Trop-2 inhibits prostate cancer cell adhesion to fibronectin through the β1 integrin-RACK1 axis.

Trop-2 is a transmembrane glycoprotein upregulated in several human carcinomas, including prostate cancer (PrCa). Trop-2 has been suggested to regulate cell-cell adhesion, given its high homology with the other member of the Trop family, Trop-1/EpCAM, and its ability to bind the tight junction proteins claudin-1 and claudin-7. However, a role for Trop-2 in cell adhesion to the extracellular matrix has never been postulated. Here, we show for the first time that Trop-2 expression in PrCa cells correlates with their aggressiveness. Using either shRNA-mediated silencing of Trop-2 in cells that endogenously express it, or ectopic expression of Trop-2 in cells that do not express it, we show that Trop-2 inhibits PrCa cell adhesion to fibronectin (FN). In contrast, expression of another transmembrane receptor, α(v) β(5) integrin, does not affect cell adhesion to this ligand. We find that Trop-2 does not modulate either protein or activation levels of the prominent FN receptors, β(1) integrins, but acts through increasing β(1) association with the adaptor molecule RACK1 and redistribution of RACK1 to the cell membrane. As a result of Trop-2 expression, we also observe activation of Src and FAK, known to occur upon β(1) -RACK1 interaction. These enhanced Src and FAK activities are not mediated by changes in either the activity of IGF-IR, which is known to bind RACK1, or IGF-IR\u27s ability to associate with β(1) integrins. In summary, our data demonstrate that the transmembrane receptor Trop-2 is a regulator of PrCa cell adhesion to FN through activation of the β(1) integrin-RACK1-FAK-Src signaling axis

Damage as Gamma-limit of microfractures in anti-plane linearized elasticity

A homogenization result is given for a material having brittle inclusions arranged in a periodic structure. <br/> According to the relation between the softness parameter and the size of the microstructure, three different limit models are deduced via Gamma-convergence. <br/> In particular, damage is obtained as limit of periodically distributed microfractures

Fare storia nella protostoria: la questione della presenza micenea a Cnosso alla luce dei dati archeologici e dei nuovi approcci antropologici

Scopo di questo contributo è fare il punto sull’annosa e controversa questione della presenza micenea a Creta e, in particolare, a Cnosso a partire dalla metà del XV secolo a.C., la cui realtà e natura negli ultimi decenni è stata messa in discussione. I principali dati che hanno indotto a credere che un gruppo di Micenei si fosse installato nel sito del palazzo di Cnosso sono rappresentati dal rinvenimento di tavolette scritte in lineare B, quindi in una forma di proto-greco, e dalla scoperta di tombe di tipo continentale con corredi caratterizzati da importanti set di armi, che fecero definire queste sepolture come “Tombe dei Guerrieri”. In anni recentissimi, particolare risonanza hanno avuto analisi archeometriche compiute su materiale osseo proveniente dalle tombe di Cnosso tramite la tecnica degli isotopi dello Stronzio (87Sr/86Sr). Tali analisi hanno dimostrato che gli individui esaminati hanno sempre vissuto a Creta, negando quindi la possibilità che provenissero da aree al di fuori dell’isola.Per chiarire i termini del problema, prenderemo in considerazione i dati archeologici, le principali interpretazioni e i contributi più recenti sull’argomento. Cenno sarà fatto anche ad alcune questioni di carattere disciplinare che negli ultimi anni hanno condizionato i risultati e gli sviluppi dell’archeologia egea dell’età del Bronzo.  The aim of this paper is to examine the long-standing and controversial question of the Mycenaean presence in Crete and, in particular, at Knossos, from the mid-15th century BC onwards. Its actuality and its nature in recent decades have been under intense scrutiny. The main points that may support the belief that a group of Mycenaeans established themselves in the palace of Knossos are represented by the discovery of texts written in Linear B, a form of proto-Greek, and tombs of the continental type called ‘Warrior graves’, containing important weapon-sets. Very recently, bio-archaeological analysis on skeletal materials from the Knossian tombs, utilizing Strontium isotopes (87Sr/86Sr), has resurrected interest in the question: the examined individuals passed their whole lives in Crete, negating accordingly the possibility they came from outside the island.To clarify the situation, the archaeological data and the main interpretations drawn from this will be reviewed in the light of more recent contributions. Some theoretical approaches that have deeply influenced Aegean archaeology of late will also be briefly evaluated

Revista ilimitada: uma proposta de publicação com a tônica de "empreendedorismo sem limites"

A revista Ilimitada é um projeto final apresentado pelas alunas Larissa Lúcia Marra Alberti e Sarita González Fernandes. Trata-se de uma revista cujo foco está no empreendedorismo, em especial nas oportunidades de se empreender na capital do país. Com uma publicação mensal, a revista traz reportagens variadas voltadas ao empreendedor, desde como proceder na abertura de um negócio até matérias que visam colaborar com o trabalho dos gestores e colaboradores do empreendimento. Traz também seções com dicas de filmes e livros, com um especialista apto para tirar dúvidas de empreendedores e futuros empresários, além de histórias de empreendedores já consolidados no mercado

Effects of balloon angioplasty and stent implantation on intrarenal echo-Doppler velocimetric indices

Effects of balloon angioplasty and stent implantation on intrarenal echo-Doppler velocimetric indices. This study was aimed at examining whether four intrarenal echo-Doppler velocimetric indices (pulsatility and resistive indices, acceleration and acceleration time) can be useful for assessing the effects of renal artery dilation obtained with either angioplasty or stent implantation. Echo-Doppler studies were performed in 63 hypertensive patients with 68 renal artery stenoses (39 atherosclerotic and 29 fibromuscular) prior to and within five days after the dilation procedures (55 angioplasties, 13 stent implantations), which resulted in an average reduction of arterial narrowing from 79% to 20%. In 24 patients, the velocimetric indices were also examined in relationship to the venoarterial differences of plasma renin activity and of angiotensin II across the stenotic kidneys. We found that after dilation the values of the four indices had returned within the normal range in all but three arteries (one false negative for resistive index and two for acceleration time). However, decrements in acceleration time was the only factor to be significantly correlated with the reduction of arterial narrowing. Moreover, post-dilation values of this index were, on average, slightly but significantly higher in arteries that at follow-up developed restenosis rather than in those that remained patent. For similar reductions in arterial narrowing the absolute changes of all indices were similar in atherosclerotic and fibromuscular stenotic arteries and, in a subset of the atheromatous arteries, were also similar after angioplasty and stent implantation. No relationship was found with the changes in the venoarterial differences of plasma renin activity and angiotensin II. It appears that these intrarenal velocimetric indices and, in particular, acceleration time reliably reflect the technical success of renal artery dilation. The acceleration time index may also be valuable for predicting the restenosis of the dilated vessel. None of the indices, however, mirrors the functional consequences of removal of renal artery stenosis as expressed through the changes in transrenal gradients of the components of the renin-angiotensin system

Penile Fractures in Young Bulls Raised in Feedlots in Southern Brazil

Background: Penile fracture is a pathology of young cattle that perform precocious and disordered breeding. The incompatibility of height between males and females and sodomy between males cause a great pressure on the sigmoid flexure and retractor muscle of the penis, which are the main causes and sites of organ injury. This study aimed to describe the epidemiological and pathological aspects of penile fractures observed in young bulls raised in pre-export feedlots (PEFs) in southern Brazil.Cases: In 2 PEFs located in the municipalities of Pelotas (property 1) and Capão do Leão (property 2), 3 male cattle [1 from property 1 and 2 from property 2] presented edema of the foreskin and perineum, associated with dysuria. The evolution of the clinical picture was approximately 20 days in all cases, with evolution to death. The bovine necropsied on property 1 had an increased volume and inguinal edema, involving the penis and scrotal sac. Necrosis of the subcutaneous tissue and local musculature was also observed. The testicles were surrounded by the necrotic tissue, and the right testis was swollen, with flaccid parenchyma adhering to the tunica albuginea. In the necropsy of 1 bull from property 2, an increase in the inguinal volume was observed, with an extensive area of necrosis and edema extending from the prepuce to the caudal musculature of the scrotal sac. There were also marked varicosis in the sigmoid flexure and necrosis of the adjacent region, without the involvement of the corpus cavernosum. During the necropsy of the 2 young bulls, fragments of organs from the abdominal, thoracic, and brain cavities were collected and fixed in 10% buffered formalin. From the bull of the property 2, an anatomical piece consisting of the penis, prepuce, and testicles was also collected and fixed in 10% buffered formalin. After 48 h, the tissue samples were cleaved, embedded in paraffin, cut into 3-µm-thick sections, and stained using hematoxylin and eosin (HE). A histological evaluation of the penile lesions in both cattle revealed intense hemorrhage, congestion, and necrosis of the muscles and tissues adjacent to the corpus cavernosum. In addition to areas of dystrophic calcification, neutrophil and macrophage infiltration was also observed. In the bull from the property 1, an intense edema and proliferation of fibrous tissue surrounding the urethra were noted. There were also marked tubular degeneration and intense infiltration of neutrophils, lymphocytes, and macrophages in the inner portion of the tunica albuginea.Discussion: In the present cases, the diagnosis was based on epidemiological data associated with clinical signs and pathology. The macroscopic lesions observed were probably due to the involvement of blood vessels adjacent to the penis, which suffered trauma during sodomy mating among cattle. These lesions have been described in other reports of this pathology and in diseases, such as acropostitis-phimosis, fibropapilloma of the glans, preputial abscess, and urolithiasis, and the differential diagnosis of these diseases must be carried out, as they have different etiologies. In the bulls of the present study, no lesions were observed in the corpus cavernosum, and this condition was attributed to the presence of varicosis and accumulation of urine in the prepuce, due to the difficulty in exposing the penis. Histologically, there were intense hemorrhage, congestion, and necrosis of the muscles and tissues adjacent to the corpus cavernosum, with the infiltration of neutrophils and macrophages, and areas of dystrophic calcification. The presence of necrotic lesions in tissues adjacent to the penis may be related to hypoxia, vascular lesions, or the action of chemical elements present in the urine. In both cases, vascular lesions were present, which were attributed to the main triggering factor for the disease.Keywords: pre-export feedlots, beef cattle, sodomy, penile trauma

Mediastinal Extraskeletal Osteosarcoma in a Canine with Pulmonary and Cerebral Metastasis

Background: Extraskeletal osteosarcoma (EOS), a rare variant of osteosarcoma (OS), is a malignant neoplasm that develops in soft tissues without primary bone involvement. This study aims to describe a case of EOS with a mediastinal location in a canine.Case: A 10-year-old male, Uruguayan, Cimarron dog was presented to the Laboratório Regional de Diagnóstico, Faculdade de Veterinária, Universidade Federal de Pelotas (LRD/FV/UFPel) for necropsy. The dog had a history of submandibular swelling, progressive hind limb paralysis, muscle atrophy, and breathing difficulties. During necropsy, in the thoracic cavity, approximately 900 mL of serosanguinous exudate and a reddish-brown, bossed mediastinal mass measuring 15.0 cm in the longest axis were also noted. The lung exhibited multifocal to coalescent, white, firm nodules extending from the pleura to the parenchyma and measuring up to 4.5 cm in diameter. In the parietal and occipital region of the brain, a matte wine mass measuring 2.3 cm in the longest axis was observed. Fragments of the neoplastic mass, organs of the abdominal and thoracic cavities, and the brain were harvested and fixed in 10% buffered formalin. After 48 h, the samples were routinely processed, incorporated in paraffin, cut into 3 µm-thick sections, and stained using Hematoxylin and Eosin (HE). Selected sections of the neoplasm, the lung, and the brain were subjected to Von Kossa staining and immunohistochemical (IHC) analysis. For IHC, primary anti-cytokeratin monoclonal antibodies (clone AE1 / AE3, BioCare Medical) at a 1:100 dilution, vimentin (clone V9, BioCare Medical) at a 1:100 dilution, S100 Protein (clone 15E2E2, BioCare Medical) at a 1:100 dilution, and Ki67 (SP6 clone, BioCare Medical) at a 1:50 dilution were used. Immunostaining was visualized using 3-3' diaminabenzidine (DAB). Histological evaluation of the mediastinal mass, the pulmonary nodules, and the central nervous system among polygonal mesenchymal cells was conducted. Marked pleomorphism with euchromatic, rounded to oval nuclei, evident nucleoli, and poorly delimited eosinophilic cytoplasm. Neoplastic cells were arranged in nests and bundles with an invasive growth pattern. Osteoid and bone matrix formation as well as multinucleated giant cells of the osteoclast type were observed. The bone matrix was better evidenced in Von Kossa staining. IHC in all analyzed sections of the neoplastic cells showed positive immunostaining for Vimentin and Ki67. In the sections incubated with anti-cytokeratin and S100 protein antibodies showed no presence of neoplastic cells.Discussion: The diagnosis of EOS was based on the absence of primary bone lesions during microscopic necroscopy and on the exclusion of other histogenetic origins using IHC. The absence of primary bone lesions was the main attribute that differentiates EOS from other variants osteosarcomas, such as central/medullary and surface OS (periosteal and paraosteal) most frequently in canine species. The origin of EOS is uncertain. However, its occurrence has been originated with in pluripotent cells or previous injuries, such as retention of surgical sponges and vaccination sites. In this case, since the animal had no clinical history of injuries or surgical procedures that could induce the formation of a mediastinal neoplasm, the probable origin of the neoplasm was pluripotent cells. In dogs, EOS occurs mainly in the mammary glands, digestive system, liver, spleen, and subcutaneous tissue. Furthermore, the mediastinal location observed in this study was described only in goats. The clinical signs are nonspecific and varies with the location of the tumor, as observed in the present report. EOS may also present mediastinal location in the canine species. Necropsy, histopathological examination, and IHC were essential to establish the diagnosis of this OS variant

Fat Body Mass and Vertebral Fracture Progression in Women With Breast Cancer

Importance Women with early breast cancer (EBC) exposed to aromatase inhibitors (AIs) may experience fragility fractures despite treatment with bone-active drugs. Risk factors for fractures in patients receiving AIs and denosumab have not been explored to date.Objectives To evaluate whether an association exists between dual x-ray absorptiometry (DXA)-measured fat body mass (FBM) and vertebral fracture (VF) progression in postmenopausal women with EBC undergoing adjuvant therapy with AIs in combination with denosumab and to examine whether VF was associated with common risk factors for bone fracture and parameters of body composition other than FBM.Design, Setting, and Participants For this prospective, single-center, cohort study, 237 patients with EBC who were undergoing adjuvant treatment with AIs and denosumab (60 mg every 6 months) were enrolled at the Breast Unit of the ASST Spedali Civili of Brescia from September 2014 to June 2018. Data analysis was conducted in June 2022.Exposure Body composition parameters, bone mineral density, and morphometric VFs were assessed by DXA at study entry and after 18 months of therapy.Main Outcomes and MeasuresVF progression, defined as either new or worsening of preexisting VFs, between the 2 time points.Results Of the 237 patients enrolled (median [range] age, 61 [28-84] years), 17 (4.4%) reported VF progression. Univariable analysis found an association between VF progression and a history of clinical fractures (odds ratio [OR], 3.22; 95% CI, 1.19-8.74; P = .02), Fracture Risk Assessment Tool (FRAX) score for major fractures (OR, 4.42; 95% CI, 1.23-13.79; P = .04), percentage of FBM (OR, 6.04; 95% CI, 1.69-21.63; P = .006), and android fat (OR, 9.58; 95% CI, 1.17-78.21; P = .04) and an inverse association with appendicular lean mass index-FBM ratio (OR, 0.25, 95% CI, 0.08-0.82; P = .02). Multivariable analysis revealed percentage of FBM (OR, 5.41; 95% CI, 1.49-19.59; P = .01) and FRAX score (OR, 3.95; 95% CI, 1.09-14.39; P = .04) as independent variables associated with VF progression.Conclusions and Relevance The findings of this study suggest that baseline FBM is an independent factor for VF progression in patients with EBC treated with adjuvant AIs and denosumab. This observation is new and indicates that diet and exercise may synergize with denosumab in the management of bone health in this patient setting

Feline rabies caused by a viral variant of insectivorous bat

ABSTRACT: Rabies is an invariably fatal infectious-contagious viral disease caused by viruses in the genus Lyssavirus, which affects the central nervous system of domestic and wild mammals. This study draws attention to the importance of insectivorous bats and domestic cats in the epidemiology of rabies. For this, two cases of rabies registered in domestic cats in the southeast region of Rio Grande do Sul were analyzed. Diagnoses were based on histological alterations and positive staining for the virus in direct immunofluorescence with confirmation by biological test, immunohistochemical evaluation and identification of the rabies virus variant by polymerase chain reaction. In Brazil, a change in the epidemiological profile of rabies has been observed, in which bats play a major role in the current chain of transmission of the disease. It is noteworthy, that the antigenic viral variant AgV-4, typical of the insectivorous bat Tadarida brasiliensis, was identified in the domestic cats affected in this study