bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Sarcopenia on the Development of Physical Disability: The Cardiovascular Health Study
Authors: Janssen Ian
Published: November 2005

OBJECTIVES: To examine the temporal relationship between sarcopenia and disability in elderly men and women.

DESIGN: Cardiovascular Health Study, a longitudinal study of cardiovascular disease and its risk factors in older people.

SETTING: Four U.S. communities.

PARTICIPANTS: Five thousand thirty‐six men and women aged 65 and older.

MEASUREMENTS: Whole‐body skeletal muscle mass was measured at baseline, and subjects were classified as having normal muscle mass, moderate sarcopenia, or severe sarcopenia based on previously established thresholds. Disability was measured via questionnaire at baseline in up to eight annual follow‐up examinations. The cross‐sectional relationship between sarcopenia and prevalent disability at baseline was examined using logistic regression models. The longitudinal relation between sarcopenia and incident disability over 8 years of follow‐up was examined using Cox proportional hazards models.

RESULTS: At baseline, the likelihood of disability was 79% greater in those with severe sarcopenia (P<.001) but was not significantly greater in those with moderate sarcopenia (P=.38) than in those with normal muscle mass. During the 8‐year follow‐up, the risk of developing disability was 27% greater in those with severe sarcopenia (P=.006) but was not statistically greater in those with moderate sarcopenia (P=.23) than in those with normal muscle mass.

CONCLUSION: Severe sarcopenia was a modest independent risk factor for the development of physical disability. The effect of sarcopenia on disability was considerably smaller in the longitudinal analysis than in the cross‐sectional analysis.
Measures of Adiposity and Risk of Breast Cancer in Older Postmenopausal Women
Authors: Krebs Erin E. , Taylor Brent C. , Cauley Jane A. , Stone Katie L. , Bowman Paula J. , Ensrud Kristine E.
Published: November 2005

OBJECTIVES: To determine whether higher adiposity is associated with greater breast cancer risk in older postmenopausal women.

DESIGN: Prospective cohort study with mean follow‐up of 11.3 years.

SETTING: Four U.S. clinical centers.

PARTICIPANTS: Seven thousand five hundred twenty‐three women (mean age 73.5) enrolled in the Study of Osteoporotic Fractures.

MEASUREMENTS: Weight, height, and waist and hip circumference were measured at baseline. Body composition was determined using bioelectrical impedance. Risk factor information was obtained by interview and questionnaire. Bone mineral density was measured using dual energy x‐ray absorptiometry. The outcome was incident invasive breast cancer, confirmed using medical records.

RESULTS: After adjustment for multiple risk factors, including bone density, women in the uppermost quartiles of weight, weight gain since age 25, body mass index, waist circumference, and percentage of body fat had higher breast cancer rates than women in the first quartiles of each measure. For example, breast cancer rates were 49% higher for women in the uppermost quartile of weight (hazard ratio (HR)=1.49, 95% confidence interval (CI)=1.05–2.10), 64% higher for women in the top quartile of weight gain since age 25 (HR=1.64, 95% CI=1.15–2.34), and 58% higher for women in the top quartile of percentage of body fat (HR=1.58, 95% CI=1.11–2.23) than for women in the lowest quartile of each measure. The associations between adiposity measures and breast cancer rates were not altered when the analyses were limited to very elderly women (≥70).

CONCLUSION: Higher adiposity is an independent risk factor for breast cancer in elderly women.
Simvastatin Causes Changes in Affective Processes in Elderly Volunteers
Authors: Morales Knashawn , Wittink Marsha , Datto Catherine , DiFilippo Suzanne , Cary Mark , TenHave Thomas , Katz Ira R.
Published: November 2005

OBJECTIVES: To test for simvastatin‐induced changes in affect and affective processes in elderly volunteers.

DESIGN: Randomized, clinical trial.

SETTING: The Geriatric Behavioral Psychopharmacology Laboratory at the University of Pennsylvania.

PARTICIPANTS: Eighty older volunteers, average age 70, with high normal/mildly elevated serum cholesterol.

INTERVENTION: Simvastatin up to 20 mg/d or placebo for 15 weeks.

MEASUREMENTS: Daily diary records of positive and negative affects and of events and biweekly measures of depressive symptoms. Affect ratings were obtained using the Lawton positive and negative affect scales; independent raters coded the valences of events.

RESULTS: Thirty‐one of 39 subjects assigned to placebo and 33 of 41 receiving simvastatin completed the study. During biweekly assessments, four subjects on simvastatin and one on placebo experienced depressive symptoms, as manifest by Center for Epidemiological Studies Depression scale scores greater than 16 (exact P=.36). Diary data demonstrated significant effects on affective processes. For positive affect, there was a significant medication‐by‐time interaction that reflected decreases in positive affect in subjects receiving simvastatin, greatest in those patients whose final total cholesterol levels were below 148 mg/dL. For negative affect, there were significant medication‐by‐event, and medication‐by‐event‐by‐time interactions, reflecting a time‐limited increase in the apparent effect of negative events.

CONCLUSION: Simvastatin has statistically significant effects on affect and affective processes in elderly volunteers. The decrease in positive affect may be significant clinically and relevant to the quality of life of many patients.
Interdisciplinary Vision: The First 25 Years of the Society for Risk Analysis (SRA), 1980–2005
Authors: Thompson Kimberly M. , Deisler Paul F. , Schwing Richard C.
Published: November 2005

In early 1979 Robert B. Cumming recognized the growing need for risk researchers and practitioners to publish their work in a dedicated professional journal. This led to the formation of an organization to support such a journal, with the Certificate of Incorporation for the Society for Risk Analysis (SRA) made official on August 28, 1980. The first issue of Risk Analysis: An International Journal appeared in March 1981. This article reviews the history of the SRA's first 25 years. It reviews the SRA's formation and growth, provides analyses of its major products (the journal, newsletter, conferences, and meetings), and discusses its impact. This article relies on published literature and a history of the SRA's first 20 years written by two of the authors. This history covers the SRA's many successes, which demonstrate the strength and vitality of the organization and provide optimism for its future. These successes include this journal, which published over 2,150 papers between March 1981 and this December 2005 issue. The successes also include its stable membership of approximately 2,000 members from 43 countries, well‐attended annual meetings, and increasing support for true international growth as demonstrated by international risk forums like the World Congress on Risk held in Brussels in June 2003. Similarly, the history also covers the SRA's challenges and difficulties, with the recognition that these provide both an important context about the organization and the opportunity to learn from past experiences. These include the challenges associated with spin‐off organizations that decreased the SRA membership in some disciplinary areas, notably in engineering and exposure assessment. This history also includes quantitative analyses of the contents of the first 25 years of Risk Analysis: An International Journal. The results show significant growth in the number of articles published each year, starting with approximately 30 articles published in the first few years to over 120 articles per year now. They also show a relatively even distribution of articles in the life, physical, and social sciences, which demonstrate the sustained commitment of the SRA and the journal to support interdisciplinary risk‐related research. The SRA organizational structure currently includes two sections (SRA‐Europe and SRA‐Japan), 22 Chapters, and nine Specialty Groups, and the structure remains somewhat in flux. We present this history in five sections that cover major themes: (1) SRA formation, (2) membership and organization, (3) publications, (4) meetings, and (5) thematic issues. Like any organization of its size, the SRA boasts a long and diverse history, and no article can possibly capture it all. We hope that in documenting the first 25 years, we strengthen the SRA by providing some perspective on its roots and a rigorous quantitative analysis of some of its products.
Legitimizing American Indian Sovereignty: Mobilizing the Constitutive Power of Law through Institutional Entrepreneurship
Authors: Steinman Erich W.
Published: November 2005

Extensive sociolegal scholarship has addressed the utility of law as a mechanism through which marginalized groups may promote social change. Within this debate, scholars employing the legal mobilization approach have thus far highlighted law's indirect impact, beyond the formal arenas of law, via effects on the “legal consciousness” of reformers and would-be reformers. This article contributes to this debate, and the legal mobilization framework in particular, by theoretically identifying and empirically documenting ways through which the constitutive power of law may be effectively used by challengers to more directly pursue changes in institutionalized practices themselves. The article examines the strategic use of law by a set of American Indian tribal leaders in the state of Washington who, over a 13-year period, consciously meshed or “cohered” legal and extrajudicial efforts to gain recognition of their sovereign political status. Through a mode of agency known as “institutional entrepreneurship,” they utilized the multiplicity of law and exploited resources and opportunities inhering within the state itself, but outside the courts. In the context of ambiguous legal precedent and widespread local challenges to tribal rights, they mobilized latent discourses of federal Indian law that legitimated the sovereign governmental status of tribes. Importantly, they circulated tribal sovereignty discourses well beyond the field of law, but through the authoritative activity and voice of the state, and in doing so, generated a precedent-setting recognition of tribal sovereignty.
Penal Excess and Surplus Meaning: Public Torture Lynchings in Twentieth-Century America
Authors: Garland David
Published: November 2005

The most notorious lynchings that occurred in the United States between 1890 and 1940 involved publicity, crowds, ritual, and abnormal cruelty. Several hundred of these “public torture lynchings” took place, most of them in the Deep South. The author develops an interpretation that takes seriously the specific forms and discourses that lynchers and their supporters used to describe and justify these events—characterizing them as criminal punishments, albeit summary, informal ones that were shaped by a white supremacist culture and a politics of racial domination. An interpretation of the penal context and meanings of these public torture lynchings helps us understand their specific forms and their claims to legitimacy. The penal character of these lynchings increased the probability that they would be tolerated by local (and even national) audiences and thus made them a strategic form of violence in struggles to maintain racial supremacy. The author argues that a consideration of these events should lead us to revise our standard narratives about the evolution of modern punishments.
Transfer of the Members of the Genus Brachiola (Microsporidia) to the Genus Anncaliia Based on Ultrastructural and Molecular Data
Authors: FRANZEN CASPAR , NASSONOVA ELENA S. , SCHÖLMERICH JÜRGEN , ISSI IRMA V.
Published: November 2005

ABSTRACT. Two microsporidian genera, AnncaliiaIssi, Krylova, & Nicolaeva 1993 and BrachiolaCali et al. 1998, possess a Nosema‐type life cycle and unique cell surface ornamentations, which include precocious electron‐dense coating of the plasmalemma and a variety of secretory structures deposited on the parasite surface and scattered in the host cell cytoplasm. Comparative analysis of ultrastructure of Anncaliia meligethi (the type species of the genus Anncaliia) and of B. vesicularum and B. algerae (the best‐studied members of the genus Brachiola) clearly demonstrated that these microsporidia share many distinctive morphological features. The comparison of small subunit ribosomal DNA sequences showed high sequence identity of A. meligethi and B. algerae. Phylogenetic analyses indicated that the rDNA sequences of A. meligethi clustered with those of B. algerae suggesting a close relatedness of these microsporidia. The combination of molecular and morphological data provided clear evidence that these microsporidia belong to the same genus and therefore, warranted emendation of the genus Anncaliia and establishments of the following new combinations: Anncaliia vesicularum nov. comb., Anncaliia algerae nov. comb., Anncaliia connori nov. comb., and Anncaliia gambiae nov. comb. The generic name Brachiola is submerged according to the rule of priority.
Molecular Phylogeny of a Potentially Parasitic Dinoflagellate Isolated from the Solitary Radiolarian, Thalassicolla nucleata
Authors: GAST REBECCA J.
Published: November 2005

ABSTRACT. Thalassicolla nucleata, a solitary radiolarian, has been described as being parasitized by two dinoflagellates, Solenodinium (Syndiniales) and Caryotoma (Blastodiniales). Several T. nucleata were stripped of their extracapsular material and allowed to regenerate their rhizopodial structures without symbionts. Within a week, two were observed to disintegrate, leaving behind non‐pigmented swimming dinoflagellate cells. Identical full‐length ribosomal sequences were recovered from both samples. Upon alignment and phylogenetic analysis, it was determined that these putative parasite sequences were distinct from Scrippsiella nutricula (the dinoflagellate symbiont of the host), and also from all other dinoflagellate parasites sequenced to date.
Treatment delay and response rate in first episode psychosis
Authors: Wunderink A. , Nienhuis F. J. , Sytema S. , Wiersma D.
Published: November 2005

Objective:  There is no consistent evidence of long duration of untreated psychosis (DUP) predicting long time to response (TTR) in first psychosis. This study aims to investigate the predictors of DUP and TTR in a first episode patient population.

Method:  An epidemiologically representative sample of 157 non‐affective first psychotic episode patients was interviewed and followed‐up for at least half a year.

Results:  The mean DUP was 46 weeks, the median 31 days. Long DUP was associated with being unemployed before treatment and male gender. Short DUP, having a job, and living with a partner before treatment predicted early response.

Conclusion:  Early intervention likely improves short‐term treatment response in first episode psychosis. The best strategy to reduce DUP probably is to direct attention to the substantial number of patients who do not engage in regular treatment.
Effects of IgG and its F(ab′)2 fragments of some patients with idiopathic thrombocytopenic purpura on platelet aggregation
Authors: Chu Xiao Xia , Hou Ming , Peng Jun , Zhu Yuan Yuan , Ji Xue Hin , Wang Lin , Zhang Feng , Ma Dao Xin
Published: November 2005

Abstract:  Objectives: To make humanized monoclonal antibodies by phage surface display technology, we screened out the specific anti‐platelet glycoproteins (GPs) IgG antibody from patients with chronic idiopathic thrombocytopenic purpura (ITP), which can inhibit platelet aggregation. Methods: We studied plasmas from 68 patients with ITP for the presence of IgG antibodies specific for GPIIb/IIIa and/or GPIb/IX using modified monoclonal antibody immobilization of platelet antigen assays. The IgG antibody and its F(ab′)2 fragments of the positive plasmas which could inhibit platelet aggregation function were prepared and purified. Their immunoreactivity to platelet GPs and effects on platelet function were further analyzed.Results: GPIIb/IIIa‐ and GPIb/IX‐specific antibodies were found in 21 and 19 patients, respectively. Six of them had antibodies against both GP complexes. Among the 34 positive plasmas, four with positive anti‐GPIIb/IIIa autoantibody showed significant inhibition of platelet aggregation induced by adenosine diphosphate (ADP), whereas one with GPIb/IX‐specific antibody inhibited ristocetin‐induced platelet aggregation. The purified IgG and its F(ab′)2 fragments from two patients not only retained the ability to bind to platelet GPs but also impaired the in vitro ADP‐induced platelet aggregation.Conclusions: F(ab′)2 portion of the IgG is a functional fragment, which is responsible for the autoantibody interaction with platelet GPs in ITP, and some of them also affect platelet function, which can be used to develop completely humanized anti‐GPIIb/IIIa small molecular phage antibody.
Low Erythrocyte Complement Receptor Type 1 (CR1, CD35) Expression in Preeclamptic Gestations
Authors: Feinberg Bruce B. , Jack Richard M. , Mok Samuel C. , Anderson Deborah J.
Published: November 2005

Problem

Erythrocyte complement receptor type 1 (E‐CR1) is the main immune complex clearance mechanism in humans. Decreased E‐CR1 expression is noted in certain inflammatory disorders. Recent evidence implicates inflammation in the pathogenesis of preeclampsia. We investigated whether E‐CR1 is decreased in preeclampsia.

Method of study

E‐CR1 protein expression was quantified by radioimmunoassay. Plasma concentration of soluble CR1 was quantified using a specific enzyme linked immunosorbent assay. Quantitative genotypes were evaluated by HindIII restriction fragment length polymorphism analysis.

Results

E‐CR1 expression was reduced in patients with preeclampsia. Lack of neoantigen expression (indicative of enzymatic cleavage of CR1) or elevated plasma‐soluble CR1 was evidence against an acquired loss of E‐CR1. Genotype analysis revealed a higher frequency of a CR1 allele associated with low E‐CR1 expression in preeclampsia when compared with normal pregnant controls.

Conclusions

E‐CR1 expression is decreased in preeclamptic patients and levels correlate with severity of disease. This condition may have a genetic basis in some patients.
Antisperm Vaccine for Contraception
Authors: Naz Rajesh K.
Published: November 2005

Problem

This study is a review of antisperm contraceptive vaccine (CV) development with the main focus on research going on in our laboratory.

Method of study

Various methods of proteomics and genomics, hybridoma technology, substractive libraries, differential display method, and phage display technology were used to obtain sperm‐specific genes and proteins. The present study will primarily focus on the sequences obtained by using the phage display technology and their role in CV development and human immunoinfertility.

Result

Four novel peptides, delineated by using the phage display technology, were found to be involved in human immunoinfertility. The vaccine based on one of these peptides, designated as YLP12, caused a reversible contraception in female mice.

Conclusions

The vaccine targeting sperm is a feasible and exciting approach to contraception. The phage display technology is a powerful tool to delineate sperm‐specific peptide sequences that can be used for the CV development and in the diagnosis and treatment of infertility mediated through antisperm antibodies.
Pre‐eclampsia is not Associated with Changes in the Levels of Regulatory T Cells in Peripheral Blood
Authors: Paeschke Steffen , Chen Frank , Horn Nadja , Fotopoulou Christina , Zambon‐Bertoja Annarosa , Sollwedel Andre , Zenclussen Maria Laura , Casalis Pablo Ariel , Dudenhausen Joachim W. , Volk Hans‐Dieter , Zenclussen Ana Claudia
Published: November 2005

Problem

The acceptance of the semi‐allogeneic fetus within the maternal environment requires tolerance mechanisms not fully characterized yet. Normal pregnancy is known to be associated with a Th2 profile. Furthermore, regulatory T cells (Tregs) were proposed to regulate the Th2/Th1 balance at early stages of pregnancy. Treg may avoid the shift to a Th1 profile, thus preventing miscarriage. Accordingly, spontaneous abortion is characterized by a Th1 dominance and diminished levels of Treg. The major aim of the present work was to investigate if pre‐eclampsia, a late immunological complication of pregnancy, is characterized by similar hallmarks.

Method of study

We measured the surface antigens CD4, CD25, CD8 and CTLA4 in peripheral blood from patients suffering from pre‐eclampsia (n = 8) and age‐matched patients undergoing normal pregnancies (n = 9) by four‐color flow cytometry.

Results

We were not able to find any significant differences in the levels of CD4+, CD25+, CD8+, CTLA4, CD4+/CD25+, CD4+/CD25bright, CD4+/CTLA4, CD25+/CTLA4, CD4+/CD25+/CTLA4, CD8+/CD25+, CD8+/CTLA4 or CD8+/CD25+/CTLA4 cell subsets.

Conclusions

Our data confirm comparable number of Tregs during pre‐eclampsia and normal pregnancy in peripheral blood. Other regulatory mechanisms might be involved during late pregnancy.
A Review of Trafficking and Activation of Uterine Natural Killer Cells
Authors: van den Heuvel Marianne J. , Xie Xuemei , Tayade Chandrakant , Peralta Crystal , Fang Yuan , Leonard Sean , Paffaro Valdemar A. , Sheikhi Abdol K. , Murrant Coral , Anne Croy Barbara
Published: November 2005

Problem

Enrichment of uterine natural killer (uNK) cells occurs during pregnancy in many species. However, functions of uNK cells and regulation of their uterine homing are not fully defined. In mice and women, uNK cells contribute to angiogenesis, a role reviewed here and now addressed in a mammal with an alternative placental type.

Methods of study

To address lymphocyte functions, RNA from murine or porcine endometrium and lymphocytes purified from endometrium were analyzed using real‐time or reverse transcription PCR. To address homing potential, human blood CD56+ lymphocytes were evaluated using both RNA and functional adhesion to endothelium presented under shear force in frozen sections of gestation day 7 C57Bl/6J implantation sites. Women were serially sampled over a menstrual cycle or a clinical preparatory cycle for embryo transfer.

Results

Activation of murine uNK cells is associated with much greater increases in transcription for Eomes than for T‐bet (Tbx21). Lymphocytes from normal porcine implantation sites transcribe vascular endothelial growth factor, placental growth factor, interferon‐gamma and hypoxia‐inducible factor (HIF)‐1α. In fertile women, increases in L‐selectin‐ and α4‐integrin‐mediated interactions between CD56+ cells and endothelium occur at luteinizing hormone (LH) surge (cycling women) to oocyte pick up or embryo transfer, then return to pre‐LH levels.

Conclusions

Uterine lymphocytes may universally promote pregnancy‐associated endometrial angiogenesis. Recruitment of uNK precursor cells from blood appears to occur in a window promoted by rising plasma estrogen and LH and limited by rising progesterone.
Characterization of testis‐specific serine–threonine kinase 3 and its activation by phosphoinositide‐dependent kinase‐1‐dependent signalling
Authors: Bucko‐Justyna Marta , Lipinski Leszek , Burgering Boudewijn M. Th. , Trzeciak Lech
Published: November 2005

The family of testis‐specific serine–threonine kinases (TSSKs) consists of four members whose expression is confined almost exclusively to testis. Very little is known about their physiological role and mechanisms of action. We cloned human and mouse TSSK3 and analysed the biochemical properties, substrate specificity and in vitro activation. In vitro TSSK3 exhibited the ability to autophosphorylate and to phosphorylate test substrates such as histones, myelin basic protein and casein. Interestingly, TSSK3 showed maximal in vitro kinase activity at 30 °C, in keeping with it being testis specific. Sequence comparison indicated the existence of a so‐called ‘T‐loop’ within the TSSK3 catalytic domain, a structure present in the AGC family of protein kinases. To test if this T‐loop is engaged in TSSK3 regulation, we mutated the critical threonine residue within the T‐loop to alanine (T168A) which resulted in inactivation of TSSK3 kinase. Furthermore, Thr168 is phosphorylated in vitro by the T‐loop kinase phosphoinositide‐dependent protein kinase‐1 (PDK1). PDK1‐induced phosphorylation increased in vitro TSSK3 kinase activity, suggesting that TSSK3 can be regulated in the same way as AGC kinase family members. Analysis of peptide sequences identifies the peptide sequence RRSSSY containing Ser5 that is a target for TSSK3 phosphorylation, as an efficient and specific substrate for TSSK3.
Identification of a copper‐repressible C‐type heme protein of Methylococcus capsulatus (Bath)
Authors: Karlsen Odd A. , Kindingstad Louise , Angelskår Solveig M. , Bruseth Live J. , Straume Daniel , Puntervoll Pål , Fjellbirkeland Anne , Lillehaug Johan R. , Jensen Harald B
Published: November 2005

Genomic sequencing of the methanotrophic bacterium, Methylococcus capsulatus (Bath), revealed an open reading frame (MCA2590) immediately upstream of the previously described mopE gene (MCA2589). Sequence analyses of the deduced amino acid sequence demonstrated that the MCA2590‐encoded protein shared significant, but restricted, sequence similarity to the bacterial di‐heme cytochrome c peroxidase (BCCP) family of proteins. Two putative C‐type heme‐binding motifs were predicted, and confirmed by positive heme staining. Immunospecific recognition and biotinylation of whole cells combined with MS analyses confirmed expression of MCA2590 in M. capsulatus as a protein noncovalently associated with the cellular surface of the bacterium exposed to the cell exterior. Similar to MopE, expression of MCA2590 is regulated by the bioavailability of copper and is most abundant in M. capsulatus cultures grown under low copper conditions, thus indicating an important physiological role under these growth conditions. MCA2590 is distinguished from previously characterized members of the BCCP family by containing a much longer primary sequence that generates an increased distance between the two heme‐binding motifs in its primary sequence. Furthermore, the surface localization of MCA2590 is in contrast to the periplasmic location of the reported BCCP members. Based on our experimental and bioinformatical analyses, we suggest that MCA2590 is a member of a novel group of bacterial di‐heme cytochrome c peroxidases not previously characterized.
Labor Mobilization Against Republican Incumbents In Congressional Elections, 1996–2004
Authors: Lefkowitz Joel
Published: November 2005

Labor political contributions significantly increased votes for Democrats challenging Republican incumbents, especially in 1996, but also in the three elections that followed, taking into account the major variables that matter in congressional elections. Those electoral victories yielded greater support for labor's legislative agenda, including regulations governing unionizing drives. But labor's electoral efforts lost effectiveness in the 2004 congressional elections, as labor made smaller contributions and targeted them less well, with smaller shares of the contributions going to competitive districts and to Democrats. Republicans who sometimes vote for union preferences funneled millions in labor contributions to staunchly antiunion Republicans, to whom labor also increasingly contributed directly. Labor resources should be shifted not necessarily between political campaigns and organizing drives, but away from ineffective or counterproductive contributions to Republicans toward Democrats, bringing serious challenges in favorable districts.
Offshoring: Still A Threat To Workers
Authors: Whalen Charles J.
Published: November 2005

Job offshoring has faded from the headlines since the 2004 presidential election, but the problem remains serious and continues to deserve public attention. A large portion of the U.S. workforce remains at risk to offshoring. Vulnerability is widespread and includes employees of nearly all sectors and skill levels. Moreover, the losses suffered by affected workers are often substantial. Fortunately, there are constructive public policies that can ease this dislocation and foster a more competitive, high‐employment economy.
How we do it: ‘The oral tube area method’: a new method for self‐assessment of nasal resistance
Authors: Pontoppidan J.M.
Published: November 2005

Keypoints

• Breathing orally through a tube, 20 subjects compared their sensation of air resistance in the tube with their sensation of resistance breathing through the nose.

• By changing the internal cross‐sectional area in the tube the subjects could choose an oral tube area where they felt the same resistance in the tube as in the nose.

• Expressed by the chosen oral tube area we had a measurement of the nasal resistance.

• The method can measure changes in nasal resistance.

• The method is inexpensive and easy to perform.
How we do it: Transnasal fibreoptic oesophagoscopy
Authors: McPartlin D.W. , Nouraei S.A.R. , Tatla T. , Howard D.J. , Sandhu G.S.
Published: November 2005

Keypoints

• Transnasal fibreoptic oesophagoscopy (TFO) allows the upper aerodigestive tract, from the nasal vestibule to the gastric cardia to be examined in the outpatients department without sedation.

• This permits patients with symptoms of upper aerodigestive pathology to be investigated at the initial consultation without the need for inpatient endoscopy or swallow studies.

• The technique is easily learned, and is statistically comparable with standard flexible nasoendoscopy in respect of procedural pain and discomfort.

• It is highly cost‐efficient, paying for itself within 1 year, and thereafter leading to cost savings of over 80%.

• Its role can be expanded to encompass investigating patients with potentially malignant disease processes, as well as outpatients ‘panendoscopy’ and biopsy, and a number of therapeutic interventions.
How we do it: The role of trans‐nasal flexible laryngo‐oesophagoscopy (TNFLO) in ENT: one year's experience in a head and neck orientated practice in the UK
Authors: Price T. , Sharma A. , Snelling J. , Bennett A.M.D. , Qayyum A. , Bradnam T. , Montgomery P.
Published: November 2005

Keypoints

• Transnasal flexible laryngo‐oesophagoscopy (TNFLO) is a safe and well‐tolerated procedure that may be performed in a procedure room in the outpatient or day‐case/main theatre setting.

• It requires a local anaesthetic and no sedation.

• It may be used to histologically diagnose or exclude pathology from the nose to the gastro‐oesophageal junction.

• It provides a ‘one stop’ diagnosis service, reducing diagnostic delays, the need for endoscopy under general anaesthesia, barium swallows and follow‐up outpatient appointments.

• Therapeutic procedures such as vocal cord medialization, endolaryngeal laser surgery, insertion of speech prostheses and foreign body removal may be performed without general anaesthesia.
Endoscopic sphenopalatine artery ligation – when, why and how to do it. An on‐line video tutorial
Authors: Loughran S. , Hilmi O. , McGarry G.W.
Published: November 2005

Keypoints

• Endoscopic ligation of the sphenopalatine artery (ESPAL) has recently become the treatment of choice for refractory epistaxis. This paper reviews the background, indications and potential complications of ESPAL.

• The main focus of this article is an online video tutorial on the anatomy and surgical technique of ESPAL. Web links lead to video clips of operative steps and therefore this paper should be read in front of a computer with access to the internet.

• To study the techniques the links detailed below should be followed. (For computers running realplayer software the .wmv extension in each of these links should be replaced with the .rm extension.)

• Incision, http://www.nhsgg.org.uk/content/streams/Figure3.wmv

• Flap elevation, http://www.nhsgg.org.uk/content/streams/Figure4.wmv

• Pedicle location, http://www.nhsgg.org.uk/content/streams/Figure5.wmv

• Clip application, http://www.nhsgg.org.uk/content/streams/Figure6.wmv
Psychological coping style versus disease extent, tumour treatment and quality of life in successfully treated head and neck squamous cell carcinoma patients
Authors: Aarstad A.K.H. , Aarstad H.J. , Bru E. , Olofsson J.
Published: November 2005

Objectives:  To study self‐reported coping style by the COPE questionnaire and the association to tumour node distant metastasis (TNM) stage, received treatment and health‐related quality of life (HRQoL) in a population of successfully treated head and neck squamous cell carcinoma (HNSCC) patients.

Design:  Disease free HNSCC patients were interviewed during a regular outpatient visit to the Department.

Setting:  All patients <80 years who had been diagnosed with HNSCC, in Western Norway, in the period from 1992 to 1997 and who were disease free in the year 2000 were included.

Main outcome measures:  The HNSCC patients were studied by the European organization for research and treatment of cancer quality of life (QoL) questionnaire and by the COPE questionnaire from which coping styles profiles were extracted. Clinical and socio‐demographic variables were also gathered.

Results:  Level of problem focused coping style was associated with the T stage and whether or not the patient was given neck radiotherapy. An avoidance‐focused coping style was generally associated with lowered HRQoL. Employment of emotional focused coping was associated with low HRQoL among the patients treated with surgery only, and associated with increased HRQoL among patients treated with radiation therapy only. The associations between HRQoL and coping style levels were stronger for HRQoL indexes reflecting cognitive/emotional function than for HRQoL indexes reflecting physical function.

Conclusions:  In former HNSCC patients, level of problem focused coping style was associated with the T stage and if given neck radiotherapy. Level of avoidance coping was inversely associated with the HRQoL, and level of emotional coping was associated with HRQoL in a complex manner.
A differential role for nitric oxide in two forms of physiological angiogenesis in mouse
Authors: Williams James L. , Cartland David , Hussain Arif , Egginton Stuart
Published: November 2005

NO plays a role in a variety of in vitro models of angiogenesis, although confounding effects of NO on non‐endothelial tissues make its role during in vivo angiogenesis unclear. We therefore examined the effects of NO on two physiological models of angiogenesis in mouse skeletal muscle: (1) administration of prazosin (50 mg l−1) thereby increasing blood flow; and (2) muscle overload from surgical ablation of a functional synergist. These models induce angiogenesis via longitudinal splitting and capillary sprouting, respectively. Administration of NG‐nitro‐l‐arginine (l‐NNA) abolished the increase in capillary to fibre ratio (C:F) in response to prazosin administration, along with the increases in luminal filopodia and large endothelial vacuoles. l‐NNA prevented luminal filopodia and vacuolisation in response to extirpation, but had no effect on abluminal sprouting, and little effect on C:F. Comparison of mice lacking endothelial (eNOS−/−) and neuronal NO synthase (nNOS−/−) showed that longitudinal splitting is eNOS‐dependent, and Western blotting demonstrated an increase in eNOS but not inducible NOS (iNOS) expression. These data show that there are two pathways of physiological angiogenesis in skeletal muscle characterised by longitudinal splitting and capillary sprouting, respectively. NO generated by eNOS plays an essential role in splitting but not in sprouting angiogenesis, which has important implications for angiogenic therapies that target NO.
Exploring and Engineering the Cell Surface Interface
Authors: Stevens Molly M. , George Julian H.
Published: November 2005

Cells are inherently sensitive to local mesoscale, microscale, and nanoscale patterns of chemistry and topography. We review current approaches to control cell behavior through the nanoscale engineering of materials surfaces. Far-reaching implications are emerging for applications including medical implants, cell supports, and materials that can be used as instructive three-dimensional environments for tissue regeneration.
DISC1 and PDE4B Are Interacting Genetic Factors in Schizophrenia That Regulate cAMP Signaling
Authors: Millar J. Kirsty , Pickard Benjamin S. , Mackie Shaun , James Rachel , Christie Sheila , Buchanan Sebastienne R. , Malloy M. Pat , Chubb Jennifer E. , Huston Elaine , Baillie George S. , Thomson Pippa A. , Hill Elaine V. , Brandon Nicholas J. , Rain Jean-Christophe , Camargo L. Miguel , Whiting Paul J. , Houslay Miles D. , Blackwood Douglas H. R. , Muir Walter J. , Porteous David J.
Published: November 2005

The
disrupted in schizophrenia 1
(
DISC1
) gene is a candidate susceptibility factor for schizophrenia, but its mechanistic role in the disorder is unknown. Here we report that the gene encoding phosphodiesterase 4B (
PDE4B
) is disrupted by a balanced translocation in a subject diagnosed with schizophrenia and a relative with chronic psychiatric illness. The PDEs inactivate adenosine 3′,5′-monophosphate (cAMP), a second messenger implicated in learning, memory, and mood. We show that DISC1 interacts with the UCR2 domain of PDE4B and that elevation of cellular cAMP leads to dissociation of PDE4B from DISC1 and an increase in PDE4B activity. We propose a mechanistic model whereby DISC1 sequesters PDE4B in resting cells and releases it in an activated state in response to elevated cAMP.
Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients
Authors: Kaeberlein Matt , Powers R. Wilson , Steffen Kristan K. , Westman Eric A. , Hu Di , Dang Nick , Kerr Emily O. , Kirkland Kathryn T. , Fields Stanley , Kennedy Brian K.
Published: November 2005

Calorie restriction increases life span in many organisms, including the budding yeast
Saccharomyces cerevisiae
. From a large-scale analysis of 564 single-gene–deletion strains of yeast, we identified 10 gene deletions that increase replicative life span. Six of these correspond to genes encoding components of the nutrient-responsive TOR and Sch9 pathways. Calorie restriction of
tor1
D or
sch9
D cells failed to further increase life span and, like calorie restriction, deletion of either
SCH9
or
TOR1
increased life span independent of the Sir2 histone deacetylase. We propose that the TOR and Sch9 kinases define a primary conduit through which excess nutrient intake limits longevity in yeast.
Prostaglandin E
2
Promotes Colon Cancer Cell Growth Through a G
s
-Axin-ß-Catenin Signaling Axis
Authors: Castellone Maria Domenica , Teramoto Hidemi , Williams Bart O. , Druey Kirk M. , Gutkind J. Silvio
Published: November 2005

How cyclooxygenase-2 (COX-2) and its proinflammatory metabolite prostaglandin E2 (PGE2) enhance colon cancer progression remains poorly understood. We show that PGE2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (G protein)–coupled receptor, EP2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase Akt by free G protein βγ subunits and the direct association of the G protein α
s
subunit with the regulator of G protein signaling (RGS) domain of axin. This leads to the inactivation and release of glycogen synthase kinase 3β from its complex with axin, thereby relieving the inhibitory phosphorylation of β-catenin and activating its signaling pathway. These findings may provide a molecular framework for the future evaluation of chemopreventive strategies for colorectal cancer.
Directionally Controlled Fluorescence Emission in Butterflies
Authors: Vukusic Pete , Hooper Ian
Published: November 2005

Recently developed, high-efficiency, light-emitting diodes use two-dimensional photonic crystals to enhance the extraction of otherwise internally trapped light and multilayer reflectors to control the direction of light emission. This work describes the characterization of a naturally evolved light-extraction system on the wing scales of a small group of Papilio butterflies. The efficient extraction of fluorescence from these scales is facilitated by a two-dimensional photonic crystal slab that uses a multilayer to help control emission direction. Its light-extraction function is analogous to that of the light-emitting diode.
Rigid Biological Systems as Models for Synthetic Composites
Authors: Mayer George
Published: November 2005

Advances that have been made in understanding the mechanisms underlying the mechanical behavior of a number of biological materials (namely mollusk shells and sponge spicules) are discussed here. Attempts at biomimicry of the structure of a nacreous layer of a mollusk shell have shown reasonable success. However, they have revealed additional issues that must be addressed if new synthetic composite materials that are based on natural systems are to be constructed. Some of the important advantages and limitations of copying from nature are also described here.
Tissue Cells Feel and Respond to the Stiffness of Their Substrate
Authors: Discher Dennis E. , Janmey Paul , Wang Yu-li
Published: November 2005

Normal tissue cells are generally not viable when suspended in a fluid and are therefore said to be anchorage dependent. Such cells must adhere to a solid, but a solid can be as rigid as glass or softer than a baby's skin. The behavior of some cells on soft materials is characteristic of important phenotypes; for example, cell growth on soft agar gels is used to identify cancer cells. However, an understanding of how tissue cells—including fibroblasts, myocytes, neurons, and other cell types—sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels (or to other cells) with which elasticity can be tuned to approximate that of tissues. Key roles in molecular pathways are played by adhesion complexes and the actinmyosin cytoskeleton, whose contractile forces are transmitted through transcellular structures. The feedback of local matrix stiffness on cell state likely has important implications for development, differentiation, disease, and regeneration.
Structure of the Quaternary Complex of Interleukin-2 with Its α, ß, and γ
c
Receptors
Authors: Wang Xinquan , Rickert Mathias , Garcia K. Christopher
Published: November 2005

Interleukin-2 (IL-2) is an immunoregulatory cytokine that acts through a quaternary receptor signaling complex containing alpha (IL-2Rα), beta (IL-2Rβ), and common gamma chain (g
c
) receptors. In the structure of the quaternary ectodomain complex as visualized at a resolution of 2.3 angstroms, the binding of IL-2Rα to IL-2 stabilizes a secondary binding site for presentation to IL-2Rβ. γ
c
is then recruited to the composite surface formed by the IL-2/IL-2Rβ complex. Consistent with its role as a shared receptor for IL-4, IL-7, IL-9, IL-15, and IL-21, γ
c
forms degenerate contacts with IL-2. The structure of γ
c
provides a rationale for loss-of-function mutations found in patients with X-linked severe combined immunodeficiency diseases (X-SCID). This complex structure provides a framework for other γ
c
-dependent cytokine-receptor interactions and for the engineering of improved IL-2 therapeutics.
Heterogeneous Hadean Hafnium: Evidence of Continental Crust at 4.4 to 4.5 Ga
Authors: Harrison T. M. , Blichert-Toft J. , Müller W. , Albarede F. , Holden P. , Mojzsis S. J.
Published: November 2005

The long-favored paradigm for the development of continental crust is one of progressive growth beginning at ∼4 billion years ago (Ga). To test this hypothesis, we measured initial
176
Hf/
177
Hf values of 4.01- to 4.37-Ga detrital zircons from Jack Hills, Western Australia. ϵ
Hf
(deviations of
176
Hf/
177
Hf from bulk Earth in parts per 10
4
) values show large positive and negative deviations from those of the bulk Earth. Negative values indicate the development of a Lu/Hf reservoir that is consistent with the formation of continental crust (Lu/Hf ≈ 0.01), perhaps as early as 4.5 Ga. Positive ϵ
Hf
deviations require early and likely widespread depletion of the upper mantle. These results support the view that continental crust had formed by 4.4 to 4.5 Ga and was rapidly recycled into the mantle.
Glial Membranes at the Node of Ranvier Prevent Neurite Outgrowth
Authors: Huang Jeffrey K. , Phillips Greg R. , Roth Alejandro D. , Pedraza Liliana , Shan Weisong , Belkaid Wiam , Mi Sha , Fex-Svenningsen Asa , Florens Laurence , Yates John R. , Colman David R.
Published: November 2005

Nodes of Ranvier are regularly placed, nonmyelinated axon segments along myelinated nerves. Here we show that nodal membranes isolated from the central nervous system (CNS) of mammals restricted neurite outgrowth of cultured neurons. Proteomic analysis of these membranes revealed several inhibitors of neurite outgrowth, including the oligodendrocyte myelin glycoprotein (OMgp). In rat spinal cord, OMgp was not localized to compact myelin, as previously thought, but to oligodendroglia-like cells, whose processes converge to form a ring that completely encircles the nodes. In OMgp-null mice, CNS nodes were abnormally wide and collateral sprouting was observed. Nodal ensheathment in the CNS may stabilize the node and prevent axonal sprouting.
Dinosaur Coprolites and the Early Evolution of Grasses and Grazers
Authors: Prasad Vandana , Strömberg Caroline A. E. , Alimohammadian Habib , Sahni Ashok
Published: November 2005

Silicified plant tissues (phytoliths) preserved in Late Cretaceous coprolites from India show that at least five taxa from extant grass (Poaceae) subclades were present on the Indian subcontinent during the latest Cretaceous. This taxonomic diversity suggests that crown-group Poaceae had diversified and spread in Gondwana before India became geographically isolated. Other phytoliths extracted from the coprolites (from dicotyledons, conifers, and palms) suggest that the suspected dung producers (titanosaur sauropods) fed indiscriminately on a wide range of plants. These data also make plausible the hypothesis that gondwanatherian mammals with hypsodont cheek teeth were grazers.
Nerves as Chemical Messengers
Authors: Carlsson Arvid
Published: November 2005

The War of the Soups and the Sparks
. The Discovery of Neurotransmitters and the Dispute over How Nerves Communicate.
By Elliot S. Valenstein
. Columbia University Press, New York, 2005. 255 pp. $31, £19.50. ISBN 0-231-13588-2.

Writing for nonspecialists, the author presents the story of the discovery of neurotransmitters through an account of the disputes between pharmacologists and neurophysiologists.
Haemophilus ducreyi
Targets Src Family Protein Tyrosine Kinases To Inhibit Phagocytic Signaling
Authors: Mock Jason R. , Vakevainen Merja , Deng Kaiping , Latimer Jo L. , Young Jennifer A. , van Oers Nicolai S. C. , Greenberg Steven , Hansen Eric J.
Published: November 2005

Haemophilus ducreyi
, the etiologic agent of the sexually transmitted disease chancroid, has been shown to inhibit phagocytosis of both itself and secondary targets in vitro. Immunodepletion of LspA proteins from
H. ducreyi
culture supernatant fluid abolished this inhibitory effect, indicating that the LspA proteins are necessary for the inhibition of phagocytosis by
H. ducreyi
. Fluorescence microscopy revealed that macrophages incubated with wild-type
H. ducreyi
, but not with a
lspA1 lspA2
mutant, were unable to complete development of the phagocytic cup around immunoglobulin G-opsonized targets. Examination of the phosphotyrosine protein profiles of these two sets of macrophages showed that those incubated with wild-type
H. ducreyi
had greatly reduced phosphorylation levels of proteins in the 50-to-60-kDa range. Subsequent experiments revealed reductions in the catalytic activities of both Lyn and Hck, two members of the Src family of protein tyrosine kinases that are known to be involved in the proximal signaling steps of Fcγ receptor-mediated phagocytosis. Additional experiments confirmed reductions in the levels of both active Lyn and active Hck in three different immune cell lines, but not in HeLa cells, exposed to wild-type
H. ducreyi
. This is the first example of a bacte-rial pathogen that suppresses Src family protein tyrosine kinase activity to subvert phagocytic signaling in hostcells.