bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetosomal matrix: ultrafine structure may template biomineralization of magnetosomes
Authors: Taylor A. P. , Barry J. C. 
Published: January 2004

SummaryThe organic matrix surrounding bullet‐shaped, cubo‐octahedral, D‐shaped, irregular arrowhead‐shaped, and truncated hexa‐octahedral magnetosomes was analysed in a variety of uncultured magnetotactic bacteria. The matrix was examined using low‐ (80 kV) and intermediate‐ (400 kV) voltage TEM. It encapsulated magnetosomes in dehydrated cells, ultraviolet‐B‐irradiated dehydrated cells and stained resin‐embedded fixed cells, so the apparent structure of the matrix does not appear to be an artefact of specimen preparation. High‐resolution images revealed lattice fringes in the matrix surrounding magnetite and greigite magnetosomes that were aligned with lattice fringes in the encapsulated magnetosomes. In all except one case, the lattice fringes had widths equal to or twice the width of the corresponding lattice fringes in the magnetosomes. The lattice fringes in the matrix were aligned with the {311}, {220}, {331}, {111} and {391} related lattice planes of magnetite and the {222} lattice plane of greigite. An unidentified material, possibly an iron hydroxide, was detected in two immature magnetosomes containing magnetite. The unidentified phase had a structure similar to that of the matrix as it contained {311}, {220} and {111} lattice fringes, which indicates that the matrix acts as a template for the spatially controlled biomineralization of the unidentified phase, which itself transforms into magnetite. The unidentified phase was thus called pre‐magnetite. The presence of the magnetosomal matrix explains all of the five properties of the biosignature of the magnetosomal chain proposed previously by Friedmann et al. and supports their claim that some of the magnetite particles in the carbonate globules in the Martian meteorite ALH84001 are biogenic. Two new morphologies of magnetite magnetosomes are also reported here (i.e. tooth‐shaped and hexa‐octahedral magnetosomes). Tooth‐shaped magnetite magnetosomes elongated in the [110] direction are reported, and are distinct from arrowhead‐shaped and bullet‐shaped magnetosomes. Elongation of magnetite magnetosomes in the [110] direction has not been reported previously. A Martian hexa‐octahedral magnetite particle was previously characterized by Thomas‐Keptra et al. and compared with truncated hexa‐octahedral magnetite magnetosomes. Hexa‐octahedral magnetite magnetosomes with the same morphology and similar sizes and axial ratios as those reported by Thomas‐Keptra et al. are characterized here. These observations support their claim that ALH84001 contains evidence for a past Martian biota.
Progress in near‐field photothermal infra‐red microspectroscopy
Authors: Hammiche A. , Bozec L. , Pollock H. M. , German M. , Reading M. 
Published: January 2004

SummaryNear‐field photothermal Fourier transform infra‐red microspectroscopy, which utilizes atomic force microscopy (AFM)‐type temperature sensors, is being developed with the aim of achieving a spatial resolution higher than the diffraction limit. Here we report on a new implementation of the technique. Sensitivity of the technique is assessed by recording infra‐red spectra from small quantities of analytes and thin films. A photothermomechanical approach, which utilizes conventional AFM probes as temperature sensors, is also discussed based on preliminary results. Early indication suggests that the photothermal approach is more sensitive than the thermomechanical one.
The Inevitability of Genetic Enhancement Technologies
Authors: Baylis Françoise , Robert Jason Scott 
Published: January 2004

ABSTRACTWe outline a number of ethical objections to genetic technologies aimed at enhancing human capacities and traits. We then argue that, despite the persuasiveness of some of these objections, they are insufficient to stop the development and use of genetic enhancement technologies. We contend that the inevitability of the technologies results from a particular guiding worldview of humans as masters of the human evolutionary future, and conclude that recognising this worldview points to new directions for ethical thinking about genetic enhancement technologies.
Coding and Consent: Moral Challenges of the Database Project in Iceland
Authors: Árnason Vilhjálmur 
Published: January 2004

ABSTRACTA major moral problem in relation to the deCODE genetics database project in Iceland is that the heavy emphasis placed on technical security of healthcare information has precluded discussion about the issue of consent for participation in the database. On the other hand, critics who have emphasised the issue of consent have most often demanded that informed consent for participation in research be obtained. While I think that individual consent is of major significance, I argue that this demand for informed consent is neither suitable nor desirable in this case. I distinguish between three aspects of the database and show that different types of consent are appropriate for each. In particular, I describe the idea of a written authorisation based on general information about the database as an alternative to informed consent and presumed consent in database research.
Risk factors and occurrence of rash in HIV‐positive patients not receiving nonnucleoside reverse transcriptase inhibitor: data from a randomized study evaluating use of protease inhibitors in nucleoside‐experienced patients with very low CD4 levels (<50 cells/mμL)
Authors: Floridia M , Bucciardini R , Fragola V , Galluzzo CM , Giannini G , Pirillo MF , Amici R , Andreotti M , Ricciardulli D , Tomino C , Vella S ,   (for the ISS‐IP1 study group, listed in Appendix)
Published: January 2004

BackgroundMost of the studies evaluating rash in HIV‐positive patients have focused on nonnucleoside reverse transcriptase inhibitors (NNRTI), particularly nevirapine, and little is known about the occurrence of rash and the risk factors for its development in patients receiving regimens not based on NNRTI.Methods We evaluated all cases of rash observed during a 48‐week randomized multicentre trial in 1251 nucleoside‐experienced patients who started treatment with protease inhibitors (ritonavir or indinavir) at CD4 counts below 50 cells/μL. Incidence rates for rash were calculated according to gender, clinical status, age, use of highly active antiretroviral therapy (HAART), Pneumocystis carinii pneumonia (PCP) prophylaxis and use of individual antiretroviral drugs at enrolment. Differences between groups defined according to the above characteristics were tested for statistical significance using the log‐rank test in a Kaplan‐Meier survival analysis. All factors that gave results in the univariate analyses below the significance level of 0.05 were included in a multivariate analysis using a Cox regression model.Results During a follow‐up period of 9690 person‐months, 66 patients (5.3%) developed rash (0.68 events/100 person‐months). In the univariate analyses, risk of rash did not differ with trial treatment (indinavir or ritonavir), clinical status, PCP prophylaxis, or age. During follow‐up, rash was observed in 7.5% of enrolled women and in 4.5% of enrolled men (P=0.03). Serious rash occurred in 4.5% of enrolled women and in 1.6% of enrolled men (P=0.003). Use of HAART (P<0.001) and inclusion of zidovudine and of zalcitabine in the prescribed regimen (P=0.02) appeared to be associated with a lower risk of rash. In the multivariate analysis, the variables that remained significantly predictive of rash were gender (risk for women compared to men: 1.65, 95% confidence interval (CI): 1.00–2.72, P=0.048) and use of a non‐HAART regimen (risk for non‐HAART patients compared to HAART: 2.73, 95% CI: 1.49–5.02, P=0.001).Conclusions In our study, about 5% of HIV‐positive patients who started treatment with protease inhibitors at very low CD4 counts developed rash, generally in the first few weeks after treatment. Risk was significantly higher in women and in patients who did not receive a HAART regimen. Our data indicate that women have a higher risk of rash than men, also with regimens that do not include NNRTI.
Treatment of primary HIV‐1 infection with nonnucleoside reverse transcriptase inhibitor‐based therapy is effective and well tolerated
Authors: Portsmouth S , Imami N , Pires A , Stebbing J , Hand J , Nelson M , Gotch F , Gazzard BG 
Published: January 2004

Objectives
Highly active antiretroviral therapy (HAART) has been advocated for the management of primary HIV‐1 infection. We investigated the use of a nonnucleoside reverse transcriptase inhibitor (NNRTI)‐based regimen in this setting.Methods
Twenty‐one antiretroviral‐naïve individuals with early HIV‐1 disease were treated with a combination of efavirenz and Combivir (GlaxoSmithKline, Uxbridge, Middlesex, UK). They were evaluated for immune and lymphocyte function by standard immunological assays.Results
The median time to an undetectable HIV‐1 viral load was 12 weeks (range 4–36 weeks). CD4 and CD16/56 counts increased during treatment and CD8 counts decreased minimally. The main side‐effects observed were transient sleep disturbances (five patients). In addition, we observed a decrease in lymphocyte activation as assessed by CD38 surface expression.Conclusions
This study demonstrates that primary HIV‐1 infection can be treated with NNRTI‐based HAART.
Determinants of long‐term highly active antiretroviral treatment efficacy
Authors: Manegold C , Thomas S , Jablonowski H , Chiwakata CB , Alwazzeh M , Adams O , Dietrich M , Häussinger D 
Published: January 2004

Objectives Predictors of the efficacy of highly active antiretroviral therapy (HAART) have been investigated in several studies. To increase current knowledge, the study aimed to acquire comprehensive data over an extended observation time, to obtain information on possible performance differences among individual drugs, and to identify factors with influence on the initial response to a HAART regimen and the sustainability of the response.Methods The data were obtained from a prospective, single University Medical School HIV cohort. Clinical, laboratory, and treatment parameters for 475 patients were collected over 4.5 years. HAART efficacy was determined by analysis of variance and multivariate survival analysis.Results The overall initial complete response (CR) (<500 HIV‐1 RNA copies/mL) was 76.3%. Use of indinavir [odds ratio (OR)=2.747, P=0.0009] and the number of new nucleoside reverse transcriptase inhibitors (NRTIs) (OR=1.862, P=0.0017) were positively associated with CR, while initial peripheral blood HIV RNA concentration (OR=0.383, P<0.0001), use of saquinavir hard gel capsules (OR=0.531, P=0.0302), the number of successive HAART regimens (OR=0.631, P<0.0001), and the number of previously used NRTIs (OR=0.728, P=0.0081) were negatively associated with CR. Sustainability of CR was positively correlated with use of indinavir [hazard ratio of relapse (HR)=0.255, P<0.0001] and haemoglobin levels (HR=0.873, P=0.0124), but negatively correlated with initial HIV RNA concentration (HR=1.273, P=0.0003) and the number of previously used NRTIs (HR=1.587, P<0.0001). A higher number of consecutive HAART regimens was associated with a markedly reduced CR, but with only a slightly higher risk of relapse.Conclusions The initial response to HAART, as well as long‐term efficacy, depends strongly on a few fundamental parameters that can easily be assessed in a clinical setting. There is a need for effective suppression of HIV replication over decades, and these factors should be considered early in treatment planning to identify patients with an unfavourable profile of risk factors for treatment failure.
Oral candidiasis and seborrheic dermatitis in HIV‐infected patients on highly active antiretroviral therapy
Authors: Dunic I , Vesic S , Jevtovic DJ 
Published: January 2004

BackgroundMucocutaneous manifestations such as oral candidiasis (OC) and seborrheic dermatitis (SD) are very common HIV‐related opportunistic events and are usually initial markers of immunodeficiency.AimThe purpose of this study was to evaluate the efficacy of highly active antiretroviral therapy (HAART) in the regression of HIV‐associated OC and SD.MethodsIn a prospective study, 120 HIV‐infected patients with OC and SD were divided into two groups: HAART‐treated patients (group 1, n=76) and non‐HAART‐treated patients (group 2, n=44). Non‐HAART‐treated patients were given antimicrobial therapy. Study subjects were matched for sex, age, risk, and stage of HIV infection. The results were analysed by χ2 test and the Kaplan‐Meier method.ResultsAt baseline, OC was evident in 59 (77.7%) of the HAART‐treated patients and in 34 (77.3%) of the non‐HAART‐treated patients, while SD was present in 19 (25.0%) of the HAART‐treated patients and in 17 (38.6%) of the non‐HAART‐treated patients. After a median follow‐up period of 22 months, regression of OC and SD occurred in 49 (83.1%) and 16 (84.2%) of the HAART‐treated patients, respectively. In the control group, regression of OC and SD occurred in only five (14.7%) and seven (41.2%) patients, respectively, during the same period.ConclusionsHAART showed greater efficacy than standard antimicrobial therapy for the treatment of OC and SD in HIV‐infected patients.
Reformative self‐control and discounting of reward value by delay or effort1
Authors: Sugiwaka Hiroko , Okouchi Hiroto 
Published: January 2004

Abstract:  The relation between reformative self‐control and discounting of reward value by delay or effort was examined. Thirty‐two Japanese undergraduates were selected based on their scores on a standardized pencil and paper test of self‐control, the Redressive–Reformative Self‐Control Scale (Sugiwaka, 1995). The subjects indicated their preference (i) between a hypothetical 100 000 yen reward available with various delays and a certain reward of variable amount available immediately; or (ii) between a hypothetical 100 000 yen reward available with various efforts and a certain reward of variable amount available without effort. The discounting of delayed reward value was described well by a hyperbolic function proposed by Mazur (1987). The slopes of the delayed discounting curves were steeper for subjects who scored low on the Reformative Self‐Control Scale, which is a measure of reformative self‐control and a subscale of the Redressive–Reformative Self‐Control Scale. The discounting by effort was also described well by the hyperbolic function. The slopes of the effortful discounting curves did not correlate to those of the delayed discounting curves. The slopes were not systematically different across the groups of subjects with different scores on the reformative self‐control scale.
Prenatal growth and development of the modern human labyrinth
Authors: Jeffery Nathan , Spoor Fred 
Published: January 2004

AbstractThe modern human bony labyrinth is morphologically distinct from that of all other primates, showing derived features linked with vestibular function and the overall shape of the cranial base. However, little is known of how this unique morphology emerges prenatally. This study examines in detail the developing fetal human labyrinth, both to document this basic aspect of cranial biology, and more specifically, to gain insight into the ontogenetic basis of its phylogenetically derived morphology. Forty‐one post‐mortem human fetuses, ranging from 9 to 29 weeks gestation, were investigated with high‐resolution magnetic resonance imaging. Quantitative analyses of the labyrinthine morphology revealed a number of interesting age‐related trends. In addition, our findings show that: (1) the prenatal labyrinth attains an adult equivalent size between 17 and 19 weeks gestation; (2) within the period investigated, shape changes to all or most of the labyrinth cease after the 17–19‐week size maturation point or after the otic capsule ossifies; (3) fetal cochlea development correlates with the surrounding petrosal morphology, but not with the midline basicranium; (4) gestational age‐related rotations of the ampullae and cochlea relative to the lateral canal, and posterior canal torsion are similar to documented phylogenetic trends whereas other trends remain distinct. Findings are discussed in terms of the ontogenetic processes and mechanisms that most likely led, in part, to the emergence of the phylogenetically derived adult modern human labyrinth.
Microvascularization of the human digit as studied by corrosion casting
Authors: Sangiorgi S. , Manelli A. , Congiu T. , Bini A. , Pilato G. , Reguzzoni M. , Raspanti M. 
Published: January 2004

AbstractThe aim of this study was to describe microcirculation in the human digit, focusing on the vascular patterns of its cutaneous and subcutaneous areas. We injected a functional supranumerary human thumb (Wassel type IV) with a low‐viscosity acrylic resin through its digital artery. The tissues around the vessels were then digested in hot alkali and the resulting casts treated for scanning electron microscopy. We concentrated on six different areas: the palmar and dorsal side of the skin, the eponychium, the perionychium, the nail bed and the nail root. On the palmar side, many vascular villi were evident: these capillaries followed the arrangement of the fingerprint lines, whereas on the dorsal side they were scattered irregularly inside the dermal papillae. In the hypodermal layer of the palmar area, vascular supports of sweat glands and many arteriovenous anastomoses were visible, along with glomerular‐shaped vessels involved in thermic regulation and tactile function. In the eponychium and perionychium, the vascular villi followed the direction of nail growth. In the face of the eponychium in contact with the nail, a wide‐mesh net of capillaries was evident. In the nail bed, the vessels were arranged in many longitudinal trabeculae parallel to the major axis of the digit. In the root of the nail, we found many columnar vessels characterized by multiple angiogenic buttons on their surface.
The use of four‐colour immunofluorescence techniques to identify mesenchymal stem cells
Authors: Schieker Matthias , Pautke Christoph , Reitz Katharina , Hemraj Indradeo , Neth Peter , Mutschler Wolf , Milz Stefan 
Published: January 2004

AbstractIn stem‐cell research a major difficulty is caused by the lack of distinctive features that allow the identification of human mesenchymal stem cells (hMSC). Until now, there has been no specific marker and the most common way to identify hMSC is by their characteristic stem‐cell properties: self‐replication and differentiation potential. However, these findings can only be revealed retrospectively, and, once differentiated, hMSC lose their stem‐cell character. The aim of this study was to establish four‐colour immunofluorescence of several markers simultaneously in order to address the problem of how to identify hMSC on the single‐cell level. The four markers collagen‐I, collagen‐IV, fibronectin and CD44 are known to be expressed by hMSC. Antibody binding was detected using secondary antibodies conjugated to FITC, Alexa546, TexasRed and AMCA. Because the distinction between Alexa546 and TexasRed was not possible on conventional digital images using standard filter sets, we performed spectral image acquisition. The image was subsequently decomposed into its pure spectral components, which permitted linear unmixing. Using this procedure we were able to demonstrate four‐colour immunofluorescence on hMSC. With the possibility of using more sophisticated marker profiles and/or additional markers, four‐colour immunofluorescence offers the opportunity of identifying hMSC on the single‐cell level without performing differentiation assays.
A multimodal, multidimensional atlas of the C57BL/6J mouse brain
Authors: MacKenzie‐Graham Allan , Lee Erh‐Fang , Dinov Ivo D. , Bota Mihail , Shattuck David W. , Ruffins Seth , Yuan Heng , Konstantinidis Fotios , Pitiot Alain , Ding Yi , Hu Guogang , Jacobs Russell E. , Toga Arthur W. 
Published: January 2004

AbstractStrains of mice, through breeding or the disruption of normal genetic pathways, are widely used to model human diseases. Atlases are an invaluable aid in understanding the impact of such manipulations by providing a standard for comparison. We have developed a digital atlas of the adult C57BL/6J mouse brain as a comprehensive framework for storing and accessing the myriad types of information about the mouse brain. Our implementation was constructed using several different imaging techniques: magnetic resonance microscopy, blockface imaging, classical histology and immunohistochemistry. Along with raw and annotated images, it contains database management systems and a set of tools for comparing information from different techniques. The framework allows facile correlation of results from different animals, investigators or laboratories by establishing a canonical representation of the mouse brain and providing the tools for the insertion of independent data into the same space as the atlas. This tool will aid in managing the increasingly complex and voluminous amounts of information about the mammalian brain. It provides a framework that encompasses genetic information in the context of anatomical imaging and holds tremendous promise for producing new insights into the relationship between genotype and phenotype. We describe a suite of tools that enables the independent entry of other types of data, facile retrieval of information and straightforward display of images. Thus, the atlas becomes a framework for managing complex genetic and epigenetic information about the mouse brain. The atlas and associated tools may be accessed at http://www.loni.ucla.edu/MAP.
Merkel cells, a new localization of prepro‐orexin and orexin receptors
Authors: Beiras‐Fernández Andrés , Gallego Rosalía , Blanco Montserrat , García‐Caballero Tomás , Diéguez Carlos , Beiras Andrés 
Published: January 2004

AbstractOrexins (OXA and OXB) are peptides derived from a common precursor called prepro‐orexin. They act through G‐protein receptors named orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R). Orexins were first demonstrated in neurons of the lateral hypothalamus and found to be related to the control of food intake. However, it has been shown that they are widely distributed in both the nervous system and peripheral tissues, including endocrine organs such as the pituitary and adrenal glands. Merkel cells are neuroendocrine cells situated in the epidermis, tactile hairs and oral mucosa, and act as mechanoreceptors. Up to the present, various neuropeptides have been detected in these cells. The aim of the present study was to detect the presence of prepro‐orexin and orexin receptors (OX1R and OX2R) in porcine Merkel cells using immunohistochemistry. Prepro‐orexin was expressed in the cytoplasm of Merkel cells in the skin of the pig snout. Immunoreactivity for prepro‐orexin was more intense in the mature side of the cell, where the dense‐cored granules are accumulated. Epidermal nerve terminals associated with Merkel cells and dermal nerve fibres showed no immunostaining. Both orexin receptors (OX1R and OX2R) were also demonstrated in the cytoplasm of Merkel cells of pig snout skin. The finding of orexins and their receptors in Merkel cells suggests that they have an autocrine function. Further studies are needed to ascertain the significance of this function.