Last glacial vegetation of northern Eurasia

In order to investigate the potential role of vegetation changes in megafaunal extinctions during the later part of the last glacial stage and early Holocene (42–10 ka BP), the palaeovegetation of northern Eurasia and Alaska was simulated using the LPJ-GUESS dynamic vegetation model. Palaeoclimatic driving data were derived from simulations made for 22 time slices using the Hadley Centre Unified Model. Modelled annual net primary productivity (aNPP) of a series of plant functional types (PFTs) is mapped for selected time slices and summarised for major geographical regions for all time slices. Strong canonical correlations are demonstrated between model outputs and pollen data compiled for the same period and region. Simulated aNPP values, especially for tree PFTs and for a mesophilous herb PFT, provide evidence of the structure and productivity of last glacial vegetation. The mesophilous herb PFT aNPP is higher in many areas during the glacial than at present or during the early Holocene. Glacial stage vegetation, whilst open and largely treeless in much of Europe, thus had a higher capacity to support large vertebrate herbivore populations than did early Holocene vegetation. A marked and rapid decrease in aNPP of mesophilous herbs began shortly after the Last Glacial Maximum, especially in western Eurasia. This is likely implicated in extinction of several large herbivorous mammals during the latter part of the glacial stage and the transition to the Holocene.

A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets

Proneural genes such as Ascl1 are known to promote cell cycle exit and neuronal differentiation when expressed in neural progenitor cells. The mechanisms by which proneural genes activate neurogenesis--and, in particular, the genes that they regulate--however, are mostly unknown. We performed a genome-wide characterization of the transcriptional targets of Ascl1 in the embryonic brain and in neural stem cell cultures by location analysis and expression profiling of embryos overexpressing or mutant for Ascl1. The wide range of molecular and cellular functions represented among these targets suggests that Ascl1 directly controls the specification of neural progenitors as well as the later steps of neuronal differentiation and neurite outgrowth. Surprisingly, Ascl1 also regulates the expression of a large number of genes involved in cell cycle progression, including canonical cell cycle regulators and oncogenic transcription factors. Mutational analysis in the embryonic brain and manipulation of Ascl1 activity in neural stem cell cultures revealed that Ascl1 is indeed required for normal proliferation of neural progenitors. This study identified a novel and unexpected activity of the proneural gene Ascl1, and revealed a direct molecular link between the phase of expansion of neural progenitors and the subsequent phases of cell cycle exit and neuronal differentiation.

Anisotropic model for granulated sea ice dynamics

A continuum model describing sea ice as a layer of granulated thick ice, consisting of many rigid, brittle floes, intersected by long and narrow regions of thinner ice, known as leads, is developed. We consider the evolution of mesoscale leads, formed under extension, whose lengths span many floes, so that the surrounding ice is treated as a granular plastic. The leads are sufficiently small with respect to basin scales of sea ice deformation that they may be modelled using a continuum approach. The model includes evolution equations for the orientational distribution of leads, their thickness and width expressed through second-rank tensors and terms requiring closures. The closing assumptions are constructed for the case of negligibly small lead ice thickness and the canonical deformation types of pure and simple shear, pure divergence and pure convergence. We present a new continuum-scale sea ice rheology that depends upon the isotropic, material rheology of sea ice, the orientational distribution of lead properties and the thick ice thickness. A new model of lead and thick ice interaction is presented that successfully describes a number of effects: (i) because of its brittle nature, thick ice does not thin under extension and (ii) the consideration of the thick sea ice as a granular material determines finite lead opening under pure shear, when granular dilation is unimportant.

The global effect of follicle-stimulating hormone and tumour necrosis factor α on gene expression in cultured bovine ovarian granulosa cells

Background Oocytes mature in ovarian follicles surrounded by granulosa cells. During follicle growth, granulosa cells replicate and secrete hormones, particularly steroids close to ovulation. However, most follicles cease growing and undergo atresia or regression instead of ovulating. To investigate the effects of stimulatory (follicle-stimulating hormone; FSH) and inhibitory (tumour necrosis factor alpha; TNFα) factors on the granulosa cell transcriptome, bovine ovaries were obtained from a local abattoir and pools of granulosa cells were cultured in vitro for six days under defined serum-free conditions with treatments present on days 3–6. Initially dose–response experiments (n = 4) were performed to determine the optimal concentrations of FSH (0.33 ng/ml) and TNFα (10 ng/ml) to be used for the microarray experiments. For array experiments cells were cultured under control conditions, with FSH, with TNFα, or with FSH plus TNFα (n = 4 per group) and RNA was harvested for microarray analyses. Results Statistical analysis showed primary clustering of the arrays into two groups, control/FSH and TNFα/TNFα plus FSH. The effect of TNFα on gene expression dominated that of FSH, with substantially more genes differentially regulated, and the pathways and genes regulated by TNFα being similar to those of FSH plus TNFα treatment. TNFα treatment reduced the endocrine activity of granulosa cells with reductions in expression of FST, INHA, INBA and AMH. The top-ranked canonical pathways and GO biological terms for the TNFα treatments included antigen presentation, inflammatory response and other pathways indicative of innate immune function and fibrosis. The two most significant networks also reflect this, containing molecules which are present in the canonical pathways of hepatic fibrosis/hepatic stellate cell activation and transforming growth factor β signalling, and these were up regulated. Upstream regulator analyses also predicted TNF, interferons γ and β1 and interleukin 1β. Conclusions In vitro, the transcriptome of granulosa cells responded minimally to FSH compared with the response to TNFα. The response to TNFα indicated an active process akin to tissue remodelling as would occur upon atresia. Additionally there was reduction in endocrine function and induction of an inflammatory response to TNFα that displays features similar to immune cells.

The Landau free energy of hard ellipses obtained from microscopic simulations

Systems of two-dimensional hard ellipses of varying aspect ratios and packing fractions are studied by Monte Carlo simulations in the generalised canonical ensemble. From this microscopic model, we extract a coarse-grained macroscopic Landau-de Gennes free energy as a function of packing fraction and orientational order parameter. We separate the free energy into the ideal orientational entropy of non-interacting two-dimensional spins and an excess free energy associated with excluded volume interactions. We further explore the isotropic-nematic phase transition using our empirical expression for the free energy and find that the nature of the phase transition is continuous for the aspect ratios we studied.

Propagation of the Madden-Julian Oscillation through the Maritime Continent and scale interaction with the diurnal cycle of precipitation

The convectively active part of the Madden-Julian Oscillation (MJO) propagates eastward through the warm pool, from the Indian Ocean through the Maritime Continent (the Indonesian archipelago) to the western Pacific. The Maritime Continent's complex topography means the exact nature of the MJO propagation through this region is unclear. Model simulations of the MJO are often poor over the region, leading to local errors in latent heat release and global errors in medium-range weather prediction and climate simulation. Using 14 northern winters of TRMM satellite data it is shown that, where the mean diurnal cycle of precipitation is strong, 80% of the MJO precipitation signal in the Maritime Continent is accounted for by changes in the amplitude of the diurnal cycle. Additionally, the relationship between outgoing long-wave radiation (OLR) and precipitation is weakened here, such that OLR is no longer a reliable proxy for precipitation. The canonical view of the MJO as the smooth eastward propagation of a large-scale precipitation envelope also breaks down over the islands of the Maritime Continent. Instead, a vanguard of precipitation (anomalies of 2.5 mm day^-1 over 10^6 km^2) jumps ahead of the main body by approximately 6 days or 2000 km. Hence, there can be enhanced precipitation over Sumatra, Borneo or New Guinea when the large-scale MJO envelope over the surrounding ocean is one of suppressed precipitation. This behaviour can be accommodated into existing MJO theories. Frictional and topographic moisture convergence and relatively clear skies ahead of the main convective envelope combine with the low thermal inertia of the islands, to allow a rapid response in the diurnal cycle which rectifies onto the lower-frequency MJO. Hence, accurate representations of the diurnal cycle and its scale interaction appear to be necessary for models to simulate the MJO successfully.

Discovery of a mammalian splice variant of myostatin that stimulates myogenesis

Myostatin plays a fundamental role in regulating the size of skeletal muscles. To date, only a single myostatin gene and no splice variants have been identified in mammals. Here we describe the splicing of a cryptic intron that removes the coding sequence for the receptor binding moiety of sheep myostatin. The deduced polypeptide sequence of the myostatin splice variant (MSV) contains a 256 amino acid N-terminal domain, which is common to myostatin, and a unique C-terminus of 65 amino acids. Western immunoblotting demonstrated that MSV mRNA is translated into protein, which is present in skeletal muscles. To determine the biological role of MSV, we developed an MSV over-expressing C2C12 myoblast line and showed that it proliferated faster than that of the control line in association with an increased abundance of the CDK2/Cyclin E complex in the nucleus. Recombinant protein made for the novel C-terminus of MSV also stimulated myoblast proliferation and bound to myostatin with high affinity as determined by surface plasmon resonance assay. Therefore, we postulated that MSV functions as a binding protein and antagonist of myostatin. Consistent with our postulate, myostatin protein was co-immunoprecipitated from skeletal muscle extracts with an MSV-specific antibody. MSV over-expression in C2C12 myoblasts blocked myostatin-induced Smad2/3-dependent signaling, thereby confirming that MSV antagonizes the canonical myostatin pathway. Furthermore, MSV over expression increased the abundance of MyoD, Myogenin and MRF4 proteins (P,0.05), which indicates that MSV stimulates myogenesis through the induction of myogenic regulatory factors. To help elucidate a possible role in vivo, we observed that MSV protein was more abundant during early post-natal muscle development, while myostatin remained unchanged, which suggests that MSV may promote the growth of skeletal muscles. We conclude that MSV represents a unique example of intra-genic regulation in which a splice variant directly antagonizes the biological activity of the canonical gene product.

Nuclear Factor-kappaB controls the reaggregation of 3D neurosphere cultures in vitro

The approach of reaggregation involves the regeneration and self-renewal of histotypical 3D spheres from isolated tissue kept in suspension culture. Reaggregated spheres can be used as tumour, genetic, biohybrid and neurosphere models. In addition the functional superiority of 3D aggregates over conventional 2D cultures developed the use of neurospheres for brain engineering of CNS diseases. Thus 3D aggregate cultures created enormous interest in mechanisms that regulate the formation of multicellular aggregates in vitro. Here we analyzed mechanisms guiding the development of 3D neurosphere cultures. Adult neural stem cells can be cultured as self-adherent clusters, called neurospheres. Neurospheres are characterised as heterogeneous clusters containing unequal stem cell sub-types. Tumour necrosis factor-alpha (TNF-alpha is one of the crucial inflammatory cytokines with multiple actions on several cell types. TNF-alpha strongly activates the canonical Nuclear Factor Kappa-B (NF- kappaB) pathway. In order to investigate further functions of TNF in neural stem cells (NSCs) we tested the hypothesis that TNF is able to modulate the motility and/or migratory behaviour of SVZ derived adult neural stem cells. We observed a significantly faster sphere formation in TNF treated cultures than in untreated controls. The very fast aggregation of isolated NSCs (<2h) is a commonly observed phenomenon, though the mechanisms of 3D neurosphere formation remain largely unclear. Here we demonstrate for the first time, increased aggregation and enhanced motility of isolated NSCs in response to the TNF-stimulus. Moreover, this phenomenon is largely dependent on activated transcription factor NF-kappaB. Both, the pharmacological blockade of NF-kappaB pathway by pyrrolidine dithiocarbamate (PDTC) or Bay11-7082 and genetic blockade by expression of a transdominant-negative super-repressor IkappaB-AA1 led to decreased aggregation.

Tumor necrosis factor alpha triggers proliferation of adult neural stem cells via IKK/NF-kappaB signaling

BACKGROUND: Brain inflammation has been recognized as a complex phenomenon with numerous related aspects. In addition to the very well-described neurodegenerative effect of inflammation, several studies suggest that inflammatory signals exert a potentially positive influence on neural stem cell proliferation, migration and differentiation. Tumor necrosis factor alpha (TNF-alpha) is one of the best-characterized mediators of inflammation. To date, conclusions about the action of TNF on neural stem or progenitor cells (NSCs, NPCs) have been conflicting. TNF seems to activate NSC proliferation and to inhibit their differentiation into NPCs. The purpose of the present study was to analyze the molecular signal transduction mechanisms induced by TNF and resulting in NSC proliferation. RESULTS: Here we describe for the first time the TNF-mediated signal transduction cascade in neural stem cells (NSCs) that results in increased proliferation. Moreover, we demonstrate IKK-alpha/beta-dependent proliferation and markedly up-regulated cyclin D1 expression after TNF treatment. The significant increase in proliferation in TNF-treated cells was indicated by increased neurosphere volume, increased bromodeoxyuridin (BrdU) incorporation and a higher total cell number. Furthermore, TNF strongly activated nuclear factor-kappa B (NF-kappaB) as measured by reporter gene assays and by an activity-specific antibody. Proliferation of control and TNF-treated NSCs was strongly inhibited by expression of the NF-kappaB super-repressor IkappaB-AA1. Pharmacological blockade of IkappaB ubiquitin ligase activity led to comparable decreases in NF-kappaB activity and proliferation. In addition, IKK-beta gene product knock-down via siRNA led to diminished NF-kappaB activity, attenuated cyclin D1 expression and finally decreased proliferation. In contrast, TGFbeta-activated kinase 1 (TAK-1) is partially dispensable for TNF-mediated and endogenous proliferation. Understanding stem cell proliferation is crucial for future regenerative and anti-tumor medicine. CONCLUSION: TNF-mediated activation of IKK-beta resulted in activation of NF-kappaB and was followed by up-regulation of the bona-fide target gene cyclin D1. Activation of the canonical NF-kappaB pathway resulted in strongly increased proliferation of NSCs.

Parasitoids select plants more heavily infested with their caterpillar hosts: a new approach to aid interpretation of plant headspace volatiles

Plants produce volatile organic compounds (VOCs) in response to herbivore attack, and these VOCs can be used by parasitoids of the herbivore as host location cues. We investigated the behavioural responses of the parasitoid Cotesia vestalis to VOCs from a plant–herbivore complex consisting of cabbage plants (Brassica oleracea) and the parasitoids host caterpillar, Plutella xylostella. A Y-tube olfactometer was used to compare the parasitoids' responses to VOCs produced as a result of different levels of attack by the caterpillar and equivalent levels of mechanical damage. Headspace VOC production by these plant treatments was examined using gas chromatography–mass spectrometry. Cotesia vestalis were able to exploit quantitative and qualitative differences in volatile emissions, from the plant–herbivore complex, produced as a result of different numbers of herbivores feeding. Cotesia vestalis showed a preference for plants with more herbivores and herbivore damage, but did not distinguish between different levels of mechanical damage. Volatile profiles of plants with different levels of herbivores/herbivore damage could also be separated by canonical discriminant analyses. Analyses revealed a number of compounds whose emission increased significantly with herbivore load, and these VOCs may be particularly good indicators of herbivore number, as the parasitoid processes cues from its external environment

Automated identification of neural correlates of continuous variables

Background: The electroencephalogram (EEG) may be described by a large number of different feature types and automated feature selection methods are needed in order to reliably identify features which correlate with continuous independent variables. New method: A method is presented for the automated identification of features that differentiate two or more groups inneurologicaldatasets basedupona spectraldecompositionofthe feature set. Furthermore, the method is able to identify features that relate to continuous independent variables. Results: The proposed method is first evaluated on synthetic EEG datasets and observed to reliably identify the correct features. The method is then applied to EEG recorded during a music listening task and is observed to automatically identify neural correlates of music tempo changes similar to neural correlates identified in a previous study. Finally,the method is applied to identify neural correlates of music-induced affective states. The identified neural correlates reside primarily over the frontal cortex and are consistent with widely reported neural correlates of emotions. Comparison with existing methods: The proposed method is compared to the state-of-the-art methods of canonical correlation analysis and common spatial patterns, in order to identify features differentiating synthetic event-related potentials of different amplitudes and is observed to exhibit greater performance as the number of unique groups in the dataset increases. Conclusions: The proposed method is able to identify neural correlates of continuous variables in EEG datasets and is shown to outperform canonical correlation analysis and common spatial patterns.

Generic intertextuality in online social activism: the case of the It Gets Better project

The It Gets Better project has been held up as a model of successful social media activism. This article explores how narrators of It Gets Better videos make use of generic intertextuality, strategically combining the canonical narrative genres of the exemplum, the testimony, and the confession in a way that allows them to claim ‘textual authority’ and to make available multiple moral positions for themselves and their listeners. This strategy is further facilitated by the ambiguous participation frameworks associated with digital media, which make it possible for storytellers to tell different kinds of stories to different kinds of listeners at the same time, to simultaneously comfort the victims of anti-gay violence, confront its perpetrators, and elicit sympathy from ‘onlookers’. This analysis highlights the potential of new practices of online storytelling for social activism, and challenges notions that new media are contributing to the demise of common narrative traditions.

The politics of slowness and the traps of modernity

This chapter re-evaluates the diachronic, evolutionist model that establishes the Second World War as a watershed between classical and modern cinemas, and ‘modernity’ as the political project of ‘slow cinema’. I will start by historicising the connection between cinematic speed and modernity, going on to survey the veritable obsession with the modern that continues to beset film studies despite the vagueness and contradictions inherent in the term. I will then attempt to clarify what is really at stake within the modern-classical debate by analysing two canonical examples of Japanese cinema, drawn from the geidomono genre (films on the lives of theatre actors), Kenji Mizoguchi’s Story of the Late Chrysanthemums (Zangiku monogatari, 1939) and Yasujiro Ozu’s Floating Weeds (Ukigusa, 1954), with a view to investigating the role of the long take or, conversely, classical editing, in the production or otherwise of a supposed ‘slow modernity’. By resorting to Ozu and Mizoguchi, I hope to demonstrate that the best narrative films in the world have always combined a ‘classical’ quest for perfection with the ‘modern’ doubt of its existence, hence the futility of classifying cinema in general according to an evolutionary and Eurocentric model based on the classical-modern binary. Rather than on a confusing politics of the modern, I will draw on Bazin’s prophetic insight of ‘impure cinema’, a concept he forged in defence of literary and theatrical screen adaptations. Anticipating by more than half a century the media convergence on which the near totality of our audiovisual experience is currently based, ‘impure cinema’ will give me the opportunity to focus on the confluence of film and theatre in these Mizoguchi and Ozu films as the site of a productive crisis where established genres dissolve into self-reflexive stasis, ambiguity of expression and the revelation of the reality of the film medium, all of which, I argue, are more reliable indicators of a film’s political programme than historical teleology. At the end of the journey, some answers may emerge to whether the combination of the long take and the long shot are sufficient to account for a film’s ‘slowness’ and whether ‘slow’ is indeed the best concept to signify resistance to the destructive pace of capitalism.

Environmental controls on the distribution and diversity of lentic Chironomidae (Insecta: Diptera) across an altitudinal gradient in tropical South America

To predict the response of aquatic ecosystems to future global climate change, data on the ecology and distribution of keystone groups in freshwater ecosystems are needed. In contrast to mid- and high-latitude zones, such data are scarce across tropical South America (Neotropics). We present the distribution and diversity of chironomid species using surface sediments of 59 lakes from the Andes to the Amazon (0.1–17°S and 64–78°W) within the Neotropics. We assess the spatial variation in community assemblages and identify the key variables influencing the distributional patterns. The relationships between environmental variables (pH, conductivity, depth, and sediment organic content), climatic data, and chironomid assemblages were assessed using multivariate statistics (detrended correspondence analysis and canonical correspondence analysis). Climatic parameters (temperature and precipitation) were most significant in describing the variance in chironomid assemblages. Temperature and precipitation are both predicted to change under future climate change scenarios in the tropical Andes. Our findings suggest taxa of Orthocladiinae, which show a preference to cold high-elevation oligotrophic lakes, will likely see range contraction under future anthropogenic-induced climate change. Taxa abundant in areas of high precipitation, such as Micropsectra and Phaenopsectra, will likely become restricted to the inner tropical Andes, as the outer tropical Andes become drier. The sensitivity of chironomids to climate parameters makes them important bio-indicators of regional climate change in the Neotropics. Furthermore, the distribution of chironomid taxa presented here is a vital first step toward providing urgently needed autecological data for interpreting fossil chironomid records of past ecological and climate change from the tropical Andes.

Finality revived: powers and intentionality

Proponents of physical intentionality argue that the classic hallmarks of intentionality highlighted by Brentano are also found in purely physical powers. Critics worry that this idea is metaphysically obscure at best, and at worst leads to panpsychism or animism. I examine the debate in detail, finding both confusion and illumination in the physical intentionalist thesis. Analysing a number of the canonical features of intentionality, I show that they all point to one overarching phenomenon of which both the mental and the physical are kinds, namely finality. This is the finality of ‘final causes’, the long-discarded idea of universal action for an end to which recent proponents of physical intentionality are in fact pointing whether or not they realise it. I explain finality in terms of the concept of specific indifference, arguing that in the case of the mental, specific indifference is realised by the process of abstraction, which has no correlate in the case of physical powers. This analysis, I conclude, reveals both the strength and weakness of rational creatures such as us, as well as demystifying (albeit only partly) the way in which powers work.