Mechanical loading induces the expression of a Pol I regulon at the onset of skeletal muscle hypertrophy

von Walden F, Casagrande V, Ostlund Farrants AK, Nader GA. Mechanical loading induces the expression of a Pol I regulon at the onset of skeletal muscle hypertrophy. Am J Physiol Cell Physiol 302: C1523-C1530, 2012. First published March 7, 2012; doi:10.1152/ajpcell.00460.2011.-The main goal of the present study was to investigate the regulation of ribosomal DNA (rDNA) gene transcription at the onset of skeletal muscle hypertrophy. Mice were subjected to functional overload of the plantaris by bilateral removal of the synergist muscles. Mechanical loading resulted in muscle hypertrophy with an increase in rRNA content. rDNA transcription, as determined by 45S pre-rRNA abundance, paralleled the increase in rRNA content and was consistent with the onset of the hypertrophic response. Increased transcription and protein expression of c-Myc and its downstream polymerase I (Pol I) regulon (POL1RB, TIF-1A, PAF53, TTF1, TAF1C) was also consistent with the increase in rRNA. Similarly, factors involved in rDNA transcription, such as the upstream binding factor and the Williams syndrome transcription factor, were induced by mechanical loading in a corresponding temporal fashion. Chromatin immunoprecipitation revealed that these factors, together with Pol I, were enriched at the rDNA promoter. This, in addition to an increase in histone H3 lysine 9 acetylation, demonstrates that mechanical loading regulates rRNA synthesis by inducing a gene expression program consisting of a Pol I regulon, together with accessory factors involved in transcription and chromatin remodeling at the rDNA promoter. Altogether, these data indicate that transcriptional and epigenetic mechanisms take place in the regulation of ribosome production at the onset of muscle hypertrophy.

The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls

Introduction: Impairments in facial emotion recognition (PER) have been reported in bipolar disorder (BD) during all mood states. FER has been the focus of functional magnetic resonance imaging studies evaluating differential activation of limbic regions. Recently, the alpha 1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene has been described as a risk gene for BD and its Met allele found to increase CACNA1C mRNA expression. In healthy controls, the CACNA1C risk (Met) allele has been reported to increase limbic system activation during emotional stimuli and also to impact on cognitive function. The aim of this study was to investigate the impact of CACNA1C genotype on FER scores and limbic system morphology in subjects with BD and healthy controls. Material and methods: Thirty-nine euthymic BD I subjects and 40 healthy controls were submitted to a PER recognition test battery and genotyped for CACNA1C. Subjects were also examined with a 3D 3-Tesla structural imaging protocol. Results: The CACNA1C risk allele for BD was associated to FER impairment in BD, while in controls nothing was observed. The CACNA1C genotype did not impact on amygdala or hippocampus volume neither in BD nor controls. Limitations: Sample size. Conclusion: The present findings suggest that a polymorphism in calcium channels interferes FER phenotype exclusively in BD and doesn't interfere on limbic structures morphology. (C) 2012 Elsevier B.V. All rights reserved.

The role of reactive oxygen species in the modulation of the contraction induced by angiotensin II in carotid artery from diabetic rat

The modulation played by reactive oxygen species on the angiotensin II-induced contraction in type I-diabetic rat carotid was investigated. Concentration-response curves for angiotensin II were obtained in endothelium-intact or endothelium-denuded carotid from control or streptozotocin-induced diabetic rats, pre-treated with tiron (superoxide scavenger), PEG-catalase (hydrogen peroxide scavenger), dimethylthiourea (hydroxyl scavenger), apocynin [NAD(P) H oxidase inhibitor], SC560 (cyclooxygenase-1 inhibitor), SC236 (cyclooxygenase-2 inhibitor) or Y-27632 (Rho-kinase inhibitor). Reactive oxygen species were measured by flow cytometry in dihydroethidium (DHE)-loaded endothelial cells. Cyclooxygenase and AT1-receptor expression was assessed by immunohistochemistry. Diabetes increased the angiotensin II-induced contraction but reduced the agonist potency in rat carotid. Endothelium removal, tiron or apocynin restored the angiotensin II-induced contraction in diabetic rat carotid to control levels. PEG-catalase, DMTU or SC560 reduced the angiotensin II-induced contraction in diabetic rat carotid at the same extent. SC236 restored the angiotensin II potency in diabetic rat carotid. Y-27632 reduced the angiotensin II-induced contraction in endothelium-intact or -denuded diabetic rat carotid. Diabetes increased the DHE-fluorescence of carotid endothelial cells. Apocynin reduced the DHE-fluorescence of endothelial cells from diabetic rat carotid to control levels. Diabetes increased the muscular cyclooxygenase-2 expression but reduced the muscular AT1-receptor expression in rat carotid. In summary, hydroxyl radical, hydrogen peroxide and superoxide anion-derived from endothelial NAD(P) H oxidase mediate the hyperreactivity to angiotensin II in type I-diabetic rat carotid, involving the participation of cyclooxygenase-1 and Rho-kinase. Moreover, increased muscular cyclooxygenase-2 expression in type I-diabetic rat carotid seems to be related to the local reduced AT1-receptor expression and the reduced angiotensin II potency. (C) 2011 Elsevier B. V. All rights reserved.

CD44(+)/CD24(-) cells and lymph node metastasis in stage I and II invasive ductal carcinoma of the breast

The presence of tumor-initiating cells (CD44(+)/CD24(-)) in solid tumors has been reported as a possible cause of cancer metastasis and treatment failure. Nevertheless, little is know about the presence of CD44(+)/CD24(-) cells within the primary tumor and metastasis. The proportion of CD44(+)/CD24(-) cells was analyzed in 40 samples and in 10 lymph node metastases using flow cytometry phenotyping. Anti-human CD326 (EpCam; FITC), antihuman CD227 (MUC-1; FITC), anti-human CD44 (APC), and anti-human CD24 (PE), anti-ABCG2 (PE), and anti-CXCR4 (PeCy7) were used for phenotype analysis. The mean patient age was 60.5 years (range, 33-87 years); mean primary tumor size (pT) was 1.8 cm (0.5-3.5 cm). The Wilcoxon or Kruskal-Wallis test was used for univariate analyses. Logistic regression was used for multivariate analysis. The median percentage of CD44(+)/CD24(-) cells within primary invasive ductal carcinomas (IDC) was 2.7% (range, 0.2-71.2). In lymph node metastases, we observed a mean of 6.1% (range, 0.07-53.7). The percentage of CD44(+)/CD24(-) cells in IDCs was not associated with age, pT, tumor grade and HER2. We observed a significantly enrichment of CD44(+)/CD24(-) and ABCG2(+) cells in ESA(+) cell population in patients with positive lymph nodes (P = 0.02 and P = 0.04, respectively). Our data suggest that metastatic dissemination is associated with an increase in tumorinitiating cells in stage I and II breast cancer.

The regulation of NHE₁ and NHE₃ activity by angiotensin II is mediated by the activation of the angiotensin II type I receptor/phospholipase C/calcium/calmodulin pathway in distal nephron cells

Angiotensin II (Ang II), acting via the AT1 receptor, induces an increase in intracellular calcium [Ca(2+)]i that then interacts with calmodulin (CaM). The Ca(2+)/CaM complex directly or indirectly activates sodium hydrogen exchanger 1 (NHE1) and phosphorylates calmodulin kinase II (CaMKII), which then regulates sodium hydrogen exchanger 3 (NHE3) activity. In this study, we investigated the cellular signaling pathways responsible for Ang II-mediated regulation of NHE1 and NHE3 in Madin-Darby canine kidney (MDCK) cells. The NHE1- and NHE3-dependent pHi recovery rates were evaluated by fluorescence microscopy using the fluorescent probe BCECF/AM, messenger RNA was evaluated with the reverse transcription polymerase chain reaction (RT-PCR), and protein expression was evaluated by immunoblot. We demonstrated that treatment with Ang II (1pM or 1 nM) for 30 min induced, via the AT1 but not the AT2 receptor, an equal increase in NHE1 and NHE3 activity that was reduced by the specific inhibitors HOE 694 and S3226, respectively. Ang II (1 nM) did not change the total expression of NHE1, NHE3 or calmodulin, but it induced CaMKII, cRaf-1, Erk1/2 and p90(RSK) phosphorylation. The stimulatory effects of Ang II (1 nM) on NHE1 or NHE3 activity or protein abundance was reduced by ophiobolin-A (CaM inhibitor), KN93 (CaMKII inhibitor) or PD98059 (Mek inhibitor). These results indicate that after 30 min, Ang II treatment may activate G protein-dependent pathways, including the AT1/PLC/Ca(2+)/CaM pathway, which induces CaMKII phosphorylation to stimulate NHE3 and induces cRaf-1/Mek/Erk1/2/p90(RSK) activity to stimulate NHE1

Manipulation of the periovulatory sex steroidal milieu affects endometrial but not luteal gene expression in early diestrus Nelore cows

In beef cattle, the ability to conceive has been associated positively with size of the preovulatory follicle (POF). Proestrus estradiol and subsequent progesterone concentrations can regulate the endometrium to affect receptivity and fertility. The aim of the present study was to verify the effect of the size of the POF on luteal and endometrial gene expression during subsequent early diestrus in beef cattle. Eighty-three multiparous, nonlactating, presynchronized Nelore cows received a progesterone-releasing device and estradiol benzoate on Day–10 (D 10). Animals received cloprostenol (large follicle-large CL group; LF-LCL; N ¼ 42) or not (small follicle-small CL group; SF-SCL; N ¼ 41) on D 10. Progesterone devices were withdrawn and cloprostenol administered 42 to 60 hours (LF-LCL) or 30 to 36 hours (SF-SCL) before GnRH treatment (D0). Tissues were collected at slaughter on D7. The LF-LCL group had larger (P < 0.0001) POF (13.24 0.33 mm vs. 10.76 0.29 mm), greater (P < 0.0007) estradiol concentrations on D0 (2.94 0.28 pg/mL vs. 1.27 0.20 pg/mL), and greater (P < 0.01) progesterone concentrations on D7 (3.71 0.25 ng/mL vs. 2.62 0.26 ng/mL) compared with the SF-SCL group. Luteal gene expression of vascular endothelial growth factor A, kinase insert domain receptor, fms-related tyrosine kinase 1, steroidogenic acute regulatory protein, cytochrome P450, family 11, subfamily A, polypeptide 1, and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid deltaisomerase 7 was similar between groups. Endometrial gene expression of oxytocin receptor and peptidase inhibitor 3, skin-derived was reduced, and estrogen receptor alpha 2, aldo-keto reductase family 1, member C4, and lipoprotein lipase expression was increased in LF-LCL versus SF-SCL. Results support the hypothesis that the size of the POF alters the periovulatory endocrine milieu (i.e., proestrus estradiol and diestrus progesterone concentrations) and acts on the uterus to alter endometrial gene expression. It is proposed that the uterine environment and receptivity might also be modulated. Additionally, it is suggested that increased progesterone secretion of cows ovulating larger follicles is likely due to increased CL size rather than increased luteal expression of steroidogenic genes.

Association of the (CA)n repeat polymorphism of insulin-like growth factor-I and -202 A/C IGF-binding protein-3 promoter polymorphism with adult height in patients with severe growth hormone deficiency

A number of mathematical models for predicting growth and final height outcome have been proposed to enable the clinician to 'individualize' growth-promoting treatment. However, despite optimizing these models, many patients with isolated growth hormone deficiency (IGHD) do not reach their target height. The aim of this study was to analyse the impact of polymorphic genotypes [CA repeat promoter polymorphism of insulin-like growth factor-I (IGF-I) and the -202 A/C promoter polymorphism of IGF-Binding Protein-3 (IGFBP-3)] on variable growth factors as well as final height in severe IGHD following GH treatment. DESIGN, PATIENTS AND CONTROLS: One hundred seventy eight (IGF-I) and 167 (IGFBP-3) subjects with severe growth retardation because of IGHD were studied. In addition, the various genotypes were also studied in a healthy control group of 211 subjects.

The European baseline series in 10 European Countries, 2005/2006--results of the European Surveillance System on Contact Allergies (ESSCA)

BACKGROUND: Continual surveillance based on patch test results has proved useful for the identification of contact allergy. OBJECTIVES: To provide a current view on the spectrum of contact allergy to important sensitizers across Europe. PATIENTS/METHODS: Clinical and patch test data of 19 793 patients patch tested in 2005/2006 in the 31 participating departments from 10 European countries (the European Surveillance System on Contact Allergies' (ESSCA) www.essca-dc.org) were descriptively analysed, aggregated to four European regions. RESULTS: Nickel sulfate remains the most common allergen with standardized prevalences ranging from 19.7% (central Europe) to 24.4% (southern Europe). While a number of allergens shows limited variation across the four regions, such as Myroxylon pereirae (5.3-6.8%), cobalt chloride (6.2-8.8%) or thiuram mix (1.7-2.4%), the differences observed with other allergens may hint on underlying differences in exposures, for example: dichromate 2.4% in the UK (west) versus 4.5-5.9% in the remaining EU regions, methylchloroisothiazolinone/methylisothiazolinone 4.1% in the South versus 2.1-2.7% in the remaining regions. CONCLUSIONS: Notwithstanding residual methodological variation (affecting at least some 'difficult' allergens) tackled by ongoing efforts for standardization, a comparative analysis as presented provides (i) a broad overview on contact allergy frequencies and (ii) interesting starting points for further, in-depth investigation.

Diagnosis and therapy of retained fetal membranes, puerperal metritis and clinical endometritis in cattle: Results of the Online-survey among Swiss practitioners. I Retained fetal membranes

The aim of this study was to obtain the diagnostic and therapeutic approach among Swiss practitioners in cows with retained fetal membranes (RFM) (part 1). All members of the Association for ruminant health were contacted per email via the newsletter. The survey was completed by 128 veterinarians, partially responded by 140 veterinarians. The manual removal of the fetal membranes is practiced by 129 of the responding veterinarians. Cows with/without fever are treated usually with intrauterine antibiotics. Cows with RFM with/without fever are most commonly treated parenterally with tetracycline or penicillin. The use of cephalosporins and quinolones in cows with fever is more common than in cows without fever. With the present results of the survey veterinarians should critically question the supposed benefits of the manual removal of the placenta and the use of antibiotics in cows with RFM.

Surface velocity and ice discharge of the ice cap on King George Island, Antarctica

Glaciers on King George Island, Antarctica, have shown retreat and surface lowering in recent decades, concurrent with increasing air temperatures. A large portion of the glacier perimeter is ocean-terminating, suggesting possible large mass losses due to calving and submarine melting. Here we estimate the ice discharge into the ocean for the King George Island ice cap. L-band synthetic aperture radar images covering the time-span January 2008 to January 2011 over King George Island are processed using an intensity-tracking algorithm to obtain surface velocity measurements. Pixel offsets from 40 pairs of radar images are analysed and inverted to estimate a weighted average surface velocity field. Ice thicknesses are derived from simple principles of ice flow mechanics using the computed surface velocity fields and in situ thickness data. The maximum ice surface speeds reach mayor que 225 m/yr, and the total ice discharge for the analysed flux gates of King George Island is estimated to be 0.720+/-0.428 Gt/yr, corresponding to a specific mass loss of 0.64+/-0.38 m w.e./yr over the area of the entire ice cap (1127 km2).

The pre-raphaelite female muse in Julia margaret cameron’s “idylls of the king” photographs

There has been little discussion of Julia Margaret Cameron’s Idylls of the King photographs over the past decade. My goal with this paper is to bring her Idylls of the King series back into discussion and address its success and relevance in both art history and literature. Scholars Helmut Gernsheim and Marylu Hill have questioned photography as a means to capture the imaginative content of Tennyson’s Arthurian stories and they declared Cameron’s photographs a failure. I argue that her theatrical style, use of props and costumes, obvious posing of her models, and nod to Victorian tableaux vivants capture the true essence of Tennyson’s epic. Her use of the Pre-Raphaelite female muse to portray the Arthurian characters of Elaine, Guinevere, and Vivien places her photographs in direct correlation with Pre-Raphaelite painting as well as popular literature. Her depictions of Tennyson’s epic poem are highly successful and I believe she achieved her personal goal of ennobling photography to the level of High Art.

(Table 1) Number of invertebrate species per bottom trawl haul in the Kapp Norvegia to Halley Bay area on cruise EASIZ I (ANT-XIII/3) and in the Kapp Norvegia - Austasen area on cruise EASIZ III (ANT-XVII/3)

Ecological work carried out on the Antarctic and Magellan shelves since the first IBMANT conference held at the UMAG, Punta Arenas in 1997 is summarized to identify areas where progress has been made and others, where impor- tant gaps have remained in understanding past and present interaction between the Antarctic and the southern tip of South America. This information is complementary to a review on shallow-water work along the Scotia Arc (Barnes, 2005) and recent work done in the deep sea (Brandt and Hilbig, 2004). While principally referring to shipboard work in deeper water, above all during the recent international EASIZ and LAMPOS campaigns, relevant work from shore stations is also included. Six years after the first IBMANT symposium, significant progress has been made along the latitudinal gradient from the Magellan region to the high Antarctic in the fields of biodiversity, biogeography and community structure, life strategies and adaptations, the role of disturbance and its significance for biodiversity, and trophic coupling of the benthic realm with the water column and sea ice. A better understanding has developed of the role of evolutionary and ecological factors in shaping past and present-day environmental conditions, species composition and distribution, and ecosystem functioning. Furthermore, the science community engaged in unravelling Antarctic-Magellan interactions has advanced in methodological aspects such as new analytical approaches for comparing biodiversity derived from visual methods, growth and age determination, trophic modelling using stable isotope ratios, and molecular approaches for taxonomic and phylogenetic purposes. At the same time, much effort has been invested to complement the species inventory of the two adjacent regions. However, much work remains to be done to fill the numerous gaps. Some perspectives are outlined in this review, and sug- gestions are made where particular emphasis should be placed in future work, much of which will be developed in the frame of SCAR's EBA (Evolution and Biodiversity in the Antarctic) programme.

Atlantic 231Pa/230Th and biogenic opal compilation of the Holocene and the LGM

The strength and geometry of the Atlantic meridional overturning circulation is tightly coupled to climate on glacial-interglacial and millennial timescales, but has proved difficult to reconstruct, particularly for the Last Glacial Maximum. Today, the return flow from the northern North Atlantic to lower latitudes associated with the Atlantic meridional overturning circulation reaches down to approximately 4,000 m. In contrast, during the Last Glacial Maximum this return flow is thought to have occurred primarily at shallower depths. Measurements of sedimentary 231Pa/230Th have been used to reconstruct the strength of circulation in the North Atlantic Ocean, but the effects of biogenic silica on 231Pa/230Th-based estimates remain controversial. Here we use measurements of 231Pa/230Th ratios and biogenic silica in Holocene-aged Atlantic sediments and simulations with a two-dimensional scavenging model to demonstrate that the geometry and strength of the Atlantic meridional overturning circulation are the primary controls of 231Pa/230Th ratios in modern Atlantic sediments. For the glacial maximum, a simulation of Atlantic overturning with a shallow, but vigorous circulation and bulk water transport at around 2,000 m depth best matched observed glacial Atlantic 231Pa/230Th values. We estimate that the transport of intermediate water during the Last Glacial Maximum was at least as strong as deep water transport today.