bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of the Bipolar Mating System of the Mushroom Coprinellus disseminatus From Its Tetrapolar Ancestors Involves Loss of Mating-Type-Specific Pheromone Receptor Function
Authors: James Timothy Y , Srivilai Prayook , Kües Ursula , Vilgalys Rytas
Published: February 2006

Mating incompatibility in mushroom fungi is controlled by the mating-type loci. In tetrapolar species, two unlinked mating-type loci exist (A and B), whereas in bipolar species there is only one locus. The A and B mating-type loci encode homeodomain transcription factors and pheromones and pheromone receptors, respectively. Most mushroom species have a tetrapolar mating system, but numerous transitions to bipolar mating systems have occurred. Here we determined the genes controlling mating type in the bipolar mushroom Coprinellus disseminatus. Through positional cloning and degenerate PCR, we sequenced both the transcription factor and pheromone receptor mating-type gene homologs from C. disseminatus. Only the transcription factor genes segregate with mating type, discounting the hypothesis of genetic linkage between the A and B mating-type loci as the causal origin of bipolar mating behavior. The mating-type locus of C. disseminatus is similar to the A mating-type locus of the model species Coprinopsis cinerea and encodes two tightly linked pairs of homeodomain transcription factor genes. When transformed into C. cinerea, the C. disseminatus A and B homologs elicited sexual reactions like native mating-type genes. Although mating type in C. disseminatus is controlled by only the transcription factor genes, cellular functions appear to be conserved for both groups of genes.
Effect of Maternal Multivitamin Supplementation on the Mental and Psychomotor Development of Children Who Are Born to HIV-1–Infected Mothers in Tanzania
Authors: McGrath Nuala , Bellinger David , Robins James , Msamanga Gernard I. , Tronick Edward , Fawzi Wafaie W.
Published: February 2006

OBJECTIVES. To determine the association between maternal multivitamin supplementation and the mental and psychomotor development of children who are born to HIV-1–infected mothers in Tanzania, as secondary endpoints in a randomized trial that investigated the effect of maternal multivitamin supplementation on HIV-1 vertical transmission and progression.

METHODS. The Bayley Scales of Infant Development, 2nd Edition, were administered at 6, 12, and 18 months of age to a subset of children (N = 327). We assessed the effect of vitamin A and multivitamin (vitamins B, C, and E) supplementation using linear regression models and Cox proportional hazard models for the Mental Development Index, the Psychomotor Development Index, and raw scores separately.

RESULTS. Multivitamin supplementation was associated significantly with a mean increase in Psychomotor Development Index score of 2.6 (95% confidence interval: 0.1–5.1). Multivitamins were also significantly protective against the risk for developmental delay on the motor scale (relative risk: 0.4; 95% confidence interval: 0.2–0.7) but not on the Mental Development Index. Vitamin A supplementation had no significant effect on these outcomes.

CONCLUSIONS. Maternal multivitamin supplements provide a low-cost intervention to reduce the risk for developmental delays among infants who are born to HIV-positive mothers in developing countries.
Shortcomings in Infant Iron Deficiency Screening Methods
Authors: Biondich Paul G. , Downs Stephen M. , Carroll Aaron E. , Laskey Antoinette L. , Liu Gilbert C. , Rosenman Marc , Wang Jane , Swigonski Nancy L.
Published: February 2006

BACKGROUND. Screening for iron deficiency anemia is a well-established practice in pediatrics, but numerous challenges surrounding current recommendations raise questions about the effectiveness of this strategy.

OBJECTIVE. To evaluate iron deficiency anemia screening approaches, by assessing rates of follow-up testing and resolution among patients meeting screening criteria in a primary care setting.

METHODS. A retrospective cohort study was performed. We extracted electronic medical record data on complete blood counts for infants who received primary care in our clinics in the past 10 years. We calculated rates of positive screening results with 9 different measurement criteria and determined rates of follow-up testing and of documented correction of iron deficiency among those who screened positive.

RESULTS. Our cohort consisted of 4984 children who were screened at 9 to 15 months of age, between 1994 and 2004. There was a wide distribution of positive detection rates (range: 1.5–14.5%) among the 9 screening criteria. Follow-up testing rates were low. No more than 25% of infants who screened positive by any criterion underwent a repeat complete blood count within 6 months. Moreover, no more than 11.6% (range: 4.4–11.6%) had documented correction of their laboratory abnormalities.

CONCLUSIONS. Significant shortcomings exist in current iron deficiency anemia screening practices. A widely agreed-on, specific, and inexpensive screening criterion, with increased emphasis on systems-based approaches to iron deficiency screening, is needed.
Vaccine Adverse Event Reporting System Reporting Source: A Possible Source of Bias in Longitudinal Studies
Authors: Goodman Michael J. , Nordin James
Published: February 2006

OBJECTIVE. The US Vaccine Adverse Event Reporting System (VAERS) is a passive reporting system to which anyone can report an event. Publicity related to potential adverse events may change reporting patterns. The objective of this paper is to show how litigation-related reports have influenced the trends in possible adverse event reports to VAERS.

METHODS. The VAERS public-use data files were downloaded in July 2004 and translated into identical SAS data sets for analysis. Cases that were related to litigation were identified using a word search algorithm. All cases for the most frequently reported symptoms in litigation (overdose, neuropathy, autism, “mental retardation,” arthralgia, and “speech disorder”) were reviewed.

RESULTS. In recent years, most case reports to VAERS that were related to overdose, neuropathy, and thimerosal were related to litigation. Many cases that were related to autism and mental retardation were as well.

CONCLUSIONS. This review shows a previously undisclosed rise in the number of reports to the VAERS related to pending litigation for vaccine injury. The implications of this for understanding longitudinal reporting patterns are discussed.
Successful Wireless Capsule Endoscopy for a 2.5-Year-Old Child: Obscure Gastrointestinal Bleeding From Mixed, Juvenile, Capillary Hemangioma-Angiomatosis of the Jejunum
Authors: Kavin Hymie , Berman James , Martin Thomas L. , Feldman Ansley , Forsey-Koukol Kimberly
Published: February 2006

The lesion responsible for obscure gastrointestinal bleeding in the pediatric population may not be determined with standard primary endoscopic methods. Wireless capsule endoscopy, now a first-line modality for evaluation of the small bowel in the adult population, is a tool that may be useful among children. We report a case of a 2.5-year-old girl who presented with melenic stools. Upper and lower endoscopy, Meckel scans, and mesenteric angiography yielded negative results. Wireless capsule endoscopy identified numerous abnormal, dilated, blood vessels in the proximal jejunum, with associated fresh blood. The patient underwent surgical exploration, with resection of the affected portion of the jejunum. Pathologically, the dilated blood vessels were consistent with mixed, juvenile, capillary hemangioma-angiomatosis of developmental or congenital origin. The patient fared well postoperatively, with no additional bleeding in 9 months of follow-up monitoring. This case report highlights the use of capsule endoscopy in the diagnosis and successful treatment of gastrointestinal bleeding in a young infant. This is the youngest reported patient treated with the use of wireless capsule endoscopy in the pediatric population.
Risk of Intracranial Pathologic Conditions Requiring Emergency Intervention After a First Complex Febrile Seizure Episode Among Children
Authors: Teng David , Dayan Peter , Tyler Sarah , Hauser W. Allen , Chan Stephen , Leary Linda , Hesdorffer Dale
Published: February 2006

OBJECTIVE. To determine the likelihood of intracranial pathologic conditions requiring emergency neurosurgical or medical intervention among children without meningitis who presented to the pediatric emergency department after a first complex febrile seizure.

METHODS. We performed a retrospective review of prospectively collected data for children in neurologically normal condition who presented to a single pediatric emergency department after a first complex febrile seizure (focal, multiple, or prolonged). The complex febrile seizure classification was determined independently by 2 epileptologists. The presence of intracranial pathologic conditions was determined through review of neuroimaging results, telephone interviews, or medical record review.

RESULTS. Data for 71 children with first complex febrile seizures were analyzed. Fifty-one (72%) had a single complex feature (20 focal, 22 multiple, and 9 prolonged), and 20 (28%) had multiple complex features. None of the 71 patients (1-sided 95% confidence interval: 4%) had intracranial pathologic conditions that required emergency neurosurgical or medical intervention.

CONCLUSIONS. For children with first complex febrile seizures, the risk of intracranial pathologic conditions that require emergency neurosurgical or medical intervention is low, which suggests that routine emergency neuroimaging for this population is unnecessary.
The Pediatrician and Disaster Preparedness
Authors:   Committee on Pediatric Emergency Medicine,   Committee on Medical Liability,   and the Task Force on Terrorism
Published: February 2006

Recent natural disasters and events of terrorism and war have heightened society's recognition of the need for emergency preparedness. In addition to the unique pediatric issues involved in general emergency preparedness, several additional issues related to terrorism preparedness must be considered, including the unique vulnerabilities of children to various agents as well as the limited availability of age- and weight-appropriate antidotes and treatments. Although children may respond more rapidly to therapeutic intervention, they are at the same time more susceptible to various agents and conditions and more likely to deteriorate if not monitored carefully.

The challenge of dealing with the threat of terrorism, natural disasters, and public health emergencies in the United States is daunting not only for disaster planners but also for our medical system and health professionals of all types, including pediatricians. As part of the network of health responders, pediatricians need to be able to answer concerns of patients and families, recognize signs of possible exposure to a weapon of terror, understand first-line response to such attacks, and sufficiently participate in disaster planning to ensure that the unique needs of children are addressed satisfactorily in the overall process. Pediatricians play a central role in disaster and terrorism preparedness with families, children, and their communities. This applies not only to the general pediatrician but also to the pediatric medical subspecialist and pediatric surgical specialist. Families view pediatricians as their expert resource, and most of them expect the pediatrician to be knowledgeable in areas of concern. Providing expert guidance entails educating families in anticipation of events and responding to questions during and after actual events. It is essential that pediatricians educate themselves regarding these issues of emergency preparedness.

For pediatricians, some information is currently available on virtually all of these issues in recently produced printed materials, at special conferences, in broadcasts of various types, and on the Internet. However, selecting appropriate, accurate sources of information and determining how much information is sufficient remain difficult challenges. Similarly, guidance is needed with respect to developing relevant curricula for medical students and postdoctoral clinical trainees.
Field determination of mechanical aperture, entry pressure and relative permeability of fractures using NAPL injection
Authors: Steele A. , Reynolds D. A. , Kueper B. H. , Lerner D. N.
Published: February 2006

An in situ field technique has been developed and implemented to measure non-aqueous phase liquid (NAPL) entry pressure and subsequently estimate mechanical aperture variability in an undisturbed, water-saturated rock fracture. The field experiment also provided the opportunity to measure wetting phase relative permeability at residual non-wetting phase saturation, kw,r(Snw,r). The radial aperture determination by the injection of oil (RADIO) method employs a constant-rate injection of a non-toxic NAPL into a fracture isolated by a double packer array. Injection pressures are recorded to provide a characteristic signature that is interpreted to reveal aperture enlargements and constrictions several metres from the borehole. Fracture aperture values are calculated by reverse modelling of the pressure signatures using the FRACAS fully compositional two-phase flow model. Pre-NAPL injection hydraulic testing established a baseline dataset of hydraulic apertures ranging from 26 μm to 259 μm with a mean value of 86 μm. Post-NAPL injection hydraulic testing gave kw,r(Snw,r) values ranging from 0·04 to 0·39 with a mean value of 0·15. Numerical modelling calculated fracture mechanical apertures vary from 36 μm to >1000 μm in test 1, and from 46 μm to >1000 μm in test 2. Single-value approximations of volume-averaged fracture apertures are two to three times larger than the respective hydraulic apertures, suggesting that volume balance calculations using the hydraulic aperture may overpredict NAPL penetration distances.
Challenges to Research in Urban Community Health Centers
Authors: Lemon Stephenie C. , Zapka Jane G. , Estabrook Barbara , Benjamin Evan
Published: February 2006

Community health centers (CHCs) are important settings for research aimed at reducing health disparities. However, CHCs pose many challenges to research at patient, provider, and system levels.

We summarized lessons learned from a multimethod, formative study to develop intervention strategies for improving colorectal cancer screening in CHCs, and make recommendations for future research. The call for research in “real world” settings such as CHCs must be matched with greater understanding of the challenges, as well as the resources to meet those challenges.
Understanding Diabetes Population Dynamics Through Simulation Modeling and Experimentation
Authors: Jones Andrew P. , Homer Jack B. , Murphy Dara L. , Essien Joyce D. K. , Milstein Bobby , Seville Donald A.
Published: February 2006

Health planners in the Division of Diabetes Translation and others from the National Center for Chronic Disease Prevention and Health Promotion of the Centers for Disease Control and Prevention used system dynamics simulation modeling to gain a better understanding of diabetes population dynamics and to explore implications for public health strategy. A model was developed to explain the growth of diabetes since 1980 and portray possible futures through 2050.

The model simulations suggest characteristic dynamics of the diabetes population, including unintended increases in diabetes prevalence due to diabetes control, the inability of diabetes control efforts alone to reduce diabetes-related deaths in the long term, and significant delays between primary prevention efforts and downstream improvements in diabetes outcomes.
Policy and Programmatic Importance of Spatial Alignment of Data Sources
Authors: Ong Paul , Graham Matthew , Houston Douglas
Published: February 2006

Geographic information systems have proven instrumental in assessing environmental impacts on individual and community health, but numerous methodological challenges are associated with analyses of highly localized phenomena in which spatially misaligned data are used.

In a case study based on child care facility and traffic data for the Los Angeles metropolitan area, we assessed the extent of facility misclassification with spatially unreconciled data from 3 different governmental agencies in an attempt to identify child care centers in which young children are at risk from high concentrations of toxic vehicle-exhaust pollutants. Relative to geographically corrected data, unreconciled information produced a modest bias in terms of aggregated number of facilities at risk and a substantial number of false positives and negatives.
Modeling hydrogen separation in high temperature silica membrane systems
Authors: Duke M. C. , Diniz da Costa J. C. , Lu G. Q. , Gray P. G.
Published: February 2006

In this work, a working model is proposed of molecular sieve silica (MSS) multistage membrane systems for CO cleanup at high temperatures (up to 500°C) in a simulated fuel cell fuel processing system. Gases are described as having little interactions with each other relative to the pore walls due to low isosteric heat of adsorption on silica surfaces and high temperatures. The Arrhenius function for activated transport of pure gases was used to predict mixture concentration in the permeate and retentate streams. Simulation predicted CO could be reduced to levels below the required 50 ppmv for polymer electrolyte membrane fuel cell anodes at a stage H2/CO selectivity of higher than 40 in 4 series membrane units. Experimental validation showed predicting mixture concentrations required only pure gas permeation data. This model has significant application for setting industrial “stretch targets” and as a robust basis for complex membrane model configurations. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Enhanced hydrogenation in a reverse flow chromatographic reactor
Authors: Viecco Guillermo A. , Carnish Brad J. , Caram Hugo S.
Published: February 2006

An experimental study of the reverse flow chromatographic reactor is carried with the equilibrium limited hydrogenation of 1,3,5‐trimethylbenzene (mesitylene, MES) to 1,3,5‐trimethylcyclohexane. The reaction is pseudo first‐order when carried out in excess hydrogen. A simple experimental setup is used to evaluate the effects of carrier flow, reactant feed concentration, and amount of catalyst on conversion. Conversions exceeding the thermodynamic equilibrium conversion are obtained for a wide variety of switching times, catalyst amounts, carrier flow rates, and reactant concentrations, showing the robustness of the system. While the qualitative features of the process can be predicted for a simple linear adsorption equilibrium model, the experimental results are best fitted by assuming a linear adsorption isotherm combined with an adjusted interfacial mass‐transfer resistance. The experimental results are very similar to those reported in previous research of the same reaction in a simulated moving‐bed chromatographic reactor. © 2006 American Institute of Chemical Engineers AIChE J, 2006
1,026 Experimental treatments in acute stroke
Authors: O'Collins Victoria E. , Macleod Malcolm R. , Donnan Geoffrey A. , Horky Laura L. , van der Worp Bart H. , Howells David W.
Published: February 2006

Objective

Preclinical evaluation of neuroprotectants fostered high expectations of clinical efficacy. When not matched, the question arises whether experiments are poor indicators of clinical outcome or whether the best drugs were not taken forward to clinical trial. Therefore, we endeavored to contrast experimental efficacy and scope of testing of drugs used clinically and those tested only experimentally.

Methods

We identified neuroprotectants and reports of experimental efficacy via a systematic search. Controlled in vivo and in vitro experiments using functional or histological end points were selected for analysis. Relationships between outcome, drug mechanism, scope of testing, and clinical trial status were assessed statistically.

Results

There was no evidence that drugs used clinically (114 drugs) were more effective experimentally than those tested only in animal models (912 drugs), for example, improvement in focal models averaged 31.3 ± 16.7% versus 24.4 ± 32.9%, p > 0.05, respectively. Scope of testing using Stroke Therapy Academic Industry Roundtable (STAIR) criteria was highly variable, and no relationship was found between mechanism and efficacy.

Interpretation

The results question whether the most efficacious drugs are being selected for stroke clinical trials. This may partially explain the slow progress in developing treatments. Greater rigor in the conduct, reporting, and analysis of animal data will improve the transition of scientific advances from bench to bedside. Ann Neurol 2006
AHI1 gene mutations cause specific forms of Joubert syndrome–related disorders
Authors: Valente Enza Maria , Brancati Francesco , Silhavy Jennifer L. , Castori Marco , Marsh Sarah E. , Barrano Giuseppe , Bertini Enrico , Boltshauser Eugen , Zaki Maha S. , Abdel‐Aleem Alice , Abdel‐Salam Ghada M. H. , Bellacchio Emanuele , Battini Roberta , Cruse Robert P. , Dobyns William B. , Krishnamoorthy Kalpathy S. , Lagier‐Tourenne Clotilde , Magee Alex , Pascual‐Castroviejo Ignacio , Salpietro Carmelo D. , Sarco Dean ,   International JSRD Study Group, Dallapiccola Bruno , Gleeson Joseph G.
Published: February 2006

Objective

Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. It is characterized by hypoplasia of the cerebellar vermis and a particular midbrain‐hindbrain “molar tooth” sign, a finding shared by a group of Joubert syndrome–related disorders (JSRDs), with wide phenotypic variability. The frequency of mutations in the first positionally cloned gene, AHI1, is unknown.

Methods

We searched for mutations in the AHI1 gene among a cohort of 137 families with JSRD and radiographically proven molar tooth sign.

Results

We identified 15 deleterious mutations in 10 families with pure JS or JS plus retinal and/or additional central nervous system abnormalities. Mutations among families with JSRD including kidney or liver involvement were not detected. Transheterozygous mutations were identified in the majority of those without history of consanguinity. Most mutations were truncating or splicing errors, with only one missense mutation in the highly conserved WD40 repeat domain that led to disease of similar severity.

Interpretation

AHI1 mutations are a frequent cause of disease in patients with specific forms of JSRD. Ann Neurol 2006
Rapamycin causes regression of astrocytomas in tuberous sclerosis complex
Authors: Franz David Neal , Leonard Jennifer , Tudor Cynthia , Chuck Gail , Care Marguerite , Sethuraman Gopalan , Dinopoulos Argirios , Thomas George , Crone Kerry R.
Published: February 2006

Objective

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by the formation of hamartomas in multiple organs. Five to 15% of affected individuals display subependymal giant cell astrocytomas, which can lead to substantial neurological and postoperative morbidity due to the production of hydrocephalus, mass effect, and their typical location adjacent to the foramen of Monro. We sought to see whether therapy with oral rapamycin could affect growth or induce regression in astrocytomas associated with TSC.

Methods

Five subjects with clinically definite TSC and either subependymal giant cell astrocytomas (n = 4) or a pilocytic astrocytoma (n = 1) were treated with oral rapamycin at standard immunosuppressive doses (serum levels 5–15ng/ml) from 2.5 to 20 months. All lesions demonstrated growth on serial neuroimaging studies. Magnetic resonance imaging scans were performed before and at regular intervals following initiation of therapy.

Results

All lesions exhibited regression and, in one case, necrosis. Interruption of therapy resulted in regrowth of subependymal giant cell astrocytomas in one patient. Resumption of therapy resulted in further regression. Treatment was well tolerated.

Interpretation

Oral rapamycin therapy can induce regression of astrocytomas associated with TSC and may offer an alternative to operative therapy of these lesions. Ann Neurol 2006
Synthesis of cyclopentadienyltricarbonylrhenium substituted benzhydryl species and oestrogen receptor binding properties
Authors: Plażuk D. , Le Bideau F. , Pérez‐Luna A. , Stéphan E. , Vessières A. , Zakrzewski J. , Jaouen G.
Published: February 2006

6‐(4‐Methoxyphenyl)fulvene has been efficiently engaged in a process implying nucleophilic attack of methyllithium followed by a transmetallation reaction in the presence of different organorhenium sources {XRe(CO)5: X = Cl, Br, OTf; BrRe(CH3CN)2(CO)3, [BrRe(CO)3THF]2} to afford the corresponding cyclopentadienyltricarbonylrhenium‐substituted compound. This study allowed us to determine the best complex for that transformation, and similar reaction conditions were used with success to provide new potential radiopharmaceuticals in the cold series. One of these compounds [the (4,4′‐dihydroxybenzhydryl)cyclopentadienyltricarbonylrhenium] displays a good recognition for the α form of the oestrogen receptor. Copyright © 2006 John Wiley & Sons, Ltd.
A murine model of mixed connective tissue disease induced with U1 small nuclear RNP autoantigen
Authors: Greidinger Eric L. , Zang Yunjuan , Jaimes Kimberly , Hogenmiller Scott , Nassiri Mehdi , Bejarano Pablo , Barber Glen N. , Hoffman Robert W.
Published: February 2006

Objective

To test whether immunizing mice with autoantigens closely linked to mixed connective tissue disease (MCTD) could induce an MCTD‐like clinical syndrome distinguishable from systemic lupus erythematosus (SLE).

Methods

Transgenic and knockout C57BL/6‐derived mice were immunized subcutaneously at age 8–12 weeks with U1–70‐kd small nuclear RNP (70K) fusion protein along with either Freund's complete adjuvant (CFA) or U1 RNA. After 2 months, mice were killed and analyzed histologically and serologically.

Results

Immunization of C57BL/6‐derived mice transgenic for human HLA–DR4 with 70K and either CFA or U1 RNA led to anti‐70K antibodies in 62% of mice (21 of 34), and diversified anti‐RNP immune responses. MCTD‐like lung disease also developed in 50% of immunized mice (17 of 34), and anti‐70K antibodies were strongly correlated with lung disease. CFA and U1 RNA were comparably able to induce this syndrome. Mice deficient in Toll‐like receptor 3 (TLR‐3) also developed this same syndrome when immunized with 70K and CFA. However, TLR‐3−/− mice failed to develop MCTD‐like lung disease when treated with 70K and U1 RNA. Rather, TLR‐3−/− mice immunized with 70K and U1 RNA developed an autoimmune syndrome characterized by glomerulonephritis typical of SLE.

Conclusion

Exposure to 70K in an appropriate context is sufficient to induce autoimmunity and target organ injury consistent with MCTD. This system represents a new model of autoimmune interstitial lung disease, and establishes a closer link between anti‐70K immunity and MCTD‐like lung disease. Of note, changes in innate immune signaling can cause the same trigger to lead to the development of SLE‐like nephritis rather than MCTD‐like lung disease.
Reproducible genetic associations between candidate genes and clinical knee osteoarthritis in men and women
Authors: Valdes Ana M. , Van Oene Mark , Hart Deborah J. , Surdulescu Gabriela L. , Loughlin John , Doherty Michael , Spector Tim D.
Published: February 2006

Objective

Osteoarthritis (OA) is recognized to have a genetic component, and in this study, we aimed to replicate in a case–control study of men and women with clinical knee OA genetic associations in 12 candidate genes previously reported to be associated with OA.

Methods

Twenty‐five single‐nucleotide polymorphisms were genotyped in 298 men and 305 women ages 50–86 who were diagnosed as having knee OA, as assessed both clinically and radiographically, and in 297 men and 299 women matched for age and ethnicity (controls). Standardized anteroposterior radiographs of the knee in extension were performed on each of the cases, and all cases met the American College of Rheumatology criteria for OA of the knee. Genotype and haplotype frequencies in cases and controls were compared separately in men and women. The 12 genes tested were AACT, ADAM12, BMP2, CD36, CILP, COX2, ESR1, NCOR2, OPG, TNA, TNFAIP6, and VDR.

Results

Eight of the candidate genes were associated in women and 5 in men, and only 3 genes (TNFAIP6, NCOR2, and CD36) were not significantly associated in either sex. The strongest associations in terms of odds ratios (ORs) were a haplotype in ADAM12 (OR 7.1 [95% confidence interval (95% CI) 3.3–33.8]) and a haplotype in ESR1 (OR 3.6 [95% CI 1.18–10.98]) in women. The same ADAM12 haplotype (OR 2.54 [95% CI 1.2–5.4]) and a haplotype in the CILP gene (OR 0.38 [95% CI 0.23–0.62]) were the strongest associations in men.

Conclusion

We found that genes previously identified by their association with subclinical features of knee OA or progression were also associated with clinical knee OA. These genetic associations may identify individuals at a particularly high risk of developing knee OA.
CD28‐dependent differentiation into the effector/memory phenotype is essential for induction of arthritis in interleukin‐1 receptor antagonist–deficient mice
Authors: Kotani Motoko , Hirata Kazuya , Ogawa Shuhei , Habiro Katsuyoshi , Ishida Yasuo , Tanuma Seiichi , Horai Reiko , Iwakura Yoichiro , Kishimoto Hidehiro , Abe Ryo
Published: February 2006

Objective

Interleukin‐1 receptor antagonist (IL‐1Ra)–deficient mice on a BALB/c background spontaneously develop a chronic inflammatory polyarthropathy closely resembling that of rheumatoid arthritis in humans. To elucidate the role of CD28 costimulatory signals in the development of this disease, we studied IL‐1Ra/CD28–double‐deficient mice.

Methods

We crossed IL‐1Ra–deficient mice with CD28–deficient mice and observed the incidence and severity of arthritis. To investigate functions of IL‐1Ra/CD28–double‐deficient T cells, cells were stimulated with CD3 monoclonal antibody or allogeneic antigen‐presenting cells (APCs) and their proliferative responses and levels of cytokine production were measured.

Results

Disease severity was lower in IL‐1Ra/CD28–double‐deficient mice than in mice that were deficient only in IL‐1Ra, although incidence of arthritis was not affected by the presence or absence of CD28. When pathogenic IL‐1Ra–KO T cells were transferred into nude mice, severe arthritis developed. Even though T cells from double‐deficient mice showed the same diminished proliferative capacity as was seen in T cells from CD28–single‐deficient animals, nude mice into which double‐deficient T cells were transferred never developed arthritis.

Conclusion

These findings indicate that IL‐1Ra/CD28–double‐deficient T cells can be activated by IL‐1Ra–deficient activated APCs, resulting in induction of arthritis; however, these T cells did not induce the disease under normal conditions, because they did not differentiate into effector/memory phenotype.
Which user interaction for cross‐language information retrieval? Design issues and reflections
Authors: Petrelli Daniela , Levin Stephen , Beaulieu Micheline , Sanderson Mark
Published: February 2006

A novel and complex form of information access is cross‐language information retrieval: searching for texts written in foreign languages based on native language queries. Although the underlying technology for achieving such a search is relatively well understood, the appropriate interface design is not. The authors present three user evaluations undertaken during the iterative design of Clarity, a cross‐language retrieval system for low‐density languages, and shows how the user‐interaction design evolved depending on the results of usability tests. The first test was instrumental to identify weaknesses in both functionalities and interface; the second was run to determine if query translation should be shown or not; the final was a global assessment and focused on user satisfaction criteria. Lessons were learned at every stage of the process leading to a much more informed view of what a cross‐language retrieval system should offer to users.
In vivo localization and identification of the antiplasmodial alkaloid dioncophylline A in the tropical liana Triphyophyllum peltatum by a combination of fluorescence, near infrared Fourier transform Raman microscopy, and density functional theory calculations
Authors: Frosch Torsten , Schmitt Michael , Schenzel Karla , Faber Johan H. , Bringmann Gerhard , Kiefer Wolfgang , Popp Jürgen
Published: February 2006

Near infrared Fourier transform (NIR FT) micro Raman spectroscopy in combination with density functional theory (DFT) calculations has been applied for an in vivo localization of the antiplasmodial naphthylisoquinoline alkaloid dioncophylline A (1) in the tropical liana Triphyophyllum peltatum. Fluorescence microscopy images suggest finding this active agent in 10 μm big inclusions located in the cortex of the stem or the beginning of the leaves. By means of spatially resolved FT Raman micro spectroscopy, we could detect dioncophylline A (1) in these inclusions. FT Raman spectroscopy is an extremely selective tool capable of differentiating between various structurally similar naphthylisoquinoline alkaloids. With the help of DFT calculations, we succeeded in assigning the differences found in the FT Raman spectra of the various naphthylisoquinolines to νCC vibrations of the naphthyl ring. The presented results are of relevance for the investigation and extraction of new antimalarial active agents. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 295–300, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
The xyloglucan–cellulose assembly at the atomic scale
Authors: Hanus Jaroslav , Mazeau Karim
Published: February 2006

The assembly of cell wall components, cellulose and xyloglucan (XG), was investigated at the atomistic scale using molecular dynamics simulations. A molecular model of a cellulose crystal corresponding to the allomorph Iβ and exhibiting a flexible complex external morphology was employed to mimic the cellulose microfibril. The xyloglucan molecules considered were the three typical basic repeat units, differing only in the size of one of the lateral chain. All the investigated XG fragments adsorb nonspecifically onto cellulose fiber; multiple arrangements are equally probable, and every cellulose surface was capable of binding the short XG molecules. The following structural effects emerged: XG molecules that do not have any long side chains tended to adapt themselves nicely to the topology of the microfibril, forming a flat, outstretched conformation with all the sugar residues interacting with the surface. In contrast, the XG molecules, which have long side chains, were not able to adopt a flat conformation that would enable the interaction of all the XG residues with the surface. In addition to revealing the fundamental atomistic details of the XG adsorption on cellulose, the present calculations give a comprehensive understanding of the way the XG molecules can unsorb from cellulose to create a network that forms the cell wall. Our revisited view of the adsorption features of XG on cellulose microfibrils is consistent with experimental data, and a model of the network is proposed. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 59–73, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Average assignment method for predicting the stability of protein mutants
Authors: Saraboji K. , Gromiha M. Michael , Ponnuswamy M. N.
Published: February 2006

Prediction of protein stability upon amino acid substitutions is an important problem in molecular biology and it will be helpful for designing stable mutants. In this work, we have analyzed the stability of protein mutants using three different data sets of 1791, 1396, and 2204 mutants, respectively, for thermal stability (ΔTm), free energy change due to thermal (ΔΔG), and denaturant denaturations (ΔΔG), obtained from the ProTherm database. We have classified the mutants into 380 possible substitutions and assigned the stability of each mutant using the information obtained with similar type of mutations. We observed that this assignment could distinguish the stabilizing and destabilizing mutants to an accuracy of 70–80% at different measures of stability. Further, we have classified the mutants based on secondary structure and solvent accessibility (ASA) and observed that the classification significantly improved the accuracy of prediction. The classification of mutants based on helix, strand, and coil distinguished the stabilizing/destabilizing mutants at an average accuracy of 82% and the correlation is 0.56; information about the location of residues at the interior, partially buried, and surface regions of a protein correctly identified the stabilizing/destabilizing residues at an average accuracy of 81% and the correlation is 0.59. The nine subclassifications based on three secondary structures and solvent accessibilities improved the accuracy of assigning stabilizing/destabilizing mutants to an accuracy of 84–89% for the three data sets. Further, the present method is able to predict the free energy change (ΔΔG) upon mutations within a deviation of 0.64 kcal/mol. We suggest that this method could be used for predicting the stability of protein mutants. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 80–92, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Solvent polarity effect on excited‐state lifetime of carotenoids and some dyes
Authors: Pavlovich Vladimir S.
Published: February 2006

The theory demonstrating the role of medium at the fluorescence quenching of polar compounds in solutions is briefly presented. It has been shown, that the rate of S1 → Xn nonradiative conversion between the intramolecular charge transfer states depends on the permanent dipole moments in the ground (S0) and excited (S1, Xn) states as well as on solvent polarity. A relation for the rate of nonradiative excited‐state energy conversion has been obtained and employed to test the known literature data for solvent effect on the S1‐state lifetime of some biologically significant carotenoids and dyes (phthalimides). For phthalimides, the solvent isotope effect on the S1‐state energy conversion, when hydrogen is replaced by deuterium in the OH groups of alcohols and water, has been analyzed. Based on the data for fluorescence quenching in solvents of different polarity, the dipole moments in the intermolecular charge transfer S1 state have been obtained for carotenoids (peridinin, fucoxanthin, uriolide acetate) and for hydrogen‐bonding complexes, which are formed by 4‐amino‐, 4‐methylamino‐, and 4‐dimethylamino‐N‐methylphthalimides in alcohols and water. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 435–441, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Surface‐enhanced resonance Raman scattering of porphyrins on gold nanoparticles attached to silanized glass plates
Authors: Procházka Marek , Hajduková Natália , S̆těpánek Josef
Published: February 2006

Surface‐enhanced resonance Raman scattering (SERRS) spectra of cationic 5,10,15,20‐tetrakis(1‐methyl‐4‐pyridyl) porphyrin (TMPyP) and anionic 5,10,15,20‐tetrakis(4‐sulfonatophenyl) porphyrin (TSPP) were measured from gold surfaces prepared by attaching citrate‐reduced colloidal nanoparticles to glass slides silanized by 3‐aminopropyltrimethoxysilane. SERRS spectra of both porphyrins obtained in a large concentration range (1 × 10−4 to 1 × 10−7M) of primary solution do not show any sign of porphyrin metalation or perturbation of its native structure. Optimal adsorption time (15–20 min) and covering concentration limit (lower than 1 × 10−5M) of porphyrins have been estimated from the concentration and soaking time dependences of SERRS spectra. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 390–393, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Electrochemically induced FTIR difference spectroscopy in the mid‐ to far infrared (200 μm) domain: A new setup for the analysis of metal–ligand interactions in redox proteins
Authors: Berthomieu Catherine , Marboutin Laure , Dupeyrat François , Bouyer Pierre
Published: February 2006

We report the setup of an electrochemical cell with chemical–vapor deposition diamond windows and the use of a Bruker 66 SX FTIR spectrometer equipped with DTGS and Si‐bolometer detectors and KBr and mylar beam splitters, to record on the same sample, FTIR difference spectra corresponding to the structural changes associated with the change in redox state of active sites in proteins in the whole 1800–50 cm–1 region. With cytochrome c we show that reliable reduced‐minus‐oxidized FTIR difference spectra are obtained, which correspond to single molecular vibrations. Redox‐sensitive IR modes of the cytochrome c are detected until 140 cm–1 with a good signal to noise. This new setup is promising to analyze the infrared spectral region where metal–ligand vibrations are expected to contribute and to extend the analysis of vibrational properties to metal sites or redox states not accessible to (resonance) Raman spectroscopy. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 363–367, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
The role of ARPC4 in tip growth and alignment of the polar axis in filaments of Physcomitrella patens
Authors: Perroud Pierre‐François , Quatrano Ralph S.
Published: February 2006

When the actin related protein 2/3 (Arp2/3) complex member arpc4 was deleted in Physcomitrella patens (moss), the resulting null mutant (Δarpc4) was viable and revealed no gross changes during morphogenesis of filaments into gametophores. However, we observed a striking reduction of filamentous tip growth, resulting in smaller, denser colonies. Although polar responses of Δarpc4 filaments to unilateral white light were unaffected, these mutant filaments were defective in their response to polarized white light. These observations strongly suggest a specific role of the Arp2/3 complex as a downstream target for signals regulating oriented tip growth. Insertion of YFP‐ARPC4 into Δarpc4 rescued the mutant phenotypes and localized ARPC4 exclusively to the tip cell of filaments, the site of actin dynamics and polarized growth. The ability of Δarpc4 to perform some but not all cellular responses will allow the study of its function in orientation of tip growth in response to directional cues (e.g. light) in a viable but mutated background. Cell Motil. Cytoskeleton 63: 2006. © 2006 Wiley‐Liss, Inc.
Quality of survival reporting in chemotherapy and surgery trials in patients with metastatic colorectal carcinoma
Authors: Martin Robert C. G. , Augenstein Vedra A. , Scoggins Charles R. , McMasters Kelly M.
Published: February 2006

BACKGROUND

Patients with metastatic colorectal carcinoma (MCC) to the liver receive conflicting management recommendations because of the lack of prospective randomized controlled trials (RCTs) clarifying the optimal management in this disease. The oabjective of the current study was to evaluate the reporting of prognostic factors in MCC from chemotherapy and surgery trials and evaluate the ability to compare these results across treatments.

METHODS

RCTs and retrospective series of greater than 75 MCC patients published between 1980–2004 were reviewed to identify 10 critical prognostic elements of overall survival reported in both types of journals.

RESULTS

A review 92 RCTs and 116 retrospective reports with 64,898 patients analyzed found 7 (3%) reporting all prognostic factors, with both studies demonstrating no difference in the success of reporting criteria met. The only criterion that was universally reported among both chemotherapy and surgery trials was the mortality rates of the study. All remaining prognostic factors in the evaluation of overall survival were significantly different between both chemotherapy and surgical studies. Considerable variation was observed in the disease‐free interval, number of hepatic metastases, size of hepatic metastases, and performance status, and were significantly different among some of the most significant factors for patients evaluating treatment: complication reporting, surgical margin evaluation, and overall response rate.

CONCLUSIONS

The reporting of results in MCC in chemotherapy trials and surgical reports is limited to general outcomes, with a paucity of prognostic factors, which hinders any ability to compare results across treatments. A mandatory reporting criteria of all metastatic colorectal trials is imperative to optimally manage these patients in both academic and community centers. Cancer 2006. © 2006 American Cancer Society.
Occult hepatitis B virus infection is associated with the development of hepatocellular carcinoma in chronic hepatitis C patients
Authors: Squadrito Giovanni , Pollicino Teresa , Cacciola Irene , Caccamo Gaia , Villari Daniela , La Masa Tiziana , Restuccia Tea , Cucinotta Eugenio , Scisca Claudio , Magazzu Domenico , Raimondo Giovanni
Published: February 2006

BACKGROUND

Occult hepatitis B virus (HBV) infection frequently occurs in patients with HBV surface antigen (HBsAg)‐negative chronic liver disease, and much evidence suggests that it is a risk factor for hepatocellular carcinoma (HCC) development. However, to the authors' knowledge, no follow‐up study has been performed to date evaluating HCC occurrence over time in chronic hepatitis patients with or without occult HBV infection.

METHODS

A cohort of the 380 HBsAg‐negative chronic hepatitis patients attending the study institution between 1991–2000 were evaluated and tested for occult HBV DNA by analysis of liver biopsy specimens.

RESULTS

There were 135 patients (35.5%) with occult HBV and 245 patients (64.5%) without occult HBV. Cirrhosis was significantly associated with occult HBV infection (P = 0.01). One hundred thirty‐four of these patients were followed for a minimum of 50 months (median, 82.8 ± 32.6 mos). Fifty‐three patients (39%) were occult HBV carriers and 81 (61%) were not. Nine patients developed HCC during the follow‐up; eight were positive and one was negative for occult HBV (P = 0.002).

CONCLUSIONS

The current observational cohort study showed that, among the HBsAg‐negative patients with chronic hepatitis, HCC develops for the most part in carriers of occult HBV. Therefore, the evaluation of HBV genomes in chronic hepatitis patients appears to be a powerful tool for the identification of individuals at higher risk of HCC development. Cancer 2006. © 2006 American Cancer Society.