bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central auditory neurons have composite receptive fields
Authors: Kozlov Andrei S. , Gentner Timothy Q. 
Published: February 2016

Significance
How neurons are selective for complex natural stimuli remains poorly understood, in part because standard statistical tools only identify one or two features of stimuli but not complete sets. Here, using a statistical method that overcomes these difficulties, we demonstrate that a set of multiple distinct acoustical features exists in individual auditory neurons in songbirds. We then use birdsongs to train an unsupervised neural network constrained by two common properties of biological neural circuits. The network rediscovers the same stimulus features observed in vivo. These results demonstrate that individual high-level auditory neurons respond not to single, but to multiple features of natural stimuli. This enables a robust, statistically optimal, representation of complex, real-world signals such as birdsong, speech, or music.
Tle1 tumor suppressor negatively regulates inflammation in vivo and modulates NF-κB inflammatory pathway
Authors: Ramasamy Selvi , Saez Borja , Mukhopadhyay Subhankar , Ding Daching , Ahmed Alwiya M. , Chen Xi , Pucci Ferdinando , Yamin Rae’e , Wang Jianfeng , Pittet Mikael J. , Kelleher Cassandra M. , Scadden David T. , Sweetser David A. 
Published: February 2016

SignificanceThis study provides the first physiological evidence, to our knowledge, that Tle1 (transducin-like enhancer of split 1) is a major negative regulator of inflammation. We show that the loss of Tle1 in mice leads to increased activity of the proinflammatory NF-κB pathway as well as decreased activity of Hes1 (hairy and enhancer of split-1), a negative regulator of inflammation. In addition, Tle1 loss resulted in decreased growth and survival with increased myelopoiesis and lung hypoplasia. Loss of Tle1 also sensitized mice to inflammatory stimuli and facilitated cancer progression. Our study opens the way to further investigations for a role of Tle1 in human inflammatory disease and cancer progression.
Slip-mediated dewetting of polymer microdroplets
Authors: McGraw Joshua D. , Chan Tak Shing , Maurer Simon , Salez Thomas , Benzaquen Michael , Raphaël Elie , Brinkmann Martin , Jacobs Karin 
Published: February 2016

Significance
Contact lines form at phase boundary intersections, quintessentially liquid/vapor interfaces at solid surfaces. Whereas classical hydrodynamic models predict that contact line motion requires infinite energy, common observations of moving droplets show that huge amounts of energy are unnecessary. Slip, wherein a fluid slides along a solid boundary, offers relief of such divergences, and has gained attention with the developing fields of micro- and nanofluidics. This article focuses on contact line motion of retracting liquid droplets with micrometric dimensions. Slip is tuned by changing a nanometric substrate surface layer. The resulting contact line motion and droplet evolutions are hugely influenced by slip, thus offering insights on the question: How do contact lines move?
Sequential activation and distinct functions for distal and proximal modules within the IgH 3′ regulatory region
Authors: Garot Armand , Marquet Marie , Saintamand Alexis , Bender Sébastien , Le Noir Sandrine , Rouaud Pauline , Carrion Claire , Oruc Zéliha , Bébin Anne-Gaëlle , Moreau Jeanne , Lebrigand Kevin , Denizot Yves , Alt Frederick W. , Cogné Michel , Pinaud Eric 
Published: February 2016

SignificanceThe immunoglobulin heavy chain (IgH) 3′regulatory region (3′RR) fine-tunesIgHgene expression during B cell development. One singularity of this region is its quasi-palindromic structure conserved in the3′RRof other species. By comparing previous mouse knockout (KO) models (3′RR-andhs3b-4KO) to a novel mutant devoid of the quasi-palindrome (3′PALKO), we highlighted common features and differences that specify two distinct regulatory entities: (i) the distal module (hs4) is sufficient for normal IgH expression up to the naïve B cell stage; (ii) during B-cell activation, the proximal module (quasi-palindrome) is important for both class switch recombination and somatic hypermutation; and (iii) in plasma cells, the quasi-palindrome is required for robust transcription of the IgH locus.
Assessment of fight outcome is needed to activate socially driven transcriptional changes in the zebrafish brain
Authors: Oliveira Rui F. , Simões José M. , Teles Magda C. , Oliveira Catarina R. , Becker Jorg D. , Lopes João S. 
Published: February 2016

SignificanceWithin social groups, there are animals of different social status that express different behavioral profiles that are paralleled by different patterns of gene expression in the brain. However, social status is not fixed, but rather depends on social interactions; hence, group living animals must be able to switch between different status-dependent behavior and brain gene expression profiles. Here we show for the first time, to our knowledge, that what triggers a genomic response to a social interaction in zebrafish is the subjects’ assessment of the interaction rather than a fixed response to a releaser cue in the environment. The occurrence of fighting assessment in zebrafish suggests that a cognitive ability classically considered complex is also present in a simple-minded vertebrate.
Winning a competition predicts dishonest behavior
Authors: Schurr Amos , Ritov Ilana 
Published: February 2016

SignificanceCompetition is prevalent. People often resort to unethical means to win (e.g., the recent Volkswagen scandal). Not surprisingly, competition is central to the study of economics, psychology, sociology, political science, and more. Although we know much about contestants’ behavior before and during competitions, we know little about contestants’ behavior after the competition has ended. Connecting postcompetition behaviors with preceding competition experience, we find that after a competition is over winners behave more dishonestly than losers in an unrelated subsequent task. Furthermore, the subsequent unethical behavior effect seems to depend on winning, rather than on mere success. Providing insight into the issue is important in gaining understanding of how unethical behavior may cascade from exposure to competitive settings.
Quantitative nanoscale imaging of orientational order in biological filaments by polarized superresolution microscopy
Authors: Valades Cruz Cesar Augusto , Shaban Haitham Ahmed , Kress Alla , Bertaux Nicolas , Monneret Serge , Mavrakis Manos , Savatier Julien , Brasselet Sophie 
Published: February 2016

Significance
Central biological processes in cells and tissues are intrinsically governed by the structural order of biomolecular assemblies. It is thus a key factor to decipher how these assemblies organize in complex molecular organizations, from the nanometric to the macroscopic scale. Polarized microscopy can access such information; however, signals are spatially averaged over the optical diffraction limit and are contaminated by the fluorophores’ orientational flexibility of their linker to the biomolecules. By bringing polarized fluorescence down to superresolution microscopy using single-molecule localization, we show that structural imaging can be scaled down to nanometric scales and is able to discriminate fluorophores’ flexibility from biomolecules’ orientational order. We demonstrate nanoscale structural imaging in fundamental biological filament organizations.
Targeting theGdnfGene in peritubular myoid cells disrupts undifferentiated spermatogonial cell development
Authors: Chen Liang-Yu , Willis William D. , Eddy Edward M. 
Published: February 2016

SignificanceGlial cell line-derived neurotrophic factor (GDNF) growth factor induces spermatogonial stem cells to proliferate in culture to produce progenitor spermatogonia. Sertoli cell GDNF was thought responsible for this in the testis. We showed that testosterone triggers GDNF secretion by peritubular myoid (PM) cells in culture and that undifferentiated spermatogonia (spermatogonial stem cells and progenitors) co-cultured with testosterone-treated PM cells and transplanted to sterile mice restored spermatogenesis. To determine if PM cell GDNF is essential to maintain the undifferentiated spermatogonial population, we made mice lacking theGdnfgene in PM cells. The number of undifferentiated spermatogonia was severely depleted in 2-wk-old mice and adults were infertile. This is the first study, to our knowledge, to show that the undifferentiated spermatogonial pool cannot be maintained without GDNF from PM cells.
Antagonistic roles for the ubiquitin ligase Asr1 and the ubiquitin-specific protease Ubp3 in subtelomeric gene silencing
Authors: McCann Tyler S. , Guo Yan , McDonald W. Hayes , Tansey William P. 
Published: February 2016

Significance
Ubiquitylation is integral to a myriad of cellular processes, including protein destruction, cell cycle control, and regulation of gene activity. Here, we show that ubiquitylation plays a role in inactivating the expression of genes that are located close to telomeres. We present evidence that the ubiquitin ligase Asr1 associates with subtelomeric DNA and ubiquitylates RNA polymerase II to prevent it from transcribing genes at these locations. We also show that Asr1 interacts with Ubp3, an enzyme that reverses ubiquitylation, and that the two play antagonistic roles in silencing subtelomeric genes. These findings show how ubiquitylation of a core component of the transcriptional machinery impacts gene activity and reveal a mechanism for controlling the expression of telomere-proximal genes.
Functional evidence for TCR-intrinsic specificity for MHCII
Authors: Parrish Heather L. , Deshpande Neha R. , Vasic Jelena , Kuhns Michael S. 
Published: February 2016

Significance
Most receptors co-evolve with specific ligands, whereas antibody–antigen pairing reflects interactions to a novel ligand (antigen) selected from a library of random antibodies. αβT-cell receptors (TCRs) lie somewhere in between. They are encoded by rearranged gene segments and screened for their ability to bind novel peptide fragments derived from foreign pathogens. But, unlike antibodies, they are restricted to recognizing peptides within allelic variants of related ligand scaffolds—MHCI and MHCII. It remains debated whether TCRs have an intrinsic specificity for MHC, like other receptor–ligand pairs, or if their recognition mirrors antibody–antigen interactions. This study presents functional evidence for TCRs interacting with MHC in an allele-independent and peptide sequence-independent manner, thus providing evidence for TCR-intrinsic recognition of MHC.
Structure of NDP-forming Acetyl-CoA synthetase ACD1 reveals a large rearrangement for phosphoryl transfer
Authors: Weiße Renato H.-J. , Faust Annette , Schmidt Marcel , Schönheit Peter , Scheidig Axel J. 
Published: February 2016

Significance
Acyl-CoA thioesters are key substrates for energy conversion. Related ATP/GTP-producing synthetases form a large superfamily with members in all kingdoms of life. In contrast to their general importance, the underlying reaction mechanism of these enzymes is still not understood in all steps. Here, we describe various structures of a nucleoside diphosphate-forming acetyl--CoA synthetase from an evolutionary very old archaeon. A large conformational rearrangement within the enzyme is observed. The structures reveal a partial unwinding and reorientation by 120° of a phosphohistidine-containing segment. This conformational rearrangement couples the acyl-CoA binding site with the nucleoside diphosphate binding site. The presented structures prove a long-standing hypothesis and provide insight into the determinants for substrate selectivity.
Geomorphic controls on elevational gradients of species richness
Authors: Bertuzzo Enrico , Carrara Francesco , Mari Lorenzo , Altermatt Florian , Rodriguez-Iturbe Ignacio , Rinaldo Andrea 
Published: February 2016

SignificanceHow biodiversity changes with elevation has long attracted the interest of researchers because it provides key clues to how biota respond to geophysical drivers. Experimental evidence reveals that biodiversity often peaks at intermediate elevations, and yet a clear explanation is still elusive. Here, we investigate a factor that has been overlooked to date: Mountainous landscapes hold fractal properties with elevational bands forming habitat patches that are characterized by different areal extent and connectivity, well-known drivers of biodiversity. When the geometry of real landscapes is taken into account, ecological dynamics naturally produce mid-peak elevational gradients of species richness. These results further biodiversity theory and our understanding of the distribution of life on Earth.
Physiological state gates acquisition and expression of mesolimbic reward prediction signals
Authors: Cone Jackson J. , Fortin Samantha M. , McHenry Jenna A. , Stuber Garret D. , McCutcheon James E. , Roitman Mitchell F. 
Published: February 2016

Significance
Associating environmental cues with their outcomes occurs through multiple strategies relying on different neural substrates. Unpredicted reward evokes dopamine release, which also develops to predictive cues, suggesting that predictive dopamine signals arise only after extensive pairings of cues with appetitive outcomes. However, recent work suggests that dopamine may also contribute to model-based learning, which does not require that cues and their appetitive outcomes be experienced in tandem. Taking advantage of the appetitive value of a hypertonic sodium solution, which radically and reversibly changes with physiological state, we show that dopamine differentially encodes hypertonic NaCl depending on sodium balance independent of prior experience. Conversely, dopamine only encoded a NaCl cue after extensive, state-dependent experience, firmly supporting dopamine’s role in experience-dependent learning.
Enhanced, targeted sampling of high-dimensional free-energy landscapes using variationally enhanced sampling, with an application to chignolin
Authors: Shaffer Patrick , Valsson Omar , Parrinello Michele 
Published: February 2016

Significance
The problem of sampling complex systems characterized by metastable states separated by kinetic bottlenecks is a universal one that has received much attention. Popular strategies involve applying a bias to a small number of collective variables. This strategy fails when the choice of collective variable is not clear or when the system’s free energy cannot be projected meaningfully on a low-dimensional manifold. We use a variational principle that allows one to construct approximate but effective multidimensional biases. We show in a practical case that the method is much more efficient than alternative methods. We expect this method to be useful for a wide variety of sampling problems in chemistry, biology, and materials science.
Selective memory retrieval of auditory what and auditory where involves the ventrolateral prefrontal cortex
Authors: Kostopoulos Penelope , Petrides Michael 
Published: February 2016

Significance
Although the involvement of the prefrontal cortex in the retrieval of verbal information has been established, there are no studies examining the role of the frontal cortex in the retrieval of auditory nonverbal information. The current experiment shows that a particular region within the large and heterogeneous prefrontal cortex, the midventrolateral prefrontal cortex, is involved in the retrieval of specific features of an auditory memory, such as the specific melody or its location. This selective retrieval is achieved via interactions with particular posterior cortical areas in the right hemisphere. Earlier research had demonstrated the importance of this region in the selective retrieval from memory of specific aspects of verbal, tactile, and visual information.
On the universal structure of human lexical semantics
Authors: Youn Hyejin , Sutton Logan , Smith Eric , Moore Cristopher , Wilkins Jon F. , Maddieson Ian , Croft William , Bhattacharya Tanmoy 
Published: February 2016

SignificanceSemantics, or meaning expressed through language, provides indirect access to an underlying level of conceptual structure. To what degree this conceptual structure is universal or is due to properties of cultural histories, or to the environment inhabited by a speech community, is still controversial. Meaning is notoriously difficult to measure, let alone parameterize, for quantitative comparative studies. Using cross-linguistic dictionaries across languages carefully selected as an unbiased sample reflecting the diversity of human languages, we provide an empirical measure of semantic relatedness between concepts. Our analysis uncovers a universal structure underlying the sampled vocabulary across language groups independent of their phylogenetic relations, their speakers’ culture, and geographic environment.
Transition state for the NSD2-catalyzed methylation of histone H3 lysine 36
Authors: Poulin Myles B. , Schneck Jessica L. , Matico Rosalie E. , McDevitt Patrick J. , Huddleston Michael J. , Hou Wangfang , Johnson Neil W. , Thrall Sara H. , Meek Thomas D. , Schramm Vern L. 
Published: February 2016

Significance
Epigenetic control by methylation of histones is essential in development. Loss of regulation of methylation pathways is involved in developmental disorders and oncogenesis. Despite interest in NSD2, there have been no selective inhibitors reported. Analogs designed to mimic the NSD2 transition state structure are potential enzyme inhibitors. A combination of experimental kinetic isotope effects and quantum chemistry was used to define the subangstrom details of reaction chemistry at the transition state of NSD2. Electrostatic potential maps of reactants and transition states provide a high-resolution map of reaction chemistry and a blueprint for design of transition state analogs for this mechanism of epigenetic regulation.
Curvature-induced stiffness and the spatial variation of wavelength in wrinkled sheets
Authors: Paulsen Joseph D. , Hohlfeld Evan , King Hunter , Huang Jiangshui , Qiu Zhanlong , Russell Thomas P. , Menon Narayanan , Vella Dominic , Davidovitch Benny 
Published: February 2016

Significance
Thin elastic sheets buckle and wrinkle to relax compressive stresses. Wrinkling metrologies have recently been developed as noninvasive probes of mechanical environment or film properties, for instance in biological tissues or textiles. This work proposes and experimentally tests a prediction for the local wavelength of wrinkles in nonuniform curved topographies.
Two types of quasi-liquid layers on ice crystals are formed kinetically
Authors: Asakawa Harutoshi , Sazaki Gen , Nagashima Ken , Nakatsubo Shunichi , Furukawa Yoshinori 
Published: February 2016

Significance
Thin liquid water layers, so-called “quasi-liquid layers” (QLLs), exist on ice surfaces just below the melting point (0 °C). The formation of QLLs governs various important phenomena on Earth, such as weather- and environment-related issues, winter sports, etc. Hence, QLLs have attracted considerable attention in the fields of ice physics, meteorology, crystal growth, and surface science. Our molecular-level observation of QLLs by advanced optical microscopy reveals that QLLs are formed kinetically as metastable phases only in supersaturated water vapor. This finding opens new horizons of understanding QLLs, which have been so far discussed thermodynamically only at an equilibrium condition.
Crystal structure of the pristine peroxidase ferryl center and its relevance to proton-coupled electron transfer
Authors: Chreifi Georges , Baxter Elizabeth L. , Doukov Tzanko , Cohen Aina E. , McPhillips Scott E. , Song Jinhu , Meharenna Yergalem T. , Soltis S. Michael , Poulos Thomas L. 
Published: February 2016

Significance
A major problem in determining the crystal structures of metalloenzymes is that the reducing power of X-rays often changes the oxidation state of the metal center, thereby complicating important mechanistic conclusions on enzyme function. This reduction is especially problematic in studying Fe(IV)=O intermediates, which are powerful oxidants used by many metalloenzymes. This problem can be circumvented using the Stanford Linear Coherent Light Source (LCLS), which generates intense X-ray pulses on the femtosecond time scale and enables structure determinations with no reduction of metal centers. Here, we report the crystal structure of the Fe(IV)=O peroxidase intermediate called compound I using data obtained from the LCLS. We also present kinetic and computational results that, together with crystal structures, provide important mechanistic insights.
T-cell–intrinsic Tif1α/Trim24 regulates IL-1R expression on TH2 cells and TH2 cell-mediated airway allergy
Authors: Perez-Lloret Jimena , Okoye Isobel S. , Guidi Riccardo , Kannan Yashaswini , Coomes Stephanie M. , Czieso Stephanie , Mengus Gabrielle , Davidson Irwin , Wilson Mark S. 
Published: February 2016

SignificanceThe increasing number of patients presenting with severe asthma throughout the world present a clear unmet medical need. This study identified putative transcriptional regulators in T-helper 2 (TH2) cells with the aim of identifying previously unidentified targets to inhibit TH2-mediated allergy. Genetic deletion ofTrim24(tripartite motif-containing 24) in T cells showed that Trim24 was essential for TH2-mediated allergy. Transcriptional analysis showed thatTrim24was required for many of the pathogenic properties of TH2 cells and that IL-1–regulated signaling is compromised in Trim24−/−cells. In vivo, in vitro, and in silico approaches identified a previously overlooked role for Trim24 in TH2-mediated allergy and validate a combined approach to interrogate transcriptional datasets to identify new therapeutic targets to prevent allergy and asthma.
ABA receptor PYL9 promotes drought resistance and leaf senescence
Authors: Zhao Yang , Chan Zhulong , Gao Jinghui , Xing Lu , Cao Minjie , Yu Chunmei , Hu Yuanlei , You Jun , Shi Haitao , Zhu Yingfang , Gong Yuehua , Mu Zixin , Wang Haiqing , Deng Xin , Wang Pengcheng , Bressan Ray A. , Zhu Jian-Kang 
Published: February 2016

Significance
We identified transgenic plants that are extremely resistant to drought from a large-scale screening of transgenic plants overexpressing the pyrabactin resistance 1-like (PYL) family of abscisic acid (ABA) receptors. We explored how these plants resist drought by examining both short-term responses, such as stomatal closure, and long-term responses, such as senescence. The physiological roles of ABA-induced senescence under stress conditions and the underlying molecular mechanism are unclear. Here, we found that ABA induces senescence by activating ABA-responsive element-binding factors and Related to ABA-Insensitive 3/VP1 transcription factors through core ABA signaling. Our results suggest that PYL9 promotes drought resistance by not only limiting transpirational water loss but also, causing summer dormancy-like responses, such as senescence, in old leaves and growth inhibition in young tissues under severe drought conditions.
Beneficial effects of IL-37 after spinal cord injury in mice
Authors: Coll-Miró Marina , Francos-Quijorna Isaac , Santos-Nogueira Eva , Torres-Espin Abel , Bufler Philip , Dinarello Charles A. , López-Vales Rubèn 
Published: February 2016

SignificanceSpinal cord injury (SCI) often results in severely impaired locomotor, sensory, and autonomic function. Although inflammation contributes to the physiopathology of SCI, several clinical trials of high doses of dexamethasone or methylprednisolone have not resulted in improved recovery of function. IL-37, a member of the IL-1 family, exerts broad antiinflammatory effects in several mouse models of inflammatory diseases. We report here that mice expressing human IL-37 exhibit reduced inflammation in the central nervous system and demonstrate significantly improved functional disabilities following SCI. The administration of recombinant forms of human IL-37 enhances motor skills after SCI, suggesting that IL-37 could provide a new therapeutic approach to limit the harmful effects of inflammation in neurologic conditions.