bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical modeling of conformal mantle cloaks for cylindrical objects using sub-wavelength printed and slotted arrays
Authors: Padooru Yashwanth R. , Yakovlev Alexander B. , Chen Pai-Yen , Alù Andrea
Published: August 2012

Following the idea of “cloaking by a surface” [A. Alù, Phys. Rev. B 80, 245115 (2009); P. Y. Chen and A. Alù, Phys. Rev. B 84, 205110 (2011)], we present a rigorous analytical model applicable to mantle cloaking of cylindrical objects using 1D and 2D sub-wavelength conformal frequency selective surface (FSS) elements. The model is based on Lorenz-Mie scattering theory which utilizes the two-sided impedance boundary conditions at the interface of the sub-wavelength elements. The FSS arrays considered in this work are composed of 1D horizontal and vertical metallic strips and 2D printed (patches, Jerusalem crosses, and cross dipoles) and slotted structures (meshes, slot-Jerusalem crosses, and slot-cross dipoles). It is shown that the analytical grid-impedance expressions derived for the planar arrays of sub-wavelength elements may be successfully used to model and tailor the surface reactance of cylindrical conformal mantle cloaks. By properly tailoring the surface reactance of the cloak, the total scattering from the cylinder can be significantly reduced, thus rendering the object invisible over the range of frequencies of interest (i.e., at microwaves and far-infrared). The results obtained using our analytical model for mantle cloaks are validated against full-wave numerical simulations.
Influence of helium mole fraction distribution on the properties of cold atmospheric pressure helium plasma jets
Authors: Xiong Ranhua , Xiong Qing , Nikiforov Anton Yu. , Vanraes Patrick , Leys Christophe
Published: August 2012

The influence of helium mole fraction distribution in air on the cold atmospheric plasma jets excited by 1.5 kHz rectangular high voltage pulse is studied in this work. Computational fluid dynamics (CFD) with incorporation of large eddy simulation (LES) model is used to simulate the helium mole fraction distribution in air under the helium flow from laminar to turbulent regime with increasing helium outlet velocity. Numerical simulation results are combined with experimental results in order to determine the influence of helium distribution on the cold plasma jets. It reveals that the structure of the helium distribution caused by diffusion or by turbulent mixing in turbulent regime determines the characteristics of the cold plasma jets. On the other hand, the curves of plasma jet length (L) versus helium outlet velocity (V) at different jet diameters (D) are unified in a map of jet Reynolds number (Re = ρHe·V·D/μHe, where μHe is the helium viscosity constant) versus dimensionless plasma jet length (l = L/D). The map is allowed to predict the flow pattern of helium jet in order to estimate and control the plasma jet length at different jet diameters.
London's Legal Elite: Recruitment through Cultural Capital and the Reproduction of Social Exclusivity in City Professional Service Fields
Authors: Cook Andrew C G , Faulconbridge James R , Muzio Daniel
Published: August 2012

The authors examine the ways in which recruitment and selection processes facilitate the reproduction of elites and elite cultures within City law firms. The research is based upon original research carried out during 2009, consisting of in-depth semistructured interviews, semiotic and content analyses of recruitment materials and websites, and the analysis of publicly available data demonstrating the educational backgrounds of lawyers practising in the City. By deploying Bourdieusian concepts including the field, ‘doxa’, cultural capital, and habitus, the authors show that, in the firms studied, homologous elite cultures and social groups are maintained and legitimated as part of attempts to reproduce ‘normalised’ expectations about the identity and practice of a City professional. Maintenance is ensured by assessing the objectified, institutionalised, and embodied cultural capital of applicants in recruitment and selection processes, with only those possessing certain types of capital being recruited. This selection by cultural capital limits social mobility in City professions, which are dominated by the upper-middle classes, and helps explain why, in the face of critique and in the context of programmes designed to widen social diversity, the City legal profession remains socially exclusive.
Governing Economic Futures through the War on Inflation
Authors: McCormack Derek P
Published: August 2012

This paper explores how efforts to understand, present, and act upon the futures of inflation participate in the governance of contemporary economic life. The point of departure is the claim that inflation is both an economic and an affective fact, subsisting as a potentially disruptive event within contemporary liberal democracies whose chief concern is to secure the conditions for the value-activating process of economic growth. Understanding efforts to secure these conditions requires attention to the anticipatory processes through which the futures of inflation are generatively disclosed in the present as matters of public concern. In attending to these processes, this paper focuses on how the problem of inflation, and efforts to fight it, are linked closely with the logics and rhetoric of warfare. First, it outlines how interest in these processes emerged, at least in part, through attempts during the Second World War to render the futures of inflation actionable via public information campaigns. Second, it highlights the role of presidential speeches and addresses in ‘the war on inflation’ in the US during the 1970s and early 1980s. Third, and finally, the paper considers the importance of the promissory logics of inflation targeting in contemporary liberal democracies, in which inflation figures as a disruptive and generalised threat lurking in economic activity. In each case, efforts to fight inflation are based upon the premise that techniques of disclosure are a necessary element of generating the very futures they seek to make public. To govern inflation is therefore as much about governing orientations towards futures as it is about acting upon a well-defined epistemic object. In concluding, the paper speculates upon the wider implications of this claim for understanding how economic life is governed.
On Shaky Ground: The Making of Risk in Bogotá
Authors: Zeiderman Austin
Published: August 2012

How does risk become a technique for governing the future of cities and urban life? Using genealogical and ethnographic methods, this paper tracks the emergence of risk management in Bogotá, Colombia, from its initial institutionalization to its ongoing implementation in governmental practice. Its specific focus is the invention of the ‘zone of high risk’ in Bogotá and the everyday work performed by the officials responsible for determining the likelihood of landslide in these areas. It addresses the ongoing formation of techniques of urban planning and governance and the active relationship between urban populations and environments and emerging forms of political authority and technical expertise. Ultimately, it reveals that techniques of risk management are made and remade as experts and nonexperts grapple with the imperative to bring heterogeneous assemblages of people and things into an unfolding technopolitical domain.
Field Expertise in Rural Land Management
Authors: Proctor Amy , Donaldson Andrew , Phillipson Jeremy , Lowe Philip
Published: August 2012

This paper explores the expertise of field-level advisors in rural land management. The context is the English uplands and negotiation over a Higher Level Stewardship agreement. An observed encounter between a hill farmer, his retained land agent, and an ecologist working for Natural England illustrates the multiple roles that field-level advisors have in regulating, directing, and influencing contemporary land management. The paper draws on field notes taken during work shadowing and in-depth interviews, to reflect upon the relationships that constitute field expertise—not only between farmer and advisor, but amongst the advisors too (and those who advise them). We argue that expert—expert interaction and the emergence of networks of practice are crucial to the development of field expertise and are key factors in the increasing complexity of the decision making underpinning contemporary land management.
Human—Landscape Relations and the Occupation of Space: Experiencing and Expressing Domestic Gardens
Authors: Stenner Paul , Church Andrew , Bhatti Mark
Published: August 2012

A consideration of occupation and space is outlined to advance nonrepresentational thinking about human—landscape relations. Empirical findings are presented from a research project based on data from the Mass Observation Archive relevant to gardens and gardening. These data are analysed to explore how ‘ordinary’ people (who have contributed to this Archive) express and experience issues concerning their home gardens. Our analysis suggests four distinct modes of occupation relevant to the ways in which these lay writers describe their garden and gardening experiences and activities. The naturalistic mode is occupied with the garden as expressive of ‘nature’; the nostalgic mode is occupied with memory and self-reflection; the pragmatic mode concerns tasks/activities that constitute the routine practices of gardening; and the mimetic mode is occupied with the interpersonal dynamics and processes of human social activity. The analysis is situated in the theoretical context of some recent developments in nonrepresentational theory. We suggest that our approach and data are compatible with the process-orientation of nonrepresentational thinkers, and that—contrary to certain objectivist tendencies within nonrepresentational theorising—this approach does not need to neglect the importance of issues of subjectivity and experience, and the relevance of textual data. We aim to lend empirical substance to recent theoretical and philosophical discussions on space, and speculations about why the home garden appears to be so important to many people.
A Sense of Momentum: Mobility Practices and Dis/Embodied Landscapes of Energy Use
Authors: Nixon Denver V
Published: August 2012

This research examines how the commute practices of driving, cycling, and walking shape individuals' sense of mobility energy use. Some scholars argue that different modes of mobility produce different ways of knowing the world. For instance, automobiles are accused by some of alienating their drivers, whereas others see the human-machine hybrids they create as inherently connecting. This paper is founded upon an epistemological position that sees knowledge as developed through sensual interactions with environments and held, sometimes inexpressibly, within the body. Transportation technologies, both as part of a person's environment and as an extension of themselves, mediate these interactions. The research draws on in-depth interviews with drivers, cyclists, and pedestrians commuting in the City of Vancouver, and their commute narratives and GPS logs, to compare the sense of energy use between mode users. Participant senses explored include the feeling of momentum, changes in elevation, and stopping. Data analyses reveal active-mode users' nuanced and sometimes tacit awareness of energy use, and how this embodied knowledge both consciously and unconsciously informs their mobility. The efficiencies gained through this tacit knowing should be recognized alongside the more common ‘neotechnological’ approaches to transportation energy conservation, and accounted for in planning, public policy, and law.
Spaces of Faith: Incorporating Emotion and Spirituality in Geographic Studies
Authors: Finlayson Caitlin Cihak
Published: August 2012

Religious experience is highly personal and is often comprised of affectual encounters and emotional responses, both within personal space and through ordained sacred spaces. Expanding on recent geographical research, with the aid of semistructured interviews, this paper explores how personal affect and emotion are experienced by members from two houses of worship. The responses highlight the transformative nature of sacred space and its unique capacity to elicit emotional experiences from participants. Further, this study demonstrates that there is a commonality to spiritual experiences, such as a feeling of peace or a sense of being ‘home’, that cuts across denominational lines, and that these experiences are often spatially grounded.
Futures in the Making: Practices to Anticipate ‘Ubiquitous Computing’
Authors: Kinsley Sam
Published: August 2012

This paper addresses the discourse for a proactive thinking of futurity, intimately concerned with technology, which comes to an influential fruition in the discussion and representation of ‘ubiquitous computing’. The imagination, proposal, or playing out of ubiquitous computing environments are bound up with particular ways of constructing futurity. This paper charts the techniques used in ubiquitous computing development to negotiate that futurity. In so doing, it engages with recent geographical debates around anticipation and futurity. The discussion accordingly proceeds in four parts. First, the spatial imagination engendered by the development of ubiquitous computing is explored. Second, particular techniques in ubiquitous computing research and development for anticipating future technology use, and their limits, are discussed through empirical findings. Third, anticipatory knowledge is explored as the basis for stable means of future orientation, which both generates and derives from the techniques for anticipating futures. Fourth, the importance of studying future orientation is situated in relation to the somewhat contradictory nature of anticipatory knowledges of ubicomp and related forms of spatial imagination.
Do rural primary health care nurses feel equipped for palliative care?
Authors: Cumming M. , Boreland F. , Perkins D.
Published: August 2012

Community primary health care nurses in rural and remote settings are required to provide palliative care as part of their generalist role. They have limited access to specialist medical and nursing support and sometimes there are no resident GPs. A study consisting of a mailed survey and follow-up interviews was conducted to explore the experiences of these nurses and to determine how personally and professionally equipped they felt for palliative care service provision. Most participants were registered nurses experienced in nursing and in rural and remote settings, who juggled multiple generalist work roles. They had only occasional palliative care patients, and more than half had provided palliative care for a friend or family member. Some nurses found palliative care rewarding, others preferred not to have to do it. However, even those who did not enjoy working with palliative care patients often went beyond the ‘call of duty’ to support a home death if that was what the patient wanted. Three-quarters had attended palliative care education in the last 2 years but 88% wanted more education. Barriers to education included competing work roles, work load, geographical isolation and lack of backfill. Support from managers and peers was considered important, as was accessing timely and relevant clinical support.
microRNA-31/factor-inhibiting hypoxia-inducible factor 1 nexus regulates keratinocyte differentiation
Authors: Peng Han , Kaplan Nihal , Hamanaka Robert B. , Katsnelson Julia , Blatt Hanz , Yang Wending , Hao Liangliang , Bryar Paul J. , Johnson Randall S. , Getsios Spiro , Chandel Navdeep S. , Lavker Robert M.
Published: August 2012

Notch plays a critical role in the transition from proliferation to differentiation in the epidermis and corneal epithelium. Furthermore, aberrant Notch signaling is a feature of diseases like psoriasis, eczema, nonmelanoma skin cancer, and melanoma where differentiation and proliferation are impaired. Whereas much is known about the downstream events following Notch signaling, factors responsible for negatively regulating Notch receptor signaling after ligand activation are incompletely understood. Notch can undergo hydroxylation by factor-inhibiting hypoxia-inducible factor 1 (FIH-1); however, the biological significance of this phenomenon is unclear. Here we show that FIH-1 expression is up-regulated in diseased epidermis and corneal epithelium. Elevating FIH-1 levels in primary human epidermal keratinocytes (HEKs) and human corneal epithelial keratinocytes (HCEKs) impairs differentiation in submerged cultures and in a “three-dimensional” organotypic raft model of human epidermis, in part, via a coordinate decrease in Notch signaling. Knockdown of FIH-1 enhances keratinocyte differentiation. Loss of FIH-1 in vivo increased Notch activity in the limbal epithelium, resulting in a more differentiated phenotype. microRNA-31 (miR-31) is an endogenous negative regulator of FIH-1 expression that results in keratinocyte differentiation, mediated by Notch activation. Ectopically expressing miR-31 in an undifferentiated corneal epithelial cell line promotes differentiation and recapitulates a corneal epithelium in a three-dimensional raft culture model. Our results define a previously unknown mechanism for keratinocyte fate decisions where Notch signaling potential is, in part, controlled through a miR-31/FIH-1 nexus.
Suicide and drought in New South Wales, Australia, 1970–2007
Authors: Hanigan Ivan C. , Butler Colin D. , Kokic Philip N. , Hutchinson Michael F.
Published: August 2012

There is concern in Australia that droughts substantially increase the incidence of suicide in rural populations, particularly among male farmers and their families. We investigated this possibility for the state of New South Wales (NSW), Australia between 1970 and 2007, analyzing data on suicides with a previously established climatic drought index. Using a generalized additive model that controlled for season, region, and long-term suicide trends, we found an increased relative risk of suicide of 15% (95% confidence interval, 8%–22%) for rural males aged 30–49 y when the drought index rose from the first quartile to the third quartile. In contrast, the risk of suicide for rural females aged >30 y declined with increased values of the drought index. We also observed an increased risk of suicide in spring and early summer. In addition there was a smaller association during unusually warm months at any time of year. The spring suicide increase is well documented in nontropical locations, although its cause is unknown. The possible increased risk of suicide during drought in rural Australia warrants public health focus and concern, as does the annual, predictable increase seen each spring and early summer. Suicide is a complex phenomenon with many interacting social, environmental, and biological causal factors. The relationship between drought and suicide is best understood using a holistic framework. Climate change projections suggest increased frequency and severity of droughts in NSW, accompanied and exacerbated by rising temperatures. Elucidating the relationships between drought and mental health will help facilitate adaptation to climate change.
Emergence of social complexity among coastal hunter-gatherers in the Atacama Desert of northern Chile
Authors: Marquet Pablo A. , Santoro Calogero M. , Latorre Claudio , Standen Vivien G. , Abades Sebastián R. , Rivadeneira Marcelo M. , Arriaza Bernardo , Hochberg Michael E.
Published: August 2012

The emergence of complex cultural practices in simple hunter-gatherer groups poses interesting questions on what drives social complexity and what causes the emergence and disappearance of cultural innovations. Here we analyze the conditions that underlie the emergence of artificial mummification in the Chinchorro culture in the coastal Atacama Desert in northern Chile and southern Peru. We provide empirical and theoretical evidence that artificial mummification appeared during a period of increased coastal freshwater availability and marine productivity, which caused an increase in human population size and accelerated the emergence of cultural innovations, as predicted by recent models of cultural and technological evolution. Under a scenario of increasing population size and extreme aridity (with little or no decomposition of corpses) a simple demographic model shows that dead individuals may have become a significant part of the landscape, creating the conditions for the manipulation of the dead that led to the emergence of complex mortuary practices.
EGFR and HER2 receptor kinase signaling mediate epithelial cell invasion by
Candida albicans
during oropharyngeal infection
Authors: Zhu Weidong , Phan Quynh T. , Boontheung Pinmanee , Solis Norma V. , Loo Joseph A. , Filler Scott G.
Published: August 2012

The fungus
Candida albicans
is the major cause of oropharyngeal candidiasis (OPC). A key feature of this disease is fungal invasion of oral epithelial cells, a process that can occur by active penetration and fungal-induced endocytosis. Two invasins, Als3 and Ssa1, induce epithelial cell endocytosis of
C. albicans
, in part by binding to E-cadherin. However, inhibition of E-cadherin function only partially reduces
C. albicans
endocytosis, suggesting that there are additional epithelial cell receptors for this organism. Here, we show that the EGF receptor (EGFR) and HER2 function cooperatively to induce the endocytosis of
C. albicans
hyphae. EGFR and HER2 interact with
C. albicans
in an Als3- and Ssa1-dependent manner, and this interaction induces receptor autophosphorylation. Signaling through both EGFR and HER2 is required for maximal epithelial cell endocytosis of
C. albicans
in vitro. Importantly, oral infection with
C. albicans
stimulates the phosphorylation of EGFR and HER2 in the oral mucosa of mice, and treatment with a dual EGFR and HER2 kinase inhibitor significantly decreases this phosphorylation and reduces the severity of OPC. These results show the importance of EGFR and HER2 signaling in the pathogenesis of OPC and indicate the feasibility of treating candidal infections by targeting the host cell receptors with which the fungus interacts.
Tumor suppressor TSC1 is critical for T-cell anergy
Authors: Xie Dan-Li , Wu Jinhong , Lou Yong-Liang , Zhong Xiao-Ping
Published: August 2012

T-cell anergy is a state of T cells that is hyporesponsive to stimulation via the T-cell receptor and costimulatory molecules and is thought to be important for self-tolerance. How T-cell anergy is regulated is still poorly understood. We report here that tuberous sclerosis (TSC)1 is critical for T-cell anergy. Deficiency of TSC1 resulted in enhanced T-cell proliferation and cytokine production in the absence of cluster of differentiation (CD)28-mediated costimulation, accompanied by enhanced T-cell metabolism. Resistance of TSC1-deficient T cells to anergy is correlated with increased signaling through the mammalian target of rapamycin complex (mTORC)1 and can be reverted by treatment of these cells with mTORC1 inhibitor rapamycin. Expression of the inducible costimulator (ICOS) is increased in TSC1-deficient T cells, which can be inhibited by rapamycin. Simultaneous blockade of both CD28 and ICOS costimulation partially restored sensitivity of TSC1-deficient T cells to anergy induction. Together, our data indicate that TSC1 is crucial for T-cell anergy by inhibiting mTORC1 signaling through both ICOS-dependent and -independent mechanisms.
Telomere fusions in early human breast carcinoma
Authors: Tanaka Hiromi , Abe Satoshi , Huda Nazmul , Tu LiRen , Beam Matthew J. , Grimes Brenda , Gilley David
Published: August 2012

Several lines of evidence suggest that defects in telomere maintenance play a significant role in the initiation of genomic instability during carcinogenesis. Although the general concept of defective telomere maintenance initiating genomic instability has been acknowledged, there remains a critical gap in the direct evidence of telomere dysfunction in human solid tumors. To address this topic, we devised a multiplex PCR-based assay, termed TAR (telomere-associated repeat) fusion PCR, to detect and analyze chromosome end-to-end associations (telomere fusions) within human breast tumor tissue. Using TAR fusion PCR, we found that human breast lesions, but not normal breast tissues from healthy volunteers, contained telomere fusions. Telomere fusions were detected at similar frequencies during early ductal carcinoma in situ and in the later invasive ductal carcinoma stage. Our results provide direct evidence that telomere fusions are present in human breast tumor tissue and suggest that telomere dysfunction may be an important component of the genomic instability observed in this cancer. Development of this robust method that allows identification of these genetic aberrations (telomere fusions) is anticipated to be a valuable tool for dissecting mechanisms of telomere dysfunction.
Sound-sized segments are significant for Mandarin speakers
Authors: Qu Qingqing , Damian Markus F. , Kazanina Nina
Published: August 2012

Do speakers of all languages use segmental speech sounds when they produce words? Existing models of language production generally assume a mental representation of individual segmental units, or phonemes, but the bulk of evidence comes from speakers of European languages in which the orthographic system codes explicitly for speech sounds. By contrast, in languages with nonalphabetical scripts, such as Mandarin Chinese, individual speech sounds are not orthographically represented, raising the possibility that speakers of these languages do not use phonemes as fundamental processing units. We used event-related potentials (ERPs) combined with behavioral measurement to investigate the role of phonemes in Mandarin production. Mandarin native speakers named colored line drawings of objects using color adjective-noun phrases; color and object name either shared the initial phoneme or were phonologically unrelated. Whereas naming latencies were unaffected by phoneme repetition, ERP responses were modulated from 200 ms after picture onset. Our ERP findings thus provide strong support for the claim that phonemic segments constitute fundamental units of phonological encoding even for speakers of languages that do not encode such units orthographically.
On the evolutionary origins of the egalitarian syndrome
Authors: Gavrilets Sergey
Published: August 2012

The evolutionary emergence of the egalitarian syndrome is one of the most intriguing unsolved puzzles related to the origins of modern humans. Standard explanations and models for cooperation and altruism—reciprocity, kin and group selection, and punishment—are not directly applicable to the emergence of egalitarian behavior in hierarchically organized groups that characterized the social life of our ancestors. Here I study an evolutionary model of group-living individuals competing for resources and reproductive success. In the model, the differences in fighting abilities lead to the emergence of hierarchies where stronger individuals take away resources from weaker individuals and, as a result, have higher reproductive success. First, I show that the logic of within-group competition implies under rather general conditions that each individual benefits if the transfer of the resource from a weaker group member to a stronger one is prevented. This effect is especially strong in small groups. Then I demonstrate that this effect can result in the evolution of a particular, genetically controlled psychology causing individuals to interfere in a bully–victim conflict on the side of the victim. A necessary condition is a high efficiency of coalitions in conflicts against the bullies. The egalitarian drive leads to a dramatic reduction in within-group inequality. Simultaneously it creates the conditions for the emergence of inequity aversion, empathy, compassion, and egalitarian moral values via the internalization of behavioral rules imposed by natural selection. It also promotes widespread cooperation via coalition formation.
Super-resolution fluorescence imaging of organelles in live cells with photoswitchable membrane probes
Authors: Shim Sang-Hee , Xia Chenglong , Zhong Guisheng , Babcock Hazen P. , Vaughan Joshua C. , Huang Bo , Wang Xun , Xu Cheng , Bi Guo-Qiang , Zhuang Xiaowei
Published: August 2012

Imaging membranes in live cells with nanometer-scale resolution promises to reveal ultrastructural dynamics of organelles that are essential for cellular functions. In this work, we identified photoswitchable membrane probes and obtained super-resolution fluorescence images of cellular membranes. We demonstrated the photoswitching capabilities of eight commonly used membrane probes, each specific to the plasma membrane, mitochondria, the endoplasmic recticulum (ER) or lysosomes. These small-molecule probes readily label live cells with high probe densities. Using these probes, we achieved dynamic imaging of specific membrane structures in living cells with 30–60 nm spatial resolution at temporal resolutions down to 1–2 s. Moreover, by using spectrally distinguishable probes, we obtained two-color super-resolution images of mitochondria and the ER. We observed previously obscured details of morphological dynamics of mitochondrial fusion/fission and ER remodeling, as well as heterogeneous membrane diffusivity on neuronal processes.
Rapid responses of soil microorganisms improve plant fitness in novel environments
Authors: Lau Jennifer A. , Lennon Jay T.
Published: August 2012

Global change is challenging plant and animal populations with novel environmental conditions, including increased atmospheric CO
2
concentrations, warmer temperatures, and altered precipitation regimes. In some cases, contemporary or “rapid” evolution can ameliorate the effects of global change. However, the direction and magnitude of evolutionary responses may be contingent upon interactions with other community members that also are experiencing novel environmental conditions. Here, we examine plant adaptation to drought stress in a multigeneration experiment that manipulated aboveground–belowground feedbacks between plants and soil microbial communities. Although drought stress reduced plant growth and accelerated plant phenologies, surprisingly, plant evolutionary responses to drought were relatively weak. In contrast, plant fitness in both drought and nondrought environments was linked strongly to the rapid responses of soil microbial community structure to moisture manipulations. Specifically, plants were most fit when their contemporary environmental conditions (wet vs. dry soil) matched the historical environmental conditions (wet vs. dry soil) of their associated microbial community. Together, our findings suggest that, when faced with environmental change, plants may not be limited to “adapt or migrate” strategies; instead, they also may benefit from association with interacting species, especially diverse soil microbial communities, that respond rapidly to environmental change.
Structural divergence of paralogous S components from ECF-type ABC transporters
Authors: Berntsson Ronnie P.-A. , ter Beek Josy , Majsnerowska Maria , Duurkens Ria H. , Puri Pranav , Poolman Bert , Slotboom Dirk-Jan
Published: August 2012

Energy coupling factor (ECF) proteins are ATP-binding cassette transporters involved in the import of micronutrients in prokaryotes. They consist of two nucleotide-binding subunits and the integral membrane subunit EcfT, which together form the ECF module and a second integral membrane subunit that captures the substrate (the S component). Different S components, unrelated in sequence and specific for different ligands, can interact with the same ECF module. Here, we present a high-resolution crystal structure at 2.1 Å of the biotin-specific S component BioY from
Lactococcus lactis
. BioY shares only 16% sequence identity with the thiamin-specific S component ThiT from the same organism, of which we recently solved a crystal structure. Consistent with the lack of sequence similarity, BioY and ThiT display large structural differences (rmsd = 5.1 
Å
), but the divergence is not equally distributed over the molecules: The S components contain a structurally conserved N-terminal domain that is involved in the interaction with the ECF module and a highly divergent C-terminal domain that binds the substrate. The domain structure explains how the S components with large overall structural differences can interact with the same ECF module while at the same time specifically bind very different substrates with subnanomolar affinity. Solitary BioY (in the absence of the ECF module) is monomeric in detergent solution and binds D-biotin with a high affinity but does not transport the substrate across the membrane.
Deletion of
claudin-10
(
Cldn10
) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis
Authors: Breiderhoff Tilman , Himmerkus Nina , Stuiver Marchel , Mutig Kerim , Will Constanze , Meij Iwan C. , Bachmann Sebastian , Bleich Markus , Willnow Thomas E. , Müller Dominik
Published: August 2012

In the kidney, tight junction proteins contribute to segment specific selectivity and permeability of paracellular ion transport. In the thick ascending limb (TAL) of Henle's loop, chloride is reabsorbed transcellularly, whereas sodium reabsorption takes transcellular and paracellular routes. TAL salt transport maintains the concentrating ability of the kidney and generates a transepithelial voltage that drives the reabsorption of calcium and magnesium. Thus, functionality of TAL ion transport depends strongly on the properties of the paracellular pathway. To elucidate the role of the tight junction protein claudin-10 in TAL function, we generated mice with a deletion of
Cldn10
in this segment. We show that claudin-10 determines paracellular sodium permeability, and that its loss leads to hypermagnesemia and nephrocalcinosis. In isolated perfused TAL tubules of claudin-10–deficient mice, paracellular permeability of sodium is decreased, and the relative permeability of calcium and magnesium is increased. Moreover, furosemide-inhibitable transepithelial voltage is increased, leading to a shift from paracellular sodium transport to paracellular hyperabsorption of calcium and magnesium. These data identify claudin-10 as a key factor in control of cation selectivity and transport in the TAL, and deficiency in this pathway as a cause of nephrocalcinosis.
Metabolic manifestations of insulin deficiency do not occur without glucagon action
Authors: Lee Young , Berglund Eric D. , Wang May-yun , Fu Xiaorong , Yu Xinxin , Charron Maureen J. , Burgess Shawn C. , Unger Roger H.
Published: August 2012

To determine unambiguously if suppression of glucagon action will eliminate manifestations of diabetes, we expressed glucagon receptors in livers of glucagon receptor-null (GcgR
−/−
) mice before and after β-cell destruction by high-dose streptozotocin. Wild type (WT) mice developed fatal diabetic ketoacidosis after streptozotocin, whereas GcgR
−/−
mice with similar β-cell destruction remained clinically normal without hyperglycemia, impaired glucose tolerance, or hepatic glycogen depletion. Restoration of receptor expression using adenovirus containing the GcgR cDNA restored hepatic GcgR, phospho-cAMP response element binding protein (P-CREB), and phosphoenol pyruvate carboxykinase, markers of glucagon action, rose dramatically and severe hyperglycemia appeared. When GcgR mRNA spontaneously disappeared 7 d later, P-CREB declined and hyperglycemia disappeared. In conclusion, the metabolic manifestations of diabetes cannot occur without glucagon action and, once present, disappear promptly when glucagon action is abolished. Glucagon suppression should be a major therapeutic goal in diabetes.
Biophysical mechanisms of MRI signal frequency contrast in multiple sclerosis
Authors: Yablonskiy Dmitriy A. , Luo Jie , Sukstanskii Alexander L. , Iyer Aditi , Cross Anne H.
Published: August 2012

Phase images obtained with gradient echo MRI provide image contrast distinct from T1- and T2-weighted images. It is commonly assumed that the local contribution to MRI signal phase directly relates to local bulk tissue magnetic susceptibility. Here, we use Maxwell’s equations and Monte Carlo simulations to provide theoretical background to the hypothesis that the local contribution to MRI signal phase does not depend on tissue bulk magnetic susceptibility but tissue magnetic architecture—distribution of magnetic susceptibility inclusions (lipids, proteins, iron, etc.) at the cellular and subcellular levels. Specifically, we show that the regular longitudinal structures forming cylindrical axons (myelin sheaths and neurofilaments) can be locally invisible in phase images. Contrary to an expectation that the phase contrast in multiple sclerosis lesions should always increase in degree along with worsening of lesion severity (which happens for all known MR magnitude-based contrast mechanisms), we show that phase contrast can actually disappear with extreme tissue destruction. We also show that the phase contrast in multiple sclerosis lesions could be altered without loss of nervous system tissue, which happens in mild injury to the myelin sheaths or axonal neurofilaments. Moreover, we predict that the sign of phase contrast in multiple sclerosis lesions indicates the predominant type of tissue injury—myelin damage (positive sign) vs. axonal neurofilament damage (negative sign). Therefore, our theoretical and experimental results shed light on understanding the relationship between gradient echo MRI signal phase and multiple sclerosis pathology.
Perioddetermination in the food-entrainable and methamphetamine-sensitive circadian oscillator(s)
Authors: Pendergast Julie S. , Oda Gisele A. , Niswender Kevin D. , Yamazaki Shin
Published: August 2012

Daily rhythmic processes are coordinated by circadian clocks, which are present in numerous central and peripheral tissues. In mammals, two circadian clocks, the food-entrainable oscillator (FEO) and methamphetamine-sensitive circadian oscillator (MASCO), are “black box” mysteries because their anatomical loci are unknown and their outputs are not expressed under normal physiological conditions. In the current study, the investigation of the timekeeping mechanisms of the FEO and MASCO in mice with disruption of all three paralogs of the canonical clock gene,Period,revealed unique and convergent findings. We found that both the MASCO and FEO inPer1−/−/Per2−/−/Per3−/−mice are circadian oscillators with unusually short (∼21 h) periods. These data demonstrate that the canonicalPeriodgenes are involved in period determination in the FEO and MASCO, and computational modeling supports the hypothesis that the FEO and MASCO use the same timekeeping mechanism or are the same circadian oscillator. Finally, these studies identifyPer1−/−/Per2−/−/Per3−/−mice as a unique tool critical to the search for the elusive anatomical location(s) of the FEO and MASCO.
Hippocampal nitric oxide contributes to sex difference in affective behaviors
Authors: Hu Yao , Wu Dan-Lian , Luo Chun-Xia , Zhu Li-Juan , Zhang Jing , Wu Hai-Yin , Zhu Dong-Ya
Published: August 2012

Mechanisms underlying the female preponderance in affective disorders are poorly understood. Here we show that hippocampal nitric oxide (NO) plays a role in the sex difference of depression-like behaviors in rodents. Female mice had substantially lower NO production in the hippocampus and were significantly more likely to display negative affective behaviors than their male littermates. Eliminating the difference in the basal hippocampal NO level between male and female mice mended the sex gap of affective behaviors. Estradiol exerted a positive control on hippocampal NO production via estrogen receptor-β–mediated neuronal NO synthase expression. Thus, low estrogen in the female hippocampus accounts for lower local NO than in the male hippocampus. Although estrogen has important significance in modulating affective behaviors, it is not estrogen but NO in the hippocampus that mediates the sex difference of affective behaviors directly, because hippocampal NO was necessary for the behavioral effects of estradiol, and NO was an independent factor in modulating behaviors. Stress promoted hippocampal NO production in males because of glucocorticoid release, thus leading to local NO excess. In contrast, stress suppressed NO production in females because of decreased estrogen, thereby resulting in hippocampal NO shortage. Whereas activating cAMP response element binding protein (CREB) rescued the depression-like effects of the intrahippocampal NO donor diethylenetriamine/nitric oxide adduct (DETA/NONOate), inactivating CREB abolished the antidepressant-like effects of the intrahippocampal NO donor DETA/NONOate. Our findings suggest a molecular mechanism underlying the sex difference of affective behaviors.
Structural investigations of a
Podoviridae streptococcus
phage C1, implications for the mechanism of viral entry
Authors: Aksyuk Anastasia A. , Bowman Valorie D. , Kaufmann Bärbel , Fields Christopher , Klose Thomas , Holdaway Heather A. , Fischetti Vincent A. , Rossmann Michael G.
Published: August 2012

The
Podoviridae
phage C1 was one of the earliest isolated bacteriophages and the first virus documented to be active against streptococci. The icosahedral and asymmetric reconstructions of the virus were calculated using cryo-electron microscopy. The capsid protein has an HK97 fold arranged into a
T
 = 4 icosahedral lattice. The C1 tail is terminated with a
φ
29-like knob, surrounded by a skirt of twelve long appendages with novel morphology. Several C1 structural proteins have been identified, including a candidate for an appendage. The crystal structure of the knob has an N-terminal domain with a fold observed previously in tube forming proteins of
Siphoviridae
and
Myoviridae
phages. The structure of C1 suggests the mechanisms by which the virus digests the cell wall and ejects its genome. Although there is little sequence similarity to other phages, conservation of the structural proteins demonstrates a common origin of the head and tail, but more recent evolution of the appendages.
Paleontological and developmental evidence resolve the homology and dual embryonic origin of a mammalian skull bone, the interparietal
Authors: Koyabu Daisuke , Maier Wolfgang , Sánchez-Villagra Marcelo R.
Published: August 2012

The homologies of mammalian skull elements are now fairly well established, except for the controversial interparietal bone. A previous experimental study reported an intriguing mixed origin of the interparietal: the medial portion being derived from the neural crest cells, whereas the lateral portion from the mesoderm. The evolutionary history of such mixed origin remains unresolved, and contradictory reports on the presence or absence and developmental patterns of the interparietal among mammals have complicated the question of its homology. Here we provide an alternative perspective on the evolutionary identity of the interparietal, based on a comprehensive study across more than 300 extinct and extant taxa, integrating embryological and paleontological data. Although the interparietal has been regarded as being lost in various lineages, our investigation on embryos demonstrates its presence in all extant mammalian “orders.” The generally accepted paradigm has regarded the interparietal as consisting of two elements that are homologized to the postparietals of basal amniotes. The tabular bones have been postulated as being lost during the rise of modern mammals. However, our results demonstrate that the interparietal consists not of two but of four elements. We propose that the tabulars of basal amniotes are conserved as the lateral interparietal elements, which quickly fuse to the medial elements at the embryonic stage, and that the postparietals are homologous to the medial elements. Hence, the dual developmental origin of the mammalian interparietal can be explained as the evolutionary consequence of the fusion between the crest-derived “postparietals” and the mesoderm-derived “tabulars.”
A kinetic model of rapidly reversible nonphotochemical quenching
Authors: Zaks Julia , Amarnath Kapil , Kramer David M. , Niyogi Krishna K. , Fleming Graham R.
Published: August 2012

Oxygen-evolving photosynthetic organisms possess nonphotochemical quenching (NPQ) pathways that protect against photo-induced damage. The majority of NPQ in plants is regulated on a rapid timescale by changes in the pH of the thylakoid lumen. In order to quantify the rapidly reversible component of NPQ, called qE, we developed a mathematical model of pH-dependent quenching of chlorophyll excitations in Photosystem II. Our expression for qE depends on the protonation of PsbS and the deepoxidation of violaxanthin by violaxanthin deepoxidase. The model is able to simulate the kinetics of qE at low and high light intensities. The simulations suggest that the pH of the lumen, which activates qE, is not itself affected by qE. Our model provides a framework for testing hypothesized qE mechanisms and for assessing the role of qE in improving plant fitness in variable light intensity.
Reduced phosphatidylinositol 4,5-bisphosphate synthesis impairs inner ear Ca
2+
signaling and high-frequency hearing acquisition
Authors: Rodriguez Laura , Simeonato Elena , Scimemi Pietro , Anselmi Fabio , Calì Bianca , Crispino Giulia , Ciubotaru Catalin D. , Bortolozzi Mario , Ramirez Fabian Galindo , Majumder Paromita , Arslan Edoardo , De Camilli Pietro , Pozzan Tullio , Mammano Fabio
Published: August 2012

Phosphatidylinositol phosphate kinase type 1γ (PIPKIγ) is a key enzyme in the generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P
2
] and is expressed at high levels in the nervous system. Homozygous knockout mice lacking this enzyme die postnatally within 24 h, whereas PIPKIγ
+/−
siblings breed normally and have no reported phenotype. Here we show that adult PIPKIγ
+/−
mice have dramatically elevated hearing thresholds for high-frequency sounds. During the first postnatal week we observed a reduction of ATP-dependent Ca
2+
signaling activity in cochlear nonsensory cells. Because Ca
2+
signaling under these conditions depends on inositol-1,4,5-trisphosphate generation from phospholipase C (PLC)-dependent hydrolysis of PI(4,5)P
2
, we conclude that (
i
) PIPKIγ is primarily responsible for the synthesis of the receptor-regulated PLC-sensitive PI(4,5)P
2
pool in the cell syncytia that supports auditory hair cells; (
ii
) spatially graded impairment of this signaling pathway in cochlear nonsensory cells causes a selective alteration in the acquisition of hearing in PIPKIγ
+/−
mice. This mouse model also suggests that PIPKIγ may determine the level of gap junction contribution to cochlear development.
Fission yeast Ags1 confers the essential septum strength needed for safe gradual cell abscission
Authors: Cortés Juan Carlos G. , Sato Mamiko , Muñoz Javier , Moreno M. Belén , Clemente-Ramos Jose Angel , Ramos Mariona , Okada Hitoshi , Osumi Masako , Durán Angel , Ribas Juan Carlos
Published: August 2012

Fungal cytokinesis requires the assembly of a dividing septum wall. In yeast, the septum has to be selectively digested during the critical cell separation process. Fission yeast cell wall α(1-3)glucan is essential, but nothing is known about its localization and function in the cell wall or about cooperation between the α- and β(1-3)glucan synthases Ags1 and Bgs for cell wall and septum assembly. Here, we generate a physiological Ags1-GFP variant and demonstrate a tight colocalization with Bgs1, suggesting a cooperation in the important early steps of septum construction. Moreover, we define the essential functions of α(1-3)glucan in septation and cell separation. We show that α(1-3)glucan is essential for both secondary septum formation and the primary septum structural strength needed to support the physical forces of the cell turgor pressure during cell separation. Consequently, the absence of Ags1 and therefore α(1-3)glucan generates a special and unique side-explosive cell separation due to an instantaneous primary septum tearing caused by the turgor pressure.