bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ten simple rules for structuring papers
Authors: Mensh Brett , Kording Konrad 
Published: December 2016

AbstractGood scientific writing is essential to career development and to the progress of science. A well-structured manuscript allows readers and reviewers to get excited about the subject matter, to understand and verify the paper’s contributions, and to integrate these contributions into a broader context. However, many scientists struggle with producing high-quality manuscripts and typically get little training in paper writing. Focusing on how readers consume information, we present a set of 10 simple rules to help you get across the main idea of your paper. These rules are designed to make your paper more influential and the process of writing more efficient and pleasurable.
NeuroNLP: a natural language portal for aggregated fruit fly brain data
Authors: Ukani Nikul H. , Tomkins Adam , Yeh Chung-Heng , Bruning Wesley , Fenichel Allison L. , Zhou Yiyin , Huang Yu-Chi , Florescu Dorian , Ortiz Carlos Luna , Richmond Paul , Lo Chung-Chuan , Coca Daniel , Chiang Ann-Shyn , Lazar Aurel A. 
Published: December 2016

SummaryNeuroNLP, is a key application on the Fruit Fly Brain Observatory platform (FFBO,http://fruitflybrain.org), that provides a modern web-based portal for navigating fruit fly brain circuit data. Increases in the availability and scale of fruit fly connectome data, demand new, scalable and accessible methods to facilitate investigation into the functions of the latest complex circuits being uncovered. NeuroNLP enables in-depth exploration and investigation of the structure of brain circuits, using intuitive natural language queries that are capable of revealing the latent structure and information, obscured due to expansive yet independent data sources. NeuroNLP is built on top of a database system call NeuroArch that codifies knowledge about the fruit fly brain circuits, spanning multiple sources. Users can probe biological circuits in the NeuroArch database with plain English queries, such as “show glutamatergic local neurons in the left antennal lobe” and “show neurons with dendrites in the left mushroom body and axons in the fan-shaped body”. This simple yet powerful interface replaces the usual, cumbersome checkboxes and dropdown menus prevalent in today’s neurobiological databases. Equipped with powerful 3D visualization, NeuroNLP standardizes tools and methods for graphical rendering, representation, and manipulation of brain circuits, while integrating with existing databases such as the FlyCircuit. The userfriendly graphical user interface complements the natural language queries with additional controls for exploring the connectivity of neurons and neural circuits. Designed with an open-source, modular structure, it is highly scalable/flexible/extensible to additional databases or to switch between databases and supports the creation of additional parsers for other languages. By supporting access through a web browser from any modern laptop or smartphone, NeuroNLP significantly increases the accessibility of fruit fly brain data and improves the impact of the data in both scientific and educational exploration.
Fractone bulbs derive from ependymal cells and their laminin composition influence the stem cell niche in the subventricular zone
Authors: Nascimento Marcos Assis , Sorokin Lydia , Coelho-Sampaio Tatiana 
Published: December 2016

AbstractFractones are extracellular matrix structures in the neural stem cell niche of the subventricular zone (SVZ), where they appear as round deposits named bulbs or thin branching lines called stems. Their cellular origin and what determines their localization at this site is poorly studied and it remains unclear whether they influence neural stem and progenitor cells formation, proliferation and/or maintenance. To address these questions, we analyzed whole mount preparations of the lateral ventricle by confocal microscopy using different extracellular matrix and cell markers. We found that bulbs are rarely connected to stems and that they contain laminin α5 and α2 chains, respectively. Fractone bulbs were profusely distributed throughout the SVZ and appeared associated with the center of pinwheels, a critical site for adult neurogenesis. We demonstrate that bulbs appear at the apical membrane of ependymal cells at the end of the first week after birth. The use of transgenic mice lacking laminin α5 gene expression (Lama5) in endothelium and in FoxJ1-expressing ependymal cells, revealed ependymal cells as the source of laminin α5-containing fractone bulbs. Loss of laminin α5 from bulbs correlated with a 60% increase in cell proliferation, as determined by PH3 staining, and with a selective reduction in the number of quiescent neural stem cells in the SVZ. These results indicate that fractones are a key component of the SVZ and suggest that laminin α5 modulates the physiology of the neural stem cell niche.Significance StatementOur work unveils key aspects of fractones, extracellular matrix structures present in the SVZ that still lack a comprehensive characterization. We show that fractones extensively interact with neural stem cells, whereas some of them are located precisely at pinwheel centers, which are hotspots for adult neurogenesis. Our results also demonstrate that fractones increase in size during aging and that their interactions with NSPCs become more complex in old mice. Lastly, we show that fractone bulbs are produced by ependymal cells and that their laminin content regulates neural stem cells.
Pharmacogenetics of antidepressant response: a polygenic approach
Authors: García-González Judit , Tansey Katherine E. , Hauser Joanna , Henigsberg Neven , Maier Wolfgang , Mors Ole , Placentino Anna , Rietschel Marcella , Souery Daniel , Žagar Tina , Czerski Piotr M. , Jerman Borut , Buttenschøn Henriette N. , Schulze Thomas G. , Zobel Astrid , Farmer Anne , Aitchison Katherine J. , Craig Ian , McGuffin Peter , Giupponi Michel , Perroud Nader , Bondolfi Guido , Evans David , O’Donovan Michael , Peters Tim J. , Wendland Jens R. , Lewis Glyn , Kapur Shitij , Perlis Roy , Arolt Volker , Domschke Katharina ,   Major Depressive Disorder Working Group of the Psychiatric Genomic Consortium, Breen Gerome , Curtis Charles , Sang-Hyuk Lee , Kan Carol , Newhouse Stephen , Patel Hamel , Baune Bernhard T. , Uher Rudolf , Lewis Cathryn M. , Fabbri Chiara 
Published: December 2016

AbstractBackgroundMajor depressive disorder (MDD) has a high personal and socio-economic burden and more than 60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait.MethodsPolygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy; 2) its overlap with MDD and schizophrenia. We constructed PRS and tested whether these predicted symptom improvement or remission from the GENDEP study (n=736) to the STAR*D study (n=1409) and vice-versa, including the whole sample or only patients treated with escitalopram or citalopram. Using summary statistics from Psychiatric Genomics Consortium for MDD and schizophrenia, we tested whether PRS from these disorders predicted symptom improvement in GENDEP, STAR*D, and five further studies (n=3756).ResultsNo significant prediction of antidepressant efficacy was obtained from PRS in GENDEP/STAR*D but this analysis might have been underpowered. There was no evidence of overlap in the genetics of antidepressant response with either MDD or schizophrenia, either in individual studies or a meta-analysis. Stratifying by antidepressant did not alter the results.DiscussionWe identified no significant predictive effect using PRS between pharmacogenetic studies. The genetic liability to MDD or schizophrenia did not predict response to antidepressants, suggesting differences between the genetic component of depression and treatment response. Larger or more homogeneous studies will be necessary to obtain a polygenic predictor of antidepressant response.
A theory of working memory without consciousness or sustained activity
Authors: Trübutschek Darinka , Marti Sébastien , Ojeda Andrés , King Jean-Rémi , Mi Yuanyuan , Tsodyks Misha , Dehaene Stanislas 
Published: December 2016

AbstractWorking memory and conscious perception are thought to share similar brain mechanisms, yet recent reports of non-conscious working memory challenge this view. Combining visual masking with magnetoencephalography, we demonstrate the reality of non-conscious working memory and dissect its neural mechanisms. In a spatial delayed-response task, participants reported the location of a subjectively unseen target above chance-level after a long delay. Conscious perception and conscious working memory were characterized by similar signatures: a sustained desynchronization in the alpha/beta band over frontal cortex, and a decodable representation of target location in posterior sensors. During non-conscious working memory, such activity vanished. Our findings contradict models that identify working memory with sustained neural firing, but are compatible with recent proposals of ‘activity-silent’ working memory. We present a theoretical framework and simulations showing how slowly decaying synaptic changes allow cell assemblies to go dormant during the delay, yet be retrieved above chance-level after several seconds.
Rapid identification of optimal drug combinations for personalized cancer therapy using microfluidics
Authors: Eduati Federica , Utharala Ramesh , Madhavan Dharanija , Neumann Ulf Peter , Cramer Thorsten , Saez-Rodriguez Julio , Merten Christoph A. 
Published: December 2016

AbstractFunctional screening of live patient cancer cells holds great potential for personalized medicine and allows to overcome the limited translatability of results from existing in-vitro and ex-vivo screening models. Here we present a plug-based microfluidics approach enabling the testing of drug combinations directly on cancer cells from patient biopsies. The entire procedure takes less than 48 hours after surgery and does not require ex vivo cultivation. We screened more than 1100 samples for different primary human tumors (each with 56 conditions and at least 20 replicates), and obtained highly specific sensitivity profiles. This approach allowed us to derive optimal treatment options which we further validated in two different pancreatic cancer cell lines. This workflow should pave the way for rapid determination of optimal personalized cancer therapies at assay costs of less than US$ 150 per patient.
Benefits of siderophore release lie in mediating diffusion limitation at low iron solubility
Authors: Leventhal Gabriel E. , Ackermann Martin , Schiessl Konstanze T. 
Published: December 2016

AbstractSiderophores are chelators released by many bacteria to take up iron. In contrast to iron receptors located at the cell surface, released siderophores are at risk of being lost to environmental sinks. Here, we asked the question whether the release itself is essential for the function of siderophores, which could explain why such a risky strategy is widespread. We developed a reaction-diffusion model to determine the impact of siderophore release on overcoming iron limitation caused by poor solubility in aerobic, pH-neutral environments. We found that secretion of siderophores can efficiently accelerate iron uptake at low solubility, since secreted siderophores solubilize slowly diffusing large iron aggregates to small, quickly diffusing iron-siderophore complexes. At high iron solubility, however, when the iron-siderophore complex is no longer considerably smaller than the iron source itself, siderophore secretion can also slow down iron uptake. In addition, we found that cells can synergistically share their siderophores, depending on their distance and the level of iron aggregation. Overall, our study helps understand why siderophore secretion is so widespread: Even though a large fraction of secreted siderophores is lost, the solubilization of iron through secreted siderophores can efficiently increase iron uptake, especially if siderophores are produced cooperatively by several cells.
Stress-induced formation of cell wall-deficient cells in filamentous actinomycetes
Authors: Ramijan K. , Ultee E. , Willemse J. , Wondergem A.J. , Heinrich D. , Briegel A. , van Wezel G.P. , Claessen D. 
Published: December 2016

ABSTRACTThe cell wall is a shape-defining structure that envelopes almost all bacteria. One of its main functions is to serve as a protection barrier to environmental stresses. Bacteria can be forced in a cell wall-deficient state under highly specialized conditions, which are invariably aimed at interrupting cell wall synthesis. Therefore, the relevance of such cells has remained obscure. Here we show that many filamentous actinomycetes have a natural ability to generate a new, cell wall-deficient cell type in response to hyperosmotic stress, which we call S-cells. This wall-deficient state is transient, as S-cells are able to switch to the canonical mycelial mode-of-growth. Remarkably, prolonged exposure of S-cells to hyperosmotic stress yielded variants that are able to proliferate indefinitely without their cell wall. This is the first report that demonstrates the formation of wall-deficient cells as a natural adaptation strategy and their potential transition into stable wall-less forms solely caused by prolonged exposure to osmotic stress. Given that actinomycetes are potent antibiotic producers, our work also provides important insights into how biosynthetic gene clusters and resistance determinants may disseminate into the environment.
Exosomes purified from a single cell type have diverse morphology and composition
Authors: Zabeo Davide , Cvjetkovic Aleksander , Lässer Cecilia , Schorb Martin , Lötvall Jan , Höög Johanna 
Published: December 2016

AbstractExtracellular vesicles (EVs) are produced by all known organisms and have important roles in cell communication and physiology. Exosomes are known in the literature to be small round EVs (40 to 100 nm in diameter) and are commonly purified with a serial ultracentrifugation protocol followed by density gradient floatation. Great morphological diversity has been described before regarding EVs found in body fluids such as blood plasma, breast milk and ejaculate. However, a detailed morphological analysis has never been performed on exosomes purified from a single cell type.Therefore, the aim of this study was to analyze and quantify via multiple electron microscopy techniques the morphology of exosomes purified from the human mast cell line HMC-1. The results revealed a novel spectrum of diversity in exosomes, which suggests that subpopulations of exosomes with different and specific functions might also exist. Our findings therefore argue that a new and more efficient way of defining exosome subpopulations is necessary. A system was proposed where exosomes were classified into nine different categories according to their size and shape. Three additional morphological features could also be found in exosomes regardless of their classification.These findings show that morphological diversity is found among exosomes purified from a single cell line, similarly to what was previously observed for EVs in body fluids. This knowledge can help improving the interpretation of experimental results and widening our general understanding of the biological functions of exosomes.
Diffusion or advection? Mass transfer and diffusive boundary layer landscapes of the brown algaFucus vesiculosus
Authors: Lichtenberg Mads , Nøerregaard Rasmus Dyrmose , Kühl Michael 
Published: December 2016

AbstractThe role of hyaline hairs on the thallus of brown-algae in the genusFucusis long debated and several functions have been proposed. We used a novel motorized setup for 2D-and 3D-mapping with O2-microsensors to investigate the spatial heterogeneity of the diffusive boundary layer (DBL) and O2flux around single and multiple tufts of hyaline hairs on the thallus ofFucus vesiculosus. Flow was a major determinant of DBL thickness, where higher flow decreased DBL thickness and increased O2flux between algal thallus and the surrounding seawater. However, the topography of the DBL varied and did not directly follow the contour of the underlying thallus. Areas around single tufts of hyaline hairs exhibited both increased and decreased DBL thickness as compared to areas over smooth thallus surfaces. Over thallus areas with several hyaline hair tufts, the overall effect was a local increase in the DBL thickness. We also found indications for advective O2transport driven by pressure gradients or vortex-shedding downstream from dense tufts of hyaline hairs alleviating local mass-transfer resistance imposed by thickened DBL. Mass-transfer dynamics around hyaline hair tufts are thus more complex than hitherto assumed and may have important implications for algal physiology and plant-microbe interactions.
Individual-versus group-optimality in the production of secreted bacterial compounds
Authors: Schiessl Konstanze T. , Ross-Gillespie Adin , Cornforth Daniel M. , Weigert Michael , Bigosch Colette , Brown Sam P. , Ackermann Martin , Kümmerli Rolf 
Published: December 2016

AbstractHow unicellular organisms optimize the production of compounds is a fundamental biological question. While it is typically thought that production is optimized at the individual-cell level, secreted compounds could also allow for optimization at the group level, leading to a division of labor where a subset of cells produces and shares the compound with everyone. Using mathematical modelling, we show that the evolution of such division of labor depends on the cost function of compound production. Specifically, for any trait with saturating benefits, linear costs promote the evolution of uniform production levels across cells. Conversely, production costs that diminish with higher output levels favor the evolution of specialization – especially when compound shareability is high. When experimentally testing these predictions with pyoverdine, a secreted iron-scavenging compound produced byPseudomonas aeruginosa, we found linear costs and, consistent with our model, detected uniform pyoverdine production levels across cells. We conclude that for shared compounds with saturating benefits, the evolution of division of labor is facilitated by a diminishing cost function. More generally, we note that shifts in the level of selection from individuals to groups do not solely require cooperation, but critically depend on mechanistic factors, including the distribution of compound synthesis costs.
Novel chromosome organization pattern in actinomycetales–overlapping replication cycles combined with diploidy
Authors: Böhm Kati , Meyer Fabian , Rhomberg Agata , Kalinowski Jörn , Donovan Catriona , Bramkamp Marc 
Published: December 2016

AbstractBacteria regulate chromosome replication and segregation tightly with cell division to ensure faithful segregation of DNA to daughter generations. The underlying mechanisms have been addressed in several model species. It became apparent that bacteria have evolved quite different strategies to regulate DNA segregation and chromosomal organization. We have investigated here how the actinobacteriumCorynebacterium glutamicumorganizes chromosome segregation and DNA replication. Unexpectedly, we find thatC. glutamicumcells are at least diploid under all conditions tested and that these organisms have overlapping C-periods during replication with both origins initiating replication simultaneously. Based on experimentally obtained data we propose growth rate dependent cell cycle models forC. glutamicum.
Domain prediction with probabilistic directional context
Authors: Ochoa Alejandro , Singh Mona 
Published: December 2016

AbstractMotivationProtein domain prediction is one of the most powerful approaches for sequence-based function prediction. While domain instances are typically predicted independently of each other, newer approaches have demonstrated improved performance by rewarding domain pairs that frequently co-occur within sequences. However, most of these approaches have ignored the order in which domains preferentially co-occur and have also not modeled domain co-occurrence probabilistically.ResultsWe introduce a probabilistic approach for domain prediction that models “directional” domain context. Our method is the first to score all domain pairs within a sequence while taking their order into account, even for non-sequential domains. We show that our approach extends a previous Markov model-based approach to additionally score all pairwise terms, and that it can be interpreted within the context of Markov random fields. We formulate our underlying combinatorial optimization problem as an integer linear program, and demonstrate that it can be solved quickly in practice. Finally, we perform extensive evaluation of domain context methods and demonstrate that incorporating context increases the number of domain predictions by ∼15%, with our approach dPUC2 (Domain Prediction Using Context) outperforming all competing approaches.AvailabilitydPUC2 is available athttp://github.com/alexviiia/dpuc2.
Workplace training programs
Authors: Brunetti Irene , Corsini Lorenzo 
Published: December 2016

Purpose
The purpose of this paper is to analyse the effect of an Italian training program on the re-employment probability of young unemployed workers. The program consists exclusively of workplace training and is coordinated by employment centers, even if it is fully implemented by firms.

Design/methodology/approach
The authors develop a discrete duration analysis. In particular, the authors compare the re-employment process of individuals that just finished their workplace training program with individuals that just ended their job. The authors specifically take into account the issue of self-selection adopting the propensity score matching estimation.

Findings
The results suggest that this workplace training program improves only the immediate re-employability of trained workers, failing to bestow them with durable human capital improvements. These results appear to be robust to spurious duration dependence and to self-selection. The analysis focuses on unobserved heterogeneity and, accounting for it, the authors show that the training implementation is useful to divide “good” trainees (in terms of unobserved heterogeneity) from “bad” ones.

Social implications
Therefore, the authors suggest that firms are exploiting training as a screening device and that the implemented program is successful in easing the connection between workers and firms, but it fails to provide a durable improvement in skills and in re-employment prospects.

Originality/value
The evaluation of this program is important because it focus specifically on the workplace component of training, whereas previous analyses focused on generic training, because it evaluates a program targeting youth unemployment which is one the most urgent economic issues and because it helps in understanding the actual processes adopted by firms when implementing workplace training.