length of each python. The terrariums contained substrate, a hiding place, possibilities for climbing, a water basin for bathing, an elevated basking spot, and living plants. The temperature was controlled automatically, and illumination was provided by a fluorescent tube and a UV lamp. The shown behavior spectrum differed significantly between the two housing systems (p< 0.05). The four behaviors basking, climbing, burrowing, and bathing could only be expressed in the terrarium. Abnormal behaviors that could indicate stereotypies were almost exclusively seen in the rack system. The results show that the housing of ball pythons in a rack system leads to a considerable restriction in species-typical behaviors; thus, the rack system does not meet the requirements for animal-appropriate housing.

It is generally assumed that gamblers, and particularly people with gambling problems (PG), are affected by negative perception and stigmatisation. However, a systematic review of empirical studies investigating the perception of gamblers has not yet been carried out. This article therefore summarises empirical evidence on the perception of gamblers and provides directions for future research. A systematic literature review based on the relevant guidelines was carried out searching three databases. The databases Scopus, PubMed and BASE were used to cover social scientific knowledge, medical-psychological knowledge and grey literature. A total of 48 studies from 37 literature references was found. The perspective in these studies varies: Several studies focus on the perception of gamblers by the general population, by subpopulations (e. g. students or social workers), or by gamblers on themselves. The perspective on recreational gamblers is hardly an issue. A strong focus on persons with gambling problems is symptomatic of the gambling discourse. The analysis of the studies shows that gambling problems are thought to be rather concealable, whereas the negative effects on the concerned persons‘ lives are rated to be quite substantial. PG are described as “irresponsible” and “greedy” while they perceive themselves as “stupid” or “weak”. Only few examples of open discrimination are mentioned. Several studies however put emphasis on the stereotypical way in which PG are portrayed in the media, thus contributing to stigmatisation. Knowledge gaps include insights from longitudinal studies, the influence of respondents‘ age, culture and sex on their views, the relevance of the type of gambling a person is addicted to, and others. Further studies in these fields are needed.

Veterinary and human medicine are still seeking a conclusive explanation of the function of sleep, including the change in sleep behaviour over the course of an individual’s lifetime. In human medicine, sleep disorders and abnormalities in the electroencephalogram are used for prognostic statements, therapeutic means and diagnoses. To facilitate such use in foal medicine, we monitored 10 foals polysomnographically for 48 h. Via 10 attached cup electrodes, brain waves were recorded by electroencephalography, eye movements by electrooculography and muscle activity by electromyography. Wireless polysomnographs allowed us to measure the foals in their home stables. In addition, each foal was simultaneously monitored with infrared video cameras. By combining the recorded data, we determined the time budgeting of the foals over 48 h, whereby the states of vigilance were divided into wakefulness, light sleep, slow-wave sleep and rapid-eye-movement sleep, and the body positions into standing, suckling, sternal recumbency and lateral recumbency. The results of the qualitative analyses showed that the brain waves of the foals differ in their morphology from those previously reported for adult horses. The quantitative data analyses revealed that foals suckle throughout all periods of the day, including night-time. The results of our combined measurements allow optimizing the daily schedule of the foals according to their sleep and activity times. We recommend that stall rest should begin no later than 9.00 p.m. and daily stable work should be done in the late afternoon.

At tripartite synapses, astrocytes enmesh synaptic contacts, but how astrocytes contribute to the formation, maturation and plasticity of synapses remains elusive. Here we show that both astrocytes and neurons abundantly express neurexin-1, a presynaptic adhesion molecule that controls synaptic properties. Using super-resolution imaging, we demonstrate that presynaptic neuronal and astrocytic neurexin-1 form discrete nanoclusters at excitatory synapses. We find that distinct patterns of heparan sulfate modification and alternative splicing confer onto astrocytic and neuronal neurexin-1 different ligand specificities, thereby enabling compartment-specific signaling by neurexin-1. At hippocampal Schaffer-collateral synapses, deletion of neurexin-1 from either astrocytes or neurons did not alter synapse numbers, but differentially impaired synapse function. Neuronal neurexin-1 was essential for NMDA-receptor-mediated synaptic responses, whereas astrocytic neurexin-1 was required for maturation of silent synapses, AMPA-receptor recruitment, and long-term potentiation. Thus, astrocytes and neurons surprisingly use the same synaptic adhesion molecule to control distinct synapse properties.

Das nested type Urothelkarzinom (UC) der Blase ist eine seltene Sonderform des UC, dessen Besonderheit sich im meist submucösem Wachstum auszeichnet. Dies führt oft zu einer verspäteten Diagnostik mit konsekutiv hohem Anteil von muskelinvasiven oder weiter fortgeschrittenen Karzinomen[zum vollständigen Text gelangen Sie über die oben angegebene URL], 46. Gemeinsame Tagung der Bayerischen Urologenvereinigung und der Österreichischen Gesellschaft für Urologie und Andrologie

Einleitung: Monozentrische ‚single-surgeon‘ - Evaluation der Lernkurve bei der Einführung eines transurethralen Enukleationsverfahrens (EEP)mit Fokus auf Komplikationen, OP-Dauer, kurzfristige Ergebnisse und Kosteneffektivität. Material und Methoden: Von 2017 bis 2019 wurden[zum vollständigen Text gelangen Sie über die oben angegebene URL], 46. Gemeinsame Tagung der Bayerischen Urologenvereinigung und der Österreichischen Gesellschaft für Urologie und Andrologie

Rationale In rodents, acute haloperidol treatment induces psychomotor impairments known as catalepsy, which models akinesia in humans and is characterized as an animal model of acute Parkinsonism, whereas sub-chronic haloperidol reduces exploratory behavior, which resembles bradykinesia. Haloperidol-induced catalepsy in rats can be ameliorated by playback of 50-kHz ultrasonic vocalizations (USV), an emotionally and motivationally relevant appetitive auditory stimulus, representing an animal model of paradoxical kinesia. In a condition like PD where patients suffer from chronic motor impairments, it is paramount to assess the long-term symptom relief in an animal model of Parkinsonism. Objectives We investigated whether 50-kHz USV playback ameliorates psychomotor deficits induced by haloperidol in a sub-chronic dosing regimen. Methods In phase 1, distance traveled and number of rearing behavior were assessed in an activity chamber in order to investigate whether sub-chronic haloperidol treatment induced psychomotor impairments. In phase 2, we investigated whether 50-kHz USV playback could overcome these impairments by assessing exploratory behaviors and approach behavior towards the sound source in the 50-kHz USV radial maze playback paradigm. Results Sub-chronic haloperidol treatment led to psychomotor deficits since the distance traveled and number of rearing behavior were reduced as compared to saline control group or baseline. These psychomotor impairments were ameliorated during playback of 50-kHz USV, with haloperidol treated rats showing a clear social approach behavior towards the sound source exclusively during playback. Conclusions This study provides evidence that 50-kHz USV playback induces paradoxical kinesia in rats exhibiting motor deficits after sub-chronic haloperidol, as we previously showed after acute haloperidol treatment.

Human genetics and genomics advances : HGG advances 3(2), 100093 (2022). doi:10.1016/j.xhgg.2022.100093, Published by Cell Press, Cambridge, Ma.

The CACNA1C gene is strongly implicated in the etiology of multiple major neuropsychiatric disorders, such as bipolar disorder, major depression, and schizophrenia, with cognitive deficits being a common feature. It is unclear, however, by which mechanisms CACNA1C variants advance the risk of developing neuropsychiatric disorders. This study set out to investigate cognitive functioning in a newly developed genetic Cacna1c rat model. Specifically, spatial and reversal learning, as well as object recognition memory were assessed in heterozygous Cacna1c +/− rats and compared to wildtype Cacna1c +/+ littermate controls in both sexes. Our results show that both Cacna1c +/+ and Cacna1c +/− animals were able to learn the rewarded arm configuration of a radial maze over the course of seven days. Both groups also showed reversal learning patterns indicative of intact abilities. In females, genotype differences were evident in the initial spatial learning phase, with Cacna1c +/− females showing hypo-activity and fewer mixed errors. In males, a difference was found during probe trials for both learning phases, with Cacna1c +/− rats displaying better distinction between previously baited and non-baited arms; and regarding cognitive flexibility in favor of the Cacna1c +/+ animals. All experimental groups proved to be sensitive to reward magnitude and fully able to distinguish between novel and familiar objects in the novel object recognition task. Taken together, these results indicate that Cacna1c haploinsufficiency has a minor, but positive impact on (spatial) memory functions in rats.

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders, characterized by early-onset deficits in social behavior and communication across multiple contexts, together with restricted, repetitive patterns of behavior, interests, or activities. ASD is among the most heritable neuropsychiatric conditions with heritability estimates higher than 80%, and while available evidence points to a complex set of genetic factors, the SHANK (also known as ProSAP) gene family has emerged as one of the most promising candidates. Several genetic Shank mouse models for ASD were generated, including Shank1 knockout mice. Behavioral studies focusing on the Shank1 knockout mouse model for ASD included assays for detecting ASD-relevant behavioral phenotypes in the following domains: (I) social behavior, (II) communication, and (III) repetitive and stereotyped patterns of behavior. In addition, assays for detecting behavioral phenotypes with relevance to comorbidities in ASD were performed, including but not limited to (IV) cognitive functioning. Here, we summarize and discuss behavioral and neuronal findings obtained in the Shank1 knockout mouse model for ASD. We identify open research questions by comparing such findings with the symptoms present in humans diagnosed with ASD and carrying SHANK1 deletions. We conclude by discussing the implications of the behavioral and neuronal phenotypes displayed by the Shank1 knockout mouse model for the development of future pharmacological interventions in ASD.

Ultrasonic vocalizations (USVs) serve important communicative functions in rodents. Different types of USVs can be triggered in the sender, for example, by maternal separation, social interactions, or exposure to predators, and they evoke affiliative or alarming behaviors in recipients. This review focusses on studies evaluating possible links between immunity and USVs. Most studies have been performed in a murine model of maternal immune activation and subsequent evaluation of effects in the offspring. This model has received large attention in recent years because it mimics behavioral abnormalities observed in certain human neuropsychiatric disorders, including autism spectrum disorder. Although there is still some controversy, the results indicate that stimulation of the immune system of mice and rats during pregnancy affects ultrasonic calling in pups. Few studies are available on immunization during adulthood and USVs. In most cases, immune stimulation led to disease, complicating conclusions about a possible direct link between vocalization and immunity. Although much work is still needed, this is certainly a rather new and promising aspect of interactions between the immune system and behavior.

Predator odours induce defensive behaviour in prey animals such as rats. The present study investigated (1) whether laboratory rats exposed to predator odours emit 22-kHz calls which may have an alarming function and (2) whether playback of such calls induces behavioural changes in conspecifics. For this, Sprague-Dawley rats were exposed to samples of fox and lion urine, as well as to the synthetic predator odour TMT. Despite that all odours induced defensive behaviour, only predator urine samples but not TMT were able to induce 22-kHz calls in a few rats. In a second experiment, naive rats were exposed to playback presentations of the 22-kHz calls recorded in the first experiment, as well as to phase-scrambled and frequency-shifted control stimuli. Low intensity playback presentations led to a reduction of locomotor activity during the presentation of the 22-kHz calls but not of the control stimuli. This effect was less specific under high intensity conditions. Taken together the present findings show that natural predator odours are able to induce emission of 22-kHz calls in rats and support the hypothesis that these calls have an alarming function. ispartof: SCIENTIFIC REPORTS vol:8 issue:1 ispartof: location:England status: published

Rat pup ultrasonic vocalizations (USV) are usually studied in outbred rats belonging to either Long-Evans, Sprague-Dawley, or Wistar stocks, but these were not compared so far. We therefore performed a stock comparison and analyzed USV of male pups (postnatal day 11) belonging to these three stocks. Pups of all three stocks showed substantial isolation-induced USV, but differed in various call features, like call numbers, peak frequency, and frequency modulation. Also, three different call types were identified by means of a quantitative approach based on peak frequency and frequency modulation, and it was found that their proportions differed between stocks. These results are discussed with respect to functional aspects of pup USV.

Comprehensive non-targeted analysis of food products normally requires two complementary chromatographic runs to achieve maximum compound coverage. In this study, we present a sensitive tandem-LC method, which combines RP and HILIC separation in a single run. The setup consists of a C18 trap column and two subsequently coupled analytical columns (HILIC and C18) which are operated in parallel. First, hydrophobic compounds are retained on the RP trap column while rather hydrophilic compounds are directly transferred onto a HILIC phase. Next, the pre-fractionated sample composition is analyzed by HILIC or RP chromatography, respectively. The presented setup allows individual and independent gradient elution as well as interfacing with mass spectrometry. The performance of the method has been proven by means of food relevant standards and analysis of complex food samples (e.g. red wine, meat extract). The simple and robust setup provides high flexibility in the selection of column combinations and does not require sophisticated instrumental setups or software. The method significantly increases the covered polarity range compared to classical one-dimensional chromatography. Our results indicate that tandem LC is a valuable and universal tool in the non-targeted screening of various types of complex food samples.

Parkinson’s disease is a chronic neurodegenerative disorder characterized by cardinal motor features, such as bradykinesia , but also vocal deficits (e.g. difficulties to articulate words and to keep the tone of voice) and depression. In the present study, rats with bilateral 6-hydroxydopamine lesion of the substantia nigra pars compacta were evaluated for changes in the emission of 50-kHz ultrasonic vocalizations , gait impairment (catwalk test), and depressive-like behaviour (sucrose preference test). Furthermore, we evaluated the effect of repeated treatment (28 days) with ketamine (5, 10, and 15 mg/kg, ip, once per week) or imipramine (15 mg/kg, ip, daily). The lesion had prominent effects on the production of 50-kHz ultrasonic vocalizations (reduced call numbers, call durations, total calling time, and increased latency to start calling), led to gait impairment (increased run duration and stand of right forelimb) and induced anhedonia (reduced sucrose preference). Also, significant correlations between gait changes, sucrose preference, and ultrasonic calling were found, yet, except for run duration and sucrose preference, these correlations were low indicating that these associations are weak. Importantly, ketamine and imipramine reversed lesion-induced anhedonia and improved gait impairments, but neither drug improved ultrasonic calling. In conclusion, the substantia nigra lesion with 6-hydroxydopamine induced subtle motor and non-motor manifestations, reflecting key features of the wide clinical spectrum of early Parkinson’s disease. Furthermore, the present results suggest a potential efficacy of ketamine on depression and gait alterations in Parkinson’s disease.

BACKGROUND: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by two core symptoms: impaired social interaction and communication, and restricted, repetitive behaviors and interests. The pathophysiology of ASD is not yet fully understood, due to a plethora of genetic and environmental risk factors that might be associated with or causal for ASD. Recent findings suggest that one putative convergent pathway for some forms of ASD might be the downregulation of the calcium-binding protein parvalbumin (PV). PV-deficient mice (PV-/-, PV+/-), as well as Shank1-/-, Shank3-/-, and VPA mice, which show behavioral deficits relevant to all human ASD core symptoms, are all characterized by lower PV expression levels. METHODS: Based on the hypothesis that PV expression might be increased by 17-β estradiol (E2), PV+/- mice were treated with E2 from postnatal days 5-15 and ASD-related behavior was tested between postnatal days 25 and 31. RESULTS: PV expression levels were significantly increased after E2 treatment and, concomitantly, sociability deficits in PV+/- mice in the direct reciprocal social interaction and the 3-chamber social approach assay, as well as repetitive behaviors, were attenuated. E2 treatment of PV+/+ mice did not increase PV levels and had detrimental effects on sociability and repetitive behavior. In PV-/- mice, E2 obviously did not affect PV levels; tested behaviors were not different from the ones in vehicle-treated PV-/- mice. CONCLUSION: Our results suggest that the E2-linked amelioration of ASD-like behaviors is specifically occurring in PV+/- mice, indicating that PV upregulation is required for the E2-mediated rescue of ASD-relevant behavioral impairments. ispartof: MOLECULAR AUTISM vol:9 ispartof: location:England status: published