bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineering of an epoxide hydrolase for efficient bioresolution of bulky pharmaco substrates
Authors: Kong Xu-Dong , Yuan Shuguang , Li Lin , Chen She , Xu Jian-He , Zhou Jiahai
Published: October 2014

Significance

Application of epoxide hydrolases in synthesizing chiral drug compounds has been hindered by their limited substrate range. The enzymatic production of bulky epoxides has proven remarkably challenging. In this work, we identified an active tunnel for substrate access and product release of an epoxide hydrolase with unusual (
R
)-enantioselectivity. Mutagenesis targeted to unblock the steric hindrance in the active pocket or the potential product release site resulted in variants with much higher activity toward α-naphthyl glycidyl ether, the precursor of β-adrenergic receptor blocking drug (
S
)-propranolol. The strategy presented here may be a useful alternative choice for rational design of enzymes toward bulky substrates.
Chemoselective tarantula toxins report voltage activation of wild-type ion channels in live cells
Authors: Tilley Drew C. , Eum Kenneth S. , Fletcher-Taylor Sebastian , Austin Daniel C. , Dupré Christophe , Patrón Lilian A. , Garcia Rita L. , Lam Kit , Yarov-Yarovoy Vladimir , Cohen Bruce E. , Sack Jon T.
Published: October 2014

Significance

Electrically excitable cells, such as neurons, exhibit tremendous variation in their patterns of electrical signals. These variations arise from the collection of ion channels present in any specific cell, but understanding which ion channels are at the root of particular electrical signals remains a significant challenge. Here, we describe novel probes, derived from a tarantula venom peptide, that are able to report the activity of voltage-gated ion channels in living cells. This technology uses state-selective binding to optically monitor the activation of ion channels during cellular electrical signaling. Activity-reporting probes based on these prototypes could potentially identify when endogenous ion channels contribute to electrical signaling, thus facilitating the identification of ion channel targets for therapeutic drug intervention.
Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013–2014 influenza season
Authors: Linderman Susanne L. , Chambers Benjamin S. , Zost Seth J. , Parkhouse Kaela , Li Yang , Herrmann Christin , Ellebedy Ali H. , Carter Donald M. , Andrews Sarah F. , Zheng Nai-Ying , Huang Min , Huang Yunping , Strauss Donna , Shaz Beth H. , Hodinka Richard L. , Reyes-Terán Gustavo , Ross Ted M. , Wilson Patrick C. , Ahmed Rafi , Bloom Jesse D. , Hensley Scott E.
Published: October 2014

Significance

Influenza viruses typically cause a higher disease burden in children and the elderly, who have weaker immune systems. During the 2013–2014 influenza season, H1N1 viruses caused an unusually high level of disease in middle-aged adults. Here, we show that recent H1N1 strains possess a mutation that allows viruses to avoid immune responses elicited in middle-aged adults. We show that current vaccine strains elicit immune responses that are predicted to be less effective in some middle-aged adults. We suggest that new viral strains should be incorporated into seasonal influenza vaccines so that proper immunity is elicited in all humans, regardless of age and pre-exposure histories.
Disruption of multisystem responses to stress in type 2 diabetes: Investigating the dynamics of allostatic load
Authors: Steptoe Andrew , Hackett Ruth A. , Lazzarino Antonio I. , Bostock Sophie , La Marca Roberto , Carvalho Livia A. , Hamer Mark
Published: October 2014

Significance

Our observations provide evidence to link epidemiological studies implicating stress-related processes with biological dysfunction in type 2 diabetes. The patterns of cardiovascular, inflammatory, neuroendocrine, and cholesterol responses exemplify the disturbances of reactivity and recovery predicted by the allostatic load model, including prolonged responses to stress due to delayed shutdown of physiological reactivity, and inadequate (blunted) responses resulting in compensatory hyperactivity in other mediating pathways. Chronic allostatic load may be a mechanism through which stress exposures contribute to diabetes risk, while also being implicated in the adverse health consequences of diabetes such as coronary heart disease and cognitive decline.
Baculovirus resistance in codling moth is virus isolate-dependent and the consequence of a mutation in viral genepe38
Authors: Gebhardt Manuela M. , Eberle Karolin E. , Radtke Pit , Jehle Johannes A.
Published: October 2014

Significance

Registered in 34 countries worldwide,Cydia pomonellagranulovirus (CpGV) is a highly important biological agent to control the codling moth in pome fruit production. Since 2005, 38 codling moth field populations resistant to CpGV products containing the Mexican isolate (CpGV-M) were discovered in Europe, and this was the first demonstrated field resistance against commercial baculovirus products. By identifying and sequencing different resistance-breaking CpGV isolates, it was found that resistance of codling moth is directed toward CpGV-M only. As shown by mutation experiments, CpGV-M is prone to resistance because of a 24-nucleotide repeat within the viral genepe38. Thus,pe38can be used as a genetic marker to identify resistance-breaking CpGV isolates for resistance management programs.
Solution structures of Mengovirus Leader protein, its phosphorylated derivatives, and in complex with nuclear transport regulatory protein, RanGTPase
Authors: Bacot-Davis Valjean R. , Ciomperlik Jessica J. , Basta Holly A. , Cornilescu Claudia C. , Palmenberg Ann C.
Published: October 2014

Significance

We describe here the first, to our knowledge, NMR structure of full-length RanGTPase protein. The protein is captured complexed to the Mengovirus Leader (L
M
) protein. The pair, once bound, triggers a lethal hyperphosphorylation cascade of nuclear pore proteins, leading to enhanced virus replication and cell death. Structures for L
M
in multiple phosphorylation states, and as bound by Ran, show induced fit reactive faces that putatively recruit and select relevant exportins and active kinases. Normal Ran cycling is irreversibly disrupted because L
M
localizes to the RanBP1 site, excluding it from hydrolysis pathways. This unique modulation of Ran effector selection is, to our knowledge, the first structure description of nucleocytoplasmic trafficking perversion by a pathogen protein that targets Ran. Potential applications include antiviral drug targets and cancer cell division therapeutics.
Deorphanization of the human leukocyte tyrosine kinase (LTK) receptor by a signaling screen of the extracellular proteome
Authors: Zhang Hongbing , Pao Lily I. , Zhou Aileen , Brace Arthur D. , Halenbeck Robert , Hsu Amy W. , Bray Thomas L. , Hestir Kevin , Bosch Elizabeth , Lee Ernestine , Wang Gang , Liu Haixia , Wong Brian R. , Kavanaugh W. Michael , Williams Lewis T.
Published: October 2014

Significance

Secreted factors and their cell-surface receptors play important roles in the communication between cells in normal and pathological conditions. There are many transmembrane receptor-like proteins whose ligands have not been identified (also known as orphan receptors). Knowledge of the ligand should help in understanding the biological role of the receptor. We used a strategy of screening the extracellular proteome, one protein at a time, to identify ligands for such receptors. We discovered the ligands for the orphan receptor leukocyte tyrosine kinase. To our knowledge, this is the first case in which secreted factor ligands were identified for an orphan receptor with this technique. This approach is especially valuable when little is known about the ligand.
Approximation of the expected value of the harmonic mean and some applications
Authors: Rao Calyampudi Radhakrishna , Shi Xiaoping , Wu Yuehua
Published: October 2014

Significance

The harmonic mean (HM) filter is better at removing positive outliers than the arithmetic mean (AM) filter. There are especially difficult issues when an accurate evaluation of expected HM is needed such as, for example, in image denoising and marginal likelihood evaluation. A major challenge is to develop a higher-order approximation of the expected HM when the central limit theorem is not applicable. A two-term approximation of the expected HM is derived in this paper. This approximation enables us to develop a new filtering procedure to denoise the noisy image with an improved performance, and construct a truncated HM estimator with a faster convergence rate in marginal likelihood evaluation.
Remodeling in bone without osteocytes: Billfish challenge bone structure–function paradigms
Authors: Atkins Ayelet , Dean Mason N. , Habegger Maria Laura , Motta Phillip J. , Ofer Lior , Repp Felix , Shipov Anna , Weiner Steve , Currey John D. , Shahar Ron
Published: October 2014

Significance

A fundamental paradigm of bone biology is that the remodeling process—by which bones detect and repair damage—is orchestrated by osteocytes. The bones of most extant fish, however, lack these cells and should be unable to repair damage in their bones. We provide evidence for intense remodeling in the anosteocytic bone of billfishes, such as swordfish and marlin. Our observations challenge the central axiom that osteocytes alone are responsible for remodeling, suggesting alternate mechanisms in bone physiology and/or variation in the roles of bone cells. In addition, billfish bone exhibits an array of striking material properties that distinguish it from mammalian bone despite having similar composition, underlining that skeletal biology concepts are limiting when based on mammalian tissues alone.
Direct in situ observations of single Fe atom catalytic processes and anomalous diffusion at graphene edges
Authors: Zhao Jiong , Deng Qingming , Avdoshenko Stanislav M. , Fu Lei , Eckert Jürgen , Rümmeli Mark H.
Published: October 2014

Significance

The single metal atom has been proposed to be a catalyst during the growth of carbon nanotubes; however, this hypothesis is still not confirmed. Our direct in situ transmission EM observation of the restructuring of the graphene edges interacting with an Fe atom directly revealed the intermediate states: pentagon and hexagon structures. In particular, our experiments and simulations show that the single Fe atom behaves differently on the graphene zigzag and armchair edges, giving insights to the growth mechanisms of various sp
2
carbon structures.
Neuroprotection and repair of 3′-blocking DNA ends by glaikit (gkt) encoding
Drosophila
tyrosyl-DNA phosphodiesterase 1 (TDP1)
Authors: Guo DongYu , Dexheimer Thomas S. , Pommier Yves , Nash Howard A.
Published: October 2014

Significance

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a novel repair enzyme that removes 3′-DNA blocking groups generated by topoisomerase cleavage complexes, oxidative DNA lesions, and base alkylation during normal transcription and replication, and by widely used anticancer drugs that induce DNA strand breaks including topoisomerase inhibitors (topotecan, irinotecan, etoposide), bleomycin, and alkylating agents (temozolomide). This report demonstrates that the
Drosophila
gene glaikit (gkt) is the ortholog of TDP1. It also demonstrates the critical importance of TDP1 (gkt) for normal neurological development and lifespan, potentially linking TDP1 and mitochondria to neurodegenerative diseases.
Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin
Authors: Yau Suk Yu , Li Ang , Hoo Ruby L. C. , Ching Yick Pang , Christie Brian R. , Lee Tatia M. C. , Xu Aimin , So Kwok-Fai
Published: October 2014

Significance

This study unmasks a previously unidentified functional role of adiponectin (a hormone secreted by adipocytes) in modulating hippocampal neurogenesis and alleviating depression-like behaviors. To our knowledge, this is the first report showing that adiponectin may be an essential factor that mediates the antidepressant effects of physical exercise on the brain by adiponectin receptor 1-mediated activation of AMP-activated protein kinase. Our results reveal a possible mechanism by which exercise increases hippocampal neurogenesis and also suggest a promising therapeutic treatment for depression.
Role of health in predicting moves to poor neighborhoods among Hurricane Katrina survivors
Authors: Arcaya Mariana C. , Subramanian S. V. , Rhodes Jean E. , Waters Mary C.
Published: October 2014

Significance

Although neighborhood outcomes and health may influence each other reciprocally, existing studies overwhelmingly focus on neighborhood effects on health. Health’s influence on neighborhood is largely viewed as a nuisance that may bias neighborhood effects estimates. However, if health shapes whether individuals attain better neighborhoods, understanding selection processes may advance both health and urban policy objectives. We follow a socially vulnerable cohort of Hurricane Katrina survivors from 2003–2010 and find that although health was not associated with neighborhood poverty before the disaster, those with pre-Katrina health problems ended up living in poorer neighborhoods years after the storm. Understanding whether and how poor health impedes poverty deconcentration efforts may help inform programs and policies designed to help low-income families move into—and stay in—higher opportunity neighborhoods.
The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants
Authors: Mergy Marc A. , Gowrishankar Raajaram , Gresch Paul J. , Gantz Stephanie C. , Williams John , Davis Gwynne L. , Wheeler C. Austin , Stanwood Gregg D. , Hahn Maureen K. , Blakely Randy D.
Published: October 2014

Significance

Dopamine (DA) signaling provides important, modulatory control of movement, at tention, and reward. Disorders linked to changes in DA signaling include Parkinson’s disease, attention-deficit hyperactivity disorder, schizophrenia, autism spectrum disorder, and addiction. We identified multiple, functional polymorphisms in the human DA transporter (DAT) gene and showed that one of these variants, which produces the amino acid substitution Val559 (wild-type DATs express Ala559), exhibits normal DA uptake accompanied by a spontaneous outward efflux of the neurotransmitter, reminiscent of the actions of the psychostimulant amphetamine. Here, we identify multiple biochemical, physiological, and behavioral perturbations that arise from DAT Val559 expression in vivo, supporting spontaneous DA efflux as a heretofore-unrecognized mechanism that may underlie multiple DA-linked neurobehavioral disorders.
Xylose phosphorylation functions as a molecular switch to regulate proteoglycan biosynthesis
Authors: Wen Jianzhong , Xiao Junyu , Rahdar Meghdad , Choudhury Biswa P. , Cui Jixin , Taylor Gregory S. , Esko Jeffrey D. , Dixon Jack E.
Published: October 2014

Significance

Proteoglycans are cellular proteins modified with long chains of repeating sugar residues connected to serine residues within the protein core by a short tetrasaccharide linker. Proteoglycans perform critical cellular functions such as formation of the extracellular matrix, binding to a diverse array of molecules, and regulation of cell motility, adhesion, and cell–cell communication. We show here that family with sequence similarity 20, member B (Fam20B) is a xylose kinase that phosphorylates a xylose sugar residue within the proteoglycan tetrasaccharide linkage. Xylose phosphorylation dramatically stimulates the activity of galactosyltransferase II (GalT-II, B3GalT6), an enzyme that adds galactose to the growing linkage. Cells lacking Fam20B cannot extend the tetrasaccharide linkage and thus have immature and nonfunctional proteoglycan, a phenotype remarkably similar to Ehlers-Danlos syndrome caused by inactivating GalT-II mutations.
Volta potential phase plate for in-focus phase contrast transmission electron microscopy
Authors: Danev Radostin , Buijsse Bart , Khoshouei Maryam , Plitzko Jürgen M. , Baumeister Wolfgang
Published: October 2014

Significance

Biological electron cryomicroscopy is limited by the radiation sensitivity of the samples and the consequent need to minimize exposure to the beam. This, in turn, results in low-contrast images with a poor signal-to-noise ratio. The current practice to improve phase contrast by defocusing results in contrast transfer functions necessitating image restoration to provide interpretable data. Phase plates enable in-focus phase contrast, but the existing ones, including the thin film Zernike-type phase plate, suffer from severe limitations, such as a short usable life span, fringing artifacts, and problems in using them in automated data acquisition procedures. The Volta phase plate presented here solves those problems and has the potential to become a practical solution for in-focus phase contrast in transmission electron microscopy.
Determination of River Herring Natal Origin using Otolith Chemical Markers: Accuracy as a Function of Spatial Scale and Choice of Markers
Authors: Turner Sara M. , Limburg Karin E.
Published: October 2014

We investigated the spatial and temporal accuracy of otolith chemistry for distinguishing populations (and subpopulations) of anadromous river herring (Alewife Alosa pseudoharengus and Blueback Herring A. aestivalis) from New York watersheds. Water chemistry of selected analytes (Sr:Ca, Ba:Ca, 87:86Sr, and δ18O) differed spatially and interannually among sites within the Hudson River as well as between the Hudson River and Long Island estuaries. Otolith chemical markers for juvenile river herring differed significantly among all sampling sites, with combined elemental and isotopic ratios differing significantly between species and between years, although the effect of year did not influence assignments at broad spatial scales (i.e., 105 m). Adult river herring collected in the Hudson River were assigned to natal sites using all juvenile otolith markers except δ18O, which had methodological problems. Adult Alewives and Blueback Herring were classified to Hudson River populations at 73% and 42%, respectively. Inclusion of δ18O in the assignment model likely would have increased the percentage of adults assigned to the Hudson River, as juvenile reclassification accuracies were lower without δ18O and oxygen isotopes are strongly correlated with latitude. Otolith chemistry matched our geochemical atlas of water and distinguished among populations and subpopulations at a range of spatial scales. However, rates of reclassification are dependent on the markers included and the geographic distances among groups.

Received March 31, 2014; accepted July 16, 2014
Spawning Patterns of Pacific Lamprey in Tributaries to the Willamette River, Oregon
Authors: Mayfield M. P. , Schultz L. D. , Wyss L. A. , Clemens B. J. , Schreck C. B.
Published: October 2014

Addressing the ongoing decline of Pacific Lamprey Entosphenus tridentatus across its range along the west coast of North America requires an understanding of all life history phases. Currently, spawning surveys (redd counts) are a common tool used to monitor returning adult salmonids, but the methods are in their infancy for Pacific Lamprey. To better understand the spawning phase, our objective was to assess temporal spawning trends, redd abundance, habitat use, and spatial patterns of spawning at multiple spatial scales for Pacific Lamprey in the Willamette River basin, Oregon. Although redd density varied considerably across surveyed reaches, the observed temporal patterns of spawning were related to physical habitat and hydrologic conditions. As has been documented in studies in other basins in the Pacific Northwest, we found that redds were often constructed in pool tailouts dominated by gravel, similar to habitat used by spawning salmonids. Across the entire Willamette Basin, Pacific Lampreys appeared to select reaches with alluvial geology, likely because this is where gravel suitable for spawning accumulated. At the tributary scale, spawning patterns were not as strong, and in reaches with nonalluvial geology redds were more spatially clumped than in reaches with alluvial geology. These results can be used to help identify and conserve Pacific Lamprey spawning habitat across the Pacific Northwest.

Received May 16, 2014; accepted July 16, 2014
Lake Sturgeon Geographic Range, Distribution, and Migration Patterns in the Saskatchewan River
Authors: Van Wishingrad , Carr Meghan K. , Pollock Michael S. , Ferrari Maud C. O. , Chivers Douglas P.
Published: October 2014

We examined geographic range, distribution, and migration patterns of Lake Sturgeon Acipenser fulvescens within the largest contiguous section of the Saskatchewan River system in Saskatchewan, Canada. Lake Sturgeon use portions of the North, South, and main‐stem Saskatchewan River during the summer months. The Forks area was observed to be an overwintering area. Lake Sturgeon were observed to migrate each year, and all Lake Sturgeon migrated at least once in the 3‐year study. Lake Sturgeon were observed to undertake significant migrations (>100 km/year) using all three rivers. Migration initiation date was consistent over the 3‐year period, whereas migration return date was more variable and may be linked to river flow rate. No significant differences in distance covered between years were identified, but Lake Sturgeon tended to migrate longer distances in years when flow rates were higher. Finally, the spatial extent of Lake Sturgeon in the Saskatchewan River System appears to be larger than that of many previously studied river and lake populations. This study provides important insights into Lake Sturgeon distribution and migration patterns within large prairie rivers, increasing our basic knowledge of this unique fish species in understudied river systems, and provides important information for conservation within their historic range.

Received January 16, 2014; accepted August 5, 2014
Quantitative Assessment of Scale Resorption in Migrating and Spawning Steelhead of the Snake River Basin
Authors: Hernandez Kala , Copeland Timothy , Wright Kristin
Published: October 2014

Scales have been used for decades as a tool to interpret life histories in steelheadOncorhynchus mykiss. Resorption can affect the accuracy of life history interpretations based on scale patterns, depending on the amount of material resorbed. For example, resorption can affect the distinctiveness and characteristics of spawn checks. Spawn checks have been reported in iteroparous salmonids, but no published experimental studies have established the precise relationship between reproduction and scale features. Our objectives were (1) to quantify scale resorption, and (2) to identify contributing factors to the observed resorption in migrating and spawning Snake River steelhead. Prespawn and postspawn scale samples from 72 fish were paired for analysis. We found considerable individual variability in the amount of material resorbed between prespawn and postspawn samples (mean, 26%; SD, 13.7%). Most resorption occurred during the winter as gonads matured and secondary sex characteristics were formed. In over half of the postspawn samples, resorption was sufficient to obscure or eliminate an annulus. In a few cases, resorption was minor enough that the eventual spawn check may be indistinct or absent. We recommend that ancillary marks be investigated as a means to help identify weak spawn checks and an index of resorption developed to determine if resorption was sufficient to cause loss of an annulus.

Received March 27, 2014; accepted August 5, 2014
Preservation Effects on Stable Isotope Values of Archived Elasmobranch Fin Tissue: Comparisons between Frozen and Ethanol‐Stored Samples
Authors: Olin Jill A. , Poulakis Gregg R. , Stevens Philip W. , DeAngelo Jacquelyn A. , Fisk Aaron T.
Published: October 2014

Elasmobranch fin tissue has been sampled and archived for decades to support genetics research. However, these collections have the potential to provide additional information on the trophic ecology of and habitat use by elasmobranch species. The use of fin tissue is especially attractive considering the threatened status of many elasmobranchs and the call for limiting mortalities. Yet, the use of fin samples for stable isotope analysis requires either that (1) storage methods do not alter tissue isotope values or (2) any alterations in isotope composition that occur during storage are predictable. In this study, paired fin tissues sampled from Smalltooth Sawfish Pristis pectinata and cownose rays Rhinoptera spp. were stored frozen and in ethanol and were subsequently analyzed for carbon (δ13C) and nitrogen (δ15N) isotope ratios. Fin δ13C and δ15N values were highly correlated between treatments for both taxa (r2 ≥ 0.80). For Smalltooth Sawfish, ethanol storage significantly increased fin δ13C values by 0.5 ± 0.1‰ (mean ± SE) and decreased fin δ15N values by 0.1 ± 0.1‰ relative to frozen samples; differences were similar for cownose rays (δ13C: 0.2 ± 0.2‰; δ15N: 0.2 ± 0.1‰) but were not significant. A range of approximately 3‰ for δ13C between treatments could have effects on data interpretation, suggesting the use of regressions for ethanol correction of δ13C values, although trends were comparable between frozen and ethanol‐preserved samples without correction. Given the low variability in δ15N values, a correction is not warranted. For endangered species such as the Smalltooth Sawfish, stable isotope analysis of ethanol‐archived fin samples can provide important information regarding habitat use and trophic ecology, with potential significance for conservation and management strategies. The general uniformity in isotope ratio shifts observed for archived samples between the two taxa suggests that these findings can be generalized across elasmobranch species.

Received March 27, 2014; accepted July 30, 2014
Weak Motivational Internalism, Lite: Dispositions, Moral Judgments, and What We're Motivated to Do
Authors: Steinberg Jesse
Published: October 2014

Motivational internalists hold that there is a necessary connection between an agent's moral judgments and what she is motivated to do. One way to express the central thesis of this view is as follows:

Necessarily, for any agent5,if5judges that some available action is morally right (or good, or obligatory, or …) for5to perform (or to refrain from performing), then5is motivated, at least to some extent, to perform (or to refrain from performing) that action.

This is, to borrow a phrase from David Lewis, quite an unlovely mouthful. Perhaps a simpler way of articulating things would be:

Necessarily, an agent's sincere moral judgment that she ought to φ provides her with some motivation to φ.

Yet another formulation of motivation internalism is:

Necessarily, if an agent makes a moral judgment, then she has some desire that favours,inter alia,any course of action that judgment entails.
Knowing Your Own Beliefs
Authors: Schwitzgebel Eric
Published: October 2014

How do you know your own beliefs? And how well do you know them? The two questions are related. I'll recommend a pluralist answer to the first question. The answer to the second question, I'll suggest, varies depending on features of the case.

Self-scanning. Shaun Nichols and Stephen Stich (2003) say this: You have in your mind a functionally defined “belief box.” To believe some propositionP is just to have a representation with the content “P” in the belief box. You also have a monitoring mechanism that can scan the contents of the belief box. Normally, you come to know what you believe by deploying that scanner, creating a new belief in the belief box, a belief with the content “I believe thatP.” Self-scanning accounts admit of many possible variations and complications (e.g., Armstrong 1968, 1981, 1999; Lycan 1996; Goldman 2006), but the basic idea is that people have one or more interior monitors or scanners that detect the presence of beliefs and produce, as output, beliefs about those beliefs (or judgments about those beliefs, or representations of those beliefs).
Knowing the Good and Knowing What One Is Doing
Authors: Tenenbaum Sergio
Published: October 2014

Most contemporary action theorists accept – or at least find plausible – a belief condition on intention (especially on intention in action) and a knowledge condition on intentional action. The belief condition says that I can only intend toɸif I believe that I willɸor am ɸ-ing, and the knowledge condition says that I am only intentionally ɸ-ing if I know that I am ɸ-ing. The belief condition in intention and the knowledge condition in action go hand in hand. After all, if intending implies belief, and if ɸ-ing intentionally implies intending to ɸ, then in ɸ-ing, I intend to be ɸ-ing, and, by the belief condition, I believe that I am ɸ-ing, and if this belief is justified, and we are not in a Gettier situation, etc., then, I will also satisfy the knowledge condition. Moreover, the claim that when intentions properly result in action, the corresponding belief constitutes knowledge is a relatively safe assumption, at least as an assumption about what it is generally the case.
The Normativity of Belief and Self-Fulfilling Normative Beliefs
Authors: Shah Nishi
Published: October 2014

As Descartes famously pointed out in theSecond Meditation,the thought that someone is thinking is true anytime anyone thinks it. Furthermore, thinking it makes it true. Conversely, anytime anyone thinks that it is not the case that someone is thinking, this thought is false, and thinking it makes it false.

l will argue that the propositions ‘There is at least one true normative proposition’ and ‘There are no true normative propositions’ have very similar properties. The proposition ‘There is at least one true normative proposition,’ like the proposition ‘Someone is thinking,’ is true anytime anyone believes it, and, in an important sense, it is made true by someone's believing it. Conversely, anytime anyone believes that there are no true normative propositions, the proposition he believes is false and his believing it makes it false.
Association of heterotrophic bacteria with aggregated Arthrospira platensis exopolysaccharides: implications in the induction of axenic cultures
Authors: Shiraishi Hideaki
Published: October 2014

Inducing an axenic culture of the edible cyanobacterium Arthrospira (Spirulina) platensis using differential filtration alone is never successful; thus, it has been thought that, in non-axenic cultures, a portion of contaminating bacteria is strongly associated with Arthrospira cells. However, examination of the behavior of these bacteria during filtration revealed that they were not associated with Arthrospira cells but with aggregates of exopolysaccharides present in the medium away from the Arthrospira cells. Based on this finding, a rapid and reliable method for preparing axenic trichomes of A. platensis was established. After verifying the axenicity of the resulting trichomes on enriched agar plates, they were individually transferred to fresh sterile medium using a handmade tool, a microtrowel, to produce axenic cultures. With this technique, axenic cultures of various A. platensis strains were successfully produced. The technique described in this study is potentially applicable to a wider range of filamentous cyanobacteria.
Sprinting performance on the Woodway Curve 3.0TM is related to muscle architecture
Authors: Mangine Gerald T. , Fukuda David H. , Townsend Jeremy R. , Wells Adam J. , Gonzalez Adam M. , Jajtner Adam R. , Bohner Jonathan D. , LaMonica Michael , Hoffman Jay R. , Fragala Maren S. , Stout Jeffrey R.
Published: October 2014

To determine if unilateral measures of muscle architecture in the rectus femoris (RF) and vastus lateralis (VL) were related to (and predictive of) sprinting speed and unilateral (and bilateral) force (FRC) and power (POW) during a 30 s maximal sprint on the Woodway Curve 3.0TM non‐motorized treadmill (TM). Twenty‐eight healthy, physically active men (n = 14) and women (n = 14) (age = 22.9 ± 2.4 years; body mass = 77.1 ± 16.2 kg; height = 171.6 ± 11.2 cm; body‐fa t = 19.4 ± 8.1%) completed one familiarization and one 30‐s maximal sprint on the TM to obtain maximal sprinting speed, POW and FRC. Muscle thickness (MT), cross‐sectional area (CSA) and echo intensity (ECHO) of the RF and VL in the dominant (DOM; determined by unilateral sprinting power) and non‐dominant (ND) legs were measured via ultrasound. Pearson correlations indicated several significant (p < 0.05) relationships between sprinting performance [POW (peak, DOM and ND), FRC (peak, DOM, ND) and sprinting time] and muscle architecture. Stepwise regression indicated that POWDOM was predictive of ipsilateral RF (MT and CSA) and VL (CSA and ECHO), while POWND was predictive of ipsilateral RF (MT and CSA) and VL (CSA); sprinting power/force asymmetry was not predictive of architecture asymmetry. Sprinting time was best predicted by peak power and peak force, though muscle quality (ECHO) and the bilateral percent difference in VL (CSA) were strong architectural predictors. Muscle architecture is related to (and predictive of) TM sprinting performance, while unilateral POW is predictive of ipsilateral architecture. However, the extent to which architecture and other factors (i.e. neuromuscular control and sprinting technique) affect TM performance remains unknown.
Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation
Authors: Klingberg Franco , Chow Melissa L. , Koehler Anne , Boo Stellar , Buscemi Lara , Quinn Thomas M. , Costell Mercedes , Alman Benjamin A. , Genot Elisabeth , Hinz Boris
Published: October 2014

Integrin-mediated force application induces a conformational change in latent TGF-β1 that leads to the release of the active form of the growth factor from the extracellular matrix (ECM). Mechanical activation of TGF-β1 is currently understood as an acute process that depends on the contractile force of cells. However, we show that ECM remodeling, preceding the activation step, mechanically primes latent TGF-β1 akin to loading a mechanical spring. Cell-based assays and unique strain devices were used to produce a cell-derived ECM of controlled organization and prestrain. Mechanically conditioned ECM served as a substrate to measure the efficacy of TGF-β1 activation after cell contraction or direct force application using magnetic microbeads. The release of active TGF-β1 was always higher from prestrained ECM as compared with unorganized and/or relaxed ECM. The finding that ECM prestrain regulates the bioavailability of TGF-β1 is important to understand the context of diseases that involve excessive ECM remodeling, such as fibrosis or cancer.
Acinus integrates AKT1 and subapoptotic caspase activities to regulate basal autophagy
Authors: Nandi Nilay , Tyra Lauren K. , Stenesen Drew , Krämer Helmut
Published: October 2014

How cellular stresses up-regulate autophagy is not fully understood. One potential regulator is the Drosophila melanogaster protein Acinus (Acn), which is necessary for autophagy induction and triggers excess autophagy when overexpressed. We show that cell type–specific regulation of Acn depends on proteolysis by the caspase Dcp-1. Basal Dcp-1 activity in developing photoreceptors is sufficient for this cleavage without a need for apoptosis to elevate caspase activity. On the other hand, Acn was stabilized by loss of Dcp-1 function or by the presence of a mutation in Acn that eliminates its conserved caspase cleavage site. Acn stability also was regulated by AKT1-mediated phosphorylation. Flies that expressed stabilized forms of Acn, either the phosphomimetic AcnS641,731D or the caspase-resistant AcnD527A, exhibited enhanced basal autophagy. Physiologically, these flies showed improvements in processes known to be autophagy dependent, including increased starvation resistance, reduced Huntingtin-induced neurodegeneration, and prolonged life span. These data indicate that AKT1 and caspase-dependent regulation of Acn stability adjusts basal autophagy levels.
Cytosolic carboxypeptidase CCP6 is required for megakaryopoiesis by modulating Mad2 polyglutamylation
Authors: Ye Buqing , Li Chong , Yang Zhao , Wang Yanying , Hao Junfeng , Wang Li , Li Yi , Du Ying , Hao Lu , Liu Benyu , Wang Shuo , Xia Pengyan , Huang Guanling , Sun Lei , Tian Yong , Fan Zusen
Published: October 2014

Bone marrow progenitor cells develop into mature megakaryocytes (MKs) to produce platelets for hemostasis and other physiological functions. However, the molecular mechanisms underlying megakaryopoiesis are not completely defined. We show that cytosolic carboxypeptidase (CCP) 6 deficiency in mice causes enlarged spleens and increased platelet counts with underdeveloped MKs and dysfunctional platelets. The prominent phenotypes of CCP6 deficiency are different from those of CCP1-deficient mice. We found that CCP6 and tubulin tyrosine ligase-like family (TTLL) members TTLL4 and TTLL6 are highly expressed in MKs. We identify Mad2 (mitotic arrest deficient 2) as a novel substrate for CCP6 and not CCP1. Mad2 can be polyglutamylated by TTLL4 and TTLL6 to modulate the maturation of MKs. CCP6 deficiency causes hyperglutamylation of Mad2 to promote activation of Aurora B, leading to suppression of MK maturation. We reveal that Mad2 polyglutamylation plays a critical role in the regulation of megakaryopoiesis.
Things Fall Apart: The Dynamics of Brand Audience Dissipation
Authors: Parmentier Marie-Agnès , Fischer Eileen
Published: October 2014

Much prior work illuminates how fans of a brand can contribute to the value enjoyed by other members of its audience, but little is known about any processes by which fans contribute to the dissipation of that audience. Using longitudinal data on America's Next Top Model, a serial brand, and conceptualizing brands as assemblages of heterogeneous components, this article examines how fans can contribute to the destabilization of a brand's identity and fuel the dissipation of audiences of which they have been members. This work suggests that explanations focusing on satiation, psychology, or semiotics are inadequate to account for dissipation in the audience for serial brands. Moreover, the perspective advanced here highlights how fans can create doppelgänger brand images and contribute to the co-destruction of serial brands they have avidly followed.
Introducing dAUTObase: a first step towards the global scale geoepidemiology of autoimmune syndromes and diseases
Authors: Gkantouna Vassiliki A. , Kambouris Manousos E. , Viennas Emmanouil S. , Ioannou Zafeiria-Marina , Paraskevas Michael , Lagoumintzis George , Zagoriti Zoi , Patrinos George P. , Tzimas Giannis E. , Poulas Konstantinos
Published: October 2014

Motivation: An autoimmune disorder occurs when the immune system mistakenly attacks and destroys its own healthy body tissues. The initiation of a geoepidemiological database, for recording autoimmune incidents with a focus to clinical manifestations, demographic parameters and geographic background is crucial to detect correlations.

Results: The dAUTObase collects an ever increasing number of publications—currently counting 435—on autoimmune diseases’ frequencies in various populations and ethnic groups. The respective data have been hosted by a web application developed for the task. It uses three data visualization tools: the PivotViewer, the Disease Treemap and the Disease World Map, to assist the effective data querying.

Availability and implementation: The dAUTObase 2.0 version (www.biodata.gr/dautobase) needs no registration for querying, but data entry and modification is reserved for registered users (curators-administrators).

Contact:  kpoulas@upatras.gr or tzimas@cti.gr
What caused seven consecutive years of low puerulus settlement in the western rock lobster fishery of Western Australia?
Authors: de Lestang Simon , Caputi Nick , Feng Ming , Denham Ainslie , Penn James , Slawinski Dirk , Pearce Alan , How Jason
Published: October 2014

Puerulus settlement in the western rock lobster fishery has remained below average for seven consecutive years (2006/2007–2012/2013), with 2008/2009 being the lowest in over 40 years. Examination of the timing of the start of spawning using fishery-independent data since the mid-2000s indicated that spawning has been occurring earlier. The low settlement appears related to higher water temperatures at the time of the onset of spawning (October) since the mid-2000s. Statistical analysis shows that the most (71%) of the variation in puerulus settlement was explained by the timing of spawning, storm activity during autumn/spring, and offshore water temperatures in February. Earlier spawning may cause a mismatch with other environmental factors such as peaks in ocean productivity and/or storms that assist the larvae return to the coast and offshore water temperatures that help the early stage larval growth. These variables produced a plausible hypothesis to explain the decline in puerulus settlement for these 7 years, including the recruitment failure of 2008/2009. They also predicted the substantial improvement in settlement for 2013/2014. Egg production levels did not to have a significant relationship with puerulus settlement levels after taking environmental variables into account. Further verification with additional years is required to see whether this relationship is maintained. Global climate change may influence these environmental factors: the timing of spawning is influenced by water temperature and there has been a reduced trend of autumn to spring storms off southwest Australia.
Exportation of excess feed from Mediterranean fish farms to local fisheries through different targeted fish species
Authors: Izquierdo-Gómez David , González-Silvera Daniel , Arechavala-López Pablo , López-Jiménez José Ángel , Bayle-Sempere Just Tomás , Sánchez-Jerez Pablo
Published: October 2014

Coastal fisheries and sea cage aquaculture coexist along the coastal zone, and it has been suggested that wild fish feed on excess feed around farms. If this occurs, the condition of wild fish can increase and their lipid profile can become modified. However, the influence of fishfarming on coastal fisheries has not been described in detail. Four targeted species of different trophic gilds, Sardinella aurita, Caranx rhonchus, Mullus barbatus, and Pomatomus saltatrix were studied and the lipid profiles of individuals captured by coastal fisheries and around fish farms were compared. Results show that fish captured at farms showed increased levels of total lipids and/or the terrestrial fatty acids contained in feed pellets. Individuals with increased terrestrial fatty acid proportions were detected in the catch of small-scale artisanal fisheries but not among trawled fish. Consequently, this study demonstrates the influence of fishfarming on coastal fisheries through the exportation of excess feed in the shape of wild fish biomass.
Longline hook testing in the mouths of pelagic odontocetes
Authors: McLellan William A. , Arthur Logan H. , Mallette Sarah D. , Thornton Steven W. , McAlarney Ryan J. , Read Andrew J. , Pabst D. Ann
Published: October 2014

Several species of odontocete cetaceans depredate bait and catch and, as a result, become hooked and entangled in pelagic longline fisheries. The present study measured how selected commercial longline hooks, including “weak hooks”, behaved within odontocete mouths. Five hooks (Mustad-16/0, Mustad-18/0, Mustad J-9/0, Korean 16, and Korean 18) were tested on three species of odontocetes known to interact with longline fisheries—short-finned pilot whales (Globicephala macrorhynchus), Risso's dolphins (Grampus griseus), and false killer whales (Pseudorca crassidens). Specimens were secured to a stanchion, hooks were placed in the mouth at multiple positions along the dorsal lip, and the force required to pull each hook free was measured. The soft tissue lips of these odontocetes were capable of resisting forces up to 250 kg before failing. The polished steel M-16, M-18, and J-9 hooks straightened at forces between 50 and 225 kg, depending on hook gauge. When straightened, these hooks exposed the sharpened barb, which sliced through the lip tissue, usually releasing the hook intact. The K-16 and K-18 hooks behaved very differently, breaking at higher forces (110–250 kg) and consistently just at the barb; usually, there was measurable soft-tissue loss and often shards of the hook were retained within those soft tissues. The different behaviours of these two hook types—the M and J type polished steel vs. the K type carbon steel—were consistent across all species tested. Mechanical tests were also conducted to determine if hooks could fracture the mandible of these same odontocetes. Only the M-18 and K-18 hooks had sufficiently large gapes to hook around the mandible, and both hook types fractured bone in short-finned pilot whales and Risso's dolphins. These results support other lines of evidence indicating that longline hooks can cause serious injury to these species, and suggest possible steps to mitigate these impacts.
Recent developments of analysis for hydrodynamic flow of nematic liquid crystals
Authors: Lin Fanghua , Wang Changyou
Published: October 2014

The study of hydrodynamics of liquid crystals leads to many fascinating mathematical problems, which has prompted various interesting works recently. This article reviews the static Oseen–Frank theory and surveys some recent progress on the existence, regularity, uniqueness and large time asymptotic of the hydrodynamic flow of nematic liquid crystals. We will also propose a few interesting questions for future investigations.
Rheological signatures in limit cycle behaviour of dilute, active, polar liquid crystalline polymers in steady shear
Authors: Forest M. Gregory , Phuworawong Panon , Wang Qi , Zhou Ruhai
Published: October 2014

We consider the dilute regime of active suspensions of liquid crystalline polymers (LCPs), addressing issues motivated by our kinetic model and simulations in Forest
et al.
(Forest
et al.
2013
Soft Matter
9
, 5207–5222 (
doi:10.1039/c3sm27736d
)). In particular, we report
unsteady
two-dimensional heterogeneous flow-orientation attractors for pusher nanorod swimmers at
dilute
concentrations where passive LCP equilibria are isotropic. These numerical limit cycles are analogous to longwave (homogeneous) tumbling and kayaking limit cycles and two-dimensional heterogeneous unsteady attractors of passive LCPs in weak imposed shear, yet these states arise exclusively at
semi-dilute
concentrations where stable equilibria are nematic. The results in Forest
et al.
mentioned above compel two studies in the dilute regime that complement recent work of Saintillan & Shelley (Saintillan & Shelley 2013
C. R. Physique
14
, 497–517 (
doi:10.1016/j.crhy.2013.04.001
)): linearized stability analysis of the isotropic state for nanorod pushers and pullers; and an analytical–numerical study of weakly and strongly sheared active polar nanorod suspensions to capture how particle-scale activation affects shear rheology. We find that weakly sheared dilute puller versus pusher suspensions exhibit steady versus unsteady responses, shear thickening versus thinning and positive versus negative first normal stress differences. These results further establish how sheared dilute nanorod pusher suspensions exhibit many of the characteristic features of sheared semi-dilute passive nanorod suspensions.
Aspects of the density field in an active nematic
Authors: Mishra Shradha , Puri Sanjay , Ramaswamy Sriram
Published: October 2014

Active nematics are conceptually the simplest orientationally ordered phase of self-driven particles, but have proved to be a perennial source of surprises. We show here through numerical solution of coarse-grained equations for the order parameter and density that the growth of the active nematic phase from the isotropic phase is necessarily accompanied by a clumping of the density. The growth kinetics of the density domains is shown to be faster than the

law expected for variables governed by a conservation law. Other results presented include the suppression of density fluctuations in the stationary ordered nematic by the imposition of an orienting field. We close by posing some open questions.