bluuebunny/crossref_metadata_2025 huggingface dataset:
Using time-delayed mutual information to discover and interpret temporal correlation structure in complex populations
Authors: Albers D. J. , Hripcsak George
Published: January 2012

This paper addresses how to calculate and interpret the time-delayed mutual information (TDMI) for a complex, diversely and sparsely measured, possibly non-stationary population of time-series of unknown composition and origin. The primary vehicle used for this analysis is a comparison between the time-delayed mutual information averaged over the population and the time-delayed mutual information of an aggregated population (here, aggregation implies the population is conjoined before any statistical estimates are implemented). Through the use of information theoretic tools, a sequence of practically implementable calculations are detailed that allow for the average and aggregate time-delayed mutual information to be interpreted. Moreover, these calculations can also be used to understand the degree of homo or heterogeneity present in the population. To demonstrate that the proposed methods can be used in nearly any situation, the methods are applied and demonstrated on the time series of glucose measurements from two different subpopulations of individuals from the Columbia University Medical Center electronic health record repository, revealing a picture of the composition of the population as well as physiological features.
Theoretical analysis of multiplicative-noise-induced complete synchronization in global coupled dynamical network
Authors: Xiao Yuzhu , Tang Sufang , Xu Yong
Published: January 2012

In this paper, based on the theory of stochastic differential equation, we study the effect of noise on the synchronization of global coupled dynamical network, when noise presents in coupling term. The theoretical result shows that noise can really induce synchronization. To verify the theoretical result, Cellular Neural Network neural model and Rössler-like system are performed as numerical examples.
Ge redistribution in SiO2/SiGe structures under thermal oxidation: Dynamics and predictions
Authors: Long Ethan , Azarov Alexander , Kløw Frode , Galeckas Augustinas , Yu Kuznetsov Andrej , Diplas Spyridon
Published: January 2012

Several fundamental aspects of the oxidation-induced redistribution of Ge in thin films of SiGe are studied. This includes the incorporation of Ge into the oxide and the formation of what is alternatively referred to as pile-up, snow-plow, or a germanium-rich layer. Experimental data from the present work shows longer oxidation times leading to an increase of Ge content in the pile-up region and eventually creating a single high Ge content pile-up layer by entirely consuming the initial SiGe layer. The pile-up effect was shown to occur at the oxidation interface, with the highest Ge content occurring at the same interface. For a given oxide thickness, the redistribution of Ge and the formation of a pile-up region was shown experimentally to be independent of temperature in the range between 800 °C and 1000 °C. Simulations using common models for the oxidation of Si and diffusion of Si in SiGe indicate that temperature does have an influence on the composition of the pile-up layer, though the range of achievable compositions is limited. The flux of Si due to diffusion of Si in SiGe relative to the oxidation-induced flux of Si out of the SiGe is integral to the formation and dimensions of a pile-up region. Two predictive relations were derived for describing the dynamics of oxidation of SiGe. The first relation is given for determining the pile-up layer thickness as a function of oxide thickness and the composition of the pile-up layer. The second relation assumes a limited supply of Si and is for determination of the minimum initial thickness of a SiGe layer to avoid oxidation of Ge. The validity of these equations was confirmed experimentally by RBS and XPS data from the present work. The proposed models may be used in nanostructuring of thin films of SiGe by oxidation and in the design of core-shell structures and transistors. This is all done with a focus on oxidation of epitaxial thin films (< 100 nm) of Si1-XGeX in dry O2 at 1 atm between 800 °C and 1000 °C.
Improved electron field emission from morphologically disordered monolayer graphene
Authors: Pandey Srikrishna , Rai Padmnabh , Patole Shashikant , Gunes Fethullah , Kwon Gi-Duk , Yoo Ji-Beom , Nikolaev Pavel , Arepalli Sivaram
Published: January 2012

Graphene was synthesized on copper foil by thermal chemical vapor deposition technique. To investigate the field electron emission property, planar graphene (PG) and morphologically disordered graphene (MDG) were fabricated on the doped silicon substrate by transfer of as-grown graphene. Incorporation of morphological disorder in graphene creates more emission sites due to the additional defects, edges, and atomic scale ripples. This resulted in (1) a dramatic increase in the maximum current density by a factor of 500, (2) considerable increase in the enhancement factor, and (3) decrease in the turn-on field of MDG compared to PG.
Performing Carbon's Materiality: The Production of Carbon Offsets and the Framing of Exchange
Authors: Lansing David M
Published: January 2012

In this paper I provide a first-hand account of a trip designed to verify the existence of a carbon forestry offset in Costa Rica. In so doing, I reflect on how various actors become the stabilized calculative agents of scientists, state bureaucrats, indigenous leaders, GPS devices, trees, signs, and field reports that such trips require. In addition, I show how various articulations of these actors, and their emergent agencies, simultaneously maintains both the carbon offset as a commodity object as well as a field of action and communication that allows for such an object to be exchanged. In short, I consider the verification of an offset as a performance. Doing so, I examine the agency of some actors in this process, and account for the uneven power relations inherent in such a process. Specifically, I advance three arguments. First, the agency of actors is constituted, in part, by various calculative devices, which themselves simultaneously occupy an unstable position of being both a material object and an abstraction. Second, the normative power of the performance I witnessed derives from its relation to the abject: spaces and ways of being that are unintelligible to the logics of offsetting that nonetheless serve to further reiterate the need for an offset's calculative frame. Third, performing an offset is a self-reflexive process, and it is through the self-reflexivity of actors involved that the qualities of ‘the forest’ emerge in ways that confound the stability of an offset commodity. In this way, the biophysical qualities of the forest are not necessarily barriers to its commodification. Instead, it is the reflexive practices inherent in performing ‘the economic’ that can serve to confound the emergence of the commodified forest.
Gentrifiers and Their Choice of Housing: Characteristics of the Households Living in New Developments in Swiss Cities
Authors: Rérat Patrick
Published: January 2012

This paper draws on the literature on residential mobility in order to address the housing choice of gentrifiers and its different dimensions (profile, trajectories, and motivations). The gentrification literature is reviewed in regard to these dimensions. Empirical material is based on questionnaires sent to the inhabitants of new high-status developments (new-build gentrification) in two Swiss cities (Zurich and Neuchâtel). By pointing out some of the characteristics found in the Swiss context, the results contribute to an understanding of the attributes of contemporary gentrifiers, such as their diversity in terms of life-course position, the transitory stage that living in a gentrified neighbourhood may represent, and the predominance of the convenience of urban life (proximity and mobility) in their motivations.
Components of Aesthetic Experience: Aesthetic Fascination, Aesthetic Appraisal, and Aesthetic Emotion
Authors: Marković Slobodan
Published: January 2012

In this paper aesthetic experience is defined as an experience qualitatively different from everyday experience and similar to other exceptional states of mind. Three crucial characteristics of aesthetic experience are discussed: fascination with an aesthetic object (high arousal and attention), appraisal of the symbolic reality of an object (high cognitive engagement), and a strong feeling of unity with the object of aesthetic fascination and aesthetic appraisal. In a proposed model, two parallel levels of aesthetic information processing are proposed. On the first level two sub-levels of narrative are processed, story (theme) and symbolism (deeper meanings). The second level includes two sub-levels, perceptual associations (implicit meanings of object's physical features) and detection of compositional regularities. Two sub-levels are defined as crucial for aesthetic experience, appraisal of symbolism and compositional regularities. These sub-levels require some specific cognitive and personality dispositions, such as expertise, creative thinking, and openness to experience. Finally, feedback of emotional processing is included in our model: appraisals of everyday emotions are specified as a matter of narrative content (eg, empathy with characters), whereas the aesthetic emotion is defined as an affective evaluation in the process of symbolism appraisal or the detection of compositional regularities.
Screening for abdominal aortic aneurysm: does it affect men’s quality of life?
Authors: Lesjak M. , Boreland F. , Lyle D. , Sidford J. , Flecknoe-Brown S. , Fletcher J.
Published: January 2012

A prospective study investigated the psychological wellbeing and quality of life of older rural men after a community-based screening for abdominal aortic aneurysm (AAA). Five hundred and sixteen men aged 65–74 years attended the screening program; 53 had an abnormal aorta detected. These and a subsample of men with a normal aorta were followed up 6 months post-screening. All men completed a pre-screening questionnaire including the Medical Outcomes Short Form 36v 2 (MOSF36) and Hospital Anxiety and Depression Scale (HADS). Six months after screening all 53 men with an abnormal and 130 with a normal aorta were sent a questionnaire including MOSF36 and HADS. Baseline and 6 month scores for both MOSF36 and HADS scores were compared between the two groups and within each group. Baseline scores for both MOSF36 and HADS were not significantly different between men who were subsequently diagnosed with an abnormal aorta and those with a normal aorta. After 6 months there was no difference in HADS scores but a significant increase in the MOSF36 dimension of general health. Those with a normal aorta reported better general health, social functioning andgreater freedom from bodily pain. AAA screening appears highly acceptable to men in the target age group and future research should focus on implementation, cost effectiveness and collateral benefits of AAA screening.
Tight coevolution of proliferating cell nuclear antigen (PCNA)-partner interaction networks in fungi leads to interspecies network incompatibility
Authors: Zamir Lyad , Zaretsky Marianna , Fridman Yearit , Ner-Gaon Hadas , Rubin Eitan , Aharoni Amir
Published: January 2012

The structure and connectivity of protein-protein interaction (PPI) networks are maintained throughout evolution by coordinated changes (coevolution) of network proteins. Despite extensive research, relatively little is known regarding the molecular basis and functional implications of the coevolution of PPI networks. Here, we used proliferating cell nuclear antigen, a hub protein that mediates DNA replication and repair in eukaryotes, as a model system to study the coevolution of PPI networks in fungi. Using a combined bioinformatics and experimental approach, we discovered that PCNA-partner interactions tightly coevolved in fungal species, leading to specific modes of recognition. We found that fungal proliferating cell nuclear antigen-partner interaction networks diverged into two distinct groups as a result of such coevolution and that hybrid networks of these groups are functionally noncompatible in
Saccharomyces cerevisiae
. Our results indicate that the coevolution of PPI networks can form functional barriers between fungal species, and thus can promote and fix speciation.
Histone density is maintained during transcription mediated by the chromatin remodeler RSC and histone chaperone NAP1 in vitro
Authors: Kuryan Benjamin G. , Kim Jessica , Tran Nancy Nga H. , Lombardo Sarah R. , Venkatesh Swaminathan , Workman Jerry L. , Carey Michael
Published: January 2012

ATPases and histone chaperones facilitate RNA polymerase II (pol II) elongation on chromatin. In vivo, the coordinated action of these enzymes is necessary to permit pol II passage through a nucleosome while restoring histone density afterward. We have developed a biochemical system recapitulating this basic process. Transcription through a nucleosome in vitro requires the ATPase remodels structure of chromatin (RSC) and the histone chaperone nucleosome assembly protein 1 (NAP1). In the presence of NAP1, RSC generates a hexasome. Despite the propensity of RSC to evict histones, NAP1 reprograms the reaction such that the hexasome is retained on the template during multiple rounds of transcription. This work has implications toward understanding the mechanism of pol II elongation on chromatin.
Aβ neurotoxicity depends on interactions between copper ions, prion protein, and
N
-methyl-
d
-aspartate receptors
Authors: You Haitao , Tsutsui Shigeki , Hameed Shahid , Kannanayakal Thomas J. , Chen Lina , Xia Peng , Engbers Jordan D. T. , Lipton Stuart A. , Stys Peter K. , Zamponi Gerald W.
Published: January 2012

N
-methyl-
d
-aspartate receptors (NMDARs) mediate critical CNS functions, whereas excessive activity contributes to neuronal damage. At physiological glycine concentrations, NMDAR currents recorded from cultured rodent hippocampal neurons exhibited strong desensitization in the continued presence of NMDA, thus protecting neurons from calcium overload. Reducing copper availability by specific chelators (bathocuproine disulfonate, cuprizone) induced nondesensitizing NMDAR currents even at physiologically low glycine concentrations. This effect was mimicked by, and was not additive with, genetic ablation of cellular prion protein (PrP
C
), a key copper-binding protein in the CNS. Acute ablation of PrP
C
by enzymatically cleaving its cell-surface GPI anchor yielded similar effects. Biochemical studies and electrophysiological measurements revealed that PrP
C
interacts with the NMDAR complex in a copper-dependent manner to allosterically reduce glycine affinity for the receptor. Synthetic human Aβ
1–42
(10 nM–5 μM) produced an identical effect that could be mitigated by addition of excess copper ions or NMDAR blockers. Taken together, Aβ
1–42
, copper chelators, or PrP
C
inactivation all enhance the activity of glycine at the NMDAR, giving rise to pathologically large nondesensitizing steady-state NMDAR currents and neurotoxicity. We propose a physiological role for PrP
C
, one that limits excessive NMDAR activity that might otherwise promote neuronal damage. In addition, we provide a unifying molecular mechanism whereby toxic species of Aβ
1–42
might mediate neuronal and synaptic injury, at least in part, by disrupting the normal copper-mediated, PrP
C
-dependent inhibition of excessive activity of this highly calcium-permeable glutamate receptor.
CD4 and CD8 T cells require different membrane gangliosides for activation
Authors: Nagafuku Masakazu , Okuyama Kaori , Onimaru Yuri , Suzuki Akemi , Odagiri Yuta , Yamashita Tadashi , Iwasaki Katsunori , Fujiwara Michihiro , Takayanagi Motoaki , Ohno Isao , Inokuchi Jin-ichi
Published: January 2012

Initial events of T-cell activation involve movement of the T-cell receptor into lipid rafts. Gangliosides are major components of lipid rafts. While investigating T-cell activation in ganglioside-deficient mice, we observed that CD4
+
and CD8
+
T cells required different ganglioside subsets for activation. Activation of CD4
+
T cells from GM3 synthase-null mice, deficient in GM3-derived gangliosides, is severely compromised, whereas CD8
+
T-cell activation is normal. Conversely, in cells from GM2/GD2 synthase-null mice, expressing only GM3 and GD3, CD4
+
T-cell activation is normal, whereas CD8
+
T-cell activation is deficient. Supplementing the cells with the corresponding missing gangliosides restores normal activation. GM3 synthase-null mice do not develop experimental asthma. Distinct expression patterns of ganglioside species in CD4
+
T and CD8
+
T cells, perhaps in uniquely functional lipid rafts, define immune functions in each T-cell subset. Control of ganglioside expression would offer a strategy targeting for specific T-cell subpopulations to treat immune diseases.
Crystal structures of two bacterial HECT-like E3 ligases in complex with a human E2 reveal atomic details of pathogen-host interactions
Authors: Lin David Yin-wei , Diao Jianbo , Chen Jue
Published: January 2012

In eukaryotes, ubiquitination is an important posttranslational process achieved through a cascade of ubiquitin-activating (E1), conjugating (E2), and ligase (E3) enzymes. Many pathogenic bacteria deliver virulence factors into the host cell that function as E3 ligases. How these bacterial “Trojan horses” integrate into the eukaryotic ubiquitin system has remained a mystery. Here we report crystal structures of two bacterial E3s,
Salmonella
SopA and
Escherichia coli
NleL, both in complex with human E2 UbcH7. These structures represent two distinct conformational states of the bacterial E3s, supporting the necessary structural rearrangements associated with ubiquitin transfer. The E2-interacting surface of SopA and NleL has little similarity to those of eukaryotic E3s. However, both bacterial E3s bind to the canonical surface of E2 that normally interacts with eukaryotic E3s. Furthermore, we show that a glutamate residue on E3 is involved in catalyzing ubiquitin transfer from E3 to the substrate, but not from E2 to E3. Together, these results provide mechanistic insights into the ubiquitin pathway and a framework for understanding molecular mimicry in bacterial pathogenesis.
Ancestral capture of
syncytin-Car1
, a fusogenic endogenous retroviral
envelope
gene involved in placentation and conserved in Carnivora
Authors: Cornelis Guillaume , Heidmann Odile , Bernard-Stoecklin Sibylle , Reynaud Karine , Véron Géraldine , Mulot Baptiste , Dupressoir Anne , Heidmann Thierry
Published: January 2012

Syncytins
are envelope protein genes of retroviral origin that have been captured for a function in placentation. Two such genes have already been identified in simians, two distinct, unrelated genes have been identified in Muridae, and a fifth gene has been identified in the rabbit. Here, we searched for similar genes in the Laurasiatheria clade, which diverged from Euarchontoglires—primates, rodents, and lagomorphs—shortly after mammalian radiation (100 Mya). In silico search for envelope protein genes with full-coding capacity within the dog and cat genomes identified several candidate genes, with one common to both species that displayed placenta-specific expression, which was revealed by RT-PCR analysis of a large panel of tissues. This gene belongs to a degenerate endogenous retroviral element, with precise proviral integration at a site common to dog and cat. Cloning of the gene for an ex vivo pseudotype assay showed fusogenicity on both dog and cat cells. In situ hybridization on placenta sections from both species showed specific expression at the level of the invasive fetal villi within the placental junctional zone, where trophoblast cells fuse into a syncytiotrophoblast layer to form the maternofetal interface. Finally, we show that the gene is conserved among a series of 26 Carnivora representatives, with evidence for purifying selection and conservation of fusogenic activity. The gene is not found in the Pholidota order and, therefore, it was captured before Carnivora radiation, between 60 and 85 Mya. This gene is the oldest
syncytin
gene identified to date, and it is the first in a new major clade of eutherian mammals.
Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection
Authors: Fanning Saranna , Hall Lindsay J. , Cronin Michelle , Zomer Aldert , MacSharry John , Goulding David , O'Connell Motherway Mary , Shanahan Fergus , Nally Kenneth , Dougan Gordon , van Sinderen Douwe
Published: January 2012

Bifidobacteria comprise a significant proportion of the human gut microbiota. Several bifidobacterial strains are currently used as therapeutic interventions, claiming various health benefits by acting as probiotics. However, the precise mechanisms by which they maintain habitation within their host and consequently provide these benefits are not fully understood. Here we show thatBifidobacterium breveUCC2003 produces a cell surface-associated exopolysaccharide (EPS), the biosynthesis of which is directed by either half of a bidirectional gene cluster, thus leading to production of one of two possible EPSs. Alternate transcription of the two opposing halves of this cluster appears to be the result of promoter reorientation. Surface EPS provided stress tolerance and promoted in vivo persistence, but not initial colonization. Marked differences were observed in host immune response: strains producing surface EPS (EPS+) failed to elicit a strong immune response compared with EPS-deficient variants. Specifically, EPS production was shown to be linked to the evasion of adaptive B-cell responses. Furthermore, presence of EPS+B. brevereduced colonization levels of the gut pathogenCitrobacter rodentium. Our data thus assigns a pivotal and beneficial role for EPS in modulating various aspects of bifidobacterial–host interaction, including the ability of commensal bacteria to remain immunologically silent and in turn provide pathogen protection. This finding enforces the probiotic concept and provides mechanistic insights into health-promoting benefits for both animal and human hosts.
Transforming growth factor beta-activated kinase 1 (TAK1)-dependent checkpoint in the survival of dendritic cells promotes immune homeostasis and function
Authors: Wang Yanyan , Huang Gonghua , Vogel Peter , Neale Geoffrey , Reizis Boris , Chi Hongbo
Published: January 2012

Homeostatic control of dendritic cell (DC) survival is crucial for adaptive immunity, but the molecular mechanism is not well defined. Moreover, how DCs influence immune homeostasis under steady state remains unclear. Combining DC-specific and -inducible deletion systems, we report that transforming growth factor beta-activated kinase 1 (TAK1) is an essential regulator of DC survival and immune system homeostasis and function. Deficiency of TAK1 in CD11c
+
cells induced markedly elevated apoptosis, leading to the depletion of DC populations, especially the CD8
+
and CD103
+
DC subsets in lymphoid and nonlymphoid tissues, respectively. TAK1 also contributed to DC development by promoting the generation of DC precursors. Prosurvival signals from Toll-like receptors, CD40 and receptor activator of nuclear factor-κB (RANK) are integrated by TAK1 in DCs, which in turn mediated activation of downstream NF-κB and AKT-Foxo pathways and established a gene-expression program. TAK1 deficiency in DCs caused a myeloid proliferative disorder characterized by expansion of neutrophils and inflammatory monocytes, disrupted T-cell homeostasis, and prevented effective T-cell priming and generation of regulatory T cells. Moreover, TAK1 signaling in DCs was required to prevent myeloid proliferation even in the absence of lymphocytes, indicating a previously unappreciated regulatory mechanism of DC-mediated control of myeloid cell-dependent inflammation. Therefore, TAK1 orchestrates a prosurvival checkpoint in DCs that affects the homeostasis and function of the immune system.
Unidirectionally aligned line patterns driven by entropic effects on faceted surfaces
Authors: Hong Sung Woo , Huh June , Gu Xiaodan , Lee Dong Hyun , Jo Won Ho , Park Soojin , Xu Ting , Russell Thomas P.
Published: January 2012

A simple, versatile approach to the directed self-assembly of block copolymers into a macroscopic array of unidirectionally aligned cylindrical microdomains on reconstructed faceted single crystal surfaces or on flexible, inexpensive polymeric replicas was discovered. High fidelity transfer of the line pattern generated from the microdomains to a master mold is also shown. A single-grained line patterns over arbitrarily large surface areas without the use of top-down techniques is demonstrated, which has an order parameter typically in excess of 0.97 and a slope error of 1.1 deg. This degree of perfection, produced in a short time period, has yet to be achieved by any other methods. The exceptional alignment arises from entropic penalties of chain packing in the facets coupled with the bending modulus of the cylindrical microdomains. This is shown, theoretically, to be the lowest energy state. The atomic crystalline ordering of the substrate is transferred, over multiple length scales, to the block copolymer microdomains, opening avenues to large-scale roll-to-roll type and nanoimprint processing of perfectly patterned surfaces and as templates and scaffolds for magnetic storage media, polarizing devices, and nanowire arrays.
Subcellular calcium dynamics in a whole-cell model of an atrial myocyte
Authors: Thul Rüdiger , Coombes Stephen , Roderick H. Llewelyn , Bootman Martin D.
Published: January 2012

In this study, we present an innovative mathematical modeling approach that allows detailed characterization of Ca
2+
movement within the three-dimensional volume of an atrial myocyte. Essential aspects of the model are the geometrically realistic representation of Ca
2+
release sites and physiological Ca
2+
flux parameters, coupled with a computationally inexpensive framework. By translating nonlinear Ca
2+
excitability into threshold dynamics, we avoid the computationally demanding time stepping of the partial differential equations that are often used to model Ca
2+
transport. Our approach successfully reproduces key features of atrial myocyte Ca
2+
signaling observed using confocal imaging. In particular, the model displays the centripetal Ca
2+
waves that occur within atrial myocytes during excitation–contraction coupling, and the effect of positive inotropic stimulation on the spatial profile of the Ca
2+
signals. Beyond this validation of the model, our simulation reveals unexpected observations about the spread of Ca
2+
within an atrial myocyte. In particular, the model describes the movement of Ca
2+
between ryanodine receptor clusters within a specific z disk of an atrial myocyte. Furthermore, we demonstrate that altering the strength of Ca
2+
release, ryanodine receptor refractoriness, the magnitude of initiating stimulus, or the introduction of stochastic Ca
2+
channel activity can cause the nucleation of proarrhythmic traveling Ca
2+
waves. The model provides clinically relevant insights into the initiation and propagation of subcellular Ca
2+
signals that are currently beyond the scope of imaging technology.
Constant-speed vibrational signaling along polyethyleneglycol chain up to 60-Å distance
Authors: Lin Zhiwei , Rubtsov Igor V.
Published: January 2012

A series of azido-PEG-succinimide ester oligomers with a number of repeating PEG units of 0, 4, 8, and 12 (azPEG0, 4, 8, and 12) was investigated using a relaxation-assisted two-dimensional infrared (RA 2DIR) spectroscopy method. The RA 2DIR method relies on the energy transport in molecules and is capable of correlating the frequencies of vibrational modes separated by large through-bond distances. Excitation of the azido group in the compounds at ca. 2,100 cm
-1
generates an excess energy which propagates in the molecule as well as dissipates into the solvent. We discovered that a part of the excess energy propagates ballistically via the covalent backbone of the molecules with a constant speed of ca. 550 m/s. The transport is described as a propagation of a vibrational wavepacket having a mean-free-path length of 10–15 Å. The discovery has the potential for developing new efficient signal transduction strategies for molecular electronics and biochemistry. It also permits extending the distances accessible in RA 2DIR structural measurements up to ca. 60 Å.
Noninvasive inference of the molecular chemotactic response using bacterial trajectories
Authors: Masson Jean-Baptiste , Voisinne Guillaume , Wong-Ng Jerome , Celani Antonio , Vergassola Massimo
Published: January 2012

The quality of sensing and response to external stimuli constitutes a basic element in the selective performance of living organisms. Here we consider the response of
Escherichia coli
to chemical stimuli. For moderate amplitudes, the bacterial response to generic profiles of sensed chemicals is reconstructed from its response function to an impulse, which then controls the efficiency of bacterial motility. We introduce a method for measuring the impulse response function based on coupling microfluidic experiments and inference methods: The response function is inferred using Bayesian methods from the observed trajectories of bacteria swimming in microfluidically controlled chemical fields. The notable advantages are that the method is based on the bacterial swimming response, it is noninvasive, without any genetic and/or mechanical preparation, and assays the behavior of the whole flagella bundle. We exploit the inference method to measure responses to aspartate and α-methylaspartate—measured previously by other methods—as well as glucose, leucine, and serine. The response to the attractant glucose is shown to be biphasic and perfectly adapted, as for aspartate. The response to the attractant serine is shown to be biphasic yet imperfectly adapted, that is, the response function has a nonzero (positive) integral. The adaptation of the response to the repellent leucine is also imperfect, with the sign of the two phases inverted with respect to serine. The diversity in the bacterial population of the response function and its dependency upon the background concentration are quantified.
Preceramic maize from Paredones and Huaca Prieta, Peru
Authors: Grobman Alexander , Bonavia Duccio , Dillehay Tom D. , Piperno Dolores R. , Iriarte José , Holst Irene
Published: January 2012

Maize (
Zea mays
ssp.
mays
) is among the world's most important and ancient domesticated crops. Although the chronology of its domestication and initial dispersals out of Mexico into Central and South America has become more clear due to molecular and multiproxy archaeobotanical research, important problems remain. Among them is the paucity of information on maize's early morphological evolution and racial diversification brought about in part by the poor preservation of macrofossils dating to the pre-5000 calibrated years before the present period from obligate dispersal routes located in the tropical forest. We report newly discovered macrobotanical and microbotanical remains of maize that shed significant light on the chronology, land race evolution, and cultural contexts associated with the crop's early movements into South America and adaptation to new environments. The evidence comes from the coastal Peruvian sites of Paredones and Huaca Prieta, Peru; dates from the middle and late preceramic and early ceramic periods (between ca. 6700 and 3000 calibrated years before the present); and constitutes some of the earliest known cobs, husks, stalks, and tassels. The macrobotanical record indicates that a diversity of racial complexes characteristic of the Andean region emerged during the preceramic era. In addition, accelerator mass spectrometry radiocarbon determinations carried out directly on different structures of preserved maize plants strongly suggest that assays on burned cobs are more reliable than those on unburned cobs. Our findings contribute to knowledge of the early diffusion of maize and agriculture and have broader implications for understanding the development of early preindustrial human societies.
Molecular architecture of the 26S proteasome holocomplex determined by an integrative approach
Authors: Lasker Keren , Förster Friedrich , Bohn Stefan , Walzthoeni Thomas , Villa Elizabeth , Unverdorben Pia , Beck Florian , Aebersold Ruedi , Sali Andrej , Baumeister Wolfgang
Published: January 2012

The 26S proteasome is at the executive end of the ubiquitin-proteasome pathway for the controlled degradation of intracellular proteins. While the structure of its 20S core particle (CP) has been determined by X-ray crystallography, the structure of the 19S regulatory particle (RP), which recruits substrates, unfolds them, and translocates them to the CP for degradation, has remained elusive. Here, we describe the molecular architecture of the 26S holocomplex determined by an integrative approach based on data from cryoelectron microscopy, X-ray crystallography, residue-specific chemical cross-linking, and several proteomics techniques. The “lid” of the RP (consisting of Rpn3/5/6/7/8/9/11/12) is organized in a modular fashion. Rpn3/5/6/7/9/12 form a horseshoe-shaped heterohexamer, which connects to the CP and roofs the AAA-ATPase module, positioning the Rpn8/Rpn11 heterodimer close to its mouth. Rpn2 is rigid, supporting the lid, while Rpn1 is conformationally variable, positioned at the periphery of the ATPase ring. The ubiquitin receptors Rpn10 and Rpn13 are located in the distal part of the RP, indicating that they were recruited to the complex late in its evolution. The modular structure of the 26S proteasome provides insights into the sequence of events prior to the degradation of ubiquitylated substrates.
Oncogene-specific activation of tyrosine kinase networks during prostate cancer progression
Authors: Drake Justin M. , Graham Nicholas A. , Stoyanova Tanya , Sedghi Amir , Goldstein Andrew S. , Cai Houjian , Smith Daniel A. , Zhang Hong , Komisopoulou Evangelia , Huang Jiaoti , Graeber Thomas G. , Witte Owen N.
Published: January 2012

Dominant mutations or DNA amplification of tyrosine kinases are rare among the oncogenic alterations implicated in prostate cancer. We demonstrate that castration-resistant prostate cancer (CRPC) in men exhibits increased tyrosine phosphorylation, raising the question of whether enhanced tyrosine kinase activity is observed in prostate cancer in the absence of specific tyrosine kinase mutation or DNA amplification. We generated a mouse model of prostate cancer progression using commonly perturbed non-tyrosine kinase oncogenes and pathways and detected a significant up-regulation of tyrosine phosphorylation at the carcinoma stage. Phosphotyrosine peptide enrichment and quantitative mass spectrometry identified oncogene-specific tyrosine kinase signatures, including activation of EGFR, ephrin type-A receptor 2 (EPHA2), and JAK2. Kinase:substrate relationship analysis of the phosphopeptides also revealed ABL1 and SRC tyrosine kinase activation. The observation of elevated tyrosine kinase signaling in advanced prostate cancer and identification of specific tyrosine kinase pathways from genetically defined tumor models point to unique therapeutic approaches using tyrosine kinase inhibitors for advanced prostate cancer.
Histone deacetylases 1 and 2 regulate autophagy flux and skeletal muscle homeostasis in mice
Authors: Moresi Viviana , Carrer Michele , Grueter Chad E. , Rifki Oktay F. , Shelton John M. , Richardson James A. , Bassel-Duby Rhonda , Olson Eric N.
Published: January 2012

Maintenance of skeletal muscle structure and function requires efficient and precise metabolic control. Autophagy plays a key role in metabolic homeostasis of diverse tissues by recycling cellular constituents, particularly under conditions of caloric restriction, thereby normalizing cellular metabolism. Here we show that histone deacetylases (HDACs) 1 and 2 control skeletal muscle homeostasis and autophagy flux in mice. Skeletal muscle-specific deletion of both HDAC1 and HDAC2 results in perinatal lethality of a subset of mice, accompanied by mitochondrial abnormalities and sarcomere degeneration. Mutant mice that survive the first day of life develop a progressive myopathy characterized by muscle degeneration and regeneration, and abnormal metabolism resulting from a blockade to autophagy. HDAC1 and HDAC2 regulate skeletal muscle autophagy by mediating the induction of autophagic gene expression and the formation of autophagosomes, such that myofibers of mice lacking these HDACs accumulate toxic autophagic intermediates. Strikingly, feeding HDAC1/2 mutant mice a high-fat diet from the weaning age releases the block in autophagy and prevents myopathy in adult mice. These findings reveal an unprecedented and essential role for HDAC1 and HDAC2 in maintenance of skeletal muscle structure and function and show that, at least in some pathological conditions, myopathy may be mitigated by dietary modifications.
Scaling of H-mode threshold power and L–H edge conditions with favourable ion grad-B drift in Alcator C-Mod tokamak
Authors: Ma Y. , Hughes J.W. , Hubbard A.E. , LaBombard B. , Churchill R.M. , Golfinopolous T. , Tsujii N. , Marmar E.S.
Published: January 2012

This paper presents the results from a systematic study of low-to-high confinement transition (L–H transition) in Alcator C-Mod lower single null plasmas, with ion ∇B drift in the favourable direction for H-mode access. The study is performed over a broad range of plasma density
, toroidal magnetic field (3.5 T < B
T < 5.4 T) and plasma current (0.6 MA < I
p < 1.4 MA). In particular, data at low plasma density of
, which were not included or carefully examined by earlier C-Mod studies, are highlighted in our analysis. With the large set of data, the scaling of H-mode threshold power (P
th) and local plasma edge conditions with
, B
T and I
p are obtained. We found the P
th dependence on
is nonlinear and exhibits a ‘U-shape’, which is not sensitive to I
p variation, and affected by B
T mainly at low density. The characterized L–H local edge conditions include the amplitude and gradient scale length of T
e, n
e profiles. In all, the scaling of L–H P
th and edge conditions are complex, neither of which can be simply represented by a relation of the type
. Local edge conditions are also evaluated in low-power L-mode and compared with the L–H companion. Noticeable differences between L-mode and L–H are mainly observed in T
e at ψ = 0.95, and L

n
, L
T near separatrix, while other parameters are found to be not significantly changed. Comparison with resistive-ballooning mode theory yields reasonable good agreement, such that the experimental data at ψ = 0.95 fit into the corresponding L-mode and H-mode domains, as well as L–H boundary predicted by theory. Finally, we see an edge T
e pedestal emerging in a low density
5.4 T discharge prior to L–H transition.
On the convex hull of symmetric stable processes
Authors: Kampf Jürgen , Last Günter , Molchanov Ilya
Published: January 2012

Let

α
∈
(
1
,
2
]

\alpha \in (1,2]

and

X
X

be an

R

d

\mathbb R^d

-valued symmetric

α
\alpha

-stable Lévy process starting at

0
0

. We consider the closure

S
t

S_t

of the path described by

X
X

on the interval

[
0
,
t
]

[0,t]

and its convex hull

Z
t

Z_t

. The first result of this paper provides a formula for certain mean mixed volumes of

Z
t

Z_t

and in particular for the expected first intrinsic volume of

Z
t

Z_t

. The second result deals with the asymptotics of the expected volume of the stable sausage

Z
t

+
B

Z_t+B

(where

B
B

is an arbitrary convex body with interior points) as

t
→
0

t\to 0

. For this we assume that

X
X

has independent components.
IMA: an R package for high-throughput analysis of Illumina's 450K Infinium methylation data
Authors: Wang Dan , Yan Li , Hu Qiang , Sucheston Lara E. , Higgins Michael J. , Ambrosone Christine B. , Johnson Candace S. , Smiraglia Dominic J. , Liu Song
Published: January 2012

Summary: The Illumina Infinium HumanMethylation450 BeadChip is a newly designed high-density microarray for quantifying the methylation level of over 450 000 CpG sites within human genome. Illumina Methylation Analyzer (IMA) is a computational package designed to automate the pipeline for exploratory analysis and summarization of site-level and region-level methylation changes in epigenetic studies utilizing the 450K DNA methylation microarray. The pipeline loads the data from Illumina platform and provides user-customized functions commonly required to perform exploratory methylation analysis for individual sites as well as annotated regions.

Availability: IMA is implemented in the R language and is freely available from http://www.rforge.net/IMA.

Contact:  song.liu@roswellpark.org
Cooperative bird differentiates between the calls of different individuals, even when vocalizations were from completely unfamiliar individuals
Authors: McDonald Paul G.
Published: January 2012

Hypotheses proposed to explain the evolution of cooperative behaviour typically require differentiation between either groups of conspecifics (e.g
.
kin/non-kin) or, more typically, individuals (e.g. reciprocal altruism). Despite this, the mechanisms that facilitate individual or class recognition have rarely been explored in cooperative species. This study examines the individual differentiation abilities of noisy miners (
Manorina melanocephala
), a species with one of the most complex avian societies known. Miners permanently occupy colonies numbering into hundreds of individuals. Within these colonies, cooperative coalitions form on a fission–fusion basis across numerous contexts, from social foraging through to mobbing predators. Birds often use individually distinctive ‘chur’ calls to recruit others to a caller's location, facilitating coalition formation. I used the habituation–discrimination paradigm to test the ability of miners to differentiate between the chur calls of two individuals that were both either: (i) familiar, or (ii) unfamiliar to the focal subject. This technique had not, to my knowledge, been used to assess vocalization differentiation in cooperative birds previously, but here demonstrated that miners could correctly use the spectral features of signals to differentiate between the vocalizations of different individuals, regardless of their familiarity. By attending to individual differences in recruitment calls, miners have a communication system that is capable of accommodating even the most complex cooperative hypotheses based upon acoustic information.
Mobbing and sitting tight at the nest as methods of avoiding brood parasitism
Authors: Rands Sean A.
Published: January 2012

The arms race between brood parasites and their hosts has led to many different host behaviours for avoiding parasitism. Some of these behaviours are social, and require the presence of conspecifics to work effectively: in response to alarm calls, some species engage in mobbing behaviour where neighbours join nest tenants in attacking and repelling an invading brood parasite. There are risks involved for the neighbours, but it has been demonstrated that social mobbing allows individuals to learn about the presence of brood parasites in the environment, suggesting that social learning is occurring. Here, I consider whether using social signals to alert naive individuals to the presence of brood parasites is a suitable strategy, compared with sitting tight on the nest in response to the signal (which should reduce the chances of being parasitized). I also compare the efficiency of these strategies with the case where individuals fail to change behaviour in response a brood parasite. Using an individual-based simulation model, I demonstrate that both mobbing and sitting tight are effective strategies in response to a signal, and that mobbing is more effective when the chances of being parasitized increase. These results are discussed and compared with known host–brood parasite relationships.
Hard spheres on the gyroid surface
Authors: Dotera Tomonari , Kimoto Masakiyo , Matsuzawa Junichi
Published: January 2012

We find that 48/64 hard spheres per unit cell on the gyroid minimal surface are entropically self-organized. Striking evidence is obtained in terms of the acceptance ratio of Monte Carlo moves and order parameters. The regular tessellations of the spheres can be viewed as hyperbolic tilings on the Poincaré disc with a negative Gaussian curvature, one of which is, equivalently, the arrangement of angels and devils in Escher's
Circle Limit IV
.
Contraction type influences the human ability to use the available torque capacity of skeletal muscle during explosive efforts
Authors: Tillin Neale A. , Pain Matthew T. G. , Folland Jonathan P.
Published: January 2012

The influence of contraction type on the human ability to use the torque capacity of skeletal muscle during explosive efforts has not been documented. Fourteen male participants completed explosive voluntary contractions of the knee extensors in four separate conditions: concentric (CON) and eccentric (ECC); and isometric at two knee angles (101°, ISO101 and 155°, ISO155). In each condition, torque was measured at 25 ms intervals up to 150 ms from torque onset, and then normalized to the maximum voluntary torque (MVT) specific to that joint angle and angular velocity. Explosive voluntary torque after 50 ms in each condition was also expressed as a percentage of torque generated after 50 ms during a supramaximal 300 Hz electrically evoked octet in the same condition. Explosive voluntary torque normalized to MVT was more than 60 per cent larger in CON than any other condition after the initial 25 ms. The percentage of evoked torque expressed after 50 ms of the explosive voluntary contractions was also greatest in CON (ANOVA;
p
< 0.001), suggesting higher concentric volitional activation. This was confirmed by greater agonist electromyography normalized to
M
max
(recorded during the explosive voluntary contractions) in CON. These results provide novel evidence that the ability to use the muscle's torque capacity explosively is influenced by contraction type, with concentric contractions being more conducive to explosive performance due to a more effective neural strategy.
Female reproductive competition within families in rural Gambia
Authors: Mace Ruth , Alvergne Alexandra
Published: January 2012

Many studies show that the extended human family can be helpful in raising offspring, with maternal grandmothers, in particular, improving offspring survival. However, less attention has been given to competition between female kin and co-residents. It has been argued that reproductive conflict between generations explains the evolution of menopause in cooperatively breeding species where females disperse, and that older females are related to the offspring of younger females through their sons, whereas younger, incoming females are unrelated to older females. This means the pattern of help will be asymmetric, so older females lose in reproductive conflict and become ‘sterile helpers'. Here, we seek evidence for female reproductive competition using longitudinal demographic data from a rural Gambian population, and examine when women are helping or harming each other's reproductive success. We find that older women benefit and younger women suffer costs of reproductive competition with women in their compound. But the opposite is found for mothers and daughters; if mother and daughter's reproductive spans overlap, the older woman reduces her reproduction if the younger woman (daughter) reproduces, whereas daughters' fertility is unaffected by their mothers' reproduction. Married daughters are not generally co-resident with their mothers, so we find not only competition effects with co-resident females, but also with daughters who have dispersed. Dispersal varies across human societies, but our results suggest reproductive conflict could be influencing reproductive scheduling whatever the dispersal pattern. A cultural norm of late male marriage reduces paternal grandmother/daughter-in-law reproductive overlap almost to zero in this population. We argue that cultural norms surrounding residence and marriage are themselves cultural adaptations to reduce reproductive conflict between generations in human families.