bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia‐inducible factor 1–mediated human GATA1 induction promotes erythroid differentiation under hypoxic conditions
Authors: Zhang Feng‐Lin , Shen Guo‐Min , Liu Xiao‐Ling , Wang Fang , Zhao Ying‐Ze , Zhang Jun‐Wu
Published: November 2011

Hypoxia‐inducible factor promotes erythropoiesis through coordinated cell type–specific hypoxia responses. GATA1 is essential to normal erythropoiesis and plays a crucial role in erythroid differentiation. In this study, we show that hypoxia‐induced GATA1 expression is mediated by HIF1 in erythroid cells. Under hypoxic conditions, significantly increased GATA1 mRNA and protein levels were detected in K562 cells and erythroid induction cultures of CD34+ haematopoietic stem/progenitor cells. Enforced HIF1α expression increased GATA1 expression, while HIF1α knockdown by RNA interference decreased GATA1 expression. In silico analysis revealed one potential hypoxia response element (HRE). The results from reporter gene and mutation analysis suggested that this element is necessary for hypoxic response. Chromatin immunoprecipitation (ChIP)‐PCR showed that the putative HRE was recognized and bound by HIF1 in vivo. These results demonstrate that the up‐regulation of GATA1 during hypoxia is directly mediated by HIF1.The mRNA expression of some erythroid differentiation markers was increased under hypoxic conditions, but decreased with RNA interference of HIF1α or GATA1. Flow cytometry analysis also indicated that hypoxia, desferrioxamine or CoCl2 induced expression of erythroid surface markers CD71 and CD235a, while expression repression of HIF1α or GATA1 by RNA interference led to a decreased expression of CD235a. These results suggested that HIF1‐mediated GATA1 up‐regulation promotes erythropoiesis in order to satisfy the needs of an organism under hypoxic conditions.
The rare occurrence of three subungual melanomas in one patient
Authors: Liu Yeqiang , Wang Lei
Published: November 2011

Subungual melanoma commonly presents with solitary longitudinal melanonychia. Herein, we report the case of a patient with subungual melanoma who developed involvement of three digits by three independent primary melanomas. A 98‐year‐old male patient presented with a two‐year history of longitudinal melanonychia on three different fingernails. Histopathologically, all three lesions were proved to be melanoma. To our knowledge, this is the first reported case in which three subungual melanomas developed in one patient. Our case indicates that that not all examples of multiple longitudinal melanonychia represent benign lesions.

Liu Y, Wang L. The rare occurrence of three subungual melanomas in one patient.
Acclimatization improves submaximal exercise economy at 5533 m
Authors: Latshang T. D. , Turk A. J. , Hess T. , Schoch O. D. , Bosch M. M. , Barthelmes D. , Merz T. M. , Hefti U. , Hefti J. Pichler , Maggiorini M. , Bloch K. E.
Published: November 2011

We tested whether the better subjective exercise tolerance perceived by mountaineers after altitude acclimatization relates to enhanced exercise economy. Thirty‐two mountaineers performed progressive bicycle exercise to exhaustion at 490 m and twice at 5533 m (days 6–7 and day 11), respectively, during an expedition to Mt. Muztagh Ata. Maximal work rate (Wmax) decreased from mean ± SD 356 ± 73 watts at 490 m to 191 ± 49 watts and 193 ± 45 watts at 5533 m, days 6–7 and day 11, respectively; corresponding maximal oxygen uptakes (VO2max) were 50.7 ± 9.5, 26.3 ± 5.6, 24.7 ± 7.0 mL/min/kg (P = 0.0001 5533 m vs 490 m). On days 6–7 (5533 m), VO2 at 75% Wmax (152 ± 37 watts) was 1.75 ± 0.45 L/min, oxygen saturation 68 ± 8%. On day 11 (5533 m), at the same submaximal work rate, VO2 was lower (1.61 ± 0.47 L/min, P < 0.027) indicating improved net efficiency; oxygen saturation was higher (74 ± 7%, P < 0.0004) but ratios of VO2 to work rate increments remained unchanged. On day 11, mountaineers climbed faster from 4497 m to 5533 m than on days 5–6 but perceived less effort (visual analog scale 50 ± 15 vs 57 ± 20, P = 0.006) and reduced symptoms of acute mountain sickness. We conclude that the better performance and subjective exercise tolerance after acclimatization were related to regression of acute mountain sickness and improved submaximal exercise economy because of lower metabolic demands for non‐external work‐performing functions.
Accuracy of professional sports drafts in predicting career potential
Authors: Koz D. , Fraser‐Thomas J. , Baker J.
Published: November 2011

The forecasting of talented players is a crucial aspect of building a successful sports franchise and professional sports invest significant resources in making player choices in sport drafts. The current study examined the relationship between career performance (i.e. games played) and draft round for the National Football League, National Hockey League, National Basketball League, and Major League Baseball for players drafted from 1980 to 1989 (n = 4874) against the assumption of a linear relationship between performance and draft round (i.e. that players with the most potential will be selected before players of lower potential). A two‐step analysis revealed significant differences in games played across draft rounds (step 1) and a significant negative relationship between draft round and games played (step 2); however, the amount of variance accounted for was relatively low (less than 17%). Results highlight the challenges of accurately evaluating amateur talent.
Cyclic loading of tendon fascicles using a novel fatigue loading system increases interleukin‐6 expression by tenocytes
Authors: Legerlotz K. , Jones G. C. , Screen H. R. C. , Riley G. P.
Published: November 2011

Repetitive strain or ‘overuse’ is thought to be a major factor contributing to the development of tendinopathy. The aims of our study were to develop a novel cyclic loading system, and use it to investigate the effect of defined loading conditions on the mechanical properties and gene expression of isolated tendon fascicles. Tendon fascicles were dissected from bovine‐foot extensors and subjected to cyclic tensile strain (1 Hz) at 30% or 60% of the strain at failure, for 0 h (control), 15 min, 30 min, 1 h, or 5 h. Post loading, a quasi‐static test to failure assessed damage. Gene expression at a selected loading regime (1 h at 30% failure strain) was analyzed 6 h post loading by quantitative real‐time polymerase chain reaction. Compared with unloaded controls, loading at 30% failure strain took 5 h to lead to a significant decrease in failure stress, whereas loading to 60% led to a significant reduction after 15 min. Loading for 1 h at 30% failure strain did not create significant structural damage, but increased Collagen‐1‐alpha‐chain‐1 and interleukin‐6 (IL6) expression, suggesting a role of IL6 in tendon adaptation to exercise. Correlating failure properties with fatigue damage provides a method by which changes in gene expression can be associated with different degrees of fatigue damage.
New insights into the functions and localization of nuclear transglutaminase 2
Authors: Kuo Ting‐Fang , Tatsukawa Hideki , Kojima Soichi
Published: November 2011

Transglutaminase 2 (TG2; EC 2.3.2.13) is the most abundantly expressed member of the transglutaminase family and exerts opposing effects on cell growth, differentiation and apoptosis via multiple activities, including transamidase, GTPase, cell adhesion, protein disulfide isomerase, kinase and scaffold activities. It is distributed in and around various parts of a cell, including the extracellular matrix, plasma membrane, cytosol, mitochondria and nucleus. Generally, nuclear TG2 represents only 5–7% of the total TG2 in a cell, and various stimuli will increase nuclear TG2 via cellular stress and/or an increased intracellular Ca2+ concentration. There is increasing evidence indicating the importance of nuclear TG2 in regulating gene expression via post‐translational modification of (or interaction with) transcriptional factors and related proteins. These include E2F1, hypoxia inducible factor 1, Sp1 and histones. Through this mechanism, TG2 controls cell growth or survival, differentiation and apoptosis, and is involved in the pathogenesis and/or treatment of neurodegenerative diseases, liver diseases and cancers. The balance between import from the cytoplasm to the nucleus, and export from the nucleus to the cytoplasm, determines the level of TG2 in the nucleus. Selective regulation of the expression, activity or localization of nuclear TG2 will be important for basic research, as well as clinical applications, suggesting a new era for this long‐studied enzyme.
Association of mannose‐binding lectin gene polymorphism with tuberculosis susceptibility and sputum conversion time
Authors: Singla N. , Gupta D. , Joshi A. , Batra N. , Singh J. , Birbian Niti
Published: November 2011

Mannose‐binding lectin (MBL) plays an important role in innate immunity. The effect of low MBL levels producing variants of MBL2 gene on tuberculosis (TB) has been controversial with some studies reporting it to confer protection against the disease, whereas others estimating a susceptibility relation. Other than conducting a case–control study to evaluate the role of MBL A/B polymorphism on TB, we conducted a longitudinal study to check whether this MBL variant can influence the host response to Mycobacterium tuberculosis infection. A total of 357 TB patients (286 pulmonary TB, 71 extrapulmonary (EP) TB) and 392 healthy controls belonging to same ethnicity were included in the study. We found the mutant allele ‘B’ allele confers a protective role against TB in our study population. This effect was absent in EP patients. On stratification on the basis of sex, the protective role of the ‘B’ allele was found to be limited to females only and males reported no significant difference. No effect of MBL A/B polymorphism on sputum conversion time was reported. We conclude that MBL ‘B’ allele is associated with protection against TB, but no influence was found on sputum conversion rate.
Nitrogen fertiliser affects the functional response and prey consumption ofHarmonia axyridis(Coleoptera: Coccinellidae) feeding on cereal aphids
Authors: Aqueel M.A. , Leather S.R.
Published: November 2011

Predator–prey interactions are influenced by nitrogen availability. Wheat (Triticum aestivumcv. Solstice) plants were provided with four levels of nitrogen and examined the responses of coccinellid predator,Harmonia axyridisto cereal aphids,Rhopalosiphum padiandSitobion avenae. Increased nitrogen application improved nitrogen contents of the plants and also the body weight of cereal aphids feeding on them. In no‐choice feeding trials,H. axyridisconsumed more aphids on low fertilised plants, suggesting a compensatory consumption to overcome reduced biomass (lower aphid size). Total biomass devoured byH. axyridison all nitrogen fertiliser treatments was not statistically different. Logistic regression analysis of the proportion of prey consumed demonstrated that all developmental stages (larval and adult) ofH. axyridisexhibited the type II functional response on all nitrogen fertiliser treatments. The rate of successful search (a′) of third and fourth instars and adults were the same across all fertiliser treatments suggesting that nitrogen fertilisation did not affecta′. Maximum handling time for the first instars ofH. axyridisonR. padi(3.81 h−1) andS. avenae(4.59 h−1) was on the highest nitrogen treatment while minimum handling time was for the adults ofH. axyridisonR. padi(0.20 h−1) andS. avenae(0.20 h−1) on the lowest nitrogen treatment. Handling time varied at varying fertiliser treatments within all instars and affected the predator's efficiency. The functional response curve, rate of successful search and handling time provide the information needed to understand the predator–prey interaction betweenH. axyridisand these cereals aphids. This could lead to the development of a better strategy for the biological control ofR. padiandS. avenaeat any particular level of nitrogen fertiliser regime in the field crops.
Myeloperoxidase‐positive acute megakaryoblastic leukemia in a dog
Authors: Ferreira Helena M.T. , Smith Sionagh H. , Schwartz Anita M. , Milne Elspeth M.
Published: November 2011

A 16‐month‐old female spayedLabrador Retriever was referred to the University ofEdinburgh for exercise intolerance, inappetence, and severe anemia. ACBCshowed severe nonregenerative anemia and moderate numbers of atypical cells with morphologic features most consistent with megakaryoblastic origin. Similar cells were identified in a bone marrow aspirate and accounted for 23% of all nucleated cells. Atypical promegakaryocytes and megakaryocytes were also noted. Myelodysplastic syndrome affecting the megakaryocytic lineage was suspected. Cytologic examination of a fine‐needle aspirate of the spleen revealed rare megakaryoblasts similar to those in blood and bone marrow. At necropsy, the bone marrow consisted of atypical megakaryoblasts and megakaryocytes that were also infiltrating spleen, liver, lymph nodes, renal perihilar tissue, and visceral adipose tissue, consistent with acute megakaryoblastic leukemia. Immunohistochemical analysis of splenic sections confirmed megakaryoblastic origin (immunoreactive forCD61 and vonWillebrand factor). Some leukemic cells were also immunoreactive for myeloperoxidase (MPO). This aberrant immunophenotype suggested both megakaryocytic and granulocytic/monocytic differentiation of the leukemic cells. To our knowledge, this is the first report ofMPO‐positive acute megakaryoblastic leukemia in a dog.
Chromatophoroma in a crevice kelpfish (Gibbonsia montereyensis)
Authors: Camus Melinda S. , Hyatt Michael W. , Clauss Tonya M. , Berliner Aimee L. , Camus Alvin C.
Published: November 2011

A captive adult crevice kelpfish, Gibbonsia montereyensis, developed a cutaneous mass, approximately 9 × 7 mm on the right side of the head in an area of nonscaled skin. Following surgical debulking, examination of both impression smears and histologic sections of the tumor revealed a predominant population of round to spindloid to polygonal cells with a moderate amount of lightly basophilic cytoplasm. The cytoplasm was filled with round, variably‐sized reddish‐brown granules that often obscured the nucleus. Nuclei were round to ovoid with coarsely granular chromatin. There was minimal anisocytosis and anisokaryosis. The cytoplasmic granules in histologic sections were weakly positive by the Fontana‐Masson method, and staining was eliminated with melanin bleach. Immunohistochemical staining was strongly positive with a murine monoclonal antibody for melan A. As the specificity of melan A for melanophores is not clearly defined in nonmammalian species, the tumor was examined by transmission electron microscopy. Melanophores were not detected. Instead, neoplastic cells were filled with numerous intracytoplasmic organelles with triple‐limiting membranes composed of concentric lamellae; these structures were most compatible with pterinosomes, which are the pigment‐containing organelles of cells called xanthophores and erythrophores. As both of these organelles are ultrastructurally indistinguishable and as kelpfish skin is known to contain both xanthophores and erythrophores, a diagnosis of a mixed pigment cell tumor or chromatophoroma was made. As the tumor was grossly reddish‐brown, the possibility of a neoplastic population of only erythrophores could not be excluded. Pigment cell tumors, arising from cells of the embryonic neural crest, are common in reptiles and bony fish.
Processing of equine bone marrow using the automated MarrowXpress System: RBC depletion, volume reduction, and mononuclear cell recovery
Authors: Owens Sean D. , Burges Julie , Johns Jennifer L. , Carrade Danielle D. , Galuppo Larry D. , Librach Fred , Borjesson Dori L.
Published: November 2011

Background

The therapeutic use of bone marrow‐derived mononuclear cells (MNCs) and mesenchymal stem cells for the treatment of soft tissue and orthopedic injuries in equine patients is expanding. After collection, bone marrow must be reduced in volume and depleted of RBCs for immediate therapeutic use or to prepare cells for culture or cryopreservation and storage. The MarrowXpress (MXP) System is an automated, closed, sterile system designed to process human bone marrow samples.

Objectives

The purpose of this study was to evaluate the capacity of the MXP System to process equine bone marrow to reduce volume, deplete RBCs, and enhance recovery of MNCs.

Methods

Bone marrow was collected from 47 horses into 2 60‐mL syringes containing heparin and processed using the MXP System. HCT, total nucleated cell (TNC) count, and MNC count were obtained for each sample before and after processing using an Advia 120 hematology analyzer. Volume reduction, RBC depletion, and recovery of TNCs and MNCs were calculated.

Results

For equine bone marrow samples, mean values were 73.2% for RBC depletion and 78.0% for volume reduction. TNC count before processing was 2.5 ± 1.2 × 107 and after processing was significantly higher at 7.8 ± 3.3 × 107 (P < .0001), with a recovery of 68.5 ± 24.5% (mean ± SD). MNC count before processing was 1.1 ± 0.9 × 107 and after processing was significantly higher at 3.8 ± 1.9 × 107 (P < .0001), with a recovery 73.0 ± 31.5%.

Conclusions

The MXP System can reliably reduce volume and deplete RBCs from aspirates of equine bone marrow aspirates. MNCs can be recovered in a reproducible and sterile manner. Further studies evaluating the effects of the MXP System on cell viability, identification of mesenchymal stem cells (MSCs), and the efficacy of MSC expansion are warranted.
The Next Generation of Psychological Autopsy Studies
Authors: Conner Kenneth R. , Beautrais Annette L. , Brent David A. , Conwell Yeates , Phillips Michael R. , Schneider Barbara
Published: November 2011

The psychological autopsy (PA) is a systematic method to understand the psychological and contextual circumstances preceding suicide. The method requires interviews with one or more proxy respondents (i.e., informants) of decedents. The methodological challenges that need to be addressed when determining the content of these research interviews for PA studies are described and recommendations are made for meeting these challenges in future PA investigations. Ways to improve the data collected about mental disorders and life events—domains that are assessed in almost all PA studies—are discussed at length. Other understudied content areas considered include the role of personality traits, medical illness and functional limitations, availability of lethal agents, medications, and select distal variables including child maltreatment and family history of mental disorders and suicide. The benefits and challenges to using common protocols across studies are also discussed.
Selective placement of DNA origami on substrates patterned by nanoimprint lithography
Authors: Penzo Erika , Wang Risheng , Palma Matteo , Wind Shalom J
Published: November 2011

Self-assembled DNA nanostructures can be used as scaffolds to organize small functional nanocomponents. In order to build working devices—electronic circuits, biochips, optical/photonics devices—controlled placement of DNA nanostructures on substrates must be achieved. Here we present a nanoimprint lithography-based process to create chemically patterned templates, rendering them capable of selectively binding DNA origami. Hexamethyldisilazane (HMDS) is used as a passivating layer on silicon dioxide substrates, which prevents DNA attachment. Hydrophilic areas, patterned by nanoimprint lithography with the same size and shape of the origami, are formed by selective removal of the HMDS, enabling the assembly of the origami scaffolds in the patterned areas. The use of nanoimprint lithography, a low cost, high throughput patterning technique, enables high precision positioning and orientation of DNA nanostructures on a surface over large areas.
Suitability of thin poly(dimethylsiloxane) as an antisticking layer for UV nanoimprinting
Authors: Okada Makoto , Haruyama Yuichi , Kanda Kazuhiro , Matsui Shinji
Published: November 2011

The antisticking capabilities and durability of thin poly(dimethylsiloxane) (PDMS) were compared to a fluorinated antisticking layer (F-ASL) to assess its suitability for use in UV nanoimprint lithography (UV-NIL). Typically, UV-NIL is used to fabricate high-throughput, low-cost, high-resolution nanostructure devices. The nanoimprint mold is typically coated with an antisticking layer to ensure easy separation of the mold from the UV nanoimprint resins. This layer must be highly durable to meet the demands of a manufacturing environment, and F-ASL is the standard type used. In PS-b-PDMS block copolymer lithography, the template is coated with a thin layer of PDMS. In this study, we focused on using PDMS as the antisticking layer for nanoimprinting and examined its antisticking capabilities and durability by step and repeat (S&R) UV nanoimprinting. Experimental results showed that the thin PDMS layer functions comparably to the F-ASL as an antisticking layer.
Development of an experimental technique for testing rheological properties of ultrathin polymer films used in nanoimprint lithography
Authors: Jarzabek Dariusz M. , Rymuza Zygmunt , Horiba Akira , Hirai Yoshihiko
Published: November 2011

A new method for the measurement of rheological properties (complex viscosity, viscosity and elasticity) of thin polymeric films is presented. The probe, which is placed on the end of an arm of a mini tuning fork, is caused to oscillate and then is put into poly(methyl methacrylate) films, whose thickness ranges from 30 nm to 1080 nm. All measured properties depend on temperature, thickness of the films, indentation depth and the molecular weight of PMMA. Complex viscosity, viscosity and elasticity are found to be lower at higher temperatures and higher with greater molecular weight. They are also lower for thicker films. The results gained from this experiment may be useful in the development of nanoimprint lithography and many other branches of nanotechnology. Furthermore, the method allows for the measurement of the rheological properties of many different thin films (nanoimprint polymers, oils, lubricants) at different temperatures.
Thermal chemistry of Mn2(CO)10 during deposition of thin manganese films on silicon oxide and on copper surfaces
Authors: Qin Xiangdong , Sun Huaxing , Zaera Francisco
Published: November 2011

The surface chemistry of dimanganese decacarbonyl on the native oxide of Si(100) wafers was characterized with the aid of x-ray photoelectron spectroscopy. Initial experiments in a small stainless-steel reactor identified a narrow range of temperatures, between approximately 445 and 465 K, in which the deposition of manganese could be achieved in a self-limiting fashion, as is desirable for atomic layer deposition. Deposition at higher temperatures leads to multilayer growth, but the extent of this Mn deposition reverses at even higher temperatures (about 625 K), and also ifhydrogen is added to the reaction mixture. Extensive decarbonylation takes place below room temperature, but limited C–O bond dissociation and carbon deposition are still seen after high exposures at 625 K. The films deposited at low (∼450 K) temperatures are mostly in the form of MnO, but at 625 K that converts to a manganese silicate, and upon higher doses a manganese silicide forms at the SiO2/Si(100) interface as well. No metallic manganese could be deposited with this precursor on either silicon dioxide or copper surfaces.
Atmospheric Blocking and Atlantic Multidecadal Ocean Variability
Authors: Häkkinen Sirpa , Rhines Peter B. , Worthen Denise L.
Published: November 2011

Changing ocean circulation patterns and sea surface temperatures affect atmospheric flow in the North Atlantic region.
Response to Comment on “Atmospheric
P
co
2
Perturbations Associated with the Central Atlantic Magmatic Province”
Authors: Schaller Morgan F. , Wright James D. , Kent Dennis V.
Published: November 2011

Rampino and Caldeira argue that the first pulse of the Central Atlantic Magmatic Province would increase the concentration of atmospheric carbon dioxide (
P
co
2
) by only 400 parts per million if erupted over 20,000 years, whereas we observed a doubling within this interval. In the absence of any data to the contrary, we suggest that a more rapid (≤1000-year) eruption is sufficient to explain this observation without relying on thermogenic degassing.
Neural Mechanisms for the Coordination of Duet Singing in Wrens
Authors: Fortune Eric S. , Rodríguez Carlos , Li David , Ball Gregory F. , Coleman Melissa J.
Published: November 2011

The brains of duetting wrens encode the entire song and not just the contribution of the individual.
The Pace of Shifting Climate in Marine and Terrestrial Ecosystems
Authors: Burrows Michael T. , Schoeman David S. , Buckley Lauren B. , Moore Pippa , Poloczanska Elvira S. , Brander Keith M. , Brown Chris , Bruno John F. , Duarte Carlos M. , Halpern Benjamin S. , Holding Johnna , Kappel Carrie V. , Kiessling Wolfgang , O’Connor Mary I. , Pandolfi John M. , Parmesan Camille , Schwing Franklin B. , Sydeman William J. , Richardson Anthony J.
Published: November 2011

Ecologically relevant measures of contemporary global climate change can predict species distributions and vulnerabilities.
Paying for Ecosystem Services—Promise and Peril
Authors: Kinzig A. P. , Perrings C. , Chapin F. S. , Polasky S. , Smith V. K. , Tilman D. , Turner B. L.
Published: November 2011

Payment mechanisms designed without regard to the properties of the services they cover may be environmentally harmful.
A Fluoride-Derived Electrophilic Late-Stage Fluorination Reagent for PET Imaging
Authors: Lee Eunsung , Kamlet Adam S. , Powers David C. , Neumann Constanze N. , Boursalian Gregory B. , Furuya Takeru , Choi Daniel C. , Hooker Jacob M. , Ritter Tobias
Published: November 2011

A palladium compound facilitates rapid incorporation of radioactive fluoride into prospective tracers for medical imaging.
Paradigm Shifts in Dye-Sensitized Solar Cells
Authors: McGehee Michael D.
Published: November 2011

Efficiency limitations from the iodine-based electron shuttle have been overcome by replacing it with cobalt compounds and by using dyes that block recombination.
Pangaea Penultima
1493
Uncovering the New World Columbus Created

by Charles C. Mann

Knopf, New York, 2011. 557 pp. $30.50, C$34.50. ISBN 9780307265722.
Authors: Farmer Jared
Published: November 2011

Mann describes the course and consequences of the ecological convulsion set off by the intercontinental maritime trade that followed Columbus's arrival in the Americas.
Copernicus and the Science of the Stars
The Copernican Question
Prognostication, Skepticism, and Celestial Order

by Robert S. Westman

University of California Press, Berkeley, 2011. 700 pp. $95, £65. ISBN 9780520254817.
Authors: Dear Peter
Published: November 2011

In a book that has been 40 years in the making, Westman shows how important astrology was to Copernicus's work and its interpretation into the early 17th century.
Growth Signaling from Inside
Authors: Abrahamsen Hilde , Stenmark Harald
Published: November 2011

Sensing of amino acids inside lysosomes by a proton pump initiates a chain of events that stimulates cell growth.
Another Reason to Exercise
Authors: Gitler Aaron D.
Published: November 2011

Can exercise slow neurodegeneration?
Understanding the Human Brain
Authors: Brenner Sydney , Sejnowski Terrence J.
Published: November 2011

Like most fields in biology, neuroscience is succumbing to an “epidomic” of data collecting. There are major projects under way to completely characterize the proteomic, metabolomic, genomic, and methylomic signatures for all of the different types of neurons and glial cells in the human brain. In addition, “connectomics” plans to provide the complete network structure of brains, and “synaptomics” aims to uncover all molecules and their interactions at synapses. This is a good time to pause and ask ourselves what we expect to find at the end of this immense omic brainbow.
Panel Endorses Anthrax Vaccine Study in Children
Authors: Couzin-Frankel Jennifer
Published: November 2011

Last week, the full National Biodefense Science Board voted 12–1 in favor of a clinical trial of the anthrax vaccine in children, assuming its ethics are approved by a review board.
Large African TB Study Reveals Powerful Strategy to Curb Disease
Authors: Cohen Jon
Published: November 2011

An ambitious study exploring two strategies to increase tuberculosis testing and treatment found that one approach led to a 22% drop in TB over 3 years, whereas the other had no effect on prevalence of the disease.
Diabetes Genes Decline Out of Africa
Authors: Gibbons Ann
Published: November 2011

A thorough analysis of all known genetic variants associated with type 2 diabetes reveals that Africans face the highest known genetic risk from this epidemic, according to a new report at the meeting.
Vigil at North Korea's Mount Doom
Authors: Stone Richard
Published: November 2011

Changbai-Paektu unleashed one of the largest eruptions in recent millennia; scientists are joining arms to discern when the volcano may roar back to life.
A Very Big Bang
Authors: Stone Richard
Published: November 2011

The millennium eruption of Changbai, a volcano that straddles the border between North Korea and China, was one of the biggest in recorded history and is an enduring riddle.
LIFE SCIENCE TECHNOLOGIES: Gene-Expression Analysis Exploits More Technologies
Authors: May Mike
Published: November 2011

To quantify the expression of specific genes, researchers can use a variety of techniques, including arrays, PCR, and high throughput sequencing. However, getting accurate results still depends on precisely carrying out these methods, even with increasingly user-friendly technologies. In fact, as more scientists study gene expression, the standards for analysis are growing more rigorous to ensure that only accurate data are published. Likewise, software has been keeping pace, helping researchers follow protocols and analyze their results.
Achy breaky makey wakey heart? A randomised crossover trial of musical prompts
Authors: Woollard Malcolm , Poposki Jason , McWhinnie Brae , Rawlins Lettie , Munro Graham , O'Meara Peter
Published: November 2011

Objective

Compared with no music (NM), does listening to ‘Achy breaky heart’ (ABH) or ‘Disco science’ (DS) increase the proportion of prehospital professionals delivering chest compressions at 2010 guideline-compliant rates of 100–120 bpm and 50–60 mm depths?

Methods

A randomised crossover trial recruiting at an Australian ambulance conference. Volunteers performed three 1-min sequences of continuous chest compressions on a manikin accompanied by NM, repeated choruses of ABH and DS, prerandomised for order.

Results

37 of 74 participants were men; median age 37 years; 61% were paramedics, 20% students and 19% other health professionals. 54% had taken cardiopulmonary resuscitation training within 1 year. Differences in compression rate (mode, IQR) were significant for NM (105, 99–116) versus ABH (120, 107–120) and DS (104, 103–107) versus ABH (p<0.001) but not NM versus DS (p=0.478). Differences in proportions of participants compressing at 100–120 bpm were significant for DS (61/74, 82%) versus NM (48/74, 65%, p=0.007) and DS versus ABH (47/74, 64%, p=0.007) but not NM versus ABH (p=1). Differences in compression depth were significant for NM (48 mm, 46–59 mm) versus DS (54 mm, 44–58 mm, p=0.042) but not NM versus ABH (54 mm, 43–59 mm, p=0.065) and DS versus ABH (p=0.879). Differences in proportions of subjects compressing at 50–60 mm were not significant (NM 31/74 (42%); ABH 32/74 (43%); DS 29/74 (39%); all p>0.5).

Conclusions

Listening to DS significantly increased the proportion of prehospital professionals compressing at 2010 guideline-compliant rates. Regardless of intervention more than half gave compressions that were too shallow. Alternative audible feedback mechanisms may be more effective.
Preanalytical mixing of whole-blood specimens in the context of the Athlete Passport
Authors: Ashenden Michael , Clarke Anthea , Sharpe Ken , d'Onofrio Giuseppe , Allbon Graeme , Gore Christopher J
Published: November 2011

Background

Full blood counts are now used as evidence that athletes have used banned blood doping. This has led to legal scrutiny of the efficacy of preanalytical procedures such as specimen homogenisation.

Aims

To characterise the impact of different mixing strategies on whole-blood homogeneity.

Methods

Manual inversion, mechanical mixing and automatic mixing performed by the Sysmex XT-2000i were evaluated.

Results

Automated mixing by the instrument, or 1 min of mechanical mixing, thoroughly homogenised specimens even for tubes that had been refrigerated and left undisturbed for 36 h. Manual inversions were almost as effective, provided that specimens were first allowed to equilibrate to ambient temperatures.

Conclusions

Current sport guidelines that mandate at least 15 min of mechanical mixing are excessive. Except where specimens are presented to the instrument manually, mechanical mixing is redundant in the context of full blood counts.
Is breast specimen shrinkage really a problem in breast-conserving surgery?
Authors: Krekel Nicole M A , van Slooten Henk Jan , Barbé Ellis , de Lange de Klerk Elly S M , Meijer Sybren , van den Tol M Petrousjka
Published: November 2011

Background

Breast-conserving surgery currently focuses on improving margin clearance and excision volume, the main pathology report parameters for oncological and cosmetic outcomes.

Aim

To quantitatively evaluate discrepancies in surgical and pathological estimates of breast specimen sizes, including the influence of formalin fixation.

Methods

This prospective multicentre study included 68 breast specimens of consecutive patients undergoing breast-conserving surgery for breast cancer in three affiliated hospitals between November 2010 to May 2011. Specimens were weighed immediately after excision. Specimen volumes were calculated from the length, width and height. Actual specimen volumes were measured using volume displacement. Specimens were weighed once again after arrival at the pathology department, and volumes recalculated. The smallest pre- and post-fixation distances to the tumour-free margin were compared.

Results

The mean surgical specimen weight was 47.7 g and was approximately similar to the actual specimen volume of 49.8 cm3. The weights of specimens immediately following surgery and on pathological appraisal were equal (p=0.94). The calculated volumes differed significantly from the actual specimen volumes (p>0.05). The mean distance to the closest tumour-free margin, 0.35 cm, was not altered by formalin fixation (p=0.1).

Conclusions

No evidence was found to suggest that surgical breast specimens shrink in the period between the surgical procedure and pathological examination, or following formalin fixation. The pathological appraisal of specimen margins and volumes is not affected by changes in specimen size. As calculations of specimen volumes are unreliable, the use of water displacement or the more readily available specimen weight is recommended for accurate volume measurement. Pathologists should be encouraged to always measure and record specimen weight.
SIGNATURES OF EXOTIC HADRONS
Authors: RENGA FRANCESCO
Published: November 2011

Hadron spectroscopy represented in the past a major tool for understanding the fundamental symmetries of strong forces. More recently, the interest on this topic has been revitalized by the discovery of new quarkonium-like resonances, that do not fit in the standard picture and whose understanding could improve our mastery of quantum chromodynamics. I review here the experimental signatures of these exotic hadrons, at present and future e+e- and hadron collider experiments.
Switching flow patterns within the last ice sheet in northern Scotland
Authors: Hall A. M. , Auton C. A. , McL Michie U. , Pearson S. G. , Riding J. B.
Published: November 2011

Synopsis

A confluence zone existed within the northern sector of the last British Ice Sheet (BIS) where ice flowing from the Northern Highlands met ice streaming out of the Moray Firth and across the plain of Caithness. At Wester Clett, a complex 35m thick sequence of glacigenic sediments provides important evidence of dynamic interactions between these ice lobes that are consistent with recent computer simulations of the behaviour the last BIS.

Sedimentological evidence suggests that early advance of Northern Highlands ice, probably between 33.5 and 30.5 ka, was followed by a first incursion of Moray Firth ice. Ice flowing out of Strath Halladale then deposited sands and gravels along its margin. Later, around the time of the Last Glacial Maximum, a powerful flow of Moray Firth ice diverted Northern Highlands ice to flow to the NW across the present coastline, depositing tills of mixed provenance. Cosmogenic exposure dates of
c
. 18 ka for summits in southern Caithness indicate that the ice sheet thinned subsequently, but flow to the NW continued. The youngest till and its associated moraine systems record a final movement of Northern Highlands ice. Subsequent ice retreat was accompanied by uncoupling of ice lobes at the Caithness–Sutherland border soon after 16 ka.
Calsequestrin (CASQ1) rescues function and structure of calcium release units in skeletal muscles of CASQ1-null mice
Authors: Tomasi Mirta , Canato Marta , Paolini Cecilia , Dainese Marco , Reggiani Carlo , Volpe Pompeo , Protasi Feliciano , Nori Alessandra
Published: November 2011

Amplitude of Ca2+ transients, ultrastructure of Ca2+ release units, and molecular composition of sarcoplasmic reticulum (SR) are altered in fast-twitch skeletal muscles of calsequestrin-1 (CASQ1)-null mice. To determine whether such changes are directly caused by CASQ1 ablation or are instead the result of adaptive mechanisms, here we assessed ability of CASQ1 in rescuing the null phenotype. In vivo reintroduction of CASQ1 was carried out by cDNA electro transfer in flexor digitorum brevis muscle of the mouse. Exogenous CASQ1 was found to be correctly targeted to the junctional SR (jSR), as judged by immunofluorescence and confocal microscopy; terminal cisternae (TC) lumen was filled with electron dense material and its width was significantly increased, as judged by electron microscopy; peak amplitude of Ca2+ transients was significantly increased compared with null muscle fibers transfected only with green fluorescent protein (control); and finally, transfected fibers were able to sustain cytosolic Ca2+ concentration during prolonged tetanic stimulation. Only the expression of TC proteins, such as calsequestrin 2, sarcalumenin, and triadin, was not rescued as judged by Western blot. Thus our results support the view that CASQ1 plays a key role in both Ca2+ homeostasis and TC structure.
Ligand-induced internalization of the type 1 cholecystokinin receptor independent of recognized signaling activity
Authors: Cawston Erin E. , Harikumar Kaleeckal G. , Miller Laurence J.
Published: November 2011

Receptor ligands, identified as antagonists, based on the absence of stimulation of signaling, can rarely stimulate receptor internalization. d-Tyr-Gly-[(Nle28,31,d-Trp30)CCK-26–32]-2-phenylethyl ester (d-Trp-OPE) is such a ligand that binds to the cholecystokinin (CCK) receptor and stimulates internalization. Here, the molecular basis of this trafficking event is explored, with the assumption that ligand binding initiates conformational change, exposing an epitope to direct endocytosis. Ligand-stimulated internalization was studied morphologically using fluorescent CCK and d-Trp-OPE. d-Trp-OPE occupation of Chinese hamster ovary cell receptors stimulated internalization into the same region as CCK. Arrestin-biased action was ruled out using morphological translocation of fluorescent arrestin 2 and arrestin 3, moving to the membrane in response to CCK, but not d-Trp-OPE. Possible roles of the carboxyl terminus were studied using truncated receptor constructs, eliminating the proline-rich distal tail, the serine/threonine-rich midregion, and the remainder to the vicinal cysteines. None of these constructs disrupted d-Trp-OPE-stimulated internalization. Possible contributions of transmembrane segments were studied using competitive inhibition with peptides that also had no effect. Intracellular regions were studied with a similar strategy using coexpressing cell lines. Peptides corresponding to ends of each loop region were studied, with only the peptide at the carboxyl end of the third loop inhibiting d-Trp-OPE-stimulated internalization but having no effect on CCK-stimulated internalization. The region contributing to this effect was refined to peptide 309–323, located below the recognized G protein-association motif. While a receptor in which this segment was deleted did internalize in response to d-Trp-OPE, it exhibited abnormal ligand binding and did not signal in response to CCK, suggesting an abnormal conformation and possible mechanism of internalization distinct from that being studied. This interpretation was further supported by the inability of peptide 309–323 to inhibit its d-Trp-OPE-stimulated internalization. Thus the 309–323 region of the type 1 CCK receptor affects antagonist-stimulated internalization of this receptor, although its mechanism and interacting partner are not yet clear.
Oxidative stress contributes to sex differences in angiotensin II-mediated hypertension in spontaneously hypertensive rats
Authors: Bhatia Kanchan , Elmarakby Ahmed A. , El-Remessey Azza , Sullivan Jennifer C.
Published: November 2011

NADPH oxidase has been implicated in ANG II-induced oxidative stress and hypertension in males; however, the contribution of oxidative stress to ANG II hypertension in females is unknown. In the present study, we tested the hypothesis that greater antioxidant capacity in female spontaneously hypertensive rats (SHR) blunts ANG II-induced oxidative stress and hypertension relative to males. Whole body and renal cortical oxidative stress levels were assessed in female and male SHR left untreated or following 2 wk of chronic ANG II infusion. Chronic ANG II infusion increased NADPH oxidase enzymatic activity in the renal cortex of both sexes; however, this increase only reached significance in female SHR. In contrast, male SHR demonstrated a greater increase in all measurements of reactive oxygen species production in response to chronic ANG II infusion. ANG II infusion increased plasma superoxide dismutase activity only in female SHR (76 ± 9 vs. 190 ± 7 Units·ml−1·mg−1, P < 0.05); however, cortical antioxidant capacity was unchanged by ANG II in either sex. To assess the functional implication of alterations in NADPH enzymatic activity and oxidative stress levels following ANG II infusion, additional experiments assessed the ability of the in vivo antioxidant apocynin to modulate ANG II hypertension. Apocynin significantly blunted ANG II hypertension in male SHR (174 ± 2 vs. 151 ± 1 mmHg, P < 0.05), with no effect in females (160 ± 11 vs. 163 ± 10 mmHg). These data suggest that ANG II hypertension in male SHR is more dependent on increases in oxidative stress than in female SHR.
Norepinephrine reduces ω-conotoxin-sensitive Ca2+ currents in renal afferent neurons in rats
Authors: Ditting Tilmann , Linz Peter , Freisinger Wolfgang , Heinlein Sonja , Reeh Peter W. , Fiedler Christian , Siegel Kirsten , Scrogin Karie E. , Neuhuber Winfried , Veelken Roland
Published: November 2011

Sympathetic efferent and peptidergic afferent renal nerves likely influence hypertensive and inflammatory kidney disease. Our recent investigation with confocal microscopy revealed that in the kidney sympathetic nerve endings are colocalized with afferent nerve fibers (Ditting T, Tiegs G, Rodionova K, Reeh PW, Neuhuber W, Freisinger W, Veelken R. Am J Physiol Renal Physiol 297: F1427–F1434, 2009; Veelken R, Vogel EM, Hilgers K, Amman K, Hartner A, Sass G, Neuhuber W, Tiegs G. J Am Soc Nephrol 19: 1371–1378, 2008). However, it is not known whether renal afferent nerves are influenced by sympathetic nerve activity. We tested the hypothesis that norepinephrine (NE) influences voltage-gated Ca2+ channel currents in cultured renal dorsal root ganglion (DRG) neurons, i.e., the first-order neuron of the renal afferent pathway. DRG neurons (T11–L2) retrogradely labeled from the kidney and subsequently cultured, were investigated by whole-cell patch clamp. Voltage-gated calcium channels (VGCC) were investigated by voltage ramps (−100 to +80 mV, 300 ms, every 20 s). NE and appropriate adrenergic receptor antagonists were administered by microperfusion. NE (20 μM) reduced VGCC-mediated currents by 10.4 ± 3.0% ( P < 0.01). This reduction was abolished by the α-adrenoreceptor inhibitor phentolamine and the α2-adrenoceptor antagonist yohimbine. The β-adrenoreceptor antagonist propranolol and the α1-adrenoceptor antagonist prazosin had no effect. The inhibitory effect of NE was abolished when N-type currents were blocked by ω-conotoxin GVIA, but was unaffected by other specific Ca2+ channel inhibitors (ω-agatoxin IVA; nimodipine). Confocal microscopy revealed sympathetic innervation of DRGs and confirmed colocalization of afferent and efferent fibers within in the kidney. Hence NE released from intrarenal sympathetic nerve endings, or sympathetic fibers within the DRGs, or even circulating catecholamines, may influence the activity of peptidergic afferent nerve fibers through N-type Ca2+ channels via an α2-adrenoceptor-dependent mechanism. However, the exact site and the functional role of this interaction remains to be elucidated.
D2-like dopamine receptors differentially regulate unitary IPSCs depending on presynaptic GABAergic neuron subtypes in rat nucleus accumbens shell
Authors: Kohnomi Shuntaro , Koshikawa Noriaki , Kobayashi Masayuki
Published: November 2011

In the nucleus accumbens (NAc), a medium spiny (MS) neuron receives GABAergic inputs from two major sources: fast-spiking (FS) neurons and other, adjacent MS neurons. These two types of inhibitory synapses are considered to play different roles in output activities, i.e., FS→MS connections suppress output from the NAc whereas MS→MS connections contribute to lateral inhibition. In the present study, we focused on the electrophysiological properties of unitary inhibitory postsynaptic currents (uIPSCs) obtained from MS→MS connections and FS→MS connections and examined the effects of quinpirole, a dopamine D2-like receptor agonist, on uIPSCs with multiple whole cell patch-clamp recording. Application of quinpirole (1 μM) reliably suppressed the amplitude of uIPSCs by 29.6% in MS→MS connections, with increases in paired-pulse ratio and failure rate. The suppressive effects of quinpirole on uIPSCs were mimicked by 1 μM PD128907, a D2/3 receptor agonist, whereas quinpirole-induced suppression of uISPCs was blocked by preapplication of 1 μM sulpiride or 10 μM nafadotride, both D2/3 receptor antagonists. On the other hand, quinpirole (1 μM) had divergent effects on FS→MS connections, i.e., quinpirole increased uIPSC amplitude in 38.1% of FS→MS connections and 23.8% of FS→MS connections were suppressed by quinpirole. Analysis of coefficient of variation in uIPSC amplitude implied the involvement of presynaptic mechanisms in quinpirole-induced effects on uIPSCs. These results suggest that activation of D2-like receptors facilitates outputs from MS neurons in the NAc by reducing lateral inhibition during a dormant period of FS neuron activities.