Synthesis, biophysical characterization and anti-HIV activity of d(TG3AG) Quadruplexes bearing hydrophobic tails at the 5'-end

Novel conjugated G-quadruplex-forming d(TG3AG) oligonucleotides, linked to hydrophobic groups through phosphodiester bonds at 50-end, have been synthesized as potential anti-HIV aptamers, via a fully automated, online phosphoramidite-based solid-phase strategy. Conjugated quadruplexes showed pronounced anti-HIV activity with some preference for HIV-1, with inhibitory activity invariably in the low micromolar range. The CD and DSC monitored thermal denaturation studies on the resulting quadruplexes, indicated the insertion of lipophilic residue at the 50-end, conferring always improved stability to the quadruplex complex (20 < DTm < 40 C). The data suggest no direct functional relationship between the thermal stability and anti-HIV activity of the folded conjugated G-quartets. It would appear that the nature of the residue at 50 end of the d(TG3AG) quadruplexes plays an important role in the thermodynamic stabilization but a minor influence on the anti-HIV activity. Moreover, a detailed CD and DSC analyses indicate a monophasic behaviour for sequences I and V, while for ODNs (II–IV) clearly show that these quadruplex structures deviate from simple two-state melting, supporting the hypothesis that intermediate states along the dissociation pathway may exis

Wavelength-shifting fibers for calorimetric measurements in a long base line neutrino oscillation experiment

Abstract The NOE Collaboration has proposed a calorimeter to measure the energy of the final states of ν interaction events. The properties of long scintillator bars with wavelength-shifting fiber readout have been studied to develop a calorimeter design option. Various prototypes have been exposed to a cosmic rays stand. The total measured light yield in the middle of a 6 m -long fiber is about 15 photoelectrons. With this photon collection performance, it has been simulated that the calorimeter can achieve 17%/ E and 50%/ E resolutions for electrons and pions, respectively

Oncoplastic and reconstructive surgery in SENONETWORK Italian breast centers: lights and shadows

Highlights: • Despite the significance of oncoplastic procedure, an italian database is lacking. • Senonetwork established a multidisciplinary survey to assess their safety and efficacy. • Reconstructive outcomes were positive across low and high-volume centers. • After mastectomy, implant-based techniques are common. DTI reconstruction is advantageuos. • This contributes to the global understanding of effective strategies against breast cancer

Capturing the often-elusive diagnosis of idiopathic myointimal hyperplasia of mesenteric veins

Only 50 cases of idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) have been reported since 1991 when it was first described. This rare etiology for chronic colonic ischemia is often debilitating to the patient's quality of life, and no effective medical treatment is available. IMHMV is frequently confused with inflammatory bowel disease because the most common presenting symptoms include abdominal pain, diarrhea, and hematochezia. Surgical resection is curative; however, the diagnosis is rarely reached preoperatively. In the present report, we have described the seventh patient with a diagnosis of IMHMV before surgery and included a literature review to help clinicians recognize this condition. © 2022Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Hypertrophic gastropathy associated with gastric sarcoma in a dog

A 14-y-old spayed female Labrador Retriever was presented with an 8-mo history of chronic vomiting. Abdominal ultrasound and gastrointestinal endoscopy revealed a mass protruding into the gastric lumen, with cytologic features suggestive of sarcoma. A partial gastrectomy was performed; the gastric body and antrum were thickened, with a cerebriform appearance of the mucosal surface. Histologic examination revealed a submucosal neoplastic proliferation of fusiform cells variably arranged in irregular bundles and scattered whorls. Fusiform cells strongly reacted to antibodies against vimentin, S100, and neuron-specific enolase; glial fibrillary acidic protein was moderately and multifocally expressed. Pancytokeratin, KIT, α–smooth muscle actin, and desmin were nonreactive. Histologic and immunohistochemical findings suggested a diagnosis of gastric sarcoma with features referable to a non-GIST (gastrointestinal stromal tumor), non–smooth muscle NIMT (non-angiogenic, non-lymphogenic intestinal mesenchymal tumor). The overlying gastric mucosa was thickened by elongated and dilated gastric glands, predominantly lined by intensely periodic acid-Schiff–stained mucous cells. This altered mucosal architecture was suggestive of Ménétrier-like disease. Although this disease has been hypothesized to predispose to gastric adenocarcinoma in dogs, an association with gastric sarcoma has not been documented previously in the veterinary literature, to our knowledge. </jats:p

Exploring the prognostic significance of new vessel formation and its relationship with CD44 and hypoxic factors immunoexpression in canine appendicular osteosarcoma.

Introduction: Angiogenesis imbalance is essential for tumour growth, with hypoxia being the most important driver. Moreover, tumour cells can contribute to forming blood vessels by vasculogenic mimicry (VM) or recalling the endothelial-progenitor-cells through vasculogenesis. Microvessel density (MVD) increase and VM are associated with poor prognosis in human osteosarcoma (OS), while their significance in canine OS is unclear. The cancer-stem-cell marker CD44 can represent a key factor due to its involvement in MVD and VM increase. The aim of this work is the investigation of MVD, VM and CD44 relationship among them and with hypoxic factors, including VEGF!, clinical-pathological features and prognosis in canine OS. Materials and Methods: MVD and VM were assessed in 23 canine appendicular OS samples through PAS-CD31 staining. MVD was quantified with Weidner’s method and VM identified as CD31-negative-PAS-positive cavities containing erythrocytes. CD44 and hypoxic factors were evaluated by immunohistochemistry. Analyses of survival and univariate Log-Rank association were used to examine all variables. Variable relationships (excluding survival data) were estimated by Student’s or Mann-Whitney test. Results: Results showed MVD increase in male dogs and high-grade tumours (p"0.05). VM was present in 7/23 cases, in association with higher CD44 immunoexpression (p"0.05) and reduced overall survival (p"0.05). A positive tendency between CD44 and VEGF! immunostaining was also observed (p&lt;0.1). Conclusions: For the first time, VM and CD44 and their positive relation were observed in canine OS tissues, together with VM prognostic value. A larger number of cases is necessary to confirm these preliminary results and understand the mechanisms involved in hypoxia-related cancer progression