A space for the living and the dead: The Chalcolithic ditched enclosured settlement of Camino de las Yeseras (San Fernando de Henares, Madrid)

Se presentan los resultados preliminares de la excavación de un gran poblado de fosos calcolítico, cuya situación estratégica ayudó a ser un centro de producción e intercambio de excedentes en materias primas (sílex, granito y piedras metamórficas) y productos agropecuarios e industriales por otros foráneos (cobre, variscita, cinabrio, marfil y oro). Los rituales funerarios son de una gran variedad, individuales y colectivos, en covachas e hipogeos, con o sin ajuar campaniforme, algunos de los últimos con ricos ajuares áureos y ebúrneos. Los datos óseos de algunos inhumados campaniformes apuntan a un aspecto físico muy llamativo en vida, mientras los depósitos con fauna, en composición taxonómica variada, indican una compleja relación simbólica con el mundo animal. El yacimiento resulta clave para un mejor conocimiento del período calcolítico y el impacto campaniforme y sus rituales funerarios en la consolidación y diferenciación de las primeras sociedades metalúrgicas del interior peninsularThe preliminary results are presented of the excavations in a large, ditched enclosured Chalcolithic settlement. The site was probably a central place in the production and long-distance exchange of surplus. The accumulations found of raw materials (flint, granite and metamorphic stones) and agricultural, stockbreeding and industrial products were exchanged by other foreign products (variscite, cinnabar, ivory and gold). Ritual data are also remarkable: a significant number of individual and collective burials have been recorded in pits, small artificial caves and hypogeos, delimited in special areas. The richer burials had Ciempozuelos-style Bell-beaker elements and prestige items, such as gold and ivory beads. Osteomorphic and size features of some Bell-beaker individuals point out a remarkable physical aspect during their life time. The faunal deposits, which included mixed species associations, evidence a complex symbolic relationship with animals. The site is essential for the knowledge of the Chalcolithic period and the impact of Bell-beaker customs and funerary rituals in the consolidation of social inequalities amidst the first metallurgical societies of the interior of the Iberian Peninsul

An improved method for statistical studies of the internal kinematics of HII regions: the case of M 83

We present the integrated Halpha emission line profile for 157 HII regions in the central 3.4' x 3.4' of the galaxy M 83 (NGC 5236). Using the Fabry-Perot interferometer GHaFaS, on the 4.2 m William Herschel on La Palma, we show the importance of a good characterization of the instrumental response function for the study of line profile shapes. The luminosity-velocity dispersion relation is also studied, and in the log(L)-log(sigma) plane we do not find a linear relation, but an upper envelope with equation log(L)=0.9 *log(sigma)+38.1. For the adopted distance of 4.5 Mpc, the upper envelope appears at the luminosity L=10^38.5 ergs, in full agreement with previous studies of other galaxies, reinforcing the idea of using HII regions as standard candles.Comment: 13 pages, 9 figures, accepted for publication in MNRA

Differentiating Acute Interstitial Nephritis From Immune Checkpoint Inhibitors From Other Causes

Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with neoplasms in advanced stages. On the other hand, ICIs have immune-related adverse events. These adverse events affect mostly other organs than the kidney, such as skin or gastrointestinal tract. The incidence of nephrotoxicity with monotherapy with any ICI is about 2%, which increases to 5% in combination therapy. Acute tubulointerstitial nephritis (AIN) is the most common pattern of kidney damage related to ICIs. Globally, without considering ICI nephrotoxicity, AIN is estimated to account for 15% to 20% of cases of acute kidney injury (AKI). This is crucial because patients who are treated with ICIs, may also be taking other drugs that potentially cause AIN, and therefore, knowing the particularities about ICI-related AIN could be helpful in clinical practice to better understand the phenotypic differences between the 2 types of AIN. In addition, several studies have now shown that being on proton pump inhibitors is a risk factor for AIN from ICI therapy

The value of selected in vitro and in silico methods to predict acute oral toxicity in a regulatory context: results from the European Project ACuteTox

ACuteTox is a project within the 6th European Framework Programme which had as one of its goals to develop, optimise and prevalidate a non-animal testing strategy for predicting human acute oral toxicity. In its last 6months, a challenging exercise was conducted to assess the predictive capacity of the developed testing strategies and final identification of the most promising ones. Thirty-two chemicals were tested blind in the battery of in vitro and in silico methods selected during the first phase of the project. This paper describes the classification approaches studied: single step procedures and two step tiered testing strategies. In summary, four in vitro testing strategies were proposed as best performing in terms of predictive capacity with respect to the European acute oral toxicity classification. In addition, a heuristic testing strategy is suggested that combines the prediction results gained from the neutral red uptake assay performed in 3T3 cells, with information on neurotoxicity alerts identified by the primary rat brain aggregates test method. Octanol-water partition coefficients and in silico prediction of intestinal absorption and blood-brain barrier passage are also considered. This approach allows to reduce the number of chemicals wrongly predicted as not classified (LD(50)>2000mg/kg b.w.).Peer Reviewe

Habitat quality affects the condition of Luciobarbus sclateri in the Guadiamar River (SW Iberian Peninsula): Effects of disturbances by the toxic spill of the Aznalcóllar mine

This study analyzes the somatic condition of southern Iberian barbel Luciobarbus sclateri (Günther, 1868) in the Guadiamar River (SW Iberian Peninsula). This river was seriously affected by a toxic spill of about 4 million cubic meters of acidic water and 2 million cubic meters of mud rich in heavy metals. Once the spill removal works concluded, sites affected and unaffected by the accident were sampled to study its effects on the fish fauna. The ecological variables registered were related to water quality, physical state of reaches, ecological quality, resources exploited by fish, and potential intra-specific interactions. From an initial 15 ecological variables, seasonal water flow and pH explained most of the variation in barbel condition. This study shows that the Guadiamar River, 56 months after the accident, is still undergoing a recovery process where, beyond ecological variables, proximity to the affected area is the most influential factor for fish condition. © 2012 Springer Science+Business Media B.V

ATR suppresses telomere fragility and recombination but is dispensable for elongation of short telomeres by telomerase

ATR recognizes critically short telomeres as fragile sites and protects them from chromosomal fusions

Spontaneous honeybee behaviour is altered by persistent organic pollutants

The effect of environmental pollutants on honeybee behaviour has focused mainly on currently used pesticides. However, honeybees are also exposed to persistent organic pollutants (POPs). The aim of this laboratory based study was to determine if exposure to sublethal field-relevant concentrations of POPs altered the spontaneous behaviour of foraging-age worker honeybees. Honeybees (Apis mellifera) were orally exposed to either a sublethal concentration of the polychlorinated biphenyl (PCB) mixture Aroclor 1254 (100 ng/ml), the organochlorine insecticide lindane (2.91 ng/ml) or vehicle (0.01% DMSO, 0.00015% ethanol in 1M sucrose) for 1–4 days. The frequency of single event behaviours and the time engaged in one of four behavioural states (walking, flying, upside down and stationary) were monitored for 15 min after 1, 2, 3 and 4 days exposure. Exposure to Aroclor 1254 but not lindane increased the frequency and time engaged in honeybee motor activity behaviours in comparison to vehicle. The Aroclor 1254—induced hyperactivity was evident after 1 day of exposure and persisted with repeated daily exposure. In contrast, 1 day of exposure to lindane elicited abdominal spasms and increased the frequency of grooming behaviours in comparison to vehicle exposure. After 4 days of exposure, abdominal spasms and increased grooming behaviours were also evident in honeybees exposed to Aroclor 1254. These data demonstrate that POPs can induce distinct behavioural patterns, indicating different toxicokinetic and toxicodynamic properties. The changes in spontaneous behaviour, particularly the PCB-induced chronic hyperactivity and the associated energy demands, may have implications for colony health

A p53-Dependent Response Limits Epidermal Stem Cell Functionality and Organismal Size in Mice with Short Telomeres

Telomere maintenance is essential to ensure proper size and function of organs with a high turnover. In particular, a dwarf phenotype as well as phenotypes associated to premature loss of tissue regeneration, including the skin (hair loss, hair graying, decreased wound healing), are found in mice deficient for telomerase, the enzyme responsible for maintaining telomere length. Coincidental with the appearance of these phenotypes, p53 is found activated in several tissues from these mice, where is thought to trigger cellular senescence and/or apoptotic responses. Here, we show that p53 abrogation rescues both the small size phenotype and restitutes the functionality of epidermal stem cells (ESC) of telomerase-deficient mice with dysfunctional telomeres. In particular, p53 ablation restores hair growth, skin renewal and wound healing responses upon mitogenic induction, as well as rescues ESCmobilization defects in vivo and defective ESC clonogenic activity in vitro. This recovery of ESC functions is accompanied by a downregulation of senescence markers and an increased proliferation in the skin and kidney of telomerase-deficient mice with critically short telomeres without changes in apoptosis rates. Together, these findings indicate the existence of a p53-dependent senescence response acting on stem/progenitor cells with dysfunctional telomeres that is actively limiting their contribution to tissue regeneration, thereby impinging on tissue fitness

INTERLOCKING RESONANCE PATTERNS IN GALAXY DISKS

We have developed a method for finding dynamical resonances in disk galaxies using the change in sense of the radial component of the in-plane velocity at a resonance radius. Using simulations we show that we would expect to find these changes at corotation radii with a weaker effect at the Lindblad resonances. The method works well with observations at high spectral and angular resolutions, and is suited to the analysis of two-dimensional velocity fields in Hα from Fabry-Perot spectroscopy. We find clear indications of resonance effects in the disk velocity fields of virtually all of the 104 galaxies. The number of resonance radii detected ranges from one to seven, with a median of four. The frequency curves Ω, Ω ± κ/2, Ω ± κ/4 against radius for all the galaxies led us to discover a pattern in over 70% of the sample: given two pattern speeds, say Ω1 and Ω2, the OLR of Ω1 coincides with the corotation of Ω2, and the inner 4:1 resonance of Ω2 coincides with the corotation of Ω1. Although the second coincidence has been predicted, a prediction of this double coincidence is not found in the literature. This pattern is found once in 42 of the galaxies, twice in a further 26, three times in 5, and even four times in 1 galaxy. We also compute the ratio of corotation radius to bar length where we have sufficient image quality, finding a mean value of 1.3, and a shallow increase toward later type galaxies