bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for chemoreceptors with bimodular ligand-binding regions harboring two signal-binding sites
Authors: Pineda-Molina Estela , Reyes-Darias José-Antonio , Lacal Jesús , Ramos Juan L. , García-Ruiz Juan Manuel , Gavira Jose A. , Krell Tino
Published: October 2012

Chemoreceptor-based signaling is a central mechanism in bacterial signal transduction. Receptors are classified according to the size of their ligand-binding region. The well-studied cluster I proteins have a 100- to 150-residue ligand-binding region that contains a single site for chemoattractant recognition. Cluster II receptors, which contain a 220- to 300-residue ligand-binding region and which are almost as abundant as cluster I receptors, remain largely uncharacterized. Here, we report high-resolution structures of the ligand-binding region of the cluster II McpS chemotaxis receptor (McpS-LBR) of
Pseudomonas putida
KT2440 in complex with different chemoattractants. The structure of McpS-LBR represents a small-molecule binding domain composed of two modules, each able to bind different signal molecules. Malate and succinate were found to bind to the membrane-proximal module, whereas acetate binds to the membrane-distal module. A structural alignment of the two modules revealed that the ligand-binding sites could be superimposed and that amino acids involved in ligand recognition are conserved in both binding sites. Ligand binding to both modules was shown to trigger chemotactic responses. Further analysis showed that McpS-like receptors were found in different classes of proteobacteria, indicating that this mode of response to different carbon sources may be universally distributed. The physiological relevance of the McpS architecture may lie in its capacity to respond with high sensitivity to the preferred carbon sources malate and succinate and, at the same time, mediate lower sensitivity responses to the less preferred but very abundant carbon source acetate.
Capturing native long-range contiguity by in situ library construction and optical sequencing
Authors: Schwartz Jerrod J. , Lee Choli , Hiatt Joseph B. , Adey Andrew , Shendure Jay
Published: October 2012

The relatively short read lengths associated with the most cost-effective DNA sequencing technologies have limited their use in de novo genome assembly, structural variation detection, and haplotype-resolved genome sequencing. Consequently, there is a strong need for methods that capture various scales of contiguity information at a throughput commensurate with the current scale of massively parallel sequencing. We propose in situ library construction and optical sequencing on the flow cells of currently available massively parallel sequencing platforms as an efficient means of capturing both contiguity information and primary sequence with a single technology. In this proof-of-concept study, we demonstrate basic feasibility by generating >30,000
Escherichia coli
paired-end reads separated by 1, 2, or 3 kb using in situ library construction on standard Illumina flow cells. We also show that it is possible to stretch single molecules ranging from 3 to 8 kb on the surface of a flow cell before in situ library construction, thereby enabling the production of clusters whose physical relationship to one another on the flow cell is related to genomic distance.
Metazoan opsin evolution reveals a simple route to animal vision
Authors: Feuda Roberto , Hamilton Sinead C. , McInerney James O. , Pisani Davide
Published: October 2012

All known visual pigments in Neuralia (Cnidaria, Ctenophora, and Bilateria) are composed of an opsin (a seven-transmembrane G protein-coupled receptor), and a light-sensitive chromophore, generally retinal. Accordingly, opsins play a key role in vision. There is no agreement on the relationships of the neuralian opsin subfamilies, and clarifying their phylogeny is key to elucidating the origin of this protein family and of vision. We used improved methods and data to resolve the opsin phylogeny and explain the evolution of animal vision. We found that the Placozoa have opsins, and that the opsins share a common ancestor with the melatonin receptors. Further to this, we found that all known neuralian opsins can be classified into the same three subfamilies into which the bilaterian opsins are classified: the ciliary (C), rhabdomeric (R), and go-coupled plus retinochrome, retinal G protein-coupled receptor (Go/RGR) opsins. Our results entail a simple scenario of opsin evolution. The first opsin originated from the duplication of the common ancestor of the melatonin and opsin genes in a eumetazoan (Placozoa plus Neuralia) ancestor, and an inference of its amino acid sequence suggests that this protein might not have been light-sensitive. Two more gene duplications in the ancestral neuralian lineage resulted in the origin of the R, C, and Go/RGR opsins. Accordingly, the first animal with at least a C, an R, and a Go/RGR opsin was a neuralian progenitor.
Self-monitoring of social facial expressions in the primate amygdala and cingulate cortex
Authors: Livneh Uri , Resnik Jennifer , Shohat Yosi , Paz Rony
Published: October 2012

Keeping track of self-executed facial expressions is essential for the ability to correctly interpret and reciprocate social expressions. However, little is known about neural mechanisms that participate in self-monitoring of facial expression. We designed a natural paradigm for social interactions where a monkey is seated in front of a peer monkey that is concealed by an opaque liquid crystal display shutter positioned between them. Opening the shutter for short durations allowed the monkeys to see each other and encouraged facial communication. To explore neural mechanisms that participate in self-monitoring of facial expression, we simultaneously recorded the elicited natural facial interactions and the neural activity of single neurons in the amygdala and the dorsal anterior cingulate cortex (dACC), two regions that are implicated with decoding of others’ gestures. Neural activity in both regions was temporally locked to distinctive facial gestures and close inspection of time lags revealed activity that either preceded (production) or lagged (monitor) initiation of facial expressions. This result indicates that single neurons in the dACC and the amygdala hold information about self-executed facial expressions and demonstrates an intimate overlap between the neural networks that participate in decoding and production of socially informative facial information.
Interactions of subunit CCT3 in the yeast chaperonin CCT/TRiC with Q/N-rich proteins revealed by high-throughput microscopy analysis
Authors: Nadler-Holly Michal , Breker Michal , Gruber Ranit , Azia Ariel , Gymrek Melissa , Eisenstein Miriam , Willison Keith R. , Schuldiner Maya , Horovitz Amnon
Published: October 2012

The eukaryotic chaperonin containing t-complex polypeptide 1 (CCT/TRiC) is an ATP-fueled machine that assists protein folding. It consists of two back-to-back stacked rings formed by eight different subunits that are arranged in a fixed permutation. The different subunits of CCT are believed to possess unique substrate binding specificities that are still mostly unknown. Here, we used high-throughput microscopy analysis of yeast cells to determine changes in protein levels and localization as a result of a Glu to Asp mutation in the ATP binding site of subunits 3 (CCT3) or 6 (CCT6). The mutation in subunit CCT3 was found to induce cytoplasmic foci termed P-bodies where mRNAs, which are not translated, accumulate and can be degraded. Analysis of the changes in protein levels and structural modeling indicate that P-body formation in cells with the mutation in CCT3 is linked to the specific interaction of this subunit with Gln/Asn-rich segments that are enriched in many P-body proteins. An in vitro gel-shift analysis was used to show that the mutation in subunit CCT3 interferes with the ability of CCT to bind a Gln/Asn-rich protein aggregate. More generally, the strategy used in this work can be used to unravel the substrate specificities of other chaperone systems.
General anesthesia selectively disrupts astrocyte calcium signaling in the awake mouse cortex
Authors: Thrane Alexander Stanley , Rangroo Thrane Vinita , Zeppenfeld Douglas , Lou Nanhong , Xu Qiwu , Nagelhus Erlend Arnulf , Nedergaard Maiken
Published: October 2012

Calcium signaling represents the principle pathway by which astrocytes respond to neuronal activity. General anesthetics are routinely used in clinical practice to induce a sleep-like state, allowing otherwise painful procedures to be performed. Anesthetic drugs are thought to mainly target neurons in the brain and act by suppressing synaptic activity. However, the direct effect of general anesthesia on astrocyte signaling in awake animals has not previously been addressed. This is a critical issue, because calcium signaling may represent an essential mechanism through which astrocytes can modulate synaptic activity. In our study, we performed calcium imaging in awake head-restrained mice and found that three commonly used anesthetic combinations (ketamine/xylazine, isoflurane, and urethane) markedly suppressed calcium transients in neocortical astrocytes. Additionally, all three anesthetics masked potentially important features of the astrocyte calcium signals, such as synchronized widespread transients that appeared to be associated with arousal in awake animals. Notably, anesthesia affected calcium transients in both processes and soma and depressed spontaneous signals, as well as calcium responses, evoked by whisker stimulation or agonist application. We show that these calcium transients are inositol 1,4,5-triphosphate type 2 receptor (IP
3
R2)-dependent but resistant to a local blockade of glutamatergic or purinergic signaling. Finally, we found that doses of anesthesia insufficient to affect neuronal responses to whisker stimulation selectively suppressed astrocyte calcium signals. Taken together, these data suggest that general anesthesia may suppress astrocyte calcium signals independently of neuronal activity. We propose that these glial effects may constitute a nonneuronal mechanism for sedative action of anesthetic drugs.
Indian Ocean warming modulates Pacific climate change
Authors: Luo Jing-Jia , Sasaki Wataru , Masumoto Yukio
Published: October 2012

It has been widely believed that the tropical Pacific trade winds weakened in the last century and would further decrease under a warmer climate in the 21st century. Recent high-quality observations, however, suggest that the tropical Pacific winds have actually strengthened in the past two decades. Precise causes of the recent Pacific climate shift are uncertain. Here we explore how the enhanced tropical Indian Ocean warming in recent decades favors stronger trade winds in the western Pacific via the atmosphere and hence is likely to have contributed to the La Niña-like state (with enhanced east–west Walker circulation) through the Pacific ocean–atmosphere interactions. Further analysis, based on 163 climate model simulations with centennial historical and projected external radiative forcing, suggests that the Indian Ocean warming relative to the Pacific’s could play an important role in modulating the Pacific climate changes in the 20th and 21st centuries.
Reduced sensitivity to emotional prosody in congenital amusia rekindles the musical protolanguage hypothesis
Authors: Thompson William Forde , Marin Manuela M. , Stewart Lauren
Published: October 2012

A number of evolutionary theories assume that music and language have a common origin as an emotional protolanguage that remains evident in overlapping functions and shared neural circuitry. The most basic prediction of this hypothesis is that sensitivity to emotion in speech prosody derives from the capacity to process music. We examined sensitivity to emotion in speech prosody in a sample of individuals with congenital amusia, a neurodevelopmental disorder characterized by deficits in processing acoustic and structural attributes of music. Twelve individuals with congenital amusia and 12 matched control participants judged the emotional expressions of 96 spoken phrases. Phrases were semantically neutral but prosodic cues (tone of voice) communicated each of six emotional states: happy, tender, afraid, irritated, sad, and no emotion. Congenitally amusic individuals were significantly worse than matched controls at decoding emotional prosody, with decoding rates for some emotions up to 20% lower than that of matched controls. They also reported difficulty understanding emotional prosody in their daily lives, suggesting some awareness of this deficit. The findings support speculations that music and language share mechanisms that trigger emotional responses to acoustic attributes, as predicted by theories that propose a common evolutionary link between these domains.
Bottom-up construction of in vitro switchable memories
Authors: Padirac Adrien , Fujii Teruo , Rondelez Yannick
Published: October 2012

Reaction networks displaying bistability provide a chemical mechanism for long-term memory storage in cells, as exemplified by many epigenetic switches. These biological systems are not only bistable but switchable, in the sense that they can be flipped from one state to the other by application of specific molecular stimuli. We have reproduced such functions through the rational assembly of dynamic reaction networks based on basic DNA biochemistry. Rather than rewiring genetic systems as synthetic biology does in vivo, our strategy consists of building simplified dynamic analogs in vitro, in an artificial, well-controlled milieu. We report successively a bistable system, a two-input switchable memory element, and a single-input push-push memory circuit. These results suggest that it is possible to build complex time-responsive molecular circuits by following a modular approach to the design of dynamic in vitro behaviors. Our approach thus provides an unmatched opportunity to study topology/function relationships within dynamic reaction networks.
Prediction of economic choice by primate amygdala neurons
Authors: Grabenhorst Fabian , Hernádi István , Schultz Wolfram
Published: October 2012

The amygdala is a key structure of the brain’s reward system. Existing theories view its role in decision-making as restricted to an early valuation stage that provides input to decision mechanisms in downstream brain structures. However, the extent to which the amygdala itself codes information about economic choices is unclear. Here, we report that individual neurons in the primate amygdala predict behavioral choices in an economic decision task. We recorded the activity of amygdala neurons while monkeys chose between saving liquid reward with interest and spending the accumulated reward. In addition to known value-related responses, we found that activity in a group of amygdala neurons predicted the monkeys’ upcoming save–spend choices with an average accuracy of 78%. This choice-predictive activity occurred early in trials, even before information about specific actions associated with save–spend choices was available. For a substantial number of neurons, choice-differential activity was specific for free, internally generated economic choices and not observed in a control task involving forced imperative choices. A subgroup of choice-predictive neurons did not show relationships to value, movement direction, or visual stimulus features. Choice-predictive activity in some amygdala neurons was preceded by transient periods of value coding, suggesting value-to-choice transitions and resembling decision processes in other brain systems. These findings suggest that the amygdala might play an active role in economic decisions. Current views of amygdala function should be extended to incorporate a role in decision-making beyond valuation.
Radiocarbon dates from the Grotte du Renne and Saint-Césaire support a Neandertal origin for the Châtelperronian
Authors: Hublin Jean-Jacques , Talamo Sahra , Julien Michèle , David Francine , Connet Nelly , Bodu Pierre , Vandermeersch Bernard , Richards Michael P.
Published: October 2012

The transition from the Middle Paleolithic (MP) to Upper Paleolithic (UP) is marked by the replacement of late Neandertals by modern humans in Europe between 50,000 and 40,000 y ago. Châtelperronian (CP) artifact assemblages found in central France and northern Spain date to this time period. So far, it is the only such assemblage type that has yielded Neandertal remains directly associated with UP style artifacts. CP assemblages also include body ornaments, otherwise virtually unknown in the Neandertal world. However, it has been argued that instead of the CP being manufactured by Neandertals, site formation processes and layer admixture resulted in the chance association of Neanderthal remains, CP assemblages, and body ornaments. Here, we report a series of accelerator mass spectrometry radiocarbon dates on ultrafiltered bone collagen extracted from 40 well-preserved bone fragments from the late Mousterian, CP, and Protoaurignacian layers at the Grotte du Renne site (at Arcy-sur-Cure, France). Our radiocarbon results are inconsistent with the admixture hypothesis. Further, we report a direct date on the Neandertal CP skeleton from Saint-Césaire (France). This date corroborates the assignment of CP assemblages to the latest Neandertals of western Europe. Importantly, our results establish that the production of body ornaments in the CP postdates the arrival of modern humans in neighboring regions of Europe. This new behavior could therefore have been the result of cultural diffusion from modern to Neandertal groups.
Neutrophils orchestrate their own recruitment in murine arthritis through C5aR and FcγR signaling
Authors: Sadik Christian D. , Kim Nancy D. , Iwakura Yoichiro , Luster Andrew D.
Published: October 2012

Neutrophil recruitment into the joint is a hallmark of inflammatory arthritides, including rheumatoid arthritis (RA). In a mouse model of autoantibody-induced inflammatory arthritis, neutrophils infiltrate the joint via multiple chemoattractant receptors, including the leukotriene B4(LTB4) receptor BLT1 and the chemokine receptors CCR1 and CXCR2. Once in the joint, neutrophils perpetuate their own recruitment by releasing LTB4and IL-1β, presumably after activation by immune complexes deposited on joint structures. Two pathways by which immune complexes may activate neutrophils include complement fixation, resulting in the generation of C5a, and direct engagement of Fcγ receptors (FcγRs). Previous investigations showed that this model of autoantibody-induced arthritis requires the C5a receptor C5aR and FcγRs, but the simultaneous necessity for both pathways was not understood. Here we show that C5aR and FcγRs work in sequence to initiate and sustain neutrophil recruitment in vivo. Specifically, C5aR activation of neutrophils is required for LTB4release and early neutrophil recruitment into the joint, whereas FcγR engagement upon neutrophils induces IL-1β release and subsequent neutrophil-active chemokine production, ensuring continued inflammation. These findings support the concept that immune complex-mediated leukocyte activation is not composed of overlapping and redundant pathways, but that each element serves a distinct and critical function in vivo, culminating in tissue inflammation.
Reversible online control of habitual behavior by optogenetic perturbation of medial prefrontal cortex
Authors: Smith Kyle S. , Virkud Arti , Deisseroth Karl , Graybiel Ann M.
Published: October 2012

Habits tend to form slowly but, once formed, can have great stability. We probed these temporal characteristics of habitual behaviors by intervening optogenetically in forebrain habit circuits as rats performed well-ingrained habitual runs in a T-maze. We trained rats to perform a maze habit, confirmed the habitual behavior by devaluation tests, and then, during the maze runs (ca.3 s), we disrupted population activity in a small region in the medial prefrontal cortex, the infralimbic cortex. In accordance with evidence that this region is necessary for the expression of habits, we found that this cortical disruption blocked habitual behavior. Notably, however, this blockade of habitual performance occurred on line, within an average of three trials (ca.9 s of inhibition), and as soon as during the first trial (<3 s). During subsequent weeks of training, the rats acquired a new behavioral pattern. When we again imposed the same cortical perturbation, the rats regained the suppressed maze-running that typified the original habit, and, simultaneously, the more recently acquired habit was blocked. These online changes occurred within an average of two trials (ca.6 s of infralimbic inhibition). Measured changes in generalized performance ability and motivation to consume reward were unaffected. This immediate toggling between breaking old habits and returning to them demonstrates that even semiautomatic behaviors are under cortical control and that this control occurs online, second by second. These temporal characteristics define a framework for uncovering cellular transitions between fixed and flexible behaviors, and corresponding disturbances in pathologies.
Dynamic network structure of interhemispheric coordination
Authors: Doron Karl W. , Bassett Danielle S. , Gazzaniga Michael S.
Published: October 2012

Fifty years ago Gazzaniga and coworkers published a seminal article that discussed the separate roles of the cerebral hemispheres in humans. Today, the study of interhemispheric communication is facilitated by a battery of novel data analysis techniques drawn from across disciplinary boundaries, including dynamic systems theory and network theory. These techniques enable the characterization of dynamic changes in the brain’s functional connectivity, thereby providing an unprecedented means of decoding interhemispheric communication. Here, we illustrate the use of these techniques to examine interhemispheric coordination in healthy human participants performing a split visual field experiment in which they process lexical stimuli. We find that interhemispheric coordination is greater when lexical information is introduced to the right hemisphere and must subsequently be transferred to the left hemisphere for language processing than when it is directly introduced to the language-dominant (left) hemisphere. Further, we find that putative functional modules defined by coherent interhemispheric coordination come online in a transient manner, highlighting the underlying dynamic nature of brain communication. Our work illustrates that recently developed dynamic, network-based analysis techniques can provide novel and previously unapproachable insights into the role of interhemispheric coordination in cognition.
Assembly of macromolecular complexes by satisfaction of spatial restraints from electron microscopy images
Authors: Velázquez-Muriel Javier , Lasker Keren , Russel Daniel , Phillips Jeremy , Webb Benjamin M. , Schneidman-Duhovny Dina , Sali Andrej
Published: October 2012

To obtain a structural model of a macromolecular assembly by single-particle EM, a large number of particle images need to be collected, aligned, clustered, averaged, and finally assembled via reconstruction into a 3D density map. This process is limited by the number and quality of the particle images, the accuracy of the initial model, and the compositional and conformational heterogeneity. Here, we describe a structure determination method that avoids the reconstruction procedure. The atomic structures of the individual complex components are assembled by optimizing a match against 2D EM class-average images, an excluded volume criterion, geometric complementarity, and optional restraints from proteomics and chemical cross-linking experiments. The optimization relies on a simulated annealing Monte Carlo search and a divide-and-conquer message-passing algorithm. Using simulated and experimentally determined EM class averages for 12 and 4 protein assemblies, respectively, we show that a few class averages can indeed result in accurate models for complexes of as many as five subunits. Thus, integrative structural biology can now benefit from the relative ease with which the EM class averages are determined.
Modulation of BK channel voltage gating by different auxiliary β subunits
Authors: Contreras Gustavo F. , Neely Alan , Alvarez Osvaldo , Gonzalez Carlos , Latorre Ramon
Published: October 2012

Calcium- and voltage-activated potassium channels (BK) are regulated by a multiplicity of signals. The prevailing view is that different BK gating mechanisms converge to determine channel opening and that these gating mechanisms are allosterically coupled. In most instances the pore forming α subunit of BK is associated with one of four alternative β subunits that appear to target specific gating mechanisms to regulate the channel activity. In particular, β1 stabilizes the active configuration of the BK voltage sensor having a large effect on BK Ca
2+
sensitivity. To determine the extent to which β subunits regulate the BK voltage sensor, we measured gating currents induced by the pore-forming BK α subunit alone and with the different β subunits expressed in
Xenopus
oocytes (β1, β2IR, β3b, and β4). We found that β1, β2, and β4 stabilize the BK voltage sensor in the active conformation. β3 has no effect on voltage sensor equilibrium. In addition, β4 decreases the apparent number of charges per voltage sensor. The decrease in the charge associated with the voltage sensor in α β4 channels explains most of their biophysical properties. For channels composed of the α subunit alone, gating charge increases slowly with pulse duration as expected if a significant fraction of this charge develops with a time course comparable to that of K
+
current activation. In the presence of β1, β2, and β4 this slow component develops in advance of and much more rapidly than ion current activation, suggesting that BK channel opening proceeds in two steps.
Allard's argument versus Baker's contention for the adaptive significance of selfing in a hermaphroditic fish
Authors: Avise John C. , Tatarenkov Andrey
Published: October 2012

Fertilization assurance (Baker's contention) and multilocus coadaptation (Allard's argument) are two distinct hypotheses for the adaptive significance of self-fertilization in hermaphroditic taxa, and both scenarios have been invoked to rationalize isogenicity via incest in various plants and invertebrate animals with predominant selfing. Here we contrast Allard's argument and Baker's contention as applied to the world's only known vertebrate that routinely self-fertilizes. We pay special attention to frequencies of locally most common multilocus genotypes in Floridian populations of the Mangrove Rivulus (
Kryptolebias marmoratus
). Isogenicity patterns in this fish appear inconsistent with Allard's argument, thus leaving Baker’s contention as the more plausible scenario (a result also supported by natural history information for this species). These results contrast with the isogenicity patterns and conclusions previously drawn from several self-fertilizing plants and invertebrate animal species. Thus, the adaptive significance of selfing apparently varies across hermaphroditic taxa.
The public library in the UK’s Big Society
Authors: Davies Steve
Published: October 2012

Steve Davies is a trade unionist and academic, working on the response of the international trade union movement to globalisation. He takes a particular interest in public sector reform and has written several reports on public libraries for the union UNISON.
Complexities and Challenges for Civil Society Building in Post-Conflict Settings
Authors: Van Leeuwen Mathijs , Verkoren Willemijn
Published: October 2012

Strengthening or even ‘building’ civil society has become a preoccupation of international development actors working in post-conflict settings. However, how to do so effectively remains a difficult and theoretically underexplored question. This article identifies two core challenges. The first is how to overcome the discrepancy between what international development actors aim to achieve in building civil society – namely the strengthening of the social contract between a state and its citizens – and strategies to achieve it that focus narrowly on local NGOs and on their roles in apolitical service delivery, leaving out the state. The second is how to take better account of the complexities of the local institutions and processes concerned, and the alternative forms of social contract that might come about. This article explores these challenges and recommends how debate and research might proceed.
Demographic Turbulence in the Arab World: Implications for Development Policy
Authors: Pool Ian
Published: October 2012

The Arab Spring's hallmarks of volatility and ‘youthfulness’ thwart sustained development, political cohesion and peace. Demographic ‘youthfulness’, due to recent high fertility, is accompanied by rapid growth. But the backstory is even bleaker. Cohort flows, producing large population waves, batter successive life-cycle stages, generating demands for services, markets, resources and capital. To overcome this, policies directed at youth (15–24) are pivotal; failure to integrate youth into the economy and society results in disadvantaged middle-aged parenting populations. This threatens longer-term, sustainable development and triggers political volatility. Yet, as is shown in this article, the international development community has failed to formulate appropriate strategies.
Analysis of a wild mouse promoter variant reveals a novel role for FcγRIIb in the control of the germinal center and autoimmunity
Authors: Espéli Marion , Clatworthy Menna R. , Bökers Susanne , Lawlor Kate E. , Cutler Antony J. , Köntgen Frank , Lyons Paul A. , Smith Kenneth G.C.
Published: October 2012

Genetic variants of the inhibitory Fc receptor FcγRIIb have been associated with systemic lupus erythematosus in humans and mice. The mechanism by which Fcgr2b variants contribute to the development of autoimmunity is unknown and was investigated by knocking in the most commonly conserved wild mouse Fcgr2b promoter haplotype, also associated with autoimmune-prone mouse strains, into the C57BL/6 background. We found that in the absence of an AP-1–binding site in its promoter, FcγRIIb failed to be up-regulated on activated and germinal center (GC) B cells. This resulted in enhanced GC responses, increased affinity maturation, and autoantibody production. Accordingly, in the absence of FcγRIIb activation–induced up-regulation, mice developed more severe collagen-induced arthritis and spontaneous glomerular immune complex deposition. Our data highlight how natural variation in Fcgr2b drives the development of autoimmune disease. They also show how the study of such variants using a knockin approach can provide insight into immune mechanisms not possible using conventional genetic manipulation, in this case demonstrating an unexpected critical role for the activation-induced up-regulation of FcγRIIb in controlling affinity maturation, autoantibody production, and autoimmunity.
Effective Antimicrobial Stewardship in a Long-Term Care Facility through an Infectious Disease Consultation Service: Keeping a LID on Antibiotic Use
Authors: Jump Robin L. P. , Olds Danielle M. , Seifi Nasim , Kypriotakis Georgios , Jury Lucy A. , Peron Emily P. , Hirsch Amy A. , Drawz Paul E. , Watts Brook , Bonomo Robert A. , Donskey Curtis J.
Published: October 2012

Design.

We introduced a long-term care facility (LTCF) infectious disease (ID) consultation service (LID service) that provides on-site consultations to residents of a Veterans Affairs (VA) LTCF. We determined the impact of the LID service on antimicrobial use and Clostridium difficile infections at the LTCF.

Setting.

A 160-bed VA LTCF.

Methods.

Systemic antimicrobial use and positive C. difficile tests at the LTCF were compared for the 36 months before and the 18 months after the initiation of the ID consultation service through segmented regression analysis of an interrupted time series.

Results.

Relative to that in the preintervention period, total systemic antibiotic administration decreased by 30% (P<.001), with significant reductions in both oral (32%; P<.001) and intravenous (25%; P = .008) agents. The greatest reductions were seen for tetracyclines (64%; P<.001), clindamycin (61%; P<.001), sulfamethoxazole/trimethoprim (38%; P<.001), fluoroquinolones (38%; P<.001), and β lactam/β-lactamase inhibitor combinations (28%; P<.001). The rate of positive C. difficile tests at the LTCF declined in the postintervention period relative to preintervention rates (P = .04).

Conclusions.

Implementation of an LTCF ID service led to a significant reduction in total antimicrobial use. Bringing providers with ID expertise to the LTCF represents a new and effective means to achieve antimicrobial stewardship.
Efficacy of Different Cleaning and Disinfection Methods against Clostridium difficile Spores: Importance of Physical Removal versus Sporicidal Inactivation
Authors: Rutala William A. , Gergen Maria F. , Weber David J.
Published: October 2012

We tested the effectiveness of disinfectants and wipe methods against Clostridium difficile spores. Wiping with nonsporicidal agents (physical removal) was effective in removing more than 2.9 log10C. difficile spores. Wiping with sporicidal agents eliminated more than 3.90 log10C. difficile spores (physical removal and/or inactivation). Spraying with a sporicide eliminated more than 3.44 log10C. difficile spores but would not remove debris.
Transfer from High-Acuity Long-Term Care Facilities Is Associated with Carriage of Klebsiella pneumoniae Carbapenemase–Producing Enterobacteriaceae: A Multihospital Study
Authors: Prabaker Kavitha , Lin Michael Y. , McNally Margaret , Cherabuddi Kartikeya , Ahmed Sana , Norris Andrea , Lolans Karen , Odeh Ruba , Chundi Vishnu , Weinstein Robert A. , Hayden Mary K. ,   Centers for Disease Control and Prevention (CDC) Prevention Epicenters Program
Published: October 2012

Objective.

To determine whether transfer from a long-term care facility (LTCF) is a risk factor for colonization with Klebsiella pneumoniae carbapenemase (KPC)–producing Enterobacteriaceae upon acute care hospital admission.

Design.

Microbiologic survey and nested case-control study.

Setting.

Four hospitals in a metropolitan area (Chicago) with an early KPC epidemic.

Patients.

Hospitalized adults.

Methods.

Patients transferred from LTCFs were matched 1 : 1 to patients admitted from the community by age (± 10 years), admitting clinical service, and admission date (± 2 weeks). Rectal swab specimens were collected within 3 days after admission and tested for KPC-producing Enterobacteriaceae. Demographic and clinical information was extracted from medical records.

Results.

One hundred eighty patients from LTCFs were matched to 180 community patients. KPC-producing Enterobacteriaceae colonization was detected in 15 (8.3%) of the LTCF patients and 0 (0%) of the community patients (P<.001). Prevalence of carriage differed by LTCF subtype: 2 of 135 (1.5%) patients from skilled nursing facilities without ventilator care (SNFs) were colonized upon admission, compared to 9 of 33 (27.3%) patients from skilled nursing facilities with ventilator care (VSNFs) and 4 of 12 (33.3%) patients from long-term acute care hospitals (LTACHs; P<.001). In a multivariable logistic regression model adjusted for a propensity score that predicted LTCF subtype, patients admitted from VSNFs or LTACHs had 7.0-fold greater odds of colonization (ie, odds ratio; 95% confidence interval, 1.3–42; P = .022) with KPC-producing Enterobacteriaceae than patients from an SNF.

Conclusions.

Patients admitted to acute care hospitals from high-acuity LTCFs (ie, VSNFs and LTACHs) were more likely to be colonized with KPC-producing Enterobacteriaceae than were patients admitted from the community. Identification of healthcare facilities with a high prevalence of colonized patients presents an opportunity for focused interventions that may aid regional control efforts.
Gordonia bronchialis Sternal Wound Infection in 3 Patients following Open Heart Surgery: Intraoperative Transmission from a Healthcare Worker
Authors: Wright Shaneka N. , Gerry Joanna S. , Busowski Mary T. , Klochko Alena Y. , McNulty Steven G. , Brown Scott A. , Sieger Barry E. , Michaels P. Ken , Wallace Mark R.
Published: October 2012

We describe an investigation of 3 postoperative Gordonia bronchialis sternal infections. A nurse anesthetist was identified as the source of the outbreak, her scrubs likely becoming contaminated by her home washing machine. The outbreak ended after disposal of the implicated washing machine. Domestic laundering of surgical scrubs may need reevaluation.
Monte Carlo study of the surface effect on the compensation and critical behaviour in a molecular-based magnetic film AFeIIFeIII(C2O4)3
Authors: Wang Wei , Jiang Wei , Lv Dan , zhang Fan
Published: October 2012

Monte Carlo simulation is used to study the magnetic properties and critical behaviour of a molecular-based magnetic film AFeIIFeIII(C2O4)3(A = N(n − C
n
H2n+1)4, n = 3–5). The effects of surface exchange coupling, surface single-ion anisotropy and layer thickness on the compensation temperature and critical temperature of a ferrimagnetic mixed spin-2 and spin-5/2 Ising model on a honeycomb lattice are discussed in detail. The results show that the surface intralayer exchange coupling R
1 = J
1S/|J
1| and surface interlayer exchange coupling R
2 = J
2S/|J
1| play important roles in the compensation and critical behaviour of the system. In particular, we have found two special points R
1c at which the compensation and critical temperatures are independent of the layer thickness L and the surface single-ion anisotropy D
1S/|J
1|. A number of characteristic phenomena, such as the possibility of two and three compensation points, are found. The effects of the layer thickness L on the susceptibility, internal energy and specific heat with temperature are numerically investigated.
Mechanical contact between rough surfaces at low load
Authors: Lu Pin , O'Shea S J
Published: October 2012

A model is developed to describe the initial contact between rough surfaces. The Greenwood–Williamson statistical approach is used with exponential or Weibull asperity height distributions, and modified with the relative displacement between the surfaces referenced to the initial contact of the highest asperity (within a given area) at zero load. This form provides a framework for investigating contact at low loads or contact over small area e.g. as found in microfabricated structures. The approach gives the expected number of asperities touching, the real area of contact and the normal force in terms of the indentation. The model results show that for hard surface materials (e.g. Silicon), very few asperities may be in contact at low loads (∼1 µN) even over large nominal surface areas (∼20 × 20 µm2), in accordance with observations drawn from microfabrication experiments. This suggests an analytical means to bridge nanoscale concepts and approaches (e.g. superlubricity, friction at a single asperity) to microscale structures.
Investigation of the mid-infrared emission of a floating water bridge
Authors: Fuchs Elmar C , Cherukupally Anvesh , Paulitsch-Fuchs Astrid H , Agostinho Luewton L F , Wexler Adam D , Woisetschläger Jakob , Freund Friedemann T
Published: October 2012

We report on the infrared emission of aqueous bridges under the application of high dc voltage (‘floating water bridge’) over the range between 400 and 2500 cm−1 (4.0–10.3 µm). Comparison with bulk water of the same temperature reveals an additional broad peak at ∼2200 cm−1 as well as water vapour emission lines. Two complementary explanations are presented for the broad peak: first, a cooperative proton transfer comprising an orientational motion along the direction of conduction is suggested. Second, the electrolysis-less current flow is explained by a proton/defect-proton band mechanism, which is in line with the cooperative proton transfer. The water vapour emissions occur due to collision ionization of space charges with micro- and nano-droplets which are electrosprayed from the liquid/gas interface.
Effects of fibre-form nanostructures on particle emissions from a tungsten surface in plasmas
Authors: Takamura S. , Miyamoto T. , Ohno N.
Published: October 2012

The effects of fibre-form nanostructure of a tungsten surface on both electron emission and sputtering in helium/argon plasmas are represented. Generally, a nano-fibre forest, the so-called ‘fuzz’, made of tungsten with helium gas inside is found to have the tendency of suppressing the particle emission substantially. The electron emission comes from the impact of high-energy primary electrons. In addition, a deeply biased tungsten target, which inhibits the influx of even energetic primary electrons, seems to produce an electron emission, and it may be suppressed on the way to nanostructure formation on the surface of the W target. Such an emission process is discussed here. The sputtering yield of the He-damaged tungsten surface with the fibre-form nanostructure depends on the surface morphology while the sputtering itself changes the surface morphology, so that the time evolutions of sputtering yield from the W surface with an originally well-developed nanostructure are found to show a minimum in sputtering yield, which is about a half for the fresh nanostructured tungsten and roughly one-fifth of the yield for the original flat normal tungsten surface. The surface morphology at that time is, for the first time, made clear with field emission scanning electron microscopy observation. The physical mechanism for the appearance of such a minimum in sputtering yield is discussed.
Membranes, viruses, detergents, and endosomes
Authors: Helenius Ari
Published: October 2012

The fluid mosaic model for biological membranes was formulated 40 years ago. Ten years later endosomes were discovered as important prelysosomal organelles. At the outset of my research career, I was fortunate to witness both these turning points in biochemistry and cell biology from close up, and to participate in some of the studies. In this short essay, I will describe how this came about, and also try to provide some background as to the general starting situation in those not so distant pioneering years of membrane biology.
A career at the interface of cell and developmental biology: a view from the crest
Authors: Bronner Marianne E.
Published: October 2012

Just as neural crest cells migrate great distances through the embryo, my journey has taken me from a childhood in a distant land to a career as a biologist. My mentoring relationships have shaped not only the careers of my trainees, but also the trajectory of my own science. One of the most satisfying aspects of mentoring comes from helping to empower the next generation of scientists to do more tomorrow than is possible today. This, together with a passion for discovery and learning new things, motivates me and makes science such a rewarding career.
Why we need more basic biology research, not less
Authors: Botstein David
Published: October 2012

Much of the spectacular progress in biomedical science over the last half-century is the direct consequence of the work of thousands of basic scientists whose primary goal was understanding of the fundamental working of living things. Despite this, many politicians, funders, and even scientists have come to believe that the pace of successful applications to medical diagnosis and therapy is limited by our willingness to focus directly on human health, rather than a continuing deficit of understanding. By this theory, curiosity-driven research, aimed at understanding, is no longer important or even useful. What is advocated instead is “translational” research aimed directly at treating disease. I believe this idea to be deeply mistaken. Recent history suggests instead that what we have learned in the last 50 years is only the beginning. The way forward is to invest more in basic science, not less.
Political advocacy by the American Society for Cell Biology and its partners
Authors: Pollard Thomas D.
Published: October 2012

I trace how the American Society for Cell Biology became a strong political advocate for the scientific community. I celebrate how good leadership and an effective staff enabled its energetic volunteer organization to have an impact, but I also ask how the effort can be made more successful.
Integrin α5/fibronectin1 and focal adhesion kinase are required for lens fiber morphogenesis in zebrafish
Authors: Hayes Julie M. , Hartsock Andrea , Clark Brian S. , Napier Hugh R. L. , Link Brian A. , Gross Jeffrey M.
Published: October 2012

Lens fiber formation and morphogenesis requires a precise orchestration of cell– extracellular matrix (ECM) and cell–cell adhesive changes in order for a lens epithelial cell to adopt a lens fiber fate, morphology, and migratory ability. The cell–ECM interactions that mediate these processes are largely unknown, and here we demonstrate that fibronectin1 (Fn1), an ECM component, and integrin α5, its cellular binding partner, are required in the zebrafish lens for fiber morphogenesis. Mutations compromising either of these proteins lead to cataracts, characterized by defects in fiber adhesion, elongation, and packing. Loss of integrin α5/Fn1 does not affect the fate or viability of lens epithelial cells, nor does it affect the expression of differentiation markers expressed in lens fibers, although nucleus degradation is compromised. Analysis of the intracellular mediators of integrin α5/Fn1 activity focal adhesion kinase (FAK) and integrin-linked kinase (ILK) reveals that FAK, but not ILK, is also required for lens fiber morphogenesis. These results support a model in which lens fiber cells use integrin α5 to migrate along a Fn-containing substrate on the apical side of the lens epithelium and on the posterior lens capsule, likely activating an intracellular signaling cascade mediated by FAK in order to orchestrate the cytoskeletal changes in lens fibers that facilitate elongation, migration, and compaction.
ADAM: automated data management for research datasets
Authors: Woodbridge Mark , Tomlinson Christopher D. , Butcher Sarah A.
Published: October 2012

Existing repositories for experimental datasets typically capture snapshots of data acquired using a single experimental technique and often require manual population and continual curation. We present a storage system for heterogeneous research data that performs dynamic automated indexing to provide powerful search, discovery and collaboration features without the restrictions of a structured repository. ADAM is able to index many commonly used file formats generated by laboratory assays and therefore offers specific advantages to the experimental biology community. However, it is not domain specific and can promote sharing and re-use of working data across scientific disciplines.

Availability and implementation: ADAM is implemented using Java and supported on Linux. It is open source under the GNU General Public License v3.0. Installation instructions, binary code, a demo system and virtual machine image and are available at http://www.imperial.ac.uk/bioinfsupport/resources/software/adam.

Contact:  m.woodbridge@imperial.ac.uk
Velocity-dependent energy gaps and dynamics of superfluid neutron stars
Authors: Gusakov M. E. , Kantor E. M.
Published: October 2012

We show that suppression of the baryon energy gaps, caused by the relative motion of superfluid and normal liquid components, can substantially influence dynamical properties and evolution of neutron stars. This effect has been previously ignored in the neutron star literature.