Proyectiles de plomo en el antiguo Perú

Se han encontrado proyectiles de piedra con hondas (warak’as) en varios sitios arqueológicos en el Perú. Esto indica que esta arma fue comúnmente utilizada por sociedades precolombinas. La honda, denominada warak’a o huaraca en quechua, posee un amplio espectro espacial y temporal, siendo documentada desde hace muchos años en el Viejo y Nuevo Mundo y usada aún con fines pastoriles en el Perú rural de hoy. Tanto en el antiguo Perú como en el Viejo Mundo, la galena con plata (soroche), fue fundida para la obtención de la plata. Con un proceso diferente de la propia galena se obtenía el plomo. A causa de su facilidad de fundición, moldeo y peso, el plomo habría proporcionado munición bien formada y con masa consistente para la warak’a, lo que mejoraba su precisión de uso. Varios artefactos precolombino de plomo del antiguo Perú han sido simplemente identificados como lingotes o pesas ; sin embargo, si prestamos atención a sus formas (bicónicas, ovoides o esféricas) (35 mm, 80-160 g), dimensiones (30-60 mm) y pesos (30-40 g), vemos cómo se asemejan a los proyectiles de plomo de las hondas antiguas de Europa.Les projectiles en pierre qui ont été découverts sur divers sites archéologiques péruviens indiquent que la fronde (quechua, warak’a, huaraca ; esp., honda) était en usage au Pérou avant la conquête espagnole. Arme ancestrale, très répandue dans l’Ancien monde, la fronde est encore utilisée dans de nombreuses zones rurales du pays, principalement pour rassembler des troupeaux d’animaux. Dans le Pérou antique, comme ailleurs dans l’Ancien monde, la galène argentifère (soroche) était un minerai exploité selon deux processus bien distincts pour sa teneur en argent et en plomb. Lourd et malléable, le plomb présente en outre un point de fusion peu élevé. Il permettait donc de façonner des projectiles de fronde de forme et de poids constants, favorisant des tirs d’une précision régulière sans précédent. Plusieurs objets péruviens en plomb datant d’avant la colonisation espagnole ont été identifiés comme des lingots ou des poids. Toutefois, il serait plus exact de les qualifier d’objets biconiques, ovoïdes (30-60 mm, 30-40 g) ou sphériques (35 mm, 80-160 g). Par leur masse, leur forme et leurs dimensions autant que leur composition, ces objets péruviens en plomb ressemblent étonnamment aux balles de fronde retrouvées sur des champs de bataille de l’Europe antique, auxquelles ils sont assimilés dans le présent document.Ancient stone sling ammunition found at several archaeological sites in Peru indicates that the Ancient stone sling ammunition found at several archaeological sites in Peru. In ancient Peru, as in the Old World, argentiferous galena (soroche) was smelted to provide silver and in a distinctly different process, lead was smelted from galena for other uses. Because of its ease of smelting, casting, and weight, lead would have provided sling ammunition with consistent form and mass, and therefore, improved and consistent accuracy. Several pre-contact lead artifacts from ancient Peru have been described as bars or weights ; however, alternatively, these artifacts might also be more accurately described as biconic to ovoid (30-60 mm, 30-40 g) and spherical (35 mm, 80-160 g). In weight, form and dimensions, and composition, these ancient Peruvian lead artifacts are strikingly similar to ancient lead sling projectiles from ancient battle sites in Europe and are herein interpreted to have served a similar function

Lung resistance-related protein as a predictor of clinical outcome in advanced testicular germ-cell tumours

This study was undertaken to investigate the expression and predictive value for outcome of multidrug resistance-associated (MDR) proteins P-glycoprotein (Pgp), MRP1, BCRP, and LRP, in advanced testicular germ-cell tumours (TGCT). Paraffin-embedded sections from 56 previously untreated patients with metastatic TGCT were immunostained for Pgp, MRP1, BCRP, and LRP. All patients received platinum-based chemotherapy after orchidectomy. Immunostaining was related to clinicopathological parameters, response to chemotherapy, and outcome. Strong and intermediate expressions of the different MDR-related proteins were: 27 and 41% (Pgp), 54 and 37% (MRP1), 86 and 7% (BCRP), and 14 and 29% (LRP). P-glycoprotein and MRP1 associated, respectively, to low AFP (P=0.026) and high LDH levels (P=0.014), whereas LRP expression associated with high beta-hCG levels (P=0.003) and stage IV tumours (P=0.029). No correlation was found between Pgp, MRP1, and BCRP expression and response to chemotherapy and survival. In contrast, patients with LRP-positive tumours (strong or intermediate expression) had shorter progression-free (P=0.0006) and overall survival (P=0.0116) than LRP-negative patients, even after individual log-rank adjustments by statistically associated variables. Our data suggest that a positive LRP immunostaining at the time of diagnosis in metastatic TGCT is associated with an adverse clinical outcome

Molecular and cellular characterization of ABCG2 in the prostate

BACKGROUND: Identification and characterization of the prostate stem cell is important for understanding normal prostate development and carcinogenesis. The flow cytometry-based side population (SP) technique has been developed to isolate putative adult stem cells in several human tissue types including the prostate. This phenotype is mainly mediated by the ATP-binding cassette membrane transporter ABCG2. METHODS: Immunolocalization of ABCG2 was performed on normal prostate tissue obtained from radical prostatectomies. Normal human prostate SP cells and ABCG2(+ )cells were isolated and gene expression was determined with DNA array analysis and RT-PCR. Endothelial cells were removed by pre-sorting with CD31. RESULTS: ABCG2 positive cells were localized to the prostate basal epithelium and endothelium. ABCG2(+ )cells in the basal epithelium constituted less than 1% of the total basal cell population. SP cells constituted 0.5–3% of the total epithelial fraction. The SP transcriptome was essentially the same as ABCG2(+ )and both populations expressed genes indicative of a stem cell phenotype, however, the cells also expressed many genes in common with endothelial cells. CONCLUSION: These results provide gene expression profiles for the prostate SP and ABCG2(+ )cells that will be critical for studying normal development and carcinogenesis, in particular as related to the cancer stem cell concept

A Genetically Encoded Tag for Correlated Light and Electron Microscopy of Intact Cells, Tissues, and Organisms

Electron microscopy (EM) achieves the highest spatial resolution in protein localization, but specific protein EM labeling has lacked generally applicable genetically encoded tags for in situ visualization in cells and tissues. Here we introduce “miniSOG” (for mini Singlet Oxygen Generator), a fluorescent flavoprotein engineered from Arabidopsis phototropin 2. MiniSOG contains 106 amino acids, less than half the size of Green Fluorescent Protein. Illumination of miniSOG generates sufficient singlet oxygen to locally catalyze the polymerization of diaminobenzidine into an osmiophilic reaction product resolvable by EM. MiniSOG fusions to many well-characterized proteins localize correctly in mammalian cells, intact nematodes, and rodents, enabling correlated fluorescence and EM from large volumes of tissue after strong aldehyde fixation, without the need for exogenous ligands, probes, or destructive permeabilizing detergents. MiniSOG permits high quality ultrastructural preservation and 3-dimensional protein localization via electron tomography or serial section block face scanning electron microscopy. EM shows that miniSOG-tagged SynCAM1 is presynaptic in cultured cortical neurons, whereas miniSOG-tagged SynCAM2 is postsynaptic in culture and in intact mice. Thus SynCAM1 and SynCAM2 could be heterophilic partners. MiniSOG may do for EM what Green Fluorescent Protein did for fluorescence microscopy

Development of a novel protocol based on blood clot to improve the sensitivity of qPCR detection of toxoplasma gondii in peripheral blood specimens

Quantitative polymerase chain reaction (qPCR) for Toxoplasma gondii multicopy genes has emerged as a promising strategy for sensitive detection of parasite DNA. qPCR can be performed from blood samples, which are minimally invasive to collect. However, there is no consensus about what type of blood specimen yields the best sensitivity. The development of a novel protocol for qPCR detection of T. gondii using blood clot, involving an appropriate DNA extraction method and the use of an internal amplification control to monitor the reaction is presented in the current study. Assays directed to the B1 and REP529 genes were performed in spiked specimens of whole blood, guanidine–ethylenediaminetetraacetic acid blood, and clot. The clot-based qPCR was shown to be more sensitive when compared with other types of specimens, detecting five and 0.05 T. gondii genomes, using B1 and REP529 targets, respectively. Finally, a comparative analysis with samples from HIV patients with clinical suspicion of toxoplasmosis was performed, demonstrating the detection of four positive suspected cases with clots compared with only one using guanidine–ethylenediaminetetraacetic acid blood. The high analytical sensitivity and the cost-effective advantages offered by clot supports this methodology as a good laboratory tool to monitor parasite burden

ATP-binding cassette (ABC) transporters in normal and pathological lung

ATP-binding cassette (ABC) transporters are a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes in an energy-dependent manner. Many ABC transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) are highly expressed in bronchial epithelium. This review aims to give new insights in the possible functions of ABC molecules in the lung in view of their expression in different cell types. Furthermore, their role in protection against noxious compounds, e.g. air pollutants and cigarette smoke components, will be discussed as well as the (mal)function in normal and pathological lung. Several pulmonary drugs are substrates for ABC transporters and therefore, the delivery of these drugs to the site of action may be highly dependent on the presence and activity of many ABC transporters in several cell types. Three ABC transporters are known to play an important role in lung functioning. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene can cause cystic fibrosis, and mutations in ABCA1 and ABCA3 are responsible for respectively Tangier disease and fatal surfactant deficiency. The role of altered function of ABC transporters in highly prevalent pulmonary diseases such as asthma or chronic obstructive pulmonary disease (COPD) have hardly been investigated so far. We especially focused on polymorphisms, knock-out mice models and in vitro results of pulmonary research. Insight in the function of ABC transporters in the lung may open new ways to facilitate treatment of lung diseases

Establishment and characterization of a bladder cancer cell line with enhanced doxorubicin resistance by mevalonate pathway activation

Resistance to chemotherapy is a major problem in the treatment of urothelial bladder cancer. Several mechanisms have been identified in resistance to doxorubicin by analysis of resistant urothelial carcinoma (UC) cell lines, prominently activation of drug efflux pumps and diminished apoptosis. We have derived a new doxorubicin-resistant cell line from BFTC-905 UC cells, designated BFTC-905DOXO-II. A doxorubicin-responsive green fluorescent protein (GFP) reporter assay indicated that resistance in BFTC905-DOXO-II was not due to increased drug efflux pump activity, whereas caspase-3/7 activation was indeed diminished. Gene expression microarray analysis revealed changes in proapoptotic and antiapoptotic genes, but additionally induction of the mevalonate (cholesterol) biosynthetic pathway. Treatmentwithsimvastatin restored sensitivity of BFTC-905DOXO-II to doxorubicin to that of the parental cell line. Induction of the mevalonate pathway has been reported as a mechanism of chemoresistance in other cancers; this is the first observation in bladder cancer. Combinations of statins with doxorubicin-containing chemotherapy regimens may provide a therapeutic advantage in such case

Multiclonal epidemic of Klebsiella pneumoniae isolates producing DHA-1 in a Spanish hospital

AbstractBetween June 2007 and January 2008, 26 Klebsiella pneumoniae isolates carrying blaDHA-1 on an IncL/M plasmid were obtained from clinical samples at Granollers Hospital, Barcelona, Spain. Three of the isolates also carried a blaCTX-M-15 gene. The 26 isolates showed 11 pulsed-field gel electrophoresis (PFGE) patterns. Multilocus sequence typing showed that PFGE patterns A, B and C belonged to sequence type (ST)17, D to ST13, E to ST427, F and G to ST416, H to ST37, I to ST440, J to ST326, and K to ST428. Results demonstrated the effectiveness of the infection control programme in place at the centre. This study reports the first characterization of STs for blaDHA-1-producing K. pneumoniae isolates