Chemotherapy accelerates immune-senescence and functional impairments of Vδ2pos T cells in elderly patients affected by liver metastatic colorectal cancer.

Human (gamma delta) γδ T cells are unconventional innate-like lymphocytes displaying a broad array of anti-tumor activities with promising perspectives in cancer immunotherapy. In this context, Vδ2pos T cells represent the preferential target of several immunotherapy protocols against solid tumors. However, the impact of both aging and chemotherapy (CHT) on Vδ2pos T cells is still unknown. The present study evaluates with multi-parametric flow cytometry the frequencies, terminal differentiation, senescence and effector-functions of peripheral blood and tumor infiltrating Vδ2pos T cells purified from liver metastases (CLM) of patients affected by colorectal cancer (CRC) compared to those of sex- and age-matched healthy donors. The peripheral blood of CLM patients underwent CHT is characterized by decreased amounts of Vδ2pos T cells showing a relative increase of terminally-differentiated CD27neg/CD45RApos (TEMRA) cells. The enrichment of this latter subset is associated with an increased expression of the senescent marker CD57. The acquisition of CD57 on TEMRA Vδ2pos T cells is also coupled with impairments in cytotoxicity and production of TNF-α and IFN-γ. These features resemble the acquisition of an immune-senescent profile by Vδ2pos T cells from CLM patients that received CHT, a phenomenon that is also associated with the loss of the co-stimulatory marker CD28 and with the induced expression of CD16. The group of CLM patients underwent CHT and older than 60 years old showed higher frequencies of CD57pos and TEMRA Vδ2pos T cells. Similar results were found for tumor infiltrating Vδ2pos T cell subset purified from CLM specimens of patients treated with CHT. The toxicity of CHT regimens also affects the homeostasis of Vδ2pos T cells by inducing higher frequencies of circulating CD57pos TEMRA subset in CLM underwent CHT and younger than 60 years old. Taken together, our data demonstrate that the enrichment of senescent Vδ2pos T cells in CLM patients is not only induced by patients' aging but also by the toxicity of CHT that further accelerates the accumulation of CD57pos TEMRA cells highly dysfunctional in their anti-tumor activities. These results are important to both predict the clinical outcome of CLM and to optimize those protocols of cell cancer immunotherapy employing unconventional Vδ2pos T cells

Experimental observation of optical rotation generated in vacuum by a magnetic field

We report the experimental observation of a light polarization rotation in vacuum in the presence of a transverse magnetic field. Assuming that data distribution is Gaussian, the average measured rotation is (3.9+/-0.5)e-12 rad/pass, at 5 T with 44000 passes through a 1m long magnet, with lambda = 1064 nm. The relevance of this result in terms of the existence of a light, neutral, spin-zero particle is discussed.Comment: 11 pages, 4 figures, submitted to Physical Review Letters Comment to version 2: minor changes to abstract and final discussion. Added 2 references Comment to version 3: corrected minor typographical errors, eliminated the distinction between scalar and pseudoscalar in the particle interpretation of the resul

miR-214 coordinates melanoma progression by upregulating ALCAM through TFAP2 and miR-148b downmodulation.

Malignant melanoma is one of the most aggressive human cancers, but the mechanisms governing its metastatic dissemination are not fully understood. Upregulation of miR-214 and ALCAM and the loss of TFAP2 expression have been implicated in this process, with TFAP2 a direct target of miR-214. Here, we link miR-214 and ALCAM as well as identify a core role for miR-214 in organizing melanoma metastasis. miR- 214 upregulated ALCAM, acting transcriptionally through TFAP2 and also posttranscriptionally through miR-148b (itself controlled by TFAP2), both negative regulators of ALCAM. We also identified several miR-214–mediated prometastatic functions directly promoted by ALCAM. Silencing ALCAM in miR-214–overexpressing melanoma cells reduced cell migration and invasion without affecting growth or anoikisin vitro, and it also impaired extravasation and metastasis formation in vivo. Conversely, cell migration and extravasation was reduced in miR-214–overexpressing cells by upregulation of either miR 148b or TFAP2. These findings were consistent with patterns of expression of miR-214, ALCAM, and miR-148b in human melanoma specimens. Overall, our results define a pathway involving miR-214, miR-148b, TFAP2, and ALCAM that is critical for establishing distant metastases in melanoma

Mechanical and physical characterization of natural and synthetic consolidants

Abstract The mechanical behavior of adhesives is strongly influenced by a large number of variables, relating to a complex interaction of mechanical-physical-chemical factors, such as its loading direction (shear, peel), the temperature and the environmental relative humidity (RH). These variables can have a large influence on the durability of restored art objects where thermoplastic adhesives have been used as a consolidant. This study aims to characterise the mechanical and physical behavior of some adhesives commonly used polymers by conservators as consolidants to restore cultural objects such as canvas paintings or historic wooden furniture. Twelve commercially available natural and synthetic adhesive materials were tested. The influence of RH at room temperature on the mechanical and physical properties of the adhesives was investigated. Shear and peel experiments were performed on adhesively bonded wood and canvas coupon to establish mechanical characterisation. The physical properties of the adhesives were determined by performing moisture adsorption measurements and Differential Scanning Calorimetry (DSC). The results of this study demonstrate that synthetic adhesive products are able to resist higher shear and peel loads than natural types. Moreover, the influence of important changes in RH on the mechanical properties of the adhesives was demonstrated. Reflecting on the combined data derived from shear and peel tests with the adhesive's sensitivity to moisture will help conservators to select the most suitable adhesives for their applications to achieve optimal durability and the best mechanical performance in versatile environmental conditions

Suggestive hypothesis on a case report: Patient presenting with cyclical ovarian cysts coupled to increased cholestatic enzymes

We describe the case of a childbearing-age woman presenting with spontaneous recurrent functional ovarian cysts and, more interestingly, chronic and asymptomatic elevation of cholestatic parameters. The patient showed no history of chronic viral infections, immunological and metabolic disorders, alcohol abuse and environmental toxins exposition. Hepatic ultrasonography and cholangio-pancreatography-magnetic-resonance excluded any morphological and structural abnormalities, while liver biopsy evidenced only minimal and not specific features of inflammation. Cholestasis indices obtained prompt recovery after each cycle of synthetic hormone therapy, implanted to treat functional ovarian cysts. She has continuously experienced the off-therapy asynchronous recurrence of liver laboratory abnormalities and functional ovarian cysts. The favorable effect of the synthetic hormone therapy to obtaining a stable recovery of this unexplained long-lasting cholestatic syndrome could be likely explained by downregulation of an endogenous ovarian overproduction, although estrogen-regulated local intracellular transduction pathways cannot be excluded

Identification of human intestinal parasites affecting an asymptomatic peri-urban Argentinian population using multi-parallel quantitative real-time polymerase chain reaction

Background: In resource-limited countries, stool microscopy is the diagnostic test of choice for intestinal parasites (soil-transmitted helminths and/or intestinal protozoa). However, sensitivity and specificity is low. Improved diagnosis of intestinal parasites is especially important for accurate measurements of prevalence and intensity of infections in endemic areas. Methods: The study was carried out in Orán, Argentina. A total of 99 stool samples from a local surveillance campaign were analyzed by concentration microscopy and McMaster egg counting technique compared to the analysis by multi-parallel quantitative real-time polymerase chain reaction (qPCR). This study compared the performance of qPCR assay and stool microscopy for 8 common intestinal parasites that infect humans including the helminths Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, and the protozoa Giardia lamblia, Cryptosporidium parvum/hominis, and Entamoeba histolytica, and investigated the prevalence of polyparasitism in an endemic area. Results: qPCR showed higher detection rates for all parasites as compared to stool microscopy except T. trichiura. Species-specific primers and probes were able to distinguish between A. duodenale (19.1 %) and N. americanus (36.4 %) infections. There were 48.6 % of subjects co-infected with both hookworms, and a significant increase in hookworm DNA for A. duodenale versus N. americanus (119.6 fg/μL: 0.63 fg/μL, P∈<∈0.001) respectively. qPCR outperformed microscopy by the largest margin in G. lamblia infections (63.6 % versus 8.1 %, P∈<∈0.05). Polyparasitism was detected more often by qPCR compared to microscopy (64.7 % versus 24.2 %, P∈<∈0.05). Conclusions: Multi-parallel qPCR is a quantitative molecular diagnostic method for common intestinal parasites in an endemic area that has improved diagnostic accuracy compared to stool microscopy. This first time use of multi-parallel qPCR in Argentina has demonstrated the high prevalence of intestinal parasites in a peri-urban area. These results will contribute to more accurate epidemiological survey, refined treatment strategies on a public scale, and better health outcomes in endemic settings.Fil: Cimino, Rubén Oscar. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Jeun, Rebecca. Baylor College Of Medicine; Estados UnidosFil: Juarez, Marisa. Universidad Nacional de Salta; ArgentinaFil: Cajal, Pamela S.. Universidad Nacional de Salta; ArgentinaFil: Vargas Flores, Paola Andrea. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Echazú, Adriana. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bryan, Patricia E.. Baylor College Of Medicine; Estados UnidosFil: Nasser, Julio Rubén. Universidad Nacional de Salta; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mejia, Rojelio. Baylor College Of Medicine; Estados Unidos. Universidad Nacional de Salta; Argentin

Cu-exchanged 3D-printed geopolymer/ZSM-5 monolith for selective catalytic reduction of NOx

Cu-exchanged zeolites with MFI structure, such as ZSM-5, represent effective catalysts for SCR processes when the application requires a good thermal stability under a wide range of temperature as for the after-treatment of exhaust gas from diesel engine. The production of zeolite in a structured form, mandatorily required for mobile applications, is quite complex due to the poor adhesion of the material. In this paper 3D-printed geopolymers containing about 37 % ZSM-5 are proposed as potentially structured catalysts for SCR applications. The production of the monolith and the pre-treatment necessary to introduce copper as active exchanged cation are investigated. The effect of pre-treatments on the physical and morphological structure of both geopolymer and zeolite and on the nature of copper introduced in the subsequent step was studied using characterization techniques such as SEM, XRD, N2 physisorption and Temperature Programmed Reduction (TPR)