Explore the vast range of titles available.

Bank voles (Myodes glareolus syn. Clethrionomys glareolus) are frequently used as an animal model in ecological and biomedical studies and are an important reservoir of viral and bacterial zoonotic pathogens, e.g., Puumala hantavirus (PUUV). Here we describe an accidental PUUV outbreak in a large bank vole laboratory colony caused by an accidental introduction of infected wild-trapped bank voles, and the successful eradication of the virus. The eradication plan was based on results of previous studies showing that maternal antibodies (MatAb) protect the young from infection for up to 40 days after weaning, four weeks longer than the estimated duration of PUUV infectivity in the environment. After ensuring that most animals were infected, 620 pairs were mated on the same day. Only females that showed PUUV-specific antibodies and produced offspring within 26 days after mating were retained. All individuals of the parental generation were euthanized before the last weaning. The weaned offspring were moved to individually ventilated cages (IVC) and repeatedly tested for the presence of PUUV-specific antibodies and RNA. A few infected or suspect animals were euthanized. The animals were then mated (in IVC) and, after producing grand-offspring generation, euthanized and tested for PUUV RNA in the lungs. No PUUV RNA was detected, and no animals showed PUUV-specific antibodies in subsequent generations. The successful clearance confirmed the protective efficiency of PUUV-specific MatAb. The procedure for PUUV clearance in the bank vole colony may represent a blueprint for similar approaches in valuable colonies of other rodents infected by similar pathogens.

Exercise performance depends on both physiological abilities (e.g., muscle strength) and behavioral characteristics (e.g., motivation). We tested the hypothesis that evolution of increased aerobic exercise performance can be facilitated by evolution of neuropsychological mechanisms responsible for motivation to undertake physical activity. We used a unique model system: lines of bank voles Myodes glareolus selected for high swim-induced aerobic metabolism (“aerobic” A lines). In generation 21, voles from the 4 A lines achieved a 57% higher “voluntary maximum” swim-induced aerobic metabolism (VO2swim) than voles from 4 unselected, “control” C lines. In C lines, VO2swim was 9% lower than the maximum forced-exercise aerobic metabolism (VO2run; P = 0.007), while in A lines it was even higher than VO2run, although not significantly (4%, P = 0.15). Thus, we hypothesized that selection changed both the aerobic capacity and the neuronal mechanisms behind motivation to undertake activity. We investigated the influence of reuptake inhibitors of dopamine (DARI), serotonin (SSRI), and norepinephrine (NERI) on VO2swim. The drugs decreased VO2swim both in C and A lines (% decrease compared with saline: DARI 8%, P < 0.001; SSRI 6%, P < 0.001; NERI 8%, P < 0.001), but the proportional response differed between selection directions only for NERI (stronger effect in C lines: P = 0.008) and the difference was marginally non-significant for SSRI (P = 0.07) and DARI (P = 0.06). Thus, the results suggest that all the 3 monoamines are involved in signaling pathways controlling the motivation to be active and that norepinephrine could have played a role in the evolution of increased aerobic exercise performance in our animal model.

Abstract Physical performance is determined both by biophysical and physiological limitations and behavioral characteristic, specifically motivation. We applied an experimental evolution approach combined with pharmacological manipulation to test the hypothesis that evolution of increased aerobic exercise performance can be triggered by evolution of motivation to undertake physical activity. We used a unique model system: bank voles from A lines, selected for high swim-induced aerobic metabolism (VO2swim), which achieved a 61% higher mass-adjusted VO2swim than those from unselected C lines. Because the voles could float on the water surface with only a minimum activity, the maximum rate of metabolism achieved in that test depended not only on their aerobic capacity, but also on motivation to undertake intensive activity. Therefore, we hypothesized that signaling of neurotransmitters putatively involved in regulating physical activity (dopamine and noradrenaline) had changed in response to selection. We measured VO2swim after intraperitoneal injections of saline or the norepinephrine and dopamine reuptake inhibitor bupropion (20 mg/kg or 30 mg/kg). Additionally, we measured forced-exercise VO2 (VO2max). In C lines, VO2swim (mass-adjusted mean ± standard error (SE): 4.0 ± 0.1 mLO2/min) was lower than VO2max (5.0 ± 0.1 mLO2/min), but in A lines VO2swim (6.0 ± 0.1 mLO2/min) was as high as VO2max (6.0 ± 0.1 mLO2/min). Thus, the selection effectively changed both the physiological–physical performance limit and mechanisms responsible for the willingness to undertake vigorous locomotor activity. Surprisingly, the drug had no effect on the achieved level of VO2swim. Thus, the results did not allow firm conclusions concerning involvement of these neurotransmitters in evolution of increased aerobic exercise performance in the experimental evolution model system.

Physical performance is determined both by biophysical and physiological limitations and behav- ioral characteristic, specifically motivation. We applied an experimental evolution approach com- bined with pharmacological manipulation to test the hypothesis that evolution of increased aerobic exercise performance can be triggered by evolution of motivation to undertake physical activity. We used a unique model system： bank voles from A lines, selected for high swim-induced aerobic metabolism （VO2swim）, which achieved a 61% higher mass-adjusted VO2swim than those from un- selected C lines. Because the voles could float on the water surface with only a minimum activity, the maximum rate of metabolism achieved in that test depended not only on their aerobic capacity, but also on motivation to undertake intensive activity. Therefore, we hypothesized that signaling of neurotransmitters putatively involved in regulating physical activity （dopamine and noradrenaline） had changed in response to selection. We measured VO2swim after intraperitoneal injections of sa- line or the norepinephrine and dopamine reuptake inhibitor bupropion （20 mg/kg or 30 mg/kg）. Additionally, we measured forced-exercise VO2 （VO2max）. In C lines, VO2swim （mass-adjusted mean ± standard error （SE）： 4.0 ± 0.1 mLO2/min） was lower than VO2max （5.0 ± 0.1 mLO2/min）, but in A lines VO2swim （6.0 ± 0.1 mLO2/min） was as high as VO2max （6.0 ± 0.1 mLO2/min）. Thus, the selection effectively changed both the physiological-physical performance limit and mechanisms responsible for the willingness to undertake vigorous locomotor activity. Surprisingly, the drug had no effect on the achieved level of VO2swim. Thus, the results did not allow firm conclusions concerning involvement of these neurotransmitters in evolution of increased aerobic exercise performance in the experimental evolution model system.

Bank voles (Myodes glareolus syn. Clethrionomys glareolus) are frequently used as an animal model in ecological and biomedical studies, and are important reservoir of viral and bacterial zoonotic pathogens, e.g. of Puumala hantavirus (PUUV). Here we describe an accidental PUUV outbreak in a large bank vole laboratory colony by incursion of infected wild-trapped bank voles, and a successful eradication of the virus. The eradication plan was based on results of previous studies, which showed that maternal antibodies (MatAb) protect the young from infection for up to 40 days after the weaning, four weeks longer than the estimated duration of maintaining infectivity of PUUV in the environment. After ensuring that most animals are infected, 620 pairs were mated on the same day. Only females that showed PUUV-specific antibodies and gave offspring within 26 days after the mating were retained. All individuals of the parental generation were euthanized before the last weaning. The weaned offspring was moved to individually ventilated cages (IVC) and repeatedly tested for the presence of PUUV-specific antibodies and RNA. A few infected and suspicious animals were euthanised. Then the animals were mated (in IVC) and after producing grand-offspring euthanised and tested for PUUV RNA in lungs. No PUUV RNA was detected, and no animals showed PUUV-specific antibodies in next generations. The successful clearance confirmed the protective efficiency of PUUV-specific MatAb. The procedure for clearance of PUUV in the bank vole colony may represent a blueprint for similar approaches in precious colonies of other rodents infected by similar pathogens. In 2006 we started a unique long-term experiment on the bank vole, a common European rodent. Our goal was to study how animals can adapt to different challenges - a process called adaptive radiation. We established 16 vole lines: four control lines and others selected for specific behavioural and physiological traits. Over the years, this colony became an important model for studying evolution, physiology, and behaviour. Unfortunately, the colony became infected with Puumala hantavirus. The virus is mild for voles but can cause serious zoonotic illness in humans, without specific medical treatment available. At first, it seemed that the entire colony would have to be destroyed - a loss of thousands of animals and many years of research. However, we used a natural advantage: young voles born to infected mothers are temporarily protected by maternal antibodies. By carefully planning breeding, isolation, and testing, we created conditions where the virus lost its strength before the young lost their protection. This simple yet challenging approach worked - we saved the colony. Because many animals respond to viruses in a similar way, our method can help rescue other valuable research populations without complex procedures like embryo transfer or cross-fostering.

Fruiting bodies of the fungi Porodaedalea pini (Brot.) Murrill and Phellinus tremulae (Brot.) A. Ames were collected in the Białowieża Forest (Poland). Morphological identification of the collected fruiting bodies was carried out and genetic tests were performed to confirm the identity of the collected specimens. Methanol extracts for biological activity tests were prepared. The methanolic extracts obtained had a plastic consistency, high viscosity and colors from brown to dark brown. The determination of selected elements in Phellinus extracts was performed by X-ray spectrofluorimetry. Thermal decomposition studies and spectroscopic analysis of the dry fruiting bodies were performed. The content of active substances was examined using GCMS chromatography. GCMS analysis showed that the extracts of the tested species contain many chemical compounds that are characterized by high antioxidant potential. These include, among others, phenolic acids (caffeic acid, p-coumaric acid, ferulic acid, 3-hydroxybenzoic acid). In the extract of P. pini , the content of phenolic acids is higher than in P. tremulae . The P. tremulae extract (83.70+/-1.00%) possesses similar antiradical activity against DPPH• as P. pini extract (80.00+/-0.58%). The extracts were tested for their antimicrobial activity against multi-resistant bacteria. Cytotoxic activity was also tested. Both extracts inhibited the growth of S. aureus 4459 (MIC = 6.25 mg/ml), the clinical strain resistant to erythromycin. Cytotoxicity assessment showed that only the P. tremulae extract significantly decreased HaCaT cell viability by 37% and 42% at concentrations of 400 and 800 µg/ml, respectively.

This study conducted a multi-directional evaluation of the chemical potential and biological properties of selected European fungal species of the genus Phellinus. We investigated 30 samples belonging to 22 Phellinus species. Fruiting bodies were collected, among other specimens, in the Białowieża Forest (Poland); Village Kozhle (North Macedonia); Estremadura, Sesimbra, and Lagoa de Albufeira (Portugal); Zlatari close to Prishtina (Kosovo); and Spoleto and the Bosco Siro Negri State Nature Reserve (Italy). Morphological identification of the collected fungi was carried out, and genetic tests were performed to confirm the identity of the collected specimens. Methanol extracts for biological activity tests were prepared. Screening of antimicrobial activity of 30 methanolic extracts was performed on strains of bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Kocuria rhizophila) and fungi (Candida albicans). Antioxidant activity tests (DPPH and ABTS) were also performed. The three most biologically active fungi species were selected (Phellinus igniarius, Fomitiporia robusta, and Porodaedalea pini) for further research. The chemical composition of the extracts was determined using GC-MS analysis. Thermal decomposition studies and spectroscopic analysis of the dry fruiting bodies were performed. The extracts were tested for their antimicrobial activity against antibiotic-resistant bacteria. Cytotoxic activity was also tested.

Pancreatic cancer (PC) is one of the deadliest cancers so there is an urgent need to develop new drugs and therapies to treat it. Liposome-based formulations of naturally-derived bioactive compounds are promising anticancer candidates due to their potential for passive accumulation in tumor tissues, protection against payload degradation, and prevention of non-specific toxicity. We chose the naturally-derived flavonoid baicalein (BAI) due to its promising effect against pancreatic ductal adenocarcinoma (PDAC) and encapsulated it into a liposomal bilayer using the passive loading method, with an almost 90% efficiency. We performed a morphological and stability analysis of the obtained BAI liposomal formulation and evaluated its activity on two-dimensional and three-dimensional pancreatic cell models. As the result, we obtained a stable BAI-encapsulated liposomal suspension with a size of 100.9 nm ± 2.7 and homogeneity PDI = 0.124 ± 0.02, suitable for intravenous administration. Furthermore, this formulation showed high cytotoxic activity towards AsPC-1 and BxPC-3 PDAC cell lines (IC50 values ranging from 21 ± 3.6 µM to 27.6 ± 4.1 µM), with limited toxicity towards normal NHDF cells and a lack of hemolytic activity. Based on these results, this new BAI liposomal formulation is an excellent candidate for potential anti-PDAC therapy.

Despite many attempts, trials, and treatment procedures, pancreatic ductal adenocarcinoma (PDAC) still ranks among the most deadly and treatment-resistant types of cancer. Hence, there is still an urgent need to develop new molecules, drugs, and therapeutic methods against PDAC. Naturally derived compounds, such as pentacyclic terpenoids, have gained attention because of their high cytotoxic activity toward pancreatic cancer cells. Ursolic acid (UA), as an example, possesses a wide anticancer activity spectrum and can potentially be a good candidate for anti-PDAC therapy. However, due to its minimal water solubility, it is necessary to prepare an optimal nano-sized vehicle to overcome the low bioavailability issue. Poly(lactic-co-glycolic acid) (PLGA) polymeric nanocarriers seem to be an essential tool for ursolic acid delivery and can overcome the lack of biological activity observed after being incorporated within liposomes. PLGA modification, with the addition of PEGylated phospholipids forming the lipid shell around the polymeric core, can provide additional beneficial properties to the designed nanocarrier. We prepared UA-loaded hybrid PLGA/lipid nanoparticles using a nanoprecipitation method and subsequently performed an MTT cytotoxicity assay for AsPC-1 and BxPC-3 cells and determined the hemolytic effect on human erythrocytes with transmission electron microscopic (TEM) visualization of the nanoparticles and their cellular uptake. Hybrid UA-loaded lipid nanoparticles were also examined in terms of their stability, coating dynamics, and ursolic acid loading. We established innovative and repeatable preparation procedures for novel hybrid nanoparticles and obtained biologically active nanocarriers for ursolic acid with an IC50 below 20 µM, with an appropriate size for intravenous dosage (around 150 nm), high homogeneity of the sample (below 0.2), satisfactory encapsulation efficiency (up to 70%) and excellent stability. The new type of hybrid UA-PLGA nanoparticles represents a further step in the development of potentially effective PDAC therapies based on novel, biologically active, and promising triterpenoids.

In clinical diagnosis, electrocardiographic repolarization abnormalities with prolongation of QT and especially TpTe intervals are important for assessing the risk of malignant ventricular arrhythmias. The aim of the study was to compare the electrocardiological values of repolarization parameters in children with and without arrhythmias, according to body weight. Repolarization parameters were compared in a group of children with excessive and normal body weight (BMI, Cole's index) with ventricular and supraventricular arrhythmias and in another group of children (matched for age and sex, with no arrhythmia and with normal weight) as the control group. The repolarization parameters TpTe, QTp and QT interval corrected Bazett (QTcB) and Fridericia (QTcF) formulas were measured in lead V5 of the 12-lead ECG. The durations of TpTe and QTcF intervals were significantly longer in children with ventricular arrhythmias with abnormal body weight compared to children with supraventricular arrhythmias with abnormal body weight. Comparing children with normal weight between the ventricular and supraventricular groups, significant prolongation of only the TpTe interval was observed. Moreover, there were statistically significant differences ( < 0.0001) in the TpTe interval among the 5 groups: children with ventricular and supraventricular arrhythmia with abnormal and normal weight, as well as the control group depending on BMI and Cole's index. In children with ventricular arrhythmia, only the TpTe parameter was significantly longer compared to children with supraventricular arrhythmia and children without arrhythmia, regardless of body weight. In children with arrhythmia, regardless of body weight, the TpTe parameter should be measured in addition to routine QT. Further studies on a larger scale are needed to assess the clinical importance of the TpTe interval in children with arrhythmias and excessive body weight.