bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifunctional solid/solid phononic crystal
Authors: Swinteck N. , Vasseur J. O. , Hladky-Hennion A. C. , Croënne C. , Bringuier S. , Deymier P. A.
Published: July 2012

A two-dimensional, solid/solid phononic crystal (PC) comprised a square array of steel cylinders in epoxy is shown to perform a variety of spectral, wave vector, and phase-space functions. Over a range of operating frequencies, the PC’s elastic band structure shows uniquely shaped equifrequency contours that are only accessible to excitations of longitudinal polarization. Under this condition, the PC is shown to behave as (1) an acoustic wave collimator, (2) a defect-less wave guide, (3) a directional source for elastic waves, (4) an acoustic beam splitter, (5) a phase-control device, and (6) a k-space multiplexer. Wave vector diagrams and finite-difference time-domain simulations are employed to authenticate the above mentioned capabilities.
Superhard behaviour, low residual stress, and unique structure in diamond-like carbon films by simple bilayer approach
Authors: Dwivedi Neeraj , Kumar Sushil , Malik Hitendra K.
Published: July 2012

Simple bilayer approach is proposed for synthesizing hard and superhard diamond-like carbon (DLC) coatings with reduced residual stress. For this, M/DLC bilayer (M = Ti and Cu) structures are grown using hybrid system involving radio frequency (RF)-sputtering and RF-plasma enhanced chemical vapor deposition techniques. Ti/DLC bilayer deposited at negative self bias of 100 V shows superhard behaviour with hardness (H) as 49 GPa. Cu/DLC bilayer grown at self bias of 100 V exhibits hard behaviour with H as 22.8 GPa. The hardness of Ti/DLC (Cu/DLC) bilayer gets changed from superhard (hard) to hard (moderate hard) regime, when the self bias is raised to 300 V. Residual stress in Ti/DLC (Cu/DLC) bilayer is found to be significantly low that varies in the range of 1 GPa–1.65 GPa (0.8 GPa–1.6 GPa). The microstructure and morphology are studied by Raman spectroscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). SEM and AFM pictures reveal the creation of nanostructured features in the deposited bilayers. Raman, SEM, and AFM analyses are correlated with the nano-mechanical properties. Owing to excellent nano-mechanical properties, these bilayers can find their direct industrial applications as hard and protective coatings.
Effects of rare-earth doping on femtosecond laser waveguide writing in zinc polyphosphate glass
Authors: Fletcher Luke B. , Witcher Jon J. , Troy Neil , Reis Signo T. , Brow Richard K. , Krol Denise M.
Published: July 2012

We have investigated waveguide writing in Er-Yb doped zinc polyphosphate glass using a femtosecond laser with a repetition rate of 1 KHz. We find that fabrication of good waveguides requires a glass composition with an O/P ratio of 3.25. The dependence on laser writing parameters including laser fluence, focusing conditions, and scan speed is reported. Waveguide properties together with absorption and emission data indicate that these glasses can be used for the fabrication of compact, high gain amplifying devices.
Generalized differential effective medium method for simulating effective elastic properties of two dimensional percolating composites
Authors: Markov M. , Kazatchenko E. , Mousatov A. , Pervago E.
Published: July 2012

In this paper, we propose an approach for calculating the effective elastic properties of composite materials taking into account the percolation phenomena. This approach is based on the generalized differential effective medium method and, in contrast to the commonly used self-consistent methods, it allows us to incorporate the percolation threshold in the homogenization scheme for simulating the effective elastic moduli of a 2D medium. In this case, a composite is treated as an elastic host where elliptical inclusions of two types are embedded: (1) soft elliptical inclusions (holes) and (2) elastic elliptical inclusions which have the same properties as the host. The comparison of theoretical simulations with the experimental data for metal plates containing holes has shown that the proposed approach describes well the behavior of the elastic moduli in a wide range of the hole concentration including the area near the percolation threshold.
On-chip three-dimensional tumor spheroid formation and pump-less perfusion culture using gravity-driven cell aggregation and balanced droplet dispensing
Authors: Kim Taeyoon , Doh Il , Cho Young-Ho
Published: July 2012

This paper presents a spheroid chip in which three-dimensional (3D) tumor spheroids are not only formed by gravity-driven cell aggregation but also cultured at the perfusion rates controlled by balanced droplet dispensing without fluidic pumps. The previous spheroid chips require additional off-chip processes of spheroid formation and extraction as well as bulky components of fluidic pumps. However, the present spheroid chip, where autonomous medium droplet dispensers are integrated on a well array, achieves the on-chip 3D tumor spheroid formation and perfusion culture using simple structure without bulky fluidic pumps. In the experimental study, we demonstrated that the spheroid chip successfully forms 3D tumor spheroids in the wide diameter range of 220 μm–3.2 mm (uniformity > 90%) using H358, H23, and A549 non-small cell lung cancer cells. At the pump-less perfusion culture (Q = 0.1–0.3 μl/min) of spheroids, the number of H358 cells in the spheroid increased up to 50% from the static culture (Q = 0 μl/min) and the viability of the cultured cells also increased about 10%. Therefore, we experimentally verified that the perfusion environment created by the spheroid chip offers a favourable condition to the spheroids with high increase rate and viability. The present chip achieves on-chip 3D tumor spheroid formation and pump-less perfusion culture with simple structure, thereby exhibiting potential for use in integrated in-vivo-like cell culture systems.
The Local Politics of Policy Mobility: Learning, Persuasion, and the Production of a Municipal Sustainability Fix
Authors: Temenos Cristina , McCann Eugene
Published: July 2012

The authors draw on the concept of a ‘sustainability fix’—a political discourse which allows development to proceed by accommodating both profit-making and environmental concerns—to analyze how municipalities muster support for development in the face of worries about negative environmental impacts. The case of Whistler, British Columbia, a tourist resort with an official orientation toward sustainable development, is used to illustrate the politics of balancing economic and environmental commitments. The authors deepen the sustainability fix concept by addressing: first, how such a fix is achieved through the assemblage of local and extralocal resources—specifically, ‘imported’ policy models which direct attention to certain definitions of problems and legitimate specific types of policy solutions; and second, how the politics of municipal policy-making is about more than contention and how it involves the sort of ongoing and broadly defined learning that has been largely undertheorized in the local politics literature. A key point is that local politics and policy making are always also extralocal in various ways. They involve a local politics of policy mobility. The authors expand on this premise to show how Whistler's model of sustainability planning has recently been circulated to other municipalities with similar social, economic, and environmental conditions.
An Examination of Behavioral Linkages across ICT Choice Dimensions: Copula Modeling of Telecommuting and Teleshopping Choice Behavior
Authors: Sener Ipek N , Reeder Phillip R
Published: July 2012

This study jointly examines two distinct ICT choice behaviors—telecommuting and teleshopping—along two different dimensions: adoption and frequency. The linkages between two adoption models, or the two frequency models, are obtained by adopting a flexible copula-based approach that accommodates dependency (results from unobserved factors) between individual's telecommuting and teleshopping adoption (or frequency) choices. Rather than preimpose restrictive assumptions regarding dependence, a copula-based approach affords unique flexibility in testing different forms of dependence between telecommuting and teleshopping choice behavior. As a result, the most appropriate form of dependence is obtained. This study relies on data drawn from the 2009 National Household Travel Survey, which provides several different individual/household demographics, work/commute-related factors, attitudinal/behavioral characteristics, and residential neighborhood variables. Several intriguing findings arise from the joint modeling of telecommuting and teleshopping frequency choices as well as the analysis of the interrelationships between adoption and frequency choices for a specific ICT behavior. The positive and asymmetric form of the best model data fit (obtained both for adoption and for frequency models) also demonstrates the clear presence of unobserved factors influencing the underlying process of telecommuting and teleshopping behavior. To our knowledge, this is the first study examining the behavioral linkages between telecommuting and teleshopping choice behavior using the flexible copula modeling approach.
Green Revolution: Impacts, limits, and the path ahead
Authors: Pingali Prabhu L.
Published: July 2012

A detailed retrospective of the Green Revolution, its achievement and limits in terms of agricultural productivity improvement, and its broader impact at social, environmental, and economic levels is provided. Lessons learned and the strategic insights are reviewed as the world is preparing a “redux” version of the Green Revolution with more integrative environmental and social impact combined with agricultural and economic development. Core policy directions for Green Revolution 2.0 that enhance the spread and sustainable adoption of productivity enhancing technologies are specified.
A quantitative quasispecies theory-based model of virus escape mutation under immune selection
Authors: Woo Hyung-June , Reifman Jaques
Published: July 2012

Viral infections involve a complex interplay of the immune response and escape mutation of the virus quasispecies inside a single host. Although fundamental aspects of such a balance of mutation and selection pressure have been established by the quasispecies theory decades ago, its implications have largely remained qualitative. Here, we present a quantitative approach to model the virus evolution under cytotoxic T-lymphocyte immune response. The virus quasispecies dynamics are explicitly represented by mutations in the combined sequence space of a set of epitopes within the viral genome. We stochastically simulated the growth of a viral population originating from a single wild-type founder virus and its recognition and clearance by the immune response, as well as the expansion of its genetic diversity. Applied to the immune escape of a simian immunodeficiency virus epitope, model predictions were quantitatively comparable to the experimental data. Within the model parameter space, we found two qualitatively different regimes of infectious disease pathogenesis, each representing alternative fates of the immune response: It can clear the infection in finite time or eventually be overwhelmed by viral growth and escape mutation. The latter regime exhibits the characteristic disease progression pattern of human immunodeficiency virus, while the former is bounded by maximum mutation rates that can be suppressed by the immune response. Our results demonstrate that, by explicitly representing epitope mutations and thus providing a genotype–phenotype map, the quasispecies theory can form the basis of a detailed sequence-specific model of real-world viral pathogens evolving under immune selection.
Twelve-month-old infants recognize that speech can communicate unobservable intentions
Authors: Vouloumanos Athena , Onishi Kristine H. , Pogue Amanda
Published: July 2012

Much of our knowledge is acquired not from direct experience but through the speech of others. Speech allows rapid and efficient transfer of information that is otherwise not directly observable. Do infants recognize that speech, even if unfamiliar, can communicate about an important aspect of the world that cannot be directly observed: a person’s intentions? Twelve-month-olds saw a person (the Communicator) attempt but fail to achieve a target action (stacking a ring on a funnel). The Communicator subsequently directed either speech or a nonspeech vocalization to another person (the Recipient) who had not observed the attempts. The Recipient either successfully stacked the ring (Intended outcome), attempted but failed to stack the ring (Observable outcome), or performed a different stacking action (Related outcome). Infants recognized that speech could communicate about unobservable intentions, looking longer at Observable and Related outcomes than the Intended outcome when the Communicator used speech. However, when the Communicator used nonspeech, infants looked equally at the three outcomes. Thus, for 12-month-olds, speech can transfer information about unobservable aspects of the world such as internal mental states, which provides preverbal infants with a tool for acquiring information beyond their immediate experience.
A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy
Authors: Zhang Yuying , Akins Meredith L. , Murari Kartikeya , Xi Jiefeng , Li Ming-Jun , Luby-Phelps Katherine , Mahendroo Mala , Li Xingde
Published: July 2012

We report the development of an all-fiber-optic scanning endomicroscope capable of high-resolution second harmonic generation (SHG) imaging of biological tissues and demonstrate its utility for monitoring the remodeling of cervical collagen during gestation in mice. The endomicroscope has an overall 2.0 mm diameter and consists of a single customized double-clad fiber, a compact rapid two-dimensional beam scanner, and a miniature compound objective lens for excitation beam delivery, scanning, focusing, and efficient SHG signal collection. Endomicroscopic SHG images of murine cervical tissue sections at different stages of normal pregnancy reveal progressive, quantifiable changes in cervical collagen morphology with resolution similar to that of bench-top SHG microscopy. SHG endomicroscopic imaging of ex vivo murine and human cervical tissues through intact epithelium has also been performed. Our findings demonstrate the feasibility of SHG endomicroscopy technology for staging normal pregnancy, and suggest its potential application as a minimally invasive tool for clinical assessment of abnormal cervical remodeling associated with preterm birth.
Variation in neural development as a result of exposure to institutionalization early in childhood
Authors: Sheridan Margaret A. , Fox Nathan A. , Zeanah Charles H. , McLaughlin Katie A. , Nelson Charles A.
Published: July 2012

We used structural MRI and EEG to examine brain structure and function in typically developing children in Romania (
n
= 20), children exposed to institutional rearing (
n
= 29), and children previously exposed to institutional rearing but then randomized to a high-quality foster care intervention (
n
= 25). In so doing, we provide a unique evaluation of whether placement in an improved environment mitigates the effects of institutional rearing on neural structure, using data from the only existing randomized controlled trial of foster care for institutionalized children. Children enrolled in the Bucharest Early Intervention Project underwent a T1-weighted MRI protocol. Children with histories of institutional rearing had significantly smaller cortical gray matter volume than never-institutionalized children. Cortical white matter was no different for children placed in foster care than never-institutionalized children but was significantly smaller for children not randomized to foster care. We were also able to explain previously reported reductions in EEG α-power among institutionally reared children compared with children raised in families using these MRI data. As hypothesized, the association between institutionalization and EEG α-power was partially mediated by cortical white matter volume for children not randomized to foster care. The increase in white matter among children randomized to an improved rearing environment relative to children who remained in institutional care suggests the potential for developmental “catch up” in white matter growth, even following extreme environmental deprivation.
Genetic data suggest a natural prehuman origin of open habitats in northern Madagascar and question the deforestation narrative in this region
Authors: Quéméré Erwan , Amelot Xavier , Pierson Julie , Crouau-Roy Brigitte , Chikhi Lounès
Published: July 2012

The impact of climate change and anthropogenic deforestation on biodiversity is of growing concern worldwide. Disentangling how past anthropogenic and natural factors contributed to current biome distribution is thus a crucial issue to understand their complex interactions on wider time scales and to improve predictions and conservation strategies. This is particularly important in biodiversity hotspots, such as Madagascar, dominated by large open habitats whose origins are increasingly debated. Although a dominant narrative argues that Madagascar was originally entirely covered by woodlands, which were destroyed by humans, a number of recent studies have suggested that past climatic fluctuations played a major role in shaping current biome distributions well before humans arrived. Here, we address the question of the origin of open habitats in the Daraina region in northern Madagascar, using a multiproxy approach combining population genetics modeling and remote-sensing analyses. We show that (
i
) contrary to most regions of Madagascar, the forest cover in Daraina remained remarkably stable over the past 60 y, and (
ii
) the golden-crowned sifaka (
Propithecus tattersalli
), a forest-dwelling lemur, underwent a strong population contraction before the arrival of the first humans, hence excluding an anthropogenic cause. Prehuman Holocene droughts may have led to a significant increase of grasslands and a reduction in the species’ habitat. This contradicts the prevailing narrative that land cover changes are necessarily anthropogenic in Madagascar but does not preclude the later role played by humans in other regions in which recent lemur bottlenecks have been observed.
Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis
Authors: Demers Mélanie , Krause Daniela S. , Schatzberg Daphne , Martinod Kimberly , Voorhees Jaymie R. , Fuchs Tobias A. , Scadden David T. , Wagner Denisa D.
Published: July 2012

Cancer-associated thrombosis often lacks a clear etiology. However, it is linked to a poor prognosis and represents the second-leading cause of death in cancer patients. Recent studies have shown that chromatin released into blood, through the generation of neutrophil extracellular traps (NETs), is procoagulant and prothrombotic. Using a murine model of chronic myelogenous leukemia, we show that malignant and nonmalignant neutrophils are more prone to NET formation. This increased sensitivity toward NET generation is also observed in mammary and lung carcinoma models, suggesting that cancers, through a systemic effect on the host, can induce an increase in peripheral blood neutrophils, which are predisposed to NET formation. In addition, in the late stages of the breast carcinoma model, NETosis occurs concomitant with the appearance of venous thrombi in the lung. Moreover, simulation of a minor systemic infection in tumor-bearing, but not control, mice results in the release of large quantities of chromatin and a prothrombotic state. The increase in neutrophil count and their priming is mediated by granulocyte colony-stimulating factor (G-CSF), which accumulates in the blood of tumor-bearing mice. The prothrombotic state in cancer can be reproduced by treating mice with G-CSF combined with low-dose LPS and leads to thrombocytopenia and microthrombosis. Taken together, our results identify extracellular chromatin released through NET formation as a cause for cancer-associated thrombosis and unveil a target in the effort to decrease the incidence of thrombosis in cancer patients.
Calculation of thermodynamic hydricities and the design of hydride donors for CO
2
reduction
Authors: Muckerman James T. , Achord Patrick , Creutz Carol , Polyansky Dmitry E. , Fujita Etsuko
Published: July 2012

We have developed a correlation between experimental and density functional theory-derived results of the hydride-donating power, or “hydricity”, of various ruthenium, rhenium, and organic hydride donors. This approach utilizes the correlation between experimental hydricity values and their corresponding calculated free-energy differences between the hydride donors and their conjugate acceptors in acetonitrile, and leads to an extrapolated value of the absolute free energy of the hydride ion without the necessity to calculate it directly. We then use this correlation to predict, from density functional theory-calculated data, hydricity values of ruthenium and rhenium complexes that incorporate the pbnHH ligand—pbnHH = 1,5-dihydro-2-(2-pyridyl)-benzo[
b
]-1,5-naphthyridine—to model the function of NADPH. These visible light-generated, photocatalytic complexes produced by disproportionation of a protonated-photoreduced dimer of a metal-pbn complex may be valuable for use in reducing CO
2
to fuels such as methanol. The excited-state lifetime of photoexcited [Ru(bpy)
2
(pbnHH)]
2+
is found to be about 70 ns, and this excited state can be reductively quenched by triethylamine or 1,4-diazabicyclo[2.2.2]octane to produce the one-electron-reduced [Ru(bpy)
2
(pbnHH)]
+
species with half-life exceeding 50 μs, thus opening the door to new opportunities for hydride-transfer reactions leading to CO
2
reduction by producing a species with much increased hydricity.
Amino acid starvation induces reactivation of silenced transgenes and latent HIV-1 provirus via down-regulation of histone deacetylase 4 (HDAC4)
Authors: Palmisano Ilaria , Della Chiara Giulia , D’Ambrosio Rosa Lucia , Huichalaf Claudia , Brambilla Paola , Corbetta Silvia , Riba Michela , Piccirillo Rosanna , Valente Sergio , Casari Giorgio , Mai Antonello , Boneschi Filippo Martinelli , Gabellini Davide , Poli Guido , Schiaffino Maria Vittoria
Published: July 2012

The epigenetic silencing of exogenous transcriptional units integrated into the genome represents a critical problem both for long-term gene therapy efficacy and for the eradication of latent viral infections. We report here that limitation of essential amino acids, such as methionine and cysteine, causes selective up-regulation of exogenous transgene expression in mammalian cells. Prolonged amino acid deprivation led to significant and reversible increase in the expression levels of stably integrated transgenes transcribed by means of viral or human promoters in HeLa cells. This phenomenon was mediated by epigenetic chromatin modifications, because histone deacetylase (HDAC) inhibitors reproduced starvation-induced transgene up-regulation, and transcriptome analysis, ChIP, and pharmacological and RNAi approaches revealed that a specific class II HDAC, namely HDAC4, plays a critical role in maintaining the silencing of exogenous transgenes. This mechanism was also operational in cells chronically infected with HIV-1, the etiological agent of AIDS, in a latency state. Indeed, both amino acid starvation and pharmacological inhibition of HDAC4 promoted reactivation of HIV-1 transcription and reverse transcriptase activity production in HDAC4+ACH-2 T-lymphocytic cells but not in HDAC4−U1 promonocytic cells. Thus, amino acid deprivation leads to transcriptional derepression of silenced transgenes, including integrated plasmids and retroviruses, by a process involving inactivation or down-regulation of HDAC4. These findings suggest that selective targeting of HDAC4 might represent a unique strategy for modulating the expression of therapeutic viral vectors, as well as that of integrated HIV-1 proviruses in latent reservoirs without significant cytotoxicity.
Developed and developing world responsibilities for historical climate change and CO
2
mitigation
Authors: Wei Ting , Yang Shili , Moore John C. , Shi Peijun , Cui Xuefeng , Duan Qingyun , Xu Bing , Dai Yongjiu , Yuan Wenping , Wei Xin , Yang Zhipeng , Wen Tijian , Teng Fei , Gao Yun , Chou Jieming , Yan Xiaodong , Wei Zhigang , Guo Yan , Jiang Yundi , Gao Xuejie , Wang Kaicun , Zheng Xiaogu , Ren Fumin , Lv Shihua , Yu Yongqiang , Liu Bin , Luo Yong , Li Weijing , Ji Duoying , Feng Jinming , Wu Qizhong , Cheng Huaqiong , He Jiankun , Fu Congbin , Ye Duzheng , Xu Guanhua , Dong Wenjie
Published: July 2012

At the United Nations Framework Convention on Climate Change Conference in Cancun, in November 2010, the Heads of State reached an agreement on the aim of limiting the global temperature rise to 2 °C relative to preindustrial levels. They recognized that long-term future warming is primarily constrained by cumulative anthropogenic greenhouse gas emissions, that deep cuts in global emissions are required, and that action based on equity must be taken to meet this objective. However, negotiations on emission reduction among countries are increasingly fraught with difficulty, partly because of arguments about the responsibility for the ongoing temperature rise. Simulations with two earth-system models (NCAR/CESM and BNU-ESM) demonstrate that developed countries had contributed about 60–80%, developing countries about 20–40%, to the global temperature rise, upper ocean warming, and sea-ice reduction by 2005. Enacting pledges made at Cancun with continuation to 2100 leads to a reduction in global temperature rise relative to business as usual with a 1/3–2/3 (CESM 33–67%, BNU-ESM 35–65%) contribution from developed and developing countries, respectively. To prevent a temperature rise by 2 °C or more in 2100, it is necessary to fill the gap with more ambitious mitigation efforts.
HLA-B may be more protective against HIV-1 than HLA-A because it resists negative regulatory factor (Nef) mediated down-regulation
Authors: Rajapaksa Ushani S. , Li Demin , Peng Yan-Chun , McMichael Andrew J. , Dong Tao , Xu Xiao-Ning
Published: July 2012

Human leukocyte antigen HLA-B alleles have better protective activity against HIV-1 than HLA-A alleles, possibly due to differences in HLA-restricted HIV-1-specific CD8+ cytotoxic T lymphocyte (CTL) function, but the mechanism is unknown. HIV-1 negative regulatory factor (Nef) mediates down-regulation of surface expression of class I HLA (HLA-I) and may therefore impair immune recognition by CTL. Because of sequence differences in the cytoplasmic domains, HLA-A and -B are down-regulated by Nef but HLA-C and -E are not affected. However, the latter are expressed at low levels and are not of major importance in the CTL responses to HIV-1. Here, we compared the role of the cytoplasmic domains of HLA-A and -B in Nef-mediated escape from CTL. We found HLA-B cytoplasmic domains were more resistant to Nef-mediated down-regulation than HLA-A cytoplasmic domains and demonstrated that these differences affect CTL recognition of virus-infected cells in vitro. We propose that the relative resistance to Nef-mediated down-regulation by the cytoplasmic domains of HLA-B compared with HLA-A contributes to the better control of HIV-1 infection associated with HLA-B-restricted CTLs.
Macrophage migration inhibitory factor mediates the antidepressant actions of voluntary exercise
Authors: Moon Hyo Youl , Kim Se Hyun , Yang Yong Ryoul , Song Parkyong , Yu Hyun Sook , Park Hong Geun , Hwang Onyou , Lee-Kwon Whaseon , Seo Jeong Kon , Hwang Daehee , Choi Jang Hyun , Bucala Richard , Ryu Sung Ho , Kim Yong Sik , Suh Pann-Ghill
Published: July 2012

Voluntary exercise is known to have an antidepressant effect. However, the underlying mechanism for this antidepressant action of exercise remains unclear, and little progress has been made in identifying genes that are directly involved. We have identified macrophage migration inhibitory factor (MIF) by analyzing existing mRNA microarray data and confirmed the augmented expression of selected genes under two experimental conditions: voluntary exercise and electroconvulsive seizure. A proinflammatory cytokine, MIF is expressed in the central nervous system and involved in innate and adaptive immune responses. A recent study reported that MIF is involved in antidepressant-induced hippocampal neurogenesis, but the mechanism remains elusive. In our data, tryptophan hydroxylase 2 (
Tph2
) and brain-derived neurotrophic factor (
Bdnf
) expression were induced after MIF treatment in vitro, as well as during both exercise and electroconvulsive seizure in vivo. This increment of
Tph2
was accompanied by increases in the levels of total serotonin in vitro. Moreover, the MIF receptor CD74 and the ERK1/2 pathway mediate the MIF-induced
Tph2
and
Bdnf
gene expression as well as serotonin content. Experiments in

Mif
−/−

mice revealed depression-like behaviors and a blunted antidepressant effect of exercise, as reflected by changes in
Tph2
and
Bdnf
expression in the forced swim test. In addition, administration of recombinant MIF protein produced antidepressant-like behavior in rats in the forced swim test. Taken together, these results suggest a role of MIF in mediating the antidepressant action of exercise, probably by enhancing serotonin neurotransmission and neurotrophic factor-induced neurogenesis in the brain.
The SHORT-ROOT protein acts as a mobile, dose-dependent signal in patterning the ground tissue
Authors: Koizumi Koji , Hayashi Tomomi , Wu Shuang , Gallagher Kimberly L.
Published: July 2012

A key question in developmental biology is how cellular patterns are created and maintained. During the formation of the
Arabidopsis
root, the endodermis, middle cortex (MC), and cortex are produced by periclinal cell divisions that occur at different positions and at different times in root development. The endodermis and cortex arise continuously from the periclinal divisions of cells that surround the quiescent center (QC) at the tip of the root. The MC arises between days 7 and 14 from periclinal divisions of the endodermis. The divisions that produce the middle cortex begin in the basal region of the root meristem away from the QC and then spread apically and circumferentially around the root. Although the transcription factor SHORT-ROOT (SHR) is required for both of these divisions, the mechanism that determines where and when SHR acts to promote cell division along the longitudinal axis of the root is unknown; SHR is present along the entire length of the root tip, but only promotes periclinal divisions at specific sites. Here we show that the abundance of the SHR protein changes dynamically as the root develops, and that the pattern of cell division within the endodermis is sensitive to the dose of this protein: high levels of SHR prevent the formation of the MC, whereas intermediate levels of SHR promote MC formation. These results provide a mechanism for the longitudinal patterning of the endodermis, and represent the first example in plants of a mobile transcription factor whose function (activator or repressor) depends upon concentration.
Double electron–electron resonance shows cytochrome P450cam undergoes a conformational change in solution upon binding substrate
Authors: Stoll Stefan , Lee Young-Tae , Zhang Mo , Wilson Richard F. , Britt R. David , Goodin David B.
Published: July 2012

Although cytochrome P450cam from
Pseudomonas putida
, the archetype for all heme monooxygenases, has long been known to have a closed active site, recent reports show that the enzyme can also be crystallized in at least two clusters of open conformations. This suggests that the enzyme may undergo significant conformational changes during substrate binding and catalytic turnover. However, these conformations were observed in the crystalline state, and information is needed about the conformations that are populated in solution. In this study, double electron–electron resonance experiments were performed to observe substrate-induced changes in distance as measured by the dipolar coupling between spin labels introduced onto the surface of the enzyme on opposite sides of the substrate access channel. The double electron–electron resonance data show a decrease of 0.8 nm in the distance between spin labels placed at S48C and S190C upon binding the substrate camphor. A rotamer distribution model based on the crystal structures adequately describes the observed distance distributions. These results demonstrate conclusively that, in the physiologically relevant solution state, the substrate-free enzyme exists in the open P450cam-O conformation and that camphor binding results in conversion to the closed P450cam-C form. This approach should be useful for investigating many other P450s, including mammalian forms, in which the role of conformational change is of central importance but not well understood.
Discovery, taxonomic distribution, and phenotypic characterization of a gene required for 3-methylhopanoid production
Authors: Welander Paula V. , Summons Roger E.
Published: July 2012

Hopanoids methylated at the C-3 position are a subset of bacterial triterpenoids that are readily preserved in modern and ancient sediments and in petroleum. The production of 3-methylhopanoids by extant aerobic methanotrophs and their common occurrence in modern and fossil methane seep communities, in conjunction with carbon isotope analysis, has led to their use as biomarker proxies for aerobic methanotrophy. In addition, these lipids are also produced by aerobic acetic acid bacteria and, lacking carbon isotope analysis, are more generally used as indicators for aerobiosis in ancient ecosystems. However, recent genetic studies have brought into question our current understanding of the taxonomic diversity of methylhopanoid-producing bacteria and have highlighted that a proper interpretation of methylhopanes in the rock record requires a deeper understanding of their cellular function. In this study, we identified and deleted a gene,
hpnR
, required for methylation of hopanoids at the C-3 position in the obligate methanotroph
Methylococcus capsulatus
strain Bath. Bioinformatics analysis revealed that the taxonomic distribution of HpnR extends beyond methanotrophic and acetic acid bacteria. Phenotypic analysis of the
M. capsulatus
hpnR
deletion mutant demonstrated a potential physiological role for 3-methylhopanoids; they appear to be required for the maintenance of intracytoplasmic membranes and cell survival in late stationary phase. Therefore, 3-methylhopanoids may prove more useful as proxies for specific environmental conditions encountered during stationary phase rather than a particular bacterial group.
Talin couples the actomyosin cortex to the plasma membrane during rear retraction and cytokinesis
Authors: Tsujioka Masatsune , Yumura Shigehiko , Inouye Kei , Patel Hitesh , Ueda Masahiro , Yonemura Shigenobu
Published: July 2012

Contraction of the cortical actin cytoskeleton underlies both rear retraction in directed cell migration and cytokinesis. Here, we show that talin, a central component of focal adhesions, has a major role in these processes. We found that
Dictyostelium
talin A colocalized with myosin II in the rear of migrating cells and the cleavage furrow. During directed cell migration, talin A-null cells displayed a long thin tail devoid of actin filaments, whereas additional depletion of SibA, a transmembrane adhesion molecule that binds to talin A, reverted this phenotype, suggesting a requirement of the link between actomyosin and SibA by talin A for rear retraction. Disruptions of talin A also resulted in detachment of the actomyosin contractile ring from the cell membrane and concomitant regression of the cleavage furrow under certain conditions. The C-terminal actin-binding domain (ABD) of talin A exhibited a localization pattern identical to that of full-length talin A. The N-terminal FERM domain was found to bind phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] and phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] in vitro. In vivo, however, PtdIns(4,5)P2, which is known to activate talin, is believed to be enriched in the rear of migrating cells and the cleavage furrow in
Dictyostelium
. From these results, we propose that talin A activated by PtdIns(4,5)P2 in the cell posterior or cleavage furrow links actomyosin cytoskeleton to adhesion molecules or other membrane proteins, and that the force is transmitted through these links to retract the tail during cell migration or to cause efficient ingression of the equator during cytokinesis.
Visual discrimination performance, memory, and medial temporal lobe function
Authors: Knutson Ashley R. , Hopkins Ramona O. , Squire Larry R.
Published: July 2012

We evaluated recent proposals that structures in the medial temporal lobe (MTL)—in particular, perirhinal cortex—support not just memory but certain kinds of perceptual abilities as well. Specifically, it has been suggested that the perirhinal cortex supports the perceptual abilities needed to accomplish visual discrimination performance when the stimuli have complex features and overlapping elements. However, the tasks that have been studied are quite challenging. Stimulus features must be held in working memory while attention shifts among the several parts of the display. When working memory capacity is exceeded, performance must depend on retrieval from long-term memory. Five patients with limited hippocampal lesions and one patient with large MTL lesions were asked to identify the unique object among twin pairs of objects that had a high degree of feature overlap and perceptual similarity. The patient groups performed similarly to controls when there were few objects and features in the displays, but exhibited abrupt declines in performance when the displays contained more objects and more features. Notably, the impairment was observed in memory-impaired patients with hippocampal lesions, not only in association with large MTL lesions that included perirhinal cortex. The pattern of performance suggested that patients encountered difficulty because working memory capacity was exceeded in the more difficult conditions such that performance needed to depend at least in part on long-term memory. Furthermore, when the burden on working memory was removed entirely, the patient with large MTL lesions performed as well as controls. Accordingly, we suggest that deficits on difficult discrimination tasks reported for patients with MTL lesions are due to impaired memory rather than impaired perception.
Surface energetics of freely suspended fluid molecular monolayer and multilayer smectic liquid crystal films
Authors: Nguyen Zoom Hoang , Park Cheol Soo , Pang Jinzhong , Clark Noel A.
Published: July 2012

A study of the surface energetics of the thinnest substrate-free liquid films, fluid molecular monolayer and multilayer smectic liquid crystal films suspended in air, is reported. In films having monolayer and multilayer domains, the monolayer areas contract, contrary to predictions from the van der Waals disjoining pressure of thin uniform slabs. This discrepancy is accounted for by modeling the environmental asymmetry of the surface layers in multilayer films, leading to the possibility that preferential end-for-end polar ordering of the rod shaped molecules can reduce the surface energy of multilayers relative to that of the monolayer, which is inherently symmetric.
Liver X receptor β protects dopaminergic neurons in a mouse model of Parkinson disease
Authors: Dai Yu-bing , Tan Xin-jie , Wu Wan-fu , Warner Margaret , Gustafsson Jan-Åke
Published: July 2012

Parkinson disease (PD) is a progressive neurodegenerative disease whose progression may be slowed, but at present there is no pharmacological intervention that would stop or reverse the disease. Liver X receptor β (LXRβ) is a member of the nuclear receptor super gene family expressed in the central nervous system, where it is important for cortical layering during development and survival of dopaminergic neurons throughout life. In the present study we have used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD to investigate the possible use of LXRβ as a target for prevention or treatment of PD. The dopaminergic neurons of the substantia nigra of LXRβ
−/−
mice were much more severely affected by MPTP than were those of their WT littermates. In addition, the number of activated microglia and GFAP-positive astrocytes was higher in the substantia nigra of LXRβ
−/−
mice than in WT littermates. Administration of the LXR agonist GW3965 to MPTP-treated WT mice protected against loss of dopaminergic neurons and of dopaminergic fibers projecting to the striatum, and resulted in fewer activated microglia and astroglia. Surprisingly, LXRβ was not expressed in the neurons of the substantia nigra but in the microglia and astroglia. We conclude that LXR agonists may have beneficial effects in treatment of PD by modulating the cytotoxic functions of microglia.
Binding and biomimetic cleavage of the RNA poly(U) by synthetic polyimidazoles
Authors: Cheng Liang , Abhilash K.G. , Breslow Ronald
Published: July 2012

Four polyimidazoles were used in the binding and cleavage studies with poly(U). The two polydisperse polyvinylimidazoles were previously described by others, while the other two new polymers of polyethyleneimines were prepared by cationic polymerization of oxazolines. The latter had imidazole units attached to each nitrogen of the polymers. They were characterized by gel permeation chromatography and had very low polydispersities. When they were partially protonated they bound to the poly(U) and catalyzed its cleavage by a process analogous to that used by the enzyme ribonuclease A. The kinetics of the cleavage were followed by an assay we had previously described using phosphodiesterase I from
Crotalus
venom after the cleavage processes. Cleavage of poly(U) with Zn
2+
was also examined, with and without the polymers. A scheme is described in which these cleavages could be made sequence selective with various RNAs, particularly with important targets, such as viral RNAs.
De novo
protein design: Crystallographic characterization of a synthetic peptide containing independent helical and hairpin domains
Authors: Karle Isabella L. , Das Chittaranjan , Balaram Padmanabhan
Published: July 2012

The Meccano (or Lego) set approach to synthetic protein design envisages covalent assembly of prefabricated units of peptide secondary structure. Stereochemical control over peptide folding is achieved by incorporation of conformationally constrained residues like α-aminoisobutyric acid (Aib) or
d
Pro that nucleate helical and β-hairpin structures, respectively. The generation of a synthetic sequence containing both a helix and a hairpin is achieved in the peptide BH17, Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Gly-Gly-Leu-Phe-Val-
d
Pro-Gly-Leu-Phe-Val-OMe (where Boc is
t
-butoxycarbonyl), as demonstrated by a crystal structure determination. The achiral -Gly-Gly- linker permits helix termination as a Schellman motif and extension to the strand segment of the hairpin. Structure parameters for C
89
H
143
N
17
O
20
⋅2H
2
O are space group P2
1
,
a
= 14.935(7) Å,
b
= 18.949(6) Å,
c
= 19.231(8) Å, β = 101.79(4)°,
Z
= 2, agreement factor
R
1
= 8.50% for 4,862 observed reflections > 4σ(F), and resolution of ≈0.98 Å.
Oligomerization of serotonin transporter and its functional consequences
Authors: Kilic Fusun , Rudnick Gary
Published: July 2012

Two forms of serotonin transporter (SERT) were prepared with different epitope tags. When co-expressed in HeLa cells, the form containing a FLAG tag (Res-FLAG) was associated with the form containing a c-myc tag (Sens-myc). Antibody against c-myc precipitated Res-FLAG from detergent extracts of cells expressing both forms, but not when Res-FLAG was expressed alone. The specificity of the interaction was demonstrated by the observation that anti-myc antibodies did not precipitate the unrelated vesicular stomatitis virus coat glycoprotein when it was co-expressed with Sens-myc. Sens-myc contained a reactive cysteine at position 172, which reacted with both (2-aminoethyl)methanethiosulfonate and
N
-biotinylaminoethyl methanethiosulfonate on the surface of intact cells. Sens-myc, but not Res-FLAG, was inactivated by these reagents. When co-expressed with Sens-myc, functionally active Res-FLAG was precipitated by immobilized streptavidin from digitonin-solubilized cells that had been treated with
N
-biotinylaminoethyl methanethiosulfonate. In cells co-expressing mixtures of Sens-myc and Res-FLAG, the amount of inactivation by (2-aminoethyl)methanethiosulfonate was less than expected if the two forms were independent. The results are consistent with a dimeric form of SERT with functional interactions between subunits, and with association of dimers into a higher order complex, possibly a tetramer.
Male–male competition magnifies inbreeding depression in wild house mice
Authors: Meagher Shawn , Penn Dustin J. , Potts Wayne K.
Published: July 2012

The detrimental effects of inbreeding on vertebrates are well documented for early stages of the life cycle in the laboratory. However, the consequences of inbreeding on long-term survival and reproductive success (Darwinian fitness) are uncertain for vertebrates in the wild. Here, we report direct experimental evidence for vertebrates that competition increases the harmful effects of inbreeding on offspring survival and reproduction. We compared the fitness of inbred (from full-sib matings) and outbred wild house mice (
Mus domesticus
) in large, seminatural enclosures. Inbred males sired only one-fifth as many surviving offspring as outbred males because of their poor competitive ability and survivorship. In laboratory conditions, inbreeding had relatively minor effects on male reproductive success and no effect on survivorship. Seminatural conditions did not increase inbreeding depression for females, probably because females were not competing for any critical resources. The overall reduction in fitness from inbreeding was 57%, which is 4.5 times as great as previous estimates from the laboratory. These results have important implications for medicine, conservation, evolutionary biology, and functional genomics.
Vaccination with Tat toxoid attenuates disease in simian/HIV-challenged macaques
Authors: Pauza C. David , Trivedi Parul , Wallace Marianne , Ruckwardt Tracy J. , Le Buanec Hélene , Lu Wei , Bizzini Bernard , Burny Arséne , Zagury Daniel , Gallo Robert C.
Published: July 2012

The Tat protein is essential for HIV type 1 (HIV-1) replication and may be an important virulence factorin vivo. We studied the role of Tat in viral pathogenesis by immunizing rhesus macaques with chemically inactivated Tat toxoid and challenging these animals by intrarectal inoculation with the simian/human immunodeficiency virus 89.6PD. Immune animals had significantly attenuated disease with lowered viral RNA, interferon-α, and chemokine receptor expression (CXCR4 and CCR5) on CD4+T cells; these features of infection have been linked toin vitroeffects of Tat and respond similarly to extracellular Tat protein produced during infection. Immunization with Tat toxoid inhibits key steps in viral pathogenesis and should be included in therapeutic or preventive HIV-1 vaccines.