bluuebunny/crossref_metadata_2025 huggingface dataset:
Aberrant immunophenotype of blasts in myelodysplastic syndromes is a clinically relevant biomarker in predicting response to growth factor treatment
Authors: Westers Theresia M. , Alhan Canan , Chamuleau Martine E. D. , van der Vorst Maurice J. D. L. , Eeltink Corien , Ossenkoppele Gert J. , van de Loosdrecht Arjan A.
Published: December 2009

Myelodysplastic syndromes (MDS) are a group of clonal disorders of the bone marrow characterized by peripheral cytopenias. Standard treatment in low- and intermediate-I–risk MDS is supportive therapy consisting of regular transfusions and growth factors, that is, erythropoietin (Epo) and granulocyte-colony-stimulating factor (G-CSF). Because flow cytometric analysis of MDS bone marrow samples can identify clinically relevant subgroups regarding transfusion dependency and disease progression, we addressed the question whether flow cytometry (FCM) was instrumental in predicting response. In 46 patients with low- and intermediate-I–risk MDS that were treated with Epo/G-CSF, low Epo level and low transfusion need were associated with response to Epo/G-CSF. Interestingly, aberrant phenotype of myeloblasts identified nonresponders among patients with the greatest response probability according to the predictive model of Hellström-Lindberg et al. Moreover, aberrant FCM of myeloblasts acted as a significant biomarker for treatment failure in multivariate analysis. A new predictive model based on the basis FCM combined with previously validated Epo levels is proposed defining 3 subgroups with 94%, 17%, and 11% response probability. In conclusion, FCM may add significantly to well-known predictive parameters in selecting MDS patients eligible for Epo/G-CSF treatment. This is of relevance regarding prevention of treatment failure.
Molecular evolution of the pDo500 satellite DNA family in Dolichopoda cave crickets (Rhaphidophoridae)
Authors: Martinsen Lene , Venanzetti Federica , Johnsen Arild , Sbordoni Valerio , Bachmann Lutz
Published: December 2009

Background

Non-coding satellite DNA (satDNA) usually has a high turn-over rate frequently leading to species specific patterns. However, some satDNA families evolve more slowly and can be found in several related species. Here, we analyzed the mode of evolution of thepDo500satDNA family ofDolichopodacave crickets. In addition, we discuss the potential of slowly evolving satDNAs as phylogenetic markers.

Results

We sequenced 199 genomic or PCR amplified satDNA repeats of thepDo500family from 12Dolichopodaspecies. For the 38 populations under study, 39pDo500consensus sequences were deduced. Phylogenetic analyses using Bayesian, Maximum Parsimony, and Maximum Likelihood approaches yielded largely congruent tree topologies. The vast majority ofpDo500sequences grouped according to species designation. Scatter plots and statistical tests revealed a significant correlation between genetic distances for satDNA and mitochondrial DNA. Sliding window analyses showed species specific patterns of variable and conserved regions. The evolutionary rate of thepDo500satDNA was estimated to be 1.63-1.78% per lineage per million years.

Conclusions

ThepDo500satDNA evolves gradually at a rate that is only slightly faster than previously published rates of insect mitochondrial COI sequences. ThepDo500phylogeny was basically congruent with the previously published mtDNA phylogenies. Accordingly, the slowly evolvingpDo500satDNA family is indeed informative as a phylogenetic marker.
Identification and dynamics of a beneficial mutation in a long-term evolution experiment with Escherichia coli
Authors: Stanek Mark T , Cooper Tim F , Lenski Richard E
Published: December 2009

Background

Twelve populations ofE. coliwere serially propagated for 20,000 generations in a glucose-supplemented minimal medium in order to study the dynamics of evolution. We sought to find and characterize one of the beneficial mutations responsible for the adaptation and other phenotypic changes, including increased cell size, in one of these populations.

Results

We used transposon-tagging followed by P1-transduction into the ancestor, screening for increased cell size and fitness, co-transduction analysis, and DNA sequencing. We identified a 1-bp insertion in the BoxG1 region located upstream ofglmUS, an operon involved in cell-wall biosynthesis. When transduced into the ancestor, this mutation increased competitive fitness by about 5%. This mutation spread through its population of origin between 500 and 1500 generations. Mutations in this region were not found in the other 11 evolving populations, even after 20,000 generations.

Conclusion

The 1-bp insertion in the BoxG1 region nearglmUSwas demonstrably beneficial in the environment in which it arose. The absence of similar mutations in the other evolved populations suggests that they substituted other mutations that rendered this particular mutation unimportant. These results show the unpredictability of adaptive evolution, whereas parallel substitutions at other loci in these same populations reveal the predictability.
Acute Myeloid Leukemia With Biallelic CEBPA Gene Mutations and Normal Karyotype Represents a Distinct Genetic Entity Associated With a Favorable Clinical Outcome
Authors: Dufour Annika , Schneider Friederike , Metzeler Klaus H. , Hoster Eva , Schneider Stephanie , Zellmeier Evelyn , Benthaus Tobias , Sauerland Maria-Cristina , Berdel Wolfgang E. , Büchner Thomas , Wörmann Bernhard , Braess Jan , Hiddemann Wolfgang , Bohlander Stefan K. , Spiekermann Karsten
Published: December 2009

Purpose

CEBPA mutations are found as either biallelic (biCEBPA) or monoallelic (moCEBPA). We set out to explore whether the kind of CEBPA mutation is of prognostic relevance in cytogenetically normal (CN) acute myeloid leukemia (AML).

Patients and Methods

Four hundred sixty-seven homogeneously treated patients with CN-AML were subdivided into moCEBPA, biCEBPA, and wild-type (wt) CEBPA patients. The subgroups were analyzed for clinical parameters and for additional mutations in the NPM1, FLT3, and MLL genes. Furthermore, we obtained gene expression profiles using oligonucleotide microarrays.

Results

Only patients with biCEBPA had an improved median overall survival when compared with patients with wtCEBPA (not reached v 20.4 months, respectively; P = .018), whereas patients with moCEBPA (20.9 months) and wtCEBPA had a similar outcome (P = .506). Multivariable analysis confirmed biCEBPA, but not moCEBPA, mutations as an independent favorable prognostic factor. Interestingly, biCEBPA mutations, compared with wtCEBPA, were never associated with mutated NPM1 (0% v 43%, respectively; P < .001) and rarely associated with FLT3 internal tandem duplication (ITD; 5% v 23%, respectively; P = .059), whereas patients with moCEBPA had a similar frequency of mutated NPM1 and a significantly higher association with FLT3-ITD compared with patients with wtCEBPA (44% v 23%, respectively; P = .037). Furthermore, patients with biCEBPA showed a homogeneous gene expression profile that was characterized by downregulation of HOX genes, whereas patients with moCEBPA showed greater heterogeneity in their gene expression profiles.

Conclusion

Biallelic disruption of the N and C terminus of CEBPA is required for the favorable clinical outcome of CEBPA-mutated patients and represents a distinct molecular subtype of CN-AML with a different frequency of associated gene mutations. These findings are of great significance for risk-adapted therapeutic strategies in AML.
Attempts to Optimize Induction and Consolidation Treatment in Acute Myeloid Leukemia: Results of the MRC AML12 Trial
Authors: Burnett Alan K. , Hills Robert K. , Milligan Donald W. , Goldstone Anthony H. , Prentice Archibald G. , McMullin Mary-Frances , Duncombe Andrew , Gibson Brenda , Wheatley Keith
Published: December 2009

Purpose

To optimize treatment for younger patients with acute myeloid leukemia and high-risk myelodysplastic syndrome by comparing induction options and the number of consolidation courses and whether consolidation should include transplantation.

Patients and Methods

We randomly assigned 1,658 patients younger than age 60 years to receive mitoxantrone/cytarabine/etoposide versus cytarabine/daunorubicin/etoposide and subsequently 1,193 patients to daunorubicin/cytarabine/thioguanine (DAT) where the cytarabine dose was standard (S-DAT) versus double the standard dose (H-DAT). Patients in this randomization were randomly assigned to all-trans-retinoic acid or not. In consolidation, 992 patients were randomly assigned between a total of four courses versus five courses, and 324 patients who were not good risk were randomly assigned to transplantation or chemotherapy as the final course.

Results

Complete remission (CR) was achieved in 74% of patients and CR without recovery was achieved in an additional 11%; overall survival (OS) at 8 years was 38%. No differences in CR, relapse-free survival, relapse, or OS were seen between any of the induction randomizations except for a reduction in relapse risk (RR) on the mitoxantrone arm, which was offset by increased myelosuppression and deaths in CR. The addition of a fifth course did not improve OS and may be detrimental in older patients. Although transplantation reduced RR, it did not improve OS for the intermediate-risk group but was probably of benefit in high-risk patients.

Conclusion

Several chemotherapy schedules achieved similar remission rates and OS. Four courses of chemotherapy are adequate, but the addition of transplantation as a final course does not improve OS. New agents are required to enhance conventional chemotherapy.
DNA Methylation Predicts Survival and Response to Therapy in Patients With Myelodysplastic Syndromes
Authors: Shen Lanlan , Kantarjian Hagop , Guo Yi , Lin E , Shan Jianqin , Huang Xuelin , Berry Donald , Ahmed Saira , Zhu Wei , Pierce Sherry , Kondo Yutaka , Oki Yasuhiro , Jelinek Jaroslav , Saba Hussain , Estey Eli , Issa Jean-Pierre J.
Published: December 2009

Purpose

The current classification systems of myelodysplastic syndromes (MDS), including the International Prognostic Scoring System (IPSS), do not fully reflect the molecular heterogeneity of the disease. Molecular characterization may predict clinical outcome and help stratify patients for targeted therapies. Epigenetic therapy using decitabine, a DNA hypomethylating agent, is clinically effective for the treatment of MDS. Therefore, we investigated the association between DNA methylation and clinical outcome in MDS.

Patients and Methods

We screened 24 patients with MDS for promoter CpG island methylation of 24 genes and identified aberrant hypermethylation at 10 genes. We then performed quantitative methylation analyses by bisulfite pyrosequencing of the identified genes in 317 patient samples from three independent studies and assessed relations between methylation and clinical outcome.

Results

In an initial training cohort of 89 patients with MDS, methylation frequencies of individual genes ranged from 7% to 70% and were highly concordant. Therefore, we defined a methylation z score based on all genes for each patient. We found that patients with higher levels of methylation, compared with patients with lower levels, had a shorter median overall survival (12.3 v 17.5 months, respectively; P = .04) and shorter median progression-free survival (6.4 v 14.9 months, respectively; P = .009). This methylation prognostic model was independent of age, sex, and IPSS group. Applied to two validation cohorts (228 patients), this model was confirmed as an independent prognostic predictor for survival. Although methylation at baseline did not correlate with clinical response to decitabine, we observed a significant correlation between reduced methylation over time and clinical responses.

Conclusion

DNA methylation predicts overall and progression-free survival in MDS.
Does Childhood Cancer Affect Parental Divorce Rates? A Population-Based Study
Authors: Syse Astri , Loge Jon H. , Lyngstad Torkild H.
Published: December 2009

Purpose

Cancer in children may profoundly affect parents' personal relationships in terms of psychological stress and an increased care burden. This could hypothetically elevate divorce rates. Few studies on divorce occurrence exist, so the effect of childhood cancers on parental divorce rates was explored.

Patients and Methods

Data on the entire Norwegian married population, age 17 to 69 years, with children age 0 to 20 years in 1974 to 2001 (N = 977,928 couples) were retrieved from the Cancer Registry, the Central Population Register, the Directorate of Taxes, and population censuses. Divorce rates for 4,590 couples who were parenting a child with cancer were compared with those of otherwise similar couples by discrete-time hazard regression models.

Results

Cancer in a child was not associated with an increased risk of parental divorce overall. An increased divorce rate was observed with Wilms tumor (odds ratio [OR], 1.52) but not with any of the other common childhood cancers. The child's age at diagnosis, time elapsed from diagnosis, and death from cancer did not influence divorce rates significantly. Increased divorce rates were observed for couples in whom the mothers had an education greater than high school level (OR, 1.16); the risk was particularly high shortly after diagnosis, for CNS cancers and Wilms tumors, for couples with children 0 to 9 years of age at diagnosis, and after a child's death.

Conclusion

This large, registry-based study shows that cancer in children is not associated with an increased parental divorce rate, except with Wilms tumors. Couples in whom the wife is highly educated appear to face increased divorce rates after a child's cancer, and this may warrant additional study.
DiSUMO-like DSUL is required for nuclei positioning, cell specification and viability during female gametophyte maturation in maize
Authors: Srilunchang Kanok-orn , Krohn Nádia Graciele , Dresselhaus Thomas
Published: December 2009

Reversible post-translational modification of numerous proteins by small ubiquitin-related modifiers (SUMOs) represents a major regulatory process in various eukaryotic cellular and developmental processes. To study the role of sumoylation during female gametophyte (FG) development in maize, we identified Zea mays genes encoding SUMO (ZmSUMO1a and ZmSUMO1b) and a diSUMO-like protein called ZmDSUL that contains two head-to-tail SUMO-like domains. Whereas ZmSUMO1a and ZmSUMO1b are almost ubiquitously expressed, ZmDSUL transcripts were detected exclusively in the egg apparatus and zygote. ZmDSUL was selected for detailed studies. ZmDSUL is processed close to the C-terminus, generating a dimeric protein that is similar to animal FAT10 and ISG15, which contain two ubiquitin-like domains. Whereas GFP fused to the ZmDSUL N-terminus was located in the cytoplasm and predominately in the nucleoplasm of some transiently transformed maize suspension cells, C-terminal GFP fusions exclusively accumulated at the nuclear surface. GFP or ZmDSUL-GFP under control of the ZmDSUL promoter first displayed GFP signals in the micropylar-most position of the FG at stage 5/6, when migration of polar nuclei and cellularization occurs. Mature FGs displayed GFP signals exclusively in the egg cell, but the strongest signals were observed shortly after fertilization and disappeared during the first asymmetric zygotic division. RNAi silencing of ZmDSUL showed that it is required for FG viability. Moreover, nuclei segregation and positioning defects occurred at stage FG 5 after mitotic nuclear divisions were completed. In summary, we report a diSUMO-like protein that appears to be essential for nuclei segregation and positioning, the prerequisite for cell specification during FG maturation.
Non-cell-autonomous retinoid signaling is crucial for renal development
Authors: Rosselot Carolina , Spraggon Lee , Chia Ian , Batourina Ekatherina , Riccio Paul , Lu Benson , Niederreither Karen , Dolle Pascal , Duester Gregg , Chambon Pierre , Costantini Frank , Gilbert Thierry , Molotkov Andrei , Mendelsohn Cathy
Published: December 2009

In humans and mice, mutations in the Ret gene result in Hirschsprung's disease and renal defects. In the embryonic kidney, binding of Ret to its ligand, Gdnf, induces a program of epithelial cell remodeling that controls primary branch formation and branching morphogenesis within the kidney. Our previous studies showed that transcription factors belonging to the retinoic acid (RA) receptor family are crucial for controlling Ret expression in the ureteric bud; however, the mechanism by which retinoid-signaling acts has remained unclear. In the current study, we show that expression of a dominant-negative RA receptor in mouse ureteric bud cells abolishes Ret expression and Ret-dependent functions including ureteric bud formation and branching morphogenesis, indicating that RA-receptor signaling in ureteric bud cells is crucial for renal development. Conversely, we find that RA-receptor signaling in ureteric bud cells depends mainly on RA generated in nearby stromal cells by retinaldehyde dehydrogenase 2, an enzyme required for most fetal RA synthesis. Together, these studies suggest that renal development depends on paracrine RA signaling between stromal mesenchyme and ureteric bud cells that regulates Ret expression both during ureteric bud formation and within the developing collecting duct system.
FGF signaling directs a center-to-pole expansion of tubulogenesis in mouse testis differentiation
Authors: Hiramatsu Ryuji , Harikae Kyoko , Tsunekawa Naoki , Kurohmaru Masamichi , Matsuo Isao , Kanai Yoshiakira
Published: December 2009

In mouse embryogenesis, Sry is transiently activated in a center-to-pole wavelike manner along the anteroposterior (AP) axis of developing XY gonads. However, the mechanism and significance of the center-to-pole expansion of testis initiation pathways downstream of Sry expression remain unclear. Here we demonstrate that FGF9 can act as a diffusible conductor for a poleward expansion of tubulogenic programs at early phases of testis differentiation. In XY genital ridge cultures of anterior, middle and posterior segments at 11.0-11.25 days post-coitum, male-specific activation of Sry and its target gene, Sox9, was still observed in both anterior and posterior pole segments despite their isolation from the central domain. However, high-level Sox9 expression was not maintained, resulting in the failure of testis cord organization in most pole segments. A reconstruction experiment using ROSA:lacZ middle segments showed rescue of the tubulogenic defect in the poles without any appreciable contribution of lacZ-positive gonadal parenchyma cells. A partition culture assay also showed a possible contribution of soluble/diffusible factors secreted from the gonadal center domain to proper tubulogenesis in the poles. Among various signaling factors, Fgf9 expression was significantly lower in both anterior and posterior pole segments than in the central domain. The supportive role of the central domain could be substituted by exogenous FGF9 supply, whereas reduction of Wnt4 activity did not rescue the tubulogenesis defect in the pole segments. These observations imply that center-to-pole FGF9 diffusion directs a poleward expansion of testiculogenic programs along the AP axis of developing XY gonads.
Tgif1 and Tgif2 regulate Nodal signaling and are required for gastrulation
Authors: Powers Shannon E. , Taniguchi Kenichiro , Yen Weiwei , Melhuish Tiffany A. , Shen Jun , Walsh Christopher A. , Sutherland Ann E. , Wotton David
Published: December 2009

Tgif1 and Tgif2 are transcriptional co-repressors that limit the response to TGFβ signaling and play a role in regulating retinoic-acid-mediated gene expression. Mutations in human TGIF1 are associated with holoprosencephaly, but it is unclear whether this is a result of deregulation of TGFβ/Nodal signaling, or of effects on other pathways. Surprisingly, mutation of Tgif1 in mice results in only relatively mild developmental phenotypes in most strain backgrounds. Here, we show that loss-of-function mutations in both Tgif1 and Tgif2 result in a failure of gastrulation. By conditionally deleting Tgif1 in the epiblast, we demonstrate that a single wild-type allele of Tgif1 in the extra-embryonic tissue allows the double null embryos to gastrulate and begin organogenesis, suggesting that extra-embryonic Tgif function is required for patterning the epiblast. Genetically reducing the dose of Nodal in embryos lacking all Tgif function results in partial rescue of the gastrulation defects. Conditional double null embryos have defects in left-right asymmetry, which are also alleviated by reducing the dose of Nodal. Together, these data show that Tgif function is required for gastrulation, and provide the first clear evidence that Tgifs limit the transcriptional response to Nodal signaling during early embryogenesis.
Role of Fgf8 signalling in the specification of rostral Cajal-Retzius cells
Authors: Zimmer Céline , Lee Jun , Griveau Amélie , Arber Silvia , Pierani Alessandra , Garel Sonia , Guillemot François
Published: December 2009

Cajal-Retzius (CR) cells play a key role in the formation of the cerebral cortex. These pioneer neurons are distributed throughout the cortical marginal zone in distinct graded distributions. Fate mapping and cell lineage tracing studies have recently shown that CR cells arise from restricted domains of the pallial ventricular zone, which are associated with signalling centres involved in the early regionalisation of the telencephalic vesicles. In this study, we identified a subpopulation of CR cells in the rostral telencephalon that expresses Er81, a downstream target of Fgf8 signalling. We investigated the role of the rostral telencephalic patterning centre, which secretes FGF molecules, in the specification of these cells. Using pharmacological inhibitors and genetic inactivation of Fgf8, we showed that production of Fgf8 by the rostral telencephalic signalling centre is required for the specification of the Er81+ CR cell population. Moreover, the analysis of Fgf8 gain-of-function in cultivated mouse embryos and of Emx2 and Gli3 mutant embryos revealed that ectopic Fgf8 signalling promotes the generation of CR cells with a rostral phenotype from the dorsal pallium. These data showed that Fgf8 signalling is both required and sufficient to induce rostral CR cells. Together, our results shed light on the mechanisms specifying rostral CR cells and further emphasise the crucial role of telencephalic signalling centres in the generation of distinct CR cell populations.
Recipient Toll-like receptors contribute to chronic graft dysfunction by both MyD88- and TRIF-dependent signaling
Authors: Wang Shijun , Schmaderer Christoph , Kiss Eva , Schmidt Claudia , Bonrouhi Mahnaz , Porubsky Stefan , Gretz Norbert , Schaefer Liliana , Kirschning Carsten J. , Popovic Zoran V. , Gröne Hermann-Josef
Published: December 2009

Toll-like receptors (TLRs) recognize specific molecular patterns derived from microbial components (exogenous ligands) or stressed cells (endogenous ligands). Stimulation of these receptors leads to a pronounced inflammatory response in a variety of acute animal models. Chronic allograft dysfunction (CAD) was regarded as a candidate disease to test whether TLRs influence chronic fibrosing inflammation. Potential endogenous renal TLR ligands, specifically for TLR2 and TLR4, have now been detected by a significant upregulation of glucose regulated protein (GRP)-94, fibrinogen, heat shock protein (HSP)-60, HSP-70, biglycan (Bgn) and high-mobility group box chromosomal protein 1 (HMGB1) in the acute and chronic transplant setting. In a genetic approach to define the contribution of TLR2 and TLR4, and their adaptor proteins MyD88 and TRIF [Toll/interleukin (IL)-1 receptor domain-containing adaptor-protein inducing interferon β], to CAD, kidney transplantation of TLR wild-type grafts to recipients who were deficient in TLR2, TLR4, TLR2/4, MyD88 and TRIF was performed. TLR and adaptor protein deficiencies significantly improved the excretory function of chronic kidney grafts by between 65% and 290%, and histopathologic signs of chronic allograft damage were significantly ameliorated. T cells, dendritic cells (DCs) and foremost macrophages were reduced in grafts by up to 4.5-fold. The intragraft concentrations of IL-6, IL-10, monocyte chemotactic protein-1 (MCP-1) and IL-12p70 were significantly lower. TLR-, MyD88- and TRIF-deficient recipients showed a significant reduction in fibrosis. α-smooth muscle actin (α-SMA)-positive cells were decreased by up to ninefold, and collagen I and III were reduced by up to twofold. These findings highlight the functional relevance of TLRs and their two major signaling pathways in graft-infiltrating mononuclear cells in the pathophysiology of CAD. A TLR signaling blockade may be a therapeutic option for the prevention of CAD.
Proteomic and physiological responses of leopard sharks (Triakis semifasciata) to salinity change
Authors: Dowd W. W. , Harris B. N. , Cech J. J. , Kültz D.
Published: December 2009

Partially euryhaline elasmobranchs may tolerate physiologically challenging, variable salinity conditions in estuaries as a trade-off to reduce predation risk or to gain access to abundant food resources. To further understand these trade-offs and to evaluate the underlying mechanisms, we examined the responses of juvenile leopard sharks to salinity changes using a suite of measurements at multiple organizational levels: gill and rectal gland proteomes (using 2-D gel electrophoresis and tandem mass spectrometry), tissue biochemistry (Na+/K+-ATPase, caspase 3/7 and chymotrypsin-like proteasome activities), organismal physiology (hematology, plasma composition, muscle moisture) and individual behavior. Our proteomics results reveal coordinated molecular responses to low salinity – several of which are common to both rectal gland and gill – including changes in amino acid and inositol (i.e. osmolyte) metabolism, energy metabolism and proteins related to transcription, translation and protein degradation. Overall, leopard sharks employ a strategy of maintaining plasma urea, ion concentrations and Na+/K+-ATPase activities in the short-term, possibly because they rarely spend extended periods in low salinity conditions in the wild, but the sharks osmoconform to the surrounding conditions by 3 weeks. We found no evidence of apoptosis at the time points tested, while both tissues exhibited proteomic changes related to the cytoskeleton, suggesting that leopard sharks remodel existing osmoregulatory epithelial cells and activate physiological acclimatory responses to solve the problems posed by low salinity exposure. The behavioral measurements reveal increased activity in the lowest salinity in the short-term, while activity decreased in the lowest salinity in the long-term. Our data suggest that physiological/behavioral trade-offs are involved in using estuarine habitats, and pathway modeling implicates tumor necrosis factor α (TNFα) as a key node of the elasmobranch hyposmotic response network.
The influence of strain and activation on the locomotor function of rat ankle extensor muscles
Authors: Hodson-Tole E. F. , Wakeling J. M.
Published: December 2009

The ankle extensor muscles of the rat have different mechanical and physiological properties, providing a means of studying how changes in locomotor demands influence muscle fascicle behaviour, force and mechanical power output in different populations of muscle fibre types. Muscle fascicle strain, strain rate and activation patterns in the soleus, plantaris and medial gastrocnemius muscles of the rat were quantified from sonomicrometric and myoelectric data, collected during treadmill locomotion under nine velocity/incline conditions. Significant differences in peak-to-peak muscle fascicle strains and strain rates were identified between the three muscles (P<0.001, all cases), with much smaller strains (<0.1) and strain rates (<0.5 s−1) occurring in soleus and plantaris compared with medial gastrocnemius (>0.2 and >1.0 s−1, respectively). The proportion of stride duration that each muscle was active (duty cycle) differed between locomotor conditions as did the timing of the activation and deactivation phases. A simple Hill-based muscle model was used to determine the influence of muscle activation relative to maximum fascicle strain and duty cycle on total force production and mechanical power output, from a slow and a fast muscle fibre, simulated through two peak-to-peak strain cycles (0.1 and 0.3). The predictions of the model did not complement conclusions that may be drawn from the observation of myoelectric timing and fascicle strain trajectories in each of the muscles. The model predicted that changes in mechanical power output were more sensitive to changes in activation parameters than to changes in strain trajectories, with subtle changes in activation phase and duty cycle significantly affecting predicted mechanical power output.
Predator detection enables juvenileLymnaeato form long-term memory
Authors: Orr M. V. , Hittel K. , Lukowiak K.
Published: December 2009

Learning and memory provide the flexibility an organism requires to respond to changing social and ecological conditions. Juvenile Lymnaea have previously been shown to have a diminished capacity to form long-term memory (LTM) following operant conditioning of aerial respiratory behavior. Juvenile Lymnaea, however, can form LTM following classical conditioning of appetitive behaviors. Here, we demonstrate that laboratory-reared juvenile Lymnaea have the ability to detect the presence of a sympatric predator (i.e. crayfish) and respond to the predator by altering their aerial respiratory behavior. In addition to increasing their total breathing time, predator detection confers on juvenile Lymnaea an enhanced capability to form LTM following operant conditioning of aerial respiratory behavior. That is, these juveniles now have the ability to form long-lasting memory. These data support the hypothesis that biologically relevant levels of stress associated with predator detection induce behavioral phenotypic alterations (i.e. enhanced LTM formation) in juveniles, which may increase their fitness. These data also support the notion that learning and memory formation in conjunction with predator detection is a form of inducible defense.
Dietary lipid levels have a remarkable impact on the expression of growth-related genes in Senegalese sole (Solea senegalensis Kaup)
Authors: Campos C. , Valente L. M. P. , Borges P. , Bizuayehu T. , Fernandes J. M. O.
Published: December 2009

In Senegalese sole (Solea senegalensis Kaup), growth is negatively correlated to dietary lipid levels. To understand the molecular basis of this effect a molecular toolbox of 12 genes, including fgf6, fst, mstn1, myf5, mrf4, myod1, myod2, myog, myHC, mylc2, igf1r and insr, was developed. The expression profiles of these genes were investigated in white muscle and liver of fish fed with three dietary lipid levels (4%, 12% and 20%). The expression of igf-I and igf-II was also examined. MRFs and myosins were only expressed in the muscle and, except for myf5, the general trend was a decrease in expression with an increase in dietary lipids. Fgf6 was identified for the first time in liver and its expression augmented in hepatic tissues with increasing dietary lipid levels. A similar tendency was observed for mstn1 and igf-I. The opposite was observed for igf1r expression in muscle and liver. Myog, mrf4, mylc2 and igf1r were highly correlated with growth and nutrient utilisation indices. In addition to its practical implications, this work provides a valuable contribution towards our understanding of the genetic networks controlling growth in teleosts.
Olfactory sensitivity to bile fluid and bile salts in the European eel (Anguilla anguilla), goldfish (Carassius auratus) and Mozambique tilapia (Oreochromis mossambicus) suggests a `broad range' sensitivity not confined to those produced by conspecifics alone
Authors: Huertas M. , Hagey L. , Hofmann A. F. , Cerdà J. , Canário A. V. M. , Hubbard P. C.
Published: December 2009

Teleosts have high olfactory sensitivity to bile salts. To assess whether this phenomenon is involved in intra-specific chemical communication alone, or is part of a more `broad range' sensitivity to bile salts produced by heterospecifics, we investigated possible differences in the odour of bile between the sexes and among different species – the eel (Anguilla anguilla), goldfish (Carassius auratus) and Mozambique tilapia (Oreochromis mossambicus) – using the electro-olfactogram (EOG). We also identified the main bile constituents by liquid chromatography and mass spectrometry. There were marked differences in olfactory response of the eel to thin-layer chromatography fractions of bile from both sexes, and mature and immature conspecifics. Smaller differences were seen in the potency of fractions of bile from male and female goldfish and tilapia. Eels, goldfish and tilapia demonstrated similar olfactory sensitivity to bile from a range of different species, with no apparent correlation between the olfactory potency of bile and a phylogenetic closeness and/or similarity of diet of the donor to the receiver. The three species were able to detect odorants in thin-layer chromatography fractions of heterospecific bile even in the absence of activity in conspecific bile. Eels, goldfish and tilapia responded to both sulphated C27 bile salts (5β-scymnol-sulphate and 5α-cyprinol sulphate) and to taurine-conjugated C24 bile salts (taurochenodeoxycholic acid, taurolithocholic acid and taurocholic acid), irrespective of whether these bile salts were present in conspecific bile. Together, these results suggest that teleosts have a broad-range olfactory sensitivity to bile salts, with potential roles in both intra-specific chemical communication and in inter-specific interactions.
Spatial vision in the purple sea urchinStrongylocentrotus purpuratus(Echinoidea)
Authors: Yerramilli D. , Johnsen S.
Published: December 2009

Recent evidence that echinoids of the genus Echinometra have moderate visual acuity that appears to be mediated by their spines screening off-axis light suggests that the urchin Strongylocentrotus purpuratus, with its higher spine density, may have even more acute spatial vision. We analyzed the movements of 39 specimens of S. purpuratus after they were placed in the center of a featureless tank containing a round, black target that had an angular diameter of 6.5 deg. or 10 deg. (solid angles of 0.01 sr and 0.024 sr, respectively). An average orientation vector for each urchin was determined by testing the animal four times, with the target placed successively at bearings of 0 deg., 90 deg., 180 deg. and 270 deg. (relative to magnetic east). The urchins showed no significant unimodal or axial orientation relative to any non-target feature of the environment or relative to the changing position of the 6.5 deg. target. However, the urchins were strongly axially oriented relative to the changing position of the 10 deg. target (mean axis from –1 to 179 deg.; 95% confidence interval ± 12 deg.; P<0.001, Moore's non-parametric Hotelling's test), with 10 of the 20 urchins tested against that target choosing an average bearing within 10 deg. of either the target center or its opposite direction (two would be expected by chance). In addition, the average length of the 20 target-normalized bearings for the 10 deg. target (each the vector sum of the bearings for the four trials) were far higher than would be expected by chance (P<10−10; Monte Carlo simulation), showing that each urchin, whether it moved towards or away from the target, did so with high consistency. These results strongly suggest that S. purpuratus detected the 10 deg. target, responding either by approaching it or fleeing it. Given that the urchins did not appear to respond to the 6.5 deg. target, it is likely that the 10 deg. target was close to the minimum detectable size for this species. Interestingly, measurements of the spine density of the regions of the test that faced horizontally predicted a similar visual resolution (8.3±0.5 deg. for the interambulacrum and 11±0.54 deg. for the ambulacrum). The function of this relatively low, but functional, acuity – on par with that of the chambered Nautilus and the horseshoe crab – is unclear but, given the bimodal response, is likely to be related to both shelter seeking and predator avoidance.
Electric signals and species recognition in the wave-type gymnotiform fishApteronotus leptorhynchus
Authors: Fugère V. , Krahe R.
Published: December 2009

Gymnotiformes are South American weakly electric fish that produce weak electric organ discharges (EOD) for orientation, foraging and communication purposes. It has been shown that EOD properties vary widely across species and could thus be used as species recognition signals. We measured and quantified the electric signals of various species using a landmark-based approach. Using discriminant function analysis to verify whether these signals are species specific based on different signal parameters, we found that the EOD waveform is a more specific cue than EOD frequency, which shows large overlap across species. Using Apteronotus leptorhynchus as a focal species, we then performed a series of playback experiments using stimuli of different species (varying in frequency, waveform, or both). In an experiment with restrained fish, we found, in contrast to what we predicted, that the choice of stimulus waveform did not affect the production of communication signals. In an experiment with free-swimming fish, the animals spent more time near the playback electrodes and produced more communication signals when the stimuli were within their conspecific frequency range. Waveform again had no measurable effect. The production of communication signals correlated with the frequency difference between the stimulus and the fish's own EOD, but approach behavior did not.
Age-dependent allocation of carotenoids to colorationversusantioxidant defences
Authors: Cote J. , Arnoux E. , Sorci G. , Gaillard M. , Faivre B.
Published: December 2009

Aging is commonly attributed to age-related changes in oxidative damage due to an increased production of reactive oxygen species (ROS) and a weakened efficacy of enzymatic antioxidants. These age-related changes might therefore modify the use of dietary antioxidants, including carotenoids. As carotenoids are closely associated with the expression of secondary sexual signals, the allocation of carotenoids to sexual signal versus antioxidant defences may vary with age. In this study, we explored how carotenoid-based ornament and antioxidant activity varied with age and how an inflammatory-induced oxidative burst affected ornament and antioxidant activity across a range of ages. Using zebra finches (Taeniopygia guttata) as a model species, we assessed circulating carotenoids, beak coloration and the plasma antioxidant status of birds of different ages before and after an inflammatory challenge. Our results show that old individuals display similar carotenoid-based sexual signals regardless of the availability of circulating carotenoids, suggesting a terminal investment of old individuals in their last reproductive event. Additionally, we found that an inflammatory insult induced a decrease in the total antioxidant activity and in the expression of a carotenoid-based sexual signal in the oldest individuals. These results suggest that old individuals pay an extra cost of immune activation possibly because the efficiency of antioxidant machinery varies with age.
Behavioural state affects motion-sensitive neurones in the fly visual system
Authors: Rosner R. , Egelhaaf M. , Warzecha A.-K.
Published: December 2009

The strength of stimulus-induced responses at the neuronal and the behavioural level often depends on the internal state of an animal. Within pathways processing sensory information and eventually controlling behavioural responses, such gain changes can originate at several sites. Using motion-sensitive lobula plate tangential cells (LPTCs) of blowflies, we address whether and in which way information processing changes for two different states of motor activity. We distinguish between the two states on the basis of haltere movements. Halteres are the evolutionarily transformed hindwings of flies. They oscillate when the animals walk or fly. LPTCs mediate, amongst other behaviours, head optomotor responses. These are either of large or small amplitude depending on the state of motor activity. Here we find that LPTC responses also depend on the motor activity of flies. In particular, LPTC responses are enhanced when halteres oscillate. Nevertheless, the response changes of LPTCs do not account for the corresponding large gain changes of head movements. Moreover, haltere activity itself does not change the activity of LPTCs. Instead, we propose that a central signal associated with motor activity changes the gain of head optomotor responses and the response properties of LPTCs.
Thermal plasticity in young snakes: how will climate change affect the thermoregulatory tactics of ectotherms?
Authors: Aubret F. , Shine R.
Published: December 2009

Climate change will result in some areas becoming warmer and others cooler, and will amplify the magnitude of year-to-year thermal variation in many areas. How will such changes affect animals that rely on ambient thermal heterogeneity to behaviourally regulate their body temperatures? To explore this question, we raised 43 captive-born tiger snakes Notechis scutatus in enclosures that provided cold (19–22°C), intermediate (19–26°C) or hot (19–37°C) thermal gradients. The snakes adjusted their diel timing of thermoregulatory behaviour so effectively that when tested 14 months later, body temperatures (mean and maximum), locomotor speeds and anti-predator behaviours did not differ among treatment groups. Thus, the young snakes modified their behaviour to compensate for restricted thermal opportunities. Then, we suddenly shifted ambient conditions to mimic year-to-year variation. In contrast to the earlier plasticity, snakes failed to adjust to this change, e.g. snakes raised at cooler treatments but then shifted to hot conditions showed a higher mean body temperature for at least two months after the onset of the new thermal regime. Hence, thermal conditions experienced early in life influenced subsequent thermoregulatory tactics; the mean selected temperature of a snake depended more upon its prior raising conditions than upon its current thermoregulatory opportunities. Behavioural plasticity thus allows snakes to adjust to suboptimal thermal conditions but this plasticity is limited. The major thermoregulatory challenge from global climate change may not be the shift in mean values (to which our young snakes adjusted) but the increased year-to-year variation (with which our snakes proved less able to deal).
Hyperthermia-induced Hsp70 and MT20 transcriptional upregulation are mediated by p38-MAPK and JNKs inMytilus galloprovincialis(Lamarck); a pro-survival response
Authors: Gourgou E. , Aggeli I.-K. , Beis I. , Gaitanaki C.
Published: December 2009

In the present study we investigated the signal transduction cascades triggered by acute thermal stress in Mytilus galloprovincialis gills. This particular species has been reported to exhibit a significant tolerance to high temperatures; thus, it was intriguing to examine the molecular mechanisms responsible for this extraordinary trait. In particular, exposure to 30°C was found to cause a significant and sustained stimulation of p38-MAPK phosphorylation while the activation profile of JNKs was transient and relatively moderate. We also observed that hyperthermia induced apoptosis as a delayed response, with both MAPK subfamilies rapidly translocating to the nucleus. The phosphorylation of cJun, ATF2 and NFκB was detected next. Using selective inhibitors, phosphorylation of these transcription factors was established to be dependent on p38-MAPK or JNKs. Subsequently, potential changes in gene expression were assessed. In this context, hyperthermia resulted in the transcriptional upregulation of Hsp70 and MT20 genes with a widely known salutary effect, preserving mussel fitness and performance under adverse environmental conditions. Interestingly, p38-MAPK and JNKs were found to mediate the hyperthermia-induced Hsp70 and MT20 upregulation as well as the delayed induction of apoptosis under the interventions studied. Overall this is, to our knowledge, the first time that an insight into the compensatory survival `programme' initiated in Mytilus galloprovincialis gills, contributing to this organism's exceptional tolerance to thermal stress, has been gained. In particular, we provide evidence demonstrating the principal role of p38-MAPK and JNKs in transducing the stress signal via mobilization of specific transcription factors and the transcriptional upregulation of cytoprotective genes.
Correlation between aquaporin and water permeability in response to vasotocin, hydrin and β-adrenergic effectors in the ventral pelvic skin of the tree frogHyla japonica
Authors: Ogushi Y. , Kitagawa D. , Hasegawa T. , Suzuki M. , Tanaka S.
Published: December 2009

The ventral pelvic skin of the tree frog Hyla japonica expresses two kinds of arginine vasotocin (AVT)-stimulated aquaporins (AQP-h2 and AQP-h3), which affect the capacity of the frog's skin to absorb water. As such, it can be used as a model system for analyzing the molecular mechanisms of water permeability. We investigated AQP dynamics and water permeability in the pelvic skin of H. japonica following challenge with AVT, hydrins (intermediate peptides of pro-AVT) and β-adrenergic effectors. In the in vivo experiment, both AQP-h2 and AQP-h3 proteins were translocated to the apical plasma membrane in the principal cells of the first-reacting cell (FRC) layer in the pelvic skin following challenge with AVT, hydrin 1 and hydrin 2, thereby increasing the water permeability of the pelvic skin. The β-adrenergic receptor agonist isoproterenol (IP) and its anatagonist propranolol (PP) in combination with AVT or hydrins were used as challenge in the in vitro experiment. IP increased water permeability whereas PP inhibited it, and both events were well correlated with the translocation of the AQPs to the apical membrane. In the PP+AVT-treated skins, labels for AQP-h2 and AQP-h3 were differentially visible among the principal cells; the apical plasma membrane of some cells was labeled while others were not, indicating that the response of PP or AVT is different from cell to cell. These results provide morphological evidence that the principal cells of the FRC layers may have two kinds of receptors: a V2 receptor and β-adrenergic receptor.
The role of granules within viscous capture threads of orb-weaving spiders
Authors: Opell B. D. , Hendricks M. L.
Published: December 2009

Sticky viscous prey capture threads form the spiral elements of spider orb-webs and are responsible for retaining insects that strike a web. These threads are formed of regularly spaced aqueous droplets that surround a pair of supporting axial fibers. When a thread is flattened on a microscope slide a small, opaque granule can usually be seen within each droplet. These granules have been thought to be the glycoprotein glue that imparts thread adhesion. Both independent contrast and standard regressions showed that granule size is directly related to droplet volume and indicated that granule volume is about 15% of droplet volume. We attempted to find support for the hypothesized adhesive role of granules by establishing an association between the contact surface area and volume of these granules and the stickiness of the viscous threads of 16 species in the context of a six-variable model that describes thread stickiness. However, we found that granule size made either an insignificant or a small negative contribution to thread stickiness. Consequently, we hypothesize that granules serve to anchor larger, surrounding layers of transparent glycoprotein glue to the axial fibers of the thread, thereby equipping droplets to resist slippage on the axial fibers as these droplets generate adhesion, elongate under a load, and transfer force to the axial fibers.