Evaluation of an automated enzyme-linked fluorescent assay for thyroxine measurement in cat and dog sera

Measurement of total thyroxine (T4) is the first testing step in the work-up of thyroid disease in small animals. We evaluated an enzyme-linked fluorescent assay (ELFA) as an in-house method to measure T4 in cats and dogs. We compared the T4 concentration in sera of 122 cats and 176 dogs measured by the ELFA with an enzyme immunoassay (EIA) to assess the concordance of the 2 methods. Bias of the ELFA in cats was -11.4% and in dogs 1.4%. Using Bland-Altman plots, limits of agreement were -81.5 to 58.7% in cats and -71.4 to 74.4% in dogs. Imprecision was calculated for both methods. Intra- and interassay coefficients of variation (CVs) of the ELFA in feline sera were 0.7 and 3.4% and of the EIA 7.6 and 15.7%, respectively. Intra- and interassay CVs of both ELFA and EIA in canine sera were <9.5%. Reference intervals for the ELFA method were established and were 13.3-49.5 nmol/L for cats and 10.1-42.9 nmol/L for dogs. Accuracy of the EIA and ELFA was scored by assessing if the measured T4 value would identify the expected T4 range (low, normal, or elevated) of patients, based on history, clinical presentation, other diagnostic means, and response to therapy. This was possible for 75 cats and 50 dogs. Both methods yielded acceptable results, but the EIA was more accurate compared to the ELFA (percentage of true-positives in cats and dogs: EIA: 97% and 100%; ELFA: 92% and 94%)

Expression and Potential Function of ␤-Amyloid Precursor Proteins during Cutaneous Wound Repair

sAPP, the secretory domain of the ␤-amyloid precursor protein (APP), exerts a growth promoting and motogenic activity on keratinocytes. Here we report on the expression of APP and its homologue, the amyloid precursor like protein 2 (APLP2), during cutaneous wound repair using a full-thickness excisional wound healing model in mice. In unwounded skin APP was predominantly expressed in the basal cell layer. During wound healing increased suprabasal expression of APP was observed in all cell layers of the hyperproliferative epithelium at the wound margin. APP mRNA was increased up to 2.3-fold, whereas the APLP2 mRNA was decreased. Immunocytochemically, all proliferation competent keratinocytes of the normal as well as the wound site epidermis showed increased expression of APP but not of APLP2. Using culture models of keratinocyte differentiation the release of sAPP was found to be significantly higher in proliferating cells, i.e., when cultured at subconfluency or at low [Ca 2؉ ], than in quiescent, partially differentiated keratinocytes cultured at confluency or at high [Ca 2؉ ]. Our results suggest that sAPP secretion is presumably also increased in proliferation competent keratinocytes of the wound margin and that sAPP due to its growth promoting and motogenic function might participate in the control of epidermal wound repair. © 2002 Elsevier Science (USA

AIM2 inflammasome-derived IL-1 beta induces postoperative ileus in mice

Postoperative ileus (POI) is an intestinal dysmotility frequently occurring after abdominal surgery. An orchestrated neuroimmune response within the muscularis externa (ME) involves activation of resident macrophages, enteric glia and infiltration of blood-derived leukocytes. Interleukin-1 receptor type-I (IL1R1) signalling on enteric glia has been shown to be involved in POI development. Herein we investigated the distinct role of the IL1R1 ligands interleukin (IL)-1 alpha and IL-1 beta and focused on the mechanism of IL-1 beta production. IL-1 alpha and IL-1 beta deficient mice were protected from POI. Bone-marrow transplantation studies indicated that IL-1 alpha originated from radio-resistant cells while IL-1 beta was released from the radio-sensitive infiltrating leukocytes. Mouse strains deficient in inflammasome formation identified the absent in melanoma 2 (AIM2) inflammasome to be crucial for IL-1 beta production in POI. Mechanistically, antibiotic-treated mice revealed a prominent role of the microbiome in IL-1 beta production. Our study provides new insights into distinct roles of IL-1 alpha and IL-1 beta signalling during POI. While IL-1 alpha release is most likely an immediate passive response to the surgical trauma, IL-1 beta production depends on AIM2 inflammasome formation and the microbiome. Selective interaction in this pathway might be a promising target to prevent POI in surgical patients

Formation and Evolution of Dwarf Elliptical Galaxies - II. Spatially resolved star-formation histories

We present optical VLT spectroscopy of 16 dwarf elliptical galaxies (or dEs) comparable in mass to NGC 205, and belonging to the Fornax cluster and to nearby groups of galaxies. Using ULySS and STECKMAP, we derive radial profiles of the SSP-equivalent ages, metallicities and star-formation histories. The old stellar population of the dEs, which dominates their mass, is likely coeval with that of massive ellipticals or bulges, but the star formation efficiency is lower. Important intermediate age (1-5 Gyr) populations, and frequently tails of star formation until recent times are detected. These histories are reminiscent of their lower mass dSph counterparts of the Local Group. Most galaxies (10/16) show significant metallicity gradients, with metallicity declining by 0.5 dex over one half-light radius on average. These gradients are already present in the old population. The flattened (or discy), rotating objects (6/16) have flat metallicity profiles. This may be consistent with a distinct origin for these galaxies or it may be due to their geometry. The central SSP-equivalent age varies between 1 and 6 Gyr, with the age slowly increasing with radius in the vast majority of objects. The group and cluster galaxies have similar radial gradients and star-formation histories. The strong and old metallicity gradients place important constraints on the possible formation scenarios of dEs. Numerical simulations of the formation of spherical low-mass galaxies reproduce these gradients, but they require a longer time for them to build up. A gentle depletion of the gas, by ram-pressure stripping or starvation, could drive the gas-rich, star-forming progenitors to the present dEs.Comment: 21 pages, 9 figures. Accepted in MNRA

HELiPOD - revolution and evolution of a helicopter borne measurements system for multidisciplinary research in demanding environments

The helicopter-borne measurement system HELiPOD is a platform for atmospheric and other environmental measurements to investigate local and regional phenomena. It can be operated in remote areas, as from a research vessel with a helicopter, without the need for a runway. This article presents the current design concept, technical details and sensor package of HELiPOD, which was completely renewed for the deployment during the MOSAiC (Multidisciplinary drifting Observatory for the Study of Arctic Climate) expedition across the North Polar Ocean in 2019/2020. It was updated for the deployment in the methane campaigns METHANE-To-Go-Poland to study methane emissions from coal mines in South Poland, and METHANE-To-Go-Nordstream, a follow-up campaign to study methane emissions from the Baltic Sea after the NordStream pipeline leaks in 2022. The HELiPOD has dimensions of 5.2 m x 2.1 m x 1.2 m and a weight of around 325 kg. It provides the possibility for flight patterns on a horizontal scale of typically 100 m to 100 km and at altitudes from 10 m up to 3 km. HELiPOD employs distributed data acquisition and central data synchronization, equipped with sensors relevant to five fields of research: atmospheric dynamics, trace gases, aerosols, radiation and surface properties. The focus of the article is the technical realization, in particular the data acquisition system for about 60 sensors, as well as concepts for energy supply and thermalmanagement. It describes the complementary use of different measurement principles and redundant sensors for improved data quality. Operational procedures are also discussed

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Optimizacija držanja čovjekolikih robota utemeljena na podacima iz čovjekovog hoda

Achieving a stable, human-like gait for humanoid robots is a challenging task. While a variety of techniques exist to generate stable walking patterns, only little attention has been paid to the resemblance to the human gait. Popular gaits, for example, apply the strategy to bend the knees and to swing the torso in the lateral direction in order to ensure stability by shifting the center of mass. As a result, the walking patterns do not look very humanlike. However, human resemblance is an important aspect whenever robots are designed to coexist and interact with humans. In this article, we present techniques to optimize a given, stable gait of a humanoid robot with respect to human resemblance. To acquire human data, we use a full-body motion capture system. We propose four different optimization algorithms that work at joint angle basis and use the joint angle difference as measure of similarity. The experiments carried out with a HOAP-2 robot in simulation demonstrate that all techniques generate a gait that is significantly more human-like compared to the robot’s initial gate. As the results show, the optimization methods based on hill climbing and policy gradient estimation yield the best performance.Postizanje stabilnog, čovjekolikog držanja čovjekolikih robota vrlo je zahtjevan zadatak. Iako postoji mnoštvo tehnika koje se koriste za postizanje stabilnih uzoraka hodanja, malo se pažnje pridaje sličnosti s ljudskim držanjem. Primjerice, neke tehnike koriste strategiju savijanja koljena i njihanja torza u lateralnom smjeru kako bi se osigurala stabilnost kroz promjenu položaja centra mase. Kao rezultat toga, uzorci hodanja nisu slični čovjekovom hodu. Ipak, sličnost čovjeku važan je aspekt u slučajevima kada su roboti izvedeni za suživot i interakciju s ljudima. U ovom su članku predstavljene tehnike za optimizaciju danih stabilnih držanja čovjekolikog robota s ciljem sličnosti čovjeku. Za prikupljanje podataka o čovjeku koristi se sustav za snimanje cjelokupnog gibanja tijela. Predložena su četiri različita algoritma optimizacije koji koriste zajedničku derivaciju kuta kao mjeru sličnosti. Eksperimenti provedeni koristeći HOAP-2 robot pokazuju da svi postupci generiraju držanje koje je značajno više nalik čovjekovom držanju u odnosu na početno držanje robota. Kao što rezultati pokazuju, metode optimizacije koje se zasnivaju na penjanju uzbrdo i estimaciji gradijenta smjera daju najbolje rezultate