bluuebunny/crossref_metadata_2025 huggingface dataset:
Once and for all—How people change strategy to ignore irrelevant information in visual tasks
Authors: Gaschler Robert , Marewski Julian N. , Frensch Peter A.
Published: September 2014

Ignoring irrelevant visual information aids efficient interaction with task environments. We studied how people, after practice, start to ignore the irrelevant aspects of stimuli. For this we focused on how information reduction transfers to rarely practised and novel stimuli. In Experiment 1, we compared competing mathematical models on how people cease to fixate on irrelevant parts of stimuli. Information reduction occurred at the same rate for frequent, infrequent, and novel stimuli. Once acquired with some stimuli, it was applied to all. In Experiment 2, simplification of task processing also occurred in a once-for-all manner when spatial regularities were ruled out so that people could not rely on learning which screen position is irrelevant. Apparently, changes in eye movements were an effect of a once-for-all strategy change rather than a cause of it. Overall, the results suggest that participants incidentally acquired knowledge about regularities in the task material and then decided to voluntarily apply it for efficient task processing. Such decisions should be incorporated into accounts of information reduction and other theories of strategy change in skill acquisition.
Selective and strain-specific NFAT4 activation by the Toxoplasma gondii polymorphic dense granule protein GRA6
Authors: Ma Ji Su , Sasai Miwa , Ohshima Jun , Lee Youngae , Bando Hironori , Takeda Kiyoshi , Yamamoto Masahiro
Published: September 2014

Toxoplasma gondii infection results in co-option and subversion of host cellular signaling pathways. This process involves discharge of T. gondii effector molecules from parasite secretory organelles such as rhoptries and dense granules. We report that the T. gondii polymorphic dense granule protein GRA6 regulates activation of the host transcription factor nuclear factor of activated T cells 4 (NFAT4). GRA6 overexpression robustly and selectively activated NFAT4 via calcium modulating ligand (CAMLG). Infection with wild-type (WT) but not GRA6-deficient parasites induced NFAT4 activation. Moreover, GRA6-deficient parasites failed to exhibit full virulence in local infection, and the treatment of WT mice with an NFAT inhibitor mitigated virulence of WT parasites. Notably, NFAT4-deficient mice displayed prolonged survival, decreased recruitment of CD11b+ Ly6G+ cells to the site of infection, and impaired expression of chemokines such as Cxcl2 and Ccl2. In addition, infection with type I parasites culminated in significantly higher NFAT4 activation than type II parasites due to a polymorphism in the C terminus of GRA6. Collectively, our data suggest that GRA6-dependent NFAT4 activation is required for T. gondii manipulation of host immune responses to maximize the parasite virulence in a strain-dependent manner.
Dysfunctional CD8+ T cells in hepatitis B and C are characterized by a lack of antigen-specific T-bet induction
Authors: Kurktschiev Peter D. , Raziorrouh Bijan , Schraut Winfried , Backmund Markus , Wächtler Martin , Wendtner Clemens-Martin , Bengsch Bertram , Thimme Robert , Denk Gerald , Zachoval Reinhart , Dick Andrea , Spannagl Michael , Haas Jürgen , Diepolder Helmut M. , Jung Maria-Christina , Gruener Norbert H.
Published: September 2014

The transcription factor T-bet regulates the production of interferon-γ and cytotoxic molecules in effector CD8 T cells, and its expression correlates with improved control of chronic viral infections. However, the role of T-bet in infections with differential outcome remains poorly defined. Here, we report that high expression of T-bet in virus-specific CD8 T cells during acute hepatitis B virus (HBV) and hepatitis C virus (HCV) infection was associated with spontaneous resolution, whereas T-bet deficiency was more characteristic of chronic evolving infection. T-bet strongly correlated with interferon-γ production and proliferation of virus-specific CD8 T cells, and its induction by antigen and IL-2 stimulation partially restored functionality in previously dysfunctional T-bet–deficient CD8 T cells. However, restoration of a strong interferon-γ response required additional stimulation with IL-12, which selectively induced the phosphorylation of STAT4 in T-bet+ CD8 T cells. The observation that T-bet expression rendered CD8 T cells responsive to IL-12 suggests a stepwise mechanism of T cell activation in which T-bet facilitates the recruitment of additional transcription factors in the presence of key cytokines. These findings support a critical role of T-bet for viral clearance and suggest T-bet deficiency as an important mechanism behind chronic infection.
Intersubunit conformational changes mediate epithelial sodium channel gating
Authors: Collier Daniel M. , Tomkovicz Vivian R. , Peterson Zerubbabel J. , Benson Christopher J. , Snyder Peter M.
Published: September 2014

The epithelial Na+ channel (ENaC) functions as a pathway for Na+ absorption in the kidney and lung, where it is crucial for Na+ homeostasis and blood pressure regulation. However, the basic mechanisms that control ENaC gating are poorly understood. Here we define a role in gating for residues forming interfaces between the extracellular domains of the three ENaC subunits. Using cysteine substitution combined with chemical cross-linking, we determined that residues located at equivalent positions in the three subunits (αK477, βE446, and γE455) form interfaces with residues in adjacent subunits (βV85, γV87, and αL120, respectively). Cross-linking of these residues altered ENaC activity in a length-dependent manner; long cross-linkers increased ENaC current by increasing its open probability, whereas short cross-linkers reduced ENaC open probability. Cross-linking also disrupted ENaC gating responses to extracellular pH and Na+, signals which modulate ENaC activity during shifts in volume status. Introduction of charged side chains at the interfacing residues altered ENaC activity in a charge-dependent manner. Current increased when like charges were present at both interfacing residues, whereas opposing charges reduced current. Together, these data indicate that conformational changes at intersubunit interfaces participate in ENaC transitions between the open and closed states; movements that increase intersubunit distance favor the open state, whereas the closed state is favored when the distance is reduced. This provides a mechanism to modulate ENaC gating in response to changing extracellular conditions that threaten Na+ homeostasis.
Amitsur’s conjecture for polynomial 𝐻-identities of 𝐻-module Lie algebras
Authors: Gordienko A.
Published: September 2014

Consider a finite dimensional

H
H

-module Lie algebra

L
L

over a field of characteristic 

0
0

where

H
H

is a Hopf algebra. We prove the analog of Amitsur’s conjecture on asymptotic behaviour for codimensions of polynomial

H
H

-identities of

L
L

under some assumptions on

H
H

. In particular, the conjecture holds when

H
H

is finite dimensional semisimple. As a consequence, we obtain the analog of Amitsur’s conjecture for graded codimensions of any finite dimensional Lie algebra graded by an arbitrary group and for

G
G

-codimensions of any finite dimensional Lie algebra with a rational action of a reductive affine algebraic group

G
G

by automorphisms and anti-automorphisms.
Potential for population-level disturbance by active sonar in herring
Authors: Sivle L.D. , Kvadsheim P.H. , Ainslie M.A.
Published: September 2014

For conservation purposes, it is important to evaluate potential population consequences of noise disturbance. Based on maximum reported sound levels of no response to sonar, a mathematical model is used to predict the potential risk to the population of herring (Clupea harengus) when these levels are exceeded. Results show that risk varies with season depending on density of fish. During widespread feeding, the risk of any population consequences is low even at sonar source levels up to 235 dB (re 1 µPa m) and exercise durations exceeding 24 h at sonar frequencies 1–2 kHz. The risk of population effects increases in periods when the population aggregates, but given that our response estimates are conservative, it seems unlikely that today’s naval sonar activity will lead to population consequences in Atlantic herring.
Management of Calonectria pseudonaviculata in Boxwood with Fungicides and Less Susceptible Host Species and Varieties
Authors: LaMondia J. A.
Published: September 2014

Calonectria pseudonaviculata causes leaf and stem lesions resulting in defoliation and dieback of boxwood. Trials were conducted to evaluate fungicide management of boxwood blight under greenhouse and container nursery conditions in Connecticut using fungicides previously determined to have in vitro activity against conidial germination or mycelial growth. Plants of different boxwood cultivars were inoculated 48 h after fungicide application. Disease progression was monitored over 6 weeks and progressed from leaf and stem lesions to defoliation. The level of disease control achieved by fungicides was generally good, with the most efficacious treatments averaging from 95 to nearly 100% control. Products containing propiconazole, myclobutanil, thiophanate-methyl, fludioxonil, pyraclostrobin, kresoxim-methyl, and chlorothalonil had significant efficacy. The combination of systemic plus protectant fungicides in a single application resulted in superior disease control compared to the use of a systemic fungicide. There were no differences between the fungicide treatments that included thiophanate-methyl and those that included propiconazole as the systemic fungicide. Korean and ‘Winter Gem’ (Buxus sinica var. insularis) were the least susceptible of the cultivars evaluated, common boxwood (B. sempervirens) and True Dwarf (B. sempervirens ‘Suffruticosa’) were the most susceptible, and ‘Green Mountain’ (B. sinica var. insularis × B. sempervirens Suffruticosa) and ‘Green Velvet’ (B. sinica var. insularis × B. sempervirens Suffruticosa) were intermediate. These results suggest that B. sinica var. insularis may have some level of resistance to boxwood blight. Management of boxwood blight will rely on integrated best management practices that include inspection of incoming plant material, sanitation, cultural controls including use of cultivars tolerant to infection, and fungicide application.
First Report of Tomato mottle mosaic virus Infection of Pepper in China
Authors: Li Y. Y. , Wang C. L. , Xiang D. , Li R. H. , Liu Y. , Li F.
Published: September 2014

Tomato mottle mosaic virus (ToMMV), a tentative member in genus Tobamovirus, was first reported from a greenhouse tomato sample collected in Mexico in 2013 (2). In August 2013, foliar mottle, shrinking, and necrosis were observed on pepper plants in several vegetable greenhouses of Lhasa, Tibet Autonomous Region, China. Seven symptomatic samples were collected and tested by dot-blot ELISA with antisera against Cucumber mosaic virus, Tobacco mosaic virus (TMV), Cucumber green mottle mosaic virus, Tomato spotted wilt virus, Turnip mosaic virus, and Broad bean wilt virus 2 (kindly provided by Dr. Xueping Zhou of Zhejiang University, China) (3). One of the bell pepper (Capsicum annuum var. grossum) samples reacted with the TMV antibody. Rod-shaped virus particles 300 nm in length were observed in this sample under electron microscopy. The results suggested that a tobamovirus closely related to TMV might be a causal agent. Total nucleic acids were then extracted from all seven samples using a CTAB method (1) and tested by RT-PCR using a pair of tobamovirus degenerate primers, TobamoF (GCWAAGGTKGTWYTBGTRGAYGG) and TobamoR (GTAATTGCTATTGDGTWCCWGC). These two primers were designed according to a conserved region of the TMV, Tomato mosaic virus, and ToMMV genomes (nt 2551-3433 of ToMMV genome [KF477193]). An amplicon of approximately 880 bp was obtained only from the TMV-positive sample. The amplicon was cloned and sequenced (GenBank Accession No. KJ605653). NCBI BLAST search showed that it shared the highest identity (99%) with ToMMV (KF477193), and shared the sequence homology of 82% to Tomato mosaic virus (AF332868) and 77% to TMV (V01408). The results indicated that the symptomatic pepper was infected with ToMMV. To investigate the distribution and incidence of ToMMV, 313 samples of symptomatic pepper, tomato, pumpkin, cucumber, radish, Chinese cabbage, broad bean, pea, and kidney bean samples were collected from 65 fields in Yunnan Province and Tibet Autonomous Region, and tested in RT-PCR with ToMMV-specific primers ToMMVF (AGAGAGATGGCGATAGGTTAAC, identical to nt 830-851 of ToMMV genome, GenBank Accession No. KF477193) and ToMMVR (CTGCAGTCATAGGATCTACTTC, complementary to nt1849-1828). The virus was detected in three tabasco peppers (C. frutescens) from Yunnan and one bell pepper plant from Tibet, suggesting that ToMMV has a restricted host range and is not common in these two regions. To our knowledge, this is the first report of natural infection of ToMMV in peppers as well as in China.

References: (1) R. Li et al. J. Virol. Methods 154:48, 2008. (2) R. Li et al. Genome Announc. 1(5):e00794-13, 2013. (3) Y. Xie et al. Virol. J. 10:142, 2013.
Identification and Characterization of a New Fungal Pathogen Causing Twisted Leaf Disease of Sugarcane in China
Authors: Lin Zhenyue , Wei Jingjing , Zhang Muqing , Xu Shiqiang , Guo Qiang , Wang Xin , Wang Jihua , Chen Baoshan , Que Youxiong , Deng Zuhu , Chen Rukai , Powell Charles A.
Published: September 2014

Sugarcane twisted leaf disease, caused by Phoma sp., was first reported in Guangxi, China, in 2012, when more than 5% of sugarcane was infected in the field. Three single-spore isolates were recovered from symptomatic leaves. Sequences from five fungal loci, 28S nrDNA (LSU), 18S nrDNA (SSU), the internal transcribed spacer regions 1 and 2 and 5.8S nrDNA (ITS), β-tubulin (TUB), and the translation elongation factor alpha (TEF-α) were amplified from the disease-associated isolates. The twisted leaf disease pathogen was identified and formally described as Phoma sorghina var. saccharum through phylogenetic analyses, morphological observations, and the pathogenicity of the isolates on sugarcane. P. sorghina var. saccharum can be differentiated from related species based on the morphology of pycnidia and chlamydospores that formed regular, glabrous, papillate ostioles. Chlamydospore-anamorph was unicellular, botryoid-alternarioid shape, as well as the binucleate, frequently branched hyphae. We also showed that mycelial growth of P. sorghina var. saccharum was optimal at pH 4.0 and 20 to 25°C. Additionally, among 13 chemical compounds tested, carbendazim was found to be the most effective in suppressing the radial growth of the fungus. Mycelial growth in vitro was completely inhibited at concentrations of 100 and 50 ppm, and 87.6% of mycelial growth was inhibited at 10 ppm. Carbendazim is therefore a potentially effective fungicide to control this disease in China.
Astrocytic adenosine: from synapses to psychiatric disorders
Authors: Hines Dustin J. , Haydon Philip G.
Published: September 2014

Although it is considered to be the most complex organ in the body, the brain can be broadly classified into two major types of cells, neuronal cells and glial cells. Glia is a general term that encompasses multiple types of non-neuronal cells that function to maintain homeostasis, form myelin, and provide support and protection for neurons. Astrocytes, a major class of glial cell, have historically been viewed as passive support cells, but recently it has been discovered that astrocytes participate in signalling activities both with the vasculature and with neurons at the synapse. These cells have been shown to release
d
-serine, TNF-α, glutamate, atrial natriuretic peptide (ANP) and ATP among other signalling molecules. ATP and its metabolites are well established as important signalling molecules, and astrocytes represent a major source of ATP release in the nervous system. Novel molecular and genetic tools have recently shown that astrocytic release of ATP and other signalling molecules has a major impact on synaptic transmission. Via actions at the synapse, astrocytes have now been shown to regulate complex network signalling in the whole organism with impacts on respiration and the sleep–wake cycle. In addition, new roles for astrocytes are being uncovered in psychiatric disorders, and astrocyte signalling mechanisms represents an attractive target for novel therapeutic agents.
Astroglial connexin 43 sustains glutamatergic synaptic efficacy
Authors: Chever Oana , Pannasch Ulrike , Ezan Pascal , Rouach Nathalie
Published: September 2014

Astrocytes dynamic interactions with neurons play an active role in neurotransmission. The gap junction (GJ) subunits connexins 43 and 30 are strongly expressed in astrocytes and have recently been shown to regulate synaptic activity and plasticity. However, the specific role of connexin 43 in the morphological and electrophysiological properties of astrocytes
in situ
as well as in synaptic transmission remains unknown. Here, we show that connexin 43, a major determinant of astroglial GJ coupling, regulates astrocyte cell volume, but has no impact on astroglial passive membrane properties. Furthermore, we demonstrate that connexin 43 modulates glutamatergic synaptic activity of hippocampal CA1 pyramidal cells. This regulation involves changes in synaptically released glutamate, with no alteration in neuronal excitability or postsynaptic function. These results reveal connexin 43 as a critical player in neuroglial interactions by supporting synaptic efficacy.
Tenascin-R promotes assembly of the extracellular matrix of perineuronal nets via clustering of aggrecan
Authors: Morawski Markus , Dityatev Alexander , Hartlage-Rübsamen Maike , Blosa Maren , Holzer Max , Flach Katharina , Pavlica Sanja , Dityateva Galina , Grosche Jens , Brückner Gert , Schachner Melitta
Published: September 2014

Perineuronal nets (PNs) in the brains of tenascin-R-deficient (
tn-r
−/−
) mice develop in temporal concordance with those of wild-type (

tn-r
+/+

) mice. However, the histological appearance of PNs is abnormal in adult
tn-r
−/−
mice. Here, we investigated whether similar defects are also seen in dissociated and organotypic cultures from hippocampus and forebrain of
tn-r
−/−
mice and whether the structure of PNs could be normalized. In
tn-r
−/−
cultures, accumulations of several extracellular matrix molecules were mostly associated with somata, whereas dendrites were sparsely covered, compared with

tn-r
+/+

mice. Experiments to normalize the structure of PNs in
tn-r
−/−
organotypic slice cultures by depolarization of neurons, or by co-culturing
tn-r
+/+
and
tn-r
−/−
brain slices failed to restore a normal PN phenotype. However, formation of dendritic PNs in cultures was improved by the application of tenascin-R protein and rescued by polyclonal antibodies to aggrecan and a bivalent, but not monovalent form of the lectin
Wisteria floribunda
agglutinin. These results show that tenascin-R and aggrecan are decisive contributors to formation and stabilization of PNs and that tenascin-R may implement these functions by clustering of aggrecan. Proposed approaches for restoration of normal PN structure are noteworthy in the context of PN abnormalities in neurological disorders, such as epilepsy, schizophrenia and addiction.
Modulation of network activity and induction of homeostatic synaptic plasticity by enzymatic removal of heparan sulfates
Authors: Korotchenko Svetlana , Cingolani Lorenzo A. , Kuznetsova Tatiana , Bologna Luca Leonardo , Chiappalone Michela , Dityatev Alexander
Published: September 2014

Heparan sulfates (HSs) are complex and highly active molecules that are required for synaptogenesis and long-term potentiation. A deficit in HSs leads to autistic phenotype in mice. Here, we investigated the long-term effect of heparinase I, which digests highly sulfated HSs, on the spontaneous bioelectrical activity of neuronal networks in developing primary hippocampal cultures. We found that chronic heparinase treatment led to a significant reduction of the mean firing rate of neurons, particularly during the period of maximal neuronal activity. Furthermore, firing pattern in heparinase-treated cultures often appeared as epileptiform bursts, with long periods of inactivity between them. These changes in network activity were accompanied by an increase in the frequency and amplitude of miniature postsynaptic excitatory currents, which could be described by a linear up-scaling of current amplitudes. Biochemically, we observed an upregulation in the expression of the glutamate receptor subunit GluA1, but not GluA2, and a strong increase in autophosphorylation of α and β Ca
2+
/calmodulin-dependent protein kinase II (CaMKII), without changes in the levels of kinase expression. These data suggest that a deficit in HSs triggers homeostatic synaptic plasticity and drastically affects functional maturation of neural network.
ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes
Authors: Boxer Lisa D. , Barajas Brook , Tao Shiying , Zhang Jiajing , Khavari Paul A.
Published: September 2014

ZNF750 controls epithelial homeostasis by inhibiting progenitor genes while inducing differentiation genes, a role underscored by pathogenic ZNF750 mutations in cancer and psoriasis. How ZNF750 accomplishes these dual gene regulatory impacts is unknown. Here, we characterized ZNF750 as a transcription factor that binds both the progenitor and differentiation genes that it controls at a CCNNAGGC DNA motif. ZNF750 interacts with the pluripotency transcription factor KLF4 and chromatin regulators RCOR1, KDM1A, and CTBP1/2 through conserved PLNLS sequences. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by high-throughput sequencing) and gene depletion revealed that KLF4 colocalizes ∼10 base pairs from ZNF750 at differentiation target genes to facilitate their activation but is unnecessary for ZNF750-mediated progenitor gene repression. In contrast, KDM1A colocalizes with ZNF750 at progenitor genes and facilitates their repression but is unnecessary for ZNF750-driven differentiation. ZNF750 thus controls differentiation in concert with RCOR1 and CTBP1/2 by acting with either KDM1A to repress progenitor genes or KLF4 to induce differentiation genes.
Molecular mechanisms underlying formation of long-term reward memories and extinction memories in the honeybee (Apis mellifera)
Authors: Eisenhardt Dorothea
Published: September 2014

The honeybee (Apis mellifera) has long served as an invertebrate model organism for reward learning and memory research. Its capacity for learning and memory formation is rooted in the ecological need to efficiently collect nectar and pollen during summer to ensure survival of the hive during winter. Foraging bees learn to associate a flower's characteristic features with a reward in a way that resembles olfactory appetitive classical conditioning, a learning paradigm that is used to study mechanisms underlying learning and memory formation in the honeybee. Due to a plethora of studies on appetitive classical conditioning and phenomena related to it, the honeybee is one of the best characterized invertebrate model organisms from a learning psychological point of view. Moreover, classical conditioning and associated behavioral phenomena are surprisingly similar in honeybees and vertebrates, suggesting a convergence of underlying neuronal processes, including the molecular mechanisms that contribute to them. Here I review current thinking on the molecular mechanisms underlying long-term memory (LTM) formation in honeybees following classical conditioning and extinction, demonstrating that an in-depth analysis of the molecular mechanisms of classical conditioning in honeybees might add to our understanding of associative learning in honeybees and vertebrates.
Isolation and characterization of novel microsatellite markers for Cymodocea serrulata (Cymodoceaceae), a seagrass distributed widely in the Indo‐Pacific region
Authors: Arriesgado Dan M. , Kurokochi Hiroyuki , Lian Chunlan , Nakajima Yuichi , Matsuki Yu , Nagai Satoshi , Yasuike Motoshige , Nakamura Yoji , Uy Wilfredo H. , Fortes Miguel D. , Campos Wilfredo L. , Nadaoka Kazuo
Published: September 2014

Cymodocea serrulata is a tropical seagrass species distributed widely in the Indo‐Pacific region. We developed 16 novel microsatellite (simple sequence repeat) markers for C. serrulata using next‐generation sequencing for use in genetic studies. The applicability of these markers was attested by genotyping of 40 individuals collected from a natural population in the Philippines. Of the 16 loci, 15 showed polymorphism. For the 15 polymorphic markers, the number of alleles per locus ranged from two to seven, and the observed and expected heterozygosities ranged from 0.131–1.000 and 0.124–0.788, respectively. These markers are useful tools for elucidating genetic diversity, connectivity, and structure in this foundational coastal species.
Metabolic changes in immigrants from Africa to a Western country: time‐lag effects of 20 years since immigration 从非洲迁到一个西方国家后移民的代谢变化：从迁移开始的20年滞后效应
Authors: Kalchiem‐Dekel Or , Shai Iris , Biderman Aya , Orenstein Anna , Cicurel Assi , Reuven Yonatan , Henkin Yaakov
Published: September 2014

Background

An increase in the prevalence of type 2 diabetes mellitus occurs in immigrants from developing regions to Western countries. However, the dynamics of these transitions in relation to the duration of residence in the new environment are not clearly defined.

Methods

Data concerning cardiovascular risk factors were retrospectively extracted from medical charts of 736 Ethiopian immigrants and 575 randomly‐chosen, age and sex matched non‐Ethiopian subjects (“reference group”). Ethiopian immigrants were designated “established” (≥20 years of residence), “intermediate” (10–15 years of residence), or “recent” (<10 years of residence).

Results

Compared to non‐Ethiopians, the age‐ and sex‐adjusted odds ratio (OR) for diabetes was 1.00 (95%CI: 0.66–1.49) for established, 0.55 (95%CI: 0.29–1.03) for intermediate, and 0.15 (95%CI: 0.04–0.50) for recent immigrants (P < 0.001). The corresponding OR for hypertension was 0.94 (95%CI: 0.68–1.31), 0.42 (95%CI: 0.26–0.69), and 0.14 (95%CI: 0.06–0.30) for the established, intermediate, and recent immigrants respectively (P < 0.001). In contrast to the gradual increase in prevalence of diabetes and hypertension, the Ethiopian immigrants maintained their lower body mass index (BMI) (28.7 ± 5 vs 25.5 ± 5 kg/m2 respectively, P < 0.001) and serum low‐density‐lipoprotein cholesterol (129 ± 36 vs 118 ± 34 mg/dL, P < 0.001) compared to the non‐Ethiopians even after 20 years of residence in Israel.

Conclusions

The prevalence of diabetes and hypertension among the immigrants increased to about half that of the local population within 15 years and became equal to that of the local population after a time‐lag of 20 years. These metabolic derangements occurred despite maintaining desirable BMI levels, reinforcing the need for re‐defining optimal BMI ranges in relation to the ethnic origin.
Biogeographical distribution of denitrifying anaerobic methane oxidizing bacteria in Chinese wetland ecosystems
Authors: Zhu Guibing , Zhou Leiliu , Wang Yu , Wang Shanyun , Guo Jianhua , Long Xi‐En , Sun Xingbin , Jiang Bo , Hou Qiaoyun , Jetten Mike S.M. , Yin Chengqing
Published: September 2014

The discovery of denitrifying anaerobic methane oxidation with nitrite as electron acceptor mediated by ‘Candidatus Methylomirabilis oxyfera’ connected the biogeochemical carbon and nitrogen cycle in a new way. However, it is important to have a comprehensive understanding about the distribution of M. oxyfera‐like bacteria in the terrestrial realm, especially the wetland ecosystems that are known as the largest natural source of atmospheric methane. Here, our molecular evidence demonstrated that a wide geographical distribution of M. oxyfera‐like bacteria at oxic/anoxic interfaces of various wetlands (n = 91) over the Chinese territory. Intriguingly, the M. oxyfera‐like bacteria were detected in some extreme environments, indicating that M. oxyfera‐like bacteria occupied a wide range of habitats. Quantitative polymerase chain reaction estimated that the abundance of M. oxyfera‐like bacteria ranged from 2.2 × 103 to 2.3 × 107 copies g−1 dry soil, and up to around 0.62% of the total number of bacteria. Moreover, the M. oxyfera‐like bacteria showed high biodiversity in wetland ecosystems based on the analysis of 462 pmoA and 287 16S rRNA gene sequences. The current study revealed the widespread distribution and biogeography of M. oxyfera‐like bacteria in the terrestrial system.
CEO Risk Preference and Investing in R&D
Authors: Rashad Abdel‐Khalik A.
Published: September 2014

This study aims at: (1) developing an index to measure CEO risk tolerance using publicly available data, and (2) examining the association between this index and investment in risky projects. Using relative pay‐at‐risk as a proxy for risk preference (tolerance) is a new proposition and is supported by having significant association with CEOs' socio‐demographic variables—the variables often studied in connection with risk aversion. Furthermore, this risk preference indicator has a positive association with risk‐taking behaviour as proxied by R&D expenditures. The in‐sample estimation and out‐of‐sample predictions support (a) using relative pay‐at‐risk as a valid proxy for risk tolerance, and (b) finding statistically significant positive association between this measure and R&D expenditures. The association has different degrees of strength for nine out of 11 industries.
Arguments in Favour of Tax Neutral Cost Allocation
Authors: Lampenius Niklas , Buerkle Tobias
Published: September 2014

When considering corporate taxes in a cost allocation context a trade‐off is generated for shareholders. On the one hand, accelerated depreciation increases the value of a project due to the depreciation tax shield. On the other hand, accelerated depreciation most likely does not induce robust goal congruency between managers and shareholders when utilizing residual income as an incentive system and, as a consequence, over‐ or underinvestment could result. In this context, the literature suggests the application of particular allocation rules. When extending the relative marginal benefits cost allocation rule (Reichelstein, 1997; Rogerson, 1997) to include corporate taxes we find it to be tax neutral and to maintain its properties of generating robust incentives. As a consequence the over‐/underinvestment problem is solved, but the depreciation tax shield is often not maximized. However, we illustrate that in competitive markets shareholders ought to prefer a tax neutral allocation scheme over an accelerated depreciation schedule. Thus, we show that shareholders as well as regulators have—for different reasons—a preference for tax neutral cost allocation.
How Top‐down and Bottom‐up Budgeting Affect Budget Slack and Performance through Social and Economic Exchange
Authors: Kramer Stephan , Hartmann Frank
Published: September 2014

This paper investigates the effects of a top‐down (TD) versus bottom‐up (BU) orientation in different stages of the budgetary target‐setting process on slack and managerial performance. We use social exchange theory to explain the outcomes of these alternative budgetary arrangements, and complement the traditional focus on budgetary participation in target setting with a process‐oriented perspective. We develop hypotheses predicting thatTDandBUorientations in the subsequent stages of the budgeting process have different effects on managers’ exchange relationships with the firm, and their behavioural responses. Using survey evidence from German managers across 127 firms we find that aTDorientation in the issuance of guidelines enhances economic exchange and that aBUorientation in the development of the initial budget proposal enhances social exchange, which in turn are associated with reduced slack and higher performance, respectively.
Pharmacokinetics and concentration–effect relationship of adalimumab in rheumatoid arthritis
Authors: Ternant David , Ducourau Emilie , Fuzibet Piéra , Vignault Céline , Watier Hervé , Lequerré Thierry , Le Loët Xavier , Vittecoq Olivier , Goupille Philippe , Mulleman Denis , Paintaud Gilles
Published: September 2014

Aims

This study aimed at describing adalimumab pharmacokinetics (PK) and the concentration–effect relationship of adalimumab using pharmacokinetic–pharmacodynamic (PK–PD) modelling in patients with rheumatoid arthritis (RA).

Methods

Adalimumab PK and PK–PD data were obtained from a multicentric observational study. Adalimumab (40 mg) was administered subcutaneously every other week, and its pharmacokinetics was described using a one‐compartment model. The relationship between adalimumab concentration and C‐reactive protein (CRP) concentration was described using an indirect response model with inhibition of CRP input, whereas the relationship between adalimumab concentration and disease activity score in 28 joints (DAS28) was described using a direct inhibition model. Dose regimens that included a loading dose of adalimumab were simulated.

Results

Thirty patients treated for RA were analysed. The following pharmacokinetic and PK–PD parameters were estimated (interidividual coefficient of variation): apparent volume of distribution (Vd/F) = 10.8 l (92%); apparent clearance (CL/F) = 0.32 l day−1 (17%); first‐order absorption rate (ka) = 0.28 day−1; CRP input (kin) = 22.0 mg l−1 day−1 (65%); adalimumab concentration leading to a 50% decrease in kin (C50) = 3.6 mg l−1 (88%); baseline DAS28 (DAS0) = 5.5 mg l−1 (11%); and adalimumab concentration leading to 50% decrease of DAS0 (IC50) = 11.0 mg l−1 (71%). Simulations showed that a 160 mg loading dose should reduce the time to reach efficacy in terms of both CRP and DAS28 after the first injection.

Conclusions

This is the first study to describe adalimumab pharmacokinetics and the concentration–effect relationship in RA. A 160 mg loading dose may lead to an increased benefit from treatment in RA patients.
Safety, pharmacokinetics, pharmacogenomics and QT concentration−effect modelling of the SirT1 inhibitor selisistat in healthy volunteers
Authors: Westerberg Goran , Chiesa Joseph A. , Andersen Claus A. , Diamanti Daniela , Magnoni Letizia , Pollio Giuseppe , Darpo Borje , Zhou Meijian
Published: September 2014

Aim

Selisistat (SEN0014196), a first‐in‐class SirT1 inhibitor, is being developed as a disease‐modifying therapy for Huntington's disease. This first‐in‐human study investigated the safety, pharmacokinetics and pharmacogenomics of single and multiple doses of selisistat in healthy male and female subjects.

Method

In this double‐blind, randomized, placebo‐controlled study, seven cohorts of eight subjects received a single dose of selisistat at dose levels of 5, 25, 75, 150, 300 and 600 mg and four cohorts of eight subjects were administered 100, 200 and 300 mg once daily for 7 days. Blood sampling and safety assessments were conducted throughout the study.

Results

Selisistat was rapidly absorbed and systemic exposure increased in proportion to dose in the 5–300 mg range. Steady‐state plasma concentrations were achieved within 4 days of repeated dosing. The incidence of drug related adverse events showed no correlation with dose level or number of doses received and was comparable with the placebo group. No serious adverse events were reported and no subjects were withdrawn due to adverse events. There were no trends in clinical laboratory parameters or vital signs. No trends in heart rate or ECG parameters, including the QTc interval and T‐wave morphology, were observed. There were no findings in physical or neurological examinations or postural control. Transcriptional alteration was observed in peripheral blood.

Conclusion

Selisistat was safe and well tolerated by healthy male and female subjects after single doses up to 600 mg and multiple doses up to 300 mg day−1.
Glutathione administration reduces mitochondrial damage and shifts cell death from necrosis to apoptosis in ageing diabetic mice hearts during exercise
Authors: Golbidi S , Botta A , Gottfred S , Nusrat A , Laher I , Ghosh S
Published: September 2014

Background and Purpose

The effect of antioxidants on ageing type 2 diabetic (T2D) hearts during exercise is unclear. We hypothesized that GSH therapy during exercise reduces mitochondrial oxidative stress (mOXS) and cell death in ageing db/db mice hearts.

Experimental Approach

The effect of GSH on cardiac mOXS and cell death was evaluated both in vivo and in vitro.

Key Results

During exercise, GSH treatment protected db/db hearts from exaggerated mOXS without reducing total cell death. Despite similar cell death, investigations on apoptosis‐specific single‐stranded DNA breaks and necrosis‐specific damage provided the first in vivo evidence of a shift from necrosis to apoptosis, with reduced fibrosis following GSH administration in exercised db/db hearts. Further support for a GSH‐regulated ‘switch’ in death phenotypes came from NIH‐3T3 fibroblasts and H9c2 cardiomyocytes treated with H2O2, a reactive oxygen species (ROS). Similar to in vivo findings, augmenting GSH by overexpressing glutamyl cysteine ligase (GCLc) protected fibroblasts and cardiomyocytes from necrosis induced by H2O2, but elevated caspase‐3 and apoptosis instead. Similar to in vivo findings, where GSH therapy in normoglycaemic mice suppressed endogenous antioxidants and augmented caspase‐3 activity, GCLc overexpression during staurosporine‐induced death, which was not characterized by ROS, increased GSH efflux and aggravated death in fibroblasts and cardiomyocytes, confirming that oxidative stress is required for GSH‐mediated cytoprotection.

Conclusions and Implications

While GSH treatment is useful for reducing mOXS and attenuating necrosis and fibrosis in ageing T2D hearts during exercise, such antioxidant treatment could be counterproductive in the healthy heart during exercise.
Roles of Basic Amino Acid Residues in the Activity of μ‐Conotoxin GIIIA and GIIIB, Peptide Blockers of Muscle Sodium Channels
Authors: Sato Kazuki , Yamaguchi Yoko , Ishida Yukisato , Ohizumi Yasushi
Published: September 2014

To study in detail the roles of basic amino acid residues in the activity of μ‐conotoxin GIIIA (μ‐GIIIA) and GIIIB (μ‐GIIIB), specific blockers of muscle sodium channels, seven analogs of μ‐GIIIA, and two analogs of μ‐GIIIB were synthesized. μ‐GIIIA analogs were synthesized by replacing systematically the three Arg residues (Arg1, Arg13, and Arg19) with one, two, and three Lys residues. μ‐GIIIB analogs were synthesized by replacing simultaneously all four Lys residues (Lys9, Lys11, Lys16, and Lys19) with Arg residues and further replacement of acidic Asp residues with neutral Ala residues. Circular dichroism spectra of the synthesized analogs suggested that the replacement did not affect the three dimensional structure. The inhibitory effects on the twitch contractions of the rat diaphragm showed that the side chain guanidino group of Arg13 of μ‐GIIIA was important for the activity, whereas that of Arg19 had little role for biological activity. Although [Arg9,11,16,19]μ‐GIIIB showed higher activity than native μ‐GIIIB, highly basic [Ala2,12, Arg9,11,16,19]μ‐GIIIB showed lower activity, suggesting that there was an appropriate molecular basicity for the maximum activity.
Eleven‐Year Follow‐Up of a Prospective Study of Zirconia Implant Abutments Supporting Single All‐Ceramic Crowns in Anterior and Premolar Regions
Authors: Zembic Anja , Philipp Alexander Otto Hermann , Hämmerle Christoph Hans Franz , Wohlwend Arnold , Sailer Irena
Published: September 2014

Background

Clinical studies on zirconia abutments report very good survival rates and biological and technical results, but few have an observation period of more than 5 years.

Purpose

The aim of this study was to assess the long‐term performance of customized zirconia implant abutments supporting all‐ceramic crowns.

Materials and Methods

Twenty‐seven patients receiving 54 single implants were included (25 incisors, 14 canines, 15 premolars in both jaws). Yttria‐stabilized zirconia abutments were screwed to the implants with a defined torque. All‐ceramic crowns were adhesively cemented onto the abutments. The implants, abutments, and crowns were clinically and radiographically examined after 11 years of use. Modified United States Public Health Service (USPHS) criteria were used to assess technical outcomes: fracture of abutment/crown framework/veneering ceramic, loosening of abutment screw/crown, marginal adaptation, anatomical form, occlusal wear, and abutment fit. The biological parameters were pocket probing depth, plaque control record, bleeding on probing, papilla index, and gingival/mucosal recession at implants and neighboring natural teeth. The cumulative success rate of abutments and crowns was calculated by the Kaplan‐Meier method. The results of the USPHS criteria were analyzed descriptively.

Results

Sixteen patients with 31 zirconia abutments were examined at 11.3 (±0.9) years after implantation. No abutment or crown was lost. The cumulative success rate was 96.3% for abutments and 90.7% for crowns. Two abutment screws loosened, and three crowns exhibited minor chipping. There were no biological complications.

Conclusions

Customized zirconia single implant abutments exhibited excellent long‐term outcomes in anterior and premolar regions.
Evaluating the costs and benefits of systematic data acquisition for conservation assessments
Authors: Hermoso Virgilio , Kennard Mark J. , Linke Simon
Published: September 2014

Effective decision‐making in conservation often is constrained by data quality. Uncertainties associated with poor quality or sparse data can lead to the misuse of limited resources and potentially the failure of conservation practice. Data acquisition, which can help improve decision‐making, is constrained by limited budgets and time. This is especially concerning for rare species, the most in need of conservation, but the most difficult to accurately represent in conservation plans. Here we test the suitability of three different sampling design strategies (two systematic vs random) designed to improve the quality of information available for conservation planning involving rare species. We modelled the spatial distribution of freshwater fish species in a data rich area in northern Australia using a large dataset (representing the best attainable data or true distribution) and simulate increasing subsets of data acquired through the three alternative sampling designs. We then evaluated omission and commission errors in conservation planning outcomes, efficiency and return on investment of data acquisition for conservation planning outcomes obtained from the different data availability × sampling design strategies. Even though we were able to find new species more effectively through systematic sampling designs, this did not 1) translate into reduced errors in conservation planning outcomes for rare species and 2) meet our goal of enhancing cost‐effectiveness of conservation planning. Our results suggest that collecting more biodiversity data, irrespective of the sampling design used, does not necessarily reduce data uncertainty issues and could lead to the misuse of the limited resources and ultimately the failure of conservation practice.
Proportion of exotics and relatedness of host species mediate the positive effect of plant richness on the species richness of fruit flies
Authors: GONTIJO LUCAS , VIEIRA MARCOS C. , DE ARAÚJO WALTER S. , ALMEIDA‐NETO MÁRIO
Published: September 2014

1. All else being equal, the greater the local species richness of plants, the greater the number of associated herbivore species. Because most herbivore insects feed on a subset of closely related plant species, plant phylogenetic diversity is expected to play a key role in determining the number of herbivore species. What is not well known, however, is how an increase in the species richness of exotic plants affects the species richness of herbivores.

2. In this study, we used plant–fruit fly interactions to investigate the influence of the proportion and species richness of exotic host plants on the species richness of herbivorous insects. We also tested whether the phylogenetic diversity of host plants increases when the number of exotic plant species increases.

3. We found that the species richness of fruit flies is more accurately predicted by the richness of native host plants than by total plant species richness (including both native and exotic species). The proportion of exotic host species and the phylogenetic diversity of host plants had negative and positive effects, respectively, on the species richness of fruit flies.

4. Our findings suggest that a positive effect of plant richness on herbivore richness occurs only when an increase in plant diversity involves plant species with which native herbivores share some evolutionary history.
Specialisation of bacterial endosymbionts that protect aphids from parasitoids
Authors: ASPLEN MARK K. , BANO NASREEN , BRADY CRISTINA M. , DESNEUX NICOLAS , HOPPER KEITH R. , MALOUINES CLARA , OLIVER KERRY M. , WHITE JENNIFER A. , HEIMPEL GEORGE E.
Published: September 2014

1. Infection by the bacterial endosymbiont Hamiltonella defensa is capable of protecting the pea aphid from parasitism by Aphidius ervi and the black bean aphid from parasitism by Lysiphlebus fabarum. Here we investigate protection of a third aphid species, the cowpea aphid, Aphis craccivora, from four parasitoid species: Binodoxys communis, B. koreanus, Lysiphlebus orientalis, and Aphidius colemani.

2. We compared parasitism of A. craccivora lines that were either infected with, or cured of H. defensa separately for the four parasitoid species. Infection by H. defensa almost completely eliminated parasitism of A. craccivora by B. communis and B. koreanus, but had no effect on parasitism by L. orientalis and A. colemani.

3. This indicates at least genus‐level specificity of protective effects by H. defensa and we discuss implications of our findings on the known world‐wide distribution of this host/symbiont interaction.
Acoustical enrichment during early postnatal development changes response properties of inferior colliculus neurons in rats
Authors: Bureš Zbyněk , Bartošová Jolana , Lindovský Jiří , Chumak Tetyana , Popelář Jiří , Syka Josef
Published: September 2014

The structure and function of the auditory system may be influenced by acoustic stimulation, especially during the early postnatal period. This study explores the effects of an acoustically enriched environment applied during the third and fourth week of life on the responsiveness of inferior colliculus neurons in rats. The enrichment comprised a spectrally and temporally modulated complex sound reinforced with several target acoustic stimuli, one of which triggered a reward release. The exposure permanently influenced neuronal representation of the sound frequency and intensity, resulting in lower excitatory thresholds at neuronal characteristic frequency, an increased frequency selectivity, larger response magnitudes, steeper rate–intensity functions and an increased spontaneous activity. The effect was general and non‐specific, spanning the entire hearing range – no changes specific to the frequency band of the target stimuli were found. The alterations depended on the activity of animals during the enrichment – a higher activity of rats in the stimulus–reward paradigm led to more profound changes compared with the treatment when the stimulus–reward paradigm was not used. Furthermore, the exposure in early life led to permanent changes in response parameters, whereas the application of the same environment in adulthood influenced only a subset of the examined parameters and had only a temporary effect. These findings indicate that a rich and stimulating acoustic environment during early development, particularly when reinforced by positive feedback, may permanently affect signal processing in the subcortical auditory nuclei, including the excitatory thresholds of neurons and their frequency and intensity resolution.