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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

Pulmonary infections caused by Bordetella pertussis used to be the prime cause of infant mortality in the pre-vaccine era and mouse models of pertussis pneumonia served in characterization of B. pertussis virulence mechanisms. However, the biologically most relevant catarrhal disease stage and B. pertussis transmission has not been adequately reproduced in adult mice due to limited proliferation of the human-adapted pathogen on murine nasopharyngeal mucosa. We used immunodeficient C57BL/6J MyD88 KO mice to achieve B. pertussis proliferation to human-like high counts of 108 viable bacteria per nasal cavity to elicit rhinosinusitis accompanied by robust shedding and transmission of B. pertussis bacteria to adult co-housed MyD88 KO mice. Experiments with a comprehensive set of B. pertussis mutants revealed that pertussis toxin, adenylate cyclase toxin-hemolysin, the T3SS effector BteA/BopC and several other known virulence factors were dispensable for nasal cavity infection and B. pertussis transmission in the immunocompromised MyD88 KO mice. In contrast, mutants lacking the filamentous hemagglutinin (FhaB) or fimbriae (Fim) adhesins infected the nasal cavity poorly, shed at low levels and failed to productively infect co-housed MyD88 KO or C57BL/6J mice. FhaB and fimbriae thus appear to play a critical role in B. pertussis transmission. The here-described novel murine model of B. pertussis-induced nasal catarrh opens the way to genetic dissection of host mechanisms involved in B. pertussis shedding and to validation of key bacterial transmission factors that ought to be targeted by future pertussis vaccines.

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]

Abstract Zinc finger 644 (Zfp644 in mouse, ZNF644 in human) gene is a transcription factor whose mutation S672G is considered a potential genetic factor of inherited high myopia. ZNF644 interacts with G9a/GLP complex, which functions as a H3K9 methyltransferase to silence transcription. In this study, we generated mouse models to unravel the mechanisms leading to symptoms associated with high myopia. Employing TALEN technology, two mice mutants were generated, either with the disease-carrying mutation (Zfp644 S673G ) or with a truncated form of Zfp644 (Zfp644 Δ8 ). Eye morphology and visual functions were analysed in both mutants, revealing a significant difference in a vitreous chamber depth and lens diameter, however the physiological function of retina was preserved as found under the high-myopia conditions. Our findings prove that ZNF644/Zfp644 is involved in the development of high-myopia, indicating that mutations such as, Zfp644 S673G and Zfp644 Δ8 are causative for changes connected with the disease. The developed models represent a valuable tool to investigate the molecular basis of myopia pathogenesis and its potential treatment.

Introduction: Hormone changes during pregnancy lead to increased plasma lipid levels. When there is added disorder of lipid metabolism, this otherwise physiological change can cause extremely high triglyceride levels with potentionally life-threatening complications, such as non-biliary acute pancreatitis. Materials and Methods: We present a case report of a 27-year-old pregnant woman with familial hyperchylomicronemia and a history of 7 hypertriglyceridemia-induced acute pancreatitis attacks. Three attacks occured during her first pregnancy with the last one leading to its termination at 33 weeks owing to the death of the fetus. During her second pregnancy, standard treatment was not able to lower the triglyceride levels sufficiently and she suffered another acute pancreatitis attack. Therapeutic plasma exchange was therefore chosen as the treatment method. Results and Conclusion: Plasma exchange was succesful in the secondary prevention of acute pancreatitis attack and she delivered a healthy baby at 36 weeks of gestation. Treatment was very well tolerated by the mother and the fetus and this supports the use of apheresis as a safe and efficient method in tackling gestational hypertriglyceridemia.

Abstract Since the mid-2000s, transhumant pastoralism and the production of artisanal sheep’s cheeses have experienced a revival in the Polish Carpathians. This revival has largely coincided with Poland’s accession to the European Union in 2004, leading to a re-valuation of extensive livestock production from an economic and environmental liability to a form of ‘High Nature Value’ farming. Supported by Common Agricultural Policy CAP European Union subsidies, Polish pastoralists have been re-classified from being producers of livestock and agricultural products to suppliers of environmental and ecosystem services. Despite these changes, however, they continue to face significant systemic challenges which are rooted in the marked decline of the communist-era pastoral economy in the late 1980s and a subsequent increasing competition for land and labour under market conditions. Based on anthropological fieldwork conducted in Poland’s Carpathian Highland region during the 2015, 2016, and 2017 pastoral seasons, this article provides insight into four sets of challenges deemed most important by working shepherds today: recruiting qualified labour, gaining access to pasture, gaining access to markets, and working within a Polish policy environment which fails to recognise the particular conditions and requirements of pastoral agriculture.

Ascites syndrome (AS) is a metabolic disorder in fast-growing broilers that is characterized by non-tumult fluid collection in the abdomen. The objective of this study was to evaluate the effects of variable feeding and rearing temperature on AS occurrence in broilers. A total of 360 one-day-old male Ross-308 chicks were assigned to three equal groups (n = 120) fed pellet, crumble or mash diets and within each group, half of birds (n = 60, starting from the 22nd day of age) were reared under two different temperatures: at 23°C (comfort) or at 14°C (cold), respectively. There were six treatments and four replicates including 15 broilers per replicate per treatment. Birds’ growth performances and blood parameters as well the incidence of ascites were assessed. The haematocrit percentage, T3 and T4 hormones activity in pellet-fed group under cold temperature conditions were significantly higher (P .05). Further, feeding of mash diet reduced broilers’ feed consumption per unit of time, especially by level of achieving energy that is reducing the growth and AS.

Excessive methylglyoxal (MG) production contributes to metabolic and vascular changes by increasing inflammatory processes, disturbing regulatory mechanisms and exacerbating tissue dysfunction. MG accumulation in adipocytes leads to structural and functional changes. We used transcriptome analysis to investigate the effect of MG on metabolic changes in the visceral adipose tissue of hereditary hypetriglyceridaemic rats, a non-obese model of metabolic syndrome. Compared to controls, 4-week intragastric MG administration impaired glucose tolerance (p < 0.05) and increased glycaemia (p < 0.01) and serum levels of MCP-1 and TNFα (p < 0.05), but had no effect on serum adiponectin or leptin. Adipose tissue insulin sensitivity and lipolysis were impaired (p < 0.05) in MG-treated rats. In addition, MG reduced the expression of transcription factor Nrf2 (p < 0.01), which controls antioxidant and lipogenic genes. Increased expression of Mcp-1 and TNFα (p < 0.05) together with activation of the SAPK/JNK signaling pathway can promote chronic inflammation in adipose tissue. Transcriptome network analysis revealed the over-representation of genes involved in insulin signaling (Irs1, Igf2, Ide), lipid metabolism (Nr1d1, Lpin1, Lrpap1) and angiogenesis (Dusp10, Tp53inp1).

The vertebrate fauna of the Late Cretaceous Mussentuchit Member of the Cedar Mountain Formation has been studied for nearly three decades, yet the fossil-rich unit continues to produce new information about life in western North America approximately 97 million years ago. Here we report on the composition of the Cliffs of Insanity (COI) microvertebrate locality, a newly sampled site containing perhaps one of the densest concentrations of microvertebrate fossils yet discovered in the Mussentuchit Member. The COI locality preserves osteichthyan, lissamphibian, testudinatan, mesoeucrocodylian, dinosaurian, metatherian, and trace fossil remains and is among the most taxonomically rich microvertebrate localities in the Mussentuchit Member. To better refine taxonomic identifications of isolated theropod dinosaur teeth, we used quantitative analyses of taxonomically comprehensive databases of theropod tooth measurements, adding new data on theropod tooth morphodiversity in this poorly understood interval. We further provide the first descriptions of tyrannosauroid premaxillary teeth and document the earliest North American record of adocid remains, extending the appearance of this ancestrally Asian clade by 5 million years in western North America and supporting studies of pre-Cenomaninan Laurasian faunal exchange across Beringia. The overabundance of mesoeucrocodylian remains at the COI locality produces a comparatively low measure of relative biodiversity when compared to other microvertebrate sites in the Mussentuchit Member using both raw and subsampling methods. Much more microvertebrate research is necessary to understand the roles of changing ecology and taphonomy that may be linked to transgression of the Western Interior Seaway or microhabitat variation.

Here we provide a detailed description of the postcranial skeleton of the holotype and referred specimens of Buitreraptor gonzalezorum. This taxon was recovered as an unenlagiine dromaeosaurid in several recent phylogenetic studies and is the best represented Gondwanan dromaeosaurid discovered to date. It was preliminarily described in a brief article, but a detailed account of its osteology is emerging in recent works. The holotype is the most complete specimen yet found, so an exhaustive description of it provides much valuable anatomical information. The holotype and referred specimens preserve the axial skeleton, pectoral and pelvic girdles, and both fore- and hindlimbs. Diagnostic postcranial characters of this taxon include: anterior cervical centra exceeding the posterior limit of neural arch; eighth and ninth cervical vertebral centra with lateroventral tubercles; pneumatic foramina only in anteriormost dorsals; middle and posterior caudal centra with a complex of shallow ridges on lateral surfaces; pneumatic furcula with two pneumatic foramina on the ventral surface; scapular blade transversely expanded at mid-length; well-projected flexor process on distal end of the humerus; dorsal rim of the ilium laterally everted; and concave dorsal rim of the postacetabular iliac blade. A paleohistological study of limb bones shows that the holotype represents an earlier ontogenetic stage than one of the referred specimens (MPCA 238), which correlates with the fusion of the last sacral vertebra to the rest of the sacrum in MPCA 238. A revised phylogenetic analysis recovered Buitreraptor as an unenlagiine dromaeosaurid, in agreement with previous works. The phylogenetic implications of the unenlagiine synapomorphies and other characters, such as the specialized pedal digit II and the distal ginglymus on metatarsal II, are discussed within the evolutionary framework of Paraves.

BACKGROUND:Eolambia caroljonesa is the most abundant dinosaur in the lower Cenomanian Mussentuchit Member of the Cedar Mountain Formation of Utah, and one of the most completely known non-hadrosaurid iguanodontians from North America. In addition to the large holotype and paratype partial skulls, copious remains of skeletally immature individuals, including three bonebeds, have been referred to E. caroljonesa. Nevertheless, aspects of the postcranial anatomy of this taxon, particularly the pelvic girdle, have remained ambiguous due to the lack of associated postcranial material of larger, more mature individuals. METHODOLOGY/PRINCIPAL FINDINGS:Here we describe a recently discovered associated partial postcranial skeleton of a large Eolambia caroljonesa. This specimen, FMNH PR 3847, provides new anatomical data regarding the vertebral column and pelvic girdle, supplementing previous diagnoses and descriptions of E. caroljonesa. A new phylogenetic analysis incorporating information from FMNH PR 3847 places E. caroljonesa as a basal hadrosauromorph closely related to Protohadros byrdi from the Cenomanian Woodbine Formation of Texas. Histological analysis of FMNH PR 3847 reveals that it represents a subadult individual eight to nine years of age. Taphonomic analysis indicates that FMNH PR 3847 was preserved in a crevasse splay deposit, along with an unusual abundance of small crocodylomorph material. CONCLUSIONS/SIGNIFICANCE:FMNH PR 3847 provides a wealth of new morphological data, adding to the anatomical and systematic characterization of Eolambia caroljonesa, and histological data, revealing new information on growth history in a basal hadrosauromorph. Taphonomic characterization of FMNH PR 3847 and associated vertebrate material will allow comparison with other vertebrate localities in the Mussentuchit Member of the Cedar Mountain Formation.

Late Cretaceous terrestrial strata of the Neuquén Basin, northern Patagonia, Argentina have yielded a rich fauna of dinosaurs and other vertebrates. The diversity of saurischian dinosaurs is particularly high, especially in the late Cenomanian-early Turonian Huincul Formation, which has yielded specimens of rebacchisaurid and titanosaurian sauropods, and abelisaurid and carcharodontosaurid theropods. Continued sampling is adding to the known vertebrate diversity of this unit.A new, partially articulated mid-sized theropod was found in rocks from the Huincul Formation. It exhibits a unique combination of traits that distinguish it from other known theropods justifying erection of a new taxon, Gualicho shinyae gen. et sp. nov. Gualicho possesses a didactyl manus with the third digit reduced to a metacarpal splint reminiscent of tyrannosaurids, but both phylogenetic and multivariate analyses indicate that didactyly is convergent in these groups. Derived characters of the scapula, femur, and fibula supports the new theropod as the sister taxon of the nearly coeval African theropod Deltadromeus and as a neovenatorid carcharodontosaurian. A number of these features are independently present in ceratosaurs, and Gualicho exhibits an unusual mosaic of ceratosaurian and tetanuran synapomorphies distributed throughout the skeleton.Gualicho shinyae gen. et sp. nov. increases the known theropod diversity of the Huincul Formation and also represents the first likely neovenatorid from this unit. It is the most basal tetatanuran to exhibit common patterns of digit III reduction that evolved independently in a number of other tetanuran lineages. A close relationship with Deltadromaeus from the Kem Kem beds of Niger adds to the already considerable biogeographic similarity between the Huincul Formation and coeval rock units in North Africa.

The partial skeleton of a leptoceratopsid dinosaur, Ischioceratops zhuchengensis gen. et sp. nov., was excavated from the bone-beds of the Upper Cretaceous Wangshi Group of Zhucheng, Shandong Province, China. This fossil represents the second leptoceratopsid dinosaur specimen recovered from the Kugou locality, a highly productive site in Zhucheng. The ischium of the new taxon is morphologically unique among known Dinosauria, flaring gradually to form an obturator process in its middle portion and resembling the shaft of a recurve bow. An elliptical fenestra perforates the obturator process, and the distal end of the shaft forms an axehead-shaped expansion. The discovery of Ischioceratops increases the known taxonomic diversity and morphological disparity of the Leptoceratopsidae.