Az élőhely-urbanizáció ökológiai és viselkedési következményeinek vizsgálata házi verebeken = Ecological and behavioral consequences of urbanization for a worldwide urban exploiter, the house sparrow

A projekt során azt vizsgáltuk, hogy (i) az élőhely-urbanizációval miként változik a táplálékkompetíció és a predációs nyomás intenzitása, (ii) a madarak viselkedése, stressz-élettana, kondíciója és szaporodási sikere, és hogy (iii) az élőhelyi különbségek környezeti hatások vagy alkalmazkodás következményeként alakultak-e ki. Kimutattuk, hogy a felnőtt városi verebek erősebb ragadozóelkerülő reakciót mutatnak, mint a vidéki egyedek, ami intenzívebb városi predációs nyomásra utal. Ugyanakkor nem találtunk élőhelyi különbséget a madarak kompetitív képességeiben. Szintén nem volt különbség a sterssz-élettani és fizikai kondíciót jellemző tulajdonságokban. A vidéki populációk madarai több és nagyobb méretű fiókát neveltek, mint a szuburbán párok. Fogságban, azonos körülmények között szaporodó madarak esetében ugyanakkor nem volt élőhelyi különbség sem a szaporodási sikerben, sem a fiókák méretében. Vizsgálataink összességében a fiókakori környezeti hatások jelentőségét erősítették meg az urbanizációs gradiens mentén tapasztalható szaporodási és morfológiai különbségek kialakulásában. Úgy véljük, hogy különösen jelentős hatású a megfelelő rovartáplálék mennyiségének és/vagy összetételének kedvezőtlenné válása a városi területeken, ami a házi verebek mellett más rovarevő állatok számára is megnehezítheti az urbanizált helyeken való megtelepedést és fennmaradást. | Our aim was (i) to test the effects of habitat urbanization on the intensity of food competition and predation risk in bird populations, (ii) to study its effects on the sterss-physiology, condition and behavior of birds, and (iii) to test whether the morphological differences we found in house sparrows along the urbanization gradient represent environmental effects or adaptation. We found stronger predatory risk avoidance in adult urban sparrows than rural ones, suggesting higher predation risk in urban habitats of the species. There was no habitat difference in the competitive ability of sparrows. We also did not find any consistent difference in the birds’ stress response and multiple estimates of body condition between differently urbanized populations. Rural birds in wild populations had higher reproductive success and reared heavier nestlings than pairs in a suburban population. On the other hand, in captivity there was no habitat-related difference in either reproductive success or nestling mass. We concluded that environmental factors, particularly nestling food may play a key role in generating reproductive and morphological differences along the urban gradient. Reduced arthropod densities in urban habitats may negatively affect the reproduction and survival of other insectivorous animals that still persist in urbanized environments

Prognostic assessment in patients operated for brain metastasis from systemic tumors

Background: Established models for prognostic assessment in patients with brain metastasis do not stratify for prior surgery. Here we tested the prognostic accuracy of the Graded Prognostic Assessment (GPA) score model in patients operated for BM and explored further prognostic factors. Methods: We included 285 patients operated for brain metastasis at the University Hospital Zurich in the analysis. Information on patient characteristics, imaging, staging, peri- and postoperative complications and survival were extracted from the files and integrated into a multivariate Cox hazard model. Results: The GPA score showed an association with outcome. We further identified residual tumor after surgery (p = 0.007, hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.1-2.3) steroid use (p = 0.021, HR 1.7, 95% CI 1.1-2.6) and number of extracranial metastasis sites (p = 0.009, HR 1.4, 95% CI 1.1-1.6) at the time of surgery as independent prognostic factors. A trend was observed for postoperative infection of the subarachnoid space (p = 0.102, HR 3.5, 95% CI 0.8-15.7). Conclusions: We confirm the prognostic capacity of the GPA score in a cohort of operated patients with brain metastasis. However, extent of resection and steroid use provide additional aid for the prognostic assessment in these patients

Peripheral circulating insulin-like growth factor-I and -II in cattle

Interrelationships between circulating concentrations of the insulin-like growth factors (IGF-I and IGF-II) were investigated in 235 blood samples taken from 145 healthy beef or dairy calves, bulls and cows of different breeds and ages. Autoradiography of Western ligand blots indicated different IGF binding protein (IGFBP) profiles between sera from different categories of cattle. Each IGF radioimmunoassay was validated by determining the effects of IGFBPs, ligand and contraligand, as well as serial dilution and comparison with results obtained after molecular sieve chromatography in acid. In female cattle mean values for IGF-I varied from 5.1 nmol/l in postparturient Holstein cows to 18.5–20.5 nmol/l in growing beef heifers, while mean IGF-II concentrations ranged from 30.0 nmol/l in the cows to 14.7–15.7 nmol/l in the beef heifer calves. In male cattle mean serum IGF-I ranged widely from 8.2 nmol/l in 1-day-old Holstein calves to 67.4 nmol/l in 16-month-old Simmental-type bulls. Mean IGF-II concentrations decreased from 22.9 nmol/l in 1-day-old Holstein bull calves to 11.9 nmol/l in 12-month-old beef bulls. Thus, total molar IGF concentrations were fairly stable in female cattle (24.7–35.1 nmol/l) but extended from 27.3 nmol/l to 81.8 nmol/l in the male cattle. The tendency for a reciprocal relationship between serum concentrations of these growth factors was most obvious in the periparturient cows

BEAR reveals that increased fidelity variants can successfully reduce the mismatch tolerance of adenine but not cytosine base editors

Base editors allow for precision engineering of the genome. Here, the authors present BEAR, a plasmid-based fluorescence assay for the measurement of CBE and ABE activity, to reveal the mechanism underlying their differences and to increase the yield of edited cells with reduced indel background

Effects of butyrate on the insulin homeostasis of chickens kept on maize- or wheat-based diets

The aim of the present study was to investigate the effects of butyrate as a feed supplement on the expression of insulin signalling proteins as potent regulators of metabolism and growth in Ross 308 broiler chickens fed maize- or wheat-based diets. Both diets were supplemented with non-protected butyrate (1.5 and 3.0 g/kg of diet, respectively) or with protected butyrate (0.2 g/kg of diet); the diet of the control groups was prepared without any additives (control). On day 42 of life, systemic blood samples were drawn for analyses of glucose and insulin concentrations, and tissue samples (liver, gastrocnemius muscle and subcutaneous adipose tissue) were taken for Western blotting examinations. The expression of key insulin signalling proteins (IRβ, PKCζ and mTOR) was assessed by semiquantitative Western blotting from the tissues mentioned. The type of diet had a remarkable influence on the insulin homeostasis of chickens. The wheat-based diet significantly increased IRβ and mTOR expression in the liver as well as mTOR and PKCζ expression in the adipose tissue when compared to animals kept on a maize-based diet. IRβ expression in the liver was stimulated by the lower dose of non-protected butyrate as well, suggesting the potential of butyrate as a feed additive to affect insulin sensitivity. Based on the results obtained, the present study shows new aspects of nutritional factors by comparing the special effects of butyrate as a feed additive and those of the cereal type, presumably in association with dietary non-starch polysaccharide- (NSP-) driven enteric shortchain fatty acid release including butyrate, influencing insulin homeostasis in chickens. As the tissues of chickens have physiologically lower insulin sensitivity compared to mammals, diet-associated induction of the insulin signalling pathway can be of special importance in improving growth and metabolic health

Effect of dietary cereal type, crude protein and butyrate supplementation on metabolic parameters of broilers

This study investigates the metabolic effects of maize- or wheat-based diets with normal (NP) and lowered (LP) dietary crude protein level [the latter supplemented with limiting amino acids and sodium (n-)butyrate at 1.5 g/kg diet] at different phases of broiler fattening. Blood samples of Ross 308 broilers were tested at the age of 1, 3 and 6 weeks. Total protein (TP) concentration increased in wheat-based and decreased in LP groups in week 3, while butyrate reduced albumin/TP ratio in week 1. Uric acid level was elevated by wheat-based diet in week 1 and by wheat-based diet and butyrate in week 3, but decreased in LP groups in weeks 3 and 6. Aspartate aminotransferase activity was increased by wheat-based diet in week 3, and creatine kinase activity was intensified by LP in weeks 3 and 6. Blood glucose level decreased in wheat-based groups in week 3; however, triglyceride concentration was augmented in the same groups in week 3. No change of glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide and insulin concentration was observed. In conclusion, an age-dependent responsiveness of broilers to dietary factors was found, dietary cereal type was a potent modulator of metabolism, and a low crude protein diet supplemented with limiting amino acids might have a beneficial impact on the growth of chickens

PEAR, a flexible fluorescent reporter for the identification and enrichment of successfully prime edited cells

Prime editing is a recently developed CRISPR/Cas9 based gene engineering tool that allows the introduction of short insertions, deletions, and substitutions into the genome. However, the efficiency of prime editing, which typically achieves editing rates of around 10%-30%, has not matched its versatility. Here, we introduce the prime editor activity reporter (PEAR), a sensitive fluorescent tool for identifying single cells with prime editing activity. PEAR has no background fluorescence and specifically indicates prime editing events. Its design provides apparently unlimited flexibility for sequence variation along the entire length of the spacer sequence, making it uniquely suited for systematic investigation of sequence features that influence prime editing activity. The use of PEAR as an enrichment marker for prime editing can increase the edited population by up to 84%, thus significantly improving the applicability of prime editing for basic research and biotechnological applications

Novel cyclic C5-curcuminoids penetrating the blood-brain barrier: design, synthesis and antiproliferative activity against astrocytoma and neuroblastoma cells

Novel series of cyclic C5-curcuminoids 17a-j and 19-22 were prepared as cytotoxic agents and evaluated against human neuroblastoma (SH-SY5Y) or human grade IV astrocytoma (CCF-STTG1) cell lines in low (∼0.1 nM - 10 nM) concentrations. Among the tested 21 derivatives, 16 displayed potent antiproliferative activity with IC50 values in the low nanomolar to picomolar range (IC50 = 7.483-0.139 nM). Highly active compounds like N-monocarboxylic derivative 19b with IC50 = 0.139 nM value against neuroblastoma and N-alkyl substituted 11 with IC50 = 0.257 nM against astrocytoma proved some degree of selectivity toward non-cancerous astrocytes and kidney cells. This potent anticancer activity did not show a strong correlation with experimental logPTLC values, but the most potent antiproliferative molecules 11-13 and 19-22 are belonging to discrete subgroups of the cyclic C5-curcuminoids. Compounds 12, 17c and 19b were subjected to blood-brain barrier (BBB) penetration studies, too. The BBB was revealed to be permeable for all of them but, as the apparent permeability coefficient (Papp) values mirrored, in different ratios. Lower toxicity of 12, 17c and 19b was observed toward primary rat brain endothelial cells of the BBB model, which means they remained undamaged under 10 µM concentrations. Penetration depends, at least in part, on albumin binding of 12, 17c and 19b and the presence of monocarboxylic acid transporters in the case of 19b. Permeation through the BBB and albumin binding, we described here, is the first example of cyclic C5-curcuminoids as to our knowledge

Developmentally regulated autophagy is required for eye formation in Drosophila

The compound eye of the fruit fly Drosophila melanogaster is one of the most intensively studied and best understood model organs in the field of developmental genetics. Herein we demonstrate that autophagy, an evolutionarily conserved selfdegradation process of eukaryotic cells, is essential for eye development in this organism. Autophagic structures accumulate in a specific pattern in the developing eye disc, predominantly in the morphogenetic furrow (MF) and differentiation zone. Silencing of several autophagy genes (Atg) in the eye primordium severely affects the morphology of the adult eye through triggering ectopic cell death. In Atg mutant genetic backgrounds however genetic compensatory mechanisms largely rescue autophagic activity in, and thereby normal morphogenesis of, this organ. We also show that in the eye disc the expression of a key autophagy gene, Atg8a, is controlled in a complex manner by the anterior Hox paralog lab (labial), a master regulator of early development. Atg8a transcription is repressed in front of, while activated along, the MF by lab. The amount of autophagic structures then remains elevated behind the moving MF. These results indicate that eye development in Drosophila depends on the cell death-suppressing and differentiating effects of the autophagic process. This novel, developmentally regulated function of autophagy in the morphogenesis of the compound eye may shed light on a more fundamental role for cellular self-digestion in differentiation and organ formation than previously thought