A case of metastatic non-teratoid ocular medulloepithelioma in an adult horse

This case reports an eight-years-old horse that presented a unilateral tumor in the left ocular orbital region diagnosed on the basis of clinical signs, gross anatomopathological and histopathological investigations. The affected area was exenteration and submitted to histopathological evaluation and was diagnosed as a non-teratoid medulloepithelioma. This is a rare ocular neoplasm that usually affects young individuals – and was composed by neuroepithelium arranged in tubules and Flexner-Wintersteiner rosettes without presence of heteroplastic components. The animals died and was submitted to post-mortem evaluation, revealing presence of medulloepithelioma metastases at the internal region of the head, lymph nodes, lungs, and liver. This neoplasm usually presents a benign frame; however, the case herein described shows that it can be highly malignant and aggressive since it can cause extensive lesions and spread metastases to visceral organs.

Site-Specific Conversion of Cysteine in a Protein to Dehydroalanine Using 2-Nitro-5-thiocyanatobenzoic Acid

Dehydroalanine exists natively in certain proteins and can also be chemically made from the protein cysteine. As a strong Michael acceptor, dehydroalanine in proteins has been explored to undergo reactions with different thiolate reagents for making close analogues of post-translational modifications (PTMs), including a variety of lysine PTMs. The chemical reagent 2-nitro-5-thiocyanatobenzoic acid (NTCB) selectively modifies cysteine to form S-cyano-cysteine, in which the S–Cβ bond is highly polarized. We explored the labile nature of this bond for triggering E2 elimination to generate dehydroalanine. Our results indicated that when cysteine is at the flexible C-terminal end of a protein, the dehydroalanine formation is highly effective. We produced ubiquitin and ubiquitin-like proteins with a C-terminal dehydroalanine residue with high yields. When cysteine is located at an internal region of a protein, the efficiency of the reaction varies with mainly hydrolysis products observed. Dehydroalanine in proteins such as ubiquitin and ubiquitin-like proteins can serve as probes for studying pathways involving ubiquitin and ubiquitin-like proteins and it is also a starting point to generate proteins with many PTM analogues; therefore, we believe that this NTCB-triggered dehydroalanine formation method will find broad applications in studying ubiquitin and ubiquitin-like protein pathways and the functional annotation of many PTMs in proteins such as histones.

Pseudohermaphroditism in a female French Bulldog

Pseudohermaphroditism is a sexual anomaly, rare in dogs, in which the individual has both male and female characteristics; normally ambiguous external genitalia and male or female gonads. This report concerns a 5-month-old female French Bulldog, where the principal concern was the presence of a structure in the internal region of the genitalia with evolution of approximately 2 months. Upon clinical examination, it was found that the patient had a characteristically female phenotype and a vagina with no apparent changes, despite the presence of a hypertrophied structure inside, similar to a clitoris and a probable penile bone. A right lateral abdominal radiography revealed the presence of a probable atrophied penile bone located inside the vulva. An ultrasound examination showed the presence of two oval, coarse and hypoechogenic structures in the inguinal (subcutaneous) region, suggesting ectopic testicles; ovaries and uterus were not observed. However, during laparotomy the absence of ovaries and the presence of uterus and testicles in the subcutaneous tissue were observed.

Addressing the phytochemical prospection of thermally treated Eucalyptus grandis wood

This work aimed to investigate phytochemical prospection in treated and untreated wood of Eucalyptus grandis to understand the dynamics of extractives in relation to heat treatment. Samples of E. grandis wood were collected and grouped into external and internal regions. Half of the samples from each region were submitted to heat treatment at 190 ºC. From the treated and untreated samples, phytochemical tests were performed to detect classes of metabolites present in the E. grandis raw wood, hydrophilic extract and lipophilic extract. Phytochemical analysis detected the presence of alkaloids, phenolic compounds and triterpenoids in all hydrophilic extracts of the studied species. Presence of flavanonols, flavanones and saponins was detected only in the internal region of the wood. Tannins, leucoanthocyanidins, triterpenoids and saponins were influenced by heat treatment. The classes of flavonoids, xanthones and alkaloids are the most resistant to heat treatment. The phytochemical analysis made it possible to identify a new class of extractives that emerged after heat treatment, flavones.

The internal region of CtIP negatively regulates DNA end resection

DNA double-strand breaks are repaired by end-joining or homologous recombination. A key-committing step of recombination is DNA end resection. In resection, phosphorylated CtIP first promotes the endonuclease of MRE11–RAD50–NBS1 (MRN). Subsequently, CtIP also stimulates the WRN/BLM–DNA2 pathway, coordinating thus both short and long-range resection. The structure of CtIP differs from its orthologues in yeast, as it contains a large internal unstructured region. Here, we conducted a domain analysis of CtIP to define the function of the internal region in DNA end resection. We found that residues 350–600 were entirely dispensable for resection in vitro. A mutant lacking these residues was unexpectedly more efficient than full-length CtIP in DNA end resection and homologous recombination in vivo, and consequently conferred resistance to lesions induced by the topoisomerase poison camptothecin, which require high MRN–CtIP-dependent resection activity for repair. This suggested that the internal CtIP region, further mapped to residues 550–600, may mediate a negative regulatory function to prevent over resection in vivo. The CtIP internal deletion mutant exhibited sensitivity to other DNA-damaging drugs, showing that upregulated resection may be instead toxic under different conditions. These experiments together identify a region within the central CtIP domain that negatively regulates DNA end resection.

REGIONAL BOUNDARY ASYMPTOTIC GRADIENT FULL ORDER OBSERVER VIA INTERNAL REGION

The purpose of this paper is to deals with the problem of regional boundary asymptotic gradient full order observer (-observer) concept by using internal regional case. Thus, we study the relation between this notion and the corresponding asymptotic detectability and sensors. More precisely, various important results have been examined and explored concern an extension of an approach which enables to reconstruct the gradient of current state from internal region. In addition, it has been shown that the characterization of -observability under which conditions to be achieved. Finally, we have illustrate that there is a dynamical system which does not represent the observer in the usual sense, but it could be interpreted as a -observer.

ANTHROPOGENIC IMPACTS ON THE WESTERN SECTOR OF SEPETIBA BAY (SE DO BRAZIL) ACCESSED BY THE PB ISOTOPE COMPOSITION OF SURFACE SEDIMENTS

This work analyses lead concentrations and isotope ratios 204Pb,206Pb,207Pb,208Pb, determined by leaching and total dissolution techniques from surface bottom sediment samples collected in the western sector of Sepetiba Bay, Rio de Janeiro (SE Brazil). The main aim of this work was to identify possible sources of Pb, particularly those related to anthropogenic activities for the study area located in the external region of this bay. Isotope ratios of 206Pb, 207Pb ranged from 1.160 to 1.259 for the total dissolution technique and from 1.175 to 1.188 for the leaching technique. The Pb isotope signature of the surface sediments of the western sector of Sepetiba Bay were compared with that obtained in other studies performed in Sepetiba Bay, including records of pre- and pos-industrial activity, and in other Brazilian regions. The isotope signature of the analyzed sediments in the western sector of Sepetiba Bay is similar to that obtained in previous works realized in the eastern and northeastern internal region of this bay which is under strong urbanization and industrial pressure. The results of Pb isotope signature obtained by the integrated use of total dissolution and leaching techniques allowed to trace the presence of sediments dredged from highly contaminated areas located in the eastern and north-eastern internal region of Sepetiba Bay probably as a consequence of dredging activities and natural processes of sediment dispersion. IMPACTOS ANTROPOGÊNICOS NO SETOR OESTE DA BAÍA DE SEPETIBA (SE DO BRASIL) ACESSADOS PELA COMPOSIÇÃO ISOTÓPICA DE PB DE SEDIMENTOS SUPERFÍCIAIS ResumoEste trabalho analisa as concentrações de chumbo (Pb) e isótopos de Pb (204Pb, 206Pb, 207Pb, 208Pb) determinados por técnicas de lixiviação e dissolução total de amostras de sedimentos de fundo, coletadas no setor oeste (região externa) da Baía de Sepetiba, no Rio de Janeiro (SE Brasil). O principal objetivo deste trabalho foi identificar possíveis fontes de Pb, principalmente aquelas relacionadas a atividades antropogênicas na área de estudo. A assinatura do isótopo Pb dos sedimentos analisados foi comparada com os dados obtidos em outros estudos realizados na Baía de Sepetiba e em outras regiões brasileiras, incluindo registros de atividade pré e pós-industrial. Na região externa da Baía de Sepetiba, os valores de 206Pb/207Pb variaram de 1.160 a 1.259 para a técnica de dissolução total e de 1.175 a 1.188 para a técnica de lixiviação. A assinatura isotópica dos sedimentos analisados é semelhante à obtida em trabalhos anteriores realizados na região interna leste e nordeste desta baía, que está sob forte influência da urbanização e pressão industrial. Os resultados da assinatura dos isótopos de Pb obtidos pelo uso integrado das técnicas de dissolução total e lixiviação permitiram rastrear, no setor oeste (região externa) da Baía de Sepetiba, a presença de sedimentos provinientes de áreas altamente contaminadas localizadas na região interna leste e nordeste da baía de Sepetiba, provavelmente como conseqüência das atividades de dragagem e processos naturais de dispersão de sedimentos. Palavras-chave: Isótopos de Pb. Geoquímica. Atividades antropogênicas. Fonte de sedimentos. Impacto de dragagem. Litoral.

The role of building fortified lines and new cities in the formation of southeastern borders of Russia in the 17th – 18th centuries

The study of the process of state territory expansion and the formation of state borders is a relevant problem of historical science. We set a goal: to show how this process went on in the Southeast of Russia in the 17th – 18th centuries. In the context of the regionalization of domestic historical science, frontier theory is an important methodological tool. It allows applying theoreti-cal and concrete historical scientists’ solutions to the study of the southeastern frontier of Russia obtained as a result of studying other border territories, in particular the southern and Volga fron-tier. The main results of this study define the southeast frontier and sets its geographic parameters, covering mainly the territory of Bashkiria, which has been part of Russia since the middle of the 16th century. We substantiate the role of fortress cities and fortified lines in the formation of the southeast frontier zone. We show the process of state borders formation in this region. We draw conclusion that, regardless of the construction motives, the fortress cities became a political tool for securing new lands within the Russian state, and contributed to the gradual transformation of the frontier territory into an internal region (county, governorate).

Involvement of the N-Terminal Deubiquitinating Protease Domain of Human Cytomegalovirus UL48 Tegument Protein in Autoubiquitination, Virion Stability, and Virus Entry

ABSTRACTHuman cytomegalovirus (HCMV) protein pUL48 is closely associated with the capsid and has a deubiquitinating protease (DUB) activity in its N-terminal region. Although this DUB activity moderately increases virus replication in cultured fibroblast cells, the requirements of the N-terminal region of pUL48 in the viral replication cycle are not fully understood. In this study, we characterized the recombinant viruses encoding UL48(ΔDUB/NLS), which lacks the DUB domain and the adjacent nuclear localization signal (NLS), UL48(ΔDUB), which lacks only the DUB, and UL48(Δ360–1200), which lacks the internal region (amino acids 360 to 1200) downstream of the DUB/NLS. While ΔDUB/NLS and Δ360–1200 mutant viruses did not grow in fibroblasts, the ΔDUB virus replicated to titers 100-fold lower than those for wild-type virus and showed substantially reduced viral gene expression at low multiplicities of infection. The DUB domain contained ubiquitination sites, and DUB activity reduced its own proteasomal degradation intrans. Deletion of the DUB domain did not affect the nuclear and cytoplasmic localization of pUL48, whereas the internal region (360–1200) was necessary for cytoplasmic distribution. In coimmunoprecipitation assays, pUL48 interacted with three tegument proteins (pUL47, pUL45, and pUL88) and two capsid proteins (pUL77 and pUL85) but the DUB domain contributed to only pUL85 binding. Furthermore, we found that the ΔDUB virus showed reduced virion stability and less efficiently delivered its genome into the cell than the wild-type virus. Collectively, our results demonstrate that the N-terminal DUB domain of pUL48 contributes to efficient viral growth by regulating its own stability and promoting virion stabilization and virus entry.IMPORTANCEHCMV pUL48 and its herpesvirus homologs play key roles in virus entry, regulation of immune signaling pathways, and virion assembly. The N terminus of pUL48 contains the DUB domain, which is well conserved among all herpesviruses. Although studies using the active-site mutant viruses revealed that the DUB activity promotes viral growth, the exact role of this region in the viral life cycle is not fully understood. In this study, using the mutant virus lacking the entire DUB domain, we demonstrate that the DUB domain of pUL48 contributes to viral growth by regulating its own stability via autodeubiquitination and promoting virion stability and virus entry. This report is the first to demonstrate the characteristics of the mutant virus with the entire DUB domain deleted, which, along with information on the functions of this region, is useful in dissecting the functions associated with pUL48.