bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between AQT Processing Speed and Neuropsychological Tests in Neuropsychiatric Patients
Authors: Nielsen Niels Peter , Ringström Roland , Wiig Elisabeth H. , Minthon Lennart
Published: July 2007

Associations between A Quick Test of Cognitive Speed (AQT) perceptual and cognitive speed and neuropsychological tests, including the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), Mini Mental State Examination (MMSE), and the Trail Making Test (TMT), were evaluated in 41 neuropsychiatric patients. Neuropsychological and neurological tests, including CT scan, were administered to all of the patients. AQT was also administered to 75 controls. All AQT means differed significantly for patients and controls. Dual-dimension naming time means in the patient group were in the atypical range and indicated generally reduced cognitive speed, whereas controls performed in the normal range. In the patient group, WAIS-III verbal, performance, and full-scale IQ means were in the normal range. AQT perceptual and cognitive speed correlated negatively with WAIS-III P IQ and MMSE scores, and the relationships were nonlinear. The findings support that AQT dual-dimension naming evaluates cognitive speed (i.e., attention, set shifting, working memory) and can be used for first-line or complementary screening for mild or progressive cognitive impairments.
Skin tissue cholesterol is not related to vascular occlusive disease
Authors: Reiter Markus , Wirth Susan , Pourazim Ali , Puchner Stefan , Baghestanian Mehrdad , Minar Erich , Bucek Robert A.
Published: July 2007

The objective of the present study was to evaluate the role of skin tissue cholesterol (SkinTc) in predicting the presence of atherosclerosis. SkinTc concentrations were determined in 318 consecutive patients by using the non-invasive PREVU POC Skin Sterol Test. Additionally, a complete lipid status and cardiovascular risk profile according to the PROCAM and Framingham scores as well as an evaluation by carotid duplex sonography and ankle—brachial blood pressure index testing was obtained from all patients. SkinTc concentrations did not differ significantly among patients suffering from cerebrovascular disease (CVD) and peripheral arterial disease (PAD) compared to the corresponding control groups and among patients with a calculated cardiovascular risk > 10% in 10 years compared to patients with a risk< 10% (all p > 0.05). Additionally, SkinTc concentrations were not significantly higher in the 245 patients with at least one documented atherosclerotic disease compared with the remaining 73 patients without evidence of atherosclerosis. In conclusion, SkinTc concentrations determined by the PREVU POC Skin Sterol Test are not related to the presence of CVD and PAD or to an elevated cardiovascular risk, indicating that this parameter cannot be used as a reliable indicator of atherosclerosis.
Thromboprophylaxis with dalteparin in medical patients: which patients benefit?
Authors: Cohen Alexander T. , Turpie Alexander G.G. , Leizorovicz Alain , Olsson Carl-Gustav , Vaitkus Paul T. , Goldhaber Samuel Z.
Published: July 2007

It is unclear whether thromboprophylaxis produces a consistent risk reduction in different subgroups of medical patients at risk from venous thromboembolism. We performed a retrospective, post hoc analysis of 3706 patients enrolled in the PREVENT study. Patients were at least 40 years old with an acute medical condition requiring hospitalization for at least 4 days and had no more than 3 days of immobilization prior to enrolment. Patients received either subcutaneous dalteparin (5000 IU) or placebo once daily. The primary end point was the composite of symptomatic deep vein thrombosis (DVT), pulmonary embolism, asymptomatic proximal DVT, or sudden death. Primary diagnosis subgroups were acute congestive heart failure, acute respiratory failure, infectious disease, rheumatological disorders, or inflammatory bowel disease. All patients, except those with congestive heart or respiratory failure, had at least one additional risk factor for venous thromboembolism. A risk reduction was shown in patients receiving dalteparin versus placebo. The relative risk (RR) was 0.73 in patients with congestive heart failure, 0.72 for respiratory failure, 0.46 for infectious disease, and 0.97 for rheumatological disorders. The RR was 0.52 in patients aged ≥ 75 years, 0.64 in obese patients, 0.34 for patients with varicose veins, and 0.71 in patients with chronic heart failure. No subgroup had a significantly different response from any other. Importantly, multivariate analysis showed that all patient groups benefited from thromboprophylaxis with dalteparin. Our findings, therefore, support the broad application of thromboprophylaxis in acutely ill hospitalized medical patients.
Health seeking behaviours among Chinese-Australian women: implications for health promotion programmes
Authors: Kwok Cannas , Sullivan Gerard
Published: July 2007

Preventive medicine is an important element of the Australian health care system. An essential aspect of the biomedical model of health care is screening for the early detection of disease in otherwise asymptomatic people. There is ample evidence that acceptance levels of western medicine vary and that a variety of health epistemologies and health practices coexist. To examine the extent to which Chinese-Australian women integrate western medicine practices in their health seeking behaviour, a qualitative study was conducted, which involved in-depth interviews in Cantonese with 20 women. Although adherence to western health beliefs and practices varied, in general these Chinese-Australian women sought medical help only after they felt unwell. Commonly, they first tried traditional remedies for minor diseases. Many saw no reason to participate in screening when they were asymptomatic. Direct communication with health care providers who speak the same language appears to be important to many Chinese-Australian women when seeking health care services. It is recommended that ethnic health workers should participate in screening programmes and other health promotion activities.
Lisfranc joint injuries
Authors: Davis Edward T.
Published: July 2007

Injuries to the tarsometatarsal (Lisfranc's) joint can be difficult injuries to diagnose. Some authors report that up to 20% of injuries are wrongly diagnosed. There remains controversy as to adequacy of closed reduction and fixation compared to open reduction with anatomical reduction and fixation. This article considers the anatomy, mechanism of injury, clinical diagnosis, radiological evaluation, classification, treatment and outcome of this injury pattern.
Managing metacarpal fractures
Authors: O'Gorman Adrian , Ashwood Neil
Published: July 2007

Thirty percent of fractures involve the hand with the same proportion involving the metacarpal. Most are treated nonoperatively with the emphasis being on achieving restoration of function for the individual. Biomechanically the index and middle fingers contribute to the central stable section of the hand with the other metacarpals including the thumb forming the mobile units. Fracture angulation, shortening and rotation are poorly tolerated in the fixed metacarpals and may require surgical intervention. Intra-articular fractures in the metacarpal head are relatively uncommon but often are associated with significant soft tissue damage or open injury. Like the more common intra-articular fractures at the base of the metacarpal, restoring large fragments back in place is the key for long term outcome and stability of the involved joint. Open injuries require thorough debridement and procedures to achieve appropriate skin cover. Involvement of specialists in hand therapy and surgery at an early stage is important in order to get those with metacarpal fractures, who are often young, back to function and employment.
Rules of engagement, credibility and the political economy of organizational dissent
Authors: Argyres Nicholas , Mui Vai-Lam
Published: July 2007

This article studies how organizations can choose dissent regimes that encourage organization members to express dissent in ways that provide the organization with informational benefits while minimizing the hazards associated with opportunistic behavior by members in the dissent process. Using a game-theoretic model, we demonstrate how logic-based and balanced rules of engagement can change various members' cost—benefit calculus in deciding whether to express dissent and thereby enable an organization to better balance the trade-off between capturing the benefits from constructive dissent and avoiding the hazards of destructive dissent.We then analyze how credibility problems faced by the leader may prevent organizations from adopting and implementing dissent regimes with such rules of engagement. We identify conditions under which an increase in the leader's reputational loss from opportunistic suppression of dissent can actually reduce the incidence of the adoption of dissent regime with rules of engagement, as well as the organization's profit. Finally, we explore implications of our analysis for the study of the role of informal leaders in organizational dissent, and for the relationship between dissent and organizational change processes.
Partisans, Nonpartisans, and the Antiwar Movement in the United States
Authors: Heaney Michael T. , Rojas Fabio
Published: July 2007

American social movements are often bitterly divided about whether their objectives are achieved better by working with one of the major political parties or by operating independently. These divisions are consequential for how social movements and political parties respond to one another. First, differing partisan attitudes shape the structure of activist networks, leading activists to join organizations with others who share their party loyalties or disloyalties. Second, partisan attitudes affect how activists participate in the movement, with strong partisans more likely to embrace institutional tactics, such as lobbying. Third, partisanship affects activists' access to the institutions of government, such as Congress. Relying on surveys of antiwar activists attending large-scale public demonstrations in 2004 and 2005 and a Capitol Hill Lobby Day in September 2005, the authors argue that some activists integrate into major party networks through the “party in the street,” an arena of significant party-movement interaction.
Changes in Habits Related to Self-care in Dementia: The Nursing Home Versus Adult Day Care
Authors: Cohen-Mansfield Jiska , Jensen Barbara
Published: July 2007

Little is known about the changes that occur for older persons with dementia in the practice of self-care routines. This study assesses the concordance of past and current self-care practices of day care and nursing home persons using spouse reports, the degree of spouse awareness of these changes, and spouse perception of how important self-care practices had been to their partner. Participants were spouses of 12 older persons with dementia in day care and spouses of 20 nursing home residents. Self-care routines were assessed using the Self-maintenance Habits and Preferences in Elderly (SHAPE) questionnaire. Day care attendees showed few changes in self-care routines compared to nursing home residents. Spouses of nursing home residents underestimate the changes in self-care that occur with nursing home admission. The importance of being aware of self-care changes lies in the value of maintaining continuity with the customary preferences and routines of the older person.
Shedding Light on the Underlying Forms of Transformative Learning Theory
Authors: Gunnlaugson Olen
Published: July 2007

This article supports the continued development of second-wave theories of transformative learning by building on the work of Mezirow and Kegan. It examines the limitations of Mezirow's ideal of critical discourse and presents a case for Scharmer's account of generative dialogue as a process map and practice for supporting and catalyzing transformative learning in groups. Finally, this article examines how generative dialogue supports transformative shifts in at least three distinct categorical forms of learner's consciousness: lines, stages, and states.
Good Words: Chief Joseph and the Production of Indian Speech(es), Texts, and Subjects
Authors: Guthrie Thomas H.
Published: July 2007

Chief Joseph, who gained fame during the Nez Perce War of 1877, is one of the best-known Indian orators in American history. Yet the two principal texts attributed to him were produced under questionable circumstances, and it is unclear to what extent they represent anything he ever said. This essay examines the publication history of these texts and then addresses two questions about the treatment of Indian oratory in the nineteenth century. First, given their uncertain provenance, how and why did these texts become so popular and come to represent Indian eloquence and an authentic Native American voice? Second, what was the political significance of Indian speech and texts of Indian oratory in the confrontation between Euro-Americans and Indians over land? I argue that the production and interpretation of Indian speech facilitated political subjugation by figuring Indians as particular kinds of subjects and positioning them in a broader narrative about the West. The discursive and political dimensions of the encounter were inseparable, as Indian “eloquence” laid the way for Indian defeat. I conclude by advocating a disruptive reading of Indian oratory that rejects the belief that a real Indian subject lies behind these texts in any straightforward sense. To make this argument, I draw on linguistic anthropology and critical theory, analyzing firsthand accounts, newspaper reports, and descriptions of Indian speech and Nez Perce history.
Dynamic recruitment of axin by Dishevelled protein assemblies
Authors: Schwarz-Romond Thomas , Metcalfe Ciara , Bienz Mariann
Published: July 2007

Dishevelled (Dvl) proteins are cytoplasmic components of the Wnt signalling pathway, which controls numerous cell fate decisions during animal development. During Wnt signalling, Dvl binds to the intracellular domain of the frizzled transmembrane receptors, and also to axin to block its activity, which results in the activation of β-catenin and, consequently, in a transcriptional switch. We have previously reported that the DIX domain of mammalian Dvl2 allows it to form dynamic protein assemblies. Here, we show that these Dvl2 assemblies recruit axin, and also casein kinase Iϵ. Using photobleaching experiments of GFP-tagged Dvl2 and axin to study the dynamics of their interaction, we found that the recruitment of axin-GFP by Dvl2 assemblies is accompanied by a striking acceleration of the dynamic properties of axin-GFP. We also show that the interaction between Dvl2 and axin remains highly dynamic even after Wnt-induced relocation to the plasma membrane. We discuss how the recruitment of casein kinase Iϵ by Dvl2 assemblies might impact on the recruitment of axin to the plasma membrane during Wnt signalling.
Show and tell: visualizing gene expression in living cells
Authors: Rafalska-Metcalf Ilona U. , Janicki Susan M.
Published: July 2007

The development of non-invasive methods of visualizing proteins and nucleic acids in living cells has provided profound insight into how they move and interact with each other in vivo. It is possible to evaluate basic mechanisms of gene expression, and to define their temporal and spatial parameters by using this methodology to label endogenous genes and make reporter constructs that allow specific DNA and RNA regulatory elements to be localized. This Commentary highlights recent reports that have used these techniques to study nuclear organization, transcription factor dynamics and the kinetics of RNA synthesis. These studies show how imaging gene expression in single living cells can reveal new regulatory mechanisms. They also expand our understanding of the role of chromatin and RNA dynamics in modulating cellular responses to developmental and environmental signals.
Identification of a novel conserved sorting motif required for retromer-mediated endosome-to-TGN retrieval
Authors: Seaman Matthew N. J.
Published: July 2007

The cation-independent mannose 6-phosphate receptor (CIMPR) cycles between the trans-Golgi network (TGN) and endosomes to mediate sorting of lysosomal hydrolases. The endosome-to-TGN retrieval of the CIMPR requires the retromer complex. Genetic, biochemical and structural data support the hypothesis that the retromer can directly bind to the tail of the CIMPR, to sort the CIMPR into vesicles and tubules for retrieval to the TGN. Presently, however, no known retromer sorting motif in the tail of the CIMPR has been identified. Using CD8-reporter proteins carrying the cytoplasmic tail of the CIMPR we have systematically dissected the CIMPR tail to identify a novel, conserved aromatic-containing sorting motif that is critical for the endosome-to-TGN retrieval of the CIMPR and for the interaction with retromer and the clathrin adaptor AP-1.
Selective Doping of Lead Ions into Normally Aligned PEO Cylindrical Nanodomains in Amphiphilic Block Copolymer Thin Films
Authors: Suzuki Souichirou , Kamata Kaori , Yamauchi Hisao , Iyoda Tomokazu
Published: July 2007

Hexagonally arranged nanocylindrical arrays of polymer-complexed multivalent metallic ions were fabricated by performing template process with amphiphilic diblock copolymer consisting of poly(ethylene oxide) and liquid crystalline poly(methacrylate) with azobenzene mesogen (PEO-b-PMA(Az)). The block copolymer exhibits PEO hexagonal cylindrical microdomains perpendicular to the substrate. Lead ions were selectively diffused into the PEO microdomains to generate the lead-doped nanocylinder array, of which size, shape, and alignment can be controlled by the block copolymer thin film as a template.
The Pure Silica Chabazite: A High Volume Molecular Spring at Low Pressure for Energy Storage
Authors: Trzpit Mickaël , Soulard Michel , Patarin Joël
Published: July 2007

Water intrusion–extrusion isotherms were performed at room temperature on hydrophobic pure silica chabazite (Si-CHA). A reversible phenomenon is observed over several cycles showing that the water–Si-CHA system displays a real spring behavior. The process occurs at a quite low pressure, and the large intruded water volume makes this system interesting for applications in energetics.
Two-coordinate Group 13 Element (Al, Ga) Centered Cations Formed by Silyl Group Migration: Synthesis and Characterization
Authors: Nakamoto Masaaki , Shimizu Kousuke , Sekiguchi Akira
Published: July 2007

Two-coordinate, sp-hybridized aluminum and gallium cationic species (2a and 2b) were synthesized by the methyl group abstraction from the t-Bu2MeSi group by Et3Si+ followed by 1,2-silyl group migration from group 13 element to the cationic silicon center. X-ray crystal structure analyses confirmed these species to be free cations stabilized by hyperconjugation with a neighboring Si–Si σ bond.
Versatile collapsible rabbit cage
Authors: McEwin R. L. , Smith T. , Barrell R. W.
Published: July 2007

The cage was designed for holding and breeding rabbits, and can also be used for holding cats for short periods. Single cages can be joined back to back: this larger cage can also be used for breeding rabbits, and the longer-term holding of cats. When not in use cages fold into compact units, saving storage space and labour, as many cages may be autoc1aved, boiled or steamed at once. Repair, maintenance and replacement costs of the cages are lower than for conventional cages.
Combination of ketamine and xylazine for effective anaesthesia of juvenile chimpanzees (Pan troglodytes)
Authors: April Milton , Tabor Edward , Gerety Robert J.
Published: July 2007

Intramuscular administration of ketamine at 15-20 mg/kg bodyweight provided effective levels of anaesthesia for venipuncture in 23 chimpanzees aged 12-36 months. For procedures such as plasmaphereses or percutaneous needle biopsy requiring longer anaesthetic times, xylazine (l mg/kg) was given with the ketamine. More than 1600 procedures were performed under anaesthesia on the 23 chimpanzees over a period of 18 months with no mortality. Recovery was smooth and uneventful.
Use of etorphine-acepromazine and diprenorphine in reversible neuroleptanalgesia of rats
Authors: Fisker Anders V. , Stage Inge , Philipsen Hans P.
Published: July 2007

The death rate due to neuroleptanalgesia (0·35%) was significantly lower than for barbiturate anaesthesia (1·59%). Complications were few even when animals received multiple, repeated, anaesthesia, and depth of anaesthesia could be adjusted easily. Further, it could effectively be reversed within minutes by the specific antagonist diprenorphine.
Urethral plug-a new secondary male sex characteristic in rat and other rodents
Authors: Kunstýř Ivo , Küpper Werner , Weisser Herwig , Naumann Susanne , Messow Claus
Published: July 2007

The plug is an eosinophilic mass, partly homogenous and partly porous, filling the proximal urethra in rats and occasionally extending into the bladder. Its average weight in 131 adult rats was 0·063 g. These plugs are normally present in the urethra of adult male rats, and this seems to be the case for all laboratory Muridae and Cavidae. The absence of a plug in an adult male may be a sign of abnormality associated with failing health. There is an interesting similarity between the amino acid composition of the content of seminal vesicles, that of the urethral plug, and that of the copulatory vaginal plug in female rodents.
Etiology and Pathogenesis of Osteochondrosis
Authors: Ytrehus B. , Carlson C. S. , Ekman S.
Published: July 2007

Osteochondrosis is a common and clinically important joint disorder that occurs in human beings and in multiple animal species, most commonly pigs, horses, and dogs. This disorder is defined as a focal disturbance of enchondral ossification and is regarded as having a multifactorial etiology, with no single factor accounting for all aspects of the disease. The most commonly cited etiologic factors are heredity, rapid growth, anatomic conformation, trauma, and dietary imbalances; however, only heredity and anatomic conformation are well supported by the scientific literature. The way in which the disease is initiated has been debated. Although formation of a fragile cartilage, failure of chondrocyte differentiation, subchondral bone necrosis, and failure of blood supply to the growth cartilage all have been proposed as the initial step in the pathogenesis, the recent literature strongly supports failure of blood supply to growth cartilage as being the most likely. The term osteochondrosis has been used to describe a wide range of different lesions among different species. We suggest a refinement of this terminology to include the modifiers latens (lesion confined to epiphyseal cartilage), manifesta (lesion accompanied by delay in endochondral ossification), and dissecans (cleft formation through articular cartilage). The purpose of this review is to provide an overview of the disease, focusing on the most commonly cited theories, recent research findings, and our own views regarding the etiology and pathogenesis of osteochondrosis, in order to provide a better understanding of this apparently complex disease.
Auricular Chondritis Caused by Metal Ear Tagging in C57BL/6 Mice
Authors: Kitagaki M. , Hirota M.
Published: July 2007

Although it has been shown that auricular chondritis in rats is caused by the use of metal identification ear tags, the pathogenesis remains unclear. Based on the hypothesis that the auricular chondritis is caused by metal ions released from metal identification ear tags, we investigated the pathogenesis in male C57BL/6 mice tagged with metal identification ear tags. Twenty-six weeks after the attachment of the ear tags, visible increases in the thickness of the auricle were observed, and the concentrations of copper and iron in the tagged ears were significantly increased ( P <.05) in the tagged ears compared with the untagged ears. There was up-regulation of metallothionein (MT)-I and MT-II mRNA in the tagged ears, and this was confirmed by immunohistologic staining of the destroyed cartilage. Histopathologically, there were observed severe chondritis with extensive granulomatous inflammation, newly formed cartilage nodules, and osseous metaplasia accompanied by cellular infiltrates, such as CD4 T lymphocyte, macrophages, neutrophils, and mast cells, and expression of Th1 cytokines, such as interferon-gamma, tumor necrosis factor-alpha, and interleukin-2 in the tagged ear. Based on these results, we concluded that the release of copper and iron ions from the metal ear tags played a major role in the onset of auricular chondritis. Subsequent cellular interactions, such as CD4 T cells, macrophages, fibroblasts, and mast cells, mediated by cytokines, such as tumor necrosis factor-alpha and interferon-gamma, caused an autoimmune response that may have led to the progression of auricular chondritis as an autoimmune disease.
Dental Benign Cementomas in Three Horses
Authors: Kreutzer R. , Wohlsein P. , Staszyk C. , Nowak M. , Sill V. , Baumgärtner W.
Published: July 2007

Cementoma is a very rare odontogenic neoplasm of mesenchymal origin. Clinically, in 3 horses, multiple bony enlargements of the upper and lower jaw extending into the oral cavity were observed. Radiographically, multiple, well-circumscribed, radiopaque masses surrounding the roots of the upper and lower incisors or an upper premolar tooth were present. Due to malocclusion and local pain, single teeth were extracted in each case. Grossly, a hard grayish-white mass surrounding the root of the incisors and the premolars was identified. Histopathologically, the tumors consisted of excessive deposition of cementum-like tissue. Cells, resembling cementoblasts, lined irregularly shaped lacunae, which were present in the tumor tissue, and showed minimal cellular pleomorphism. Mitotic figures were not present. Macroscopically and histologically, all 3 equine cases displayed great similarities to cementomas in other species. However, due to their high degree of differentiation, hypercementosis must be considered as a differential diagnosis.
Cholesterol Granuloma Associated with Otitis Media and Destruction of the Tympanic Bulla in a Dog
Authors: Fliegner R. A. , Jubb K. V. F. , Lording P. M.
Published: July 2007

An 8-year-old, male neutered Irish Setter was presented with a 2-week history of pain upon opening the mouth and chronic otitis externa. Computed tomography examination revealed destruction of the left tympanic bulla with a soft-tissue density within the remains of the tympanic cavity. Cytology of aspirates collected from tissue adjacent to the tympanic bulla revealed suppurative inflammation and bacteria. A ventral bulla osteotomy was performed. Histopathology of granulation tissue within the remains of the tympanic cavity was diagnostic of cholesterol granuloma.
Aberrant Splicing of an Alternative Exon in the Drosophila Troponin-T Gene Affects Flight Muscle Development
Authors: Nongthomba Upendra , Ansari Maqsood , Thimmaiya Divesh , Stark Meg , Sparrow John
Published: July 2007

During myofibrillogenesis, many muscle structural proteins assemble to form the highly ordered contractile sarcomere. Mutations in these proteins can lead to dysfunctional muscle and various myopathies. We have analyzed the Drosophila melanogaster troponin T (TnT) up1 mutant that specifically affects the indirect flight muscles (IFM) to explore troponin function during myofibrillogenesis. The up1 muscles lack normal sarcomeres and contain “zebra bodies,” a phenotypic feature of human nemaline myopathies. We show that the up1 mutation causes defective splicing of a newly identified alternative TnT exon (10a) that encodes part of the TnT C terminus. This exon is used to generate a TnT isoform specific to the IFM and jump muscles, which during IFM development replaces the exon 10b isoform. Functional differences between the 10a and 10b TnT isoforms may be due to different potential phosphorylation sites, none of which correspond to known phosphorylation sites in human cardiac TnT. The absence of TnT mRNA in up1 IFM reduces mRNA levels of an IFM-specific troponin I (TnI) isoform, but not actin, tropomyosin, or troponin C, suggesting a mechanism controlling expression of TnT and TnI genes may exist that must be examined in the context of human myopathies caused by mutations of these thin filament proteins.
Fractioned DNA Pooling: A New Cost-Effective Strategy for Fine Mapping of Quantitative Trait Loci
Authors: Korol A , Frenkel Z , Cohen L , Lipkin E , Soller M
Published: July 2007

Selective DNA pooling (SDP) is a cost-effective means for an initial scan for linkage between marker and quantitative trait loci (QTL) in suitable populations. The method is based on scoring marker allele frequencies in DNA pools from the tails of the population trait distribution. Various analytical approaches have been proposed for QTL detection using data on multiple families with SDP analysis. This article presents a new experimental procedure, fractioned-pool design (FPD), aimed to increase the reliability of SDP mapping results, by “fractioning” the tails of the population distribution into independent subpools. FPD is a conceptual and structural modification of SDP that allows for the first time the use of permutation tests for QTL detection rather than relying on presumed asymptotic distributions of the test statistics. For situations of family and cross mapping design we propose a spectrum of new tools for QTL mapping in FPD that were previously possible only with individual genotyping. These include: joint analysis of multiple families and multiple markers across a chromosome, even when the marker loci are only partly shared among families; detection of families segregating (heterozygous) for the QTL; estimation of confidence intervals for the QTL position; and analysis of multiple-linked QTL. These new advantages are of special importance for pooling analysis with SNP chips. Combining SNP microarray analysis with DNA pooling can dramatically reduce the cost of screening large numbers of SNPs on large samples, making chip technology readily applicable for genomewide association mapping in humans and farm animals. This extension, however, will require additional, nontrivial, development of FPD analytical tools.
Early Events in the Evolution of the Silene latifolia Y Chromosome: Male Specialization and Recombination Arrest
Authors: Zluvova Jitka , Georgiev Sevdalin , Janousek Bohuslav , Charlesworth Deborah , Vyskot Boris , Negrutiu Ioan
Published: July 2007

Understanding the origin and evolution of sex chromosomes requires studying recently evolved X–Y chromosome systems such as those in some flowering plants. We describe Y chromosome deletion mutants of Silene latifolia, a dioecious plant with heteromorphic sex chromosomes. The combination of results from new and previously described deletions with histological descriptions of their stamen development defects indicates the presence of two distinct Y regions containing loci with indispensable roles in male reproduction. We determined their positions relative to the two main sex determination functions (female suppressing and the other male promoting). A region proximal to the centromere on the Y p arm containing the putative stamen promoting sex determination locus includes additional early stamen developmental factors. A medial region of the Y q arm carries late pollen fertility factors. Cytological analysis of meiotic X–Y pairing in one of the male-sterile mutants indicates that the Y carries sequences or functions specifically affecting sex chromosome pairing.
Mapping Regions Within Cosmopolitan Inversion In(3R)Payne Associated With Natural Variation in Body Size in Drosophila melanogaster
Authors: Kennington W Jason , Hoffmann Ary A , Partridge Linda
Published: July 2007

Associations between genotypes for inversions and quantitative traits have been reported in several organisms, but little has been done to localize regions within inversions controlling variation in these traits. Here, we use an association mapping technique to identify genomic regions controlling variation in wing size within the cosmopolitan inversion In(3R)Payne in Drosophila melanogaster. Previous studies have shown that this inversion strongly influences variation in wing size, a trait highly correlated with body size. We found three alleles from two separate regions within In(3R)Payne with significant additive effects on wing size after the additional effect of the inversion itself had been taken into account. There were also several alleles with significant genotype-by-inversion interaction effects on wing size. None of the alleles tested had a significant additive effect on development time, suggesting different genes control these traits and that clinal patterns in them have therefore arisen independently. The presence of multiple regions within In(3R)Payne controlling size is consistent with the idea that inversions persist in populations because they contain multiple sets of locally adapted alleles, but more work needs to be done to test if they are indeed coadapted.
Topoisomerase I-Dependent Viability Loss in Saccharomyces cerevisiae Mutants Defective in Both SUMO Conjugation and DNA Repair
Authors: Chen Xiaole L , Silver Hannah R , Xiong Ling , Belichenko Irina , Adegite Caroline , Johnson Erica S
Published: July 2007

Siz1 and Siz2/Nfi1 are the two Siz/PIAS SUMO E3 ligases in Saccharomyces cerevisiae. Here we show that siz1Δ siz2Δ mutants fail to grow in the absence of the homologous recombination pathway or the Fen1 ortholog RAD27. Remarkably, the growth defects of mutants such as siz1Δ siz2Δ rad52Δ are suppressed by mutations in TOP1, suggesting that these growth defects are caused by topoisomerase I activity. Other mutants that affect SUMO conjugation, including a ulp1 mutant and the nuclear pore mutants nup60Δ and nup133Δ, show similar top1-suppressible synthetic defects with DNA repair mutants, suggesting that these phenotypes also result from reduced SUMO conjugation. siz1Δ siz2Δ mutants also display TOP1-independent genome instability phenotypes, including increased mitotic recombination and elongated telomeres. We also show that SUMO conjugation, TOP1, and RAD27 have overlapping roles in telomere maintenance. Top1 is sumoylated, but Top1 does not appear to be the SUMO substrate involved in the synthetic growth defects. However, sumoylation of certain substrates, including Top1 itself and Tri1 (YMR233W), is enhanced in the absence of Top1 activity. Sumoylation is also required for growth of top1Δ cells. These results suggest that the SUMO pathway has a complex effect on genome stability that involves several mechanistically distinct processes.
Rapid Detection of Positive Selection in Genes and Genomes Through Variation Clusters
Authors: Wagner Andreas
Published: July 2007

Positive selection in genes and genomes can point to the evolutionary basis for differences among species and among races within a species. The detection of positive selection can also help identify functionally important protein regions and thus guide protein engineering. Many existing tests for positive selection are excessively conservative, vulnerable to artifacts caused by demographic population history, or computationally very intensive. I here propose a simple and rapid test that is complementary to existing tests and that overcomes some of these problems. It relies on the null hypothesis that neutrally evolving DNA regions should show a Poisson distribution of nucleotide substitutions. The test detects significant deviations from this expectation in the form of variation clusters, highly localized groups of amino acid changes in a coding region. In applying this test to several thousand human–chimpanzee gene orthologs, I show that such variation clusters are not generally caused by relaxed selection. They occur in well-defined domains of a protein's tertiary structure and show a large excess of amino acid replacement over silent substitutions. I also identify multiple new human–chimpanzee orthologs subject to positive selection, among them genes that are involved in reproductive functions, immune defense, and the nervous system.
Major Histocompatibility Complex Heterozygosity Reduces Fitness in Experimentally Infected Mice
Authors: Ilmonen Petteri , Penn Dustin J , Damjanovich Kristy , Morrison Linda , Ghotbi Laleh , Potts Wayne K
Published: July 2007

It is often suggested that heterozygosity at major histocompatibility complex (MHC) loci confers enhanced resistance to infectious diseases (heterozygote advantage, HA, hypothesis), and overdominant selection should contribute to the evolution of these highly polymorphic genes. The evidence for the HA hypothesis is mixed and mainly from laboratory studies on inbred congenic mice, leaving the importance of MHC heterozygosity for natural populations unclear. We tested the HA hypothesis by infecting mice, produced by crossbreeding congenic C57BL/10 with wild ones, with different strains of Salmonella, both in laboratory and in large population enclosures. In the laboratory, we found that MHC influenced resistance, despite interacting wild-derived background loci. Surprisingly, resistance was mostly recessive rather than dominant, unlike in most inbred mouse strains, and it was never overdominant. In the enclosures, heterozygotes did not show better resistance, survival, or reproductive success compared to homozygotes. On the contrary, infected heterozygous females produced significantly fewer pups than homozygotes. Our results show that MHC effects are not masked on an outbred genetic background, and that MHC heterozygosity provides no immunological benefits when resistance is recessive, and can actually reduce fitness. These findings challenge the HA hypothesis and emphasize the need for studies on wild, genetically diverse species.
Dal81 Enhances Stp1- and Stp2-Dependent Transcription Necessitating Negative Modulation by Inner Nuclear Membrane Protein Asi1 in Saccharomyces cerevisiae
Authors: Boban Mirta , Ljungdahl Per O
Published: July 2007

The yeast transcription factors Stp1 and Stp2 are synthesized as latent cytoplasmic precursors. In response to extracellular amino acids, the plasma membrane SPS sensor endoproteolytically excises the N-terminal domains that mediate cytoplasmic retention, enabling the processed forms to efficiently enter the nucleus and induce gene expression. Cytoplasmic retention is not absolute, low levels of full-length Stp1 and Stp2 “leak” into the nucleus, and the concerted action of inner nuclear membrane proteins Asi1, Asi2, and Asi3 restricts their promoter access. In cells lacking Asi function, the precursor forms bind promoters and constitutively induce gene expression. To understand the requirement of Asi-dependent repression, spontaneous mutations in Required for Latent Stp1/2-mediated transcription (RLS) genes that abolish the constitutive expression of SPS sensor-regulated genes in an asi1Δ strain were selected. A single gene, allelic with DAL81, was identified. We show that Dal81 indiscriminately amplifies the transactivation potential of both full-length and processed Stp1 and Stp2 by facilitating promoter binding. In dal81Δ mutants, the repressing activity of the Asi proteins is dispensable, demonstrating that without amplification, the levels of full-length Stp1 and Stp2 that escape cytoplasmic retention are insufficient to activate transcription. Conversely, the high levels of processed Stp1 and Stp2 that accumulate in the nucleus of induced cells activate transcription in the absence of Dal81.
A Linkage Map Reveals a Complex Basis for Segregation Distortion in an Interpopulation Cross in the Moss Ceratodon purpureus
Authors: McDaniel Stuart F , Willis John H , Shaw A Jonathan
Published: July 2007

We report the construction of a linkage map for the moss Ceratodon purpureus (n = 13), based on a cross between geographically distant populations, and provide the first experimental confirmation of maternal chloroplast inheritance in bryophytes. From a mapping population of 288 recombinant haploid gametophytes, genotyped at 121 polymorphic AFLP loci, three gene-based nuclear loci, one chloroplast marker, and sex, we resolved 15 linkage groups resulting in a map length of ∼730 cM. We estimate that the map covers more than three-quarters of the C. purpureus genome. Approximately 35% of the loci were sex linked, not including those in recombining pseudoautosomal regions. Nearly 45% of the loci exhibited significant segregation distortion (α = 0.05). Several pairs of unlinked distorted loci showed significant deviations from multiplicative genotypic frequencies, suggesting that distortion arises from genetic interactions among loci. The distorted autosomal loci all exhibited an excess of the maternal allele, suggesting that these interactions may involve nuclear–cytoplasmic factors. The sex ratio of the progeny was significantly male biased, and the pattern of nonrandom associations among loci indicates that this results from interactions between the sex chromosomes. These results suggest that even in interpopulation crosses, multiple mechanisms act to influence segregation ratios.
Cost-effectiveness of Alternative Strategies for Tuberculosis Screening Before Kindergarten Entry
Authors: Flaherman Valerie J. , Porco Travis C. , Marseille Elliot , Royce Sarah E.
Published: July 2007

OBJECTIVE. We undertook a decision analysis to evaluate the economic and health effects and incremental cost-effectiveness of using targeted tuberculin skin testing, compared with universal screening or no screening, before kindergarten.

METHODS. We constructed a decision tree to determine the costs and clinical outcomes of using targeted testing compared with universal screening or no screening. Baseline estimates for input parameters were taken from the medical literature and from California health jurisdiction data. Sensitivity analyses were performed to determine plausible ranges of associated outcomes and costs. We surveyed California health jurisdictions to determine the prevalence of mandatory universal tuberculin skin testing.

RESULTS. In our base-case scenario, the cost to prevent an additional case of tuberculosis by using targeted testing, compared with no screening, was $524897. The cost to prevent an additional case by using universal screening, compared with targeted testing, was $671398. The incremental cost of preventing a case through screening remained above $100000 unless the prevalence of tuberculin skin testing positivity increased to >10%. More than 51% of children entering kindergarten in California live where tuberculin skin testing is mandatory.

CONCLUSIONS. The cost to prevent a case of tuberculosis by using either universal screening or targeted testing of kindergarteners is high. If targeted testing replaced universal tuberculin skin testing in California, then $1.27 million savings per year would be generated for more cost-effective strategies to prevent tuberculosis. Improving the positive predictive value of the risk factor tool or applying it to groups with higher prevalence of latent tuberculosis would make its use more cost-effective. Universal tuberculin skin testing should be discontinued, and targeted testing should be considered only when the prevalence of risk factor positivity and the prevalence of tuberculin skin testing positivity among risk factor–positive individuals are high enough to meet acceptable thresholds for cost-effectiveness.
Prenatal Cocaine and Tobacco Effects on Children's Language Trajectories
Authors: Lewis Barbara A. , Kirchner H. Lester , Short Elizabeth J. , Minnes Sonia , Weishampel Paul , Satayathum Sudtida , Singer Lynn T.
Published: July 2007

OBJECTIVE. The objective of this study was to examine the effects of prenatal cocaine and polydrug exposure on language development of preschool children using a prospective longitudinal model, controlling for confounders.

METHODS. Children who were exposed to cocaine in utero (n = 209) and nonexposed children (n = 189) were followed prospectively at birth and at 1, 2, 4, and 6 years of age and were compared on receptive, expressive, and total language scores across time using random coefficient models, controlling for confounders.

RESULTS. A significant, stable effect of cocaine exposure on language development was observed over time for all language domains, with cocaine exposure related to poorer language performance. Cigarette exposure was related to lower receptive language scores. Environmental influences on language scores were also observed. Both the cocaine-exposed and nonexposed children declined in language performance over time.

CONCLUSIONS. Prenatal cocaine exposure has a stable negative effect on language skills during the first 6 years of life. Both cocaine-exposed and nonexposed children showed decreased language growth over time; however, cocaine-exposed children demonstrated linguistic deficits compared with nonexposed peers and did not catch up. Cigarette and environmental influences were also noted.
Obesity Risk for Female Victims of Childhood Sexual Abuse: A Prospective Study
Authors: Noll Jennie G. , Zeller Meg H. , Trickett Penelope K. , Putnam Frank W.
Published: July 2007

OBJECTIVE. Efforts are under way to articulate environmental, psychosocial, and biological conditions that may predispose the development and maintenance of obesity. There is increasing evidence that adverse childhood experiences such as childhood abuse may be implicated in the development of obesity. Given the dearth of prospective evidence for this link, the objective of this study was to track body mass across development (from childhood, through adolescence, and into young adulthood [ie, ages 6–27]) in a prospective, longitudinal study of abused and nonabused female subjects.

METHODS. Height and weight were obtained for 84 female subjects with substantiated childhood sexual abuse and 89 demographically similar comparison female subjects at 6 points during development. Obesity status was examined at various stages during development, and body-mass growth trajectories were contrasted across the 2 groups. It was hypothesized that, in comparison with their nonabused peers, abused female subjects would be more likely to (1) manifest obesity by early adulthood and (2) manifest high-risk growth trajectories throughout development.

RESULTS. Obesity rates were not different across groups in childhood or adolescence. By young adulthood (ages 20–27), abused female subjects were significantly more likely to be obese (42.25%) than were comparison female subjects (28.40%). Hierarchical linear modeling growth-trajectory analyses indicated that abused female subjects, on average, acquired body mass at a significantly steeper rate from childhood through young adulthood than did comparison female subjects after controlling for minority status and parity.

CONCLUSIONS. Psychosocial difficulties (eg, depression) and psychobiological conditions (eg, hypothalamic-pituitary-adrenal axis dysregulation) that have been shown to be related to both childhood abuse and obesity may help to explain these results. The identification of high-risk growth trajectories may improve health outcomes for victims. Systematic study of the mechanistic pathways and mediating processes that would help to explain the connection between childhood sexual abuse and later obesity is encouraged.