bluuebunny/crossref_metadata_2025 huggingface dataset:
Winning a competition predicts dishonest behavior
Authors: Schurr Amos , Ritov Ilana
Published: February 2016

Significance

Competition 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.
Intrinsic regulation of FIC-domain AMP-transferases by oligomerization and automodification
Authors: Stanger Frédéric V. , Burmann Björn M. , Harms Alexander , Aragão Hugo , Mazur Adam , Sharpe Timothy , Dehio Christoph , Hiller Sebastian , Schirmer Tilman
Published: February 2016

Significance

FIC-domain enzymes are found in all kingdoms of life and catalyze posttranslational modifications of various target proteins to modulate their function. Because the vast majority of Fic proteins are expressed in an inhibited form, their physiological importance has escaped attention for a long time. This article reveals an autonomous mechanism of inhibition relief for class III Fic proteins, which hinges on autoadenylylation of an inhibitory helix. Because the process occurs
in cis
, the Fic enzyme constitutes a molecular timer that operates independent of enzyme concentration. Furthermore, we show that Fic-mediated adenylylation of DNA gyrase leads to bacterial growth arrest. Thus, the time-dependent inactivation of DNA gyrase may serve as a switch to bacterial dormancy under starvation or other stress conditions.
G protein-gated
I

KACh

channels as therapeutic targets for treatment of sick sinus syndrome and heart block
Authors: Mesirca Pietro , Bidaud Isabelle , Briec François , Evain Stéphane , Torrente Angelo G. , Le Quang Khai , Leoni Anne-Laure , Baudot Matthias , Marger Laurine , Chung You Chong Antony , Nargeot Joël , Striessnig Joerg , Wickman Kevin , Charpentier Flavien , Mangoni Matteo E.
Published: February 2016

Significance

The “sick sinus” syndrome (SSS) is characterized by abnormal formation and/or propagation of the cardiac impulse. SSS is responsible for about half of the total implantations of electronic pacemakers, which constitute the only currently available therapy for this disorder. We show that genetic ablation or pharmacological inhibition of the muscarinic-gated K
+
channel (
I

KACh

) prevents SSS and abolishes atrioventricular block in model mice without affecting the relative degree of heart rate regulation. We propose that “compensatory” genetic or pharmacological targeting of
I

KACh

channels may constitute a new paradigm for restoring defects in the balance between inward and outward currents in pacemaker cells. Our study may thus open a new therapeutic perspective to manage dysfunction of formation and conduction of the cardiac impulse.
Targeting theGdnfGene in peritubular myoid cells disrupts undifferentiated spermatogonial cell development
Authors: Chen Liang-Yu , Willis William D. , Eddy Edward M.
Published: February 2016

Significance

Glial 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.
Distinct signaling of
Drosophila
chemoreceptors in olfactory sensory neurons
Authors: Cao Li-Hui , Jing Bi-Yang , Yang Dong , Zeng Xiankun , Shen Ying , Tu Yuhai , Luo Dong-Gen
Published: February 2016

Significance

Drosophila
is a popular model system for the study of olfaction. However, the physiological properties of its olfactory sensory neurons, both intrinsic and responsive, remain unclear. We have succeeded, for the first time, in patch-clamp recording from targeted
Drosophila
OSNs, revealing the distinct signaling of odorant receptors (Ors) and ionotropic receptors (Irs). We found that Ir-driven receptor currents did not adapt, whereas Or responses strongly adapted. Surprisingly, although Or adaptation increased odor sensitivity at high odor backgrounds, it reduced odor sensitivity at low backgrounds. Adaptation permeates all senses, and the finding of dynamic gain control by adaptation in
Drosophila
Or-expressing OSNs sheds light on the understanding of adaptation in other sensory systems.
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

Significance

How 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.
Integrated in vivo and in vitro nascent chain profiling reveals widespread translational pausing
Authors: Chadani Yuhei , Niwa Tatsuya , Chiba Shinobu , Taguchi Hideki , Ito Koreaki
Published: February 2016

Significance

The synthesis of a protein takes tens of seconds to a few minutes, in which amino acids are polymerized linearly. Nonuniform progression of this elongation process is thought to be important for the subsequent fates of newly synthesized proteins. However, there have been few attempts to profile elongation intermediates, polypeptidyl–tRNAs, directly. Here we attempted to detect systematically the accumulation of tRNA-linked nascent chain intermediates during the translation of
Escherichia coli
proteins in vivo and in vitro. The results revealed the widespread occurrence of translational pausing in a manner correlated with the subcellular localization and solubility properties of proteins. Our in vivo/in vitro integrated nascent chain profiling provides groundwork information for our understanding of genetic message translation into functional proteins.
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

Significance

Semantics, 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.
Complexation and coacervation of like-charged polyelectrolytes inspired by mussels
Authors: Kim Sangsik , Huang Jun , Lee Yongjin , Dutta Sandipan , Yoo Hee Young , Jung Young Mee , Jho YongSeok , Zeng Hongbo , Hwang Dong Soo
Published: February 2016

Significance

Conventional coacervates can form on mixing oppositely charged polyelectrolytes in aqueous solutions, due to electrostatic attraction between the oppositely charged polymers. This report describes the first instance (to the best of our knowledge) of complexation and coacervation of two positively charged polyelectrolytes by overcoming longer-range electrostatic repulsion. The molecular force measurements and theoretical simulations demonstrate that the complexation of the like-charged coacervate is most likely driven by strong cation–
π
interactions inspired by marine mussel adhesives. This like-charged coacervation mechanism provides new insights into biological self-assembly processes and a new paradigm for engineering strong, reversible interactions between polymers underwater, which has various potential applications like encapsulation and dispersion of particles and cells.
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.
Legionella pneumophila
S1P-lyase targets host sphingolipid metabolism and restrains autophagy
Authors: Rolando Monica , Escoll Pedro , Nora Tamara , Botti Joëlle , Boitez Valérie , Bedia Carmen , Daniels Craig , Abraham Gilu , Stogios Peter J. , Skarina Tatiana , Christophe Charlotte , Dervins-Ravault Delphine , Cazalet Christel , Hilbi Hubert , Rupasinghe Thusitha W. T. , Tull Dedreia , McConville Malcolm J. , Ong Sze Ying , Hartland Elizabeth L. , Codogno Patrice , Levade Thierry , Naderer Thomas , Savchenko Alexei , Buchrieser Carmen
Published: February 2016

Significance

Legionella pneumophila
is the causative agent of Legionnaires’ disease. It translocates a large repertoire of effectors into the host cell through a specialized secretion system to subvert cellular defenses. A key characteristic of this pathogen is that the majority of its effectors are encoded by eukaryotic-like genes acquired through horizontal gene transfer. We determined the crystal structure of one of these effectors, sphingosine-1 phosphate lyase (
Lp
Spl), and show that it has high similarity with its eukaryotic homologue. We demonstrate that
Lp
Spl possesses lyase activity and that it disrupts sphingolipid metabolism in the host cells.
Lp
Spl plays a critical and previously unknown role in decreasing autophagy and is a unique virulence factor facilitating intracellular replication of
L. pneumophila
.
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

Significance

The 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

Significance

Spinal 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.
Quantitative proteomics and phosphoproteomics on serial tumor biopsies from a sorafenib-treated HCC patient
Authors: Dazert Eva , Colombi Marco , Boldanova Tujana , Moes Suzette , Adametz David , Quagliata Luca , Roth Volker , Terracciano Luigi , Heim Markus H. , Jenoe Paul , Hall Michael N.
Published: February 2016

Significance

Elucidation of evasive resistance to targeted therapies is a major challenge in cancer research. As a proof-of-concept study, we describe quantitative proteomics and phosphoproteomics on serial tumor biopsies from a sorafenib-treated hepatocellular carcinoma (HCC) patient. This approach reveals signaling pathway activity in a tumor and how it evades therapy. The described method will allow precision medicine based on phenotypic data. In particular, application of the method to a patient cohort will potentially identify new biomarkers, drug targets, and signaling pathways that mediate evasive resistance.
Promoting axon regeneration in the adult CNS by modulation of the melanopsin/GPCR signaling
Authors: Li Songshan , Yang Chao , Zhang Li , Gao Xin , Wang Xuejie , Liu Wen , Wang Yuqi , Jiang Songshan , Wong Yung Hou , Zhang Yifeng , Liu Kai
Published: February 2016

Significance

Damage to axons in the CNS typically results in permanent functional deficits. Boosting intrinsic programs such as mammalian target of rapamycin (mTOR) signaling can dramatically augment the axon regenerative capacity of injured neurons. Because certain types of neurons respond to axotomy by maintaining their mTOR activation, we hypothesized that it might be helpful to use this property to promote axon regeneration. We found that the light-responsive G protein-coupled receptor (GPCR) melanopsin could promote axonal regeneration after optic nerve crush by activating mTOR. We also showed that light, Gq/11 signaling, and neuronal activity contribute to the mechanism that underlies this effect. Activating Gq signaling through a chemogenetic approach promoted axon regeneration. Thus, we provided evidence for modulating neuronal activity through GPCR signaling in regulating intrinsic axon growth capacity.
Gene therapy blockade of dorsal striatal p11 improves motor function and dyskinesia in parkinsonian mice
Authors: Marongiu Roberta , Arango-Lievano Margarita , Francardo Veronica , Morgenstern Peter , Zhang Xiaoqun , Cenci M. Angela , Svenningsson Per , Greengard Paul , Kaplitt Michael G.
Published: February 2016

Significance

Medications for Parkinson’s disease (PD) are designed to replace lost dopamine. Although effective, they often cause abnormal involuntary movements (AIMs), also called dyskinesias, which can be difficult to resolve without worsening PD symptoms. We report that p11, a small protein necessary for neurotransmitter receptor function, is critical to dopamine responses in a mouse PD model. Blocking p11 production in the dorsal striatum, a brain region that responds to dopamine and regulates movement, can improve forced movements and normalize spontaneous movements in parkinsonian mice while dramatically reducing AIMs after dopamine replacement therapy. Our data identify a new target for therapeutic development to both improve symptoms and reduce drug-related side effects in human PD.
X-ray structure of the MMTV-A nucleosome core
Authors: Frouws Timothy D. , Duda Sylwia C. , Richmond Timothy J.
Published: February 2016

Significance

The DNA in eukaryotic organisms is packaged in nucleosomes, the fundamental repeating unit of chromatin. The ability of essential transcription regulatory factors to bind genomic recognition sites is contingent on the sequence-dependent conformation of DNA bound in nucleosomes. Our knowledge of the structure of nucleosome DNA is severely limited. The crystal structure of the nucleosome core particle reported here incorporating mouse mammary tumor virus promoter DNA provides new insight into the sequence-dependent structure of DNA as it exists in chromatin.
An ecocultural model predicts Neanderthal extinction through competition with modern humans
Authors: Gilpin William , Feldman Marcus W. , Aoki Kenichi
Published: February 2016

Significance

Ecocultural niche modeling and radiocarbon dating suggest a causal role for interspecific competition in the extinction of Neanderthals. Most archaeologists argue that the advantage to modern humans lay in a higher culture level (a sizable minority dispute this view). Competition between the two species may have occurred when a modern human propagule entered a region occupied by a larger Neanderthal population. We present a model for this replacement, stressing the importance of the founder effect. Our findings shed light on the disappearance of the Neanderthals, showing that endogenous factors such as relative culture level, rather than such extrinsic factors as epidemics or climate change, could have caused the eventual exclusion of a comparatively larger population by an initially smaller one.
Onion-like glycodendrimersomes from sequence-defined Janus glycodendrimers and influence of architecture on reactivity to a lectin
Authors: Xiao Qi , Zhang Shaodong , Wang Zhichun , Sherman Samuel E. , Moussodia Ralph-Olivier , Peterca Mihai , Muncan Adam , Williams Dewight R. , Hammer Daniel A. , Vértesy Sabine , André Sabine , Gabius Hans-Joachim , Klein Michael L. , Percec Virgil
Published: February 2016

Significance

The known role of the sugar
d
-mannose (Man) as a postal code in intracellular cargo routing has herein inspired the design of Man-presenting synthetic glycolipid-like mimics termed Janus glycodendrimers (GDs). Simple injection of a solution of Janus GDs prepared into a water-miscible solvent into buffer produces, via self-assembly, monodisperse multilamellar onion-like glycodendrimersomes (GDSs). Janus GD structural design impacts the resulting GDS architecture including surface display of Man. The latter is shown to tune reactivity to a lectin. Thus GDSs provide a model system to enable systematic studies of physiologically relevant glycan/lectin pairing.
Multiscale model of light harvesting by photosystem II in plants
Authors: Amarnath Kapil , Bennett Doran I. G. , Schneider Anna R. , Fleming Graham R.
Published: February 2016

Significance

Plants thrive in natural sunlight in part because photosystem II (PSII) flexibly captures sunlight. PSII is composed of pigment–protein complexes that densely pack the thylakoid membrane in chloroplasts. We explain the mechanisms underlying the high quantum efficiency of PSII light harvesting in ideal conditions using a quantum mechanical model of excitation energy transport in the membrane. We show that the diffusion length of excitation energy determines the way in which modifications to the membrane affect PSII’s, and ultimately a plant’s, photosynthetic efficiency. The model could be useful for developing artificial light-harvesting materials that are robust to the fluctuations inherent in natural sunlight and rationally engineered crops that achieve higher yields in adverse environments.
CHK2
–
BRCA1
tumor-suppressor axis restrains oncogenic Aurora-A kinase to ensure proper mitotic microtubule assembly
Authors: Ertych Norman , Stolz Ailine , Valerius Oliver , Braus Gerhard H. , Bastians Holger
Published: February 2016

Significance

Inactivation of the tumor-suppressor gene breast cancer susceptibility type 1 (
BRCA1
) triggers abnormal microtubule assembly during mitosis, causing chromosome missegregation and aneuploidy. Unraveling how BRCA1 is regulated during mitosis and how it contributes to microtubule assembly is pivotal to understand its tumor-suppressor function. We showed that BRCA1 is positively regulated during mitosis by the tumor-suppressor kinase checkpoint kinase 2 (Chk2). This regulation is required for the recruitment of a protein phosphatase, which restrains oncogenic Aurora-A kinase activity bound to BRCA1. Unleashed Aurora-A, in turn, can negatively regulate the mitotic function of BRCA1. Thus we define a network in which the Chk2–
BRCA1
tumor-suppressor axis restrains oncogenic Aurora-A to ensure proper function of BRCA1 in mitosis essential for normal regulation of microtubule dynamics and chromosome segregation.
Heightened self-reactivity associated with selective survival, but not expansion, of naïve virus-specific CD8
+
T cells in aged mice
Authors: Quinn Kylie M. , Zaloumis Sophie G. , Cukalac Tania , Kan Wan-Ting , Sng Xavier Y. X. , Mirams Michiko , Watson Katherine A. , McCaw James M. , Doherty Peter C. , Thomas Paul G. , Handel Andreas , La Gruta Nicole L.
Published: February 2016

Significance

Compromised CD8
+
T-cell immunity is associated with significant morbidity and mortality in the elderly. Whereas the number of naïve CD8
+
T cells declines with age, the drivers of loss and consequences for clonal composition are unclear. We show that aging disproportionately impacts small naïve CD8
+
T-cell populations. For one CD8
+
T-cell population, loss of diversity was minimally attributable to expansion but rather was associated with diminished cell number and selective retention of cells exhibiting markers of heightened self, but not foreign, recognition. Thus, vaccine formulations for the elderly may benefit from targeting naïve antigen-specific populations with relatively high precursor frequency and self-reactivity, and retention of high-quality T cells may be achieved through repeated low-level T-cell receptor stimulation.
S1PR1-mediated IFNAR1 degradation modulates plasmacytoid dendritic cell interferon-α autoamplification
Authors: Teijaro John R. , Studer Sean , Leaf Nora , Kiosses William B. , Nguyen Nhan , Matsuki Kosuke , Negishi Hideo , Taniguchi Tadatsugu , Oldstone Michael B. A. , Rosen Hugh
Published: February 2016

Significance

The sphingosine 1-phosphate receptor (S1PR1) is known to act by multiple mechanisms: limiting lymphocyte egress from secondary lymphoid organs, suppressing proinflammatory endothelial cell function, and acting directly on neurons and astrocytes. Here, we report that sphingosine 1-phosphate (S1P)-S1PR1 signaling in plasmacytoid dendritic cells (pDCs) directly inhibits IFN-α autoamplification by induced degradation of the interferon alpha receptor 1 (IFNAR1) receptor and suppression of signal transducer and activator of transcription 1 (STAT1) signaling. An endosomal regulatory interaction of a lipid G-protein coupled receptor (GPCR) and IFNAR1 balances effective and detrimental components of immune responses and provides a previously unidentified pathway that contributes to significant and unexpected efficacy in clinical trials in multiple sclerosis, ulcerative colitis, psoriasis, and likely other diseases with aberrant IFN-α signatures.
Metabolic model for diversity-generating biosynthesis
Authors: Tianero Ma. Diarey , Pierce Elizabeth , Raghuraman Shrinivasan , Sardar Debosmita , McIntosh John A. , Heemstra John R. , Schonrock Zachary , Covington Brett C. , Maschek J. Alan , Cox James E. , Bachmann Brian O. , Olivera Baldomero M. , Ruffner Duane E. , Schmidt Eric W.
Published: February 2016

Significance

How is chemical diversity generated by biological systems? Some biosynthetic pathways are constrained to produce one metabolite, but others are relatively relaxed and can produce a set of diverse compounds. Using the example of the
tru
pathway to cyanobactins, we propose a model of diversity-generating metabolism in which pathway flux and properties are strikingly different from the canonical design of conventional metabolic pathways.
Role of growth hormone-releasing hormone in dyslipidemia associated with experimental type 1 diabetes
Authors: Romero Maritza J. , Lucas Rudolf , Dou Huijuan , Sridhar Supriya , Czikora Istvan , Mosieri Eby M. , Rick Ferenc G. , Block Norman L. , Sridhar Subbaramiah , Fulton David , Weintraub Neal L. , Bagi Zsolt , Schally Andrew V.
Published: February 2016

Significance

Growth hormone-releasing hormone (GHRH) antagonist MIA-602 reduces hyperlipidemia in rats with type 1 diabetes (T1D). Elevated triglyceride-rich lipoprotein (TRL) and LDL levels correlate with renal and cardiovascular disease in T1D. Activity of GLP-1 in the intestine to lower TRL, glucagon, and postprandial glucose levels is impaired in T1D subjects. Expression of GHRH receptor was upregulated in the small intestine, involved in chylomicron synthesis in T1D rats. MIA-602 restored GLP-1 actions on hyperlipidemia and hyperglucagonemia in T1D rats and reduced generation of Apo-B48 induced by oleic acid in intestinal epithelial cells in vitro in a GLP-1–dependent manner. MIA-602 significantly improved proteinuria and vasorelaxation capacity in T1D rats. These findings unravel a previously unidentified pathway in T1D mediated by GHRH associated with impaired GLP-1 signaling and hyperlipidemia.
Myotubes derived from human-induced pluripotent stem cells mirror in vivo insulin resistance
Authors: Iovino Salvatore , Burkart Alison M. , Warren Laura , Patti Mary Elizabeth , Kahn C. Ronald
Published: February 2016

Significance

In this manuscript, we have exploited induced pluripotent stem cells (iPS cells) to generate an in vitro model of human skeletal muscle insulin resistance using cells from patients affected by a monogenic form of insulin resistance (Donohue syndrome/leprechaunism). Following differentiation into skeletal muscle cells, these cells show dramatic defects in insulin signaling, glucose uptake, and glycogen accumulation, as well as insulin-regulated gene expression. To our knowledge, this represents the first use of human iPS cells differentiated into muscle to study diabetes and demonstrates that these cells can robustly reproduce insulin resistance in vitro.
miR-H28 and miR-H29 expressed late in productive infection are exported and restrict HSV-1 replication and spread in recipient cells
Authors: Han Zhiyuan , Liu Xianjie , Chen Xiaoqing , Zhou Xusha , Du Te , Roizman Bernard , Zhou Guoying
Published: February 2016

Significance

Herpes simplex virus-1 (HSV-1) is transmitted by contact between the infected tissues of a transmitter and those of an uninfected recipient. Effective spread requires that the lesions be small and not repulsive in appearance. For successful transmission HSV must control both its replication and its spread from infected to uninfected cells. Here we report that two HSV microRNAs (miRNAs) made late in productive infection are exported in exosomes. Ectopic expression in transfected cells before infection reduces the synthesis of viral gene products and the spread from infected to uninfected cells. The miRNAs accumulate in neurons after latent virus is induced to reactivate. The miRNAs conform to the expectations of gene products that control viral replication and spread.
Global informatics and physical property selection in protein sequences
Authors: Scheraga Harold A. , Rackovsky S.
Published: February 2016

Significance

Many bioinformatic investigations of protein sequence–structure relationships are based on preselected sets of amino acid physical properties. We investigate the extent to which such preselection is justified on information–theoretical grounds. It is shown that neither sequence-dependent nor -averaged properties can be identified as informatically negligible and that no physical properties can be identified that carry sufficient information about other variables to act as surrogates. This result implies that knowledge-based studies of proteins must be based on complete, nonredundant physical property sets.
Use of small specimen creep data in component life management: A review
Authors: Dyson C. C. , Sun W. , Hyde C. J. , Brett S. J. , Hyde T. H.
Published: February 2016

Small specimen creep testing techniques are novel mechanical test techniques that have been developed over the past 25 years. They mainly include the sub-size uniaxial test, the small punch creep test, the impression creep test, the small ring creep test and the two-bar creep test. This paper outlines the current methods in practice for data interpretation as well as the state-of-the-art procedures for conducting the tests. Case studies for the use of impression creep testing and material strength ranking of creep resistant steels are reviewed along with the requirement for the standardisation of the impression creep test method. A database of small specimen creep testing is required to prove the validity of the tests.
Robust and Defensible Mark–Recapture Methodologies for Salmonid Escapement: Modernizing the Use of Data and Resources
Authors: Vélez-Espino L. Antonio , Irvine James R. , Winther Ivan , Dunlop Roger , Mullins Geoff , Singer Kristin , Trouton Nicole
Published: February 2016

Estimates of population size, required for most ecological investigations, are often achieved by mark–recapture experiments, frequently by applying pooled or stratified Petersen estimators. Unfortunately, the closure assumption required by Petersen estimators is frequently violated in the estimation of salmonid escapement, even though the consequences of this violation have been known for decades. We illustrate how biologists and analysts can and should make better use of statistical, mathematical, and computational advances in their analysis of mark–recapture data. Modern, easily applied approaches address and minimize the effects of violations to the model assumptions on which abundance estimators are based. Using examples from research estimating the numbers of Chinook Salmon Oncorhynchus tshawytscha escaping fisheries to spawn, this study demonstrates and provides evidence in support of the use of a robust and defensible approach to salmonid escapement estimation based on the analysis of individual encounter histories. The main attributes of the approach include (1) testing for demographic closure, (2) allowing different hypotheses about the demographic attributes and capture history of the studied population to be expressed within a model selection framework, encompassing suites of open- or closed-population approaches, and (3) optimizing the use of information by embracing the opportunities that mark–recapture experiments generate to increase our knowledge of salmonid ecology and hence improve both future study designs and management decisions. This study also demonstrates that discrepancies (positive) in abundance estimates produced with the Petersen estimator relative to those produced by the “best models” from robust estimators are inversely proportional to sampling rates.

Received May 20, 2015; accepted October 22, 2015
Stability of the retained austenite in low-alloyed transformation induced plasticity-aided steels during friction stir welding
Authors: Miura T. , Ueji R. , Fujii H. , Murakami T. , Kobashi T.
Published: February 2016

To clarify the possibility to maintain the retained austenite even in the joint area of the low-alloyed transformation induced plasticity-aided steel sheets, friction stir welding (FSW) was investigated with a special focus on the effects of the FSW tool rotation rate and initial microstructure on the microstructural evolution and mechanical properties. The experimental results clarified that the lower tool rotation rate and the use of a finer initial microstructure are preferable in order to obtain the retained austenite and the retained austenite obtained by FSW with preferable conditions contributed to maintaining both the strength and ductility of the joints.
Learning faces from variability
Authors: Ritchie Kay L. , Burton A. Mike
Published: February 2016

Research on face learning has tended to use sets of images that vary systematically on dimensions such as pose and illumination. In contrast, we have proposed that exposure to naturally varying images of a person may be a critical part of the familiarization process. Here, we present two experiments investigating face learning with “ambient images”—relatively unconstrained photos taken from internet searches. Participants learned name and face associations for unfamiliar identities presented in high or low within-person variability—that is, images of the same person returned by internet search on their name (high variability) versus different images of the same person taken from the same event (low variability). In Experiment 1 we show more accurate performance on a speeded name verification task for identities learned in high than in low variability, when the test images are completely novel photos. In Experiment 2 we show more accurate performance on a face matching task for identities previously learned in high than in low variability. The results show that exposure to a large range of within-person variability leads to enhanced learning of new identities.
Affine permutations and rational slope parking functions
Authors: Gorsky Eugene , Mazin Mikhail , Vazirani Monica
Published: February 2016

We introduce a new approach to the enumeration of rational slope parking functions with respect to the

area
\operatorname {area}

and a generalized

dinv
\operatorname {dinv}

statistics, and relate the combinatorics of parking functions to that of affine permutations. We relate our construction to two previously known combinatorial constructions: Haglund’s bijection

ζ
\zeta

exchanging the pairs of statistics

(
area
,
dinv
)

(\operatorname {area},\operatorname {dinv})

and

(
bounce
,
area
)

(\operatorname {bounce}, \operatorname {area})

on Dyck paths, and the Pak-Stanley labeling of the regions of

k
k

-Shi hyperplane arrangements by

k
k

-parking functions. Essentially, our approach can be viewed as a generalization and a unification of these two constructions. We also relate our combinatorial constructions to representation theory. We derive new formulas for the Poincaré polynomials of certain affine Springer fibers and describe a connection to the theory of finite-dimensional representations of DAHA and non-symmetric Macdonald polynomials.