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In view of the planned abandonment of routine beak-trimming in turkeys in Germany, two different blunting methods were evaluated at the "Education, Research and Demonstration Centre of Poultry and Small Animal Farming" in Kitzingen (Germany) and the effects on selected welfare indicators for non beak-trimmed turkeys were examined. Altogether 746 male B. U. T. 6 turkey chicks of the breeding company Moorgut Kartzfehn von Kameke GmbH & Co. KG, Bösel, Germany were housed. For the first five weeks the chicks were reared in twelve compartments with a stocking density of 11.8 kg/m2. For the actual examination during the fattening period (6.-21. live week), a total of 600 male turkeys were randomized to a total of 24 experimental compartments after the fifth week of life (planned stocking density: 51,9 kg/m²) and the respective blunting method was installed into the pan feeding system of the compartments. The following control and experimental groups were used: K1: beak-trimmed turkeys without blunting (n = 150 animals); K2: non beak-trimmed turkeys without blunting (n = 150 animals); V1: non beak-trimmed turkeys with screed grinding disc as blunting method (n = 150 animals) and V2: non beak-trimmed turkeys with metal grid disc (n = 150 animals). In 28-days rhythms the turkeys were scored, the beak was measured and the weight of the animals was recorded. In addition, data on indoor and outdoor climate such as light intensity, gaseous ammonia content, temperature and humidity was collected. In addition 12 randomly selected turkeys from each variant were slaughtered in Kitzingen after the 17th and 21st week of life, and their heads examined macroscopically and histologically at the Bavarian State Office for Health and Food Safety in Erlangen (Bavaria, Germany). There were significant differences (p = 0.05) between the experimental groups in the beak rating, concerning the length of the beak, the beak supernatant and the slaughter weight. Strong differences were found between the beak-trimmed and the non beak-trimmed turkeys. Significant (p = 0.05) differences were also noted between the two blunting methods, for example in the upper beak supernatant: with screed grinding disc 3.02 mm and with the metal grid disc 4.00 mm. With regard to the morphology of the beak, a significant higher abrasion was achieved with screed grinding discs without any injury to the tactile organ. [ABSTRACT FROM AUTHOR]

Abstract Background Exercise electrocardiography (ECG) is frequently used in the work-up of patients with suspected coronary artery disease (CAD), however the accuracy is reduced in women. Cardiovascular magnetic resonance (CMR) stress testing can accurately diagnose CAD in women. To date, a direct comparison of CMR to ECG has not been performed. Methods and results We prospectively enrolled 88 consecutive women with chest pain or other symptoms suggestive of CAD. Patients underwent a comprehensive clinical evaluation, exercise ECG, a CMR stress test including perfusion and infarct imaging, and x-ray coronary angiography (CA) within 24 hours. CAD was defined as stenosis ≥70% on quantitative analysis of CA. Exercise ECG, CMR and CA was completed in 68 females (age 66.4 ± 8.8 years, number of CAD risk factors 3.5 ± 1.4). The prevalence of CAD on CA was 29%. The Duke treadmill score (DTS) in the entire group was −3.0 ± 5.4 and was similar in those with and without CAD (−4.5 ± 5.8 and −2.4 ± 5.1; P = 0.12). Sensitivity, specificity and accuracy for CAD diagnosis was higher for CMR compared with exercise ECG (sensitivities 85% and 50%, P = 0.02, specificities 94% and 73%, P = 0.01, and accuracies 91% and 66%, P = 0.0007, respectively). Even after applying the DTS the accuracy of CMR was higher compared to exercise ECG (area under ROC curve 0.94 ± 0.03 vs 0.56 ± 0.07; P = 0.0001). Conclusions In women with intermediate-to-high risk for CAD who are able to exercise and have interpretable resting ECG, CMR stress perfusion imaging has higher accuracy for the detection of relevant obstruction of the epicardial coronaries when directly compared to exercise ECG.

Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by inborn errors of cytotoxicity. Patients with biallelic PRF1 null mutations (encoding perforin) usually develop excessive immune cell activation, hypercytokinemia, and life-threatening immunopathology in the first 6 months of life, often without an apparent infectious trigger. In contrast, perforin-deficient (PKO) mice only develop HLH after systemic infection with lymphocytic choriomeningitis virus (LCMV). We hypothesized that restricted microbe-immune cell interactions due to specific pathogen-free (SPF) housing might explain the need for this specific viral trigger in PKO mice. To investigate the influence of a "wild" microbiome in PKO mice, we fostered PKO newborns with Wildling microbiota ('PKO-Wildlings') and monitored them for signs of HLH. PKO-Wildlings survived long-term without spontaneous disease. Also, systemic infection with vaccinia virus did not reach the threshold of immune activation required to trigger HLH in PKO-Wildlings. Interestingly, after infection with LCMV, PKO-Wildlings developed an altered HLH pattern. This included lower IFN-γ serum levels along with improved IFN-γ-driven anemia, but more elevated levels of IL-17 and increased liver inflammation compared with PKO-SPF mice. Thus, wild microbiota alone is not sufficient to trigger HLH in PKO mice, but host-microbe interactions shape inflammatory cytokine patterns, thereby influencing manifestations of HLH immunopathology., (© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)

Inositol 1,4,5-trisphosphate (IP3) receptor type 1 ( ITPR1 ), 2 ( ITPR2 ), and 3 ( ITPR3 ) encode the IP3 receptor (IP3R), a key player in intracellular calcium release. In four unrelated patients, we report that an identical ITPR3 de novo variant-NM_002224.3:c.7570C>T, p.Arg2524Cys-causes, through a dominant-negative effect, a complex multisystemic disorder with immunodeficiency. This leads to defective calcium homeostasis, mitochondrial malfunction, CD4 + lymphopenia, a quasi-absence of naïve CD4 + and CD8 + cells, an increase in memory cells, and a distinct TCR repertoire. The calcium defect was recapitulated in Jurkat knock-in. Site-directed mutagenesis displayed the exquisite sensitivity of Arg 2524 to any amino acid change. Despite the fact that all patients had severe immunodeficiency, they also displayed variable multisystemic involvements, including ectodermal dysplasia, Charcot-Marie-Tooth disease, short stature, and bone marrow failure. In conclusion, unlike previously reported ITPR1-3 deficiencies leading to narrow, mainly neurological phenotypes, a recurrent dominant ITPR3 variant leads to a multisystemic disease, defining a unique role for IP3R3 in the tetrameric IP3R complex.

High-dimensional brain activity is often organized into lower-dimensional neural manifolds. However, the neural manifolds of the visual cortex remain understudied. Here, we study large-scale multi-electrode electrophysiological recordings of macaque (Macaca mulatta) areas V1, V4, and DP with a high spatiotemporal resolution. We find that the population activity of V1 contains two separate neural manifolds, which correlate strongly with eye closure (eyes open/closed) and have distinct dimensionalities. Moreover, we find strong top-down signals from V4 to V1, particularly to the foveal region of V1, which are significantly stronger during the eyes-open periods. Finally, in silico simulations of a balanced spiking neuron network qualitatively reproduce the experimental findings. Taken together, our analyses and simulations suggest that top-down signals modulate the population activity of V1. We postulate that the top-down modulation during the eyes-open periods prepares V1 for fast and efficient visual responses, resulting in a type of visual stand-by state., Competing Interests: Declaration of interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Forschungszentrum Juelich GmbH. Published by Elsevier Inc. All rights reserved.)

Scientific research demands reproducibility and transparency, particularly in data-intensive fields like electrophysiology. Electrophysiology data are typically analyzed using scripts that generate output files, including figures. Handling these results poses several challenges due to the complexity and iterative nature of the analysis process. These stem from the difficulty to discern the analysis steps, parameters, and data flow from the results, making knowledge transfer and findability challenging in collaborative settings. Provenance information tracks data lineage and processes applied to it, and provenance capture during the execution of an analysis script can address those challenges. We present Alpaca (Automated Lightweight Provenance Capture), a tool that captures fine-grained provenance information with minimal user intervention when running data analysis pipelines implemented in Python scripts. Alpaca records inputs, outputs, and function parameters and structures information according to the W3C PROV standard. We demonstrate the tool using a realistic use case involving multichannel local field potential recordings of a neurophysiological experiment, highlighting how the tool makes result details known in a standardized manner in order to address the challenges of the analysis process. Ultimately, using Alpaca will help to represent results according to the FAIR principles, which will improve research reproducibility and facilitate sharing the results of data analyses., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Köhler et al.)

Neuroscience is moving toward a more integrative discipline where understanding brain function requires consolidating the accumulated evidence seen across experiments, species, and measurement techniques. A remaining challenge on that path is integrating such heterogeneous data into analysis workflows such that consistent and comparable conclusions can be distilled as an experimental basis for models and theories. Here, we propose a solution in the context of slow-wave activity (<1 Hz), which occurs during unconscious brain states like sleep and general anesthesia and is observed across diverse experimental approaches. We address the issue of integrating and comparing heterogeneous data by conceptualizing a general pipeline design that is adaptable to a variety of inputs and applications. Furthermore, we present the Collaborative Brain Wave Analysis Pipeline (Cobrawap) as a concrete, reusable software implementation to perform broad, detailed, and rigorous comparisons of slow-wave characteristics across multiple, openly available electrocorticography (ECoG) and calcium imaging datasets., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

During free viewing, we move our eyes and fixate on objects to recognize the visual scene of our surroundings. To investigate the neural representation of objects in this process, we studied individual and population neuronal activity in three different visual regions of the brains of macaque monkeys ( Macaca fuscata ): the primary and secondary visual cortices (V1, V2) and the inferotemporal cortex (IT). We designed a task where the animal freely selected objects in a stimulus image to fixate on while we examined the relationship between spiking activity, the order of fixations, and the fixated objects. We found that activity changed across repeated fixations on the same object in all three recorded areas, with observed reductions in firing rates. Furthermore, the responses of individual neurons became sparser and more selective with individual objects. The population activity for individual objects also became distinct. These results suggest that visual neurons respond dynamically to repeated input stimuli through a smaller number of spikes, thereby allowing for discrimination between individual objects with smaller energy., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Yamane et al.)