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PARP-1 has been linked to the progression of several types of cancer. We have recently reported that PARP-1 influences tumor progression in CRC through the regulation of CSCs in a p53-dependent manner. In this study, we propose that nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) could act as a mediator. We evaluated the expression of iNOS in a cohort of patients previously used to analyze the effects of PARP-1 on CRC in relation to p53 status. We also developed an in vitro model in which PARP-1 was stably overexpressed. In CRC patients, iNOS expression correlated with the differentiation grade, and with a high expression of CSC markers, although only in wild-type p53 tumors, as previously found for PARP-1. In vitro, overexpression of PARP-1 induced increased growth and stemness in wild-type p53 cells, while exerting the opposite effect on mutated ones, as expected. Treatment with 1400 W, a selective inhibitor of iNOS, or gene silencing of the gene counteracted the effects of PARP-1 in both p53 wild-type and p53 mutated cells. Given that the development of resistance has been demonstrated after treatment with PARP-1 inhibitors, iNOS could be considered a new therapeutic target in CRC, although only in patients with wild-type p53 tumors. [ABSTRACT FROM AUTHOR]

Veterinary pathology credentials serve as a concise means attesting to educational attainments and experiences indicating a readiness for professional practice. Given the cost, time, and stress associated with obtaining different qualifications, pathologists must consider what credentials enhance their readiness. In this commentary, the authors describe how their various degrees and certifications have facilitated their individual and organizational success. The minimum credentials for proficient veterinary pathology practice are a veterinary medical degree (DVM or equivalent) and advanced pathology training (residency and/or on-the-job "apprenticeship") ideally culminating in board certification in pathology (American College of Veterinary Pathologists [ACVP] diplomate status or equivalent). Graduate degrees (MS, PhD, MPH, etc) and/or other qualifications in allied biomedical fields (eg, board certification in internal medicine, laboratory animal medicine, poultry medicine, preventive medicine, or toxicology) may improve employability by affirming specialty knowledge in another complementary discipline. The authors note that pathology positions may be obtained without a long list of degrees or certifications, and that more credentials may provide occupational flexibility for some employers. However, a good work ethic, experience in the field, ability to adapt to changes, job satisfaction, good attitude, and demonstrated productivity are also important, and indeed, they are often the paramount criteria for career success as a veterinary pathologist. [ABSTRACT FROM AUTHOR]

Western North America preserves iconic dinosaur faunas from the Upper Jurassic and Upper Cretaceous, but this record is interrupted by an approximately 20 Myr gap with essentially no terrestrial vertebrate fossil localities. This poorly sampled interval is nonetheless important because it is thought to include a possible mass extinction, the origin of orogenic controls on dinosaur spatial distribution, and the origin of important Upper Cretaceous dinosaur taxa. Therefore, dinosaurbearing rocks from this interval are of particular interest to vertebrate palaeontologists. In this study, we report on one such locality from Highwood Pass, Alberta. This locality has yielded a multitaxic assemblage, with the most diagnostic material identified so far including ankylosaurian osteoderms and a turtle plastron element. The fossil horizon lies within the upper part of the Pocaterra Creek Member of the Cadomin Formation (Blairmore Group). The fossils are assigned as Berriasian (earliest Cretaceous) in age, based on previous palynomorph analyses of the Pocaterra Creek Member and underlying and overlying strata. The fossils lie within numerous cross-bedded sandstone beds separated by pebble lenses. These sediments are indicative of a relatively high-energy depositional environment, and the distribution of these fossils over multiple beds indicates that they accumulated over multiple events, possibly flash floods. The fossils exhibit a range of surface weathering, having intact to heavily weathered cortices. The presence of definitive dinosaur material from near the Jurassic--Cretaceous boundary of Alberta establishes the oldest record of dinosaur body fossils in western Canada and provides a unique opportunity to study the Early Cretaceous dinosaur faunas of western North America. Key words: Ankylosauria, Berriasian, Blairmore Group, Cadomin Formation, Early Cretaceous, Kananaskis, osteoderm, Pocaterra Creek Member, Rocky Mountains, Testudines. Des assemblages de dinosaures emblematiques du Jurassique superieur au Cretace superieur sont preserves dans l'ouest de l'Amerique du Nord, mais ce registre est interrompu par une pause d'environ 20 millions d'annees caracterisee par l'absence presque totale de localites a fossiles de vertebres terrestres. Cet intervalle mal represente n'en est pas moins important parce qu'il comprendrait une possible extinction massive, l'origine de controles orogeniques de la repartition spatiale de dinosaures et l'origine d'importants taxons de dinosaures du Cretace superieur. Les roches renfermant des dinosaures de cet intervalle sont donc particulierement interessantes pour les paleontologues s'interessant aux vertebres. Nous faisons etat d'une telle localite a Highwood Pass (Alberta), qui a produit un assemblage multitaxons duquel le materiau le plus diagnostic obtenu a ce jour comprend des osteodermes ankylosauriens et un element de plastron de tortue. L'horizon fossilifere se trouve dans la partie superieure du membre de Pocaterra Creek de la Formation de Cadomin (Groupe de Blairmore). Un age berriasien (debut du Cretace) est attribue aux fossiles a la lumiere d'analyses anterieures de palynomorphes dans le membre de Pocaterra Creek et des strates sous-jacentes et sus-jacentes. Les fossiles sont presents dans de nombreux lits de gres a stratification croisee separes par des lentilles de galets. Ces sediments indiquent un milieu de depot assez dynamique, et la repartition des fossiles dans plusieurs lits indique qu'ils se sont accumules au fil de plusieurs evenements, possiblement des crues eclairs. Les fossiles presentent un eventail de types de meteorisation, montrant des cortex intacts a fortement meteorises. La presence de materiau definitivement dinosaurien a proximite de la limite Jurassique--Cretace de l'Alberta etablit la presence la plus ancienne de fossiles de corps de dinosaure dans l'Ouest canadien et offre une occasion unique d'etudier les assemblages de dinosaures du Cretace precoce de l'ouest de l'Amerique du Nord. [Traduit par la Redaction] Mots-cles : ankylosaures, Berriasien, Groupe de Blairmore, Formation de Cadomin, Cretace precoce, Kananaskis, osteoderme, membre de Pocaterra Creek, montagnes Rocheuses, testudines., Introduction The fossil record of dinosaurs is best sampled in North America, due to extensive deposits and ease of access. This is particularly the case in western North America, where [...]

Embolomeres have been considered candidate stem-amniotes by many authors, but recent work has shown that anatomical and phylogenetic support for this hypothesis may be ambiguous. Newer phylogenetic approaches focus on the anatomy of the endochondral bones surrounding the brain (neurocranium) and associated dermal investing bones, so accurate description of the neurocranium of tetrapods, and particularly embolomeres, is critical to assess the phylogenetic context of amniote origins. I here amend prior descriptions of the neurocranium of the abundant Early Permian embolomere, Archeria crassidisca , with a description of a previously unreported partial braincase. This specimen reveals features broadly associated with stem-tetrapods of the fin-to-limb transition and recently described in aïstopod stem-tetrapods, including a cranial notochordal remnant, a possible buccohypophyseal canal, and anteroventrally projecting saccular fossae that extend deep into the basioccipital. I present an amended description and reconstruction of the neurocranium and a phylogenetic analysis integrating these codings, which recovers embolomeres more robustly within the tetrapod stem. I review characters previously used to assign embolomeres to the amniote stem and find this evidence is ambiguous or incorrect. I then outline strong character support for a stem-tetrapod position of embolomeres, and implications for the ancestral body plan of crown-group tetrapods. [ABSTRACT FROM AUTHOR]

Dorsal root ganglia (DRG), trigeminal ganglia (TG), other sensory ganglia, and autonomic ganglia may be injured by some test article classes, including anti-neoplastic chemotherapeutics, adeno-associated virus-based gene therapies, antisense oligonucleotides, nerve growth factor inhibitors, and aminoglycoside antibiotics. This article reviews ganglion anatomy, cytology, and pathology (emphasizing sensory ganglia) among common nonclinical species used in assessing product safety for such test articles (TAs). Principal histopathologic findings associated with sensory ganglion injury include neuron degeneration, necrosis, and/or loss; increased satellite glial cell and/or Schwann cell numbers; and leukocyte infiltration and/or inflammation. Secondary nerve fiber degeneration and/or glial reactions may occur in nerves, dorsal spinal nerve roots, spinal cord (dorsal and occasionally lateral funiculi), and sometimes the brainstem. Ganglion findings related to TA administration may result from TA exposure and/or trauma related to direct TA delivery into the central nervous system or ganglia. In some cases, TA-related effects may need to be differentiated from a spectrum of artifactual and/or spontaneous background changes. [ABSTRACT FROM AUTHOR]

The group of Permo-Carboniferous tetrapods known as Recumbirostra have recently been hypothesized to represent the earliest radiation of fossorial reptiles. Therefore, understanding the anatomy and diversity of this clade is essential to understanding the origin and early evolution of amniotes. Here, we redescribe the diminutive 'microsaur' Odonterpeton triangulare from the Moscovian-age deposit of Linton, Ohio, revealing new details on the structure of the cranium and palate, including the presence of a conspicuous transverse flange of the pterygoid, which is a feature traditionally associated with early amniotes. Phylogenetic analysis supports the placement of Odonterpeton triangulare within Recumbirostra as sister taxon to the recently described Joermungandr bolti from the slightly older Mazon Creek, Illinois, Lagerstätte. Together, these two diminutive recumbirostrans are placed in an Odonterpetidae clade. Furthermore, we provide a discussion of newly recognized anatomical features in recumbirostrans and discuss major features of recumbirostran phylogeny. We designate a new recumbirostran clade, Chthonosauria (Brachystelechidae + Molgophidae), which is supported by a number of shared derived cranial features. [ABSTRACT FROM AUTHOR]