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Kristina Jakic,1 Michal Selc,1,2 Filip Razga,3 Veronika Nemethova,3 Petra Mazancova,3 Filip Havel,4,5 Michal Sramek,5 Monika Zarska,5 Jan Proska,4 Vlasta Masanova,6 Iveta Uhnakova,6 Peter Makovicky,7 Marta Novotova,8 Vit Vykoukal,9 Andrea Babelova1,2 1Department of Nanobiology, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia; 2Centre for Advanced Material Application, Slovak Academy of Sciences, Bratislava, Slovakia; 3Selecta Biotech SE, Bratislava, Slovakia; 4Department of Physical Electronics, Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University in Prague, Prague, Czech Republic; 5Department of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic; 6Department of Metallomics, Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia; 7Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia; 8Department of Cellular Cardiology, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia; 9Department of Chemistry, Faculty of Science, Masaryk University, Brno, Czech RepublicCorrespondence: Andrea Babelova, Department of Nanobiology, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia, Tel +421-2-32295-189, Fax +421-2-5477-4284, Email andrea.babelova@savba.skIntroduction: Gold nanoparticles are promising candidates as vehicles for drug delivery systems and could be developed into effective anticancer treatments. However, concerns about their safety need to be identified, addressed, and satisfactorily answered. Although gold nanoparticles are considered biocompatible and nontoxic, most of the toxicology evidence originates from in vitro studies, which may not reflect the responses in complex living organisms.Methods: We used an animal model to study the long-term effects of 20 nm spherical AuNPs coated with bovine serum albumin. Mice received a 1 mg/kg single intravenous dose of nanoparticles, and the biodistribution and accumulation, as well as the organ changes caused by the nanoparticles, were characterized in the liver, spleen, and kidneys during 120 days.Results: The amount of nanoparticles in the organs remained high at 120 days compared with day 1, showing a 39% reduction in the liver, a 53% increase in the spleen, and a 150% increase in the kidneys. The biological effects of chronic nanoparticle exposure were associated with early inflammatory and fibrotic responses in the organs and were more pronounced in the kidneys, despite a negligible amount of nanoparticles found in renal tissues.Conclusion: Our data suggest, that although AuNPs belong to the safest nanomaterial platforms nowadays, due to their slow tissue elimination leading to long-term accumulation in the biological systems, they may induce toxic responses in the vital organs, and so understanding of their long-term biological impact is important to consider their potential therapeutic applications. Keywords: AuNPs, in vivo, long-term accumulation, biodistribution, inflammation, fibrosis

Linear scores and measures of both udder and teat shape and size (thirteen traits) were assessed in 83 ewes of Improved Valachian breed (IV) and in crossbreds with East Friesian breed (EF 25% or EF 50%). At the same time, cistern measures and cross-section areas (fourteen traits) as well as milk yield and milkability were scanned using ultrasound technique or measured in the same individuals (130 measurements in each trait). Crossbreds with EF 50% had the largest udders in terms of depth, width, and height, as determined by either a nine-point linear score or exact measurements. Additionally, these crossbreds had teats that were more horizontally placed and the most appropriate udder attachment and shape. more horizontally and most appropriate udder attachment and shape. Ultrasound scans revealed that the areas of both the left and right udder cisterns scanned by ultrasound were the highest in EF 50% crosses. Overall cistern cross-section areas scanned from the side were 2934.6 mm² in IV, 2932.6 mm² in crosses of EF 25% and 3559.4 mm² in crosses of EF 50% (P<0.05). Crossbreds of EF 50% had more appropriate machine milked milk and total milk yield (311.1 and 424.7 ml) than purebred IV (231.8 and 336.1 ml; P>0.05). On average, the proportion of machine-stripped milk was 33.2%, and non-significant influence of genotype was shown. Furthermore, all traits under study showed nonsignificant differences between crosses of EF 25% and 50%. [ABSTRACT FROM AUTHOR]

Soft tissue reconstructions of fossil vertebrates provide valuable data and support for functional interpretations. Here, we present the pelvic and hindlimb muscular reconstruction of Buitreraptor gonzalezorum, a unenlagiine dromaeosaurid theropod. Dromaeosaurids employed their hindlimbs for locomotion and predation, with a specialised pedal digit II. Using the ‘extant phylogenetic bracket’ methodology, we reconstruct 29 muscles out of the 37 typically found in extant archosaur hindlimbs. Some characteristics resemble those of specialised cursorial tetrapods. For example, M. iliotibialis shows an increased hip abduction moment arm, while primary protractors exhibit an increased hip flexion moment arm, and main retractors display a decreased hip extension moment arm. However, positive allometric growth of limb inertia relative to body mass and the gradual transition to a ‘knee-based’ locomotion observed in extant birds may have influenced muscle moment arms. Regarding predatory functions, the muscular features and length proportions of the metatarsus and pedal digit II phalanges suggest faster movements compared to derived dromaeosaurids. Also, a robust flexor muscle, likely M. flexor perforans et perforatus digiti II, was inserted on the proximoventral heel of the second phalanx of pedal digit II. These functional interpretations suggest the presence of specialised behaviours different from those observed in more derived dromaeosaurids. [ABSTRACT FROM AUTHOR]

The present study aimed to identify the novel mechanisms regulating rabbit fecundity. For this purpose, the association between litter size variability, fecundity, ovarian morphology, and markers of proliferation, apoptosis, steroidogenesis, and the presence of regulatory proteins were examined in ovarian cells from two rabbit lines divergently selected for low (LL) and high (HL) variability in litter size throughout sixteen generations. Ovaries and uteri were isolated from multiparous non-lactating female rabbits from each line at sixteen generations of selection. One part of the ovary was subjected to histomorphometric analysis of folliculogenesis. From the rest of ovary, ovarian granulosa cells (OGCs) were isolated, cultured, and cell viability, proliferation (accumulation of PCNA and of cyclin B1, and BrdU-positive cells), and apoptosis (accumulation of caspase 3, bax and DNA fragmentation) were evaluated by the Trypan blue exclusion test and BrdU, quantitative immunocytochemistry, and cell death detection assays. Furthermore, OGCs were subjected to proteomic analysis by using the nano HPLC-Chip-MS/MS method. The release of progesterone and oestradiol was measured by ELISA. The LL had more than one kit per litter than the HL (7.6 kits vs. 6.5 kits, p ≤ 0.05). No differences were found in the diameter of primordial and primary ovarian follicles, theca, and granulosa thickness, but the diameter of oocytes in the primary and secondary follicles was higher in the LL than in the HL (88.49 µm in the LL vs. 77.86 µm in the HL for oocytes of primary follicles, p ≤ 0.05; 122.10 µm in the LL vs. 109.87 µm in the HL for oocytes of secondary follicles, p ≤ 0.05). Preovulatory follicles were presented only in the ovaries of the LL. The LL had higher incorporation of BrdU and reduced accumulation of bax within OGCs (0.92% in the LL vs. 0.44% in the HL for incorporation of BrdU, p ≤ 0.05; 41% in the LL vs. 48% in the HL for accumulation of bax, p ≤ 0.05). Ovarian fragments from the LL produced less progesterone and oestradiol than those of the HL (12 ng/mg tissue/day in the LL vs, 45 ng/mg tissue/day in the HL for progesterone, p ≤ 0.05; 11 ng/mg tissue/day in the LL vs. 30 ng/mg tissue/day in the HL for oestradiol, p ≤ 0.05). Besides, the OGCs from the LL produced a higher number of specific regulatory proteins involved in cell differentiation, proliferation, and adhesion than the HL (50 vs 38, p ≤ 0.05). In conclusion, higher prolificacy in the LL line would be caused by: (1) the selection of growing primordial ovarian follicles; (2) better transformation to preovulatory follicles; (3) increased cytoplasmic maturation of oocytes; (4) increased DNA synthesis and decreased cytoplasmic apoptosis in OGCs; (5) changes in ovarian steroidogenesis; and (6) changes in the number of peptides involved in cell differentiation, proliferation, and adhesion.HIGHLIGHTS Assessing fecundity in two divergently rabbit lines for variability in litter size. Fecundity and its variability are related to the diameter and quality of oocytes. Selection and better growth of preovulatory follicles have been related to fecundity.

Peripheral nerve sheath tumours (PNSTs) are rare in the mammary glands of dogs. Here, we report a case of a schwannoma, composed of two parts, of the mammary gland of a dog. The first part consists of clusters of uncircumscribed, alternating, more concentrated and looser regions. In the more concentrated parts, typical fascicularly arranged schwannoma intermingle in plexiform arrangement, more subtle in appearance than in neuronal tumour areas. The second part undergoes regression consisting predominantly of residual shorter rosettes of cells with the presence of a peculiar variably sized swirling of target-like formations consisting of compact, thicker, pinkish lamellae also with occasional adjacent cells. Immunohistochemically, the tumour cells are positive for evidence of vimentin and neuro-specific enolase. They exhibit the variable expression of the S-100 protein, show mild CD56 positivity, and focally mildly accentuated proliferative activity as assessed by Ki-67. The tumour elements are negative for evidence of cytokeratin 7, cytokeratin 20, and oestrogen receptors. Hybrid tumours may change their morphology in combination with atypical localisation and may be underdiagnosed in veterinary biopsy practice. They differ from epithelial tumours prognostically, as well as in their development and behaviour, therefore it is essential to clearly differentiate them.

Linear scores and measures of both udder and teat shape and size (thirteen traits) were assessed in 83 ewes of Improved Valachian breed (IV) and in crossbreds with East Friesian breed (EF 25% or EF 50%). At the same time, cistern measures and cross-section areas (fourteen traits) as well as milk yield and milkability were scanned using ultrasound technique or measured in the same individuals (130 measurements in each trait). Crossbreds with EF 50% had the largest udders in terms of depth, width, and height, as determined by either a nine-point linear score or exact measurements. Additionally, these crossbreds had teats that were more horizontally placed and the most appropriate udder attachment and shape. more horizontally and most appropriate udder attachment and shape. Ultrasound scans revealed that the areas of both the left and right udder cisterns scanned by ultrasound were the highest in EF 50% crosses. Overall cistern cross-section areas scanned from the side were 2934.6 mm2 in IV, 2932.6 mm2 in crosses of EF 25% and 3559.4 mm2 in crosses of EF 50% (P0.05). On average, the proportion of machine-stripped milk was 33.2%, and non-significant influence of genotype was shown. Furthermore, all traits under study showed non significant differences between crosses of EF 25% and 50%.

The Late Cretaceous of western North America supported diverse dinosaur assemblages, though understanding patterns of dinosaur diversity, evolution, and extinction has been historically limited by unequal geographic and temporal sampling. In particular, the existence and extent of faunal endemism along the eastern coastal plain of Laramidia continues to generate debate, and finer scale regional patterns remain elusive. Here, we report a new centrosaurine ceratopsid, Lokiceratops rangiformis, from the lower portion of the McClelland Ferry Member of the Judith River Formation in the Kennedy Coulee region along the Canada-USA border. Dinosaurs from the same small geographic region, and from nearby, stratigraphically equivalent horizons of the lower Oldman Formation in Canada, reveal unprecedented ceratopsid richness, with four sympatric centrosaurine taxa and one chasmosaurine taxon. Phylogenetic results show that Lokiceratops, together with Albertaceratops and Medusaceratops, was part of a clade restricted to a small portion of northern Laramidia approximately 78 million years ago. This group, Albertaceratopsini, was one of multiple centrosaurine clades to undergo geographically restricted radiations, with Nasutuceratopsini restricted to the south and Centrosaurini and Pachyrostra restricted to the north. High regional endemism in centrosaurs is associated with, and may have been driven by, high speciation rates and diversity, with competition between dinosaurs limiting their geographic range. High speciation rates may in turn have been driven in part by sexual selection or latitudinally uneven climatic and floral gradients. The high endemism seen in centrosaurines and other dinosaurs implies that dinosaur diversity is underestimated and contrasts with the large geographic ranges seen in most extant mammalian megafauna.

The coronavirus pandemic has resulted in over 775 million cases and 7 million deaths worldwide, driving efforts to develop therapeutic strategies to control the viral infection. Therapeutic oligonucleotides have shown promise in treating many pathological conditions, including those of viral origin. The present study assessed the in vivo efficacy and safety of ASC1R, a novel therapeutic oligonucleotide of unconventional design targeting the conserved viral RdRp sequence essential for replication. In functional studies, ASC1R was administered to transfected C57BL/6 mice at doses of 1 and 10 mg/kg. Safety assessments included acute toxicity evaluations at doses ranging from 30 to 100 mg/kg, and subacute toxicity evaluations of repeated doses of 1 and 10 mg/kg. Evaluations included general clinical observations, findings at necropsy, measurements of organ weight, and histopathological examinations of the liver, lungs, spleen, and kidneys. ASC1R effectively reduced RdRp levels >94 % within 24 hours following a single 1 mg/kg dose, with no observed organ toxicity. Acute and subacute toxicity assessments found that mice receiving high (≥30 mg/kg) or repeated (10 mg/kg for 7 days) doses of ASC1R showed an increase in relative spleen weight, without histopathological changes. The marked ability of a single low dose of ASC1R (1 mg/kg) to reduce viral RNA suggests its potential for clinical applications, balancing therapeutic efficacy with minimal side effects. Our findings indicate that ASC1R has promise as a viable treatment option for patients with COVID-19., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Selecta Biotech holds the intellectual property rights to ASC1R, with Veronika Nemethova and Filip Razga listed as inventors. Veronika Nemethova and Filip Razga are co-founders and own stock options in Selecta Biotech. The authors have no other conflicts of interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Peripheral nerve sheath tumours (PNSTs) are rare in the mammary glands of dogs. Here, we report a case of a schwannoma, composed of two parts, of the mammary gland of a dog. The first part consists of clusters of uncircumscribed, alternating, more concentrated and looser regions. In the more concentrated parts, typical fascicularly arranged schwannoma intermingle in plexiform arrangement, more subtle in appearance than in neuronal tumour areas. The second part undergoes regression consisting predominantly of residual shorter rosettes of cells with the presence of a peculiar variably sized swirling of target-like formations consisting of compact, thicker, pinkish lamellae also with occasional adjacent cells. Immunohistochemically, the tumour cells are positive for evidence of vimentin and neuro-specific enolase. They exhibit the variable expression of the S-100 protein, show mild CD56 positivity, and focally mildly accentuated proliferative activity as assessed by Ki-67. The tumour elements are negative for evidence of cytokeratin 7, cytokeratin 20, and oestrogen receptors. Hybrid tumours may change their morphology in combination with atypical localisation and may be underdiagnosed in veterinary biopsy practice. They differ from epithelial tumours prognostically, as well as in their development and behaviour, therefore it is essential to clearly differentiate them., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Makovicka et al.)

Objectives: The aim of the study was to evaluate pulmonary sequestration (PS). We report on location, blood supply, histology, clinical manifestation, and surgical treatment of PS, as well as on postoperative course in patients with PS., Background: PS is a rare congenital defect of the lower respiratory tract, it represents locus minoris resistentiae of the body. Occasionally, PS is diagnosed for the first time in adulthood., Methods: We evaluated 7 cases of PS treated at the Centre of Thoracic Surgery in Vyšné Hágy, Slovakia, between years 2013 and 2020., Results: Four of our seven patients were asymptomatic; the PS was found incidentally upon chest imaging. Three patients had recurrent bronchopneumonia related specifically to the intralobar type of sequestration. The most significant complication, observed in a singular patient, was a life-threatening episode of haemoptysis, requiring urgent surgical intervention. In the other 6 cases, the sequestra were surgically resected during the period when they were asymptomatic. and their sputum was confirmed negative upon microbiological examination. Anatomical resection of the affected pulmonary lobe by thoracotomy was the most common type of operation performed (4 cases, n = 7). There was no surgical mortality., Conclusion: To prevent complications, it is crucial to perform surgical treatment for pulmonary sequestration in patients who have sufficient functional capacity (Tab. 2, Fig. 4, Ref. 30). Text in PDF www.elis.sk Keywords: pulmonary sequestration, anatomic lobectomy, haemoptysis.