bluuebunny/crossref_metadata_2025 huggingface dataset:
A network theory of mental disorders
Authors: Borsboom Denny
Published: January 2017

In recent years, the network approach to psychopathology has been advanced as an alternative way of conceptualizing mental disorders. In this approach, mental disorders arise from direct interactions between symptoms. Although the network approach has led to many novel methodologies and substantive applications, it has not yet been fully articulated as a scientific theory of mental disorders. The present paper aims to develop such a theory, by postulating a limited set of theoretical principles regarding the structure and dynamics of symptom networks. At the heart of the theory lies the notion that symptoms of psychopathology are causally connected through myriads of biological, psychological and societal mechanisms. If these causal relations are sufficiently strong, symptoms can generate a level of feedback that renders them self‐sustaining. In this case, the network can get stuck in a disorder state. The network theory holds that this is a general feature of mental disorders, which can therefore be understood as alternative stable states of strongly connected symptom networks. This idea naturally leads to a comprehensive model of psychopathology, encompassing a common explanatory model for mental disorders, as well as novel definitions of associated concepts such as mental health, resilience, vulnerability and liability. In addition, the network theory has direct implications for how to understand diagnosis and treatment, and suggests a clear agenda for future research in psychiatry and associated disciplines.
Effects of Olive Trees Age on the Minor Components of Oueslati Virgin Olive Oils Produced from Olives Harvested at Different Ripening Degrees
Authors: Chtourou Fatma , Valli Enrico , Bendini Alessandra , Lazzez Aida , Toschi Tullia Gallina , Bouaziz Mohamed
Published: January 2017

Phenolics, volatiles, squalene, tocopherols, and fatty acids of virgin olive oils (VOO) from adult and young olive trees of the Oueslati variety, typically cultivated in the Center of Tunisia, were analyzed at three different harvesting periods. Significant differences in contents of saturated fatty acids (p < 0.05), squalene (p < 0.05), alpha‐tocopherol and total tocopherol (p < 0.02) and oxidized form of decarboxymethyl oleuropein aglycon (p < 0.05) were seen between VOO from adult and young trees during maturation. Moreover, the volatile profiles of VOO from adult and young trees showed significant differences in the amounts of hexanal, 1‐penten‐3‐ol (p < 0.05), (Z)‐3‐hexenal and (Z)‐2‐penten‐1‐ol (p < 0.01). Principal component analysis showed that olives from adult trees should be harvested at the cherry stage of maturation to obtain a satisfactory level of oil quality, while olives from young trees should be harvested at the black maturation stage.
Hydrothermal co-liquefaction of microalgae, wood, and sugar beet pulp
Authors: Brilman D. W. F. , Drabik N. , Wądrzyk M.
Published: January 2017

Hydrothermal co-liquefaction of mixed (wet and dry) biomass residue streams would greatly enhance the viability and scale up potential of the technology as platform in bioenergy and biorefinery applications. This study aims to identify possible interaction effects between three different feeds (protein-rich microalgae, lignocellulosic wood, and carbohydrate-rich sugar beet pulp) and to broaden the data set for evaluating this concept. Co-liquefaction was evaluated at 250 and 350 °C at 10 min of holding time, using 10 wt%( in water) binary mixtures (1:1 wt basis) and a (1:1:1 wt basis) ternary mixture. Results show that interaction during co-liquefaction does play a role and especially reduced the amount of biocrude produced. The biocrude yields obtained are around 15 and 40% below the estimated values for binary and ternary mixtures, on basis of linear averaging the results for the single feeds. For mixtures including algal biomass, a more than proportional nitrogen content and fraction of high molecular mass components was found in the biocrude. For the predictability of biocrude yield and composition in case of biomass mixtures, more work is needed to unravel these interactions.
The Kato smoothing effect for regularized Schrödinger equations in exterior domains
Authors: Robbiano Luc , Aloui Lassaad , Khenissi Moez
Published: January 2017

We prove, under the exterior geometric control condition, the Kato smoothing effect for solutions of an inhomogeneous and damped Schrödinger equation on exterior domains.
Maintenance Pharmacotherapy for Recurrent Major Depressive Disorder in Primary Care: A 5-year Follow-up Study
Authors: Riihimäki K. , Vuorilehto M. , Isometsä E.
Published: January 2017

Background

Most practice guidelines recommend maintenance antidepressant treatment for recurrent major depressive disorder. However, the degree to which such guidance is actually followed in primary health care has remained obscure. We investigated the provision of maintenance antidepressant treatment within a representative primary care five-year cohort study.

Methods

In the Vantaa Primary Care Depression Study, a stratified random sample of 1119 adult patients was screened for depression using the Prime-MD. Depressive and comorbid psychiatric disorders were diagnosed using SCID-I/P and SCID-II interviews. Of the 137 patients with depressive disorders, 82% completed the prospective five-year follow-up. A graphic life chart enabling evaluation of the longitudinal course of episodes plus duration of pharmacotherapies was used. In accordance with national guidelines, an indication for maintenance treatment was defined to exist after three or more lifetime major depressive episodes (MDEs); maintenance treatment was to commence four months after onset of full remission.

Results

Of the cohort patients, 34% (46/137) had three or more lifetime MDEs, thus indicating the requirement for maintenance pharmacotherapy. Of these, half (54%, 25/46) received maintenance treatment, for only 29% (489/1670) of the months indicated.

Conclusions

In this cohort of depressed primary care patients, half of patients with indications for maintenance treatment actually received it, and only for a fraction of the time indicated. Antidepressant maintenance treatment for the prevention of recurrences is unlikely to be subject to large-scale actualization as recommended, which may significantly undermine the potential public health benefits of treatment.
Migrant workers into contract farmers: processes of labour mobilization in colonial and contemporary Mozambique
Authors: Pérez Niño Helena
Published: January 2017

As contract farming gains ground as a form of agricultural production in Southern Africa, there is growing interest in its effects on patterns of investment and production as well as in its potential to provide small farmers with access to export markets. However, the relation between contract farming and the region's long history of labour migration has largely escaped analysts and scholars working on Southern Africa. This article traces the changing livelihoods of those who experienced the demise of the migrant labour system and displacement during the civil war, and who now engage in contract farming in Angónia, a densely populated district in Tete Province, central Mozambique. In the decades since the end of the war, contract farming thrived among former migrants with access to land and few alternative sources of income and employment. If historical labour migration from Angónia involved attempts by employers to externalize the responsibility for social reproduction onto households, contract farming amounts to the internalization by households of the opportunities, risks and tensions involved in the production of high-value export commodities. By analysing farmers’ accounts of producing under contract and linking this to their households’ longer histories of labour mobilization, this article sheds light on people's experiences of working for wages, working on their own account and hiring workers, as households became the new sites of commodity production.
The making of a ‘superstar’: the politics of playback and live performance in post-genocide Rwanda
Authors: Grant Andrea Mariko
Published: January 2017

This article considers the reconstruction of Rwanda's post-genocide music industry through the national music competition, Primus Guma Guma Super Star. It explores local ideas about ‘playback’ and ‘live’ music, and argues that these two performative categories can be understood as wider metaphors for the relationship between the Rwandan state and its citizens, particularly Rwandan youth. On the one hand, Guma Guma aims to create the ideal post-genocide celebrity subject who will ‘play back’ a unified, de-ethnicized Rwandan identity with body and words. On the other, during the first two seasons of the competition, audiences demanded ‘live’ performance and Guma Guma prompted heated debate about ‘taboo’ topics, revealing enduring differences along socio-economic, ethnic and regional lines. Rather than affirm an inclusive Rwandan identity, Guma Guma hinted at its fragility and underscored the multiple and conflicting ways in which young people identify themselves and evaluate ‘truth’ in the post-genocide era. The article contributes not only to literature on popular culture in Africa, but also to studies that focus on mediation and changes in recording technology. Although scholars have quite rightly attempted to dissolve the boundary between the live and the mediated, I suggest that the boundary continues to do cultural and political work, particularly in developmental states.
Effects of L-carnitine supplementation of diets differing in energy levels on performance, abdominal fat content, and yield and composition of edible meat of broilers
Authors: Rabie Mahmoud H. , Szilágyi Mihály
Published: January 2017

Responses to supplemental dietaryl-carnitine of broilers fed on diets with different levels of metabolizable energy (ME) were investigated using growth performance and some carcass measurements. Three isonitrogenous diets containing 13.5, 12.8 or 12.2 MJ ME/kg were formulated, with or without supplementall-carnitine (50mg/kg) and fedad libitumfrom 18 to 53 d of age. Supplementall-carnitine increased body-weight gain (BWG) and improved feed conversion (FC) during the first 2 weeks of study. FC was also improved during the fourth week of the experiment. Weights of breast yield and thigh meat yield were significantly increased, whereas quantity and percentage of abdominal fat were reduced by supplementall-carnitine. A significant interaction between supplemental dietaryl-carnitine and dietary energy level was noted for BWG and FC during the second week of study.
The Whittaker-Henderson Method of Graduation
Authors: Joseph A. W.
Published: January 2017

Mr Elphinstone, in his recent paper to the Faculty of Actuaries, has reawakened interest in the method of graduation devised by Sir Edmund T. Whittaker some 32 years ago. Except for Professor A. C. Aitken who, in a paper( in the Proceedings of the Royal Society of Edinburgh and a note in the Transactions of the Faculty of Actuaries, gave a brilliant alternative solution of the equations on which Whittaker's method depends, English and Scottish writers have paid little attention to the method. Robert Henderson's paper published in 1924 stimulated American actuaries, and their investigations have continued up to the present time. The book by Kingsland Camp (reviewed J.I.A. lxxvii, 327) gives numerous practical developments of Robert Henderson's work. Students should not overlook a most valuable paper by Charles A. Spoerl which deals comprehensively with almost every aspect of the subject.
Ultrafast laser-scanning time-stretch imaging at visible wavelengths
Authors: Wu Jiang-Lai , Xu Yi-Qing , Xu Jing-Jiang , Wei Xiao-Ming , Chan Antony CS , Tang Anson HL , Lau Andy KS , Chung Bob MF , Cheung Shum Ho , Lam Edmund Y , Wong Kenneth KY , Tsia Kevin K
Published: January 2017

Optical time-stretch imaging enables the continuous capture of non-repetitive events in real time at a line-scan rate of tens of MHz—a distinct advantage for the ultrafast dynamics monitoring and high-throughput screening that are widely needed in biological microscopy. However, its potential is limited by the technical challenge of achieving significant pulse stretching (that is, high temporal dispersion) and low optical loss, which are the critical factors influencing imaging quality, in the visible spectrum demanded in many of these applications. We present a new pulse-stretching technique, termed free-space angular-chirp-enhanced delay (FACED), with three distinguishing features absent in the prevailing dispersive-fiber-based implementations: (1) it generates substantial, reconfigurable temporal dispersion in free space (>1 ns nm−1) with low intrinsic loss (<6 dB) at visible wavelengths; (2) its wavelength-invariant pulse-stretching operation introduces a new paradigm in time-stretch imaging, which can now be implemented both with and without spectral encoding; and (3) pulse stretching in FACED inherently provides an ultrafast all-optical laser-beam scanning mechanism at a line-scan rate of tens of MHz. Using FACED, we demonstrate not only ultrafast laser-scanning time-stretch imaging with superior bright-field image quality compared with previous work but also, for the first time, MHz fluorescence and colorized time-stretch microscopy. Our results show that this technique could enable a wider scope of applications in high-speed and high-throughput biological microscopy that were once out of reach.
Deformation-resembling microstructure created by fluid-mediated dissolution–precipitation reactions
Authors: Spruzeniece Liene , Piazolo Sandra , Maynard-Casely Helen E.
Published: January 2017

Deformation microstructures are widely used for reconstructing tectono-metamorphic events recorded in rocks. In crustal settings deformation is often accompanied and/or succeeded by fluid infiltration and dissolution–precipitation reactions. However, the microstructural consequences of dissolution–precipitation in minerals have not been investigated experimentally. Here we conducted experiments where KBr crystals were reacted with a saturated KCl-H2O fluid. The results show that reaction products, formed in the absence of deformation, inherit the general crystallographic orientation from their parents, but also display a development of new microstructures that are typical in deformed minerals, such as apparent bending of crystal lattices and new subgrain domains, separated by low-angle and, in some cases, high-angle boundaries. Our work suggests that fluid-mediated dissolution–precipitation reactions can lead to a development of potentially misleading microstructures. We propose a set of criteria that may help in distinguishing such microstructures from the ones that are created by crystal-plastic deformation.
Cell-like pressure sensors reveal increase of mechanical stress towards the core of multicellular spheroids under compression
Authors: Dolega M. E. , Delarue M. , Ingremeau F. , Prost J. , Delon A. , Cappello G.
Published: January 2017

The surrounding microenvironment limits tumour expansion, imposing a compressive stress on the tumour, but little is known how pressure propagates inside the tumour. Here we present non-destructive cell-like microsensors to locally quantify mechanical stress distribution in three-dimensional tissue. Our sensors are polyacrylamide microbeads of well-defined elasticity, size and surface coating to enable internalization within the cellular environment. By isotropically compressing multicellular spheroids (MCS), which are spherical aggregates of cells mimicking a tumour, we show that the pressure is transmitted in a non-trivial manner inside the MCS, with a pressure rise towards the core. This observed pressure profile is explained by the anisotropic arrangement of cells and our results suggest that such anisotropy alone is sufficient to explain the pressure rise inside MCS composed of a single cell type. Furthermore, such pressure distribution suggests a direct link between increased mechanical stress and previously observed lack of proliferation within the spheroids core.
Interfacial Ca2+ environments in nanocrystalline apatites revealed by dynamic nuclear polarization enhanced 43Ca NMR spectroscopy
Authors: Lee Daniel , Leroy César , Crevant Charlène , Bonhomme-Coury Laure , Babonneau Florence , Laurencin Danielle , Bonhomme Christian , De Paëpe Gaël
Published: January 2017

The interfaces within bones, teeth and other hybrid biomaterials are of paramount importance but remain particularly difficult to characterize at the molecular level because both sensitive and selective techniques are mandatory. Here, it is demonstrated that unprecedented insights into calcium environments, for example the differentiation of surface and core species of hydroxyapatite nanoparticles, can be obtained using solid-state NMR, when combined with dynamic nuclear polarization. Although calcium represents an ideal NMR target here (and de facto for a large variety of calcium-derived materials), its stable NMR-active isotope, calcium-43, is a highly unreceptive probe. Using the sensitivity gains from dynamic nuclear polarization, not only could calcium-43 NMR spectra be obtained easily, but natural isotopic abundance 2D correlation experiments could be recorded for calcium-43 in short experimental time. This opens perspectives for the detailed study of interfaces in nanostructured materials of the highest biological interest as well as calcium-based nanosystems in general.
Proton pumping accompanies calcification in foraminifera
Authors: Toyofuku Takashi , Matsuo Miki Y. , de Nooijer Lennart Jan , Nagai Yukiko , Kawada Sachiko , Fujita Kazuhiko , Reichart Gert-Jan , Nomaki Hidetaka , Tsuchiya Masashi , Sakaguchi Hide , Kitazato Hiroshi
Published: January 2017

Ongoing ocean acidification is widely reported to reduce the ability of calcifying marine organisms to produce their shells and skeletons. Whereas increased dissolution due to acidification is a largely inorganic process, strong organismal control over biomineralization influences calcification and hence complicates predicting the response of marine calcifyers. Here we show that calcification is driven by rapid transformation of bicarbonate into carbonate inside the cytoplasm, achieved by active outward proton pumping. Moreover, this proton flux is maintained over a wide range of pCO2 levels. We furthermore show that a V-type H+ ATPase is responsible for the proton flux and thereby calcification. External transformation of bicarbonate into CO2 due to the proton pumping implies that biomineralization does not rely on availability of carbonate ions, but total dissolved CO2 may not reduce calcification, thereby potentially maintaining the current global marine carbonate production.
Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16
Authors: Maruthappu Thiviyani , Chikh Anissa , Fell Benjamin , Delaney Paul J. , Brooke Matthew A. , Levet Clemence , Moncada-Pazos Angela , Ishida-Yamamoto Akemi , Blaydon Diana , Waseem Ahmad , Leigh Irene M. , Freeman Matthew , Kelsell David P.
Published: January 2017

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2−/− mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this ‘stress’ keratin is regulated.
A mechanosensory receptor required for food texture detection in Drosophila
Authors: Sánchez-Alcañiz Juan Antonio , Zappia Giovanna , Marion-Poll Frédéric , Benton Richard
Published: January 2017

Textural properties provide information on the ingestibility, digestibility and state of ripeness or decay of sources of nutrition. Compared with our understanding of the chemosensory assessment of food, little is known about the mechanisms of texture detection. Here we show that Drosophila melanogaster can discriminate food texture, avoiding substrates that are either too hard or too soft. Manipulations of food substrate properties and flies' chemosensory inputs indicate that texture preferences are revealed only in the presence of an appetitive stimulus, but are not because of changes in nutrient accessibility, suggesting that animals discriminate the substrates’ mechanical characteristics. We show that texture preference requires NOMPC, a TRP-family mechanosensory channel. NOMPC localizes to the sensory dendrites of neurons housed within gustatory sensilla, and is essential for their mechanosensory-evoked responses. Our results identify a sensory pathway for texture detection and reveal the behavioural integration of chemical and physical qualities of food.
mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis
Authors: Hallowell R. W. , Collins S. L. , Craig J. M. , Zhang Y. , Oh M. , Illei P. B. , Chan-Li Y. , Vigeland C. L. , Mitzner W. , Scott A. L. , Powell J. D. , Horton M. R.
Published: January 2017

Alternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic metabolism. Here we show a critical role for mTORC2 signalling in the generation of M2 macrophages. Abrogation of mTORC2 signalling in macrophages by selective conditional deletion of the adaptor molecule Rictor inhibits the generation of M2 macrophages while leaving the generation of classically activated macrophages (M1) intact. Selective deletion of Rictor in macrophages prevents M2 differentiation and clearance of a parasitic helminth infection in mice, and also abrogates the ability of mice to regulate brown fat and maintain core body temperature. Our findings define a role for mTORC2 in macrophages in integrating signals from the immune microenvironment to promote innate type 2 immunity, and also to integrate systemic metabolic and thermogenic responses.
A Lin28 homologue reprograms differentiated cells to stem cells in the moss Physcomitrella patens
Authors: Li Chen , Sako Yusuke , Imai Akihiro , Nishiyama Tomoaki , Thompson Kari , Kubo Minoru , Hiwatashi Yuji , Kabeya Yukiko , Karlson Dale , Wu Shu-Hsing , Ishikawa Masaki , Murata Takashi , Benfey Philip N. , Sato Yoshikatsu , Tamada Yosuke , Hasebe Mitsuyasu
Published: January 2017

Both land plants and metazoa have the capacity to reprogram differentiated cells to stem cells. Here we show that the moss Physcomitrella patens Cold-Shock Domain Protein 1 (PpCSP1) regulates reprogramming of differentiated leaf cells to chloronema apical stem cells and shares conserved domains with the induced pluripotent stem cell factor Lin28 in mammals. PpCSP1 accumulates in the reprogramming cells and is maintained throughout the reprogramming process and in the resultant stem cells. Expression of PpCSP1 is negatively regulated by its 3′-untranslated region (3′-UTR). Removal of the 3′-UTR stabilizes PpCSP1 transcripts, results in accumulation of PpCSP1 protein and enhances reprogramming. A quadruple deletion mutant of PpCSP1 and three closely related PpCSP genes exhibits attenuated reprogramming indicating that the PpCSP genes function redundantly in cellular reprogramming. Taken together, these data demonstrate a positive role of PpCSP1 in reprogramming, which is similar to the function of mammalian Lin28.
A non-canonical mismatch repair pathway in prokaryotes
Authors: Castañeda-García A. , Prieto A. I. , Rodríguez-Beltrán J. , Alonso N. , Cantillon D. , Costas C. , Pérez-Lago L. , Zegeye E. D. , Herranz M. , Plociński P. , Tonjum T. , García de Viedma D. , Paget M. , Waddell S. J. , Rojas A. M. , Doherty A. J. , Blázquez J.
Published: January 2017

Mismatch repair (MMR) is a near ubiquitous pathway, essential for the maintenance of genome stability. Members of the MutS and MutL protein families perform key steps in mismatch correction. Despite the major importance of this repair pathway, MutS–MutL are absent in almost all Actinobacteria and many Archaea. However, these organisms exhibit rates and spectra of spontaneous mutations similar to MMR-bearing species, suggesting the existence of an alternative to the canonical MutS–MutL-based MMR. Here we report that Mycobacterium smegmatis NucS/EndoMS, a putative endonuclease with no structural homology to known MMR factors, is required for mutation avoidance and anti-recombination, hallmarks of the canonical MMR. Furthermore, phenotypic analysis of naturally occurring polymorphic NucS in a M. smegmatis surrogate model, suggests the existence of M. tuberculosis mutator strains. The phylogenetic analysis of NucS indicates a complex evolutionary process leading to a disperse distribution pattern in prokaryotes. Together, these findings indicate that distinct pathways for MMR have evolved at least twice in nature.
Sub-wavelength modulation of χ(2) optical nonlinearity in organic thin films
Authors: Yan Yixin , Yuan Yakun , Wang Baomin , Gopalan Venkatraman , Giebink Noel C.
Published: January 2017

Modulating the second-order nonlinear optical susceptibility (χ(2)) of materials at the nanoscale represents an ongoing technological challenge for a variety of integrated frequency conversion and nonlinear nanophotonic applications. Here we exploit the large hyperpolarizability of intermolecular charge transfer states, naturally aligned at an organic semiconductor donor–acceptor (DA) interface, as a means to control the magnitude and sign of χ(2) at the nanoscale. Focusing initially on a single pentacene-C60 DA interface, we confirm that the charge transfer transition is strongly aligned orthogonal to the heterojunction and find that it is responsible for a large interfacial nonlinearity probed via second harmonic generation that is sufficient to achieve d33>10 pm V−1, when incorporated in a non-centrosymmetric DA multilayer stack. Using grating-shadowed oblique-angle deposition to laterally structure the DA interface distribution in such multilayers subsequently enables the demonstration of a χ(2) grating with 280 nm periodicity, which is the shortest reported to date.
Rapid evolution of dispersal ability makes biological invasions faster and more variable
Authors: Ochocki Brad M. , Miller Tom E. X.
Published: January 2017

Genetic variation in dispersal ability may result in the spatial sorting of alleles during range expansion. Recent theory suggests that spatial sorting can favour the rapid evolution of life history traits at expanding fronts, and therefore modify the ecological dynamics of range expansion. Here we test this prediction by disrupting spatial sorting in replicated invasions of the bean beetleCallosobruchus maculatusacross homogeneous experimental landscapes. We show that spatial sorting promotes rapid evolution of dispersal distance, which increases the speed and variability of replicated invasions: after 10 generations of range expansion, invasions subject to spatial sorting spread 8.9% farther and exhibit 41-fold more variable spread dynamics relative to invasions in which spatial sorting is suppressed. Correspondingly, descendants from spatially evolving invasions exhibit greater mean and variance in dispersal distance. Our results reveal an important role for rapid evolution during invasion, even in the absence of environmental filters, and argue for evolutionarily informed forecasts of invasive spread by exotic species or climate change migration by native species.
Enzyme I facilitates reverse flux from pyruvate to phosphoenolpyruvate in Escherichia coli
Authors: Long Christopher P. , Au Jennifer , Sandoval Nicholas R. , Gebreselassie Nikodimos A. , Antoniewicz Maciek R.
Published: January 2017

The bacterial phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) consists of cascading phosphotransferases that couple the simultaneous import and phosphorylation of a variety of sugars to the glycolytic conversion of phosphoenolpyruvate (PEP) to pyruvate. As the primary route of glucose uptake in E. coli, the PTS plays a key role in regulating central carbon metabolism and carbon catabolite repression, and is a frequent target of metabolic engineering interventions. Here we show that Enzyme I, the terminal phosphotransferase responsible for the conversion of PEP to pyruvate, is responsible for a significant in vivo flux in the reverse direction (pyruvate to PEP) during both gluconeogenic and glycolytic growth. We use 13C alanine tracers to quantify this back-flux in single and double knockouts of genes relating to PEP synthetase and PTS components. Our findings are relevant to metabolic engineering design and add to our understanding of gene-reaction connectivity in E. coli.
αV-class integrins exert dual roles on α5β1 integrins to strengthen adhesion to fibronectin
Authors: Bharadwaj Mitasha , Strohmeyer Nico , Colo Georgina P. , Helenius Jonne , Beerenwinkel Niko , Schiller Herbert B. , Fässler Reinhard , Müller Daniel J.
Published: January 2017

Upon binding to the extracellular matrix protein, fibronectin, αV-class and α5β1 integrins trigger the recruitment of large protein assemblies and strengthen cell adhesion. Both integrin classes have been functionally specified, however their specific roles in immediate phases of cell attachment remain uncharacterized. Here, we quantify the adhesion of αV-class and/or α5β1 integrins expressing fibroblasts initiating attachment to fibronectin (≤120 s) by single-cell force spectroscopy. Our data reveals that αV-class integrins outcompete α5β1 integrins. Once engaged, αV-class integrins signal to α5β1 integrins to establish additional adhesion sites to fibronectin, away from those formed by αV-class integrins. This crosstalk, which strengthens cell adhesion, induces α5β1 integrin clustering by RhoA/ROCK/myosin-II and Arp2/3-mediated signalling, whereas overall cell adhesion depends on formins. The dual role of both fibronectin-binding integrin classes commencing with an initial competition followed by a cooperative crosstalk appears to be a basic cellular mechanism in assembling focal adhesions to the extracellular matrix.
Spatial and temporal boundaries of NMDA receptor hypofunction leading to schizophrenia
Authors: Nakazawa Kazu , Jeevakumar Vivek , Nakao Kazuhito
Published: January 2017

The N-methyl-d-aspartate receptor hypofunction is one of the most prevalent models of schizophrenia. For example, healthy subjects treated with uncompetitive N-methyl-d-aspartate receptor antagonists elicit positive, negative, and cognitive-like symptoms of schizophrenia. Patients with anti-N-methyl-d-aspartate receptor encephalitis, which is likely caused by autoantibody-mediated down-regulation of cell surface N-methyl-d-aspartate receptors, often experience psychiatric symptoms similar to schizophrenia initially. However, where and when N-methyl-d-aspartate receptor hypofunction occurs in the brain of schizophrenic patients is poorly understood. Here we review the findings from N-methyl-d-aspartate receptor antagonist and autoantibody models, postmortem studies on N-methyl-d-aspartate receptor subunits, as well as the global and cell-type-specific knockout mouse models of subunit GluN1. We compare various conditional GluN1 knockout mouse strains, focusing on the onset of N-methyl-d-aspartate receptor deletion and on the cortical cell-types. Based on these results, we hypothesize that N-methyl-d-aspartate receptor hypofunction initially occurs in cortical GABAergic neurons during early postnatal development. The resulting GABA neuron maturation deficit may cause reduction of intrinsic excitability and GABA release, leading to disinhibition of pyramidal neurons. The cortical disinhibition in turn could elicit glutamate spillover and subsequent homeostatic down regulation of N-methyl-d-aspartate receptor function in pyramidal neurons in prodromal stage. These two temporally-distinct N-methyl-d-aspartate receptor hypofunctions may be complimentary, as neither alone may not be able to fully explain the entire schizophrenia pathophysiology. Potential underlying mechanisms for N-methyl-d-aspartate receptor hypofunction in cortical GABA neurons are also discussed, based on studies of naturally-occurring N-methyl-d-aspartate receptor antagonists, neuregulin/ErbB4 signaling pathway, and theoretical analysis of excitatory/inhibitory balance.
Automated analysis of connected speech reveals early biomarkers of Parkinson’s disease in patients with rapid eye movement sleep behaviour disorder
Authors: Hlavnička Jan , Čmejla Roman , Tykalová Tereza , Šonka Karel , Růžička Evžen , Rusz Jan
Published: January 2017

For generations, the evaluation of speech abnormalities in neurodegenerative disorders such as Parkinson’s disease (PD) has been limited to perceptual tests or user-controlled laboratory analysis based upon rather small samples of human vocalizations. Our study introduces a fully automated method that yields significant features related to respiratory deficits, dysphonia, imprecise articulation and dysrhythmia from acoustic microphone data of natural connected speech for predicting early and distinctive patterns of neurodegeneration. We compared speech recordings of 50 subjects with rapid eye movement sleep behaviour disorder (RBD), 30 newly diagnosed, untreated PD patients and 50 healthy controls, and showed that subliminal parkinsonian speech deficits can be reliably captured even in RBD patients, which are at high risk of developing PD or other synucleinopathies. Thus, automated vocal analysis should soon be able to contribute to screening and diagnostic procedures for prodromal parkinsonian neurodegeneration in natural environments.
Using effect size benchmarks to assess when alien impacts are actually alien
Authors: Smith Helen M. , Dickman Chris R. , Banks Peter B.
Published: January 2017

Alien predators have on average twice the impact on native prey populations than do native predators, and are a severe threat to wildlife globally. Manipulation experiments can be used to quantify the impact of an alien predator on its prey population/s, but unless the results are compared to benchmarks, it is unclear whether this impact is indeed greater than that of a native predator. Here we use the Australian garden skink Lampropholis delicata and alien black rat Rattus rattus to test if black rats are an additive source of predation for the skink, and to judge whether the effect size of rat-impact on the skink represents that of an alien or native predator. We used replicated experiments to exclude black rats at local and landscape scales to test how rats affect skink activity and trapping frequency. Both manipulations had positive effects on skinks, however, the population-level effect size was lower than that described for alien predators but similar to that expected for native predators. We suggest that Australian skinks may respond appropriately to predatory alien rats because they coevolved with endemic Rattus species. This adds novel insights into the varying levels of impact that alien predators have on native prey.
Functional characterization of NES and GES responsible for the biosynthesis of (E)-nerolidol and (E,E)-geranyllinalool in Tripterygium wilfordii
Authors: Su Ping , Hu Tianyuan , Liu Yujia , Tong Yuru , Guan Hongyu , Zhang Yifeng , Zhou Jiawei , Huang Luqi , Gao Wei
Published: January 2017

Triptolide and celastrol, two principal bioactive compounds in Tripterygium wilfordii, are produced from geranylgeranyl diphosphate (GGPP) and farnesyl diphosphate ((E,E)-FPP) through terpenoid biosynthesis pathway. However, little is known about T. wilfordii terpene synthases which could competitively utilize GGPP and (E,E)-FPP as substrates, producing C15 and C20 tertiary alcohols. Here we firstly cloned the genes encoding nerolidol synthase (NES) and geranyllinalool synthases (GES1, GES2), which are responsible for the biosynthesis of (E)-nerolidol and (E,E)-geranyllinalool. In vitro characterization of recombinant TwNES and TwGES1 revealed both were functional enzymes that could catalyze the conversion of (E,E)-FPP and GGPP to (E)-nerolidol and (E,E)-geranyllinalool, which were consistent with the results of yeast fermentation. Biochemical characterization revealed TwNES and TwGES1 had strong dependency for Mg2+, Km and Kcat/Km values of TwNES for (E,E)-FPP were 12.700 μM and 0.029 s−1/μM, and TwGES1 for GGPP were 2.039 μM and 0.019 s−1/μM. Real-time PCR analysis showed the expression levels of NES and GES1 increased by several fold in the suspension cells treated with alamethicin, indicating TwNES and TwGES1 are likely to utilize GGPP and (E,E)-FPP to generate tertiary alcohols as precursor of plant volatiles, which play important roles in the ecological interactions between T. wilfordii and other organisms.
A UK wide cohort study describing management and outcomes for infants with surgical Necrotising Enterocolitis
Authors: Allin Benjamin , Long Anna-May , Gupta Amit , Knight Marian , Lakhoo Kokila ,   British Association of Paediatric Surgeons Congenital Anomalies Surveillance System Necrotising Enterocolitis Collaboration, Kazmierski Marcin , Kenny Simon , Lopes Joana , Cusick Eleri , Parsons Gilian , McCabe Amanda , Upadhyaya Manasvi , Walker Gregor , De Coppi Paulo , Besarovic Sania , Thakkar Hemanshoo , Tullie Lucinda , Sutcliffe Jonathan , Eradi Bala , Ross Andrew , Maphango Nomsa , Motiwale Sandeep , Salloum Adnan , Pardy Caroline , Waly Ramy , Charlesworth Paul , Craigie Ross , Lall Anupam , Lindley Richard , Johal Navroop , Njere Ike , Mortell Alan , Nandi Bip , Jones Abigail , Fouad Dina , tan Yew-Wei , Kufeji Dorothy , Stanwell Joanna , Lakshminarayanan Bhanu , Burge David , Wetherill Charlotte , Niyogi Anindya , Parsons Chris , Doyle Miriam , Turner Alex , Yardley Ian , Shrestha Ram , Mullassery Dhanya , Paramalingham Saravankumar , Ragazzi Simone
Published: January 2017

The Royal College of Surgeons have proposed using outcomes from necrotising enterocolitis (NEC) surgery for revalidation of neonatal surgeons. The aim of this study was therefore to calculate the number of infants in the UK/Ireland with surgical NEC and describe outcomes that could be used for national benchmarking and counselling of parents. A prospective nationwide cohort study of every infant requiring surgical intervention for NEC in the UK was conducted between 01/03/13 and 28/02/14. Primary outcome was mortality at 28-days. Secondary outcomes included discharge, post-operative complication, and TPN requirement. 236 infants were included, 43(18%) of whom died, and eight(3%) of whom were discharged prior to 28-days post decision to intervene surgically. Sixty infants who underwent laparotomy (27%) experienced a complication, and 67(35%) of those who were alive at 28 days were parenteral nutrition free. Following multi-variable modelling, presence of a non-cardiac congenital anomaly (aOR 5.17, 95% CI 1.9–14.1), abdominal wall erythema or discolouration at presentation (aOR 2.51, 95% CI 1.23–5.1), diagnosis of single intestinal perforation at laparotomy (aOR 3.1 95% CI 1.05–9.3), and necessity to perform a clip and drop procedure (aOR 30, 95% CI 3.9–237) were associated with increased 28-day mortality. These results can be used for national benchmarking and counselling of parents.
Sodium-myoinositol cotransporter-1, SMIT1, mediates the production of reactive oxygen species induced by hyperglycemia in the heart
Authors: Van Steenbergen Anne , Balteau Magali , Ginion Audrey , Ferté Laura , Battault Sylvain , Ravenstein Christophe de Meester de , Balligand Jean-Luc , Daskalopoulos Evangelos-Panagiotis , Gilon Patrick , Despa Florin , Despa Sanda , Vanoverschelde Jean-Louis , Horman Sandrine , Koepsell Hermann , Berry Gerard , Hue Louis , Bertrand Luc , Beauloye Christophe
Published: January 2017

Hyperglycemia (HG) stimulates the production of reactive oxygen species in the heart through activation of NADPH oxidase 2 (NOX2). This production is independent of glucose metabolism but requires sodium/glucose cotransporters (SGLT). Seven SGLT isoforms (SGLT1 to 6 and sodium-myoinositol cotransporter-1, SMIT1) are known, although their expression and function in the heart remain elusive. We investigated these 7 isoforms and found that only SGLT1 and SMIT1 were expressed in mouse, rat and human hearts. In cardiomyocytes, galactose (transported through SGLT1) did not activate NOX2. Accordingly, SGLT1 deficiency did not prevent HG-induced NOX2 activation, ruling it out in the cellular response to HG. In contrast, myo-inositol (transported through SMIT1) reproduced the toxic effects of HG. SMIT1 overexpression exacerbated glucotoxicity and sensitized cardiomyocytes to HG, whereas its deletion prevented HG-induced NOX2 activation. In conclusion, our results show that heart SMIT1 senses HG and triggers NOX2 activation. This could participate in the redox signaling in hyperglycemic heart and contribute to the pathophysiology of diabetic cardiomyopathy.
Functional characterization of a gibberellin receptor and its application in alfalfa biomass improvement
Authors: Wang Xuemin , Li Jun , Ban Liping , Wu Yudi , Wu Xinming , Wang Yunqi , Wen Hongyu , Chapurin Vladimir , Dzyubenko Nikolay , Li Zhiyong , Wang Zan , Gao Hongwen
Published: January 2017

Bioactive gibberellins (GAs) are essential phytohormones involved in the regulation of many aspects of plant development. GA receptors are crucial in GA signal transduction in plants. The GA receptor GoGID1 promotes plant elongation and improves biomass production when ectopically expressed in tobacco. Here, we discovered that GoGID1 can interact with the DELLA proteins of Arabidopsis in the presence of gibberellic acid. GoGID1 partially or completely functionally rescued the phenotypes of the Arabidopsis double-mutants atgid1a/atgid1c and atgid1a/atgid1b. The overexpression of GoGID1 led to increases in plant height and biomass production in transgenic Arabidopsis plants. The GoGID1 gene enhanced GA sensitivity of the transgenic plants. More importantly, transgenic alfalfa plants overexpressing GoGID1 exhibited increased growth rates, heights and biomass and produced larger leaves when compared with the control plants. Thus, GoGID1 functions as a GA receptor, playing multiple roles in plant growth and development. The GoGID1 gene has the potential to be used in the genetic engineering of forage crops for biomass improvement.
Counteracting wetland overgrowth increases breeding and staging bird abundances
Authors: Lehikoinen Petteri , Lehikoinen Aleksi , Mikkola-Roos Markku , Jaatinen Kim
Published: January 2017

Human actions have led to loss and degradation of wetlands, impairing their suitability as habitat especially for waterbirds. Such negative effects may be mitigated through habitat management. To date scientific evidence regarding the impacts of these actions remains scarce. We studied guild specific abundances of breeding and staging birds in response to habitat management on 15 Finnish wetlands. In this study management actions comprised several means of vegetation removal to thwart overgrowth. Management cost efficiency was assessed by examining the association between site-specific costs and bird abundances. Several bird guilds exhibited positive connections with both habitat management as well as with invested funds. Most importantly, however, red-listed species and species with special conservation concern as outlined by the EU showed positive correlations with management actions, underlining the conservation value of wetland management. The results suggest that grazing was especially efficient in restoring overgrown wetlands. As a whole this study makes it clear that wetland habitat management constitutes a feasible conservation tool. The marked association between invested funds and bird abundance may prove to be a valuable tool for decision makers when balancing costs and impact of conservation measures against one another.
Evaluation of 10 SLE susceptibility loci in Asian populations, which were initially identified in European populations
Authors: Zhang Yue-miao , Zhou Xu-jie , Nath Swapan K. , Sun Celi , Zhao Ming-hui , Zhang Hong
Published: January 2017

Ten novel loci have been found to be associated with systemic lupus erythematosus (SLE) susceptibility by a recent genome-wide association study conducted in Europeans. To test their disease associations and genetic similarities/differences in Asians and Europeans, we genotyped the 10 novel single nucleotide polymorphisms (SNPs) and performed an association study. A Chinese cohort from Northern China was recruited as the discovery population, and three East Asian cohorts were included for independent replication. The 10 SNPs were genotyped using TaqMan allele discrimination assays. To prioritize the associated SNPs, different layers of the public functional data were integrated. Among the 10 SNPs, rs564799 in IL12A was shared in both ethnicities (Padjust = 5.91 × 10−4; odds ratio = 1.22, 1.10–1.35). We also confirmed the reported polymorphism rs7726414 in TCF7 in the current study (Padjust = 4.12 × 10−8; odds ratio = 1.46, 1.28–1.66). The directions and magnitudes of the allelic effects for most of the 10 SNPs were comparable between Europeans and Asians. However, higher risk allele frequencies and population-attributable risk percentages were observed in Asians than in Europeans. We also identified the most likely functional SNPs at each locus. In conclusion, both genetic similarities and differences across ethnicities have been observed, providing further evidence for a genetic basis of the high incidence of SLE in Asian ancestry.
Striatal Neurons Expressing D1 and D2 Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice
Authors: Gagnon D. , Petryszyn S. , Sanchez M. G. , Bories C. , Beaulieu J. M. , De Koninck Y. , Parent A. , Parent M.
Published: January 2017

The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. Consequences on MSNs expressing both receptors (D1/D2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D1/D2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D1/D2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D1 and D2 MSNs, D1/D2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D1/D2 MSNs, but also of D1 and D2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D1 and D2 MSNs, the extent of dendritic arborization of D1/D2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D1/D2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson’s disease.