bluuebunny/crossref_metadata_2025 huggingface dataset:
Costimulatory ligand CD70 allows induction of CD8+ T-cell immunity by immature dendritic cells in a vaccination setting
Authors: Keller Anna M. , Xiao Yanling , Peperzak Victor , Naik Shalin H. , Borst Jannie
Published: March 2009

The use of dendritic cells (DCs) as anticancer vaccines holds promise for therapy but requires optimization. We have explored the potential of costimulatory ligand CD70 to boost the capacity of DCs to evoke effective CD8+ T-cell immunity. We show that immature conventional DCs, when endowed with CD70 expression by transgenesis, are converted from a tolerogenic state into an immunogenic state. Adoptively transferred CD70-expressing immature DCs could prime CD8+ T cells, by CD27, to become tumor-eradicating cytolytic effectors and memory cells with a capacity for robust secondary expansion. The CD8+ T-cell response, including memory programming, was independent of CD4+ T-cell help, because the transferred immature DCs were loaded with major histocompatibility complex class I–restricted peptide only. Without CD70 expression, the DCs generated abortive clonal expansion, dysfunctional antitumor responses, and no CD8+ T-cell memory. CD70-expressing CD8+ DCs were the primary subset responsible for CD8+ T-cell priming and performed comparably to fully matured DCs. These data highlight the importance of CD27/CD70 interactions at the T-cell/DC interface and indicate that CD70 should be considered in the design of DC vaccination strategies.
Ectopic HOXB4 overcomes the inhibitory effect of tumor necrosis factor-α on Fanconi anemia hematopoietic stem and progenitor cells
Authors: Milsom Michael D. , Schiedlmeier Bernhard , Bailey Jeff , Kim Mi-Ok , Li Dandan , Jansen Michael , Ali Abdullah Mahmood , Kirby Michelle , Baum Christopher , Fairbairn Leslie J. , Williams David A.
Published: March 2009

Ectopic delivery of HOXB4 elicits the expansion of engrafting hematopoietic stem cells (HSCs). We hypothesized that inhibition of tumor necrosis factor-α (TNF-α) signaling may be central to the self-renewal signature of HOXB4. Because HSCs derived from Fanconi anemia (FA) knockout mice are hypersensitive to TNF-α, we studied Fancc−/− HSCs to determine the physiologic effects of HOXB4 on TNF-α sensitivity and the relationship of these effects to the engraftment defect of FA HSCs. Overexpression of HOXB4 reversed the in vitro hypersensitivity to TNF-α of Fancc−/− HSCs and progenitors (P) and partially rescued the engraftment defect of these cells. Coexpression of HOXB4 and the correcting FA-C protein resulted in full correction compared with wild-type (WT) HSCs. Ectopic expression of HOXB4 resulted in a reduction in both apoptosis and reactive oxygen species in Fancc−/− but not WT HSC/P. HOXB4 overexpression was also associated with a significant reduction in surface expression of TNF-α receptors on Fancc−/− HSC/P. Finally, enhanced engraftment was seen even when HOXB4 was expressed in a time-limited fashion during in vivo reconstitution. Thus, the HOXB4 engraftment signature may be related to its effects on TNF-α signaling, and this pathway may be a molecular target for timed pharmacologic manipulation of HSC during reconstitution.
Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases
Authors: Bradford Porcia T. , Devesa Susan S. , Anderson William F. , Toro Jorge R.
Published: March 2009

There have been no prior large population-based studies focusing on cutaneous lymphomas (CL) in the United States. Using the Surveillance, Epidemiology and End Results (SEER) program data, we analyzed age-adjusted CL incidence rates (IRs) and survival rates by sex and race/ethnicity. There were 3884 CLs diagnosed during 2001-2005. Cutaneous T-cell lymphomas (CTCLs) accounted for 71% (age-adjusted incidence rate [IR] = 7.7/1 000 000 person-years), whereas cutaneous B-cell lymphomas(CBCLs) accounted for 29% (IR = 3.1/1 000 000 person-years). Males had a statistically significant higher IR of CL than females (14.0 vs 8.2/1 000 000 person-years, respectively; male-female IR ratio [M/F IRR] = 1.72; P < .001). CL IRs were highest among blacks and non-Hispanic whites (both 11.5/1 000 000 person-years), followed by Hispanic whites (7.9) and Asian/Pacific Islanders (7.1). The CTCL IR was highest among blacks (10.0/1 000 000 person-years), whereas the CBCL IR was highest among non-Hispanic whites (3.5). Over the past 25 years, the CL IR increased from 5.0/1 000 000 person-years during 1980-1982 to 14.3 during 2001-2003. During 2004-2005, the CL IR was 12.7. This recent apparent change could be incomplete case ascertainment or potential leveling off of IRs. CLs rates vary markedly by race and sex, supporting the notion that they represent distinct disease entities.
Syk to death
Authors: Bergsagel P. Leif
Published: March 2009

Using elegant mouse models of B-cell lymphoma, Young and colleagues validate targeting syk-mediated B-cell receptor signaling as an effective antitumor strategy for the treatment of non-Hodgkin lymphoma.
A family of splice variants of CstF-64 expressed in vertebrate nervous systems
Authors: Shankarling Ganesh S , Coates Penelope W , Dass Brinda , MacDonald Clinton C
Published: March 2009

Background

Alternative splicing and polyadenylation are important mechanisms for creating the proteomic diversity necessary for the nervous system to fulfill its specialized functions. The contribution of alternative splicing to proteomic diversity in the nervous system has been well documented, whereas the role of alternative polyadenylation in this process is less well understood. Since the CstF-64 polyadenylation protein is known to be an important regulator of tissue-specific polyadenylation, we examined its expression in brain and other organs.

Results

We discovered several closely related splice variants of CstF-64 – collectively called βCstF-64 – that could potentially contribute to proteomic diversity in the nervous system. The βCstF-64 splice variants are found predominantly in the brains of several vertebrate species including mice and humans. The major βCstF-64 variant mRNA is generated by inclusion of two alternate exons (that we call exons 8.1 and 8.2) found between exons 8 and 9 of the CstF-64 gene, and contains an additional 147 nucleotides, encoding 49 additional amino acids. Some variants of βCstF-64 contain only the first alternate exon (exon 8.1) while other variants contain both alternate exons (8.1 and 8.2). In mice, the predominant form of βCstF-64 also contains a deletion of 78 nucleotides from exon 9, although that variant is not seen in any other species examined, including rats. Immunoblot and 2D-PAGE analyses of mouse nuclear extracts indicate that a protein corresponding to βCstF-64 is expressed in brain at approximately equal levels to CstF-64. Since βCstF-64 splice variant family members were found in the brains of all vertebrate species examined (including turtles and fish), this suggests that βCstF-64 has an evolutionarily conserved function in these animals. βCstF-64 was present in both pre- and post-natal mice and in different regions of the nervous system, suggesting an important role for βCstF-64 in neural gene expression throughout development. Finally, experiments in representative cell lines suggest that βCstF-64 is expressed in neurons but not glia.

Conclusion

This is the first report of a family of splice variants encoding a key polyadenylation protein that is expressed in a nervous system-specific manner. We propose that βCstF-64 contributes to proteomic diversity by regulating alternative polyadenylation of neural mRNAs.
Prevalence of pathogenetic MC4R mutations in Italian children with early Onset obesity, tall stature and familial history of obesity
Authors: Santoro Nicola , Cirillo Grazia , Xiang Zhimin , Tanas Rita , Greggio Nella , Morino Giuseppe , Iughetti Lorenzo , Vottero Alessandra , Salvatoni Alessandro , Di Pietro Mario , Balsamo Antonio , Crinò Antonino , Grandone Anna , Haskell-Luevano Carrie , Perrone Laura , del Giudice Emanuele Miraglia
Published: March 2009

Background

Melanocortin-4-receptor (MC4R) mutations represent the most frequent genetic cause of non-syndromic early onset obesity. Children carrying MC4R mutations seem to show a particular phenotype characterized by early onset, severe obesity and high stature. To verify whether MC4R mutations are associated with this particular phenotype in the Italian pediatric population, we decided to screen the MC4R gene in a group of obese children selected on the basis of their phenotype.

Methods

To perform this study, a multicentric approach was designed. Particularly, to be enrolled in the study subjects needed to meet the following criteria: Body mass index ≥ 3 deviation scores according to age and sex, familiar history of obesity (at least one parent obese), obesity onset before the 10 years old, height ≥ 2 deviation scores. The coding region of MC4R gene was screened in 240 obese children (mean age 8.3 ± 3.1, mean BMI 30.8 ± 5.4) and in 200 controls (mean age 8.1 ± 2.8; mean BMI 14.2 ± 2.5).

Results

Three mutations have been found in five obese children. The S127L (C380T), found in three unrelated children, had been described and functionally characterized previously. The Q307X (C919T) and the Y332H (T994C) mutations were found in two patients. Functional studies showed that only Q307X impaired protein function.

Conclusion

The low prevalence of MC4R mutations (1.6%) in this group of obese children selected according to the obesity degree, the tall stature and the family history of obesity was similar to the prevalence observed in previous screenings performed in obese adults and in not phenotypically selected obese children.
Better estimation of protein-DNA interaction parameters improve prediction of functional sites
Authors: Nagaraj Vijayalakshmi H , O'Flanagan Ruadhan A , Sengupta Anirvan M
Published: March 2009

Background

Characterizing transcription factor binding motifs is a common bioinformatics task. For transcription factors with variable binding sites, we need to get many suboptimal binding sites in our training dataset to get accurate estimates of free energy penalties for deviating from the consensus DNA sequence. One procedure to do that involves a modified SELEX (Systematic Evolution of Ligands by Exponential Enrichment) method designed to produce many such sequences.

Results

We analyzed low stringency SELEX data forE. coliCatabolic Activator Protein (CAP), and we show here that appropriate quantitative analysis improves our ability to predictin vitroaffinity. To obtain large number of sequences required for this analysis we used a SELEX SAGE protocol developed by Rouletet al. The sequences obtained from here were subjected to bioinformatic analysis. The resulting bioinformatic model characterizes the sequence specificity of the protein more accurately than those sequence specificities predicted from previous analysis just by using a few known binding sites available in the literature. The consequences of this increase in accuracy for prediction of in vivo binding sites (and especially functional ones) in theE. coligenome are also discussed. We measured the dissociation constants of several putative CAP binding sites by EMSA (Electrophoretic Mobility Shift Assay) and compared the affinities to the bioinformatics scores provided by methods like the weight matrix method and QPMEME (Quadratic Programming Method of Energy Matrix Estimation) trained on known binding sites as well as on the new sites from SELEX SAGE data. We also checked predicted genome sites for conservation in the related speciesS. typhimurium. We found that bioinformatics scores based on SELEX SAGE data does better in terms of prediction of physical binding energies as well as in detecting functional sites.

Conclusion

We think that training binding site detection algorithms on datasets from binding assays lead to better prediction. The improvements in accuracy came from the unbiased nature of the SELEX dataset rather than from the number of sites available. We believe that with progress in short-read sequencing technology, one could use SELEX methods to characterize binding affinities of many low specificity transcription factors.
Connexins: a myriad of functions extending beyond assembly of gap junction channels
Authors: Dbouk Hashem A , Mroue Rana M , El-Sabban Marwan E , Talhouk Rabih S
Published: March 2009

Connexins constitute a large family of trans-membrane proteins that allow intercellular communication and the transfer of ions and small signaling molecules between cells. Recent studies have revealed complex translational and post-translational mechanisms that regulate connexin synthesis, maturation, membrane transport and degradation that in turn modulate gap junction intercellular communication. With the growing myriad of connexin interacting proteins, including cytoskeletal elements, junctional proteins, and enzymes, gap junctions are now perceived, not only as channels between neighboring cells, but as signaling complexes that regulate cell function and transformation. Connexins have also been shown to form functional hemichannels and have roles altogether independent of channel functions, where they exert their effects on proliferation and other aspects of life and death of the cell through mostly-undefined mechanisms. This review provides an updated overview of current knowledge of connexins and their interacting proteins, and it describes connexin modulation in disease and tumorigenesis.
A rapid biosensor-based method for quantification of free and glucose-conjugated salicylic acid
Authors: DeFraia Christopher T , Schmelz Eric A , Mou Zhonglin
Published: March 2009

Background

Salicylic acid (SA) is an important signalling molecule in plant defenses against biotrophic pathogens. It is also involved in several other processes such as heat production, flowering, and germination. SA exists in the plant as free SA and as an inert glucose conjugate (salicylic acid 2-O-β-D-glucoside or SAG). Recently, Huanget al. developed a bacterial biosensor that responds to free SA but not SAG, designated asAcinetobactersp. ADPWH_lux. In this paper we describe an improved methodology forAcinetobactersp. ADPWH_lux-based free SA quantification, enabling high-throughput analysis, and present an approach for the quantification of SAG from crude plant extracts.

Results

On the basis of the original biosensor-based method, we optimized extraction and quantification. SAG content was determined by treating crude extracts with β-glucosidase, then measuring the released free SA with the biosensor. β-glucosidase treatment released more SA in acetate buffer extract than in Luria-Bertani (LB) extract, while enzymatic hydrolysis in either solution released more free SA than acid hydrolysis. The biosensor-based method detected higher amounts of SA in pathogen-infected plants than did a GC/MS-based method. SA quantification of control and pathogen-treated wild-type andsid2(SA induction-deficient) plants demonstrated the efficacy of the method described. Using the methods detailed here, we were able to detect as little as 0.28 μg SA/g FW. Samples typically had a standard deviation of up to 25% of the mean.

Conclusion

The ability ofAcinetobactersp. ADPWH_luxto detect SA in a complex mixture, combined with the enzymatic hydrolysis of SAG in crude extract, allowed the development of a simple, rapid, and inexpensive method to simultaneously measure free and glucose-conjugated SA. This approach is amenable to a high-throughput format, which would further reduce the cost and time required for biosensor-based SA quantification. Possible applications of this approach include characterization of enzymes involved in SA metabolism, analysis of temporal changes in SA levels, and isolation of mutants with aberrant SA accumulation.
The Neuroscience Peer Review Consortium
Authors: Saper Clifford B , Maunsell John HR
Published: March 2009

As the Neuroscience Peer Review Consortium (NPRC) ends its first year, it is worth looking back to see how the experiment has worked.

In order to encourage dissemination of the details outlined in this Editorial, it will also be published in other journals in the Neuroscience Peer Review Consortium.
Decomposing complex reaction networks using random sampling, principal component analysis and basis rotation
Authors: Barrett Christian L , Herrgard Markus J , Palsson Bernhard
Published: March 2009

Background

Metabolism and its regulation constitute a large fraction of the molecular activity within cells. The control of cellular metabolic state is mediated by numerous molecular mechanisms, which in effect position the metabolic network flux state at specific locations within a mathematically-definable steady-state flux space. Post-translational regulation constitutes a large class of these mechanisms, and decades of research indicate that achieving a network flux state through post-translational metabolic regulation is both a complex and complicated regulatory problem. No analysis method for the objective, top-down assessment of such regulation problems in large biochemical networks has been presented and demonstrated.

Results

We show that the use of Monte Carlo sampling of the steady-state flux space of a cell-scale metabolic system in conjunction with Principal Component Analysis and eigenvector rotation results in a low-dimensional and biochemically interpretable decomposition of the steady flux states of the system. This decomposition comes in the form of a low number of small reaction sets whose flux variability accounts for nearly all of the flux variability in the entire system. This result indicates an underlying simplicity and implies that the regulation of a relatively low number of reaction sets can essentially determine the flux state of the entire network in the given growth environment.

Conclusion

We demonstrate how our top-down analysis of networks can be used to determine key regulatory requirements independent of specific parameters and mechanisms. Our approach complements the reductionist approach to elucidation of regulatory mechanisms and facilitates the development of our understanding of global regulatory strategies in biological networks.
Conventional intramuscular sedatives versus ziprasidone for severe agitation in adolescents: case-control study
Authors: Jangro William C , Preval Horacio , Southard Robert , Klotz Steven G , Francis Andrew
Published: March 2009

Objective

The objective of this study was to compare intramuscular (IM) ziprasidone to conventional IM medications (haloperidol combined with lorazepam) for the treatment of severe agitation in adolescents (age 12–17).

Methods

We retrospectively identified consecutive severe agitation episodes (defined as requiring physical restraint) in adolescents treated with either IM ziprasidone or conventional IM agents in a psychiatric emergency room. For ziprasidone, the dosage was 20 mg for 23 episodes and 10 mg for 5 episodes. For 24 episodes treated with combined haloperidol and lorazepam, the dosages were 4.8 ± 0.3 SEM mg and 1.9 ± 0.4 mg respectively. Outcomes were the duration of restraint and need for adjunctive "rescue" medications within 60 minutes. These outcomes were decided prior to reviewing any records.

Results

No difference was found in restraint duration (ziprasidone, N = 28, 55 ± 5 minutes; haloperidol with lorazepam N = 24, 65 ± 7 minutes, P = NS). Use of "rescue" medications did not differ between the two groups. No changes in blood pressure were found, but pulse decreased 8.3 ± 2.4 for haloperidol with lorazepam and 8.9 ± 4.24 for ziprasidone (P = NS). No instances of excessive sedation or extra-pyramidal symptoms were documented.

Conclusion

In this study, IM ziprasidone appeared effective, well tolerated, and similar in clinical profile to combined conventional IM medications for treating severe agitation in adolescents. Given the reportedly favorable acute side effect profile of parenteral atypical agents, they may provide an alternative to conventional antipsychotics for treating acute agitation in both adult and adolescent populations. Future randomized, controlled studies are needed.
Sonic to ultrasonic Q of sandstones and limestones: Laboratory measurements at in situ pressures
Authors: McCann Clive , Sothcott Jeremy
Published: March 2009

Laboratory measurements of the attenuation and velocity dispersion of compressional and shear waves at appropriate frequencies, pressures, and temperatures can aid interpretation of seismic and well-log surveys as well as indicate absorption mechanisms in rocks. Construction and calibration of resonant-bar equipment was used to measure velocities and attenuations of standing shear and extensional waves in copper-jacketed right cylinders of rocks ([Formula: see text] in length, [Formula: see text] in diameter) in the sonic frequency range and at differential pressures up to [Formula: see text]. We also measured ultrasonic velocities and attenuations of compressional and shear waves in [Formula: see text]-diameter samples of the rocks at identical pressures. Extensional-mode velocities determined from the resonant bar are systematically too low, yielding unreliable Poisson’s ratios. Poisson’s ratios determined from the ultrasonic data are frequency corrected and used to calculate thesonic-frequency compressional-wave velocities and attenuations from the shear- and extensional-mode data. We calculate the bulk-modulus loss. The accuracies of attenuation data (expressed as [Formula: see text], where [Formula: see text] is the quality factor) are [Formula: see text] for compressional and shear waves at ultrasonic frequency, [Formula: see text] for shear waves, and [Formula: see text] for compressional waves at sonic frequency. Example sonic-frequency data show that the energy absorption in a limestone is small ([Formula: see text] greater than 200 and stress independent) and is primarily due to poroelasticity, whereas that in the two sandstones is variable in magnitude ([Formula: see text] ranges from less than 50 to greater than 300, at reservoir pressures) and arises from a combination of poroelasticity and viscoelasticity. A graph of compressional-wave attenuation versus compressional-wave velocity at reservoir pressures differentiates high-permeability ([Formula: see text], [Formula: see text]) brine-saturated sandstones from low-permeability ([Formula: see text], [Formula: see text]) sandstones and shales.
Acoustic and petrophysical properties of a clastic deepwater depositional system from lithofacies to architectural elements’ scales
Authors: Slatt Roger M. , Eslinger Eric V. , Van Dyke Staffan K.
Published: March 2009

An analysis of acoustic, petrophysical, and stratigraphic heterogeneities has been completed at three scales for an outcropping/subcropping deep-water stratigraphic sequence: lithofacies (core/plug), lithostratigraphic unit (well log), and architectural element (seismic). Measurement techniques/instruments included outcrop measured sections; behind-outcrop drilling/logging/coring (and subsequent core and log analysis); ground-penetrating radar; shallow seismic reflection; and electromagnetic induction. At the lithofacies scale, four rock types are defined: (1) heterogeneous sandstones and (2) uniform sandstones, which differ in their grain composition and sedimentary structures, but do not differ significantly in average porosity, permeability, and acoustic impedance; and (3) organic-rich shales and (4) organic-poor shales, which exhibit significantly higher acoustic impedance than either sandstone type. There is an inverse relation between porosity and permeability versus acoustic impedance ofthe lithofacies at this scale. At the lithostratigraphic unit scale, three units of interbedded lithofacies are defined: (1) uniform sandstone prone, (2) heterogeneous sandstone prone, and (3) shale prone. Successive merging of thinner beds with thicker beds results in clear differences in average rock properties between the lithostratigraphic units, but there is insufficient variation about the averages to preclude statistically significant differentiation of the sandstones. Lithostratigraphic unit properties also vary laterally. At the architectural element scale, two architectural elements are channel element and lobe element. Only wellbore acoustic impedance differs significantly between these two elements. However, the internal lateral architecture of these two elements is quite different. The results highlight the difficulty in evaluating stratigraphic patterns away from the wellbore. More research in this area is warranted. Attempts to quantify lateral variability of properties in a geologically realistic manner are encouraged because lateral variability is as important to reservoir characterization and performance as is vertical variability.
Transcription factor Gbx2 acts cell-nonautonomously to regulate the formation of lineage-restriction boundaries of the thalamus
Authors: Chen Li , Guo Qiuxia , Li James Y. H.
Published: March 2009

Relatively little is known about the development of the thalamus,especially its differentiation into distinct nuclei. We demonstrate here that Gbx2-expressing cells in mouse diencephalon contribute to the entire thalamic nuclear complex. However, the neuronal precursors for different thalamic nuclei display temporally distinct Gbx2 expression patterns. Gbx2-expressing cells and their descendents form sharp lineage-restriction boundaries delineating the thalamus from the pretectum,epithalamus and prethalamus, revealing multiple compartmental boundaries within the mouse diencephalon. Without Gbx2, cells originating from the thalamus abnormally contribute to the epithalamus and pretectum. This abnormality does not result from an overt defect in patterning or cell-fate specification in Gbx2 mutants. Chimeric and genetic mosaic analysis demonstrate that Gbx2 plays a cell-nonautonomous role in controlling segregation of postmitotic thalamic neurons from the neighboring brain structures that do not express Gbx2. We propose that, within the developing thalamus, the dynamic and differential expression of Gbx2may be involved in the specific segregation of thalamic neurons, leading to partition of the thalamus into different nuclei.
Activin/Nodal signalling maintains pluripotency by controlling Nanog expression
Authors: Vallier Ludovic , Mendjan Sasha , Brown Stephanie , Chng Zhenzhi , Teo Adrian , Smithers Lucy E. , Trotter Matthew W. B. , Cho Candy H.-H. , Martinez Amelie , Rugg-Gunn Peter , Brons Gabrielle , Pedersen Roger A.
Published: March 2009

The pluripotent status of embryonic stem cells (ESCs) confers upon them the capacity to differentiate into the three primary germ layers, ectoderm,mesoderm and endoderm, from which all the cells of the adult body are derived. An understanding of the mechanisms controlling pluripotency is thus essential for driving the differentiation of human pluripotent cells into cell types useful for clinical applications. The Activin/Nodal signalling pathway is necessary to maintain pluripotency in human ESCs and in mouse epiblast stem cells (EpiSCs), but the molecular mechanisms by which it achieves this effect remain obscure. Here, we demonstrate that Activin/Nodal signalling controls expression of the key pluripotency factor Nanog in human ESCs and in mouse EpiSCs. Nanog in turn prevents neuroectoderm differentiation induced by FGF signalling and limits the transcriptional activity of the Smad2/3 cascade,blocking progression along the endoderm lineage. This negative-feedback loop imposes stasis in neuroectoderm and mesendoderm differentiation, thereby maintaining the pluripotent status of human ESCs and mouse EpiSCs.
The basis of vagal efferent control of heart rate in a neotropical fish,the pacu,Piaractus mesopotamicus
Authors: Taylor E. W. , Leite C. A. C. , Florindo L. H. , Beläo T. , Rantin F. T.
Published: March 2009

The role of the parasympathetic nervous system, operating via the vagus nerve, in determining heart rate (fH) and cardiorespiratory interactions was investigated in the neotropical fish Piaractus mesopotamicus. Motor nuclei of branches of cranial nerves VII, IX and X, supplying respiratory muscles and the heart, have an overlapping distribution in the brainstem, while the Vth motor nucleus is more rostrally located. Respiration-related efferent activity in the cardiac vagus appeared to entrain the heart to ventilation. Peripheral stimulation of the cardiac vagus with short bursts of electrical stimuli entrained the heart at a ratio of 1:1 over a range of frequencies, both below and sometimes above the intrinsic heart rate. Alternatively, at higher bursting frequencies the induced fH was slower than the applied stimulus, being recruited by a whole number fraction (1:2 to 1:6) of the stimulus frequency. These effects indicate that respiration-related changes in fH in pacu are under direct, beat-to-beat vagal control. Central burst stimulation of respiratory branches of cranial nerves VII, IX and X also entrained the heart, which implies that cardiorespiratory interactions can be generated reflexly. Central stimulation of the Vth cranial nerve was without effect on heart rate, possibly because its central projections do not overlap with cardiac vagal preganglionic neurons in the brainstem. However, bursts of activity recorded from the cardiac vagus were concurrent with bursts in this nerve, suggesting that cardiorespiratory interactions can arise within the CNS, possibly by irradiation from a central respiratory pattern generator, when respiratory drive is high.
T3 and the thyroid hormone β-receptor agonist GC-1 differentially affect metabolic capacity and oxidative damage in rat tissues
Authors: Venditti P. , Chiellini G. , Bari A. , Di Stefano L. , Zucchi R. , Columbano A. , Scanlan T. S. , Di Meo S.
Published: March 2009

We compared the changes in tissue aerobic metabolism and oxidative damage elicited by hypothyroid rat treatment with T3 and its analog GC-1. Aerobic capacities, evaluated by cytochrome oxidase activities, were increased more by T3 than by GC-1. Furthermore, the response of the tissues to T3 was similar, whereas the response to GC-1 was high in liver,low in muscle and scarce in heart. Both treatments induced increases in ADP-stimulated O2 consumption, which were consistent with those in aerobic capacities. However, unlike T3, GC-1 differentially affected pyruvate/malate- and succinate-supported respiration, suggesting that respiratory chain components do not respond as a unit to GC-1 stimulation. According to the positive relationship between electron carrier levels and rates of mitochondrial generation of oxidative species, the most extensive damage to lipids and proteins was found in T3-treated rats. Examination of antioxidant enzyme activities and scavenger levels did not clarify whether oxidative damage extent also depended on different antioxidant system effectiveness. Conversely, the analysis of parameters determining tissue susceptibility to oxidants showed that pro-oxidant capacity was lower in GC-1- than in T3-treated rats, while antioxidant capacity was similar in treatment groups. Interestingly, both agonists decreased serum cholesterol levels, but only GC-1 restored euthyroid values of heart rate and indices of tissue oxidative damage, indicating that GC-1 is able to lower cholesterolemia, bypassing detrimental effects of T3.
The learning and maintenance of local vectors in desert ant navigation
Authors: Collett Matthew , Collett Thomas S.
Published: March 2009

The desert ant Cataglyphis fortis has at least three types of navigational strategy that can guide it between its nest and a familiar food site. The initial strategy after first finding a food site is based on a path integration memory of the position of the food site with respect to the nest. A second strategy is based on visual snapshot memories of features viewed from near or on the way to the food site. A third strategy uses local vector memories of the direction and length of habitual route segments. We show here that while such local vectors encode sufficient information to guide an individual along both the direction and distance of a route segment, its acquisition and long-term maintenance requires support from the other two strategies. We trained ants along an L-shaped route, designed to show that ants can learn local vectors on the way to a food site. The sharp turn appears to present particular difficulties for the ants. When low bushes 20–30 m from the route were removed, local vectors were briefly unaffected, but then deteriorated. The vectors improved again once the missing bushes were replaced by artificial landmarks. The fragility of local vector memories may permit an ant the flexibility to adapt its route to fluctuations in the distribution of its resources.
Changes in efficiency and myosin expression in the small-muscle phenotype of mice selectively bred for high voluntary running activity
Authors: McGillivray David G. , Garland Theodore , Dlugosz Elizabeth M. , Chappell Mark A. , Syme Douglas A.
Published: March 2009

Mice from lines selectively bred for high levels of voluntary wheel running express a high incidence of a small muscle phenotype (`mini-muscles') that may confer an adaptive advantage with respect to endurance-running capacity. Plantar flexors in the mini-muscle phenotype exhibit a high capacity for aerobic activity, including altered enzyme activities, loss of expression of type IIb myosin heavy chain (MHC), increased expression of type I,IIx and IIa MHC, and mechanical performance consistent with slower, more fatigue-resistant muscles. We hypothesized that these changes may accompany enhanced efficiency of contraction, perhaps in support of the enhanced capacity for endurance running. To assess efficiency, we measured work and associated oxygen consumption from isolated soleus and medial gastrocnemius muscles from mice with mini-muscle and normal phenotypes. We also measured the MHC expression of the plantar flexor muscles to better understand the physiological basis of any differences in efficiency. The proportion of the various MHC isoforms in the soleus was shifted toward a slightly faster phenotype in the mini-muscle mice, whereas in the gastrocnemius and plantaris it was shifted toward a markedly slower phenotype,with large reductions in type IIb MHC and large increases in type I, IIa, and IIx MHC. Soleus muscles from normal and mini-muscle mice showed no statistical differences in efficiency, but medial gastrocnemius from mini-muscle mice were significantly less efficient than those from normal mice, despite the distinctly slower MHC phenotype in mini-muscle mice. Thus, based on measures of efficiency from isolated muscles under conditions near optimal for power output, the shift toward a slower phenotype in `mini' gastrocnemius muscles does not appear to confer advantages directly through increased efficiency. Rather, the slower phenotype may reduce energy used by the muscles and be permissive to enhanced running ability,perhaps by reducing reliance on anaerobic metabolism.
Geometric Identification of an Elastokinematic Model in a Car Suspension
Authors: Meissonnier J , Fauroux J-C , Gogu G , Montezin C
Published: March 2009

This paper deals with the modelling of a car suspension including rubber bushings. Significant differences are found between data from the numerical elastokinematic model and experimental results. One reason for these differences comes from geometrical shifts of bushing centres in the real suspension with respect to the numerical model. The aim of the present work is to reduce the differences by identifying the geometric parameters of the elastokinematic model. To achieve this goal, a method is proposed for computing the location and orientation of each part and joint in the assembled suspension. The first stage of the method uses measurements on separate parts to define joint location in the coordinate system local to the part. In the second stage, measurements are performed on the assembled suspension mechanism using a portable coordinate measuring machine for locating parts and joints in a global coordinate system. Based on these data and elastic joint stiffnesses, bushing deflection is computed at the static equilibrium of the vehicle and used to identify the real joint locations on parts. This identification method is tested on a pseudo-McPherson suspension and improves model behaviour during vertical wheel movement.
Study of Detracking Risks of Track Systems
Authors: Wong J Y , Huang Wei
Published: March 2009

Detracking is a complex phenomenon. It may occur to a tracked vehicle during turning manoeuvres, moving over obstacles, or operating on uneven surfaces. A fundamental study of detracking is lacking. As a first step in the study of this complex process, this paper focuses on the analysis of the necessary condition for detracking under steady state operations, such as in a steady turning manoeuvre on deformable terrain. The necessary condition for detracking is that the slacks in certain track segments are such that they enable the track to override the outside diameter of the sprocket or idler. Based on the analysis, detracking risk indicators have been developed for evaluating and comparing the risk for disengagement of track drive lugs or track guides from the sprocket or idler. These indicators have been applied to the evaluation of detracking risks of a segmented metal track system commonly used in current fighting vehicles and a rubber-band track system proposed for future combat vehicles. It has been found that track system configuration (including the location of the sprocket and idler), initial track tension, and braking or driving torque applied to the sprocket have significant influences on detracking. The track longitudinal stiffness and suspension stiffness have relatively insignificant effects on detracking.
Automotive Damper Model for Use in Multi-Body Dynamic Simulations
Authors: Allen P J , Hameed A , Goyder H
Published: March 2009

The subject of this study is the Warrior armoured personnel carrier rotary suspension damper. This is a simple passive device where energy is dissipated by the resistance to oil flowing through an orifice. In principle the mechanism of this damper is simple, but the requirement for a compact unit that can withstand high dynamic loads means that the design is complex in detail. Because of this complexity it is possible for air to remain in the oil chambers if care is not taken when priming the device. Measurements show that the nonlinear response of the damper is primarily due to turbulent oil flow through the orifice and the compression of entrapped air, but that friction is negligible. The most appropriate model for this system in multi-body dynamic simulations is to represent the damper as two discrete components: a non-linear dashpot (representing oil flow through the orifice) and a non-linear spring (representing the compression of entrapped air). From measurements, a splined curve is determined that describes the non-linear torque-velocity relationship due to orifice flow characteristics. By applying Henry's law and assuming isothermal compression, a function is derived that describes the compression of air in oil. This modelling method closely reproduces the measured response of the damper.
Rational Design and Functions of Electron Donor–Acceptor Dyads with Much Longer Charge-Separated Lifetimes than Natural Photosynthetic Reaction Centers
Authors: Ohkubo Kei , Fukuzumi Shunichi
Published: March 2009

The natural photosynthetic reaction center utilizes sequential multi-step electron transfer from the excited chromophore to the terminal electron acceptor via electron mediators to attain a long lifetime of the final charge-separated (CS) state. Contrary to natural systems, simple electron donor–acceptor dyads have been developed to attain a long-lived CS state, where the donor and acceptor molecules are linked with a short spacer. In the case of a directly linked zinc chlorin–fullerene dyad, the lifetime of the CS state at −150 °C is as long as 120 s. This value is the longest CS lifetime ever reported for porphyrin-based donor–acceptor linked systems. The use of 9-mesityl-10-methylacridinium ion, which has an extremely long-lived CS state, enables the construction of highly efficient photocatalytic systems such as oxygenation of aromatic compounds and hydrogen evolution.
Effects of Metal Doping on the Spin-Crossover Properties of an Iron(II) Complex with Extended π-Conjugated Schiff-Base Ligand Having an N4O2 Donor Set
Authors: Yu Zhong , Kuroda-Sowa Takayoshi , Kume Hiroaki , Okubo Takashi , Maekawa Masahiko , Munakata Megumu
Published: March 2009

The spin-crossover (SCO) complex [Fe(qnal)2]·CH2Cl2 (1), (Hqnal: N-(8′-quinolyl)-2-hydroxy-1-naphthaldimine) with an N4O2 donor set, has been synthesized and characterized. Investigation of magnetic properties shows that the complex exhibits an abrupt and complete spin transition with a 5 K wide thermal hysteresis loop. The X-ray diffraction analysis of complex 1 reveals that the molecules are connected into a quasi one-dimensional chain through extended π–π interactions between aromatic rings of ligands. The effects of metal doping on SCO properties have been investigated in the mixed-metal system [Fe1−xMx(qnal)2]·CH2Cl2 (M = zinc(II) and nickel(II)). The results reveal that metal doping increases the gradual character of spin transition, and no marked differences found between zinc and nickel doping, which suggest the dominant effect of the doping-degree (concentration) rather than metal species on cooperativity. However, the metal doping shows different effects on critical temperature (T1/2), where a more pronounced descending of T1/2 is observed in response to increased Zn-doping than in Ni-doping, indicating the noticeable consequence of internal pressure due to the different radii of doping metal ions.
Stereoselective Syntheses of (E)-α,β-Didehydroamino Acid and Peptide Containing Its Residue Utilizing Oxazolidinone Derivative
Authors: Kometani Miki , Ihara Kohki , Kimura Rumi , Kinoshita Hideki
Published: March 2009

Reaction of methyl N-Boc-N-phenoxycarbonylglycinate with various aldehydes afforded the corresponding cis-4,5-oxazolidinone derivatives, which were effectively converted to (E)-α,β-didehydroamino acids by means of a base. Furthermore, N-deprotection of the oxazolidinone derivatives and subsequent coupling reaction with Boc-amino acid furnished the corresponding dipeptides, which were transformed to dipeptide containing α,β-didehydroamino acid with high E selectivity.
Palladium-Catalyzed 1-Methylene-2-propenylation Reactions of Aryl Bromides with 3,4-Alkadien-1-ols via Carbon–Carbon Bond Cleavage for the Synthesis of 2-Aryl-1,3-butadiene Derivatives
Authors: Imoto Junichi , Hayashi Sayuri , Hirano Koji , Yorimitsu Hideki , Oshima Koichiro
Published: March 2009

A method for the synthesis of 2-aryl-1,3-alkadienes has been developed. Treatment of aryl bromides with 3,4-alkadien-1-ols in the presence of a palladium catalyst results in 1-methylene-2-propenyl group transfer to aryl bromides. Taking advantage of palladium-mediated retro-allylation as an sp3C–sp3C bond cleavage reaction, one can regard 3,4-alkadien-1-ols as 1-methylene-2-propenyl metal equivalents that are easy to prepare and are not sensitive to air and moisture. In the event that the Diels–Alder dimerization of the product during the 1-methylene-2-propenylation reaction is problematic, addition of N-methylpyrrole to the reaction mixture can efficiently suppress the dimerization. The reactions of aryl bromides with 2-substituted 3,4-alkadien-1-ols yield the corresponding (E)-2-aryl-1,3-alkadienes stereoselectively.
Synthesis of 3,5-Dibromopyridines with –NH(CH2)mSO3Na (m = 3 and 4) Groups at the 2-Position of Pyridine and Use of the Dibromo Compound for Polymer Synthesis
Authors: Shiramizu Kohei , Harada Yosuke , Yamamoto Takakazu
Published: March 2009

Reactions of 2-amino-3,5-dibromopyridine with sultones gave 3,5-dibromopyridines with –NH(CH2)mSO3Na (m = 3 and 4) groups at the 2-position of pyridine. The obtained compound served as a starting material for polypyridine with –NH(CH2)mSO3H side chains.
Effects of environmental enrichment on the amyotrophic lateral sclerosis mouse model
Authors: Sorrells A D , Corcoran-Gomez K , Eckert K A , Fahey A G , Hoots B L , Charleston L B , Charleston J S , Roberts C R , Markowitz H
Published: March 2009

The manner in which an animal's environment is furnished may have significant implications for animal welfare as well as research outcomes. We evaluated four different housing conditions to determine the effects of what has been considered standard rodent enrichment and the exercise opportunities those environments allow on disease progression in the amyotrophic lateral sclerosis mouse model. Forty-eight copper/zinc superoxide dismutase mice (strain: B6SJL-TgN [SOD1-G931]1Gur) (SOD1) and 48 control (C) (strain: B6SJL-TgN[SOD1]2Gur) male mice were randomly assigned to four different conditions where 12 SOD1 and 12 C animals were allotted to each condition ( n = 96). Conditions tested the effects of standard housing, a forced exercise regime, access to a mouse house and opportunity for ad libitum exercise on a running wheel. In addition to the daily all-occurrence behavioural sampling, mice were weighed and tested twice per week on gait and Rotor-Rod™ performance until the mice reached the age of 150 days (C) or met the criteria for our humane endpoint (SOD1). The SOD1 mice exposed to the forced exercise regime and wheel access did better in average lifespan and Rotor-Rod™ performance, than SOD1 mice exposed to the standard cage and mouse house conditions. In SOD1 mice, stride length remained longest throughout the progression of the disease in mice exposed to the forced exercise regime compared with other SOD1 conditions. Within the control group, mice in the standard cage and forced exercise regime conditions performed significantly less than the mice with the mouse house and wheels on the Rotor-Rod™. Alpha motor neuron counts were highest in mice with wheels and in mice exposed to forced exercise regime in both mouse strains. All SOD1 mice had significantly lower alpha neuron counts than controls ( P < 0.05). These data show that different enrichment strategies affect behaviour and disease progression in a transgenic mouse model, and may have implications for the effects of these strategies on experimental outcomes.
The effect of defect localization on spontaneous repair of osteochondral defects in a Göttingen minipig model: a retrospective analysis of the medial patellar groove versus the medial femoral condyle
Authors: Jung Martin , Breusch Steffen , Daecke Wolfgang , Gotterbarm Tobias
Published: March 2009

Various animal models for experimental osteochondral defect healing have been used in orthopaedic research. Two main defect locations were chosen: the patellar groove or the central part of the medial femoral condyles (MFC). To date, it is not clear whether both locations display similar patterns in critical size osteochondral defect healing. We retrospectively analysed both locations in our minipig model hypothesizing that they show similar healing pattern. Thirty-five defects were analysed after three or 12 months. Osteochondral defects were 10 mm deep and 6.3 mm (MFC, n = 19) in diameter or 8 mm and 5.4 mm, respectively (trochlear groove [TG], n = 16). Semi-quantitative histological scoring and histomorphological evaluation were carried out. Both defect locations showed fillings of fibrous and fibrocartilage-like repair tissue. The osseous defect was closed by endochondral bone formation in the MFC. Semi-quantitative scoring did not show differences, whereas qualitative histomorphological analysis more frequently showed cartilaginous repair tissue in MFC defects. There was more frequent subchondral bone cyst formation in MFC location ( P = 0.05), TG defects resulted in lower postoperative pain. Both defect localizations are suitable for studies on osteochondral healing. Since regenerating with less hyaline-like repair tissue and less subchondral cyst formation, TG is more favourable for experimental osteochondral defect healing in this model.