Potenciales fuentes de aprovisionamiento para la manufactura cerámica: sitio Guayacas, Paysandú, Uruguay

En el presente trabajo se exponen los resultados obtenidos del estudio del material cerámico del sitio Guayacas, con el objetivo de identificar las fuentes de aprovisionamiento de arcillas o fangos y antiplásticos. El sitio se ubica en el departamento de Paysandú, en la zona de Guayacas, emplazado en una lomada sobre el río Daymán, 7 km al este del río Uruguay (31°30’24.58’’S y 57°56’50.88’’O). La ocupación del sitio, según fechados de TL sobre material cerámico, se encuentra entre 1471±12 y 1556±18 años DC. Mediante el análisis de DRX se identificaron potenciales sitios canteras, vinculados a aluviones modernos en las proximidades del sitio. Por otro lado, en el análisis de corte de lámina delgada se observó la presencia en las pastas de partículas biosilíceas (principalmente espículas de espongiarios) cuya concentración alertó sobre la posibilidad de su incorporación intencional como antiplástico. A los fines de contrastar dicha hipótesis, se procedió al análisis microscópico de muestras provenientes de depósitos naturales de arcilla y de colecciones de referencia de espongiarios. Asimismo, se realizaron estudios experimentales, elaborando plaquetas cerámicas con distintas combinaciones de arcillas y antiplásticos biosilíceos, procediendo a su posterior estudio microscópico. Los resultados de estos estudios sugieren una manufactura local con fuentes de aprovisionamiento de arcillas a no más de 2 km del sitio y la inclusión intencional de partículas biosilíceas en las pastas cerámicas. Este tipo de práctica ha sido ampliamente referida en la etnografía del sur de Brasil, vinculándose a propiedades tecnofuncionales de los recipientes cerámicos.The following paper presents pottery studies results from the Guayacas archaeological site. The main research goal was to identify clay or mud and temper sources. The site is located at 31°30’24.58’’S and 57°56’50.88’’W in Paysandú County, Guayacas area, over a gentle hill by the Daymán river, 7 km east of Uruguay river. According to TLD performed on pottery, the site was inhabited among 1471±12 and 1556±18 AD. DRX analysis allowed the identification of potential source areas, which are linked to modern alluvial deposits in the site surroundings. Thin section analysis highlighted the presence of biosiliceous material in the ceramic pastes (mainly sponge spicules) at an unusual concentration that suggests intentional use as a temper agent. To contrast such hypothesis, samples from natural clay deposits and sponge spicules reference collections were screened under microscopy. Simultaneously, experimental studies were carried out, making pottery tablets by combining different concentrations of clay and biosilica, and the resulting pottery was also microscopically analyzed. Obtained results allowed to infer that the whole pottery making process was locally undertook, with clay sources at no more than 2 km away from the site, and that the inclusion of sponge spicules in the raw mix was intentional. Such behavior or technical particularity has been widely reported by southern Brazil ethnographers and could be linked with pottery techno-functional attributes.Facultad de Ciencias Naturales y Muse

Potenciales fuentes de aprovisionamiento para la manufactura cerámica: sitio Guayacas, Paysandú, Uruguay

En el presente trabajo se exponen los resultados obtenidos del estudio del material cerámico del sitio Guayacas, con el objetivo de identificar las fuentes de aprovisionamiento de arcillas o fangos y antiplásticos. El sitio se ubica en el departamento de Paysandú, en la zona de Guayacas, emplazado en una lomada sobre el río Daymán, 7 km al este del río Uruguay (31°30’24.58’’S y 57°56’50.88’’O). La ocupación del sitio, según fechados de TL sobre material cerámico, se encuentra entre 1471±12 y 1556±18 años DC. Mediante el análisis de DRX se identificaron potenciales sitios canteras, vinculados a aluviones modernos en las proximidades del sitio. Por otro lado, en el análisis de corte de lámina delgada se observó la presencia en las pastas de partículas biosilíceas (principalmente espículas de espongiarios) cuya concentración alertó sobre la posibilidad de su incorporación intencional como antiplástico. A los fines de contrastar dicha hipótesis, se procedió al análisis microscópico de muestras provenientes de depósitos naturales de arcilla y de colecciones de referencia de espongiarios. Asimismo, se realizaron estudios experimentales, elaborando plaquetas cerámicas con distintas combinaciones de arcillas y antiplásticos biosilíceos, procediendo a su posterior estudio microscópico. Los resultados de estos estudios sugieren una manufactura local con fuentes de aprovisionamiento de arcillas a no más de 2 km del sitio y la inclusión intencional de partículas biosilíceas en las pastas cerámicas. Este tipo de práctica ha sido ampliamente referida en la etnografía del sur de Brasil, vinculándose a propiedades tecnofuncionales de los recipientes cerámicos.The following paper presents pottery studies results from the Guayacas archaeological site. The main research goal was to identify clay or mud and temper sources. The site is located at 31°30’24.58’’S and 57°56’50.88’’W in Paysandú County, Guayacas area, over a gentle hill by the Daymán river, 7 km east of Uruguay river. According to TLD performed on pottery, the site was inhabited among 1471±12 and 1556±18 AD. DRX analysis allowed the identification of potential source areas, which are linked to modern alluvial deposits in the site surroundings. Thin section analysis highlighted the presence of biosiliceous material in the ceramic pastes (mainly sponge spicules) at an unusual concentration that suggests intentional use as a temper agent. To contrast such hypothesis, samples from natural clay deposits and sponge spicules reference collections were screened under microscopy. Simultaneously, experimental studies were carried out, making pottery tablets by combining different concentrations of clay and biosilica, and the resulting pottery was also microscopically analyzed. Obtained results allowed to infer that the whole pottery making process was locally undertook, with clay sources at no more than 2 km away from the site, and that the inclusion of sponge spicules in the raw mix was intentional. Such behavior or technical particularity has been widely reported by southern Brazil ethnographers and could be linked with pottery techno-functional attributes.Facultad de Ciencias Naturales y Muse

COX-2 Silencing in Canine Malignant Melanoma Inhibits Malignant Behaviour

Metastatic melanoma is a very aggressive form of cancer in both humans and dogs. Dogs primarily develop oral melanoma of mucosal origin. Although oral melanoma in humans is rare, both diseases are highly aggressive with frequent metastases. This disease represents a “One Health” opportunity to improve molecular and mechanistic understanding of melanoma progression. Accumulating evidence suggests that cyclooxygenase-2 (COX-2) may play a critical role in the malignant behaviour of melanoma. In this study we analysed 85 histologically confirmed melanomas from canine patients and showed that COX-2 is overexpressed in both oral and cutaneous melanomas and that COX-2 expression correlates with established markers of poor prognosis. To determine the role of COX-2 in melanoma we developed two melanoma cell lines with stable integration of an inducible doxycycline-regulated expression vector containing a COX-2 targeted micro-RNA (miRNA). Using this system, we showed that cellular proliferation, migration and invasion are COX-2 dependent, establishing a direct relationship between COX-2 expression and malignant behaviour in canine melanoma. We have also developed a powerful molecular tool to aid further dissection of the mechanisms by which COX-2 regulates melanoma progression

Exciton-plasmon states in nanoscale materials: breakdown of the Tamm-Dancoff approximation

Within the Tamm-Dancoff approximation ab initio approaches describe excitons as packets of electron-hole pairs propagating only forward in time. However, we show that in nanoscale materials excitons and plasmons hybridize, creating exciton--plasmon states where the electron-hole pairs oscillate back and forth in time. Then, as exemplified by the trans-azobenzene molecule and carbon nanotubes, the Tamm-Dancoff approximation yields errors as large as the accuracy claimed in ab initio calculations. Instead, we propose a general and efficient approach that avoids the Tamm--Dancoff approximation, and correctly describes excitons, plasmons and exciton-plasmon states

Cost-Utility Analysis of a Medication Review with Follow-Up Service for Older Adults with Polypharmacy in Community Pharmacies in Spain: The conSIGUE Program

© 2015, Springer International Publishing Switzerland. Background: The concept of pharmaceutical care is operationalized through pharmaceutical professional services, which are patient-oriented to optimize their pharmacotherapy and to improve clinical outcomes. Objective: The objective of this study was to estimate the incremental cost-effectiveness ratio (ICER) of a medication review with follow-up (MRF) service for older adults with polypharmacy in Spanish community pharmacies against the alternative of having their medication dispensed normally. Methods: The study was designed as a cluster randomized controlled trial, and was carried out over a time horizon of 6 months. The target population was older adults with polypharmacy, defined as individuals taking five or more medicines per day. The study was conducted in 178 community pharmacies in Spain. Cost-utility analysis adopted a health service perspective. Costs were in euros at 2014 prices and the effectiveness of the intervention was estimated as quality-adjusted life-years (QALYs). In order to analyze the uncertainty of ICER results, we performed a non-parametric bootstrapping with 5000 replications. Results: A total of 1403 older adults, aged between 65 and 94 years, were enrolled in the study: 688 in the intervention group (IG) and 715 in the control group (CG). By the end of the follow-up, both groups had reduced the mean number of prescribed medications they took, although this reduction was greater in the IG (0.28 ± 1.25 drugs; p < 0.001) than in the CG (0.07 ± 0.95 drugs; p = 0.063). Older adults in the IG saw their quality of life improved by 0.0528 ± 0.20 (p < 0.001). In contrast, the CG experienced a slight reduction in their quality of life: 0.0022 ± 0.24 (p = 0.815). The mean total cost was €977.57 ± 1455.88 for the IG and €1173.44 ± 3671.65 for the CG. In order to estimate the ICER, we used the costs adjusted for baseline medications and QALYs adjusted for baseline utility score, resulting in a mean incremental total cost of −€250.51 ± 148.61 (95 % CI −541.79 to 40.76) and a mean incremental QALY of 0.0156 ± 0.004 (95 % CI 0.008–0.023). Regarding the results from the cost-utility analysis, the MRF service emerged as the dominant strategy. Conclusion: The MRF service is an effective intervention for optimizing prescribed medication and improving quality of life in older adults with polypharmacy in community pharmacies. The results from the cost-utility analysis suggest that the MRF service is cost effective

Kidins220 sets the threshold for survival of neural stem cells and progenitors to sustain adult neurogenesis

In the adult mammalian brain, neural stem cells (NSCs) located in highly restricted niches sustain the generation of new neurons that integrate into existing circuits. A reduction in adult neurogenesis is linked to ageing and neurodegeneration, whereas dysregulation of proliferation and survival of NSCs have been hypothesized to be at the origin of glioma. Thus, unravelling the molecular underpinnings of the regulated activation that NSCs must undergo to proliferate and generate new progeny is of considerable relevance. Current research has identified cues promoting or restraining NSCs activation. Yet, whether NSCs depend on external signals to survive or if intrinsic factors establish a threshold for sustaining their viability remains elusive, even if this knowledge could involve potential for devising novel therapeutic strategies. Kidins220 (Kinase D-interacting substrate of 220 kDa) is an essential effector of crucial pathways for neuronal survival and differentiation. It is dramatically altered in cancer and in neurological and neurodegenerative disorders, emerging as a regulatory molecule with important functions in human disease. Herein, we discover severe neurogenic deficits and hippocampal-based spatial memory defects accompanied by increased neuroblast death and high loss of newly formed neurons in Kidins220 deficient mice. Mechanistically, we demonstrate that Kidins220-dependent activation of AKT in response to EGF restraints GSK3 activity preventing NSCs apoptosis. We also show that NSCs with Kidins220 can survive with lower concentrations of EGF than the ones lacking this molecule. Hence, Kidins220 levels set a molecular threshold for survival in response to mitogens, allowing adult NSCs growth and expansion. Our study identifies Kidins220 as a key player for sensing the availability of growth factors to sustain adult neurogenesis, uncovering a molecular link that may help paving the way towards neurorepair

Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer

Cetuximab is a standard-of-care treatment for RAS wild-type metastatic colorectal cancer (mCRC) but not for those harbor a KRAS mutation since MAPK pathway is constitutively activated. Nevertheless, cetuximab also exerts its effect by its immunomodulatory activity despite the presence of RAS mutation. The aim of this study was to determine the impact of polymorphism FcγRIIIa V158F and killer immunoglobulin-like receptor (KIR) genes on the outcome of mCRC patients with KRAS mutations treated with cetuximab. This multicenter Phase II clinical trial included 70 mCRC patients with KRAS mutated. We found KIR2DS4 gene was significantly associated with OS (HR 2.27; 95% CI, 1.08–4.77; P = 0.03). In non-functional receptor homozygotes the median OS was 2.6 months longer than in carriers of one copy of full receptor. Multivariate analysis confirmed KIR2DS4 as a favorable prognostic marker for OS (HR 6.71) in mCRC patients with KRAS mutation treated with cetuximab. These data support the potential therapeutic of cetuximab in KRAS mutated mCRC carrying non-functional receptor KIR2DS4 since these patients significantly prolong their OS even after heavily treatment. KIR2DS4 typing could be used as predictive marker for identifying RAS mutated patients that could benefit from combination approaches of anti-EGFR monoclonal antibodies and other immunotherapies to overcome the resistance mediated by mutation in RAS.This clinical trial was approved and supported by Merck S.L., an affiliate of Merck KGaA, Darmstadt. Germany [research project number 2010-023580-18, date: 05-06-2014

Canine distemper virus induces apoptosis in cervical tumor derived cell lines

Apoptosis can be induced or inhibited by viral proteins, it can form part of the host defense against virus infection, or it can be a mechanism for viral spread to neighboring cells. Canine distemper virus (CDV) induces apoptotic cells in lymphoid tissues and in the cerebellum of dogs naturally infected. CDV also produces a cytopathologic effect, leading to apoptosis in Vero cells in tissue culture. We tested canine distemper virus, a member of the Paramyxoviridae family, for the ability to trigger apoptosis in HeLa cells, derived from cervical cancer cells resistant to apoptosis. To study the effect of CDV infection in HeLa cells, we examined apoptotic markers 24 h post infection (pi), by flow cytometry assay for DNA fragmentation, real-time PCR assay for caspase-3 and caspase-8 mRNA expression, and by caspase-3 and -8 immunocytochemistry. Flow cytometry showed that DNA fragmentation was induced in HeLa cells infected by CDV, and immunocytochemistry revealed a significant increase in the levels of the cleaved active form of caspase-3 protein, but did not show any difference in expression of caspase-8, indicating an intrinsic apoptotic pathway. Confirming this observation, expression of caspase-3 mRNA was higher in CDV infected HeLa cells than control cells; however, there was no statistically significant change in caspase-8 mRNA expression profile. Our data suggest that canine distemper virus induced apoptosis in HeLa cells, triggering apoptosis by the intrinsic pathway, with no participation of the initiator caspase -8 from the extrinsic pathway. In conclusion, the cellular stress caused by CDV infection of HeLa cells, leading to apoptosis, can be used as a tool in future research for cervical cancer treatment and control

Excitotoxic inactivation of constitutive oxidative stress detoxification pathway in neurons can be rescued by PKD1

Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). This step turns off the IKK/NF-κB/SOD2 antioxidant pathway. Neuronal PKD1 inactivation by pharmacological inhibition or lentiviral silencing in vitro, or by genetic inactivation in neurons in vivo, strongly enhances excitotoxic neuronal death. In contrast, expression of an active dephosphorylation-resistant PKD1 mutant potentiates the IKK/NF-κB/SOD2 oxidative stress detoxification pathway and confers neuroprotection from in vitro and in vivo excitotoxicity. Our results indicate that PKD1 inactivation underlies excitotoxicity-induced neuronal death and suggest that PKD1 inactivation may be critical for the accumulation of oxidation-induced neuronal damage during aging and in neurodegenerative disorders