Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase.

Propionyl-coenzyme A carboxylase (PCC), a mitochondrial biotin-dependent enzyme, is essential for the catabolism of the amino acids Thr, Val, Ile and Met, cholesterol and fatty acids with an odd number of carbon atoms. Deficiencies in PCC activity in humans are linked to the disease propionic acidaemia, an autosomal recessive disorder that can be fatal in infants. The holoenzyme of PCC is an alpha(6)beta(6) dodecamer, with a molecular mass of 750 kDa. The alpha-subunit contains the biotin carboxylase (BC) and biotin carboxyl carrier protein (BCCP) domains, whereas the beta-subunit supplies the carboxyltransferase (CT) activity. Here we report the crystal structure at 3.2-A resolution of a bacterial PCC alpha(6)beta(6) holoenzyme as well as cryo-electron microscopy (cryo-EM) reconstruction at 15-A resolution demonstrating a similar structure for human PCC. The structure defines the overall architecture of PCC and reveals unexpectedly that the alpha-subunits are arranged as monomers in the holoenzyme, decorating a central beta(6) hexamer. A hitherto unrecognized domain in the alpha-subunit, formed by residues between the BC and BCCP domains, is crucial for interactions with the beta-subunit. We have named it the BT domain. The structure reveals for the first time the relative positions of the BC and CT active sites in the holoenzyme. They are separated by approximately 55 A, indicating that the entire BCCP domain must translocate during catalysis. The BCCP domain is located in the active site of the beta-subunit in the current structure, providing insight for its involvement in the CT reaction. The structural information establishes a molecular basis for understanding the large collection of disease-causing mutations in PCC and is relevant for the holoenzymes of other biotin-dependent carboxylases, including 3-methylcrotonyl-CoA carboxylase (MCC) and eukaryotic acetyl-CoA carboxylase (ACC).

Phase Structure of Radar Stratigraphic Horizons Within Antarctic Firn

We have recorded reflection profiles of firn through large areas of West Antarctica and part of the East Antarctic plateau using 400 MHz short-pulse radar. The locations show accumulation rates that vary from well above to well below the vertical radar resolution. Most reflection horizons have extensive lateral continuity, and are composed of distinctive wavelets with a consistent phase polarity sequence within their successive half-cycles. We modeled these waveforms, and conclude that they arise from thin, double layers of ice over hoar, which is consistent with the standard model of firn stratification. In addition, we conclude that ice/hoar layers are extensive throughout West Antarctica and also present (although more sparsely) beneath the Antarctic Plateau.

Small-Scale Features of Marine Sediments and Their Importance to the Study of Deposit-Feeding

Techniques currently in use by sedimentologists for the study of marine sedment microfabric are of limited use for understandmg the relationship between sediment organic matter and mineral grains. In this article it is shown that by combining standard histological protocols for fixation and dehydration with petrological protocols for resin embedding and thin sectioning, very fine details of the sediment structure can be seen. Because of the ubiquitous presence of the organic matrix, organicmineral aggregates are not seen in situ. Other features of the sediment of importance to deposit-feeders, such as the presence of intact chloroplasts, can be observed through the use of epifluorescence illumination, while partially crossed polarizers help to delimit the grain boundaries. It is suggested that if these procedures can be combined with histological staining techniques, it may be possible to determine the potential food value of sedment on a scale equivalent to that perceived by infaunal deposit-feeders.

High-density large-scale field emitter arrays for x-ray free electron laser cathodes

High brightness electron sources are of great importance for the operation of the hard X-ray free electron lasers. Field emission cathodes based on the double-gate metallic field emitter arrays (FEAs) can potentially offer higher brightness than the currently used ones. We report on the successful application of electron beam lithography for fabrication of the large-scale single-gate as well as double-gate FEAs. We demonstrate operational high-density single-gate FEAs with sub-micron pitch and total number of tips up to 106 as well as large-scale double-gate FEAs with large collimation gate apertures. The details of design, fabrication procedure and successful measurements of the emission current from the single- and double-gate cathodes are presented.

Impartiality in humans is predicted by brain structure of dorsomedial prefrontal cortex.

The moral force of impartiality (i.e. the equal treatment of all human beings) is imperative for providing justice and fairness. Yet, in reality many people become partial during intergroup interactions; they demonstrate a preferential treatment of ingroup members and a discriminatory treatment of outgroup members. Some people, however, do not show this intergroup bias. The underlying sources of these inter-individual differences are poorly understood. Here we demonstrate that the larger the gray matter volume and thickness of the dorsomedial prefrontal cortex (DMPFC), the more individuals in the role of an uninvolved third-party impartially punish outgroup and ingroup perpetrators. Moreover, we show evidence for a possible mechanism that explains the impact of DMPFC's gray matter volume on impartiality, namely perspective-taking. Large gray matter volume of DMPFC seems to facilitate equal perspective-taking of all sides, which in turn leads to impartial behavior. This is the first evidence demonstrating that brain structure of the DMPFC constitutes an important source underlying an individual's propensity for impartiality.

Sparse computation for large-scale binary classification

Well-known data mining algorithms rely on inputs in the form of pairwise similarities between objects. For large datasets it is computationally impossible to perform all pairwise comparisons. We therefore propose a novel approach that uses approximate Principal Component Analysis to efficiently identify groups of similar objects. The effectiveness of the approach is demonstrated in the context of binary classification using the supervised normalized cut as a classifier. For large datasets from the UCI repository, the approach significantly improves run times with minimal loss in accuracy.

Altered structure of cortical sulci in gilles de la Tourette syndrome: Further support for abnormal brain development.

Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by the presence of motor and vocal tics. We hypothesized that patients with this syndrome would present an aberrant pattern of cortical formation, which could potentially reflect global alterations of brain development. Using 3 Tesla structural neuroimaging, we compared sulcal depth, opening, and length and thickness of sulcal gray matter in 52 adult patients and 52 matched controls. Cortical sulci were automatically reconstructed and identified over the whole brain, using BrainVisa software. We focused on frontal, parietal, and temporal cortical regions, in which abnormal structure and functional activity were identified in previous neuroimaging studies. Partial correlation analysis with age, sex, and treatment as covariables of noninterest was performed amongst relevant clinical and neuroimaging variables in patients. Patients with Gilles de la Tourette syndrome showed lower depth and reduced thickness of gray matter in the pre- and post-central as well as superior, inferior, and internal frontal sulci. In patients with associated obsessive-compulsive disorder, additional structural changes were found in temporal, insular, and olfactory sulci. Crucially, severity of tics and of obsessive-compulsive disorder measured by Yale Global Tic severity scale and Yale-Brown Obsessive-Compulsive scale, respectively, correlated with structural sulcal changes in sensorimotor, temporal, dorsolateral prefrontal, and middle cingulate cortical areas. Patients with Gilles de la Tourette syndrome displayed an abnormal structural pattern of cortical sulci, which correlated with severity of clinical symptoms. Our results provide further evidence of abnormal brain development in GTS. © 2015 International Parkinson and Movement Disorder Society.

Continental-Scale Footprint of Balancing and Positive Selection in a Small Rodent (Microtus arvalis)

Genetic adaptation to different environmental conditions is expected to lead to large differences between populations at selected loci, thus providing a signature of positive selection. Whereas balancing selection can maintain polymorphisms over long evolutionary periods and even geographic scale, thus leads to low levels of divergence between populations at selected loci. However, little is known about the relative importance of these two selective forces in shaping genomic diversity, partly due to difficulties in recognizing balancing selection in species showing low levels of differentiation. Here we address this problem by studying genomic diversity in the European common vole (Microtus arvalis) presenting high levels of differentiation between populations (average FST = 0.31). We studied 3,839 Amplified Fragment Length Polymorphism (AFLP) markers genotyped in 444 individuals from 21 populations distributed across the European continent and hence over different environmental conditions. Our statistical approach to detect markers under selection is based on a Bayesian method specifically developed for AFLP markers, which treats AFLPs as a nearly codominant marker system, and therefore has increased power to detect selection. The high number of screened populations allowed us to detect the signature of balancing selection across a large geographic area. We detected 33 markers potentially under balancing selection, hence strong evidence of stabilizing selection in 21 populations across Europe. However, our analyses identified four-times more markers (138) being under positive selection, and geographical patterns suggest that some of these markers are probably associated with alpine regions, which seem to have environmental conditions that favour adaptation. We conclude that despite favourable conditions in this study for the detection of balancing selection, this evolutionary force seems to play a relatively minor role in shaping the genomic diversity of the common vole, which is more influenced by positive selection and neutral processes like drift and demographic history.

Large-scale land acquisitions: Focus on South-East Asia: International Development Policy

Large-scale land acquisition, or "land grabbing", has become a key research topic among scholars interested in agrarian change, development, and the environment. The term "land acquisitions" refers to a highly contested process in terms of governance and impacts on livelihoods and human rights. This book focuses on South-East Asia. A series of thematic and in-depth case studies put "land grabbing" into specific historical and institutional contexts. The volume also offers a human rights analysis of the phenomenon, examining the potential and limits of human rights mechanisms aimed at preventing and mitigating land grabs' negative consequences.

Large-scale land acquisitions in Peru: Land (re)-concentration, agrarian change and reactions from rural communities

More than 40 years after the agrarian reform, Peru is experiencing a renewed process of concentration of land ownership in the hands of large-scale investors, favoring the development of a sugar cane production cluster along the northern coast. The expansion of the agricultural frontier by means of large irrigation projects – originally developed to benefit medium- and small-scale farmers – is carried out today in order to be sold to large-scale investors for the production of export crops. In the region of Piura the increasing presence of large-scale biofuel investors puts substantial pressure on land and water resources, not only changing the use of and access to land for local communities, but also generating water shortages vis-à-vis the multiple water demands of local food producers. The changes in land relations and the agro-ecosystem, the altering food production regime as well as the increasing proletarization of smallholders, is driving many locals – even those which (initially) welcomed the investment – into resistance activities against the increasing control of land, water and other natural resources in the hands of agribusinesses. The aim of this presentation is to discuss the contemporary political, social and cultural dynamics of agrarian change along the northern Peruvian coast as well as the «reactions from below» emanating from campesino communities, landless laborers, brick producers, pastoralists as well as other marginalized groups. The different strategies, forms and practices of resistance with the goal of the «protection of the territory» shall be explored as well as the reasons for their rather scattered occurrence and the lack of alliances on the land issue. This input shall make a contribution to the on-going debate on individual and communal property rights and the question of what is best in terms of collective defense against land grabbing.

Millennial to orbital-scale variations of drought intensity in the Eastern Mediterranean

Millennial to orbital-scale rainfall changes in the Mediterranean region and corresponding variations in vegetation patterns were the result of large-scale atmospheric reorganizations. In spite of recent efforts to reconstruct this variability using a range of proxy archives, the underlying physical mechanisms have remained elusive. Through the analysis of a new high-resolution sedimentary section from Lake Van (Turkey) along with climate modeling experiments, we identify massive droughts in the Eastern Med- iterranean for the past four glacial cycles, which have a pervasive link with known intervals of enhanced North Atlantic glacial iceberg calving, weaker Atlantic Meridional Overturning Circulation and Dansgaard-Oeschger cold conditions. On orbital timescales, the topographic effect of large Northern Hemisphere ice sheets and periods with minimum insolation seasonality further exacerbated drought intensities by suppressing both summer and winter precipitation.

Rotational constants and structure of para-difluorobenzene determined by femtosecond Raman coherence spectroscopy: A new transient type

Femtosecond Raman rotational coherence spectroscopy (RCS) detected by degenerate four-wave mixing is a background-free method that allows to determine accurate gas-phase rotational constants of non-polar molecules. Raman RCS has so far mostly been applied to the regular coherence patterns of symmetric-top molecules, while its application to nonpolar asymmetric tops has been hampered by the large number of RCS transient types, the resulting variability of the RCS patterns, and the 10³–10⁴ times larger computational effort to simulate and fit rotational Raman RCS transients. We present the rotational Raman RCS spectra of the nonpolar asymmetric top 1,4-difluorobenzene (para-difluorobenzene, p-DFB) measured in a pulsed Ar supersonic jet and in a gas cell over delay times up to ~2.5 ns. p-DFB exhibits rotational Raman transitions with ΔJ = 0, 1, 2 and ΔK = 0, 2, leading to the observation of J −, K −, A −, and C–type transients, as well as a novel transient (S–type) that has not been characterized so far. The jet and gas cell RCS measurements were fully analyzed and yield the ground-state (v = 0) rotational constants Aₒ = 5637.68(20) MHz, Bₒ = 1428.23(37) MHz, and Cₒ = 1138.90(48) MHz (1σ uncertainties). Combining the Aₒ, Bₒ, and Cₒ constants with coupled-cluster with single-, double- and perturbatively corrected triple-excitation calculations using large basis sets allows to determine the semi-experimental equilibrium bond lengths rₑ(C₁–C₂) = 1.3849(4) Å, rₑ(C₂–C³) = 1.3917(4) Å, rₑ(C–F) = 1.3422(3) Å, and rₑ(C₂–H₂) = 1.0791(5) Å.

WEAVE: Efficient Geographical Routing in Large-Scale Networks

We propose WEAVE, a geographical 2D/3D routing protocol that maintains information on a small number of waypoints and checkpoints for forwarding packets to any destination. Nodes obtain the routing information from partial traces gathered in incoming packets and use a system of checkpoints along with the segments of routes to weave end-to-end paths close to the shortest ones. WEAVE does not generate any control traffic, it is suitable for routing in both 2D and 3D networks, and does not require any strong assumption on the underlying network graph such as the Unit Disk or a Planar Graph. WEAVE compares favorably with existing protocols in both testbed experiments and simulations.

Large-scale land acquisition and its effects on the water balance in investor and host countries

This study examines the validity of the assumption that international large-scale land acquisition (LSLA) is motivated by the desire to secure control over water resources, which is commonly referred to as ‘water grabbing’. This assumption was repeatedly expressed in recent years, ascribing the said motivation to the Gulf States in particular. However, it must be considered of hypothetical nature, as the few global studies conducted so far focused primarily on the effects of LSLA on host countries or on trade in virtual water. In this study, we analyse the effects of 475 intended or concluded land deals recorded in the Land Matrix database on the water balance in both host and investor countries. We also examine how these effects relate to water stress and how they contribute to global trade in virtual water. The analysis shows that implementation of the LSLAs in our sample would result in global water savings based on virtual water trade. At the level of individual LSLA host countries, however, water use intensity would increase, particularly in 15 sub-Saharan states. From an investor country perspective, the analysis reveals that countries often suspected of using LSLA to relieve pressure on their domestic water resources—such as China, India, and all Gulf States except Saudi Arabia—invest in agricultural activities abroad that are less water-intensive compared to their average domestic crop production. Conversely, large investor countries such as the United States, Saudi Arabia, Singapore, and Japan are disproportionately externalizing crop water consumption through their international land investments. Statistical analyses also show that host countries with abundant water resources are not per se favoured targets of LSLA. Indeed, further analysis reveals that land investments originating in water-stressed countries have only a weak tendency to target areas with a smaller water risk.

Grabbing or investment? On judging large-scale land acquisitions

Although analyses of large-scale land acquisitions (LSLA) often contain an explicit or implicit normative judgment about such projects, they rarely deduce such judgment from a nuanced balancing of pros and cons. This paper uses assessments about a well-researched LSLA in Sierra Leone to show that a utilitarian approach tends to lead to the conclusion that positive effects prevail, whereas deontological approaches lead to an emphasis on negative aspects. LSLA are probably the most radical land-use change in the history of humankind. This process of radical transformation poses a challenge for balanced evaluations. Thus, we line out a framework that focuses on the options of local residents but sets boundaries of acceptability through the core contents of human rights. In addition, systemic implications of a project need to be regarded.