bluuebunny/crossref_metadata_2025 huggingface dataset:
DIFFERENCES IN POLYSACCHARIDE STRUCTURE BETWEEN CALCIFIED AND UNCALCIFIED SEGMENTS IN THE CORALLINE CALLIARTHRON CHEILOSPORIOIDES (CORALLINALES, RHODOPHYTA)1
Authors: Martone Patrick T. , Navarro Diego A. , Stortz Carlos A. , Estevez José M.
Published: April 2010

The articulated coralline Calliarthron cheilosporioides Manza produces segmented fronds composed of calcified segments (intergenicula) separated by uncalcified joints (genicula), which allow fronds to bend and reorient under breaking waves in the wave‐swept intertidal zone. Genicula are formed when calcified cells decalcify and restructure to create flexible tissue. The present study has identified important differences in the main agaran disaccharidic repeating units [→3)‐β‐d‐Galp (1→ 4)‐α‐l‐Galp(1→] synthesized by genicular and intergenicular segments. Based on chemical and spectroscopical analyses, we report that genicular cells from C. cheilosporioides biosynthesize a highly methoxylated galactan at C‐6 position with low levels of branching with xylose side stubs on C‐6 of the [→3)‐β‐d‐Galp (1→] units, whereas intergenicular segments produce xylogalactans with high levels of xylose and low levels of 6‐O‐methyl β‐d‐Gal units. These data suggest that, during genicular development, xylosyl branched, 3‐linked β‐d‐Galp units present in the xylogalactan backbones from intergenicular walls are mostly replaced by 6‐O‐methyl‐d‐galactose units. We speculate that this structural shift is a consequence of a putative and specific methoxyl transferase that blocks the xylosylation on C‐6 of the 3‐linked β‐d‐Galp units. Changes in galactan substitutions may contribute to the distinct mechanical properties of genicula and may lend insight into the calcification process in coralline algae.
Advancing Alcohol Biomarkers Research
Authors: Bearer Cynthia F. , Bailey Shannon M. , Hoek Jan B.
Published: April 2010

Biomarkers to detect past alcohol use and identify alcohol‐related diseases have long been pursued as important tools for research into alcohol use disorders as well as for clinical and treatment applications and other settings. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) sponsored a workshop titled “Workshop on Biomarkers for Alcohol‐Induced Disorders” in June 2008. The intent of this workshop was to review and discuss recent progress in the development and implementation of biomarkers for alcohol use and alcohol‐related disorders with a goal to formulate a set of recommendations to use to stimulate and advance research progress in this critical area of alcoholism research. Presentations at this workshop reviewed the current status of alcohol biomarkers, providing a summary of the history of biomarkers and the major goals of alcohol biomarker research. Moreover, presentations provided a comprehensive overview of the current status of several well‐recognized biomarkers of alcohol use, a summary of recent studies to characterize novel biomarkers and their validation, along with perspectives and experiences from other NIH institutes and from other federal agencies and industry, related to regulatory issues. Following these presentations, a panel discussion focused on a set of issues presented by the organizers of this workshop. These discussion points addressed: (i) issues related to strategies to be adopted to stimulate biomarker discovery and application, (ii) the relevance of animal studies in biomarker development and the status of biomarkers in basic science studies, and (iii) issues related to the opportunities for clinical and commercial applications. This article summarizes these perspectives and highlights topics that constituted the basis for recommendations to enhance alcohol biomarker research.
Sensory Processing and Adaptive Behavior Deficits of Children Across the Fetal Alcohol Spectrum Disorder Continuum
Authors: Carr Joshua L. , Agnihotri Sabrina , Keightley Michelle
Published: April 2010

Background:  Prenatal alcohol exposure can have detrimental effects on a child’s development of adaptive behaviors necessary for success in the areas of academic achievement, socialization, and self‐care. Sensory processing abilities have been found to affect a child’s ability to successfully perform adaptive behaviors. The current study explored whether significant differences in sensory processing abilities, adaptive behavior, and neurocognitive functioning are observed between children diagnosed with partial Fetal Alcohol Syndrome (pFAS), Alcohol‐Related Neurodevelopmental Disorder (ARND), or children who were prenatally exposed to alcohol (PEA), but did not meet criteria for an FASD diagnosis. The influence of IQ on adaptive behavior as well as further exploration of the relationship between sensory processing and adaptive behavior deficits among these children was also examined.

Methods:  A secondary analysis was conducted on some of the Short Sensory Profile (SSP) scores, Adaptive Behavior Assessment System—Second Edition (ABAS‐II) scores, and Wechsler Intelligence Scale—Fourth Edition/Wechsler Preschool and Primary Scale of Intelligence—Third Edition (WISC‐ IV/WPPSI—III) scores of 46 children between 3 and 14 years of age with pFAS, ARND, or who were PEA.

Results:  Greater sensory processing deficits were found in children with a diagnosis of pFAS and ARND compared to those in the PEA group. Children with an ARND diagnosis scored significantly worse on measures of adaptive behavior than the PEA group. Children with pFAS scored significantly lower than children with ARND or PEA on perceptual/performance IQ. No correlation was found between IQ scores and adaptive behaviors across the FASD diagnostic categories. A significant positive correlation was found between SSP and ABAS‐II scores.

Conclusions:  Regardless of the diagnosis received under the FASD umbrella, functional difficulties that could not be observed using traditional measures of intelligence were found, supporting guidelines that a broad range of standardized assessments be included when screening children for FASD.
The United Kingdom's Fossil Resource Consumption Between 1968 and 2000
Authors: Papathanasopoulou Eleni , Jackson Tim
Published: April 2010

This article presents the trends of two indicators measuring fossil resource consumption in the United Kingdom (UK). First, a domestic material consumption (DMC) indicator for fossil resources (DMCfossil) in the mass unit million tonnes is calculated. DMCfossil shows that between 1970 and 2000 UK fossil resource consumption decreased by 10%, which suggests absolute dematerialization for this resource. Investigation into the mix of fossil resources during this period highlighted the shift from the heavy fossil resource coal to the lighter, more energy‐dense natural gas, which resulted in decreased mass of resource required. Second, an alternative indicator, resource consumption by a nation (RCN) for fossil resources (RCNfossil) was calculated, which includes the indirect fossil resources attributable to traded goods and is measured in million tonnes of oil equivalent. RCNfossil shows that between 1970 and 2000 United Kingdom's fossil resource consumption increased by 14%, which emphasizes that even though there has been a decrease in the mass of fossil resources demanded, it has been accompanied by an increase in the volume of resource consumed. Additionally, deconstruction of RCNfossil shows that indirectly used resources attributable to exports and imports for the United Kingdom are significant. RCNfossil indicates that on the basis of past trends, fossil resources attributable to UK imports will overtake fossil resources attributable to its exports, which will make it dependent on imported resources. We conclude that further debate on appropriate aggregate and complementary indicators is needed.
Functionally Unrevascularized Chronic Total Occlusions: A Step Closer to Indentifying the CTO Patient Who Benefits from PCI
Authors: ROMICK BENJAMIN G. , SRINIVAS VANKEEPURAM S.
Published: April 2010

(J Interven Cardiol 2010;23:149‐151)
Effects of Gd3+ Substitution on the Fabrication of Transparent (Y1−xGdx)3Al5O12 Ceramics
Authors: Li Xiaodong , Li Ji‐Guang , Xiu Zhimeng , Huo Di , Sun Xudong
Published: April 2010

Gadolinium has been frequently used in scintillators to enhance the X‐ray stopping power and in phosphors to improve the luminescent properties. In this paper, the fabrication of Gd3+‐substituted transparent (Y1−xGdx)3Al5O12 (x=0.01, 0.5, 0.75, and 1) ceramics via solid reactive sintering has been investigated. The effects of Gd3+ substitution on the phase evolution of the powder mixture, sintering behavior of the powder compact, and properties of the resultant ceramics were mainly demonstrated. It is shown that Gd3+ substitution favors the formation of kinetically stable intermediate compounds, particularly REAlO3 (RE=Y+Gd), and thus retards the crystallization of an RE3Al5O12 garnet. The samples of x=1 composition cracked upon vacuum sintering at temperatures above 1600°C, mainly due to the volumetric expansion induced by garnet formation. The transparent Y1.48Gd1.5Ce0.02Al5O12 ceramic (inline transmittance: ∼65% at 800 nm) vacuum sintered at 1700°C shows an emission band peaked at ∼570 nm upon UV excitation at 340 nm, exhibiting a red‐shift by ∼40 nm in comparison with the regular emission from YAG:Ce.
Growth and Mechanism of Network‐Like Branched Si3N4 Nanostructures
Authors: Peng Zhijian , Zhu Na , Fu Xiuli , Wang Chengbiao , Fu Zhiqiang , Qi Longhao , Miao Hezhuo
Published: April 2010

The high‐yield synthesis of network‐like branched silicon nitride (Si3N4) nanostructures by a simple template catalyst‐assisted pyrolysis of a polymer precursor, perhydropolysilazane, was reported. The templates were silicon wafers deposited with Fe films of 5–20 nm in thickness. The processes simply involved thermal cross‐linking of the preceramic polymer, crushing of the solidified polymer chunks into fine powder, and thermal pyrolysis of the powder under flowing high‐purity nitrogen. The collected white network‐like branched nanostructures are α‐Si3N4 of hexagonal phase, and their microstructures, in which the diameters of each linear part of the network‐like nanostructure varied in a very wide range from tens of nanometers to hundreds of nanometers, strongly depend on the applied growth parameters, where the key factors are the heating rate and catalyst thickness for change in the diameters. It was proposed that the Si3N4 nanonetworks were formed through “metal‐absorption on the surface of nanostructures” model by vapor–liquid–solid mechanism. The reaction mechanism of Si3N4 nanonetworks was also discussed.
A Descriptive Comparison of Ultrasound‐guided Central Venous Cannulation of the Internal Jugular Vein to Landmark‐based Subclavian Vein Cannulation
Authors: Theodoro Daniel , Bausano Brian , Lewis Lawrence , Evanoff Bradley , Kollef Marin
Published: April 2010

Objectives:  The safest site for central venous cannulation (CVC) remains debated. Many emergency physicians (EPs) advocate the ultrasound‐guided internal jugular (USIJ) approach because of data supporting its efficiency. However, a number of physicians prefer, and are most comfortable with, the subclavian (SC) vein approach. The purpose of this study was to describe adverse event rates among operators using the USIJ approach, and the landmark SC vein approach without US.

Methods:  This was a prospective observational trial of patients undergoing CVC of the SC or internal jugular veins in the emergency department (ED). Physicians performing the procedures did not undergo standardized training in either technique. The primary outcome was a composite of adverse events defined as hematoma, arterial cannulation, pneumothorax, and failure to cannulate. Physicians recorded the anatomical site of cannulation, US assistance, indications, and acute complications. Variables of interest were collected from the pharmacy and ED record. Physician experience was based on a self‐reported survey. The authors followed outcomes of central line insertion until device removal or patient discharge.

Results:  Physicians attempted 236 USIJ and 132 SC cannulations on 333 patients. The overall adverse event rate was 22% with failure to cannulate being the most common. Adverse events occurred in 19% of USIJ attempts, compared to 29% of non–US‐guided SC attempts. Among highly experienced operators, CVCs placed at the SC site resulted in more adverse events than those performed using USIJ (relative risk [RR] = 1.89, 95% confidence interval [CI] = 1.05 to 3.39).

Conclusions:  While limited by observational design, our results suggest that the USIJ technique may result in fewer adverse events compared to the landmark SC approach.

ACADEMIC EMERGENCY MEDICINE 2010; 17:416–422 © 2010 by the Society for Academic Emergency Medicine
Integrated DNA and Fingerprint Analyses in the Identification of 60‐Year‐Old Mummified Human Remains Discovered in an Alaskan Glacier
Authors: Loreille Odile M. , Parr Ryan L. , McGregor Kevin A. , Fitzpatrick Colleen M. , Lyon Chriss , Yang Dongya Y. , Speller Camilla F. , Grimm Michael R. , Grimm Michael J. , Irwin Jodi A. , Robinson Edward M.
Published: April 2010

Abstract:  This report describes the identification of a merchant mariner who perished in 1948 when Northwest Airlines Flight 4422, a DC‐4 carrying 24 seamen and six crew members crashed into Mount Sanford, Alaska. Fifty‐one years later, a human forearm and hand were found close by the wreckage of the plane, prompting identification efforts using DNA and fingerprints. There were significant challenges to both the fingerprint and DNA analyses. The hand was badly desiccated, making fingerprint friction‐ridge detail almost invisible and the remains had been embalmed upon discovery, making DNA amplification difficult. We present the results of an interdisciplinary approach that successfully addressed these challenges and ultimately led to the identification of the remains. These efforts relied on efficient fingerprint rejuvenation and imaging techniques that improved print resolution, as well as new DNA extraction techniques optimized for aggressively embalmed remains.
Bone alterations at implant‐supported FDPs in relation to inter‐unit distances: a 5‐year radiographic study
Authors: Chang Moontaek , Wennström Jan L.
Published: April 2010

Objectives: The aim of this 5‐year study was to longitudinally evaluate bone alterations around implants with a conical implant–abutment interface in relation to implant–tooth and inter–implant distances.

Material and methods: The patient sample comprised 43 partially dentate patients with a total of 48 implant‐supported fixed dental prostheses (FDPs) supported by 130 Astra Tech® implants. Following FDP placement (baseline), the patients were enrolled in an individually designed supportive care program. Radiographic examinations were performed at the time of FDP installation, 1 and 5 years of follow‐up. Variables regarding implant position and proximal bone topography at tooth/implant units (n=36) and implant/implant units (n=67) were assessed with the use of a software program after scanning of the radiographs.

Results: At tooth/implant units, the mean 5‐year marginal bone loss at the tooth, the implant and the mid‐proximal bone crest was 0.1, 0.4 and 0.2 mm, respectively. The mean longitudinal bone loss at the implant/implant units was 0.5 mm at the implants and 0.3 mm mid‐proximally. Multilevel regression analysis revealed that at implant/implant units, the change in the bone‐to‐implant contact level was a significant predictor with regard to the 5‐year mid‐proximal bone‐level change, whereas the horizontal inter‐unit distance showed a borderline significance (P=0.052). At tooth/implant units, no statistically significant associations were identified.

Conclusions: The results of this 5‐year study revealed differences between inter‐implant and tooth–implant proximal areas with regard to bone crest alterations and associated factors.

To cite this article:
 Chang M, Wennström JL. Bone alterations at implant‐supported FDPs in relation to inter‐unit distances: a 5‐year radiographic study. Clin. Oral Impl. Res. 21, 2010; 735–740. doi: 10.1111/j.1600‐0501.2009.01893.x
The effects of patch richness on con‐specific interference in the parasitoidIbalia leucospoides(Hymenoptera: Ibaliidae)
Authors: Fernández‐Arhex Valeria , Corley Juan Carlos
Published: April 2010

Abstract We experimentally studied con‐specific interference inIbalia leucospoides, a parasitoid of the woodwaspSirex noctilio, on pine logs containing variable numbers of woodwasp larvae. Competiton occurred when two different‐sized female parasitoids foraged on a host patch, and consequently the small female always abandoned the patch. Regardless of host density, con‐specific presence did not affect the attack rate, the number of hosts attacked, nor patch residence time by the winner, when compared to a control female that foraged alone. In contrast, con‐specific presence reduced patch time and the number of hosts attacked by the loser. Finally patch time (by both) as well as number of hosts attacked (by the winner only) increased with host density per patch. Our results suggest that con‐specific presence has different consequences for different‐sized females during patch exploitation.
Impacts of transgenic Bt cotton on the stylet penetration behaviors of Bemisia tabaci biotype B: Evidence from laboratory experiments
Authors: Yin Hai‐Di , Wang Xiao‐Ying , Xue Kun , Huang Cui‐Hong , Wang Rong‐Jiang , Yan Feng‐Ming , Xu Chong‐Ren
Published: April 2010

Abstract  Stylet penetration behaviors of Bemisia tabaci biotype B on two transgenic cotton lines “GK12” and “GK19” expressing Bt toxic protein Cry1A (Bt cotton) and a non‐Bt conventional cotton line “Simian‐3” (CK cotton) were recorded with the direct current electrical penetration graph (DC‐EPG) technique. Our results suggested that EPG waveform patterns, types and characteristics [non‐probe (NP), pathway (C), potential drops (pd) and phloem phase (E(pd))] of Bemisia tabaci biotype B were very similar on the three cotton lines. There were no obvious differences of pathway variables among whiteflies on the three cotton lines. Some phloem variables related to E(pd)1 differed. Duration of 1st E(pd)1 and mean duration of E(pd)1 on both GK12 and GK19 were significantly shorter than that on CK cotton (P < 0.05). Fewer whiteflies on GK have long E(pd)1. Other phloem variables including total duration of E(pd) summed, mean E(pd) duration and percentage of whiteflies reaching the phloem phase were similar among the three cotton lines.
Comparison of gut‐associated and nest‐associated microbial communities of a fungus‐growing termite (Odontotermes yunnanensis)
Authors: Long Yan‐Hua , Xie Lei , Liu Ning , Yan Xing , Li Ming‐Hui , Fan Mei‐Zhen , Wang Qian
Published: April 2010

Abstract  The digestion of cellulose by fungus‐growing termites involves a complex of different organisms, such as the termites themselves, fungi and bacteria. To further investigate the symbiotic relationships of fungus‐growing termites, the microbial communities of the termite gut and fungus combs of Odontotermes yunnanensis were examined. The major fungus species was identified as Termitomyces sp. To compare the micro‐organism diversity between the digestive tract of termites and fungus combs, four polymerase chain reaction clone libraries were created (two fungus‐targeted internal transcribed spacer [ITS]– ribosomal DNA [rDNA] libraries and two bacteria‐targeted 16S rDNA libraries), and one library of each type was produced for the host termite gut and the symbiotic fungus comb. Results of the fungal clone libraries revealed that only Termitomyces sp. was detected on the fungus comb; no non‐Termitomyces fungi were detected. Meanwhile, the same fungus was also found in the termite gut. The bacterial clone libraries showed higher numbers and greater diversity of bacteria in the termite gut than in the fungus comb. Both bacterial clone libraries from the insect gut included Firmicutes, Bacteroidetes, Proteobacteria, Spirochaetes, Nitrospira, Deferribacteres, and Fibrobacteres, whereas the bacterial clone libraries from the fungal comb only contained Firmicutes, Bacteroidetes, Proteobacteria, and Acidobacteris.
FIAT, the factor‐inhibiting ATF4‐mediated transcription, also represses the transcriptional activity of the bZIP factor FRA‐1
Authors: St‐Arnaud René , Mandic Vice , Elchaarani Bilal
Published: April 2010

FIAT is a leucine zipper protein whose name was coined for its interaction with ATF4 and subsequent blockage of ATF4‐directed osteocalcin gene transcription. FIAT lacks a basic DNA‐binding domain but contains three leucine zippers; it heterodimerizes with ATF4 to prohibit binding to DNA. FIAT could also potentially interact with additional basic domain‐leucine zipper transcriptional regulators of osteoblast activity, such as FRA‐1. We have found that FIAT inhibits transcriptional activation by a FRA‐1/c‐JUN heterodimer without affecting transcription mediated by a c‐JUN homodimer. The repressor effect of FIAT on FRA‐1‐dependent transcription was measured using reporter constructs for the natural FRA‐1 targets, Mmp‐9 and Mgp. The FIAT–FRA‐1 interaction is mediated through the second leucine zipper of FIAT. These data confirm an additional target of the FIAT transcriptional repressor activity and suggest that FIAT can both modulate early osteoblast activity by interacting with ATF4 and regulate later osteoblast function through inhibition of FRA‐1.
Inhibition of antigen presentation and T cell costimulation blocks PTH‐induced bone loss
Authors: Bedi Brahmchetna , Li Jau‐Yi , Grassi Francesco , Tawfeek Hesham , Weitzmann M. Neale , Pacifici Roberto
Published: April 2010

T cells are required for continuous parathyroid hormone (cPTH) treatment to induce bone loss as they sensitize stromal cells to PTH through CD40 ligand (CD40L), a surface molecule of activated T cells. Since CD40L expression is a feature of activated T cells, we investigated whether antigen (Ag)‐mediated T cell activation is required for PTH to exert its catabolic activity. We report that inhibition of Ag presentation through silencing of either class I or class II MHC‐T cell receptor (TCR) interaction prevents the cortical bone loss induced by in vivo cPTH treatment. We also show that the bone loss and the stimulation of bone resorption induced by cPTH treatment are prevented by CTLA4‐Ig, an inhibitor of T cell costimulation approved for the treatment of rheumatoid arthritis. Since inhibition of antigen‐driven T cell activation by blockade of either TCR signaling or T cell costimulation is sufficient to silence the catabolic activity of cPTH, antigen‐presenting cells and T lymphocyte interactions therefore play a critical role in the mechanism of action of PTH.
Depression and bone mass
Authors: Bab Itai A. , Yirmiya Raz
Published: April 2010

Although it has been repeatedly suggested that low bone mineral density (BMD) is disproportionately prevalent among patients with depressive disorders, so far depression has not been officially acknowledged as a risk factor for osteoporosis. In a recent meta‐analysis comparing depressed with nondepressed individuals we report that BMD is lower in depressed than nondepressed subjects. The association between depression and BMD is stronger in women than men, and in premenopausal than postmenopausal women. Only women psychiatrically diagnosed for major depression display significantly low BMD; women diagnosed by self‐rating questionnaires do not. Using a mouse model for depression, we demonstrate a causal relationship between depressive‐like behavior and bone loss. The depression‐induced bone loss is associated with increases in skeletal norepinephrine and serum corticosterone levels. Bone loss, but not the depressive behavior, could be prevented by a β‐blocker. Hence, depression appears as a significant risk factor for low BMD, causing bone loss through stimulation of the sympathetic nervous system.
Regulation of bone turnover by calcium‐regulated calcium channels
Authors: Robinson Lisa J. , Blair Harry C. , Barnett John B. , Zaidi Mone , Huang Christopher L.‐H.
Published: April 2010

Calcium plays multiple roles in osteoclast formation, survival, and activity. Intracellular calcium is determined both by the release of intracellular stores and the influx of extracellular calcium through a variety of calcium channels. Osteoclasts express several classes of calcium channels, including ryanodine receptors (RyRs), inositol‐1,4,5‐trisphosphate receptors (IP3Rs), and calcium release‐activated calcium channels (CRACs), which respond to depletion of intracellular stores. IP3R2 is expressed in osteoclast precursors and activated by cytokines that stimulate osteoclast differentiation. In mature osteoclasts, the IP3R1 isoform is highly expressed and is implicated in nitric oxide‐cGMP‐stimulated processes. RyR calcium channels may contribute to the release of intracellular calcium stores, while RyR2 in the plasma membrane may act to limit osteoclast activity based on extracellular calcium concentration. Orai, through regulation by endoplasmic reticular store‐sensing proteins, including Stim‐1, may also mediate calcium influx and act as a signal amplifier for calcium release by other calcium channels. Together, these receptors allow intracellular Ca2+ signals to modulate bone turnover and, through calcium‐sensing functions, allow coupling of osteoclast activity to extracellular conditions and integrating additional cytokine and nitric oxide signals via transient intracellular calcium signals.
Nitric oxide and bone
Authors: Wimalawansa Sunil J.
Published: April 2010

Age‐associated decrease in nitric oxide (NO) production may be related to an increase in cardiovascular events, sexual dysfunction, and osteoporosis. Relative NO deficiency is a plausible biological basis for NO replacement therapy. Hormone replacement therapy (HRT) enhances local NO production and rectifies NO deficiency in postmenopausal women. However, excess local production of NO aggravates bone destruction in inflammatory arthropathies. In addition to its use in alleviating angina and erectile dysfunction, NO compounds could be a valuable supplemental therapy for chronic conditions including osteoporosis. Estrogen mediates its beneficial effects in bone, in part via the NO/cGMP pathway; hence NO donor therapy is an alternative to estrogen, estrogen agonists‐antagonists, and androgen receptor modulator therapy in the prevention and treatment of osteoporosis. Large numbers of animal studies and human pilot studies support the concept of using NO donors for preventing bone loss. Administration of exogenous NO or prolonging endogenous NO activity are practical ways to supplement NO.
Bone loss across the menopausal transition
Authors: Neer Robert M. ,   on behalf of the SWAN Investigators
Published: April 2010

The Study of Women's Health Across the Nation (SWAN) is an NIH‐funded, multidisciplinary, longitudinal observational study of middle‐aged U.S. women of multiple ethnicities in or near Boston, Newark, Pittsburgh, Detroit, Chicago, Oakland, and Los Angeles. SWAN measures multiple variables annually, including spine and hip areal bone mineral density (aBMD), serum and urine indices of bone remodeling, and pituitary, ovarian, and adrenal hormones. This chapter outlines the findings of the SWAN study so far.
Posttranslational modifications of collagens as targets of hypoxia and Hif‐1α in endochondral bone development
Authors: Schipani Ernestina
Published: April 2010

In recent years, it has been proposed that oxygen is not only an indispensable metabolic substrate, but also a regulatory signal, and that gradients of oxygenation turn on a specific genetic program. A crucial mediator of the adaptive response of cells to hypoxia is the transcription factor hypoxia‐inducible factor 1α (Hif‐1α). The fetal growth plate, which is an avascular structure of mesenchymal origin, has a unique out‐in gradient of oxygenation. Hif‐1α is required for chondrogenesis in vivo by controlling a complex homeostatic response that allows chondrocytes to survive and differentiate in an hypoxic environment. Preliminary evidence suggests that regulation of posttranslational modifications of collagens could be an important component of this adaptive response.
Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis
Authors: Goldring Mary B. , Goldring Steven R.
Published: April 2010

The articular surface plays an essential role in load transfer across the joint, and conditions that produce increased load transfer or altered patterns of load distribution accelerate the development of osteoarthritis (OA). Current knowledge segregates the risk factors into two fundamental mechanisms related to the adverse effects of “abnormal” loading on normal cartilage or “normal” loading on abnormal cartilage. Although chondrocytes can modulate their functional state in response to loading, their capacity to repair and modify the surrounding extracellular matrix is limited in comparison to skeletal cells in bone. This differential adaptive capacity underlies the more rapid appearance of detectable skeletal changes, especially after acute injuries that alter joint mechanics. The imbalance in the adaptation of the cartilage and bone disrupts the physiological relationship between these tissues and further contributes to OA pathology. This review focuses on the specific articular cartilage and skeletal features of OA and the putative mechanisms involved in their pathogenesis.
Heritable sclerosing bone disorders
Authors: de Vernejoul Marie‐Christine , Kornak Uwe
Published: April 2010

Sclerosing bone disorders can be subdivided according to their clinical presentation, the primarily affected cell type, and the cellular pathways. Osteoclast‐rich osteopetrosis and related disorders have been related in most cases to mutations in genes required for osteoclast function. More recently, osteoclast‐poor forms of osteopetrosis have been described as being connected to factors that govern osteoclast differentiation. However, increased bone formation can also cause osteosclerosis. Camurati–Engelman disease and osteopoikilosis are both related transforming growth factor‐β signaling. Rare recessive or dominant sclerosing disorders, such as endosteal hyperostosis, sclerosteosis, van Buchem disease, high bone‐mass syndrome, and osteopathia striata, are caused by mutations in genes involved in the Wnt pathway, which regulates osteoblast differentiation. Finally, a third entity, including Ghosal syndrome and pachydermoperiostosis, is related to mutations in genes of the eicosanoid pathway. Clinical aspects and the consequences for our understanding of bone biology are discussed.
Integrins, growth factors, and the osteoclast cytoskeleton
Authors: Zou Wei , Teitelbaum Steven L.
Published: April 2010

The unique ability of the osteoclast to degrade skeletal tissue depends upon formation of a resorptive microenvironment between the osteoclast and the bone surface. Generation of this privileged space is substantially mediated by signals emanating from αvβ3 integrin, which transits to its active high‐affinity conformation by growth factor‐initiated intracellular events targeting the matrix receptor's cytoplasmic domain. The activated liganded integrin stimulates a signaling complex consisting of c‐Src, Syk, immunoreceptor tyrosine‐based activation motif proteins, Slp‐76, Vav3, and members of the Rho family of GTPases. These events contribute to secretory lysososme insertion into the bone‐apposed plasma membrane to form the ruffled border that delivers the bone‐degrading molecules (HCl and cathepsin K) into the resorptive microenvironment. Integrin/bone recognition also promotes formation of actin rings, which surround the ruffled border, thereby isolating the focus of skeletal degradation from the general extracellular space.
Dynamics of the transition from osteoblast to osteocyte
Authors: Dallas Sarah L. , Bonewald Lynda F.
Published: April 2010

Osteocytes are derived from osteoblasts and make up over 90% of the cells in bone. However, the mechanisms that control the differentiation of osteoblasts into osteocytes embedded in bone matrix are not well understood. With the recent developments of transgenic models for manipulating gene expression in osteocytes and of transgenic mice carrying lineage reporters for osteoblasts and osteocytes, unprecedented new insights are becoming possible. In this article we review recent advances, such as comparative gene and protein expression studies, that are delineating the changes in gene and protein expression that accompany osteocyte differentiation. We also review recent studies in which time‐lapse dynamic imaging approaches have been used to visualize osteoblast and osteocyte populations within bone. These approaches reveal the key role of cell motility in bone cell function and highlight the dynamic nature of mineralized tissues. Changes in motile properties of the cell may be key in the transition from osteoblast to osteocyte, as reflected in the altered expression of many molecules involved in cytoskeletal function.
Generation of a mouse model with expression of bone morphogenetic protein type II receptor lacking the cytoplasmic domain in osteoblasts
Authors: Yang Chaozhe , Yang Lei , Wan Mei , Cao Xu
Published: April 2010

Different working modes were proposed to explain how bone morphogenetic protein (BMP) type I and II receptors are involved in Smad phosphorylation cascades. In addition, both parathyroid hormone (PTH) and Wnts are also known to regulate phosphorylation of Smads. Here we established a mouse model in which a C‐terminal truncated BMP type II receptor (BMPRII) is expressed specifically in osteoblasts as a dominant negative form in the BMP/Smad signaling pathway. Smad1/5/8 phosphorylation levels were reduced in bone marrow stromal cells from the transgenic mice. The sizes of embryos were smaller, and the mineralization of calvarial bones and lumbar vertebrae were delayed in mice expressing the transgene. In adult transgenic mice, total bone volume was reduced with no significant changes observed in cortical bone. Thus, osteoblast‐targeted expression of dominant negative BMPRII leads to inhibited Smad1 phosphorylation, delayed skeletal development, and decreased bone formation in the adult mice. This study provides an in vivo tool to study the role of BMPRII in BMP/Smad signaling and the regulation of this pathway by PTH and Wnts.
Gs signaling in osteoblasts and hematopoietic stem cells
Authors: Kronenberg Henry M.
Published: April 2010

The heterotrimeric G protein Gs is a major mediator of the actions of several G protein‐coupled receptors that target cells of the osteoblast lineage. For this reason, we generated chimeric mice with normal host cells and cells derived from embryonic stem cells missing the gene encoding the α subunit of Gs. While the mutant cells contributed to cortical osteoblasts and to hematopoietic cells in the liver, the marrow space contained few if any osteoblasts or hematopoietic cells missing Gs. Subsequent studies using the Cre–lox approach to delete Gsα from early cells of the osteoblast lineage and from hematopoietic stem cells were performed. These studies demonstrated the crucial roles of Gsα in osteoblastic cells in regulating the differentiation of osteoblasts and in supporting B‐cell development as well as the essential role for Gsα in hematopoietic stem cells in allowing the homing of these cells to the marrow.
CITED2 mechanoregulation of matrix metalloproteinases
Authors: Sun Hui B.
Published: April 2010

Joint tissues are exquisitely sensitive to their mechanical environment. Indeed, mechanical loading may be the most important external factor regulating the development and long‐term maintenance of joint tissues. Moderate mechanical loading maintains the integrity of articular cartilage, and under these conditions of homeostasis, matrix metalloproteinases (MMPs) are expressed at modest levels. However, both disuse and overuse can result in altered likely high levels of MMP expression, leading to cartilage degradation. The transcriptional regulator ED‐rich tail 2 (CITED2) is expressed in chondrocytes in a load‐dependent manner but in a pattern inversely related to that of MMPs. CITED2 mediates the moderate load‐induced suppression of MMPs, possibly by competing with Ets‐1, a known MMP transactivator, for binding to the co‐activator p300, suggesting a mechanism for transcriptional suppression by CITED2. These findings suggest that CITED2 may act as a mechanosensitive molecular switch regulating cartilage matrix breakdown. This regulatory pathway could be exploited clinically to limit pathologic cartilage degradation.
Nandrolone slows hindlimb bone loss in a rat model of bone loss due to denervation
Authors: Cardozo Christopher P. , Qin Weiping , Peng Yuanzhen , Liu Xuan , Wu Yong , Pan Jiangping , Bauman William A. , Zaidi Mone , Sun Li
Published: April 2010

Nandrolone is an anabolic steroid that has been demonstrated to reduce the loss of bone and muscle from hindlimb unweighting and to slow muscle atrophy after nerve transection. To determine whether nandrolone has the ability to protect bone against loss due to disuse after denervation, male rats underwent sciatic nerve transaction, followed 28 days later by treatment with nandrolone or vehicle for 28 days. Bone mineral density (BMD) was determined 28 days later or 56 days after nerve transection. Denervation led to reductions in BMD of 7% and 12% for femur and tibia, respectively. Nandrolone preserved 80% and 60% of BMD in femur and tibia, respectively, demonstrating that nandrolone administration significantly reduced loss of BMD from denervation. This study offers a potential novel pharmacological strategy for use of nandrolone to reduce bone loss in severe disuse‐ and denervation‐related bone loss, such as that which occurs after spinal cord injury.
Noninvasive methods of measuring bone blood perfusion
Authors: Dyke J.P. , Aaron R.K.
Published: April 2010

Measurement of bone blood flow and perfusion characteristics in a noninvasive and serial manner would be advantageous in assessing revascularization after trauma and the possible risk of avascular necrosis. Many disease states, including osteoporosis, osteoarthritis, and bone neoplasms, result in disturbed bone perfusion. A causal link between bone perfusion and remodeling has shown its importance in sustained healing and regrowth following injury. Measurement of perfusion and permeability within the bone was performed with small and macromolecular contrast media, using dynamic contrast‐enhanced magnetic resonance imaging in models of osteoarthritis and the femoral head. Bone blood flow and remodeling was estimated using 18F‐Fluoride positron emission tomography in fracture healing and osteoarthritis. Multimodality assessment of bone blood flow, permeability, and remodeling by using noninvasive imaging techniques may provide information essential in monitoring subsequent rates of healing and response to treatment as well as identifying candidates for additional therapeutic or surgical interventions.
Transient receptor potential vanilloid 4
Authors: Guilak Farshid , Leddy Holly A. , Liedtke Wolfgang
Published: April 2010

The critical discovery in the past two decades of the transient receptor potential (TRP) superfamily of ion channels has revealed the potential mechanisms by which cells sense diverse stimuli beyond the prototypical “five senses,” identifying ion channels that are gated by heat, cold, mechanical loading, osmolarity, and other physical and chemical stimuli. TRP vanilloid 4 (TRPV4) is a Ca2+‐permeable nonselective cation channel that appears to play a mechanosensory or osmosensory role in several musculoskeletal tissues. In articular cartilage, TRPV4 exhibits osmotic sensitivity, controlling cellular volume recovery, and other physiologic responses to osmotic stress. TRPV4 is expressed in both osteoblasts and osteoclasts, and the absence of TRPV4 prevents disuse‐induced bone loss. TRPV4 activation promotes chondrogenesis by inducing SOX9 transcription, whereas a TRPV4 gain‐of‐function mutation leads to a developmental skeletal dysplasia, suggesting a critical role for TRPV4 in skeletal development. These studies provide mounting evidence for a regulatory role for the sensory channel TRPV4 in control of musculoskeletal tissues.
Cooperation of β2‐ and β3‐adrenergic receptors in hematopoietic progenitor cell mobilization
Authors: Méndez‐Ferrer Simón , Battista Michela , Frenette Paul S.
Published: April 2010

CXCL12/SDF‐1 dynamically regulates hematopoietic stem cell (HSC) attraction in the bone marrow (BM). Circadian regulation of bone formation and HSC traffic is relayed in bone and BM by β‐adrenergic receptors (β‐AR) expressed on HSCs, osteoblasts, and mesenchymal stem/progenitor cells. Circadian HSC release from the BM follows rhythmic secretion of norepinephrine from nerve terminals, β3‐AR activation, and Cxcl12 downregulation, possibly from reduced Sp1 nuclear content. Here, we show that β‐AR stimulation in stromal cells causes Sp1 degradation, partially mediated by the 26S proteasome. Inverted trends of circulating hematopoietic progenitors and BM Cxcl12 mRNA levels change acutely after light onset, shown to induce sympathetic efferent activity. In BM stromal cells, activation of β3‐AR downregulates Cxcl12, whereas β2‐AR stimulation induces clock gene expression. Double deficiency in β2‐ and β3‐ARs compromises enforced mobilization. Therefore, β2‐ and β3‐ARs have specific roles in stromal cells and cooperate during progenitor mobilization.
Effects of Chronic Red Wine Consumption on the Expression of Vascular Endothelial Growth Factor, Angiopoietin 1, Angiopoietin 2, and Its Receptors in Rat Erectile Tissue
Authors: Neves Delminda R.G.L.M. , Tomada Inês M.A.S.C.M. , Assunção Marco M.B. , Marques Franklim A.P. , Almeida Henrique M.N. , Andrade José P.A.V.
Published: April 2010

ABSTRACT:  Long‐term consumption of red wine (RW) apparently confers some protection against cardiovascular diseases due to antiatherosclerotic properties of polyphenols and ethanol (EtOH). There is some evidence indicating that they do so by regulating angiogenesis, but the mechanism and the modulator factors involved are largely unknown. The aim of this study was to evaluate the effects of chronic ingestion of RW in vascular structure and in the pattern of expression of vascular growth factors in the rat corpus cavernosum. Male Wistar rats aged 6 mo were treated with RW or an equivalent EtOH solution, as the only liquid source for 6 mo. Expression of vascular endothelial growth factor (VEGF), angiopoietin 1 and angiopoietin 2, and their receptors (VEGFR1, VEGFR2, and Tie2) in cavernous tissue was assayed by immunofluorescence and Western blotting. A reduction of VEGF and VEGFR2 expression, respectively, in smooth muscle and endothelial cells was observed in RW‐treated animals, which was balanced by an increase in angiopoietins/Tie2 expression. In EtOH rats, only a decrease in expression of the receptors VEGFR2 and Tie2 was observed. These results, taken together, suggest that antioxidants present in RW activate selected mechanisms for the maintenance of cavernous tissue vascularization. However, functional studies will be necessary to elucidate if RW is of benefit in the prevention of deleterious vascular events associated with ED.
Loop‐Mediated Isothermal Amplification (LAMP) for the Rapid and Sensitive Detection of Salmonella Typhimurium from Pork
Authors: Techathuvanan Chayapa , Draughon Frances Ann , D'Souza Doris Helen
Published: April 2010

ABSTRACT:  Loop‐mediated isothermal amplification (LAMP) is a novel molecular detection method that is more rapid and simpler than PCR. Products can be detected by turbidity using one temperature without the need for expensive PCR equipment. Our objective was to sensitively detect Salmonella Typhimurium from pork products within 1 d using the LAMP assay. Pork chop and pork sausage samples (25 g) were inoculated with high (108 to 106 CFU) and low (105 to 100 CFU) inocula of S. Typhimurium. Serial dilutions in phosphate buffered saline were plated on XLT4 agar either immediately or after selective preenrichment in tetrathionate broth (225 mL) for 10‐h at 37 °C. Nucleic acid was extracted using the TRIzol® method from 1‐mL samples. The LAMP assay using 6 specific invA gene primers and Bst DNA polymerase reaction mix was carried out at 62 °C for 90 min in a waterbath. Turbid products were detected visually and by agarose gel electrophoresis. Improved Salmonella detection at 102 CFU/25 g for both pork chop and sausage was obtained after 10‐h enrichment and 106 CFU/25 g without enrichment for both products. This assay can detect Salmonella from pork within 1 d, significantly faster than traditional methods that take >5 d. This method shows tremendous potential for routine diagnostics and monitoring of Salmonella by the pork industry.

Practical Application: The novel loop‐mediated isothermal amplification (LAMP) assay is a rapid, specific, and sensitive method that has potential application for routine diagnostics of Salmonella from pork products. The isothermal method does not require expensive equipment such as a PCR thermocylcer but only a simple waterbath for amplification within 90 min. Detection is even simpler by visual eye or turbidimeters that are less expensive than fluorescent spectrophotometers or real‐time PCR machines. All these advantages make it a practical approach for routine use by processing industries to rapidly detect Salmonella in their environment and to implement appropriate control strategies. To improve detection sensitivities, preenrichment followed by selective enrichment may be necessary. Even so, the entire assay can be completed at the most within two 8‐h working shifts.
Physical and Oxidative Stabilization of Omega‐3 Fatty Acids in Surimi Gels
Authors: Tolasa Sebnem , Lee Chong M. , Cakli Sukran
Published: April 2010

ABSTRACT:  The objective of the study was to compare the dispersion and oxidative stability of omega‐3 fatty acid oil in high‐ and low‐quality surimi gels during 4‐mo refrigerated and frozen storage. Low‐quality surimi was prepared by subjecting Alaska pollock surimi to 7 freeze–thaw cycles. Surimi gels were prepared with 4% modified starch, 2% salt, and 0.5% or 1% algal DHA or concentrated fish EPA‐DHA oil, and stored at −18 or 3 °C for 4 mo after being vacuumed packed and pasteurized. The effect of surimi gel properties on oil dispersion was examined using light microscopy equipped with image process software. The extent of lipid oxidation was monitored by thiobarbituric acid reactive substances (TBARS), peroxide value (PV), and fatty acid methly esters (DHA and EPA). Very fine and uniform oil dispersion was observed in the high‐quality surimi gel with the average droplet size of 12.37 μm2 and dispersion of 1.73 × 10−3 droplets/μm2 compared to 84.32 μm2 and 0.57 × 10−3 droplets/μm2 in the low‐quality gel. Throughout the 4 mo storage, TBARS and PV of high‐quality surimi gel were significantly (P < 0.05) lower than those of low‐quality surimi gel. The decreases in omega‐3 fatty acids in the high‐quality surimi gels were lower than those in the low‐quality surimi gels under both storage conditions. Results confirm that a highly cohesive gel matrix is required to have a fine dispersion and oxidative stability of omega‐3 fatty acids in the surimi gel system.

Practical Application: Uniform dispersion and oxidative stability of omega‐3 fatty acid oil can be achieved in the highly cohesive surimi gel system without use of antioxidants. This suggests that surimi can be used as a protein‐based carrier in developing high omega‐3 fatty acids‐containing seafood products.