Deterministically Driven Avalanche Models of Solar Flares

We develop and discuss the properties of a new class of lattice-based avalanche models of solar flares. These models are readily amenable to a relatively unambiguous physical interpretation in terms of slow twisting of a coronal loop. They share similarities with other avalanche models, such as the classical stick--slip self-organized critical model of earthquakes, in that they are driven globally by a fully deterministic energy loading process. The model design leads to a systematic deficit of small scale avalanches. In some portions of model space, mid-size and large avalanching behavior is scale-free, being characterized by event size distributions that have the form of power-laws with index values, which, in some parameter regimes, compare favorably to those inferred from solar EUV and X-ray flare data. For models using conservative or near-conservative redistribution rules, a population of large, quasiperiodic avalanches can also appear. Although without direct counterparts in the observational global statistics of flare energy release, this latter behavior may be relevant to recurrent flaring in individual coronal loops. This class of models could provide a basis for the prediction of large solar flares.Comment: 24 pages, 11 figures, 2 tables, accepted for publication in Solar Physic

Down, then up: non-parallel genome size changes and a descending chromosome series in a recent radiation of the Australian allotetraploid plant species, Nicotiana section Suaveolentes (Solanaceae)

Background and aims: The extent to which genome size and chromosome numbers evolve in concert is little understood, particularly after polyploidy (whole-genome duplication), when a genome returns to a diploid-like condition (diploidisation). We study this phenomenon in 46 species of allotetraploid Nicotiana section Suaveolentes (Solanaceae), which formed less than six million years ago and radiated in the arid centre of Australia.Methods: We analysed newly assessed genome sizes and chromosome numbers within the context of a restriction site-associated nuclear DNA (RADseq) phylogenetic framework.Key results: RADseq generated a well-supported phylogenetic tree, in which multiple accessions from each species formed unique genetic clusters. Chromosome numbers and genome sizes vary from n = 2x = 15-24 and 2.7-5.8 pg/1 C nucleus, respectively. Decreases in both genome size and chromosome number occur, although neither consistently nor in parallel. Species with the lowest chromosome numbers (n = 15-18) do not possess the smallest genome sizes, and although N. heterantha has retained the ancestral chromosome complement, n = 2x = 24, it nonetheless has the smallest genome size, even smaller than that of the modern representatives of ancestral diploids.Conclusions: The results indicate that decreases in genome size and chromosome number occur in parallel down to a chromosome number threshold, n = 20, below which genome size increases, a phenomenon potentially explained by decreasing rates of recombination over fewer chromosomes. We hypothesize that, more generally in plants, major decreases in genome size post-polyploidization take place while chromosome numbers are still high because in these stages elimination of retrotransposons and other repetitive elements is more efficient. Once such major genome size change has been accomplished, then dysploid chromosome reductions take place to reorganize these smaller genomes, producing species with small genomes and low chromosome numbers such as those observed in many annual angiosperms, including Arabidopsis. Mark W Chase, Rosabelle Samuel, Andrew R Leitch, Maïté S Guignard, John G Conran, Felipe Nollet, Paul Fletcher, Aljaž Jakob, Luiz A Cauz-Santos, Gabriel Vignolle, Steven Dodsworth, Maarten J M Christenhusz, Maria Teresa Buril, Ovidiu Pau

Anti-inflammatory phytotherapeutics: a valuable alternative to NSAID treatment in horses?

ABSTRACT In equine practice, phytotherapy is meeting the increasing demand of horse owners for "natural", safe treatment methods. Long-term use of NSAIDs can cause severe adverse effects, hence the growing popularity of anti-inflammatory phytotherapeutics. At the current time, several different herbal mixes are being commercialized, which makes it difficult for horse owners and veterinarians alike to make a well-founded choice. Harpagophytum procumbens (devil's claw), Salix spp. (willow) and Ribes nigrum (blackcurrant), three plants that are often used in these mixes, have been evaluated both in vitro and in vivo. Based on published studies and the evaluation of these studies, for example by the Cochrane Collaboration, there seems to be some evidence for Harpagophytum procumbens and Salix spp. having a stronger analgesic and anti-inflammatory effect than placebos in humans. In horses, however, only one limited clinical study on Harpagophytum has been performed up until now, while no studies were found on the use of Salix in horses. More research is needed before any claims concerning efficacy or safety can be made regarding the use of these plants in treating horses. It has also been claimed that Ribes nigrum leaves have an anti-inflammatory effect, though this has not yet been clinically proven either in humans or in horses. Although veterinary phytotherapy is as old as animal husbandry itself, little scientific proof can be found regarding its uses. More research is needed before phytotherapy can be advertised as a valuable and safe alternative to the more conventional treatment protocols. SAMENVATTING In de paardengeneeskunde is fytotherapie een antwoord op de toenemende vraag van eigenaren naar "natuurlijke", veilige behandelmethoden. Het langdurig gebruik van NSAID's kan ernstige bijwerkingen geven, vandaar de groeiende populariteit van ontstekingsremmende fytotherapeutica. Momenteel zijn er meerdere kruidenpreparaten commercieel beschikbaar maar het is moeilijk voor de paardeneigenaar en de dierenarts om hier een verantwoorde keuze uit te maken. Harpagophytum procumbens (duivelsklauw), Salix spp. (wilg) en Ribes nigrum (zwarte bes of cassisbes), drie planten die veel gebruikt worden in de commerciële preparaten, werden zowel in vitro als in vivo geëvalueerd. Op basis van gepubliceerde studies en de beoordeling van deze studies door onder andere de Cochrane Collaboration zijn er aanwijzingen dat Harpagophytum procumbens en Salix spp. bij de mens een groter analgetisch en ontstekingsremmend effect hebben dan een placebo. Bij paarden is er echter slechts één beperkte klinische studie met Harpagophytum uitgevoerd, en het effect van Salix werd nog nooit onderzocht. Om de werkzaamheid en veiligheid van deze planten bij het paard te kunnen beoordelen, dient er meer onderzoek verricht te worden. De bladeren van Ribes nigrum zouden ook een ontstekingsremmende werking hebben, maar dit is momenteel noch bij de mens, noch bij het paard klinisch aangetoond. Hoewel de veterinaire fytotherapie al even lang bestaat als de dierhouderij, is er weinig wetenschappelijk bewijs omtrent een efficiënte werking ervan. Vooraleer men de fytotherapie kan aanraden als een waardevol en veilig alternatief voor de conventionele behandelmethoden, is er duidelijk nog meer onderzoek nodig

The fundamental constants and their variation: observational status and theoretical motivations

This article describes the various experimental bounds on the variation of the fundamental constants of nature. After a discussion on the role of fundamental constants, of their definition and link with metrology, the various constraints on the variation of the fine structure constant, the gravitational, weak and strong interactions couplings and the electron to proton mass ratio are reviewed. This review aims (1) to provide the basics of each measurement, (2) to show as clearly as possible why it constrains a given constant and (3) to point out the underlying hypotheses. Such an investigation is of importance to compare the different results, particularly in view of understanding the recent claims of the detections of a variation of the fine structure constant and of the electron to proton mass ratio in quasar absorption spectra. The theoretical models leading to the prediction of such variation are also reviewed, including Kaluza-Klein theories, string theories and other alternative theories and cosmological implications of these results are discussed. The links with the tests of general relativity are emphasized.Comment: 56 pages, l7 figures, submitted to Rev. Mod. Phy

Evolutionary Changes in the Complexity of the Tectum of Nontetrapods: A Cladistic Approach

Background: The tectum is a structure localized in the roof of the midbrain in vertebrates, and is taken to be highly conserved in evolution. The present article assessed three hypotheses concerning the evolution of lamination and citoarchitecture of the tectum of nontetrapod animals: 1) There is a significant degree of phylogenetic inertia in both traits studied (number of cellular layers and number of cell classes in tectum); 2) Both traits are positively correlated accross evolution after correction for phylogeny; and 3) Different developmental pathways should generate different patterns of lamination and cytoarchitecture. Methodology/Principal Findings: The hypotheses were tested using analytical-computational tools for phylogenetic hypothesis testing. Both traits presented a considerably large phylogenetic signal and were positively associated. However, no difference was found between two clades classified as per the general developmental pathways of their brains. Conclusions/Significance: The evidence amassed points to more variation in the tectum than would be expected by phylogeny in three species from the taxa analysed; this variation is not better explained by differences in the main course of development, as would be predicted by the developmental clade hypothesis. Those findings shed new light on th

Monoclonal Antibodies Recognizing the Non-Tandem Repeat Regions of the Human Mucin MUC4 in Pancreatic Cancer

The MUC4 mucin is a high molecular weight, membrane-bound, and highly glycosylated protein. It is a multi-domain protein that is putatively cleaved into a large mucin-like subunit (MUC4α) and a C-terminal growth-factor like subunit (MUC4β). MUC4 plays critical roles in physiological and pathological conditions and is aberrantly overexpressed in several cancers, including those of the pancreas, cervix, breast and lung. It is also a potential biomarker for the diagnosis, prognosis and progression of several malignancies. Further, MUC4 plays diverse functional roles in cancer initiation and progression as evident from its involvement in oncogenic transformation, proliferation, inhibition of apoptosis, motility and invasion, and resistance to chemotherapy in human cancer cells. We have previously generated a monoclonal antibody 8G7, which is directed against the TR region of MUC4, and has been extensively used to study the expression of MUC4 in several malignancies. Here, we describe the generation of anti-MUC4 antibodies directed against the non-TR regions of MUC4. Recombinant glutathione-S-transferase (GST)-fused MUC4α fragments, both upstream (MUC4α-N-Ter) and downstream (MUC4α-C-Ter) of the TR domain, were used as immunogens to immunize BALB/c mice. Following cell fusion, hybridomas were screened using the aforementioned recombinant proteins ad lysates from human pancreatic cell lines. Three anti MUC4α-N-Ter and one anti-MUC4α-C-Ter antibodies were characterized by several inmmunoassays including enzyme-linked immunosorbent assay (ELISA), immunoblotting, immunofluorescene, flow cytometry and immunoprecipitation using MUC4 expressing human pancreatic cancer cell lines. The antibodies also reacted with the MUC4 in human pancreatic tumor sections in immunohistochemical analysis. The new domain-specific anti-MUC4 antibodies will serve as important reagents to study the structure-function relationship of MUC4 domains and for the development of MUC4-based diagnostics and therapeutics

MUC4 and MUC5AC are highly specific tumour-associated mucins in biliary tract cancer

Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase–PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) cases, but not in other benign and malignant biliary diseases (P<0.01 and P=0.06). qPCR revealed a 1.9-fold increased MUC4 mRNA expression in BTC patients' bile compared with benign disease. In archived tissues, MUC4 protein was detected in 37% of BTC but in none of the benign samples (P=0.03). In serum, MUC5AC was found exclusively in BTC and PSC sera (44% and 13%, respectively; P<0.001 for BTC vs non-BTC) and correlated negatively with BTC survival. Biliary MUC4 and serum MUC5AC are highly specific tumour-associated mucins that may be useful in the diagnosis and formulation of therapeutic strategies in BTC

Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH-expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation.

RATIONALE: Selective rapid eye movement sleep (REMS) deprivation using the platform-on-water ("flower pot") method causes sleep rebound with increased REMS, decreased REMS latency, and activation of the melanin-concentrating hormone (MCH) expressing neurons in the hypothalamus. MCH is implicated in the pathomechanism of depression regarding its influence on mood, feeding behavior, and REMS. OBJECTIVES: We investigated the effects of the most selective serotonin reuptake inhibitor escitalopram on sleep rebound following REMS deprivation and, in parallel, on the activation of MCH-containing neurons. METHODS: Escitalopram or vehicle (10 mg/kg, intraperitoneally) was administered to REMS-deprived (72 h) or home cage male Wistar rats. During the 3-h-long "rebound sleep", electroencephalography was recorded, followed by an MCH/Fos double immunohistochemistry. RESULTS: During REMS rebound, the time spent in REMS and the number of MCH/Fos double-labeled neurons in the lateral hypothalamus increased markedly, and REMS latency showed a significant decrease. All these effects of REMS deprivation were significantly attenuated by escitalopram treatment. Besides the REMS-suppressing effects, escitalopram caused an increase in amount of and decrease in latency of slow wave sleep during the rebound. CONCLUSIONS: These results show that despite the high REMS pressure caused by REMS deprivation procedure, escitalopram has the ability to suppress REMS rebound, as well as to diminish the activation of MCH-containing neurons, in parallel. Escitalopram caused a shift from REMS to slow wave sleep during the rebound. Furthermore, these data point to the potential connection between the serotonergic system and MCH in sleep regulation, which can be relevant in depression and in other mood disorders

Expression of Ksp-cadherin during kidney development and in renal cell carcinoma

Cadherins are a large family of cell–cell adhesion molecules acting in a homotypic, homophilic manner that play an important role in the maintenance of tissue integrity. In the human kidney, several members of the cadherin family (including E- and N-cadherin, cadherin-6, -8 and -11) are expressed in a controlled spatiotemporal pattern. Cadherin-16, also called kidney-specific (Ksp-) cadherin, is exclusively expressed in epithelial cells of the adult kidney. In renal cell carcinomas (RCCs), which are considered to originate from epithelial kidney tubular cells, a complex pattern of cadherin expression can be observed, but Ksp-cadherin expression has not been analysed so far. In the present study, we show that the expression of Ksp-cadherin is completely abrogated in RCCs. Whereas Ksp-cadherin can be detected at later stages of tubulogenesis during human renal development and in the distal tubules of adult kidneys, no expression was found by immunohistochemistry or Western blot analysis in RCC tumour tissues and several RCC cell lines. However, despite the lack of protein expression, mRNA synthesis of Ksp-cadherin could be detected by reverse transcriptase–polymerase chain reaction analysis in all RCC tissues and most of the RCC cell lines studied, although at a reduced level. The loss of Ksp-cadherin protein was only observed in the malignant part of the tumour kidneys, whereas in the normal part of the affected kidneys Ksp-cadherin expression was clearly detected. These results indicate a downregulation of Ksp-cadherin in RCC and suggest a role for this cell adhesion molecule in tumour suppression