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Abstract The antiarrhythmic and cardiac electrophysiological effects of SZV-2649 that contains a 2,6-diiodophenoxy moiety but lacks the benzofuran ring system present in amiodarone, were studied in mammalian cell line, rat and dog cardiac preparations. SZV-2649 exerted antiarrhythmic effects against coronary artery occlusion/reperfusion induced ventricular arrhythmias in rats and in acetylcholine- and burst stimulation induced atrial fibrillation in dogs. SZV-2649 inhibited hERG and GIRK currents in HEK cells (IC50: 342 and 529 nM, respectively). In canine ventricular myocytes, SZV-2649 (10 µM) decreased the densities of IKr, and Ito outward and INaL and ICaL inward currents. The compound (2.5–10 µM) elicited Class IB type Vmax reducing and Class III type action potential duration prolonging effects in dog right ventricular muscle preparations. In canine atrial muscle, SZV-2629 (2.5–10 µM) moderately prolonged action potential duration and this effect was greatly augmented in preparations pretreated with 1 µM carbachol. In conclusion, SZV-2649, has antiarrhythmic effects based on its multiple ion channel blocking properties. Since its chemical structure substantially differs from that of amiodarone, it is expected that SZV-2649 would exhibit fewer adverse effects than the currently used most effective multichannel inhibitor drug amiodarone and may be a promising molecule for further development.

This article presents the authors’ perspectives on modelling best practices for nature-based solutions (NBS). The authors led a workshop on NBS modelling as part of the 8th IWA Water Resource Recovery Modelling Seminar (WRRmod2022+) in January 2023, where the discussion centred around the design, use cases, and potential applications of NBS models. Four real-world case studies, encompassing an aerated lagoon, a biofilm-enhanced aerated lagoon, a stormwater basin, and a constructed wetland were reviewed to demonstrate practical applications and challenges in modelling NBS systems. The initial proposed modelling framework was derived from these case studies and encompassed eight sub-models used for these NBS types. The framework was subsequently extended to include eight additional NBS categories, requiring a total of 10 sub-models. In a subsequent step, with a different perspective, the framework was refined to focus on 13 primary use cases of NBS, identifying 10 sub-models needed or potentially required for these specific NBS applications. These frameworks help to identify the necessary sub-models for the NBS system at hand or the use case. This article also discusses the benefits and challenges of applying water resource recovery modelling best practices to NBS, along with recommendations for future research in this area. HIGHLIGHTS Data scarcity is a primary challenge to NBS modelling, with limited data available for model calibration and validation.; The numerous use cases and categories of NBS technologies complicate the development of a broad and flexible modelling framework.; Inspired by four NBS case studies, the paper addresses diverse objectives and challenges in NBS modelling.; The proposed frameworks offer a structured approach to NBS modelling, considering various categories, use cases, and essential sub-models.;

Introduction: Natalizumab (NAT), a highly effective disease modifying therapy (DMT) in relapsing-remitting multiple sclerosis (RRMS), was approved for clinical use in Hungary on February 1, 2010. In this study we aimed to assess its effectiveness in view of the concept of “No Evidence of Disease Activity” (NEDA-3), furthermore evaluate its effect on limb function, pathopsychological symptoms (cognition, fatigue, depression) and quality of life (QoL). Patients and methods: From February 1, 2010, to December 1, 2022, 121 eligible patients were consecutively enrolled from the MS center of the University of Szeged, Hungary. Here, we report data on 6-years of follow-up. First, we evaluated the proportion of patients reaching the NEDA-3 state and any possible influencing factors. Then, we assessed the change of upper and lower limb functions via the 9-hole-peg test (9HPT) and the 25-feet walk test (TW25F). Finally, we assessed the change of pathopsychological symptoms (cognition, fatigue, depression) and QoL via the BICAMS, FIS, BDI-II and MSQoL-54 questionnaires, and the possible influencing factors behind it. Results: Cumulatively, 97 patients (80.2 %) achieved NEDA-3 throughout the follow-up period. On a year-by-year basis, the proportion changed from 95.9 % in the 1st year to 84.3 %, 81.3 %, 76.4 %, 74.5 % and 78.9 % in the 2nd, 3rd, 4th, 5th and 6th year respectively (p

In rats decreased bioavailability of nitric oxide induces oxidative stress and right heart failure. Oxidative stress can activate matrix metalloproteinase-2 (MMP2). We addressed the question whether increasing oxidative defense by administration of the SOD mimetic Tempol or direct inhibition of MMP2 activity by SB-3CT mitigates right heart failure. Rats received l-NAME for four weeks and during week three and four treatment groups received either Tempol or SB-3CT in addition. After four weeks heart function was analyzed by echocardiography, organ weights and expression of NPPB and COL1A1 were analyzed, oxidative stress was monitored by DHE-staining and MMP2 activity was quantified by proteolytic auto-activation, zymography, and troponin I degradation. l-NAME induced oxidative stress and MMP2 activity stronger in the right ventricle than in the left ventricle. Troponin I, a MMP2 substrate, was degraded in right ventricles. Tempol reduced oxidative stress and preferentially affected the expression of fibrotic genes (i.e. COL1A1) and fibrosis. Tempol and SB-3CT mitigated right but not left ventricular hypertrophy. Neither SB-3CT nor Tempol alone strongly improved right ventricular function. In conclusion, both MMP2 activity and oxidative stress contribute to right ventricular failure but neither is MMP2 activation linked to oxidative stress nor does oxidative stress and MMP2 activity have common targets.

Bullying, harassment, and sexual harassment in the workplace are not new issues; they have always existed in various forms. Recent studies have highlighted their impacts on workers and their well-being at work. However, the perception of these problems differ across the United States, Europe, and Asia. These differences are reflected not only in terms of sensitivities, workplace policies, and relevant laws, but also in the language/vocabulary used to designate the same. Psychological harassment is a bitter issue for many who are affected by it. Unfortunately, it remains a less popular topic in academic research. This may be due to the sensitivity associated with the topic, the possible shame and value judgements of those involved, and the myriad cultural differences that complicate its perceptions. This study deals with the characteristics of psychological harassment in workplaces across Hungary and Slovakia. It addresses the following questions: How are the sources of psychological bullying perceived in the two countries, how do victims tolerate the abuse they are subjected to, and what factors influence the same. The study also examines whether the company’s tools for combating psychological bullying in the workplace have an impact on an employee’s decision to leave the organization as a result of mobbing. It conducted quantitative surveys involving 500 Hungarian and 108 Slovakian employees. The results were analyzed by the authors using SPSS version 28 with univariate and multivariate statistical methods. Frequency analysis, ANOVA, T- test and factor analysis, among others, were performed. The results show that the perception of the sources of psychological bullying and the tolerance of the related phenomena depend on a number of personal factors. However, the tools that firms use to deal with mobbing do not necessarily play a determining role in an employee’s decision to leave their workplace following psychological harassment.

Abstract The estrus cycle in female rodents has been shown to affect a variety of physiological functions. However, little is known about its presumably thorough effect on auditory processing during the sleep–wake cycle and sleep deprivation. Vertex auditory evoked potentials (vAEPs) were evoked by single click tone stimulation and recorded during different stages of the estrus cycle and sleep deprivation performed in metestrus and proestrus in female rats. vAEPs showed a strong sleep-dependency, with the largest amplitudes present during slow wave sleep while the smallest ones during wakefulness. Higher amplitudes and longer latencies were seen in the light phase during all vigilance stages. The largest amplitudes were found during proestrus (light phase) while the shortest latencies were seen during estrus (dark phase) compared to the 2nd day diestrus baseline. High-amplitude responses without latency changes were also seen during metestrus with increased homeostatic sleep drive. More intense and faster processing of auditory information during proestrus and estrus suggesting a more effective perception of relevant environmental cues presumably in preparation for sexual receptivity. A 4-h sleep deprivation resulted in more pronounced sleep recovery in metestrus compared to proestrus without difference in delta power replacement suggesting a better tolerance of sleep deprivation in proestrus. Sleep deprivation decreased neuronal excitability and responsiveness in a similar manner both during metestrus and proestrus, suggesting that the negative consequences of sleep deprivation on auditory processing may have a limited correlation with the estrus cycle stage.

Abstract In this work we aim to provide a quantitative method allowing the probing of the physiological status of honeybee colonies by providing them with a gentle, short, external artificial vibrational shockwave, and recording their response. The knock is provided by an external electromagnetic shaker attached to the outer wall of a hive, driven by a computer with a 0.1 s long, monochromatic vibration at 340Hz set to an amplitude that occasionally yields a mild response from the bees, recorded by an accelerometer placed in the middle of the central frame of the colony. To avoid habituation, the stimulus is supplied at randomised times, approximately every hour. The method is pioneered with a pilot study on a single colony hosted indoors, then extended onto eight outdoors colonies. The results show that we can quantitatively sense the colony’s overall mobility, independently from another physiological aspect, which is phenomenologically explored. Using this, a colony that is queenless is easily discriminated from the others.

The eradication of bacterial biofilms remains a persistent challenge in medicine, particularly because an increasing number of biofilms exhibit resistance to conventional antibiotics. This underscores the importance of searching for novel compounds that present antibacterial and biofilm inhibition activity. Various types of honey and essential oil were proven to be effective against a number of biofilm-forming bacterial strains. The current study demonstrated the effectiveness of the relatively unexplored fennel honey (FH), fennel essential oil (FEO), and their combination against biofilm-forming bacterial strains Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and Escherichia coli, with a series of in vitro experiments. The authenticity of FH and FEO was checked with light microscopy and gas chromatography-mass spectrometry, respectively. Minimum inhibitory concentrations were determined using the microdilution method, and antibiofilm activity was assessed with crystal violet assay. Structural changes in bacterial cells and biofilms, induced by the treatments, were monitored with scanning electron microscopy. FEO and FH inhibited the biofilm formation of each bacterial strain, with FEO being more effective compared to FH. Their combination was the most effective, with inhibitory rates ranging between 87 and 92%, depending on the bacterial strain. The most sensitive bacterium was E. coli, while P. aeruginosa was the most resistant. These results provide justification for the combined use of honey and essential oil to suppress bacterial biofilms and can serve as a starting point to develop an effective surface disinfectant with natural ingredients.

The measurement of organizational satisfaction is a popular topic in organizational science; however, less attention is given to organizational happiness. There are very few measuring tools designed to evaluate organizational happiness. While the value-mediating role of higher education is indisputable, to the best of our knowledge, this is the first study to address organizational happiness in the context of higher education. In addition, this study proposes new data-driven approaches to analyze patterns of answers (i.e. regarding individual happiness); therefore, the relationships among individuals, groups, and organizational happiness can be better analyzed. This study is based on survey data; nevertheless, in addition to measuring organizational happiness in Hungarian higher education, this paper proposes using infrequently used data-driven approaches to determine who feels happy/unhappy in what areas.

Although hearing impaired people represent a significant group of handicapped people, only a few studies examine their physical activities. This study was performed in the Spring of 2019 in Debrecen, Hungary by recruiting 86 hearing impaired people. Here the frequency and type of their physical activity as well as their motivation was examined. Average age of the subjects was 42.0±16.9 years, 41.9% of them performs regular physical activity. Out of them 54.1% excercises twice a week, the rest even more often. Soccer, jogging, and cycling were the most preferred sports. Percentage of hearing impaired people performing regular physical activity was about the same as it was for people with normal hearing. Reason for motivation – it makes them happy and they feel better due to the physical activity – or staying at home – their health condition limits them and they have little free time – was also similar in both groups. However, 80% of the people with impaired hearing preferred to do physicial activity together other hearing impaired.

Fatigue is one of the most frequent complaints of patients with multiple sclerosis (MS). The Fatigue Impact Scale (FIS), one of the 30 available fatigue questionnaires, is commonly applied because it evaluates multidimensional aspects of fatigue. The chief objectives of this study were to validate FIS and evaluate the psychometric properties of MS patients in Serbia. One hundred and twenty-one (121) MS patients and one hundred and twenty-two (122) age-, gender- and education-matched healthy control (HC) subjects completed the FIS and the Beck Depression Inventory. Internal consistency of the FIS subscales was determined using Cronbach’s Alpha Coefficient. Test/retest reliability with an intra-class correlation coefficient (ICC) for each FIS subscale was performed. The total FIS score and subscale scores showed statistically significant differences between the MS patients and the HC subjects in both FIS sessions. Cronbach’s Alpha was 0.966. All ICCs were statistically significant (p < 0.05). The Serbian version of this instrument may be useful as a clinical measure for fatigue and functionality in patients with MS.

In recent years, the use of high-level IT systems and the digitalisation of organisational processes has become increasingly important in business organisations. This means that digitalisation is one of the most frequently mentioned objectives in the development of organisations. This study aims to examine how well-prepared organisations are on the path towards these goals and how can organisational culture help. The quantitative international research involved 692 respondents in 34 countries across 6 continents. Responses were assessed using SPSS software. The results show that an organisational culture that is open to change and based on trust supports digital transformation processes, leadership attitudes, human responses and interactions. Regardless of geographical location and economic performance, organisations face similar challenges and there are no marked differences internationally in terms of preparedness for digital transformation. The characteristics of the learning organisation culture studied have the greatest impact on leadership behaviour and the least influence on the digital tools used.

Ова студија бави се пустињом Ота Толнаија, Африком у његовим песмама, пустаром из детињства у Кањижи и материјама везаним за њу (песком, златом и прашином). Анализа се заснива на Толнаијевој збирци од тридесет и две песме о Африци, која представља један од узбудљивих експеримената у вези с Толнаијевом алхемијом као вредношћу и начином за стварање својеврсне уметничке аутономије, и подстицајан покушај за „радикално и аутономно стварање културе“. Његова збирка песама под насловом Сенка Микела Барсела објављена је 2006. године, а српски превод Арпада Вицка објављен је 2019. И премда Толнаи никада није био у Африци, он је кадар да континент и његове пустиње замисли на јединствено фасцинантан начин, кроз интерпретацију различитих уметничких и књижевних творевина попут Барселових слика, Рембоове поезије и биографије, путних наратива и песама Лорана Гаспара, Камијевих пустињских наратива, текстова Антоана де Сент-Егзиперија и номадолошке концепције Делеза и Гатарија. Мањински песник уграђује ове импресије у искуство властитог завичаја, истовремено избегавајући употребу стереотипа, клишеа или колонијалног схватања Африке као црног (непознатог, тамног) или егзотичног континета. За Толнаија пустиња постаје терен (уметничке) идентификације: открива се егзистенцијално и естетичко искуство бивствовања у радикално различитом простору (Африци), а скреће се пажња и на активну солидарност. У анализи афричких песама, проблеми уметничке аутономије, политичке идеологије и моћи тумаче се пре свега у оквирима мањинске и номадолошке теорије Делеза и Гатарија.

Abstract Little is known about mite gait, but it has been suggested that there could be greater variation in locomotory styles for arachnids than insects. The Varroa destructor mite is a devastating ectoparasite of the honeybee. We aim to automatically detect Varroa-specific signals in long-term vibrational recordings of honeybee hives and additionally provide the first quantification and characterisation of Varroa gait through the analysis of its unique vibrational trace. These vibrations are used as part of a novel approach to achieve remote, non-invasive Varroa monitoring in honeybee colonies, requiring discrimination between mite and honeybee signals. We measure the vibrations occurring in samples of freshly collected capped brood-comb, and through combined critical listening and video recordings we build a training database for discrimination and classification purposes. In searching for a suitable vibrational feature, we demonstrate the outstanding value of two-dimensional-Fourier-transforms in invertebrate vibration analysis. Discrimination was less reliable when testing datasets comprising of Varroa within capped brood-cells, where Varroa induced signals are weaker than those produced on the cell surface. We here advance knowledge of Varroa vibration and locomotion, whilst expanding upon the remote detection strategies available for its control.

The study aims to examine the relationship and interaction between learning organization culture and the factors influencing digital transformation (leadership style, training, digital readiness, and trust), as well as identify factors that significantly influence learning organization functioning by exploring the extension of a grounded theory framework. The survey was conducted using an online questionnaire. The survey population was composed of managers of Eastern European manufacturing companies who were reached through the Orbis database. The survey yielded 618 evaluable responses (n = 618). The PLS-SEM method was used because the structural model is complex, with many constructs (some of which are formatively measured) and model relationships. Leadership behavior and a supportive management style inspire the development and training of employees, through which the level of readiness for digitalization and Industry 4.0 technologies can be increased. Training in these skills will increase confidence in digitalization technologies. Leadership support also influences digital trust and employee response to the use of digital technologies, as does participation in training, which directly supports digitalization and I4.0 readiness. The results of the research not only support previous research findings but also complement them by focusing specifically on the impact on the learning organization in the context of digitalization. This study provides evidence that leadership that is supportive of the learning organization's culture plays a key role. Overall, leadership is a dominant influence in the digital transformation of organizations and in shaping the learning organization culture this requires, but all the relationships represented in the model have a significant positive relationship. Doi: 10.28991/ESJ-2023-SIED2-09 Full Text: PDF

Abstract Transorbital sonography (TOS) could be a swift and convenient method to detect the atrophy of the optic nerve, possibly providing a marker that might reflect other quantitative structural markers of multiple sclerosis (MS). Here we evaluate the utility of TOS as a complementary tool for assessing optic nerve atrophy, and investigate how TOS-derived measures correspond to volumetric brain markers in MS. We recruited 25 healthy controls (HC) and 45 patients with relapsing–remitting MS and performed B-mode ultrasonographic examination of the optic nerve. Patients additionally underwent MRI scans to obtain T1-weighted, FLAIR and STIR images. Optic nerve diameters (OND) were compared between HC, MS patients with and without history of optic neuritis (non-ON) using a mixed-effects ANOVA model. The relationship between within-subject-average OND and global and regional brain volumetric measures was investigated using FSL SIENAX, voxel-based morphometry and FSL FIRST. OND was significantly different between HC-MS (HC = 3.2 ± 0.4 mm, MS = 3 ± 0.4 mm; p

Implementation of marker-assisted selection (MAS) in modern beekeeping would improve sustainability, especially in breeding programs aiming for resilience against the parasitic mite Varroa destructor. Selecting honey bee colonies for natural resistance traits, such as brood-intrinsic suppression of varroa mite reproduction, reduces the use of chemical acaricides while respecting local adaptation. In 2019, eight genomic variants associated with varroa non-reproduction in drone brood were discovered in a single colony from the Amsterdam Water Dune population in the Netherlands. Recently, a new study tested the applicability of these eight genetic variants for the same phenotype on a population-wide scale in Flanders, Belgium. As the properties of some variants varied between the two studies, one hypothesized that the difference in genetic ancestry of the sampled colonies may underly these contribution shifts. In order to frame this, we determined the allele frequencies of the eight genetic variants in more than 360 Apis mellifera colonies across the European continent and found that variant type allele frequencies of these variants are primarily related to the A. mellifera subspecies or phylogenetic honey bee lineage. Our results confirm that population-specific genetic markers should always be evaluated in a new population prior to using them in MAS programs.

Introduction: Ischemic conditionings (ICon) were intensively investigated and several protective signaling pathways were identified. Previously, we have shown the role of matrix metalloproteinases (MMP) in myocardial ischemia/reperfusion injury (MIRI) and the cardioprotective role of biglycan (BGN), a small leucine-rich proteoglycan in vitro. Here, we hypothesized that cardiac MMP and BGN signaling are involved in the protective effects of ICon. Methods: A reverse target-microRNA prediction was performed by using the miRNAtarget™ 2.0 software to identify human microRNAs with a possible regulatory effect on MMP and BGN, such as on related genes. To validate the identified 1289 miRNAs in the predicted network, we compared them to two cardioprotective miRNA omics datasets derived from pig and rat models of MIRI in the presence of ICons. Results: Among the experimentally measured miRNAs, we found 100% sequence identity to human predicted regulatory miRNAs in the case of 37 porcine and 24 rat miRNAs. Upon further analysis, 42 miRNAs were identified as MIRI-associated miRNAs, from which 24 miRNAs were counter-regulated due to ICons. Conclusions: Our findings highlight 24 miRNAs that potentially regulate cardioprotective therapeutic targets associated with MMPs and BGN in a highly translatable porcine model of acute myocardial infarction.

AbstractThe measurement of organizational satisfaction is a popular topic in organizational science; however, less attention is given to organizational happiness. There are very few measuring tools designed to evaluate organizational happiness. While the value-mediating role of higher education is indisputable, to the best of our knowledge, this is the first study to address organizational happiness in the context of higher education. In addition, this study proposes new data-driven approaches to analyze patterns of answers (i.e. regarding individual happiness); therefore, the relationships among individuals, groups, and organizational happiness can be better analyzed. This study is based on survey data; nevertheless, in addition to measuring organizational happiness in Hungarian higher education, this paper proposes using infrequently used data-driven approaches to determine who feels happy/unhappy in what areas.

AbstractThe majority of research on competitiveness is based on the analysis of quantitative data. There is significantly less research on the soft elements of competitiveness. This research aims to fill this gap in the literature. Starting from the national culture, the authors investigated the impact of trust characteristics of organisational culture on the characteristics of strategy, knowledge management and organisational effectiveness. Respondents (∑943) from five countries on three continents (USA, China, Hungary, Slovakia, Romania) took part in the quantitative research conducted with a questionnaire survey. The analysis was performed using the SPSS and AMOS 27 programs based on the SEM model. The results show that there is a significant relationship between the examined elements of competitiveness (strategy and management), which also show a significant relationship with organisational trust. Through a culture of trust, the interaction between the elements has a significant impact on the characteristics influencing the efficient operation of the organisation and its competitiveness, regardless of the value of Hofstede’s characteristics of different national cultures.

Research in recent years has shown that IT-enabled companies have higher productivity than their competitors. The new and latest technological solutions enrich the range of tools available to workers, ensuring that information is always available, communication is easier, and customers are better served. At the same time, these opportunities also create psycho-social pressures that strain workers’ working and private lives and can lead to further problems of techno-addiction. The study aims to investigate the relationships between the characteristics of technostress and their combined impact on trust within the organization between human-human and human-technology relationships. The quantitative study involved 531 respondents. Responses were analyzed using IBM SPSS 28 and IBM AMOS 27. The results show that there is undoubtedly a close relationship and a mutually generating effect between technostress characteristics, which substantially impact trust within the organization. However, trust is still stronger in personal relationships than in human-technology relationships. According to the respondents, the level of preparedness, technological knowledge, and expectations influence trust in the use of technology, which also affects performance and work-life balance. AcknowledgmentThis study is supported by the Research Centre at Faculty of Business and Economics (No. PE-GTK-GSKK A095000000-4) of University of Pannonia (Veszprém, Hungary).

Besides the health benefits of regular exercise, high-level training--above an optimal level--may have adverse effects. In this study, we investigated the effects of long-term vigorous training and its potentially detrimental structural-functional changes in a small animal athlete's heart model. Thirty-eight 4-month-old male guinea pigs were randomized into sedentary and exercised groups. The latter underwent a 15-week-long endurance-training program. To investigate the effects of the intense long-term exercise, in vivo (echocardiography, electrocardiography), ex vivo, and in vitro (histopathology, patch-clamp) measurements were performed. Following the training protocol, the exercised animals exhibited structural left ventricular enlargement and a significantly higher degree of myocardial fibrosis. Furthermore, resting bradycardia accompanied by elevated heart rate variability occurred, representing increased parasympathetic activity in the exercised hearts. The observed prolonged QTc intervals and increased repolarization variability parameters may raise the risk of electrical instability in exercised animals. Complex arrhythmias did not occur in either group, and there were no differences between the groups in ex vivo or cellular electrophysiological experiments. Accordingly, the high parasympathetic activity may promote impaired repolarization in conscious exercised animals. The detected structural-functional changes share similarities with the human athlete's heart; therefore, this model might be useful for investigations on cardiac remodeling. Key words: long-term endurance training, cardiac remodeling, echocardiography, electrocardiography, histology En dehors des bienfaits pour la sante qu'apporte l'exercice physique regulier, l'entrainement de haut niveau-au-dela d'un degre optimal-pourrait avoir des effets indesirables. Cette etude portait sur les effets de l'entrainement vigoureux a long terme de meme que sur des variations structurelles ou fonctionnelles potentiellement deleteres dans un modele de coeur d'athlete chez un petit animal. Nous avons reparti aleatoirement 38 cobayes males ages de 4 mois dans des groupes de sedentarite et d'exercice physique. Les animaux de ce dernier groupe ont suivi un programme d'entrainement en endurance sur 15 semaines. Nous avons procede a des epreuves in vivo (echocardiographie, electrocardiographie), ex vivo et in vitro (histopathologie, << patch-clamp >>) en vue d'etudier les effets de l'exercice intense a long terme. A la suite du protocole, les animaux entraines ont presente une augmentation structurelle de la taille du ventricule gauche et une augmentation marquee du degre de fibrose myocardique. En outre, nous avons observe une bradycardie au repos accompagnee d'une augmentation de la variabilite de la frequence cardiaque chez les animaux entraines, ce qui represente une augmentation de l'activite parasympathique cardiaque dans leur cas. La prolongation des intervalles QTc et la hausse des parametres de la variabilite de la repolarisation pourraient entrainer un accroissement du risque d'instabilite electrique chez les animaux entraines. Nous n'avons pas observe d'arythmies complexes dans l'un ou l'autre groupe, ni de difference entre eux quant aux mesures ex vivo ou dans le cadre des experiences d'electrophysiologie cellulaire. Consequemment, l'augmentation de l'activite parasympathique a des degres eleves pourrait favoriser l'apparition d'anomalies de la repolarisation chez les animaux entraines conscients. Les variations structurelles et fonctionnelles que nous avons decelees presentent des points communs avec le coeur d'athlete chez l'humain. Par consequent, ce modele pourrait etre utile en vue d'etudier le remodelage cardiaque. [Traduit par la Redaction] Mots-cles : entrainement en endurance a long terme, remodelage cardiaque, echocardiographie, electrocardiographie, histologie, Introduction The positive impact of regular exercise on a healthy and fulfilling lifestyle is undoubted (Deslandes et al. 2009; Lavie et al. 2019). Therefore, active athletes are considered the healthiest [...]

Abstract Photoelectrochemical (PEC) hydrogen evolution reaction (HER) was studied on exfoliated, pristine and Pt‐decorated tungsten diselenide (p‐WSe2) nanoflake samples, using a previously developed microdroplet PEC microscopy approach. The WSe2 nanoflakes had well‐defined thicknesses as measured by atomic force microscopy, and the Pt nanoparticles (NPs) were deposited by a variable number of atomic layer deposition (ALD) cycles. An exceptionally high photocurrent density of 49.6 mA cm−2 (under 220 mW cm−2 irradiation) and internal‐photon‐to‐electron‐conversion efficiency (∼90% at 550 nm) were demonstrated on these Pt‐decorated WSe2 (WSe2‐Pt) photocathodes. The Pt NP loading and thickness of WSe2 nanoflakes (in the 24–235 nm range) were used to fine‐tune their PEC activity for HER. We found similar charge transfer and surface recombination kinetics of pristine and WSe2‐Pt specimens (as assessed by intensity‐modulated photocurrent spectroscopy), which indicated significant differences in their bulk properties. X‐ray and ultraviolet photoelectron spectroscopies were performed to identify defect states and quantify the density of states around the valence band of WSe2. The elevated temperature of the ALD process and the evolving Pt NP phase conspired to passivate the sub‐surface (i.e., bulk) defects in the WSe2 nanoflakes, resulting in their vastly improved PEC performance.

Electroporation is used to induce homologous recombination in the genome of the murine ES (embryonic stem) cells. Routinelly subconfluent ES cells are recommended to be used in such experiments. Electroporation of immunoglobulin specific targeting vectors with different length of homology leads to reduced number of selected colonies. The enrichment of double selected colonies is high and thus the amount of HM-1 ES cell colonies for the analysis is very low. Here we show that the electroporation of confluent HM-1 ES cells leads to an increased amount of simple and double selected colonies.

The efficiency of homologous recombination relies on the lenght of the homology arms and the chromatin compactation of the locus. In ES cells the immuoglobulin locu is compacted. Thus, the homologous recombination events occur at a very low frequency. A high number of ES cell colonies have to be analysed to detect a homologous recombination event. Here we describe a reliable and rapid protocol for the analysis of targeted mutagenesis in the immunoglobulin locus using Southern Blot analysis.

Gynogenesis is a technique used to generate diploid individuals with genetic material exclusively of maternal origin. In this study we test the hypothesis that heat shock treatment of rainbow trout eggs, activated with UV irradiated sperms, leads to the generation of a uniform populations of diploid gynogenetic females. Activation of fertilized eggs with UV irradiated semen, by heat shock at 27.5°C for 10 min. directly after fertilization induces diploid gynogenesis. Diploid individuals are obtained at a rate of 73.33%. Triploid individuals are obtained at a rate of 26.67%. The enhanced number of triploid individuals may be due to insufficient irradiation of heritable material of sperm.

Sensor technologies have sufficiently advanced to provide low-cost devices that can quantify carbon dioxide levels in honeybee hives with high temporal resolution and in a small enough package for hive deployment. Recent publications have shown that summer carbon dioxide levels vary throughout the day and night over ranges that typically exceed 5000 ppm. Such dramatic changes in a measurable parameter associated with bee physiology are likely to convey information about the colony health. In this work, we present data from four UK-based hives collected through the winter of 2022/2023, with a focus on seeing if carbon dioxide can indicate when colonies are at risk of failure. These hives have been fitted with two Sensirion SCD41 photoacoustic non-dispersive infrared (NDIR) carbon dioxide sensors, one in the queen excluder, at the top of the brood box, and one in the crown board, at the top of the hive. Hive scales have been used to monitor the hive mass, and internal and external temperature sensors have been included. Embedded accelerometers in the central frame of the brood box have been used to measure vibrations. Data showed that the high daily variation in carbon dioxide continued throughout the coldest days of winter, and the vibrational data suggested that daily fanning may be responsible for restoring lower carbon dioxide levels. The process of fanning will draw in colder air to the hive at a time when the bees should be using their energy to maintain the colony temperature. Monitoring carbon dioxide may provide feedback, prompting human intervention when the colony is close to collapse, and a better understanding may contribute to discussions on future hive design.

Honey bee colonies have great societal and economic importance. The main challenge that beekeepers face is keeping bee colonies healthy under ever-changing environmental conditions. In the past two decades, beekeepers that manage colonies of Western honey bees (Apis mellifera) have become increasingly concerned by the presence of parasites and pathogens affecting the bees, the reduction in pollen and nectar availability, and the colonies’ exposure to pesticides, among others. Hence, beekeepers need to know the health condition of their colonies and how to keep them alive and thriving, which creates a need for a new holistic data collection method to harmonize the flow of information from various sources that can be linked at the colony level for different health determinants, such as bee colony, environmental, socioeconomic, and genetic statuses. For this purpose, we have developed and implemented the B-GOOD (Giving Beekeeping Guidance by computational-assisted Decision Making) project as a case study to categorize the colony’s health condition and find a Health Status Index (HSI). Using a 3-tier setup guided by work plans and standardized protocols, we have collected data from inside the colonies (amount of brood, disease load, honey harvest, etc.) and from their environment (floral resource availability). Most of the project’s data was automatically collected by the BEEP Base Sensor System. This continuous stream of data served as the basis to determine and validate an algorithm to calculate the HSI using machine learning. In this article, we share our insights on this holistic methodology and also highlight the importance of using a standardized data language to increase the compatibility between different current and future studies. We argue that the combined management of big data will be an essential building block in the development of targeted guidance for beekeepers and for the future of sustainable beekeeping.

Abstract Aims Volume overload (VO) induced hypertrophy is one of the hallmarks to the development of heart diseases. Understanding the compensatory mechanisms involved in this process might help preventing the disease progression. Methods and results Therefore, the present study used 2 months old Wistar rats, which underwent an aortocaval fistula to develop VO‐induced hypertrophy. The animals were subdivided into four different groups, two sham operated animals served as age‐matched controls and two groups with aortocaval fistula. Echocardiography was performed prior termination after 4‐ and 8‐month. Functional and molecular changes of several sarcomeric proteins and their signalling pathways involved in the regulation and modulation of cardiomyocyte function were investigated. Results The model was characterized with preserved ejection fraction in all groups and with elevated heart/body weight ratio, left/right ventricular and atrial weight at 4‐ and 8‐month, which indicates VO‐induced hypertrophy. In addition, 8‐months groups showed increased left ventricular internal diameter during diastole, RV internal diameter, stroke volume and velocity‐time index compared with their age‐matched controls. These changes were accompanied by increased Ca2+ sensitivity and titin‐based cardiomyocyte stiffness in 8‐month VO rats compared with other groups. The altered cardiomyocyte mechanics was associated with phosphorylation deficit of sarcomeric proteins cardiac troponin I, myosin binding protein C and titin, also accompanied with impaired signalling pathways involved in phosphorylation of these sarcomeric proteins in 8‐month VO rats compared with age‐matched control group. Impaired protein phosphorylation status and dysregulated signalling pathways were associated with significant alterations in the oxidative status of both kinases CaMKII and PKG explaining by this the elevated Ca2+ sensitivity and titin‐based cardiomyocyte stiffness and perhaps the development of hypertrophy. Conclusions Our findings showed VO‐induced cardiomyocyte dysfunction via deranged phosphorylation of myofilament proteins and signalling pathways due to increased oxidative state of CaMKII and PKG and this might contribute to the development of hypertrophy.

Abstract Background Epidemiological emerging evidence shows that human exposure to some nanosized materials present in the environment would contribute to the onset and/or progression of Alzheimer’s disease (AD). The cellular and molecular mechanisms whereby nanoparticles would exert some adverse effects towards neurons and take part in AD pathology are nevertheless unknown. Results Here, we provide the prime evidence that titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) bind the cellular form of the prion protein (PrPC), a plasma membrane protein well known for its implication in prion diseases and prion-like diseases, such as AD. The interaction between TiO2- or CB-NPs and PrPC at the surface of neuronal cells grown in culture corrupts PrPC signaling function. This triggers PrPC-dependent activation of NADPH oxidase and subsequent production of reactive oxygen species (ROS) that alters redox equilibrium. Through PrPC interaction, NPs also promote the activation of 3-phosphoinositide-dependent kinase 1 (PDK1), which in turn provokes the internalization of the neuroprotective TACE α-secretase. This diverts TACE cleavage activity away from (i) TNFα receptors (TNFR), whose accumulation at the plasma membrane augments the vulnerability of NP-exposed neuronal cells to TNFα -associated inflammation, and (ii) the amyloid precursor protein APP, leading to overproduction of neurotoxic amyloid Aβ40/42 peptides. The silencing of PrPC or the pharmacological inhibition of PDK1 protects neuronal cells from TiO2- and CB-NPs effects regarding ROS production, TNFα hypersensitivity, and Aβ rise. Finally, we show that dysregulation of the PrPC-PDK1-TACE pathway likely occurs in the brain of mice injected with TiO2-NPs by the intra-cerebro-ventricular route as we monitor a rise of TNFR at the cell surface of several groups of neurons located in distinct brain areas. Conclusion Our in vitro and in vivo study thus posits for the first time normal cellular prion protein PrPC as being a neuronal receptor of TiO2- and CB-NPs and identifies PrPC-coupled signaling pathways by which those nanoparticles alter redox equilibrium, augment the intrinsic sensitivity of neurons to neuroinflammation, and provoke a rise of Aβ peptides. By identifying signaling cascades dysregulated by TiO2- and CB-NPs in neurons, our data shed light on how human exposure to some NPs might be related to AD.

The aim of this paper was to establish some correlations between certain morphometric parameters and embryo quality. The morphometric parameters taken into consideration were: zona pellucida thickness, outer and inner diameter, and outer and inner perimeter. For experiments we used embryos recovered at 24 hours from mouse females superovulated with gonadotrope hormones (eCG and hCG). The embryos recovered were cultivated in KSOM media, supplemented with amino acids, and during the in vitro cultivation they were measured at different time intervals for establishing morphometric parameters. The data obtained were statistically analyzed using Minitab 15, using Fitted Line Plot regression that allows testing of the linear and polynomial regression of one variable. After statistical analyze of the data we found that the thickness of the zona pellucida can constitute a morphometric parameter that can be used as an indicator of subsequent development of the 2 cell embryos to morula and blastocyst stage respectively. The other morphometric parameters studied (outer and inner diameter, and outer and inner perimeter) cannot be used as indicators of the embryo development.

The aim of this paper was to investigate if morphometric parameters can be used in establishing the viability of the mouse embryos. For the experiments, we used mouse mature oocytes and embryos in vivo obtained. The morphometric parameters taken into consideration were: pellucid zone thickness, outer and inner diameter, and outer and inner perimeter and for oocytes and zygotes the cellular mass diameter was also measured. The oocytes were measured immediately after recovery then they were in vitro fertilized. After 4-6 hours after fecundation the oocytes that manifested the extrusion of the second polar body (zygotes) were measured, and at 24 hours after fecundation the unfertilized oocytes were also measured. The embryos were obtained from mouse females superovulated with gonadotrope hormones (eCG and hCG). For the experiments we used embryos in different developmental stages (2, 4 and 8 cells, morula and blastocyst). After recovery the embryos were morphologically analyzed and divided in viable (quality code 1, 2 and 3) and nonviable embryos (quality code 4) (IETS Manual, 1989) and they were measured for establishing the morphometric parameters value. The data obtained were statistically analyzed using Minitab 15, and T test. For the oocytes it was noticed that the pellucid zone thickness is registering a slightly increase if the oocyte is fertilized, without significantly difference from recovery, but if the oocyte is not fertilized the pellucid zone thickness decrease from 8.3±1.5 µm to 8.0±1.5 µm. For the embryos in early developmental stages only the thickness of the pellucid zone can be an indication of the viability. For the embryos in morula stage the thickness of the pellucid zone and inner diameter can be used as indicator of viability. For the embryos in blastocyst stage the thickness of the pellucid zone, the inner and outer diameter can be used as a viability indicator.

The conception rate is defined as the aptitude of a female to romaine pregnant after the first A.I. and represents the proportion between the number of pregnant cows at first A.I and the number of cows inseminated in that period. In our experiments of estrus induction and synchronization, in order to increase the pregnancy rates, we used the Ovsynch protocol and other protocols for PgF2α and GnRH. In order to establish the pregnancy rates, the number of females that have not return in heats after A.I. were taken in consideration. The conception rates were 45.5 – 52.6%. The estrus synchronization offers the possibility to increase the pregnancy rates at first service after calving and creates the possibility to inseminate at certain time without heat detection.

In Romania, the Transylvanian Naked Neck hen breed is considered to be an “endangered” population, reason for which we consider that a special attention should have been given until now. Plymouth Rock breed was imported for the first time to Romania from the Studler Company, France in 1969. This paper is aiming to perform a profound analysis of the development patterns of the somite number in the two breeds, by measurements carried out at 26, 30, 40, 50, and 60 hours of incubation. Observations demonstrate that somite forming is carrying on in a similar way as the other embryo complex characteristics following an undulatory curve whose curls are different in the two breeds, but the forming speed during the whole studied period is similar. We estimate that the two breeds have a good combinative capacity, which recommend the utilization of these genetic materials to obtain hybrids for producing “peasant-type” chicken meat, very well-appreciated by the Europeans between the two World Wars.