bluuebunny/crossref_metadata_2025 huggingface dataset:
Eastern hemlock (Tsuga canadensis) regeneration in the presence of hemlock woolly adelgid (Adelges tsugae) and elongate hemlock scale (Fiorinia externa)
Authors: Preisser Evan L. , Miller-Pierce Mailea R. , Vansant Jacqueline , Orwig David A.
Published: November 2011

The hemlock woolly adelgid (Adelges tsugae Annand) is an invasive hemipteran that poses a major threat to eastern hemlock (Tsuga canadensis (L.) Carrière) forests in the United States. We conducted three surveys over a five-year period that assessed the density of hemlock woolly adelgid (HWA) and a second invasive pest, the elongate hemlock scale (EHS; Fiorinia externa Ferris), overstory hemlock mortality, and hemlock regeneration in ~140 hemlock stands (mean size, 44 ha; range, 7–305 ha) within a 7500 km2 north–south transect of southern New England (USA). In each stand, we rated HWA and EHS density on 50 hemlock trees using a 0–3 scale (0, none; 1, 1–10 organisms/m branch; 2, 11–100 organisms/m branch; 3, >100 organisms/m branch). Data on the presence or absence of regeneration were taken in 2005; in 2007 and 2009, we quantitatively assessed regeneration by counting the number of hemlock seedlings in three 16 m2 plots per stand. In 2005, 81% of sampled stands had HWA, 72% had EHS, and 66% had hemlock regeneration. In 2007, 86% of sampled stands had HWA, 79% had EHS, and 46% had hemlock regeneration. In 2009, 91% of stands had HWA, 87% had EHS, and 37% had hemlock regeneration. The proportion of stands with hemlock regeneration declined 46% between 2005 and 2009, and hemlock seedling density declined 71% between 2007 and 2009. A best-fit model selection algorithm found that this decrease was inversely correlated with stand-level adelgid density. There was no correlation between the change in seedling density and stand-level density of the elongate hemlock scale. The apparent decline in regeneration suggests that the ecosystem-level changes currently occurring in southern New England may be difficult to reverse.
Transgenic overexpression of intraislet ghrelin does not affect insulin secretion or glucose metabolism in vivo
Authors: Bando Mika , Iwakura Hiroshi , Ariyasu Hiroyuki , Hosoda Hiroshi , Yamada Go , Hosoda Kiminori , Adachi Souichi , Nakao Kazuwa , Kangawa Kenji , Akamizu Takashi
Published: November 2011

Whereas ghrelin is produced primarily in the stomach, a small amount of it is produced in pancreatic islets. Although exogenous administration of ghrelin suppresses insulin secretion in vitro or in vivo, the role of intraislet ghrelin in the regulation of insulin secretion in vivo remains unclear. To understand the physiological role of intraislet ghrelin in insulin secretion and glucose metabolism, we developed a transgenic (Tg) mouse model, rat insulin II promoter ghrelin-internal ribosomal entry site-ghrelin O-acyl transferase (RIP-GG) Tg mice, in which mouse ghrelin cDNA and ghrelin O-acyltransferase are overexpressed under the control of the rat insulin II promoter. Although pancreatic desacyl ghrelin levels were elevated in RIP-GG Tg mice, pancreatic ghrelin levels were not altered in animals on a standard diet. However, when Tg mice were fed a medium-chain triglyceride-rich diet (MCTD), pancreatic ghrelin levels were elevated to ∼16 times that seen in control animals. It seems likely that the gastric ghrelin cells possess specific machinery to provide the octanoyl acid necessary for ghrelin acylation but that this machinery is absent from pancreatic β-cells. Despite the overexpression of ghrelin, plasma ghrelin levels in the portal veins of RIP-GG Tg mice were unchanged from control levels. Glucose tolerance, insulin secretion, and islet architecture in RIP-GG Tg mice were not significantly different even when the mice were fed a MCTD. These results indicate that intraislet ghrelin does not play a major role in the regulation of insulin secretion in vivo.
C6orf176: a novel possible regulator of cAMP-mediated gene expression
Authors: Reitmair Armin , Sachs George , Im Wha Bin , Wheeler Larry
Published: November 2011

cAMP mediates diverse cellular signals including prostaglandin (PG) E2-mediated intraocular pressure (IOP)-lowering activity in human ocular ciliary smooth muscle cells (hCSM). We have identified gene regulatory networks and key genes upon activation of the cAMP pathway in hCSM, using novel agonists highly selective for PGE2 receptor subtypes EP2 or EP4, which are G protein-coupled receptors well known to activate cAMP signaling. Here we describe a novel, EP2/EP4-induced, primate-specific gene of hitherto unknown function, also known as C6orf176 (chromosome 6 open reading frame 176) and recently reclassified as noncoding RNA in NCBI's database. Its expression, as determined by quantitative real-time RT-PCR (qRT-PCR), is dramatically upregulated (>2,000-fold) subsequent to transduction of EP2/EP4/Gs/cAMP signaling not only in hCSM, but also in HEK cells overexpressing the recombinant receptors. Moreover, activation of other IOP lowering, Gs-coupled prostanoid receptors, such as DP1 and IP, as well as a direct activator of adenylyl cyclase, forskolin, also substantially upregulated C6orf176 in hCSM, while FP and TP, which are Gq-coupled prostanoid receptor subtypes, did not. Novel transcript variants carrying open reading frames, derived from an at least 67 kb genomic locus on chromosome 6q27 with putative alternative transcription start sites, were identified. Transcriptional upregulation of transcript variants as well as of two genes expressed in antisense orientation that partially overlap the transcribed C6orf176 region was observed, to varying degrees, subsequent to induction of cAMP signaling using various agonists. Small interfering RNA-mediated C6orf176 gene silencing experiments showed modulation of several cAMP-responsive genes. These transcriptional activities identify C6orf176 as a potential biomarker and/or therapeutic target in context with diseases linked to deregulated cAMP signaling. Also, the cAMP-inducible C6orf176 gene locus could be useful as a model system for studying transcriptional regulation by chromatin and RNA polymerase II.
Use of contiguous congenic strains in analyzing compound QTLs
Authors: Rapp John P. , Joe Bina
Published: November 2011

Genetic analysis of polygenic traits in rats and mice has been very useful for finding the approximate chromosomal locations of the genes causing quantitative phenotypic variation, so-called quantitative trait loci (QTL). Further localization of the causative genes and their ultimate identification has, however, proven to be slow and frustrating. A major technique for gene identification in such models utilizes series of congenic strains with progressively smaller chromosomal segments introgressed from one inbred strain into another inbred strain. Under the assumption that a single causative locus underlies a QTL, nested series of congenic strains were earlier suggested as an appropriate configuration for the congenic strains. It is now known that most QTL are compound, that is, the QTL signal is caused by clusters of loci where alleles exert positive, negative, and interactive effects on the trait in a given strain comparison. It is argued that in this situation an initial series of nonoverlapping contiguous congenic strains over a relatively large chromosomal region will lead to a better appreciation of the underlying complexity of the QTL and therefore more rapid gene identification. Examples from the literature where this strategy would be helpful, as well as a case where it would be potentially counterproductive, are given.
Androgen Deprivation Causes Epithelial–Mesenchymal Transition in the Prostate: Implications for Androgen-Deprivation Therapy
Authors: Sun Yuting , Wang Bu-Er , Leong Kevin G. , Yue Peng , Li Li , Jhunjhunwala Suchit , Chen Darrell , Seo Kyounghee , Modrusan Zora , Gao Wei-Qiang , Settleman Jeffrey , Johnson Leisa
Published: November 2011

Androgen deprivation is currently a standard-of-care, first-line therapy for prostate cancer in the United States. Although this regimen effectively regresses androgen-dependent disease, relapse often occurs in an androgen-independent manner and is associated with poor prognosis. Such castration-resistant prostate cancer represents a major clinical challenge, and the mechanisms underlying castration resistance are not fully understood. Epithelial–mesenchymal transition (EMT) is a key developmental process and has also been implicated in cancer metastasis and therapeutic resistance in recent years. However, the factors contributing to EMT in human cancers remain unclear. Here, we show that both normal mouse prostate tissue and human LuCaP35 prostate tumor explants display an EMT as well as increased stem cell–like features following androgen deprivation. Importantly, we observed similar changes in mesenchymal features in prostate tumors from patients treated with androgen-deprivation therapy. In addition, we have delineated a feedback loop involving the androgen receptor and the Zeb1 transcription factor that seems to mediate this transition. In summary, we show for the first time that androgen deprivation induces EMT in both normal prostate and prostate cancer, revealing a potentially important consequence of a standard-of-care treatment for prostate cancer. This finding could have significant implications for second-line treatment strategies in this clinical setting. Cancer Res; 72(2); 527–36. ©2011 AACR.
Differences in the Pattern and Regulation of Mineral Deposition in Human Cell Lines of Osteogenic and Non-Osteogenic Origin
Authors: Rashidi Hassan , Strohbuecker Stephanie , Jackson Leigh , Kalra Spandan , Blake Alexander J. , France Louise , Tufarelli Cristina , Sottile Virginie
Published: November 2011

Bone marrow-derived mesenchymal stem cells (MSCs) are widely used as a cellular model of bone formation, and can mineralize in vitro in response to osteogenic medium (OM). It is unclear, however, whether this property is specific to cells of mesenchymal origin. We analysed the OM response in 3 non-osteogenic lines, HEK293, HeLa and NTera, compared to MSCs. Whereas HEK293 cells failed to respond to OM conditions, the 2 carcinoma-derived lines NTera and HeLa deposited a calcium phosphate mineral comparable to that present in MSC cultures. However, unlike MSCs, HeLa and NTera cultures did so in the absence of dexamethasone. This discrepancy was confirmed, as bone morphogenetic protein inhibition obliterated the OM response in MSCs but not in HeLa or NTera, indicating that these 2 models can deposit mineral through a mechanism independent of established dexamethasone or bone morphogenetic protein signalling.
Regional Variations in the Management of Testicular or Ovotesticular Disorders of Sex Development
Authors: Josso N. , Audi L. , Shaw G.
Published: November 2011

Disorders of sex development arise in parts of the world with different socio-economic and cultural characteristics. We wished to determine the regional variations in the management of these conditions. A questionnaire was e-mailed to the 650 members of the European Society for Paediatric Endocrinology (ESPE), an international society with a mainly European membership but which also includes professionals from other continents. Results were subjected to statistical analysis. A total of 62 answers were received, a satisfactory rate given that not all members are involved in this issue. Results show statistically significant regional differences for available diagnostic resources, age of the patient at gender assignment, parameters considered important for gender assignment, and timing of discussion of various issues with parents and patient. The regional variations exist not only between different continents, as already demonstrated by others, but also between Northern, Latin and Eastern European countries. This suggests that ‘one-fits-all’ guidelines for management are not appropriate.
Low-Flow, Low-Gradient Severe Aortic Stenosis Despite Normal Ejection Fraction Is Associated With Severe Left Ventricular Dysfunction as Assessed by Speckle-Tracking Echocardiography
Authors: Adda Jérôme , Mielot Christopher , Giorgi Roch , Cransac Frédéric , Zirphile Xavier , Donal Erwan , Sportouch-Dukhan Catherine , Réant Patricia , Laffitte Stéphane , Cade Stéphane , Le Dolley Yvan , Thuny Franck , Touboul Nathalie , Lavoute Cécile , Avierinos Jean-François , Lancellotti Patrizio , Habib Gilbert
Published: November 2011

Background—

Low-flow low-gradient (LFLG) is sometimes observed in severe aortic stenosis (AS) despite normal ejection fraction, but its frequency and mechanisms are still debated. We aimed to describe the characteristics of patients with LFLG AS and assess the presence of longitudinal left ventricular dysfunction in these patients.

Methods and Results—

In a multicenter prospective study, 340 consecutive patients with severe AS and normal ejection fraction were studied. Longitudinal left ventricular function was assessed by 2D-strain and global afterload by valvulo-arterial impedance. Patients were classified according to flow and gradient: low flow was defined as a stroke volume index ≤35 mL/m
2
, low gradient as a mean gradient ≤40 mm Hg. Most patients (n=258, 75.9%) presented with high-gradient AS, and 82 patients (24.1%) with low-gradient AS. Among the latter, 52 (15.3%) presented with normal flow and low gradient and 30 (8.8%) with LFLG. As compared with normal flow and low gradient, patients with LFLG had more severe AS (aortic valve area=0.7±0.12 cm
2
versus 0.86±0.14 cm
2
), higher valvulo-arterial impedance (5.5±1.1 versus 4±0.8 mm Hg/mL/m
2
), and worse longitudinal left ventricular function (basal longitudinal strain=−11.6±3.4 versus −14.8±3%;
P
<0.001 for all).

Conclusions—

LFLG AS is observed in 9% of patients with severe AS and normal ejection fraction and is associated with high global afterload and reduced longitudinal systolic function. Patients with normal-flow low-gradient AS are more frequent and present with less severe AS, normal afterload, and less severe longitudinal dysfunction. Severe left ventricular longitudinal dysfunction is a new explanation to the concept of LFLG AS.
Kinematic Signatures of Telic and Atelic Events in ASL Predicates
Authors: Malaia Evie , Wilbur Ronnie B.
Published: November 2011

This article presents an experimental investigation of kinematics of verb sign production in American Sign Language (ASL) using motion capture data. The results confirm that event structure differences in the meaning of the verbs are reflected in the kinematic formation: for example, in the telic verbs (THROW, HIT), the end-point of the event is marked in the verb sign movement by significantly greater deceleration, as compared to atelic verbs (SWIM, TRAVEL). This end-point marker is highly robust regardless of position of the verb in the sentence (medial vs. final), although other prominent kinematic measures, including sign duration and peak speed of dominant hand motion within the sign, are affected by prosodic processes such as Phrase Final Lengthening. The study provides the first kinematic confirmation that event structure is expressed in movement profiles of ASL verbs, up to now only supported by apparent perceptual distinctions. The findings raise further questions about the psychology of event representation both in human languages and in the human mind.
Population Pharmacokinetics of Fingolimod Phosphate in Healthy Participants
Authors: Wu Kai , Mercier Francois , David Olivier J. , Schmouder Robert L. , Looby Michael
Published: November 2011

Fingolimod (FTY720) is a sphingosine 1‐phosphate receptor (S1PR) modulator currently being evaluated for the treatment of multiple sclerosis. Fingolimod undergoes phosphorylation in vivo to yield fingolimod phosphate (fingolimod‐P), which modulates S1PRs expressed on lymphocytes and cells in the central nervous system. The authors developed a population model, using pooled data from 7 phase 1 studies, to enable characterization of fingolimod‐P pharmacokinetics following oral administration of fingolimod and to evaluate the impact of key demographic variables on exposure. The fingolimod‐P concentration‐time course after either single or multiple doses of fingolimod was described by a 2‐compartment model with first‐order apparent formation and elimination, lag time in the apparent formation, and dose‐dependent relative bioavailability and apparent central volume of distribution. Body weight and ethnicity were identified as demographic covariates correlated with the disposition of fingolimod‐P. Model predictions indicated no need for dose adjustment of fingolimod based on body weight; the effect of ethnicity on the disposition of fingolimod requires further investigation. The accurate prediction of the pharmacokinetic profile of fingolimod‐P determined empirically in 2 large phase 3 trials provides external validation of the model.
Veteran Electability to the Presidency
Authors: Karsten Peter
Published: November 2011

Academics and other commentators have posited a voter preference for veterans in American Presidential elections. Indeed, Albert Somit, in an oft cited article in Public Opinion Quarterly (Vol. 12, 1948, 192-200), went so far as to maintain that on the basis of the historical record, “a party nominating a military hero [for president] would be enhancing its chances of winning the election,” and called for such nominations to provide “a real test of this thesis.” (p. 200) This research note raises questions about Somit’s research methodology, offers one of its own, and finds Somit’s and other commentators’ claims to be unfounded. It concludes with some considerations as to why these claims were faulty.
Convergence and nonconvergence in the quality of adolescent relationships and its association with adolescent adjustment and young-adult relationship quality
Authors: Jager Justin
Published: November 2011

With the aim of identifying and examining both convergence (matched relationship quality across one’s set of relationships) and nonconvergence (mixed relationship quality across one’s set of relationships), the present study used a pattern-centered approach to examine the different ways adolescent relationships pattern together among a large, national sample of U.S. adolescents (aged 13–19). The study also examined how adolescent adjustment and young-adult relationship quality varied across the different relationship patterns or constellations. The current study used latent class analysis and data from Add Health ( n = 4,233), a national U.S. longitudinal study that spans adolescence and young adulthood, to uncover heterogeneity in adolescent relations with parents, friends, romantic partners, peers, and teachers. As predicted, patterns of both convergence and nonconvergence were found, though patterns of nonconvergence were more common than expected. Some patterns of nonconvergence appear more stable (i.e., similar pattern found during both adolescence and young adulthood) than others. Also, no “high” converging pattern was found, indicating that few adolescents have “first-rate” relations in every relational domain.
The power of disclosure
Authors: Allen Amy
Published: November 2011

This article discusses the relationship between power and reflective disclosure in Nikolas Kompridis' book Critique and Disclosure. Although the concept of power is not explicitly theorized in great detail in this book, I argue that power is highly relevant for Kompridis' account of reflective disclosure. I offer a few ways in which a thematization of power relations might complicate and enrich Kompridis' understanding of disclosure.
Recommendations for the Evaluation of Pathology Data in Nonclinical Safety Biomarker Qualification Studies
Authors: Burkhardt John E. , Pandher Karamjeet , Solter Phillip F. , Troth Sean P. , Boyce Rogely Waite , Zabka Tanja S. , Ennulat Daniela
Published: November 2011

A set of best practices for the conduct of histopathology evaluation in nonclinical safety studies was endorsed by the Society of Toxicologic Pathology (STP) in 2004. These best practices indicate that the study pathologist should have knowledge of the treatment group and access to all available study-related data for the animal from which the tissue was obtained. A new set of best practices for the conduct of histopathology review for safety biomarker qualification for nonclinical studies has been endorsed by the STP and is summarized in this document. These best practices are generally similar to those for nonclinical safety studies, specifically that the pathologist be “unblinded” or have access to study data. Although histopathology evaluation in biomarker qualification studies must be performed without knowledge of novel biomarker data, the study pathologist(s) should be involved in the attendant meta-analyses of these data. Blinded evaluation is an experimental tool in biomarker qualification studies that is appropriate only when well-defined criteria for specific histopathologic findings are identified prior to blinded review. Additionally, this paper also considers the management of bias, the use of a tiered evaluation approach, the importance of using qualified pathologists and standard reporting, and the management of spontaneous findings.
Integrating the American Criminal Justice and Mental Health Service Systems to Focus on Victimization
Authors: Jennings Wesley G. , Gover Angela R. , Piquero Alex R.
Published: November 2011

Although most research and policy in the mental health and criminal justice arenas have operated independently of one another, there is a growing consensus suggesting the need for an integration of these two disparate, yet complementary systems. Furthermore, in light of the adverse mental health consequences that often accompany victimization experiences, it is apparent that these two systems should develop and foster overlapping services for crime victims. The research reviewed herein provides an examination of issues such as these, identifies some of the barriers that stand in the way of a successful integration of the two systems, and attempts to provide some guidance and direction for future integrated mental health and criminal justice system approaches. An outline of research gaps and directions for future study are offered for the integration of criminal justice and mental health systems, as such collaborations are likely to alleviate some of the deleterious mental health outcomes evident among crime victims and at the same time reduce the occurrence of repeat victimization.
Emotional labour and emotional strain among Swedish prison officers
Authors: Nylander Per-Åke , Lindberg Odd , Bruhn Anders
Published: November 2011

This article explores emotional labour strategies among Swedish prison officers, and shows how these affect their well-being. Case studies of five Swedish prisons and a national survey of prison officers are used. Analysis indicates that prison officers perform complex forms of emotional labour. Owing to differences in subcultures and informal norms, the strategies officers use in managing their displays of emotion vary between wings and roles. Different strategies may cause different kinds of emotional strain. So-called ‘surface acting’ may lead to cynicism and alienation, whereas ‘deep acting’ may lead to stress and exhaustion. Finally, the lack of opportunities for recovery is discussed.
Exceptional prison conditions and the quality of prison life: Prison size and prison culture in Norwegian closed prisons
Authors: Johnsen Berit , Granheim Per Kristian , Helgesen Janne
Published: November 2011

This paper discusses the quality of prison life and prison size in relation to the notion of ‘Scandinavian exceptionalism’. Using the questionnaires ‘Measuring the Quality of Prison Life’ (MQPL) for prisoners and ‘Staff Measuring the Quality of Prison Life’ (SQL) for staff, data were collected from all 32 closed prisons in Norway. Based on the assumption that prison officers’ working lives, their perspectives and their values influence prisoners’ quality of life, the main focus in the paper is on the officers. Small prisons (fewer than 50 prisoners) obtain more positive results than medium-sized (50–100) and large (more than 100) prisons, on several dimensions measured. The relationship between officers and prisoners seems to be of better quality in small prisons than in medium-sized and large prisons. Officers in small prisons also report more positive relationships with senior management than their colleagues in medium-sized and large prisons. The results are discussed in light of previous studies on officers and prison working life dynamics.
Cognitive Reserve and Lifestyle in Spanish Individuals With Sporadic Alzheimer’s Disease
Authors: Rodríguez Juan Luis Sánchez , Torrellas Clara , Martín Javier , Fernandez María José
Published: November 2011

Background: Some authors suggest that besides the fundamental components, cognitive reserve (CR) also reflects the influence of a combination of factors that improve mental health. Method: After obtaining the sociodemographic profile of each participant and evaluating their neurologic and neuropsychologic abilities, first, homogeneity analysis was used as a technique to select variables and reduce the number of categories with similar behavior; then CR construct was identified through a latent class analysis model. It was then possible to categorize participants according to their level in this construct and compare the neuropsychological performance of the subgroups that emerged, using a t test of differences of means for independent samples. Results: Participants with Alzheimer’s disease with low CR scores exhibited significantly greater deficits in measures of memory, attention, and language than patients with high CR. Conclusions: Our results ratify the effect of higher education, higher professional performance, and ludic activities on CR.
Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients
Authors: Shapiro Amy D. , Ragni Margaret V. , Valentino Leonard A. , Key Nigel S. , Josephson Neil C. , Powell Jerry S. , Cheng Gregory , Thompson Arthur R. , Goyal Jaya , Tubridy Karen L. , Peters Robert T. , Dumont Jennifer A. , Euwart Donald , Li Lian , Hallén Bengt , Gozzi Peter , Bitonti Alan J. , Jiang Haiyan , Luk Alvin , Pierce Glenn F.
Published: November 2011

Current factor IX (FIX) products display a half-life (t1/2) of ∼ 18 hours, requiring frequent intravenous infusions for prophylaxis and treatment in patients with hemophilia B. This open-label, dose-escalation trial in previously treated adult subjects with hemophilia B examined the safety and pharmacokinetics of rFIXFc. rFIXFc is a recombinant fusion protein composed of FIX and the Fc domain of human IgG1, to extend circulating time. Fourteen subjects received a single dose of rFIXFc; 1 subject each received 1, 5, 12.5, or 25 IU/kg, and 5 subjects each received 50 or 100 IU/kg. rFIXFc was well tolerated, and most adverse events were mild or moderate in intensity. No inhibitors were detected in any subject. Dose-proportional increases in rFIXFc activity and Ag exposure were observed. With baseline subtraction, mean activity terminal t1/2 and mean residence time for rFIXFc were 56.7 and 71.8 hours, respectively. This is ∼ 3-fold longer than that reported for current rFIX products. The incremental recovery of rFIXFc was 0.93 IU/dL per IU/kg, similar to plasma-derived FIX. These results show that rFIXFc may offer a viable therapeutic approach to achieve prolonged hemostatic protection and less frequent dosing in patients with hemophilia B. The trial was registered at www.clinicaltrials.gov as NCT00716716.
Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain
Authors: Su Lin , Wang Chao , Yu Yong-hao , Ren Yong-ying , Xie Ke-liang , Wang Guo-lin
Published: November 2011

Background

Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8) ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI) to the sciatic nerve.

Results

Mechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG) ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia.

Conclusions

TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.
Genetic susceptibility of intervertebral disc degeneration among young Finnish adults
Authors: Kelempisioti Anthi , Eskola Pasi J , Okuloff Annaleena , Karjalainen Ulla , Takatalo Jani , Daavittila Iita , Niinimäki Jaakko , Sequeiros Roberto B , Tervonen Osmo , Solovieva Svetlana , Kao Patrick YP , Song You-Qiang , Cheung Kenneth MC , Chan Danny , Ala-Kokko Leena , Järvelin Marjo-Riitta , Karppinen Jaro , Männikkö Minna
Published: November 2011

Background

Disc degeneration (DD) is a common condition that progresses with aging. Although the events leading to DD are not well understood, a significant genetic influence has been found. This study was undertaken to assess the association between relevant candidate gene polymorphisms and moderate DD in a well-defined and characterized cohort of young adults. Focusing on young age can be valuable in determining genetic predisposition to DD.

Methods

We investigated the associations of existing candidate genes for DD among 538 young adults with a mean age of 19 belonging to the 1986 Northern Finland Birth Cohort. Nineteen single nucleotide polymorphisms (SNP) in 16 genes were genotyped. We evaluated lumbar DD using the modified Pfirrmann classification and a 1.5-T magnetic resonance scanner for imaging.

Results

Of the 538 individuals studied, 46% had no degeneration, while 54% had DD and 51% of these had moderate DD. The risk of DD was significantly higher in subjects with an allele G of IL6 SNPs rs1800795 (OR 1.45, 95% CI 1.07-1.96) and rs1800797 (OR 1.37, 95% CI 1.02-1.85) in the additive inheritance model. The role of IL6 was further supported by the haplotype analysis, which resulted in an association between the GGG haplotype (SNPs rs1800797, rs1800796 and rs1800795) and DD with an OR of 1.51 (95% CI 1.11-2.04). In addition, we observed an association between DD and two other polymorphisms, SKT rs16924573 (OR 0.27 95% CI 0.07-0.96) and CILP rs2073711 in women (OR 2.04, 95% CI 1.07-3.89).

Conclusion

Our results indicate that IL6, SKT and CILP are involved in the etiology of DD among young adults.
Cross-sectional and longitudinal study of association between circulating thiobarbituric acid-reacting substance levels and clinicobiochemical parameters in 1,178 middle-aged Japanese men - the Amagasaki Visceral Fat Study
Authors: Okauchi Yukiyoshi , Kishida Ken , Funahashi Tohru , Noguchi Midori , Ogawa Tomoko , Okita Kohei , Iwahashi Hiromi , Ohira Tetsuya , Imagawa Akihisa , Nakamura Tadashi , Shimomura Iichiro
Published: November 2011

Background

Circulating thiobarbituric acid-reacting substance (TBARS) levels, a marker of systemic oxidative stress, are predictive of cardiovascular events. However, they has not been evaluated in Japanese, especially with regard to the factors that contribute to the changes in circulating TBARS levels. We investigated the cross-sectional and longitudinal relationships between circulating TBARS levels and various clinicobiochemical parameters in middle-aged men.

Methods

In this population-based study (The Amagasaki Visceral Fat Study), 1,178 Japanese male urban workers who had undergone health check-ups in 2006, 2007 and 2008 and were not on medications for metabolic disorders during the follow-up period, were enrolled. Serum TBARS levels were measured by the method of Yagi. The estimated visceral fat area (eVFA) by bioelectrical impedance was measured annually. After health check-ups, subjects received health education with lifestyle modification by medical personnel.

Results

The number of cardiovascular risk factors (hypertension, hyperglycemia, low HDL-C, hypertriglyceridemia, hyperuricemia, hyper-LDL-C and impaired renal function) augmented with the increases in log-eVFA (p < 0.0001) and log-TBARS (p < 0.0001). The combination of TBARS and eVFA had a multiplicative effect on risk factor accumulation (F value = 79.1, p = 0.0065). Stepwise multiple regression analysis identified log-eVFA, as well as age, log-body mass index (BMI), LDL-C, log-adiponectin, γ-glutamyl transpeptidase (γ-GTP) and uric acid as significant determinants of log-TBARS. Stepwise multiple regression analysis identified one-year changes in eVFA as well as BMI, γ-GTP and estimated glomerular filtration rate (eGFR) as significant determinants of one-year change in TBARS, and biennial changes in eVFA as well as BMI and γ-GTP, eGFR as significant determinants of biennial change in TBARS.

Conclusions

The present study showed a significant cross-sectional and longitudinal correlation between TBARS and eVFA, as well as BMI and γ- GTP, eGFR. Visceral fat reduction may independently associate with the improvement in systemic ROS in middle-aged Japanese men.

Trial Registration

The Amagasaki Visceral Fat Study UMIN000002391.
miRNA signature associated with outcome of gastric cancer patients following chemotherapy
Authors: Kim Chang Hee , Kim Hark K , Rettig R Luke , Kim Joseph , Lee Eunbyul T , Aprelikova Olga , Choi Il J , Munroe David J , Green Jeffrey E
Published: November 2011

Background

Identification of patients who likely will or will not benefit from cytotoxic chemotherapy through the use of biomarkers could greatly improve clinical management by better defining appropriate treatment options for patients. microRNAs may be potentially useful biomarkers that help guide individualized therapy for cancer because microRNA expression is dysregulated in cancer. In order to identify miRNA signatures for gastric cancer and for predicting clinical resistance to cisplatin/fluorouracil (CF) chemotherapy, a comprehensive miRNA microarray analysis was performed using endoscopic biopsy samples.

Methods

Biopsy samples were collected prior to chemotherapy from 90 gastric cancer patients treated with CF and from 34 healthy volunteers. At the time of disease progression, post-treatment samples were additionally collected from 8 clinical responders. miRNA expression was determined using a custom-designed Agilent microarray. In order to identify a miRNA signature for chemotherapy resistance, we correlated miRNA expression levels with the time to progression (TTP) of disease after CF therapy.

Results

A miRNA signature distinguishing gastric cancer from normal stomach epithelium was identified. 30 miRNAs were significantly inversely correlated with TTP whereas 28 miRNAs were significantly positively correlated with TTP of 82 cancer patients (P<0.05). Prominent among the upregulated miRNAs associated with chemosensitivity were miRNAs known to regulate apoptosis, including let-7g, miR-342, miR-16, miR-181, miR-1, and miR-34. When this 58-miRNA predictor was applied to a separate set of pre- and post-treatment tumor samples from the 8 clinical responders, all of the 8 pre-treatment samples were correctly predicted as low-risk, whereas samples from the post-treatment tumors that developed chemoresistance were predicted to be in the high-risk category by the 58 miRNA signature, suggesting that selection for the expression of these miRNAs occurred as chemoresistance arose.

Conclusions

We have identified 1) a miRNA expression signature that distinguishes gastric cancer from normal stomach epithelium from healthy volunteers, and 2) a chemoreresistance miRNA expression signature that is correlated with TTP after CF therapy. The chemoresistance miRNA expression signature includes several miRNAs previously shown to regulate apoptosis in vitro, and warrants further validation.
Model-based parameter estimation applied to electromagnetic characterization of dispersive civil engineering media
Authors: Chahine Khaled
Published: November 2011

Geophysics publishes abstracts of dissertations and titles of master’s theses both in print and online. Recent graduates are invited to submit their abstracts or titles by completing and submitting the appropriate form found at http://seg.org/dissertationabstracts. Abstracts and titles will be reviewed and accepted or rejected based on their relevance to the readers of Geophysics. Abstracts must be written in English and defended in 2009 or later.
Effects of reservoir compaction on seismic and gravity monitoring
Authors: Tempone Pamela
Published: November 2011

Geophysics publishes abstracts of dissertations and titles of master’s theses both in print and online. Recent graduates are invited to submit their abstracts or titles by completing and submitting the appropriate form found at http://seg.org/dissertationabstracts. Abstracts and titles will be reviewed and accepted or rejected based on their relevance to the readers of Geophysics. Abstracts must be written in English and defended in 2009 or later.
On the value of information for spatial problems in the earth sciences
Authors: Trainor-Guitton Whitney
Published: November 2011

Geophysics publishes abstracts of dissertations and titles of master’s theses both in print and online. Recent graduates are invited to submit their abstracts or titles by completing and submitting the appropriate form found at http://seg.org/dissertationabstracts. Abstracts and titles will be reviewed and accepted or rejected based on their relevance to the readers of Geophysics. Abstracts must be written in English and defended in 2009 or later.
VDR/RXR and TCF4/β-Catenin Cistromes in Colonic Cells of Colorectal Tumor Origin: Impact on c-FOS and c-MYC Gene Expression
Authors: Meyer Mark B. , Goetsch Paul D. , Pike J. Wesley
Published: November 2011

Many of the transcriptional and growth regulating activities of 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in the intestine and colon are recapitulated in the human colorectal cancer cell LS180. We therefore used this line together with chromatin immunoprecipitation-seq and gene expression analyses to identify the vitamin D receptor (VDR)/retinoid X receptor (RXR) and transcription factor 7-like 2 (TCF7L2/TCF4)/β-catenin cistromes and the genes that they regulate. VDR and RXR colocalized to predominantly promoter distal, vitamin D response element-containing sites in a largely ligand-dependent manner. These regulatory sites control the expression of both known as well as novel 1,25-(OH)2D3 target genes. TCF4 and β-catenin cistromes partially overlapped, contained TCF/lymphoid enhancer-binding factor consensus elements, and were only modestly influenced by 1,25-(OH)2D3. However, the two heterodimer complexes colocalized at sites near a limited set of genes that included c-FOS and c-MYC; the expression of both genes was modulated by 1,25-(OH)2D3. At the c-FOS gene, both VDR/RXR and TCF4/β-catenin bound to a single distal enhancer located 24 kb upstream of the transcriptional start site. At the c-MYC locus, however, binding was noted at a cluster of sites between −139 and −165 kb and at a site located −335 kb upstream. Examined as isolated enhancer fragments, these regions exhibited basal and 1,25-(OH)2D3-inducible activities that were interlinked to both VDR and β-catenin activation. These data reveal additional complexity in the regulation of target genes by 1,25-(OH)2D3 and support a direct action of both VDR and the TCF4/β-catenin regulatory complex at c-FOS and c-MYC.
Regulation of insulin-producing cells in the adult Drosophila brain via the tachykinin peptide receptor DTKR
Authors: Birse Ryan T. , Söderberg Jeannette A. E. , Luo Jiangnan , Winther Åsa M. E. , Nässel Dick R.
Published: November 2011

Drosophila insulin-like peptides (DILPs) play important hormonal roles in the regulation of metabolic carbohydrates and lipids, but also in reproduction, growth, stress resistance and aging. In spite of intense studies of insulin signaling in Drosophilag the regulation of DILP production and release in adult fruit flies is poorly understood. Here we investigated the role of Drosophila tachykinin-related peptides (DTKs) and their receptors, DTKR and NKD, in the regulation of brain insulin-producing cells (IPCs) and aspects of DILP signaling. First, we show DTK-immunoreactive axon terminations close to the presumed dendrites of the IPCs, and DTKR immunolabeling in these cells. Second, we utilized targeted RNA interference to knock down expression of the DTK receptor, DTKR, in IPCs and monitored the effects on Dilp transcript levels in the brains of fed and starved flies. Dilp2 and Dilp3, but not Dilp5, transcripts were significantly affected by DTKR knockdown in IPCs, both in fed and starved flies. Both Dilp2 and Dilp3 transcripts increased in fed flies with DTKR diminished in IPCs whereas at starvation the Dilp3 transcript plummeted and Dilp2 increased. We also measured trehalose and lipid levels as well as survival in transgene flies at starvation. Knockdown of DTKR in IPCs leads to increased lifespan and a faster decrease of trehalose at starvation but has no significant effect on lipid levels. Finally, we targeted the IPCs with RNAi or ectopic expression of the other DTK receptor, NKD, but found no effect on survival at starvation. Our results suggest that DTK signaling, via DTKR, regulates the brain IPCs.
Induced and constitutive responses of digestive enzymes to plant toxins in an herbivorous mammal
Authors: Kohl Kevin D. , Dearing M. Denise
Published: November 2011

Many plants produce plant secondary compounds (PSCs) that bind and inhibit the digestive enzymes of herbivores, thus limiting digestibility for the herbivore. Herbivorous insects employ several physiological responses to overcome the anti-nutritive effects of PSCs. However, studies in vertebrates have not shown such responses, perhaps stemming from the fact that previously studied vertebrates were not herbivorous. The responses of the digestive system to dietary PSCs in populations of Bryant's woodrat (Neotoma bryanti) that vary in their ecological and evolutionary experience with the PSCs in creosote bush (Larrea tridentata) were compared. Individuals from naïve and experienced populations were fed diets with and without added creosote resin. Animals fed diets with creosote resin had higher activities of pancreatic amylase, as well as luminal amylase and chymotrypsin, regardless of prior experience with creosote. The experienced population showed constitutively higher activities of intestinal maltase and sucrase. Additionally, the naïve population produced an aminopeptidase-N enzyme that was less inhibited by creosote resin when feeding on the creosote resin diet, whereas the experienced population constitutively expressed this form of aminopeptidase-N. Thus, the digestive system of an herbivorous vertebrate responds significantly to dietary PSCs, which may be important for allowing herbivorous vertebrates to feed on PSC-rich diets.
The mechanics and control of pitching manoeuvres in a freely flying hawkmoth (Manduca sexta)
Authors: Cheng Bo , Deng Xinyan , Hedrick Tyson L.
Published: November 2011

Insects produce a variety of exquisitely controlled manoeuvres during natural flight behaviour. Here we show how hawkmoths produce and control one such manoeuvre, an avoidance response consisting of rapid pitching up, rearward flight, pitching down (often past the original pitch angle), and then pitching up slowly to equilibrium. We triggered these manoeuvres via a sudden visual stimulus in front of free-flying hawkmoths (Manduca sexta) while recording the animals' body and wing movements via high-speed stereo videography. We then recreated the wing motions in a dynamically scaled model to: (1) associate wing kinematic changes with pitch torque production and (2) extract the open-loop dynamics of an uncontrolled moth. Next, we characterized the closed-loop manoeuvring dynamics from the observed flight behaviour assuming that hawkmoths use feedback control based on translational velocity, pitch angle and angular velocity, and then compared these with the open-loop dynamics to identify the control strategy used by the moth. Our analysis revealed that hawkmoths produce active pitch torque via changes in mean wing spanwise rotation angle. Additionally, body translations produce passive translational damping and pitch torque, both of which are linearly dependent on the translational velocity. Body rotations produce similar passive forces and torques, but of substantially smaller magnitudes. Our comparison of closed-loop and open-loop dynamics showed that hawkmoths rely largely on passive damping to reduce the body translation but use feedback control based on pitch angle and angular velocity to control their orientation. The resulting feedback control system remains stable with sensory delays of more than two wingbeats.
Dynorphin regulates the phagocytic activity of splenic phagocytes in wall lizards: involvement of a κ-opioid receptor-coupled adenylate-cyclase–cAMP–PKA pathway
Authors: Kumar Sunil , Rai Umesh
Published: November 2011

This in vitro study of the wall lizard Hemidactylus flaviviridis demonstrates the role of the opioid peptide dynorphin A(1–17) [dyn A(1–17)] in the regulation of the phagocytic activity of splenic phagocytes. Dyn A(1–17) in a concentration-dependent manner inhibited the phagocytic activity, and the maximum inhibition was recorded at a concentration of 10–9 mol l–1. To explore the receptor-mediated effect of dyn A(1–17), cells were treated simultaneously with the non-selective opioid receptor blocker naltrexone and dyn A(1–17). Naltrexone completely blocked the inhibitory effect of dyn A(1–17) on phagocytosis. Moreover, the involvement of selective opioid receptors was investigated using selective opioid receptor antagonists. CTAP and naltrindole, selective μ- and δ-opioid receptor blockers, respectively, failed to block the inhibitory effect of dyn A(1–17) on phagocytosis. However, the selective κ-opioid receptor blocker NorBNI completely antagonized the inhibitory effect of dyn A(1–17). Regarding the κ-opioid receptor-coupled downstream signaling cascade, the adenylate cyclase (AC) inhibitor SQ 22536 and protein kinase A (PKA) inhibitor H-89 decreased the inhibitory effect of dyn A(1–17) on phagocytosis. Furthermore, treatment with dyn A(1–17) caused an increase in intracellular cAMP content in splenic phagocytes. Thus, it can be concluded that, in H. flaviviridis, dyn A(1–17) negatively regulates the phagocytic activity of splenic phagocytes by acting through κ-opioid receptors that are coupled with the AC–cAMP–PKA signal transduction mechanism.