bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial characterization of the human central proteome
Authors: Burkard Thomas R , Planyavsky Melanie , Kaupe Ines , Breitwieser Florian P , Bürckstümmer Tilmann , Bennett Keiryn L , Superti-Furga Giulio , Colinge Jacques
Published: January 2011

Background

On the basis of large proteomics datasets measured from seven human cell lines we consider their intersection as an approximation of the human central proteome, which is the set of proteins ubiquitously expressed in all human cells. Composition and properties of the central proteome are investigated through bioinformatics analyses.

Results

We experimentally identify a central proteome comprising 1,124 proteins that are ubiquitously and abundantly expressed in human cells using state of the art mass spectrometry and protein identification bioinformatics. The main represented functions are proteostasis, primary metabolism and proliferation. We further characterize the central proteome considering gene structures, conservation, interaction networks, pathways, drug targets, and coordination of biological processes. Among other new findings, we show that the central proteome is encoded by exon-rich genes, indicating an increased regulatory flexibility through alternative splicing to adapt to multiple environments, and that the protein interaction network linking the central proteome is very efficient for synchronizing translation with other biological processes. Surprisingly, at least 10% of the central proteome has no or very limited functional annotation.

Conclusions

Our data and analysis provide a new and deeper description of the human central proteome compared to previous results thereby extending and complementing our knowledge of commonly expressed human proteins. All the data are made publicly available to help other researchers who, for instance, need to compare or link focused datasets to a common background.
Actinomadura meyerae osteitis following wound contamination with hay in a woman in France: a case report
Authors: Bonnet Emilie , Flecher Xavier , Paratte Sebastien , Argenson Jean-Noël , Raoult Didier , Fournier Pierre-Edouard
Published: January 2011

Introduction

Mycetoma is a chronic granulomatous infection caused by environmental fungi or bacteria. It affects dermal and subcutaneous tissues, with putative contiguous extension to muscles or bones. While common in tropical and subtropical areas, mycetoma is rare in Europe.

Case presentation

We describe a case of Actinomadura meyerae osteitis in a 49-year-old Caucasian woman who suffered a tibia open fracture contaminated with hay; to the best of our knowledge the first case of autochthonous A. meyerae infection reported in France. The bacterium was cultivated from a bone biopsy. Following surgical osteosynthesis and six months of treatment with cotrimoxazole, our patient made a full recovery.

Conclusion

Our case report suggests that A. meyerae is a potential agent of wound infection in farm workers in contact with hay.
Peritoneal mesothelioma in a woman who has survived for seven years: a case report
Authors: Pillai Krishna , Akhter Javed , Pourgholami Mohammad H , Morris David L
Published: January 2011

Introduction

Malignant peritoneal mesothelioma is a rare cancer with poor patient survival. Female gender has been identified as a positive prognostic factor. Recently, it has been suggested that the expression of estrogen receptor β in malignant mesothelioma leads to tumor suppression and a better prognosis.

Case presentation

We report the case of a 48-year-old Caucasian woman who is alive and disease-free seven years after the initial diagnosis and treatment of malignant peritoneal mesothelioma.

Conclusion

This patient's long survival may be attributable to a combination of factors, including minimal disease, complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy plus the estrogen receptor β positivity of the tumor.
A novel SNP analysis method to detect copy number alterations with an unbiased reference signal directly from tumor samples
Authors: Lisovich Alex , Chandran Uma R , Lyons-Weiler Maureen A , LaFramboise William A , Brown Ashley R , Jakacki Regina I , Pollack Ian F , Sobol Robert W
Published: January 2011

Background

Genomic instability in cancer leads to abnormal genome copy number alterations (CNA) as a mechanism underlying tumorigenesis. Using microarrays and other technologies, tumor CNA are detected by comparing tumor sample CN to normal reference sample CN. While advances in microarray technology have improved detection of copy number alterations, the increase in the number of measured signals, noise from array probes, variations in signal-to-noise ratio across batches and disparity across laboratories leads to significant limitations for the accurate identification of CNA regions when comparing tumor and normal samples.

Methods

To address these limitations, we designed a novel "Virtual Normal" algorithm (VN), which allowed for construction of an unbiased reference signal directly from test samples within an experiment using any publicly available normal reference set as a baseline thus eliminating the need for an in-lab normal reference set.

Results

The algorithm was tested using an optimal, paired tumor/normal data set as well as previously uncharacterized pediatric malignant gliomas for which a normal reference set was not available. Using Affymetrix 250K Sty microarrays, we demonstrated improved signal-to-noise ratio and detected significant copy number alterations using the VN algorithm that were validated by independent PCR analysis of the target CNA regions.

Conclusions

We developed and validated an algorithm to provide a virtual normal reference signal directly from tumor samples and minimize noise in the derivation of the raw CN signal. The algorithm reduces the variability of assays performed across different reagent and array batches, methods of sample preservation, multiple personnel, and among different laboratories. This approach may be valuable when matched normal samples are unavailable or the paired normal specimens have been subjected to variations in methods of preservation.
Genetic variation of ESR1 and its co-activator PPARGC1B is synergistic in augmenting the risk of estrogen receptor-positive breast cancer
Authors: Li Yuqing , Li Yi , Wedrén Sara , Li Guoliang , Charn Tze Howe , Desai Kartiki Vasant , Bonnard Carine , Czene Kamila , Humphreys Keith , Darabi Hatef , Einarsdóttir Kristjana , Heikkinen Tuomas , Aittomäki Kristiina , Blomqvist Carl , Chia Kee Seng , Nevanlinna Heli , Hall Per , Liu Edison T , Liu Jianjun
Published: January 2011

Introduction

Given the role of estrogen in breast carcinogenesis and the modification of estrogen receptor (ER) activity by its biochemical cofactors, we hypothesize that genetic variation within ER cofactor genes alters cellular response to estrogen exposure and consequently modifies the risk for ER-positive breast cancer.

Methods

We genotyped 790 tagging SNPs within 60 ER cofactor genes in 1,257 cases and 1,464 controls from Sweden and in 2,215 cases and 1,265 controls from Finland, and tested their associations with either ER-positive or ER-negative breast cancer.

Results

Seven SNPs showed consistent association with ER-positive breast cancer in the two independent samples, and six of them were located within PPARGC1B, encoding an ER co-activator, with the strongest association at rs741581 (odds ratio = 1.41, P = 4.84 × 10-5) that survived Bonferroni correction for multiple testing in the combined ER-positive breast cancer sample (Pcorrected = 0.03). Moreover, we also observed significant synergistic interaction (P
interaction
= 0.008) between the genetic polymorphisms within PPARGC1B and ESR1 in ER-positive breast cancer. By contrast, no consistent association was observed in ER-negative breast cancer. Furthermore, we found that administration of estrogen in the MCF-7 cell line induced PPARGC1B expression and enhanced occupancies of ER and RNA polymerase II within the region of SNP association, suggesting the upregulation of PPARGC1B expression by ESR1 activation.

Conclusions

Our study revealed that DNA polymorphisms of PPARGC1B, coding a bona fide ER co-activator, are associated with ER-positive breast cancer risk. The feed-forward transcriptional regulatory loop between PPARGC1B and ESR1 further augments their protein interaction, which provides a plausible mechanistic explanation for the synergistic genetic interaction between PPARGC1B and ESR1 in ER-positive breast cancer. Our study also highlights that biochemically and genomically informed candidate gene studies can enhance the discovery of interactive disease susceptibility genes.
Effect of erythropoietin on level of circulating endothelial progenitor cells and outcome in patients after acute ischemic stroke
Authors: Yip Hon-Kan , Tsai Tzu-Hsien , Lin Hung-Sheng , Chen Shu-Fang , Sun Cheuk-Kwan , Leu Steve , Yuen Chun-Man , Tan Teng-Yeow , Lan Min-Yu , Liou Chia-Wei , Lu Cheng-Hsien , Chang Wen-Neng
Published: January 2011

Introduction

Erythropoietin (EPO) enhances the circulating level of endothelial progenitor cells (EPCs), which has been reported to be associated with prognostic outcome in ischemic stroke (IS) patients. The aim of this study was to evaluate the time course of circulating EPC level and the impact of EPO therapy on EPC level and clinical outcome in patients after acute IS.

Methods

In total, 167 patients were prospectively randomized to receive either EPO therapy (group 1) (5,000 IU each time, subcutaneously) at 48 h and 72 h after acute IS, or serve as placebo (group 2). The circulating level of EPCs (double-stained markers: CD31/CD34 (E1), CD62E/CD34 (E2) and KDR/CD34 (E3)) was determined using flow cytometry at 48 h and on days 7 and 21 after IS. EPC level was also evaluated once in 60 healthy volunteers.

Results

Circulating EPC (E1 to E3) level at 48 h after IS was remarkably higher in patients than in control subjects (P < 0.02). At 48 h and on Day 7 after IS, EPC (E1 to E3) level did not differ between groups 1 and 2 (all P > 0.1). However, by Day 21, EPC (E1 to E3) level was significantly higher in group 1 than in group 2 (all P < 0.03). Additionally, 90-day recurrent stroke rate was notably lower in group 1 compared with group 2 (P = 0.022). Multivariate analysis demonstrated that EPO therapy (95% confidence interval (CI), 0.153 to 0.730; P = 0.006) and EPC (E3) (95% CI, 0.341 to 0.997; P = 0.049) levels were significantly and independently predictive of a reduced 90-day major adverse neurological event (MANE) (defined as recurrent stroke, National Institutes of Health Stroke scale ≥8, or death).

Conclusions

EPO therapy significantly improved circulating EPC level and 90-day MANE.

Trial registration number

ISRCTN: ISRCTN96340690
Thyroid Hormone and COUP-TF1 Regulate Kallikrein-Binding Protein (KBP) Gene Expression
Authors: Liu Yan-Yun , Nakatani Teruyo , Kogai Takahiko , Mody Kaizeen , Brent Gregory A.
Published: January 2011

Kallikrein-binding protein (KBP) is a component of the kallikrein-kinin system that mediates vasodilation and inhibits tumor growth by antagonizing vascular endothelial growth factor-mediated angiogenesis. We demonstrate that KBP gene expression is repressed by T3 and modulated by the orphan nuclear receptor, chicken ovalbumin upstream promoter transcription factor 1 (COUP-TF1). In hypothyroid mice, KBP mRNA expression in the testis was increased 2.1-fold compared with euthyroid mice. We have identified two negative thyroid hormone response elements (nTREs) in the mouse KBP gene, nTRE1 located in the 5′ flanking region (−53 to −29) and nTRE2, located in the first intron (104–132). We used functional assays, cofactor knockdown, and chromatin immunoprecipitation assays to characterize nTRE1 and nTRE2 in hepatic (HepG2) and testes (GC-1spg) cell lines. Reporter expression directed by both elements was enhanced with addition of thyroid hormone receptor and repressed with the addition of T3. COUP-TF1 enhanced basal expression of both elements but blunted unliganded thyroid hormone receptor enhancement and T3 repression of nTRE1 but not nTRE2. Both nTREs bound nuclear corepressor and binding increased in response to T3. Nuclear corepressor knockdown resulted in loss of T3 repression of both nTRE1 and nTRE2. COUP-TF1, which usually represses T3 induction of positive thyroid hormone response elements, reverses T3 repression mediated by nTRE1 in the mouse KBP gene. Endogenous KBP expression is repressed by T3 and two functional nTREs, both of which are required, have been characterized in the KBP gene. COUP-TF1 may be an important factor to modulate expression of genes that are repressed by T3.
β2-Adrenergic Receptor Signaling in Osteoblasts Contributes to the Catabolic Effect of Glucocorticoids on Bone
Authors: Ma Yun , Nyman Jeffry S. , Tao Huan , Moss Heather H. , Yang Xiangli , Elefteriou Florent
Published: January 2011

The sympathetic nervous system is a physiological regulator of bone homeostasis. Autonomic nerves are indeed present in bone, bone cells express the β2-adrenergic receptors (β2AR), and pharmacological or genetic disruption of sympathetic outflow to bone induces bone gain in rodents. These recent findings implied that conditions that affect β2AR signaling in osteoblasts and/or sympathetic drive to bone may contribute to bone diseases. In this study, we show that dexamethasone stimulates the expression of the β2AR in differentiated primary calvarial osteoblasts, as measured by an increase in Adrβ2 mRNA and β2AR protein level after short-term dexamethasone treatment. Isoproterenol-induced cAMP accumulation and the expression of the β2AR target gene Rankl were also significantly increased after dexamethasone pretreatment, indicating that dexamethasone promotes the responsiveness of differentiated osteoblasts to adrenergic stimulation. These in vitro results led to the hypothesis that glucocorticoid-induced bone loss, provoked by increased endogenous or high-dose exogenous glucocorticoids given for the treatment of inflammatory diseases, might, at least in part, be mediated by increased sensitivity of bone-forming cells to the tonic inhibitory effect of sympathetic nerves on bone formation or their stimulatory effect on bone resorption. Supporting this hypothesis, both pharmacological and genetic β2AR blockade in mice significantly reduced the bone catabolic effect of high-dose prednisolone in vivo. This study emphasizes the importance of sympathetic nerves in the regulation of bone homeostasis and indicates that this neuroskeletal signaling axis can be modulated by hormones or drugs and contribute to enhance pathological bone loss.
Subacute Endotoxemia Induces Adipose Inflammation and Changes in Lipid and Lipoprotein Metabolism in Cats
Authors: Osto M. , Zini E. , Franchini M. , Wolfrum C. , Guscetti F. , Hafner M. , Ackermann M. , Reusch C. E. , Lutz T. A.
Published: January 2011

Acute inflammation in humans is associated with transient insulin resistance (IR) and dyslipidemia. Chronic low-grade inflammation is a pathogenic component of IR and adipose tissue dysfunction in obesity-induced type 2 diabetes. Because feline diabetes closely resembles human type 2 diabetes, we studied whether lipopolysaccharide (LPS)-induced subacute inflammation, in the absence of obesity, is the potential primary cause of IR and metabolic disorders. Cats received increasing iv doses (10–1000 ng/kg−1 · h−1) of LPS (n = 5) or saline (n = 5) for 10 d. Body temperature, proinflammatory and metabolic markers, and insulin sensitivity were measured daily. Tissue mRNA and protein expression were quantified on d 10. LPS infusion increased circulating and tissue markers of inflammation. Based on the homeostasis model assessment, endotoxemia induced transient IR and β-cell dysfunction. At the whole-body level, IR reverted after the 10-d treatment; however, tissue-specific indications of IR were observed, such as down-regulation of adipose glucose transporter 4, hepatic peroxisome proliferative activated receptor-γ1 and -2, and muscle insulin receptor substrate-1. In adipose tissue, increased hormone-sensitive lipase activity led to reduced adipocyte size, concomitant with increased plasma and hepatic triglyceride content and decreased total and high-density lipoprotein cholesterol levels. Prolonged LPS-induced inflammation caused acute IR, followed by long-lasting tissue-specific dysfunctions of lipid-, glucose-, and insulin metabolism-related targets; this ultimately resulted in dyslipidemia but not whole-body IR. Endotoxemia in cats may provide a promising model to study the cross talk between metabolic and inflammatory responses in the development of adipose tissue dysfunction and IR.
Identification of S100A16 as a Novel Adipogenesis Promoting Factor in 3T3-L1 Cells
Authors: Liu Yun , Zhang Rihua , Xin Jing , Sun Yan , Li Jie , Wei Dong , Zhao Allan Z.
Published: January 2011

S100A16 is a member of S100 protein super family that carries calcium-binding EF-hand motifs. Its expression is ubiquitous and elevated in various types of tumors. The functions of S100 proteins are still being defined, although many members of S100 protein family are traditionally considered as markers of tumor tissues. Using 3T3-L1 preadipocyte model, we investigated the expression and function of S100A16 during differentiation into adipocytes as well as the potential roles of S100A16 in the regulation of insulin sensitivity. We found that the expression of S100A16 was increased during differentiation and that elevation of intracellular Ca2+ via calcium ionophores led to its nucleus exclusion. Overexpression of S100A16 in 3T3-L1 preadipocytes increased their proliferation and markedly enhanced adipogenesis but resulted in significant reduction of insulin-stimulated glucose uptake and phosphorylation of AKT. In contrast, suppression of S100A16 expression with two different types of RNA interference significantly inhibited adipogenesis and preadipocyte proliferation. Immunoprecipitation analysis revealed that S100A16 could physically interact with tumor suppressor protein p53, also a known inhibitor of adipogenesis. Overexpression or RNA interference–initiated reduction of S100A16 led to the inhibition or activation of the expression of p53-responsive genes, respectively. Interestingly, Western blot assays showed that S100A16 protein levels were markedly higher in the adipose tissues of diet-induced obese mice and the ob/ob mice than that in control lean mice. Thus, we reveal for the first time that S100A16 protein is a novel adipogenesis-promoting factor and that increased expression of S100A16 in 3T3-L1 adipocytes can have a negative impact on insulin sensitivity.
Purinergic P2X7 receptor regulates lung surfactant secretion in a paracrine manner
Authors: Mishra Amarjit , Chintagari Narendranath Reddy , Guo Yujie , Weng Tingting , Su Lijing , Liu Lin
Published: January 2011

Alveolar epithelium is composed of alveolar epithelial cells of type I (AEC I) and type II (AEC II). AEC II secrete lung surfactant by means of exocytosis. P2X7 receptor (P2X7R), a P2 purinergic receptor, has been implicated in the regulation of synaptic transmission and inflammation. Here, we report that P2X7R, which is expressed in AEC I but not AEC II, is a novel mediator for the paracrine regulation of surfactant secretion in AEC II. In primary co-cultures of AEC I and AEC II benzoyl ATP (BzATP; an agonist of P2X7R) increased surfactant secretion, which was blocked by the P2X7R antagonist Brilliant Blue G. This effect was observed in AEC II co-cultured with human embryonic kidney HEK-293 cells stably expressing rat P2X7R, but not when co-cultured with AEC I in which P2X7R was knocked down or in co-cultures of AEC I and AEC II isolated from P2X7R−/− mice. BzATP-mediated secretion involved P2Y2 receptor signaling because it was reduced by the addition of the ATP scavengers apyrase and adenosine deaminase and the P2Y2 receptor antagonist suramin. However, the stimulation with BzATP might also release other substances that potentially increase surfactant secretion as a greater stimulation of secretion was observed in AEC II incubated with BzATP when co-cultured with E10 or HEK-293-P2X7R cells than with ATP alone. P2X7R−/− mice failed to increase surfactant secretion in response to hyperventilation, pointing to the physiological relevance of P2X7R in maintaining surfactant homeostasis in the lung. These results suggest that the activation of P2X7R increases surfactant secretion by releasing ATP from AEC I and subsequently stimulating P2Y2 receptors in AEC II.
Punctuated actin contractions during convergent extension and their permissive regulation by the non-canonical Wnt-signaling pathway
Authors: Kim Hye Young , Davidson Lance A.
Published: January 2011

Actomyosin networks linked to the micro-environment through the plasma membrane are thought to be key players in regulating cell behaviors within multicellular tissues, such as converging and extending mesoderm. Here, we observe the dynamics of actin contractions called ‘punctuated actin contractions’ in the mid-cell body of embryonic mesenchymal cells in the mesoderm. These contraction dynamics are a common feature of Xenopus embryonic tissues and are important for cell shape changes during morphogenesis. Quantitative morphological analysis of these F-actin dynamics indicates that frequent and aligned movements of multiple actin contractions accompany mesoderm cells as they intercalate and elongate. Using inhibitors combined with fluorescence recovery after photobleaching (FRAP) analysis, we find that the dynamics of actin contractions are regulated by both myosin contractility and F-actin polymerization. Furthermore, we find that the non-canonical Wnt-signaling pathway permissively regulates levels of punctuated actin contractions. Overexpression of Xfz7 (Fzd7) can induce early maturation of actin contractions in mesoderm and produce mesoderm-like actin contractions in ectoderm cells. By contrast, expression of the dominant-negative Xenopus disheveled construct Xdd1 blocks the progression of actin contractions into their late mesoderm dynamics but has no effect in ectoderm. Our study reveals punctuated actin contractions within converging and extending mesoderm and uncovers a permissive role for non-canonical Wnt-signaling, myosin contractility and F-actin polymerization in regulating these dynamics.
Temporal changes in Hec1 phosphorylation control kinetochore–microtubule attachment stability during mitosis
Authors: DeLuca Keith F. , Lens Susanne M. A. , DeLuca Jennifer G.
Published: January 2011

Precise control of the attachment strength between kinetochores and spindle microtubules is essential to preserve genomic stability. Aurora B kinase has been implicated in regulating the stability of kinetochore–microtubule attachments but its relevant kinetochore targets in cells remain unclear. Here, we identify multiple serine residues within the N-terminus of the kinetochore protein Hec1 that are phosphorylated in an Aurora-B-kinase-dependent manner during mitosis. On all identified target sites, Hec1 phosphorylation at kinetochores is high in early mitosis and decreases significantly as chromosomes bi-orient. Furthermore, once dephosphorylated, Hec1 is not highly rephosphorylated in response to loss of kinetochore–microtubule attachment or tension. We find that a subpopulation of Aurora B kinase remains localized at the outer kinetochore even upon Hec1 dephosphorylation, suggesting that Hec1 phosphorylation by Aurora B might not be regulated wholly by spatial positioning of the kinase. Our results define a role for Hec1 phosphorylation in kinetochore–microtubule destabilization and error correction in early mitosis and for Hec1 dephosphorylation in maintaining stable attachments in late mitosis.
Centriolar satellites are assembly points for proteins implicated in human ciliopathies, including oral-facial-digital syndrome 1
Authors: Lopes Carla A. M. , Prosser Suzanna L. , Romio Leila , Hirst Robert A. , O'Callaghan Chris , Woolf Adrian S. , Fry Andrew M.
Published: January 2011

Ciliopathies are caused by mutations in genes encoding proteins required for cilia organization or function. We show through colocalization with PCM-1, that OFD1 (the product of the gene mutated in oral-facial-digital syndrome 1) as well as BBS4 and CEP290 (proteins encoded by other ciliopathy genes) are primarily components of centriolar satellites, the particles surrounding centrosomes and basal bodies. RNA interference experiments reveal that satellite integrity is mutually dependent upon each of these proteins. Upon satellite dispersal, through mitosis or forced microtubule depolymerization, OFD1 and CEP290 remain centrosomal, whereas BBS4 and PCM-1 do not. OFD1 interacts via its fifth coiled-coil motif with the N-terminal coiled-coil domain of PCM-1, which itself interacts via its C-terminal non-coiled-coil region with BBS4. OFD1 localization to satellites requires its N-terminal region, encompassing the LisH motif, whereas expression of OFD1 C-terminal constructs causes PCM-1 and CEP290 mislocalization. Moreover, in embryonic zebrafish, OFD1 and BBS4 functionally synergize, determining morphogenesis. Our observation that satellites are assembly points for several mutually dependent ciliopathy proteins provides a further possible explanation as to why the clinical spectrum of OFD1, Bardet–Biedl and Joubert syndromes overlap. Furthermore, definition of how OFD1 and PCM-1 interact helps explain why different OFD1 mutations lead to clinically variable phenotypes.
Mutation in the βA3/A1-crystallin gene impairs phagosome degradation in the retinal pigmented epithelium of the rat
Authors: Zigler J. Samuel , Zhang Cheng , Grebe Rhonda , Sehrawat Gitanjali , Hackler Laszlo , Adhya Souvonik , Hose Stacey , McLeod D. Scott , Bhutto Imran , Barbour Walid , Parthasarathy Geetha , Zack Donald J. , Sergeev Yuri , Lutty Gerard A. , Handa James T. , Sinha Debasish
Published: January 2011

Phagocytosis of the shed outer segment discs of photoreceptors is a major function of the retinal pigmented epithelium (RPE). We demonstrate for the first time that βA3/A1-crystallin, a major structural protein of the ocular lens, is expressed in RPE cells. Further, by utilizing the Nuc1 rat, in which the βA3/A1-crystallin gene is mutated, we show that this protein is required by RPE cells for proper degradation of outer segment discs that have been internalized in phagosomes. We also demonstrate that in wild-type RPE, βA3/A1-crystallin is localized to the lysosomes. However, in the Nuc1 RPE, βA3/A1-crystallin fails to translocate to the lysosomes, perhaps because misfolding of the mutant protein masks sorting signals required for proper trafficking. The digestion of phagocytized outer segments requires a high level of lysosomal enzyme activity, and cathepsin D, the major enzyme responsible for proteolysis of the outer segments, is decreased in mutant RPE cells. Interestingly, our results also indicate a defect in the autophagy process in the Nuc1 RPE, which is probably also linked to impaired lysosomal function, because phagocytosis and autophagy might share common mechanisms in degradation of their targets. βA3/A1-crystallin is a novel lysosomal protein in RPE, essential for degradation of phagocytosed material.
N-dimensional animal energetic niches clarify behavioural options in a variable marine environment
Authors: Wilson Rory P. , McMahon Clive R. , Quintana Flavio , Frere Esteban , Scolaro Alejandro , Hays Graeme C. , Bradshaw Corey J. A.
Published: January 2011

Animals respond to environmental variation by exhibiting a number of different behaviours and/or rates of activity, which result in corresponding variation in energy expenditure. Successful animals generally maximize efficiency or rate of energy gain through foraging. Quantification of all features that modulate energy expenditure can theoretically be modelled as an animal energetic niche or power envelope; with total power being represented by the vertical axis and n-dimensional horizontal axes representing extents of processes that affect energy expenditure. Such an energetic niche could be used to assess the energetic consequences of animals adopting particular behaviours under various environmental conditions. This value of this approach was tested by constructing a simple mechanistic energetics model based on data collected from recording devices deployed on 41 free-living Magellanic penguins (Spheniscus magellanicus), foraging from four different colonies in Argentina and consequently catching four different types of prey. Energy expenditure was calculated as a function of total distance swum underwater (horizontal axis 1) and maximum depth reached (horizontal axis 2). The resultant power envelope was invariant, irrespective of colony location, but penguins from the different colonies tended to use different areas of the envelope. The different colony solutions appeared to represent particular behavioural options for exploiting the available prey and demonstrate how penguins respond to environmental circumstance (prey distribution), the energetic consequences that this has for them, and how this affects the balance of energy acquisition through foraging and expenditure strategy.
Stable isotopes of captive cetaceans (killer whales and bottlenose dolphins)
Authors: Caut Stéphane , Laran Sophie , Garcia-Hartmann Emmanuel , Das Krishna
Published: January 2011

There is currently a great deal of interest in using stable isotope methods to investigate diet, trophic level and migration in wild cetaceans. In order to correctly interpret the results stemming from these methods, it is crucial to understand how diet isotopic values are reflected in consumer tissues. In this study, we investigated patterns of isotopic discrimination between diet and blood constituents of two species of cetaceans (killer whale, Orcinus orca, and bottlenose dolphin, Tursiops truncatus) fed controlled diets over 308 and 312 days, respectively. Diet discrimination factors (Δ; mean ± s.d.) for plasma were estimated to Δ13C=2.3±0.6‰ and Δ15N=1.8±0.3‰, respectively, for both species and to Δ13C=2.7±0.3‰ and Δ15N=0.5±0.1‰ for red blood cells. Delipidation did not have a significant effect on carbon and nitrogen isotopic values of blood constituents, confirming that cetacean blood does not serve as a reservoir of lipids. In contrast, carbon isotopic values were higher in delipidated samples of blubber, liver and muscle from killer whales. The potential for conflict between fisheries and cetaceans has heightened the need for trophic information about these taxa. These results provide the first published stable isotope incorporation data for cetaceans, which are essential if conclusions are to be drawn on issues concerning trophic structures, carbon sources and diet reconstruction.
Egg yolk environment differentially influences physiological and morphological development of broiler and layer chicken embryos
Authors: Ho Dao H. , Reed Wendy L. , Burggren Warren W.
Published: January 2011

Maternal effects are important in epigenetic determination of offspring phenotypes during all life stages. In the chicken (Gallus gallus domesticus), transgenerational transfer of egg yolk factors may set the stage for morphological and physiological phenotypic differences observed among breeds. To investigate the effect of breed-specific yolk composition on embryonic broiler and layer chicken phenotypes, we employed an ex ovo, xenobiotic technique that allowed the transfer of broiler and layer chicken embryos from their natural yolks to novel yolk environments. Embryonic day two broiler embryos developing on broiler yolk culture medium (YCM) had significantly higher heart rates than layer embryos developing on layer YCM (176±7 beats min–1 and 147±7 beats min–1, respectively). Broiler embryos developing on layer YCM exhibited heart rates typical of layer embryos developing normally on layer YCM. However, layer embryo heart rates were not affected by development on broiler YCM. Unlike O2 consumption, development rate and body mass of embryos were significantly affected by exposure to different yolk types, with both broiler and layer embryos displaying traits that reflected yolk source rather than embryo genotype. Analysis of hormone concentrations of broiler and layer egg yolks revealed that testosterone concentrations were higher in broiler yolk (4.63±2.02 pg mg–1vs 3.32±1.92 pg mg–1), whereas triiodothyronine concentrations were higher in layer yolk (1.05±0.18 pg mg–1vs 0.46±0.22 pg mg–1). Thus, a complex synergistic effect of breed-specific genotype and yolk environment exists early in chicken development, with yolk thyroid hormone and yolk testosterone as potential mediators of the physiological and morphological effects.
The effect of substrate compliance on the biomechanics of gibbon leaps
Authors: Channon Anthony J. , Günther Michael M. , Crompton Robin H. , D'Août Kristiaan , Preuschoft Holger , Vereecke Evie E.
Published: January 2011

The storage and recovery of elastic strain energy in the musculoskeletal systems of locomoting animals has been extensively studied, yet the external environment represents a second potentially useful energy store that has often been neglected. Recent studies have highlighted the ability of orangutans to usefully recover energy from swaying trees to minimise the cost of gap crossing. Although mechanically similar mechanisms have been hypothesised for wild leaping primates, to date no such energy recovery mechanisms have been demonstrated biomechanically in leapers. We used a setup consisting of a forceplate and two high-speed video cameras to conduct a biomechanical analysis of captive gibbons leaping from stiff and compliant poles. We found that the gibbons minimised pole deflection by using different leaping strategies. Two leap types were used: slower orthograde leaps and more rapid pronograde leaps. The slower leaps used a wider hip joint excursion to negate the downward movement of the pole, using more impulse to power the leap, but with no increase in work done on the centre of mass. Greater hip excursion also minimised the effective leap distance during orthograde leaps. The more rapid leaps conversely applied peak force earlier in stance where the pole was effectively stiffer, minimising deflection and potential energy loss. Neither leap type appeared to usefully recover energy from the pole to increase leap performance, but the gibbons demonstrated an ability to best adapt their leap biomechanics to counter the negative effects of the compliant pole.
Physiological flexibility and acclimation to food shortage in a heterothermic primate
Authors: Canale Cindy I. , Perret Martine , Théry Marc , Henry Pierre-Yves
Published: January 2011

As ecosystems undergo changes worldwide, physiological flexibility is likely to be an important adaptive response to increased climate instability. Extreme weather fluctuations impose energetical constraints such as unpredictable food shortage. We tested how grey mouse lemurs (Microcebus murinus) could adjust their daily heterothermy and locomotor activity to these ‘energetic accidents’ with a food restriction experiment. The experimental design consisted of acute calorie restriction (2 weeks, 80% restriction) in the middle of winter, after a fattening season with low (11 weeks, 40% restriction) versus high (ad libitum) food availability. This design aimed at simulating the combined effects of the quality of the fattening season (acclimation effect) and a sudden, severe food shortage during the lean season. Hour of start and duration of torpor were the most flexible components of energy savings, increasing in response to the acute food shortage with facilitation by chronic restriction (acclimation effect). Modulations of locomotor activity did not support the hypothesis of energy savings, as total locomotor activity was not reduced. Nonetheless, acutely restricted individuals modified their temporal pattern of locomotor activity according to former food availability. We provide the first experimental evidence of different temporal levels of flexibility of energy-saving mechanisms in a heterotherm exposed to food shortage. The acclimation effect of past food scarcity suggests that heterothermic organisms are better able to respond to unpredicted food scarcity during the lean season. The flexible control of energy expenditure conferred by heterothermy may facilitate the plastic response of heterothermic species to more frequent climatic hazards.
Ordinary glomeruli in the antennal lobe of male and female tortricid moth Grapholita molesta (Busck) (Lepidoptera: Tortricidae) process sex pheromone and host-plant volatiles
Authors: Varela Nélia , Avilla Jesús , Gemeno César , Anton Sylvia
Published: January 2011

Both sexes of Grapholita molesta, a key pest of stone fruits, are able to detect host-plant volatiles and the sex pheromone emitted by females, and to modify their behaviour accordingly. How olfactory information is processed in the central nervous system is unknown. Intracellular recordings and stainings were used to characterize antennal lobe (AL) neuron responses to single pheromone components, a behaviourally active blend of five peach volatiles and a pear-fruit ester. AL neurons with different response patterns responded to pheromone components and plant volatiles. In males more neurons responded specifically to the main pheromone component than in females, whereas neurons responding to all three pheromone components were more abundant in females. Neurons responding to all three pheromone components often responded also to the tested plant volatiles in both sexes. Responses to all pheromone components were dose dependent in males and females, but dose–response relationships differed between neurons and tested pheromone components. Among the five AL projection neurons identified neuroanatomically in males, no arborizations were observed in the enlarged cumulus (Cu), although all of them responded to pheromone compounds. In one of two stained projection neurons in females, however, the glomerulus, which is thought to be homologous to the Cu, was targeted. The processing of pheromone information by ordinary glomeruli rather than by the macroglomerular complex is thus a striking feature of this species, indicating that pheromone and plant volatile processing are not entirely separate in this tortricid moth AL. However, the absence of recorded pheromone responses in the Cu needs to be confirmed.
Mechanisms underlying rhythmic locomotion: body–fluid interaction in undulatory swimming
Authors: Chen J. , Friesen W. O. , Iwasaki T.
Published: January 2011

Swimming of fish and other animals results from interactions of rhythmic body movements with the surrounding fluid. This paper develops a model for the body–fluid interaction in undulatory swimming of leeches, where the body is represented by a chain of rigid links and the hydrodynamic force model is based on resistive and reactive force theories. The drag and added-mass coefficients for the fluid force model were determined from experimental data of kinematic variables during intact swimming, measured through video recording and image processing. Parameter optimizations to minimize errors in simulated model behaviors revealed that the resistive force is dominant, and a simple static function of relative velocity captures the essence of hydrodynamic forces acting on the body. The model thus developed, together with the experimental kinematic data, allows us to investigate temporal and spatial (along the body) distributions of muscle actuation, body curvature, hydrodynamic thrust and drag, muscle power supply and energy dissipation into the fluid. We have found that: (1) thrust is generated continuously along the body with increasing magnitude toward the tail, (2) drag is nearly constant along the body, (3) muscle actuation waves travel two or three times faster than the body curvature waves and (4) energy for swimming is supplied primarily by the mid-body muscles, transmitted through the body in the form of elastic energy, and dissipated into the water near the tail.
Ott's protein osmotic pressure of serum and interstitial fluid in chickens (Gallus gallus): effect of age and gender
Authors: Peltonen Liisa M. , Sankari Satu
Published: January 2011

Protein, or colloid, osmotic pressure (COP) is of sufficient magnitude to exert a powerful effect on Starling forces across the capillary wall. Although avian skin lacks active mechanisms for fluid transmission, such as sweating, it is now hypothesized that passive oncotic forces may regulate fluid flow and distribution in the skin and related phenomena. In this study, serum protein profiles, as well as COP in serum (COPs) and in suction blister fluid (COPsbf), were determined in juvenile, young and adult female and male chickens. For assessing COP, the Ott-Ahlqvist equation was applied. This equation can formulate the effects of multiple serum proteins on COP, according to their molecular mass. The COP values determined in chickens were lower than those previously found in mammals. COPs increased with age in males, and was higher in adult males than in adult females. In contrast, COPsbf decreased with age in females, although it was better preserved in adult males. The age-dependent decrease in COP was associated with a parallel decrease in the concentration of α1-globulin and albumin, and a positive correlation between packed cell volume (PCV) and COP was found. It is concluded that ageing affects Ott's COP around the vessel wall, and that an oncotic mechanism preserves plasma volume. The preservation of COPsbf in males suggests better maintenance of the interstitial ground substance. Females seem to lose more of a tissue's COPs counteracting force than males, probably as a result of gender-specific changes in the composition of the interstitial matrix. Further studies are required to elucidate the structure and function of avian lymphatics and their role in skin rheology.
Underwater and surface behavior of homing juvenile northern elephant seals
Authors: Matsumura Moe , Watanabe Yuuki Y. , Robinson Patrick W. , Miller Patrick J. O. , Costa Daniel P. , Miyazaki Nobuyuki
Published: January 2011

Northern elephant seals, Mirounga angustirostris, travel between colonies along the west coast of North America and foraging areas in the North Pacific. They also have the ability to return to their home colony after being experimentally translocated. However, the mechanisms of this navigation are not known. Visual information could serve an important role in navigation, either primary or supplementary. We examined the role of visual cues in elephant seal navigation by translocating three seals and recording their heading direction continuously using GPS, and acceleration and geomagnetic data loggers while they returned to the colony. The seals first reached the coast and then proceeded to the colony by swimming along the coast. While underwater the animals exhibited a horizontally straight course (mean net-to-gross displacement ratio=0.94±0.02). In contrast, while at the surface they changed their headings up to 360 deg. These results are consistent with the use of visual cues for navigation to the colony. The seals may visually orient by using landmarks as they swim along the coast. We further assessed whether the seals could maintain a consistent heading while underwater during drift dives where one might expect that passive spiraling during drift dives could cause disorientation. However, seals were able to maintain the initial course heading even while underwater during drift dives where there was spiral motion (to within 20 deg). This behavior may imply the use of non-visual cues such as acoustic signals or magnetic fields for underwater orientation.
Loss of Angiotensin-converting enzyme-related (ACER) peptidase disrupts night-time sleep in adult Drosophila melanogaster
Authors: Carhan Ahmet , Tang Ke , Shirras Christine A. , Shirras Alan D. , Isaac R. Elwyn
Published: January 2011

Drosophila Acer (Angiotensin-converting enzyme-related) encodes a member of the angiotensin-converting enzyme family of metallopeptidases that have important roles in the endocrine regulation of blood homeostasis in mammals. Acer is expressed in the embryonic heart of Drosophila and expression in the adult head appears to be regulated by two clock genes. To study the role of Acer in development and in circadian activity, we have generated Acer null mutants by imprecise excision of a P-element and have compared their development and circadian behaviour with that of wild-type flies with the same genetic background. We show that Acer is not required for normal development, but that night sleep, which is clock regulated, is disrupted in adult flies lacking ACER. Acer null adults have reduced night-time sleep and greater sleep fragmentation, but normal levels of daytime sleep. The quality of night sleep in flies fed inhibitors of ACER is affected in a very similar manner. We have shown, using specific antibodies, that ACER is present in the adult fat body of the head and abdomen, and is secreted into the haemolymph. ACER might therefore have a role in cleaving regulatory peptides involved in metabolism and activity behaviour. There are similarities with mammals, where ACE peptidases are also expressed in adipose tissue and are thought to be part of a signalling system linking metabolism with sleep.
Muscle damage and muscle remodeling: no pain, no gain?
Authors: Flann Kyle L. , LaStayo Paul C. , McClain Donald A. , Hazel Mark , Lindstedt Stan L.
Published: January 2011

Skeletal muscle is a dynamic tissue that responds adaptively to both the nature and intensity of muscle use. This phenotypic plasticity ensures that muscle structure is linked to patterns of muscle use throughout the lifetime of an animal. The cascade of events that result in muscle restructuring – for example, in response to resistance exercise training – is often thought to be initiated by muscle damage. We designed this study to test the hypothesis that symptomatic (i.e. detectable) damage is a necessary precursor for muscle remodeling. Subjects were divided into two experimental populations: pre-trained (PT) and naive (NA). Demonstrable muscle damage was avoided in the PT group by a three-week gradual ‘ramp-up’ protocol. By contrast, the NA group was subjected to an initial damaging bout of exercise. Both groups participated in an eight-week high-force eccentric-cycle ergometry program (20 min, three times per week) designed to equate the total work done during training between the groups. The NA group experienced signs of damage, absent in the PT group, as indicated by greater than five times higher levels of plasma creatine kinase (CK) and self-reporting of initial perceived soreness and exertion, yet muscle size and strength gains were not different for the two groups. RT-PCR analysis revealed similar increases in levels of the growth factor IGF-1Ea mRNA in both groups. Likewise, the significant (P<0.01) increases in mean cross-sectional area (and total muscle volume) were equal in both groups. Finally, strength increases were identical for both groups (PT=25% and NA=26% improvement). The results of this study suggest that muscle rebuilding – for example, hypertrophy – can be initiated independent of any discernible damage to the muscle.