Drought response of five conifer species under contrasting water availability suggests high vulnerability of Norway spruce and European larch.

The ability of tree species to cope with anticipated decrease in water availability is still poorly understood. We evaluated the potential of Norway spruce, Scots pine, European larch, black pine, and Douglas-fir to withstand drought in a drier future climate by analyzing their past growth and physiological responses at a xeric and a mesic site in Central Europe using dendroecological methods. Earlywood, latewood, and total ring width, as well as the δ(13) C and δ(18) O in early- and latewood were measured and statistically related to a multiscalar soil water deficit index from 1961 to 2009.

Structure and dynamics in yttrium-based molten rare earth alkali fluorides.

The transport properties of molten LiF-YF3 mixtures have been studied by pulsed field gradient nuclear magnetic resonance spectroscopy, potentiometric experiments, and molecular dynamics simulations. The calculated diffusion coefficients and electric conductivities compare very well with the measurements across a wide composition range. We then extract static (radial distribution functions, coordination numbers distributions) and dynamic (cage correlation functions) quantities from the simulations.

The effect of targeted rheumatoid arthritis therapies on anti-citrullinated protein autoantibody levels and B cell responses.

Rheumatoid arthritis (RA) is a complex inflammatory disorder associated with synovitis and joint destruction that affects an estimated 1·3 million Americans and causes significant morbidity, a reduced life-span and lost work productivity. The use of biological therapies for the treatment of RA is costly, and the selection of therapies is still largely empirical and not guided by the underlying biological features of the disease in individual patients. The synovitis associated with RA is characterized by an influx of B and T cells, macrophages and neutrophils and the expansion of fibroblast-like synoviocytes, which form pannus and lead to cartilage and bone destruction.

Temporal lobe epileptiform activity following systemic administration of 4-aminopyridine in rats.

Purpose:   The K(+) channel blocker 4-aminopyridine (4AP) induces epileptiform synchronization in brain slices maintained in vitro without interfering with γ-aminobutyric acid (GABA)A receptor-mediated inhibition and, actually, even enhancing it. The hypothesis that similar electrographic epileptiform patterns occur in vivo following systemic 4AP injection was tested here.

Methods:   Sprague-Dawley rats (n = 13) were implanted with bipolar electrodes aimed at the hippocampal CA3 region, entorhinal cortex, subiculum, dentate gyrus, and amygdala.

Hypoxia contributes to melanoma heterogeneity by triggering HIF1α-dependent phenotype switching.

We have previously reported a model for melanoma progression in which oscillation between melanoma cell phenotypes characterized by invasion or proliferation is fundamental to tumor heterogeneity and disease progression. In this study we examine the possible role of hypoxia as one of the microenvironmental influences driving metastatic progression by promoting a switch from a proliferative to an invasive phenotype. Immunohistochemistry on primary human cutaneous melanoma biopsies showed intratumoral heterogeneity for cells expressing melanocytic markers, and a loss of these markers correlated with hypoxic regions.

New tools for the identification of developmentally regulated enhancer regions in embryonic and adult zebrafish.

We have conducted a screen to identify developmentally regulated enhancers that drive tissue-specific Gal4 expression in zebrafish. We obtained 63 stable transgenic lines with expression patterns in embryonic or adult zebrafish. The use of a newly identified minimal promoter from the medaka edar locus resulted in a relatively unbiased set of expression patterns representing many tissue types derived from all germ layers.

Looking beyond the DNA sequence: the relevance of DNA methylation processes for the stress-diathesis model of depression.

The functioning of the hypothalamic-pituitary-adrenal (HPA) axis and serotonergic (5-HT) system are known to be intertwined with mood. Alterations in these systems are often associated with depression. However, neither are sufficient to cause depression in and of themselves.

Molecular Density Functional Theory of Water.

Three-dimensional implementations of liquid-state theories offer an efficient alternative to computer simulations for the atomic-level description of aqueous solutions in complex environments. In this context, we present a (classical) molecular density functional theory (MDFT) of water that is derived from first principles and is based on two classical density fields, a scalar one, the particle density, and a vectorial one, the multipolar polarization density. Its implementation requires as input the partial charge distribution of a water molecule and three measurable bulk properties, namely, the structure factor and the k-dependent longitudinal and transverse dielectric constants.

The maternal transcriptome of the crustacean Parhyale hawaiensis is inherited asymmetrically to invariant cell lineages of the ectoderm and mesoderm.

Background: The embryo of the crustacean Parhyale hawaiensis has a total, unequal and invariant early cleavage pattern. It specifies cell fates earlier than other arthropods, including Drosophila, as individual blastomeres of the 8-cell stage are allocated to the germ layers and the germline. Furthermore, the 8-cell stage is amenable to embryological manipulations.

Single-chromosome transcriptional profiling reveals chromosomal gene expression regulation.

We report intron chromosomal expression FISH (iceFISH), a multiplex imaging method for measuring gene expression and chromosome structure simultaneously on single chromosomes. We find substantial differences in transcriptional frequency between genes on a translocated chromosome and the same genes in their normal chromosomal context in the same cell. Correlations between genes on a single chromosome pointed toward a cis chromosome-level transcriptional interaction spanning 14.

Melanoma immunotherapy: historical precedents, recent successes and future prospects.

The idea of cancer immunotherapy has been around for more than a century; however, the first immunotherapeutic ipilimumab, an anti-CTLA-4 antibody, has only recently been approved by the US FDA for melanoma. With an increasing understanding of the immune response, it is expected that more therapies will follow. This review aims to provide a general overview of immunotherapy in melanoma.

Identification of workers exposed concomitantly to heat stress and chemicals.

In the context of climate change, concomitant exposure to heat stress and chemicals takes on great importance. However, little information is available in this regard. The purpose of this research, therefore, was to develop an approach aimed at identifying worker groups that would be potentially most at risk.

Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism.

Autosomal-recessive albinism is a hypopigmentation disorder with a broad phenotypic range. A substantial fraction of individuals with albinism remain genetically unresolved, and it has been hypothesized that more genes are to be identified. By using homozygosity mapping of an inbred Faroese family, we identified a 3.

Genetic lineage labeling in zebrafish uncovers novel neural crest contributions to the head, including gill pillar cells.

At the protochordate-vertebrate transition, a new predatory lifestyle and increased body size coincided with the appearance of a true head. Characteristic innovations of this head are a skull protecting and accommodating a centralized nervous system, a jaw for prey capture and gills as respiratory organs. The neural crest (NC) is a major ontogenetic source for the 'new head' of vertebrates and its contribution to the cranial skeleton has been intensively studied in different model organisms.

Molecular diffusion between walls with adsorption and desorption.

The time dependency of the diffusion coefficient of particles in porous media is an efficient probe of their geometry. The analysis of this quantity, measured, e.g.

Rituximab therapy for primary Sjögren's syndrome: an open-label clinical trial and mechanistic analysis.

Objective: To study the safety and clinical efficacy of rituximab therapy for primary Sjögren's syndrome, as well as to investigate its mechanisms.

Methods: Patients with primary Sjögren's syndrome were enrolled in an open-label trial, were given rituximab (1 gm) infusions on days 1 and 15, and were monitored through week 52. The primary end point was safety, with secondary end points evaluating clinical and biologic efficacy.

Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance.

Mutational activation of BRAF is the most prevalent genetic alteration in human melanoma, with ≥50% of tumours expressing the BRAF(V600E) oncoprotein. Moreover, the marked tumour regression and improved survival of late-stage BRAF-mutated melanoma patients in response to treatment with vemurafenib demonstrates the essential role of oncogenic BRAF in melanoma maintenance. However, as most patients relapse with lethal drug-resistant disease, understanding and preventing mechanism(s) of resistance is critical to providing improved therapy.

Two different interictal spike patterns anticipate ictal activity in vitro.

4-Aminopyridine (4AP, 50 μM) induces interictal- and ictal-like discharges in brain slices including parahippocampal areas such as the entorhinal cortex (EC) but the relation between these two types of epileptiform activity remains undifined. Here, by employing field potential recordings in rat EC slices during 4AP application, we found that: (i) interictal events have a wide range of duration (0.4-3.

Patients with idiopathic pulmonary fibrosis with antibodies to heat shock protein 70 have poor prognoses.

Rationale: Diverse autoantibodies are present in most patients with idiopathic pulmonary fibrosis (IPF). We hypothesized that specific autoantibodies may associate with IPF manifestations.

Objectives: To identify clinically relevant, antigen-specific immune responses in patients with IPF.

Solvation of complex surfaces via molecular density functional theory.

We show that classical molecular density functional theory, here in the homogeneous reference fluid approximation in which the functional is inferred from the properties of the bulk solvent, is a powerful new tool to study, at a fully molecular level, the solvation of complex surfaces and interfaces by polar solvents. This implicit solvent method allows for the determination of structural, orientational, and energetic solvation properties that are on a par with all-atom molecular simulations performed for the same system, while reducing the computer time by two orders of magnitude. This is illustrated by the study of an atomistically-resolved clay surface composed of over a thousand atoms wetted by a molecular dipolar solvent.

Centrosome loss or amplification does not dramatically perturb global gene expression in Drosophila.

Centrosome defects are a common feature of many cancers, and they can predispose fly brain cells to form tumours. In flies, centrosome defects perturb the asymmetric division of the neural stem cells, but it is unclear how this might lead to malignant transformation. One possibility is that centrosome defects might also perturb cellular homeostasis: for example, stress pathways are often activated in response to centrosome defects in cultured cells, and stress contributes to tumourigenesis in some fly models.

Real-life experience with pegylated interferon and conventional interferon in adjuvant melanoma therapy.

Interferon (IFN) is the most studied and the only approved adjuvant therapy for melanoma. There are 2 formulations of IFN, conventional IFN and pegylated IFN (peg-IFN), which have been investigated in multiple randomized clinical trials. We have compared the feasibility and tolerability of low-dose conventional IFN and peg-IFN in real life, outside the controlled settings of clinical trials.

Pain perception in schizophrenia: evidence of a specific pain response profile.

Objective: Ever since the characterization of schizophrenia, clinicians have noted abnormal pain sensitivity in their patients. The published literature, however, is inconsistent concerning the nature of the change reported. The objective of this study was to characterize the pain response profile of schizophrenic patients by providing both acute and prolonged (i.

Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial.

Objective: To assess the safety and efficacy of rituximab in a randomized, double-blind, placebo-phase trial in adult and pediatric myositis patients.

Methods: Adults with refractory polymyositis (PM) and adults and children with refractory dermatomyositis (DM) were enrolled. Entry criteria included muscle weakness and ≥2 additional abnormal values on core set measures (CSMs) for adults.