Immunohistochemical Investigation into Protein Expression Patterns of FOXO4, IRF8 and LEF1 in Canine Osteosarcoma.

Osteosarcoma (OSA) is the most common type of primary bone malignancy in people and dogs. Our previous molecular comparisons of canine OSA against healthy bone resulted in the identification of differentially expressed protein-expressing genes (forkhead box protein O4 (FOXO4), interferon regulatory factor 8 (IRF8), and lymphoid enhancer binding factor 1 (LEF1)). Immunohistochemistry (IHC) and H-scoring provided semi-quantitative assessment of nuclear and cytoplasmic staining alongside qualitative data to contextualise staining (n = 26 patients). FOXO4 was expressed predominantly in the cytoplasm with significantly lower nuclear H-scores. IRF8 H-scores ranged from 0 to 3 throughout the cohort in the nucleus and cytoplasm. LEF1 was expressed in all patients with significantly lower cytoplasmic staining compared to nuclear. No sex or anatomical location differences were observed. While reduced levels of FOXO4 might indicate malignancy, the weak or absent protein expression limits its primary use as diagnostic tumour marker. IRF8 and LEF1 have more potential for prognostic and diagnostic uses and facilitate further understanding of their roles within their respective molecular pathways, including Wnt/beta-catenin/LEF1 signalling and differential regulation of tumour suppressor genes. Deeper understanding of the mechanisms involved in OSA are essential contributions towards the development of novel diagnostic, prognostic, and treatment options in human and veterinary medicine contexts.

Modulation of the pre-metastatic bone niche: molecular changes mediated by bone-homing prostate cancer extracellular vesicles.

Prostate cancer (PCa) is a leading male malignancy worldwide, often progressing to bone metastasis, with limited curative options. Extracellular vesicles (EVs) have emerged as key players in cancer communication and metastasis, promoting the formation of supportive microenvironments in distant sites. Our previous studies have highlighted the role of PCa EVs in modulating osteoblasts and facilitating tumor progression. However, the early pre-metastatic changes induced by PCa EVs within the bone microenvironment remain poorly understood. To investigate the early effects of repeated exposure to PCa EVs in vivo, mimicking EVs being shed from the primary tumor, PCa EVs isolated from cell line PC3MLuc2a were fluorescently labelled and repeatedly administered via tail vein injection to adult CD1 NuNu male mice for a period of 4 weeks. In vivo imagining, histological analysis and gene expression profiling were performed to assess the impact of PCa EVs on the bone microenvironment. We demonstrate for the first time that PCa EVs home to both bone and lymph nodes following repeated exposures. Furthermore, the accumulation of EVs within the bone leads to distinct molecular changes indicative of disrupted bone homeostasis (e.g., changes to signaling pathways such as Paxillin p = 0.0163, Estrogen Receptor p = 0.0271, RHOA p = 0.0287, Ribonucleotide reductase p = 0.0307 and ERK/MAPK p = 0.0299). Changes in key regulators of these pathways were confirmed in vitro on human osteoblasts. In addition, our data compares the known gene signature of osteocytes and demonstrates a high proportion of overlap (52.2%), suggesting a potential role for this cell type in response to PCa EV exposure. No changes in bone histology or immunohistochemistry were detected, indicating that PCa EV mediated changes were induced at the molecular level. This study provides novel insights into the alterations induced by PCa EVs on the bone microenvironment. The observed molecular changes indicate changes in key pathways and suggest a role for osteocytes in these EV mediated early changes to bone. Further research to understand these early events may aid in the development of targeted interventions to disrupt the metastatic cascade in PCa.

Changes in Immune Response during Pig Gestation with a Focus on Cytokines.

Pigs have the highest percentage of embryonic death not associated with specific diseases of all livestock species, at 20-45%. During gestation processes, a series of complex alterations can arise, including embryonic migration and elongation, maternal immunological recognition of pregnancy, and embryonic competition for implantation sites and subsequent nutrition requirements and development. Immune cells and cytokines act as mediators between other molecules in highly complex interactions between various cell types. However, other non-immune cells, such as trophoblast cells, are important in immune pregnancy regulation. Numerous studies have shed light on the crucial roles of several cytokines that regulate the inflammatory processes that characterize the interface between the fetus and the mother throughout normal porcine gestation, but most of these reports are limited to the implantational and peri-implantational periods. Increase in some proinflammatory cytokines have been found in other gestational periods, such as placental remodeling. Porcine immune changes during delivery have not been studied as deeply as in other species. This review details some of the immune system cells actively involved in the fetomaternal interface during porcine gestation, as well as the principal cells, cytokines, and molecules, such as antibodies, that play crucial roles in sow pregnancy, both in early and mid-to-late gestation.

Quantitative expression of oestrogen receptor in breast cancer: Clinical and molecular significance.

BACKGROUND: Oestrogen receptor (ER) positive breast cancer (BC) patients are eligible for endocrine therapy (ET), regardless of ER immunohistochemical expression level. There is a wide spectrum of ER expression and the response to ET is not uniform. This study aimed to assess the clinical and molecular consequences of ER heterogeneity with respect to ET-response. METHODS: ER expression, categorised by percentage and staining intensity in a large BC cohort (n = 7559) was correlated with clinicopathological parameters and patient ET response. The Cancer Genome Atlas Data BC cohort (n = 1047) was stratified by ER expression and transcriptomic analysis completed to better understand the molecular basis of ER heterogeneity. RESULTS: The quantitative proportional increase in ER expression was positively associated with favourable prognostic parameters. Tumours with 1-9% ER expression were characteristically similar to ER-negative (<1%) tumours. Maximum ET-response was observed in tumours with 100% ER expression, with responses significantly different to tumours exhibiting ER at < 100% and significantly decreased survival rates were observed in tumours with 50% and 10% of ER expression. The Histochemical-score (H-score), which considers both staining intensity and percentage, added significant prognostic value over ER percentage alone with significant outcome differences observed at H-scores of 30, 100 and 200. There was a positive correlation between ER expression and ESR1 mRNA expression and expression of ER-regulated genes. Pathway analysis identified differential expression in key cancer-related pathways in different ER-positive groups. CONCLUSION: ET-response is statistically proportionally related to ER expression with significant differences observed at 10%, 50% and 100%. The H-score adds prognostic and predictive information.

Characterisation of luminal and triple-negative breast cancer with HER2 Low protein expression.

BACKGROUND: Breast cancer (BC) expressing low levels of human epidermal growth factor receptor 2 (HER2 Low) is an emerging category that needs further refining. This study aims to provide a comprehensive clinico-pathological and molecular profile of HER2 Low BC including response to therapy and patient outcome in the adjuvant and neoadjuvant settings. METHODS: Two different independent and well-characterised BC cohorts were included. Nottingham cohort (A) (n = 5744) and The Cancer Genome Atlas (TCGA) BC cohort (B) (n = 854). The clinical, molecular, biological and immunological profile of HER2 Low BC was investigated. Transcriptomic and pathway enrichment analyses were performed on the TCGA BC cohort and validated through next-generation sequencing in a subset of Nottingham cases. RESULTS: Ninety percent of HER2 Low tumours were hormone receptor (HR) positive (HR+), enriched with luminal intrinsic molecular subtype, lacking significant expression of HER2 oncogenic signalling genes and of favourable clinical behaviour compared to HER2 negative (HER2-) BC. In HR+ BC, no significant prognostic differences were detected between HER2 Low and HER2- tumours. However, in HR- BC, HER2 Low tumours were less aggressive with longer patient survival. Transcriptomic data showed that the majority of HR- /HER2 Low tumours were of luminal androgen receptor (LAR) intrinsic subtype, enriched with T-helper lymphocytes, activated dendritic cells and tumour associated neutrophils, while most HR-/HER2- tumours were basal-like, enriched with tumour associated macrophages. CONCLUSION: HER2 Low BC is mainly driven by HR signalling in HR+ tumours. HR-/HER2 Low tumours tend to be enriched with LAR genes with a unique immune profile.

Heart ventricles of the dromedary camel (Camelus dromedarius): new insights from sectional anatomy, 3D computed tomography, and morphometry.

BACKGROUND: Dromedary camel heart morphology is a crucial research topic with clinical applications. The study aims to understand the dromedary camel anatomy, morphology, and architecture of the ventricular mass. RESULTS: Sagittal and transverse gross sections were compared to sagittal, transverse, and 3D render volume reconstruction computed tomography (CT) scans. The subepicardial fat, which covered the heart base, the coronary groove (sulcus coronarius), the left longitudinal interventricular groove (sulcus interventricularis paraconalis), and the right longitudinal interventricular groove (sulcus interventricularis subsinuosus), had a relatively low density with a homogeneous appearance in the 3D render volume CT. The pericardium in the color cardiac window was identified better than the black and white window (ghost). Transverse and sagittal CT scans demonstrated the internal structures of the heart, including the right atrioventricular orifice (ostium atrioventriculare dextrum), right atrioventricular orifice (ostium atrioventriculare sinistrum), and aortic orifice (ostium aortae), chordae tendineae, the cusps of the valves (cuspis valvae), and the papillary muscles (musculi papillares). The papillary muscle (musculi papillares) was presented with a more moderate density than the rest of the heart, and the cusps of the valves (cuspis valvae) had a lower density. The ventricular wall (margo ventricularis) exhibited different densities: the outer part was hyperdense, while the inner part was hypodense. The thicknesses of the ventricular mural wall and the interventricular septum (septum atrioventriculare) were highest at the midpoint of the ventricular mass, and the lowest value was present toward the apical part. The coronary groove (sulcus coronarius) circumference measured 51.14 ± 0.72 cm, and the fat in the coronary groove (sulcus coronarius) (56 ± 6.55 cm2) represented 28.7% of the total cross-sectional area. CONCLUSION: The current study provided more information about ventricular mass measurements by gross and CT analysis on the heart, which provides a valuable guide for future cardiac CT investigations in camels in vivo.

Characterizing Two New Henneguya Species in the Respiratory Organs of African Sharptooth Catfish.

Henneguya species are myxozoans, a suborder of Cnidaria, which can affect the gills and extrarespiratory organs of the African sharptooth catfish, Clarias gariepinus. This research describes natural infection-induced histological alterations caused by the Henneguya species present. The Henneguya species were also identified molecularly using DNA sequenced from infected tissue cysts, and phylogenetically analyzed. Clinical investigations revealed cyst-like nodules on the fish gill filaments and extrarespiratory organs. Within a milky fluid inside the cysts were several Henneguya-like spores. Henneguya sp. infested 27.5% of the fish, with the highest prevalence in the gills compared to the extrarespiratory organs. The Henneguya species parasitized the gill and the dendritic tissues, resulting in histopathological characteristics. The plasmodia's developmental stages resulted in destructive damage which manifested as marked necrosis, which was replaced by a focal aggregation of inflammatory cells. Amplification of the 18S ribosomal DNA from the fish parasites was followed by sequencing, which confirmed their identities as new species Henneguya qenabranchiae n. sp. and Henneguya qenasuprabranchiae n. sp. with 99.53 and 99.64% identities, respectively, to Henneguya sp. 1 HS-2015. The two C. gariepinus myxozoans shared some characteristics based on morphologic and phylogenetic analysis as previously published, where it was proposed that they were a sister lineage to Henneguya species in Egypt, and it is now proposed that they are new species.

Morphology of migrating telocytes and their potential role in stem cell differentiation during cartilage development in catfish (Clarias gariepinus).

Telocytes (TCs) are present in a broad range of species and regulate processes including homeostasis, tissue regeneration and immunosurveillance. This novel study describes the morphological features of migrating TCs and their role during cartilage development within the air-breathing organ in Clarias gariepinus, the African sharptooth catfish. Light microscopy (LM), transmission electron microscopy (TEM), and immunohistochemistry (IHC) were used to examine the TCs. TCs had a cell body and telopodes which formed 3D networks in the cartilage canals and extended their telopodes to become the foremost cellular elements penetrating the cartilage matrix. The TCs were also rich in lysosomes that secreted products to the extracellular matrix (ECM). In addition, TCs formed a homocellular synaptic-like structure that had a synaptic cleft, and the presynaptic portion consisted of a slightly expanded terminal of the telopodes which contained intermediate filaments and secretory vesicles. Gap junctions were also identified between TCs, which also connected to mesenchymal stem cells, differentiating chondrogenic cells, macrophages, apoptotic cells, and endothelial cells. In addition to describing the basic morphology of TCs, the current study also investigated migrating TCs. The TC telopodes acquired an irregular contour when migrating rather than exhibiting an extended profile. Migrating TCs additionally had ill-defined cell bodies, condensed chromatin, thickened telopodes, and podoms which were closely attached to the cell body. The TCs also expressed markers for MMP-9, CD117, CD34 and RhoA. In conclusion, TCs may play multiple roles during development and maturation, including promoting angiogenesis, cell migration, and regulating stem cell differentiation. RESEARCH HIGHLIGHTS: Clarias gariepinus telocytes form 3D networks, extend their telopodes and contain lysosomes. Telocytes form a homocellular synaptic-like structure including clefts and a slightly expanded terminal of the telopodes which contains intermediate filaments and secretory vesicles. Gap junctions form between telocytes, which also connect to mesenchymal stem cells, differentiating chondrogenic cells, macrophages, apoptotic cells, and endothelial cells. Migrating telocytes were discovered which had ill-defined cell bodies, condensed chromatin, thickened telopodes exhibiting irregular contours, and podoms which were closely attached to the cell body.

Anatomical oropharyngeal cavity specialisations in the cutlassfish (Trichiurus lepturus, Linnaeus, 1758).

Trichiurus lepturus is a carnivorous fish, and most of the previous anatomical research has focused on computed tomography imaging and histology of their teeth and fangs, while the remaining structures of pharyngeal cavity remain unexplored. The present research is the first to use anatomical examinations alongside scanning electron microscopy to investigate the T. lepturus oral cavity. The oropharyngeal roof included teeth, upper lip, rostral and caudal velum and the palate. The middle of the palate showed a median groove flanked by two folds, followed by a median band flanked by micro-folds, thereafter the palate became crescent shaped. The lateral regions of the palate exhibited longitudinal folds that extended rostrally towards the fangs. The oropharyngeal floor had two cavities which acted as a scabbard for the premaxillary fangs and upper velum, while the caudal sublingual cavity contained two oyster-shaped structures on the outer surface plus sublingual ridges and sublingual clefts. The tongue apex exhibited a spoon-like shape, its body demonstrated a median elevation and the root with two lateral branches contained only dome-shaped papillae. Taste buds were located on the upper velum, lower lip and the caudal part of the interbranchial septum. Images and descriptions of T. lepturus tooth structure are also provided. The present research, using anatomical dissection and morphological observation using scanning electron microscopy, has identified the structures of the dentition system, a variety in shapes of the folds and microridges, and identified the taste buds and mucous pores in the T. lepturus oropharyngeal cavity.

The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer.

Histone H3 lysine 4 (H3K4) methylation is key epigenetic mark associated with active transcription and is a substrate for the KDM1A/LSD1 and KDM5B/JARID1B lysine demethylases. Increased expression of KDM1A and KDM5B is implicated in many cancer types, including prostate cancer (PCa). Both KDM1A and KDM5B interact with AR and promote androgen regulated gene expression. For this reason, there is great interested in the development of new therapies targeting KDM1A and KDM5B, particularly in the context of castrate resistant PCa (CRPC), where conventional androgen deprivation therapies and androgen receptor signalling inhibitors are no longer effective. As there is no curative therapy for CRPC, new approaches are urgently required to suppress androgen signalling that prevent, delay or reverse progression to the castrate resistant state. While the contribution of KDM1A to PCa is well established, the exact contribution of KDM5B to PCa is less well understood. However, there is evidence that KDM5B is implicated in numerous pro-oncogenic mechanisms in many different types of cancer, including the hypoxic response, immune evasion and PI3/AKT signalling. Here we elucidate the individual and cooperative functions of KDM1A and KDM5B in PCa. We show that KDM5B mRNA and protein expression is elevated in localised and advanced PCa. We show that the KDM5 inhibitor, CPI-455, impairs androgen regulated transcription and alternative splicing. Consistent with the established role of KDM1A and KDM5B as AR coregulators, we found that individual pharmacologic inhibition of KDM1A and KDM5 by namoline and CPI-455 respectively, impairs androgen regulated transcription. Notably, combined inhibition of KDM1A and KDM5 downregulates AR expression in CRPC cells. Furthermore, combined KDM1A and KDM5 inhibition impairs PCa cell proliferation and invasion more than individual inhibition of KDM1A and KDM5B. Collectively our study has identified individual and cooperative mechanisms involving KDM1A and KDM5 in androgen signalling in PCa. Our findings support the further development of KDM1A and KDM5B inhibitors to treat advanced PCa. Further work is now required to confirm the therapeutic feasibility of combined inhibition of KDM1A and KDM5B as a novel therapeutic strategy for targeting AR positive CRPC.

Encapsulated papillary carcinoma of the breast: does it have a native basement membrane?

BACKGROUND: Encapsulated papillary carcinoma (EPC) is surrounded by a thick fibrous capsule-like structure, which is interpreted as a thickened basement membrane (BM). This study aimed to describe the geometric characteristics of the EPC capsule and to refine whether it is an expansion of the BM or a stromal reactive process. MATERIAL AND METHODS: In all, 100 cases were divided into four groups: EPC, ductal carcinoma in situ (DCIS), normal breast tissue and invasive tumours, with an additional encapsulated papillary thyroid carcinoma (EPTC) control group. Representative slides from each case were stained with picrosirius red (PSR) stain and examined using polarised microscopy. Images were analysed using ImageJ, CT-FIRE, and Curve align image analysis programmes. RESULTS: Compared to the normal and DCIS BM, the EPC group showed a significant increase of collagen fibre width, straightness, and density, and a decrease of fibre length. The EPC capsule showed less alignment of fibres with a more perpendicular arrangement, and it was enriched with disorganised collagen type I (stromal collagen) fibres. Compared to other groups, the EPC capsule showed significant variation in the thickness, evenness, distribution of collagen fibres, and significant intracapsular heterogeneity. Compared to BM-like material in the invasive group, the EPC capsule showed a higher density of collagen fibres with longer, straighter, and more aligned fibres, but there was no difference in the distribution of both collagen types I and III. Conversely, compared to EPTC, there were no differences between both EPC and EPTC capsules except that the fibres in the EPC capsule were straighter. Although differences between normal ducts and lobules and DCIS BM collagen fibre density, straightness, orientation, and alignment were detected, both were significantly different from EPC capsule. CONCLUSION: This study provided evidence that the EPC capsule is a reactive process rather than a thickened native BM characteristic of normal and in situ lesions, which provides further evidence that EPC is an indolent invasive carcinoma based on capsule characteristics.

Topographic anatomy and vascularization of the glandula thyroidea in rats.

Topographical anatomy and detailed measurements of the glandula thyroidea (thyroid gland) and the glandula parathyroidea (parathyroid gland) were determined in rats, with significant differences identified between the sexes. In the rats (N = 10 male, 10 female), the glandula thyroidea were positioned at the level of the C1 and C2 vertebrae. One glandula parathyroidea was present in each glandula thyroidea lobe, localized in the cranial part of the lateral lobes in 60% of the animals. There was no glandula thyroidea left lobe in one female and no isthmus in two females. Both the A. thyroidea cranialis and the A. pharyngea ascendens originated from the A. carotis externa, which acted as a common trunk. On the left, the A. thyroidea caudalis originated from the truncus brachiocephalicus in all rats and on the right side was found to originate from both the truncus costocervicalis and the A. subclavia dextra in three females, and only from the truncus costocervicalis in seven females. The V. thyroidea cranialis opened into the V. jugularis interna in the neck region and at the level of the apertura thoracis cranialis, and the V. jugularis interna united with the V. thyroidea caudalis. In addition, on the right, the V. thyroidea cranialis joined the V. jugularis interna, at the level of the A. subclavia. The veins on both sides opened into the V. cava cranialis. Significant differences were observed between the sexes and detailed anatomical analysis of the glandula thyroidea and the glandula parathyroidea, and related vasculature and innervation, have been described in this paper.

Morphological and cytochemical characteristics of Varanus niloticus (Squamata, Varanidae) blood cells.

Varanus niloticus is a lizard residing within the Varanidae family. To date no studies detailing its blood morphology and characteristics have been conducted. This study used histologically stained blood and bone marrow samples to visualize the cells and their characteristics. The erythrocytes were nucleated, these nuclei were located in the middle of the elliptical cells. Hemoglobin filled the erythrocyte cytoplasm. Eosinophils were large cells with lobed nuclei and spherical acidophilic granules. Large granulocytes called heterophils were present and characterized by their fusiform/pleomorphic cytoplasmic granules. Small spherical granulocytes, known as basophils, presented with round, deeply stained metachromatic granules that gave the cytoplasm a dusty or cobblestoned appearance which was able to cover the nucleus, which in turn had an unusual shape. Thrombocytes ranged in shape from ellipsoidal to fusiform. They featured an elliptical, centrally located nucleus and a pale cytoplasm, with small vacuoles, and fine acidophilic granulation. The smallest variety of non-granular leukocytes was the lymphocytes. Their cytoplasm was sparse, finely granular, light blue, had tiny cytoplasmic projections, featuring a high nucleus: cytoplasm ratio. Larger and smaller sized populations of lymphocytes were distinguished, with the larger cells similar in size to azurophils. In general, the pleomorphic monocytes were the biggest mononuclear leucocytes, displaying cytoplasmic projections. Their nuclei were ovoid, kidney- or bean-shaped, with vacuolated and granular cytoplasms. Round cells were common among the monocytic azurophils, and they had a granular cytoplasm, and their nuclei were typically eccentric. The present research identifies the cell types and morphologies within the Varanus niloticus. HIGHLIGHTS: H&E, PAS, toluidine blue, methylene blue, and Safranin O stains provided morphological and morphometric descriptions of Varanus niloticus blood cells from blood smears and bone marrow. The Varanus niloticus had nucleated erythrocytes and white blood cells, mostly granulocytes (heterophils, eosinophils, and basophils) and mononuclear cells (azurophils, lymphocytes, and monocytes). Aquatic vertebrate Varanus niloticus had larger erythrocytes than terrestrial counterparts. Blood cell morphological and cytochemical features were similar to other reptilian species, with some species-specific differences, which likely accommodate differing environmental conditions. These results may help clinical researchers track the pathological conditions and support conservation of these wild animals.

The importance of m6A topology in chicken embryo mRNA: a precise mapping of m6A at the conserved chicken ß-actin zipcode.

N6-methyladenosine (m6A) in mRNA regulates almost every stage in the mRNA life cycle, and the development of methodologies for the high-throughput detection of methylated sites in mRNA using m6A-specific methylated RNA immunoprecipitation with next-generation sequencing (MeRIPSeq) or m6A individual-nucleotide-resolution cross-linking and immunoprecipitation (miCLIP) have revolutionized the m6A research field. Both of these methods are based on immunoprecipitation of fragmented mRNA. However, it is well documented that antibodies often have nonspecific activities, thus verification of identified m6A sites using an antibody-independent method would be highly desirable. We mapped and quantified the m6A site in the chicken ß-actin zipcode based on the data from chicken embryo MeRIPSeq results and our RNA-Epimodification Detection and Base-Recognition (RedBaron) antibody-independent assay. We also demonstrated that methylation of this site in the ß-actin zipcode enhances ZBP1 binding in vitro, while methylation of a nearby adenosine abolishes binding. This suggests that m6A may play a role in regulating localized translation of ß-actin mRNA, and the ability of m6A to enhance or inhibit a reader protein's RNA binding highlights the importance of m6A detection at nucleotide resolution.

Defining invasion in breast cancer: the role of basement membrane.

Basement membrane (BM) is an amorphous, sheet-like structure separating the epithelium from the stroma. BM is characterised by a complex structure comprising collagenous and non-collagenous proteoglycans and glycoproteins. In the breast, the thickness, density and composition of the BM around the ductal lobular system vary during differing development stages. In pathological conditions, the BM provides a physical barrier that separates proliferating intraductal epithelial cells from the surrounding stroma, and its absence or breach in malignant lesions is a hallmark of invasion and metastases. Currently, diagnostic services often use special stains and immunohistochemistry (IHC) to identify the BM in order to distinguish in situ from invasive lesions. However, distinguishing BM on stained sections, and differentiating the native BM from the reactive capsule or BM-like material surrounding some invasive malignant breast tumours is challenging. Although diagnostic use of the BM is being replaced by myoepithelial cell IHC markers, BM is considered by many to be a useful marker to distinguish in situ from invasive lesions in ambiguous cases. In this review, the structure, function and biological and clinical significance of the BM are discussed in relation to the various breast lesions with emphasis on how to distinguish the native BM from alternative pathological tissue mimicking its histology.

Ossa cordis and os aorta in the one-humped camel: Computed tomography, light microscopy and morphometric analysis.

The present study describes the morphological characteristics of the camel heart Ossa cordis, and os aorta using computed tomography soft tissue window (CT) alongside 3D render volume reconstructions and light microscopy. The current study techniques demonstrated the Ossa cordis and os aorta in the cardiac window with more precision than the black and white (ghost), and angiography images. Transverse and sagittal CT images additionally demonstrated the presence of Ossa cordis and os aorta. This study is the first to record two small Ossa cordis sinistrum and one os aorta in the camel heart, in addition to the more commonly observed singular, large, os cordis dextrum. The os cordis dextrum was always located in the upper part of the interventricular septum, near to its junction with the atrium, forming an elongated rectangular shape when observed transversally. The wider cranial part was composed from bone, whereas the caudal aspect was narrow and contained both bone and cartilage. Light microscopy identified that the os cordis dextrum consisted of trabecular bone, marrow spaces, and hyaline cartilage. Two Ossa cordis sinistrum were detected on the left side of the heart, one in the right fibrous ring and another in the interventricular septum, microscopy showed that both contained only trabecular bone with osteocytes, osteoblasts, and osteoclasts. At the level of ascending aorta, there was also trabecular bone containing osteocytes, an os aorta.

Impact of COVID-19 on student attainment and pedagogical needs when undertaking independent scientific research.

Research is often an essential component of completing a veterinary medicine degree, with universities worldwide aiming to teach students a variety of techniques and general research comprehension and skills. As universities worldwide navigated the COVID-19 pandemic, it was often necessary to move towards distance learning, this was employed for the research module at The University of Nottingham, School of Veterinary Medicine and Science. Following completion of their independent research project, each student cohort was sent a student evaluation of the module questionnaire and quantitative and qualitative analysis was undertaken. In addition, assessment outcomes based on dissertation grade, supervisor grade and overall module score were analysed quantitatively. This was conducted on both the individual cohorts and between the pre- and peri-pandemic groups, ranging from 2017-2018 through to 2021-2022 cohorts. The students received increased dissertation and supervisor grades (by nearly 6%) during the 2021-2022 peri-pandemic cohort, when compared to the pre-pandemic cohorts, but did differ significantly compared to the 2020-2021 cohort. The pre- and peri-pandemic Likert-scale ratings for module organisation and assessment criteria were similar, workload management and the ability to explore concepts and ideas was reduced in the peri-pandemic cohorts, whereas the accessibility to resources was increased in the peri-pandemic students compared to those taught prior to the pandemic. Student feedback can provide essential information when designing and managing research projects and when compared to assessment grades it can help us understand attainment, essential information when providing a quality university level education whilst supporting student welfare following the COVID-19 pandemic.

Canine osteosarcoma in comparative oncology: Molecular mechanisms through to treatment discovery.

Cancer is a leading cause of non-communicable morbidity and mortality throughout the world, similarly, in dogs, the most frequent cause of mortality is tumors. Some types of cancer, including osteosarcoma (OSA), occur at much higher rates in dogs than people. Dogs therefore not only require treatment themselves but can also act as an effective parallel patient population for the human disease equivalent. It should be noted that although there are many similarities between canine and human OSA, there are also key differences and it is important to research and highlight these features. Despite progress using chorioallantoic membrane models, 2D and 3D in vitro models, and rodent OSA models, many more insights into the molecular and cellular mechanisms, drug development, and treatment are being discovered in a variety of canine OSA patient populations.

The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer.

Prostate cancer (PCa) is a leading cause of cancer-related deaths and is driven by aberrant androgen receptor (AR) signalling. For this reason, androgen deprivation therapies (ADTs) that suppress androgen-induced PCa progression either by preventing androgen biosynthesis or via AR signalling inhibition (ARSi) are common treatments. The N6-methyladenosine (m6A) RNA modification is involved in regulating mRNA expression, translation, and alternative splicing, and through these mechanisms has been implicated in cancer development and progression. RNA-m6A is dynamically regulated by the METTL3 RNA methyltransferase complex and the FTO and ALKBH5 demethylases. While there is evidence supporting a role for aberrant METTL3 in many cancer types, including localised PCa, the wider contribution of METTL3, and by inference m6A, in androgen signalling in PCa remains poorly understood. Therefore, the aim of this study was to investigate the expression of METTL3 in PCa patients and study the clinical and functional relevance of METTL3 in PCa. It was found that METTL3 is aberrantly expressed in PCa patient samples and that siRNA-mediated METTL3 knockdown or METTL3-pharmacological inhibition significantly alters the basal and androgen-regulated transcriptome in PCa, which supports targeting m6A as a novel approach to modulate androgen signalling in PCa.