bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of cold-tolerant fungal symbionts permits winter fungiculture by leafcutter ants at the northern frontier of a tropical ant–fungus symbiosis
Authors: Mueller Ulrich G. , Mikheyev Alexander S. , Hong Eunki , Sen Ruchira , Warren Dan L. , Solomon Scott E. , Ishak Heather D. , Cooper Mike , Miller Jessica L. , Shaffer Kimberly A. , Juenger Thomas E.
Published: February 2011

The obligate mutualism between leafcutter ants and their
Attamyces
fungi originated 8 to 12 million years ago in the tropics, but extends today also into temperate regions in South and North America. The northernmost leafcutter ant
Atta texana
sustains fungiculture during winter temperatures that would harm the cold-sensitive
Attamyces
cultivars of tropical leafcutter ants. Cold-tolerance of
Attamyces
cultivars increases with winter harshness along a south-to-north temperature gradient across the range of
A. texana
, indicating selection for cold-tolerant
Attamyces
variants along the temperature cline. Ecological niche modeling corroborates winter temperature as a key range-limiting factor impeding northward expansion of
A. texana
. The northernmost
A. texana
populations are able to sustain fungiculture throughout winter because of their cold-adapted fungi and because of seasonal, vertical garden relocation (maintaining gardens deep in the ground in winter to protect them from extreme cold, then moving gardens to warmer, shallow depths in spring). Although the origin of leafcutter fungiculture was an evolutionary breakthrough that revolutionized the food niche of tropical fungus-growing ants, the original adaptations of this host-microbe symbiosis to tropical temperatures and the dependence on cold-sensitive fungal symbionts eventually constrained expansion into temperate habitats. Evolution of cold-tolerant fungi within the symbiosis relaxed constraints on winter fungiculture at the northern frontier of the leafcutter ant distribution, thereby expanding the ecological niche of an obligate host–microbe symbiosis.
Fish as major carbonate mud producers and missing components of the tropical carbonate factory
Authors: Perry Chris T. , Salter Michael A. , Harborne Alastair R. , Crowley Stephen F. , Jelks Howard L. , Wilson Rod W.
Published: February 2011

Carbonate mud is a major constituent of recent marine carbonate sediments and of ancient limestones, which contain unique records of changes in ocean chemistry and climate shifts in the geological past. However, the origin of carbonate mud is controversial and often problematic to resolve. Here we show that tropical marine fish produce and excrete various forms of precipitated (nonskeletal) calcium carbonate from their guts (“low” and “high” Mg-calcite and aragonite), but that very fine-grained (mostly < 2 μm) high Mg-calcite crystallites (i.e.,

MgCO
3
) are their dominant excretory product. Crystallites from fish are morphologically diverse and species-specific, but all are unique relative to previously known biogenic and abiotic sources of carbonate within open marine systems. Using site specific fish biomass and carbonate excretion rate data we estimate that fish produce ∼6.1 × 10
6
 kg CaCO
3
/year across the Bahamian archipelago, all as mud-grade (the < 63 μm fraction) carbonate and thus as a potential sediment constituent. Estimated contributions from fish to total carbonate mud production average ∼14% overall, and exceed 70% in specific habitats. Critically, we also document the widespread presence of these distinctive fish-derived carbonates in the finest sediment fractions from all habitat types in the Bahamas, demonstrating that these carbonates have direct relevance to contemporary carbonate sediment budgets. Fish thus represent a hitherto unrecognized but significant source of fine-grained carbonate sediment, the discovery of which has direct application to the conceptual ideas of how marine carbonate factories function both today and in the past.
Synaptic neuropeptide release induced by octopamine without Ca
2+
entry into the nerve terminal
Authors: Shakiryanova Dinara , Zettel Geoffrey M. , Gu Tingting , Hewes Randall S. , Levitan Edwin S.
Published: February 2011

Synaptic release of neurotransmitters is evoked by activity-dependent Ca
2+
entry into the nerve terminal. However, here it is shown that robust synaptic neuropeptide release from
Drosophila
motoneurons is evoked in the absence of extracellular Ca
2+
by octopamine, the arthropod homolog to norepinephrine. Genetic and pharmacology experiments demonstrate that this surprising peptidergic transmission requires cAMP-dependent protein kinase, with only a minor contribution of exchange protein activated by cAMP (epac). Octopamine-evoked neuropeptide release also requires endoplasmic reticulum Ca
2+
mobilization by the ryanodine receptor and the inositol trisphosphate receptor. Hence, rather than relying exclusively on activity-dependent Ca
2+
entry into the nerve terminal, a behaviorally important neuromodulator uses synergistic cAMP-dependent protein kinase and endoplasmic reticulum Ca
2+
signaling to induce synaptic neuropeptide release.
Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice
Authors: Safdar Adeel , Bourgeois Jacqueline M. , Ogborn Daniel I. , Little Jonathan P. , Hettinga Bart P. , Akhtar Mahmood , Thompson James E. , Melov Simon , Mocellin Nicholas J. , Kujoth Gregory C. , Prolla Tomas A. , Tarnopolsky Mark A.
Published: February 2011

A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian aging is supported by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in the proofreading-exonuclease activity of mitochondrial polymerase gamma, exhibits accelerated aging phenotypes characteristic of human aging, systemic mitochondrial dysfunction, multisystem pathology, and reduced lifespan. Epidemiologic studies in humans have demonstrated that endurance training reduces the risk of chronic diseases and extends life expectancy. Whether endurance exercise can attenuate the cumulative systemic decline observed in aging remains elusive. Here we show that 5 mo of endurance exercise induced systemic mitochondrial biogenesis, prevented mtDNA depletion and mutations, increased mitochondrial oxidative capacity and respiratory chain assembly, restored mitochondrial morphology, and blunted pathological levels of apoptosis in multiple tissues of mtDNA mutator mice. These adaptations conferred complete phenotypic protection, reduced multisystem pathology, and prevented premature mortality in these mice. The systemic mitochondrial rejuvenation through endurance exercise promises to be an effective therapeutic approach to mitigating mitochondrial dysfunction in aging and related comorbidities.
Interconversions of P and F intermediates of cytochrome
c
oxidase from
Paracoccus denitrificans
Authors: von der Hocht Iris , van Wonderen Jessica H. , Hilbers Florian , Angerer Heike , MacMillan Fraser , Michel Hartmut
Published: February 2011

Cytochrome
c
oxidase (C
c
O) is the terminal enzyme of the respiratory chain. This redox-driven proton pump catalyzes the four-electron reduction of molecular oxygen to water, one of the most fundamental processes in biology. Elucidation of the intermediate structures in the catalytic cycle is crucial for understanding both the mechanism of oxygen reduction and its coupling to proton pumping. Using C
c
O from
Paracoccus denitrificans
, we demonstrate that the artificial
F
state, classically generated by reaction with an excess of hydrogen peroxide, can be converted into a new
P
state (in contradiction to the conventional direction of the catalytic cycle) by addition of ammonia at pH 9. We suggest that ammonia coordinates directly to Cu
B
in the binuclear active center in this
P
state and discuss the chemical structures of both oxoferryl intermediates
F
and
P
. Our results are compatible with a superoxide bound to Cu
B
in the
F
state.
Multiple coregulatory control of tyrosine hydroxylase gene transcription
Authors: Reddy Sirigiri Divijendra Natha , Rayala Suresh K. , Ohshiro Kazufumi , Pakala Suresh B. , Kobori Nobuhide , Dash Pramod , Yun Sung , Qin Jun , O'Malley Bert W. , Kumar Rakesh
Published: February 2011

Despite ubiquitous expression and a high level of metastasis-associated protein 1 (MTA1) coregulator, the physiological role of the MTA1 coactivator remains unknown. We found that MTA1 is a bona fide coactivator and stimulator of tyrosine hydroxylase (
TH
) transcription in neuronal cells and that MTA1-null mice had lower
TH
expression in the striatum and substantial nigra. MTA1 physically achieves these functions by interacting directly with DJ1 (Parkinson disease 7) and in turn recruits the DJ1/MTA1/RNA polymerase II complex to the bicoid binding element (BBE) in the
TH
promoter. Furthermore, we found that the MTA1/DJ1 complex is required for optimum stimulation of the
TH
expression by paired like homeodomain transcription factor (Pitx3) homeodomain transcription factor and that the MTA1/DJ1 complex is recruited to the
TH
gene chromatin via the direct interaction of MTA1 with Pitx3. These findings reveal a role for MTA1 as an upstream coactivator of
TH
and advance the notion of polygenic regulation of a disease-causing gene by coordinated interactions of three regulatory proteins.
Balanced NMDA receptor activity in dopamine D1 receptor (D1R)- and D2R-expressing medium spiny neurons is required for amphetamine sensitization
Authors: Beutler Lisa R. , Wanat Matthew J. , Quintana Albert , Sanz Elisenda , Bamford Nigel S. , Zweifel Larry S. , Palmiter Richard D.
Published: February 2011

Signaling through
N
-methyl-
d
-aspartate–type glutamate receptors (NMDARs) is essential for the development of behavioral sensitization to psychostimulants such as amphetamine (AMPH). However, the cell type and brain region in which NMDAR signaling is required for AMPH sensitization remain unresolved. Here we use selective inactivation of
Grin1
, the gene encoding the essential NR1 subunit of NMDARs, in dopamine neurons or their medium spiny neuron (MSN) targets, to address this issue. We show that NMDAR signaling in dopamine neurons is not required for behavioral sensitization to AMPH. Conversely, removing NMDARs from MSNs that express the dopamine D1 receptor (D1R) significantly attenuated AMPH sensitization, and conditional, virus-mediated restoration of NR1 in D1R neurons in the nucleus accumbens (NAc) of these animals rescued sensitization. Interestingly, sensitization could also be restored by virus-mediated inactivation of NR1 in all remaining neurons in the NAc of animals lacking NMDARs on D1R neurons, or by removing NMDARs from all MSNs. Taken together, these data indicate that unbalanced loss of NMDAR signaling in D1R MSNs alone prevents AMPH sensitization, whereas a balanced loss of NMDARs from both D1R and dopamine D2 receptor-expressing (D2R) MSNs is permissive for sensitization.
Narrative case study research: On endings and six session reviews
Authors: Etherington Kim , Bridges Nell
Published: February 2011

Background: An in‐depth, small scale narrative inquiry into ex‐clients' experiences of counselling was undertaken, using a local community counselling agency which highlighted several important themes, including reviews and endings. Aim: To show clients' lived experience of reviews and endings. Methods: Narrative case study methods were used, alongside researcher reflexivity. The meanings were co‐constructed between the ex‐clients, their counsellors and the researchers. Results: Clients stories show the inter‐relationship between reviews and endings, and that even when experienced negatively, clients can see the value of reviews. This paper also notes the therapeutic importance of mutuality and negotiation in decision making about endings. Conclusions: The process of undertaking collaborative, narrative inquiry can be empowering for all involved. Clients, counsellors and managers can question funders about their assumptions about the number of sessions offered when they inform themselves with research.
Systematic case study research: A practice‐oriented introduction to building an evidence base for counselling and psychotherapy
Authors: McLeod John , Elliott Robert
Published: February 2011

Background: Historically, clinical case studies have played a central role in counselling and psychotherapy training and practice, by allowing practitioners to learn about ideas and interventions being developed by colleagues. In recent years, the development of methods for systematic collection and analysis of case data has made it possible for case study research to begin to make a contribution to the evidence base for therapy policy and practice. Aim: This paper provides an overview of the characteristics of rigorous case study research, introduces a set of studies that exemplify these principles, and reviews the relevance of systematic case study inquiry for policy, practice and training. Conclusions: If case study research is to fulfil its potential as a source of research‐based knowledge, it is essential for practitioners to publish more systematic case studies that document the range and scope of everyday therapeutic practice. It is also necessary to carry out further research into a variety of methodological issues associated with single‐case inquiry, as a means of further developing this approach to practice‐based research.
Why Do Temporal Generalization Gradients Change When People Make Decisions as Quickly as Possible?
Authors: Klapproth Florian , Wearden John H.
Published: February 2011

Three experiments investigated temporal generalization performance under conditions in which participants were instructed to make their decisions as quickly as possible (speed), or were allowed to take their time (accuracy). A previous study (Klapproth & Müller, 2008) had shown that under speeded conditions people were more likely to confuse durations shorter than the standard with the standard than in the accuracy conditions, and a possible explanation of this result is that longer stimulus durations are “truncated” (i.e., people make a judgement about them before they have terminated, thereby shortening their effective duration) and that these truncated durations affect the standard used for the task. Experiment 1 investigated performance under speed and accuracy conditions when comparison durations were close to the standard or further away. No performance difference was found as a function of stimulus spacing, even though responses occurred on average before the longest durations had terminated, but this lack of effect was attributed to “task difficulty” effects changing decision thresholds. In Experiment 2, the standard duration was either the longest or the shortest duration in the comparison set, and differences between speed and accuracy groups occurred only when the comparisons were longer than the standard, supporting the “truncation” hypothesis. A third experiment showed that differences between speed and accuracy groups only occurred if some memory of the standard that was valid for more than one trial was used. In general, the results suggest that the generalization gradient shifts in speeded conditions occur because of truncation of longer comparison durations, which influences the effective standard used for the task.
Assessment of the Influence of Test Characteristics on the Clinical and Cost Impacts of Methicillin-ResistantStaphylococcus aureusScreening Programs in US Hospitals
Authors: Olchanski Natalia , Mathews Charles , Fusfeld Lauren , Jarvis William
Published: February 2011

Objective.

To compare the impacts of different methicillin-resistantStaphylococcus aureus(MRSA) screening test options (eg, polymerase chain reaction [PCR], rapid culture) and program characteristics on the clinical outcomes and budget of a typical US hospital.

Methods.

We developed an Excel-based decision-analytic model, using published literature to calculate and compare hospital costs and MRSA infection rates for PCR- or culture-based MRSA screening and then used multivariate sensitivity analysis to evaluate key variables. Same-day PCR testing for a representative 370-bed teaching hospital in the United States was assessed in different populations (high-risk patients, intensive care unit [ICU] patients, or all patients) and compared with other test options.

Results.

Different screening program populations (all patients, high-risk patients, ICU patients, or patients with previous MRSA colonization or infection only) represented a potential savings of $12,158-$76,624 per month over no program ($188,618). Analysis of multiple test options in high-risk population screening indicated that same-day PCR testing of high-risk patients resulted in fewer infections over 1,720 patient-days (2.9, compared with 3.5 for culture on selective media and 3.8 for culture on nonselective media) and the lowest total cost ($112,012). The costs of other testing approaches ranged from $113,742 to $123,065. Sensitivity analysis revealed that variations in transmission rate, conversion to infection, prevalence increases, and hospital size are important to determine program impact. Among test characteristics, turnaround time is highly influential.

Conclusion.

All screening options showed reductions in infection rates and cost impact improvement over no screening program. Among the options, same-day PCR testing for high-risk patients slightly edges out the others in terms of fewest infections and greatest potential cost savings.
Use of UV Powder for Surveillance to Improve Environmental Cleaning
Authors: Munoz-Price L. Silvia , Ariza-Heredia Ella , Adams Stephen , Olivier Micheline , Francois Lisa , Socarras Maria , Coro Gabriel , Adedokun Amos , Pappas Theodora , Tamayo Madelaine , McDade Regina , Dezfulian Cameron
Published: February 2011

Commercially available UV powder was applied weekly to high-risk objects within patient rooms and inspected after 48 hours. We found a baseline cleaning rate of 41.8% that increased up to 80% (P < .001) after the institution of weekly electronic feedback (unit rates and rankings) to environmental services, hospital leadership, and unit administrators.
MPID-T2: a database for sequence–structure–function analyses of pMHC and TR/pMHC structures
Authors: Khan Javed Mohammed , Cheruku Harish Reddy , Tong Joo Chuan , Ranganathan Shoba
Published: February 2011

Summary: Sequence–structure–function information is critical in understanding the mechanism of pMHC and TR/pMHC binding and recognition. A database for sequence–structure–function information on pMHC and TR/pMHC interactions, MHC-Peptide Interaction Database-TR version 2 (MPID-T2), is now available augmented with the latest PDB and IMGT/3Dstructure-DB data, advanced features and new parameters for the analysis of pMHC and TR/pMHC structures.

Availability:  http://biolinfo.org/mpid-t2.

Contact:  shoba.ranganathan@mq.edu.au

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Lévy fluctuations and mixing in dilute suspensions of algae and bacteria
Authors: Zaid Irwin M. , Dunkel Jörn , Yeomans Julia M.
Published: February 2011

Swimming micro-organisms rely on effective mixing strategies to achieve efficient nutrient influx. Recent experiments, probing the mixing capability of unicellular biflagellates, revealed that passive tracer particles exhibit anomalous non-Gaussian diffusion when immersed in a dilute suspension of self-motile
Chlamydomonas reinhardtii
algae. Qualitatively, this observation can be explained by the fact that the algae induce a fluid flow that may occasionally accelerate the colloidal tracers to relatively large velocities. A satisfactory quantitative theory of enhanced mixing in dilute active suspensions, however, is lacking at present. In particular, it is unclear how non-Gaussian signatures in the tracers' position distribution are linked to the self-propulsion mechanism of a micro-organism. Here, we develop a systematic theoretical description of anomalous tracer diffusion in active suspensions, based on a simplified tracer-swimmer interaction model that captures the typical distance scaling of a microswimmer's flow field. We show that the experimentally observed non-Gaussian tails are generic and arise owing to a combination of truncated Lévy statistics for the velocity field and algebraically decaying time correlations in the fluid. Our analytical considerations are illustrated through extensive simulations, implemented on graphics processing units to achieve the large sample sizes required for analysing the tails of the tracer distributions.
A density functional theory study of the adsorption of uracil on the Au(100) surface
Authors: Irrera Simona , de Leeuw Nora H.
Published: February 2011

We have used plane-wave density functional theory methods to explore the adsorption modes and configurations of uracil molecules on a gold surface to gain insight into the rational design of surface functionalization. We have investigated at the molecular level, the interactions of the RNA pyrimidine base uracil molecule isolated on the single crystal (100) surface of the gold substrate to determine the structure of uracil and orientation. Our calculations have shown that the most stable adsorbate structure is the enol tautomer of uracil, which adsorbs flat onto the gold surface through one of its carbonyl atoms. This configuration, which is compatible with previous experimental findings, is thermodynamically preferred over the adsorbed keto structure by approximately 0.23 eV (22.2 kJ mol
−1
).
Predation and protection in the macroevolutionary history of conifer cones
Authors: Leslie Andrew B.
Published: February 2011

Conifers are an excellent group in which to explore how changing ecological interactions may have influenced the allocation of reproductive tissues in seed plants over long time scales, because of their extensive fossil record and their important role in terrestrial ecosystems since the Palaeozoic. Measurements of individual conifer pollen-producing and seed-producing cones from the Pennsylvanian to the Recent show that the relative amount of tissue invested in pollen cones has remained constant through time, while seed cones show a sharp increase in proportional tissue investment in the Jurassic that has continued to intensify to the present day. Since seed size in conifers has remained similar through time, this increase reflects greater investment in protective cone tissues such as robust, tightly packed scales. This shift in morphology and tissue allocation is broadly concurrent with the appearance of new vertebrate groups capable of browsing in tree canopies, as well as a diversification of insect-feeding strategies, suggesting that an important change in plant–animal interactions occurred over the Mesozoic that favoured an increase in seed cone protective tissues.
Excluding access to invasion hubs can contain the spread of an invasive vertebrate
Authors: Florance Daniel , Webb Jonathan K. , Dempster Tim , Kearney Michael R. , Worthing Alex , Letnic Mike
Published: February 2011

Many biological invasions do not occur as a gradual expansion along a continuous front, but result from the expansion of satellite populations that become established at ‘invasion hubs’. Although theoretical studies indicate that targeting control efforts at invasion hubs can effectively contain the spread of invasions, few studies have demonstrated this in practice. In arid landscapes worldwide, humans have increased the availability of surface water by creating artificial water points (AWPs) such as troughs and dams for livestock. By experimentally excluding invasive cane toads (
Bufo marinus
) from AWP, we show that AWP provide a resource subsidy for non-arid-adapted toads and serve as dry season refuges and thus invasion hubs for cane toads in arid Australia. Using data on the distribution of permanent water in arid Australia and the dispersal potential of toads, we predict that systematically excluding toads from AWP would reduce the area of arid Australia across which toads are predicted to disperse and colonize under average climatic conditions by 38 per cent from 2 242 000 to 1 385 000 km
2
. Our study shows how human modification of hydrological regimes can create a network of invasion hubs that facilitates a biological invasion, and confirms that targeted control at invasion hubs can reduce landscape connectivity to contain the spread of an invasive vertebrate.
A general model for ontogenetic growth under food restriction
Authors: Hou Chen , Bolt Kendra M. , Bergman Aviv
Published: February 2011

Food restriction (FR) retards animals' growth. Understanding the underlying mechanisms of this phenomenon is important to conceptual problems in life-history theory, as well as to applied problems in animal husbandry and biomedicine. Despite a considerable amount of empirical data published since the 1930s, there is no relevant general theoretical framework that predicts how animals vary their energy budgets and life-history traits under FR. In this paper, we develop such a general quantitative model based on fundamental principles of metabolic energy allocation during ontogeny. This model predicts growth curves under varying conditions of FR, such as the compensatory growth, different age at which FR begins, its degree and its duration. Our model gives a quantitative explanation for the counterintuitive phenomenon that under FR, lower body temperature and lower metabolism lead to faster growth and larger adult size. This model also predicts that the animals experiencing FR reach the same fraction of their adult mass at the same age as their ad libitum counterparts. All predictions are well supported by empirical data from mammals and birds of varying body size, under different conditions of FR.
Role of glucose and CcpA in capsule expression and virulence of Streptococcus suis
Authors: Willenborg J. , Fulde M. , de Greeff A. , Rohde M. , Smith H. E. , Valentin-Weigand P. , Goethe R.
Published: February 2011

Streptococcus suisis one of the most important pathogens in pigs and is also an emerging zoonotic agent. After crossing the epithelial barrier,S. suiscauses bacteraemia, resulting in meningitis, endocarditis and bronchopneumonia. Since the host environment seems to be an important regulatory component for virulence, we related expression of virulence determinants ofS. suisto glucose availability during growth and to the sugar metabolism regulatorcatabolitecontrolproteinA(CcpA). We found that expression of the virulence-associated genesarcB, representingarcABCoperon expression,cps2A, representing capsular locus expression, as well assly,ofs,saoandepf, differed significantly between exponential and early stationary growth of a highly virulent serotype 2 strain. Deletion ofccpAaltered the expression of the surface-associated virulence factorsarcB,saoandeno, as well as the two currently proven virulence factors in pigs,ofsandcps2A, in early exponential growth. Global expression analysis using a cDNA expression array revealed 259 differentially expressed genes in early exponential growth, of which 141 were more highly expressed in the CcpA mutant strain 10ΔccpAand 118 were expressed to a lower extent. Interestingly, among the latter genes, 18 could be related to capsule and cell wall synthesis. Correspondingly, electron microscopy characterization of strain 10ΔccpArevealed a markedly reduced thickness of the capsule. This phenotype correlated with enhanced binding to porcine plasma proteins and a reduced resistance to killing by porcine neutrophils. Taken together, our data demonstrate that CcpA has a significant effect on the capsule synthesis and virulence properties ofS. suis.
The KEEP ON GOING Protein of Arabidopsis Recruits the ENHANCED DISEASE RESISTANCE1 Protein to Trans-Golgi Network/Early Endosome Vesicles
Authors: Gu Yangnan , Innes Roger W.
Published: February 2011

Loss-of-function mutations in the Arabidopsis (Arabidopsis thaliana) ENHANCED DISEASE RESISTANCE1 (EDR1) gene confer enhanced resistance to powdery mildew infection, enhanced senescence, and enhanced programmed cell death under both abiotic and biotic stress conditions. All edr1-mediated phenotypes can be suppressed by a specific missense mutation (keg-4) in the KEEP ON GOING (KEG) gene, which encodes a multidomain protein that includes a RING E3 ligase domain, a kinase domain, ankyrin repeats, and HERC2-like (for HECT and RCC1-like) repeats. The molecular and cellular mechanisms underlying this suppression are poorly understood. Using confocal laser scanning microscopy and fluorescent protein fusions, we determined that KEG localizes to trans-Golgi network/early endosome (TGN/EE) vesicles. Both the keg-4 mutation, which is located in the carboxyl-terminal HERC2-like repeats, and deletion of the entire HERC2-like repeats reduced endosomal localization of KEG and increased localization to the endoplasmic reticulum and cytosol, indicating that the HERC2-like repeats facilitate the TGN/EE targeting of KEG. EDR1 colocalized with KEG to the TGN/EE when coexpressed but localized primarily to the endoplasmic reticulum when expressed alone. Yeast two-hybrid and coimmunoprecipitation analyses revealed that EDR1 and KEG physically interact. Deletion of the HERC2-like repeats abolished the interaction between KEG and EDR1 as well as the KEG-induced TGN/EE localization of EDR1, indicating that the recruitment of EDR1 to the TGN/EE is based on a direct interaction between EDR1 and KEG mediated by the HERC2-like repeats. Collectively, these data suggest that EDR1 and KEG function together to regulate endocytic trafficking and/or the formation of signaling complexes on TGN/EE vesicles during stress responses.
The J-Domain Protein J3 Mediates the Integration of Flowering Signals in Arabidopsis
Authors: Shen Lisha , Kang Yin Ga Germain , Liu Lu , Yu Hao
Published: February 2011

The timing of the switch from vegetative to reproductive development in Arabidopsis  thaliana is controlled by an intricate network of flowering pathways, which converge on the transcriptional regulation of two floral pathway integrators, FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1). SHORT VEGETATIVE PHASE (SVP) acts as a key flowering regulator that represses the expression of FT and SOC1. Here, we report the identification of another potent flowering promoter, Arabidopsis DNAJ HOMOLOG 3 (J3), which mediates the integration of flowering signals through its interaction with SVP. J3 encodes a type I J-domain protein and is ubiquitously expressed in various plant tissues. J3 expression is regulated by multiple flowering pathways. Loss of function of J3 results in a significant late-flowering phenotype, which is partly due to decreased expression of SOC1 and FT. We further show that J3 interacts directly with SVP in the nucleus and prevents in vivo SVP binding to SOC1 and FT regulatory sequences. Our results suggest a flowering mechanism by which J3 integrates flowering signals from several genetic pathways and acts as a transcriptional regulator to upregulate SOC1 and FT through directly attenuating SVP binding to their regulatory sequences during the floral transition.
Introduction to haemostasis from a pharmacodynamic perspective
Authors: Kluft Cornelis , Burggraaf Jacobus
Published: February 2011

Biochemical characterization of the haemostatic system has advanced significantly in the past decades. Sub‐systems, such as coagulation, fibrinolysis, blood cells and platelets and the vessel wall have been studied by specialists, mostly separately and independently. The time has come to integrate the approaches, and, in particular, to develop tests to document the state of the whole system and to have available adequate pharmacodynamic tests to evaluate treatments. Many examples are available to show that traditional general methods of clotting and lysis do not provide the information that is desired. The present tendency is to use specific methods for specific factors or effects which are very limited in pharmacological information. There is also increasing awareness of the occurrence of rather broad interindividual variability in the haemostatic system. This suggests that individually tailored treatments are required. This is the more relevant since haemostasis is a balance and treatment should be positioned between efficacy and safety. The conclusion is reached that there is a need for integrated or global methods or sets of methods that reflect the complexity and individual status appropriately and allow the practitioner to judge the effects of interventions and their individual aspects.
Alloantigen specific deletion of primary human T cells by Fas ligand (CD95L)‐transduced monocyte‐derived killer‐dendritic cells
Authors: Schütz Christian , Hoves Sabine , Halbritter Dagmar , Zhang Huang‐Ge , Mountz John D. , Fleck Martin
Published: February 2011

Numerous studies have been performed in vitro and in various animal models to modulate the interaction of dendritic cells (DC) and T cells by Fas (CD95/Apo‐1) signalling to delete activated T cells via induction of activation‐induced cell death (AICD). Previously, we could demonstrate that Fas ligand (FasL/CD95L)‐expressing ‘killer‐antigen‐presenting cells’ can be generated from human monocyte‐derived mature DC (mDC) using adenoviral gene transfer. To evaluate whether these FasL‐expressing mDC (mDC‐FasL) could eliminate alloreactive primary human T cells in vitro, co‐culture experiments were performed. Proliferation of human T cells was markedly reduced in primary co‐cultures with allogeneic mDC‐FasL, whereas a strong proliferative T‐cell response could be observed in co‐cultures with enhanced green fluorescent protein‐transduced mDC. Inhibition of T‐cell proliferation was related to the transduction efficiency, and the numbers of mDC‐FasL present in co‐cultures. In addition, proliferation of pre‐activated alloreactive CD4+ and CD8+ T cells could be almost completely inhibited in secondary co‐cultures using mDC‐FasL as stimulatory cells, which was the result of induction of apoptosis in the majority of preactivated T cells. The specific deletion of alloreactive T cells by mDC‐FasL was confirmed by an unaffected proliferative response of surviving T cells towards allogeneic ‘third‐party’ peripheral blood mononuclear cells in a third stimulation, or upon unspecific stimulation with anti‐CD3/CD28 beads. The results of this study demonstrate that allospecifically activated T cells are efficiently eliminated by mDC‐FasL, supporting further investigations to apply FasL‐expressing ‘killer‐DC’ as a novel strategy for the treatment of allograft rejection.
A comparison between jerk‐cost derived from a jaw‐tracking system with that from an accelerometer
Authors: MINAMI I. , ZHAO N. , OOGAI K. , NEMOTO T. , WHITTLE T. , MURRAY G. M.
Published: February 2011

Summary  Jerk‐cost is an inverse measure of movement smoothness and can be calculated from the first‐time derivative of acceleration obtained from a tri‐axial piezoelectric accelerometer (TPA), or from the third‐time derivative of position obtained from a jaw‐tracking device. The aims of this study were to determine, in 10 asymptomatic subjects who are chewing gum, (i) jerk‐cost measures derived from displacement/time data obtained from the JAWS3D jaw‐tracking device and from acceleration data obtained from a TPA used in the same jaw movement recordings, (ii) whether there was a significant relationship between jerk‐cost measures derived from both devices and (iii) the degree of agreement between the two measures. Jerk‐cost data were calculated in the opening phase, the closing phase, and over the full chewing cycle as the first‐time derivative from acceleration obtained from the TPA, and the third‐time derivative from JAWS3D for each of the X‐, Y‐ and Z‐direction series. There was a significant correlation between both measures of jerk‐cost over the full chewing cycle and during jaw‐opening (r = 0·65, 0·75, respectively; P < 0·001). There was no significant correlation in the closing phase (r = −0·02, P = 0·99). The Bland–Altman test showed that jerk‐cost derived from the JAWS3D can differ by up to 78% below and 21% above that derived from the TPA. These results suggest that jerk‐cost measures derived from a jaw‐tracking system cannot substitute for jerk‐cost measures derived from an accelerometer.
Review: The neurobiology of varicella zoster virus infection
Authors: Gilden D. , Mahalingam R. , Nagel M. A. , Pugazhenthi S. , Cohrs R. J.
Published: February 2011

D. Gilden, R. Mahalingam, M. A. Nagel, S. Pugazhenthi and R. J. Cohrs (2011) Neuropathology and Applied Neurobiology37, 441–463

The neurobiology of varicella zoster virus infection

Varicella zoster virus (VZV) is a neurotropic herpesvirus that infects nearly all humans. Primary infection usually causes chickenpox (varicella), after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. Although VZV cannot be isolated from human ganglia, nucleic acid hybridization and, later, polymerase chain reaction proved that VZV is latent in ganglia. Declining VZV‐specific host immunity decades after primary infection allows virus to reactivate spontaneously, resulting in shingles (zoster) characterized by pain and rash restricted to one to three dermatomes. Multiple other serious neurological and ocular disorders also result from VZV reactivation. This review summarizes the current state of knowledge of the clinical and pathological complications of neurological and ocular disease produced by VZV reactivation, molecular aspects of VZV latency, VZV virology and VZV‐specific immunity, the role of apoptosis in VZV‐induced cell death and the development of an animal model provided by simian varicella virus infection of monkeys.
Assessing the role of root plasma membrane and tonoplast Na+/H+ exchangers in salinity tolerance in wheat: in planta quantification methods
Authors: CUIN TRACEY A. , BOSE JAYAKUMAR , STEFANO GIOVANNI , JHA DEEPA , TESTER MARK , MANCUSO STEFANO , SHABALA SERGEY
Published: February 2011

This work investigates the role of cytosolic Na+ exclusion in roots as a means of salinity tolerance in wheat, and offers in planta methods for the functional assessment of major transporters contributing to this trait. An electrophysiological protocol was developed to quantify the activity of plasma membrane Na+ efflux systems in roots, using the microelectrode ion flux estimation (MIFE) technique. We show that active efflux of Na+ from wheat root epidermal cells is mediated by a SOS1‐like homolog, energized by the plasma membrane H+‐ATPase. SOS1‐like efflux activity was highest in Kharchia 65, a salt‐tolerant bread wheat cultivar. Kharchia 65 also had an enhanced ability to sequester large quantities of Na+ into the vacuoles of root cells, as revealed by confocal microscopy using Sodium Green. These findings were consistent with the highest level of expression of both SOS1 and NHX1 transcripts in plant roots in this variety. In the sensitive wheat varieties, a greater proportion of Na+ was located in the root cell cytosol. Overall, our findings suggest a critical role of cytosolic Na+ exclusion for salinity tolerance in wheat and offer convenient protocols to quantify the contribution of the major transporters conferring this trait, to screen plants for salinity tolerance.
Possible association of Henoch–Schönlein purpura in adults with odontogenic focal infection
Authors: Igawa Ken , Satoh Takahiro , Yokozeki Hiroo
Published: February 2011

Background  Odontogenic focal infection (OFI) is considered to be an important precipitating factor in some cases of palmoplantar pustulosis and psoriasis. In Henoch–Schönlein purpura (HSP), it is clear that acute bacterial infection is one of the causes. However, it remains unclear how OFI participates in the pathogenesis of HSP.

Methods  To clarify how OFI is related to the disease activity of HSP in terms of skin lesions and organ involvement, we conducted a retrospective study of 28 cases of adult‐type HSP.

Results  Panoramic x‐ray screening detected OFI in 14 of the 28 patients. Patients with OFI had higher incidences of renal and gastrointestinal complications than those without OFI. Seven patients had severe OFI and underwent tooth extraction, resulting in a marked improvement of their skin lesions. Five of those seven patients exhibited transient flare‐up after the tooth extraction.

Conclusions  Latent OFI is an important infectious focus that is involved in the pathogenesis of HSP and influences its disease activity.
Photodamaging effects of porphyrins and chitosan on primary human keratinocytes and carcinoma cell cultures
Authors: Susan Mirela , Baldea Ioana , Senila Simona , Macovei Victorina , Dreve Simina , Ion Rodica Mariana , Cosgarea Rodica
Published: February 2011

Background  Photodynamic therapy (PDT) is a non‐surgical method for treating non‐melanoma skin cancer and precancerous lesions which involves the activation of a photosensitizer by visible light to produce activated oxygen species within target cells, resulting in the destruction of the latter. The present study evaluates the effect of PDT on primary normal and basal cell carcinoma cultures in vitro.

Methods  Primary human keratinocytes and carcinoma cell cultures were exposed to various concentrations of 5,10,15,20‐tetra‐(para‐methoxyphenyl) porphyrin (TMP) and its zinc compound (Zn‐TMP) for 24 hours, with or without chitosan, and then irradiated using a PDT lamp (630 nm, 6 J/cm2). The effects of PDT were assessed using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium inner salt (MTS) assay and an immunocytochemical method with Annexin V‐FITC for detecting apoptosis.

Results  Both tested substances, TMP and Zn‐TMP, had a phototoxic effect on primary human carcinoma cell cultures in concentrations of 1–100 μg/ml, which positively correlated with the concentration of the photosensitizer. There was no phototoxic effect on primary keratinocytes, probably because of the preferential accumulation of photosensitizing substances in tumoral cells. Administration of chitosan in association with photosensitizing substances increased cell viability compared with photosensitizers alone, exerting a cytoprotective effect.

Conclusions  The study demonstrates that the photodynamic activity of TMP and its metalloporphyrin derivative is limited to primary human carcinoma cells and suggests that these porphyrins could be efficiently used in PDT in vivo.
Cutaneous sarcoidosis developing after treatment with pegylated interferon and ribavirin: a new case and review of the literature
Authors: López Verónica , Molina Inmaculada , Monteagudo Carlos , Jordá Esperanza
Published: February 2011

Sarcoidosis is a multisystem granulomatous disease that affects multiple organs in adults between 20 and 50 years old. Interferon alpha (IFN‐α) is an immunomodulator that has been used in a wide range of diseases, including hepatitis C virus infection, multiple sclerosis, and other types of neoplasias, including leukemia, lymphoma, Kaposi’s sarcoma, and melanoma. Standard IFN‐α‐induced sarcoidosis has been reported, but there are few reports of cutaneous sarcoidosis with pegylated IFN‐α therapy. We present a new case of cutaneous sarcoidosis after treatment with pegylated IFN, and a review of the literature.
Research of UL54‐specific siRNA on herpes simplex virus type II replication
Authors: Qing Guo , Weili Weng , Fanqin Zeng , Rongchang Zheng , Yijin Luo , Jianqun Du
Published: February 2011

To determine how UL54‐specific siRNA affects virus replication and protection of host cells, we examined virus titer and the activity of the cells at 12 hours, 24 hours, 36 hours, 48 hours, 60 hours and 72 hours after process of RNAi, including: four UL54‐specific siRNAs and the positive/negative control siRNAs synthesized in vitro by chemical processes. The Vero cells were transfected with siRNAs using lipofectamine 2000 followed by infection by HSV‐II. Our studies reveal that the groups with UL54‐specific siRNA decreased significantly in virus titer at 12–24 hours, and only slightly decreased after that; groups with UL54‐specific siRNA had higher OD values shown by MTT colorimetric assay than blank cells and survived better; R2 and R4 groups had lower virus titer and better survival than other groups. UL54‐specific siRNA can inhibit HSV‐II replication, while protecting host cells. There are effective and ineffective siRNA, which were synthesized in accordance with the same principles.
Nanoparticles: small and mighty
Authors: Wiesenthal Alison , Hunter Lindsey , Wang Shuguang , Wickliffe Jeffrey , Wilkerson Michael
Published: February 2011

The properties of engineered nanomaterials and nanoparticles such as zinc oxide and titanium dioxide may differ substantially from naturally occurring materials and particles. Nanoparticles have unique physical properties making them ideal for use in various skin care products currently on the market. Nano‐preparations are currently under investigation as novel treatments of acne vulgaris, recurrent condyloma accuminata, atopic dermatitis, hyperpigmented skin lesions, and other non‐dermatologic diseases. Because of their increased surface area, nanoparticles have increased reactivity and a small size allowing for enhanced mobility through the human body and environment. As their use becomes more prevalent, nanoparticles are being scrutinized for their safety and long‐term effects. This review discusses the benefits of nanoparticles in dermatological therapies and skin care products as well as potential disadvantages and possible mechanisms of toxicity.
Turning signals into meaning –‘Shared decision making’ meets communication theory
Authors: Kasper Jürgen , Légaré France , Scheibler Fülöp , Geiger Friedemann
Published: February 2011

Shared decision making (SDM) is being increasingly challenged for promoting an innovative role model while adhering to an archaic approach to patient‐clinician communication, both in clinical practice and the research field. Too often, SDM has been studied at the individual level, which ignores the interpersonal system between patients and physicians. We aimed to encourage debate by reflecting on the essentials of SDM in terms of epistemology. We operationalized the SDM core concept of information exchange in terms of social systems theory. An epistemological analysis of the term information refers to its inherent process character. Exchange of information thereby becomes synonymous with social sense construction, indicating that, rather than just being a vehicle, the act of communication itself is the information. We plead for the adoption of existing dyadic analytical methods such as those offered by the interpersonal paradigm. Implications of an updated concept of information for the use of SDM‐evaluation methods, for SDM‐goal setting, and for clinical practice of SDM are described.