Eastern tropical Pacific corals monitor low latitude climate of the past 400 years

EXTRACT (SEE PDF FOR FULL ABSTRACT): We have measured coral growth band thickness and skeletal stable isotopic composition through a 371-year transect (AD 1583-1954) from a massive specimen of Pavona clavus from the Galápagos Islands. ... We observe a general cooling trend during 1860-1954, corresponding to the end of the Little Ice Age, an interval characterized by general warming at many mid-latitude sites. Variance at sunspot cycle frequencies in growth rate, stable isotopic, and trace element composition implies a direct or indirect link between the solar cycle and climate modulation in the eastern Pacific.

Paleorecords of interdecadal variability from mid-latitude varved sediments and tropical corals of the eastern Pacific [abstract]

EXTRACT (SEE PDF FOR FULL ABSTRACT): Reconstruction of proxy variables from massive corals and varved sediments of the eastern Pacific allow us to compare variability in the ocean climate from equatorial and mid-latitude sites for a significantly longer period than is available from the instrumental record.

Oceanographic variability at Clipperton Atoll since the 1880s: stable isotopic evidence from massive corals [abstract]

EXTRACT (SEE PDF FOR FULL ABSTRACT): Clipperton Atoll (10°18'N, 109°13'W), lies within the eastern Pacific elongated warm water pool centered at 10°N and is situated at the boundary of the North Equatorial Counter-Current (NECC) and westward-flowing eddy currents moving away from Central America. ... Fifteen coral cores were collected from massive heads of Porites lobata in April 1994 for the purpose of reconstructing oceanographic and climatic conditions at this open ocean site in the eastern Pacific.

Oxygen isotope analysis of corals from the Gulf of California and the Gulf of Panama: application and implications for coral-based paleoclimate reconstructions [abstract]

EXTRACT (SEE PDF FOR FULL ABSTRACT): Coral-based reconstruction of past variability of sea surface conditions is improving our understanding of the tropical ocean-atmosphere system. We present oxygen isotope records from corals collected near the tip of Baja California (Baja) and the Gulf of Panama (Saboga).

Super-villains of the "real world": the political use of the characterization of villains in Chistopher Nolan's "Dark Knight Trilogy"

It is almost a tradition that celluloid (or digital) villains are represented with some characteristics that remind us the real political enemies of the producer country of the film, or even enemies within the country according to the particular ideology that sustains the film. The case of Christopher Nolan The Dark Knight trilogy, analyzed here, is representative of this trend for two reasons. First, because it gets marked by political radicalization conducted by the US government after the attack of September 11, 2001. Secondly, because it offers a profuse gallery of villains who are outside the circle of friends as the new doctrine “either with us or against us” opened by George Bush for the XXI century. This gallery includes from the very terrorists who justify the War on Terror (Ra's al Ghul, the Joker), to the “radical left” (Bane, Talia al Ghul) including liberal politicians (Harvey Dent), and corrupt that take advantage of the softness of the law to commit crimes with impunity (Dr. Crane, the Scarecrow).

Atomistic Insights into Rhodopsin Activation from a Dynamic Model

Rhodopsin, the light sensitive receptor responsible for blue-green vision, serves as a prototypical G protein-coupled receptor (GPCR). Upon light absorption, it undergoes a series of conformational changes that lead to the active form, metarhodopsin II (META II), initiating a signaling cascade through binding to the G protein transducin (G(t)). Here, we first develop a structural model of META II by applying experimental distance restraints to the structure of lumi-rhodopsin (LUMI), an earlier intermediate. The restraints are imposed by using a combination of biased molecular dynamics simulations and perturbations to an elastic network model. We characterize the motions of the transmembrane helices in the LUMI-to-META II transition and the rearrangement of interhelical hydrogen bonds. We then simulate rhodopsin activation in a dynamic model to study the path leading from LUMI to our META II model for wild-type rhodopsin and a series of mutants. The simulations show a strong correlation between the transition dynamics and the pharmacological phenotypes of the mutants. These results help identify the molecular mechanisms of activation in both wild type and mutant rhodopsin. While static models can provide insights into the mechanisms of ligand recognition and predict ligand affinity, a dynamic model of activation could be applicable to study the pharmacology of other GPCRs and their ligands, offering a key to predictions of basal activity and ligand efficacy.

Targeting treatment resistant breast cancer stem cells with FKBPL and its peptide derivative, AD-01, via the CD44 pathway

PURPOSE: FKBPL and its peptide derivative, AD-01, have already demonstrated tumour growth inhibition and CD44 dependent anti-angiogenic activity. Here we explore the ability of AD-01 to target CD44 positive breast cancer stem cells (BCSCs). EXPERIMENTAL DESIGN: Mammosphere assays and flow cytometry were utilized to analyse the effect of FKBPL overexpression/knockdown and AD-01 treatment ± other anti-cancer agents on BCSCs using breast cancer cell lines (MCF-7/MDA-231/ZR-75), primary patient samples and xenografts. Delays in tumour initiation were evaluated in vivo. The anti-stem cell mechanisms were determined using clonogenic assays, qPCR and immunofluorescence. RESULTS: AD-01 treatment was highly effective at inhibiting the BCSC population by reducing mammosphere forming efficiency (MFE) and ESA+/CD44+/CD24- or ALDH+ cell subpopulations in vitro and tumour initiation in vivo. The ability of AD-01 to inhibit the self-renewal capacity of BCSCs was confirmed; mammospheres were completely eradicated by the third generation. The mechanism appears to be due to AD-01-mediated BCSC differentiation demonstrated by a significant decrease in the number of holoclones and an associated increase in meroclones/paraclones; the stem cell markers, Nanog, Oct4 and Sox2, were also significantly reduced. Furthermore, we demonstrated additive inhibitory effects when AD-01 was combined with the Notch inhibitor, DAPT. AD-01 was also able to abrogate a chemo- and radiotherapy induced enrichment in BCSCs. Finally, FKBPL knockdown led to an increase in Nanog/Oct4/Sox2 and an increase in BCSCs, highlighting a role for endogenous FKBPL in stem cell signalling. CONCLUSIONS: AD-01 has dual anti-angiogenic and anti-BCSC activity which will be advantageous as this agent enters clinical trial.