bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure‐Function Analysis of the Soluble Glycoprotein, sGP, of Ebola Virus
Authors: Falzarano Darryl , Krokhin Oleg , Wahl‐Jensen Victoria , Seebach Jochen , Wolf Kristin , Schnittler Hans‐Joachim , Feldmann Heinz
Published: September 2006

In addition to the transmembrane protein, GP1,2, the Ebola virus glycoprotein gene encodes the soluble glycoproteins sGP and Δ‐peptide. Two more soluble proteins, GP1 and GP1,2ΔTM, are generated from GP1,2 as a result of disulfide‐bond instability and proteolytic cleavage, respectively, and are shed from the surface of infected cells. The sGP glycoprotein is secreted as a disulfide‐linked homodimer, but there have been conflicting reports on whether it is arranged in a parallel or antiparallel orientation. Off‐line HPLC‐MALDI‐TOF MS (MS/MS) was used to identify the arrangement of all disulfide bonds and simultaneously determine site‐specific information regarding N‐glycosylation. Our data prove that sGP is a parallel homodimer that contains C53–C53’ and C306–C306’ disulfide bonds, and although there are six predicted N‐linked carbohydrate sites, only five are consistently glycosylated. The disulfide bond arrangement was confirmed by using cysteine to glycine mutations at amino acid positions 53 and 306. The mutants had a reduced ability to rescue the barrier function of TNF‐α‐treated endothelial cells—a function previously reported for sGP. This indicates that these disulfide bonds are critical for the proposed anti‐inflammatory function of sGP.
Efficient Charge Injection from the S2 Photoexcited State of Special‐Pair Mimic Porphyrin Assemblies Anchored on a Titanium‐Modified ITO Anode
Authors: Morisue Mitsuhiko , Haruta Noriko , Kalita Dipak , Kobuke Yoshiaki
Published: September 2006

A novel surface fabrication methodology has been accomplished, aimed at efficient anodic photocurrent generation by a photoexcited porphyrin on an ITO (indium–tin oxide) electrode. The ITO electrode was submitted to a surface sol–gel process with titanium n‐butoxide in order to deposit a titanium monolayer. Subsequently, porphyrins were assembled as monolayers on the titanium‐treated ITO surface via phosphonate, isophthalate, and thiolate groups. Slipped‐cofacial porphyrin dimers, the so‐called artificial special pair at the photoreaction center, were organized through imidazolyl‐to‐zinc complementary coordination of imidazolylporphyrinatozinc(II) units, which were covalently immobilized by ring‐closing olefin metathesis of allyl side chains. The modified surfaces were analyzed by means of X‐ray photoelectron spectroscopy. Photoirradiation of the porphyrin dimer generated a large anodic photocurrent in aqueous electrolyte solution containing hydroquinone as an electron sacrificer, due to the small reorganization energy of the dimer. The use of different linker groups led to significant differences in the efficiencies of anodic photocurrent generation. The apparent flat‐band potentials evaluated from the photocurrent properties at various pH values and under biased conditions imply that the band structure of the ITO electrode is modified by the anchoring species. The quantum yield for the anodic photocurrent generation by photoexcitation at the Soret band is increased to 15 %, a surprisingly high value without a redox cascade structure on the ITO electrode surface, while excitation at the Q band is not so significant. Extensive exploration of the photocurrent properties has revealed that hot injection of the photoexcited electron from the S2 level into the conduction band of the ITO electrode takes place before internal conversion to the S1* state, through the strong electronic communication of the phosphonyl anchor with the sol–gel‐modified ITO surface.
Therapeutic role of lymph node resection in endometrioid corpus cancer
Authors: Chan John K. , Cheung Michael K. , Huh Warner K. , Osann Kathryn , Husain Amreen , Teng Nelson N. , Kapp Daniel S.
Published: September 2006

BACKGROUND.

The purpose of the current study was to determine the potential therapeutic role of lymphadenectomy in women with endometrioid corpus cancer.

METHODS.

Demographic and clinicopathologic information were obtained from the Surveillance, Epidemiology, and End Results Program between 1988–2001. Data were analyzed using Kaplan‐Meier methods and Cox proportional hazards regression.

RESULTS.

In all, 12,333 women (median age, 64) underwent surgical staging with lymph node assessment, including 9,009, 1,211, 1,223, and 890 with Stage I‐IV disease. Over the time intervals 1988–1992, 1993–1997, and 1998–2001, the percentage of patients undergoing lymph node staging increased from 22.6%, 29.6%, to 40.9% (P < .001). In the intermediate/high‐risk patients (Stage IB, Grade 3; Stage IC and II‐IV, all grades), a more extensive lymph node resection (1, 2–5, 6–10, 11–20, and >20) was associated with improved 5‐year disease‐specific survivals across all 5 groups at 75.3%, 81.5%, 84.1%, 85.3%, and 86.8%, respectively (P < .001). For Stage IIIC‐IV patients with nodal disease, the extent of node resection significantly improved the survival from 51.0%, 53.0%, 53.0%, 60.0%, to 72.0%, (P < .001). However, no significant benefit of lymph node resection in low‐risk patients could be demonstrated (Stage IA, all grades; Stage IB, Grades 1 and 2 disease; P = .23). In multivariate analysis, a more extensive node resection remained a significant prognostic factor for improved survival in intermediate/high‐risk patients after adjusting for other factors including age, year of diagnosis, stage, grade, adjuvant radiotherapy, and the presence of positive nodes (P < .001).

CONCLUSIONS.

The findings of the current study suggest that the extent of lymph node resection improves the survival of women with intermediate/high‐risk endometrioid uterine cancer. Cancer 2006. © 2006 American Cancer Society.
Predictors of invasion in patients with core‐needle biopsy‐diagnosed ductal carcinoma in situ and recommendations for a selective approach to sentinel lymph node biopsy in ductal carcinoma in situ
Authors: Huo Lei , Sneige Nour , Hunt Kelly K. , Albarracin Constance T. , Lopez Adriana , Resetkova Erika
Published: September 2006

BACKGROUND

Among patients with core‐needle biopsy (CNB)‐diagnosed ductal carcinoma in situ (DCIS), the guidelines for the selection of patients to undergo sentinel lymph node (SLN) biopsy are not well defined, and many patients with no invasion undergo an unnecessary SLN biopsy. The objective of this study was to identify the predictors of invasion in patients with CNB‐diagnosed DCIS and, thus, to help determine the most appropriate candidates for SLN biopsy.

METHODS

The authors retrospectively evaluated 200 consecutive patients with CNB‐diagnosed DCIS who underwent final excision at their institution between May 1, 2002 and June 30, 2005. Demographic data, the size and type of lesion on imaging studies, histologic features of DCIS on CNB, the number of cores taken, and the number of cores involved by DCIS were correlated with invasion on excision and SLN biopsy outcome.

RESULTS

Forty‐one of 200 patients (21%) had invasive carcinoma diagnosed on final excision. Parameters that correlated with invasion were a mass lesion, lesion size >1.5 cm, high nuclear grade, and the presence of lobular cancerization on CNB. A multivariate logistic regression model was developed to predict invasion. At the time of breast surgery, 103 of 200 patients (52%) underwent SLN biopsy, and 34 had invasion diagnosed on final excision. Three patients had 1 positive SLN each.

CONCLUSIONS

A mass lesion, lesion size >1.5 cm, and the presence of lobular cancerization on CNB were significant, independent predictors of invasion in patients with DCIS. The authors recommended the inclusion of these predictors in the guidelines for selecting patients for SLN biopsy to reduce the number of unnecessary procedures. Cancer 2006. © 2006 American Cancer Society.
Quality‐of‐life and health benefits of early treatment of mild anemia
Authors: Straus David J. , Testa Marcia A. , Sarokhan Brenda J. , Czuczman Myron S. , Tulpule Anil , Turner Ralph R. , Riggs Shirley A.
Published: September 2006

BACKGROUND

Chemotherapy‐related anemia is prevalent among patients with hematologic malignancies. A randomized, open‐label, multicenter trial of early versus late epoetin alfa in this population was conducted, focusing on quality of life (QOL).

METHODS

Patients with non‐Hodgkin lymphoma, Hodgkin lymphoma, chronic lymphocytic leukemia, or multiple myeloma and baseline hemoglobin of 10 to 12 g/dL who were scheduled for ≥4 months of myelosuppressive chemotherapy were randomized to receive ≤16 weeks of epoetin alfa at a dose of 40,000 U once weekly immediately (early) or to wait and only receive epoetin alfa if hemoglobin decreased to <9 g/dL (late). Those patients with a hemoglobin level >12 g/dL after 3 chemotherapy cycles were not randomized. The primary endpoint was a mean change in the Functional Assessment of Cancer Therapy‐Anemia (FACT‐An) total.

RESULTS

In all, 269 patients with a hemoglobin level ≤12 g/dL were randomized. The mean total FACT‐An increased 3.84 (95% confidence interval [95% CI], 0.21–7.46) in early patients and decreased 4.37 (95% CI, −7.99 to −0.74) in late patients (P = .003). Early patients had significantly (P < .05) higher mean scores for total FACT‐General; FACT‐General physical and functional well‐being subscales, total anemia scale, and fatigue subscale; and daily activity, energy, and important activity Linear Analog Scale Assessment scales, as well as reduced bedrest days and restricted activity days. The mean hemoglobin increased 1.2 g/dL (95% CI, 0.98–1.46) in early patients but decreased 0.2 g/dL (95% CI, −0.32–0.12) in late patients (P < .0001). Adverse events were similar between groups (with fatigue being the most prevalent); clinically relevant thromboembolic events were more common in early patients.

CONCLUSIONS

Treating mild anemia immediately with epoetin alfa during chemotherapy for hematologic malignancy significantly improved QOL, productivity, and hemoglobin compared with delaying treatment until the hemoglobin level decreases to <9.0 g/dL. Cancer 2006. © 2006 American Cancer Society.
Survival of DA neurons is independent of CREM upregulation in absence of CREB
Authors: Parlato R. , Rieker C. , Turiault M. , Tronche F. , Schütz G.
Published: September 2006

cAMP response element binding protein (CREB) and the related factors CREM (cAMP response element modulator) and ATF1 (activation transcription factor 1) are bZIP‐domain‐containing transcription factors activated through cAMP and other signaling pathways. The disruption of CREB function in developing and mature neurons affects their development and survival when associated with loss of CREM. Since dopaminergic (DA) neurons are affected in several neurological diseases, we generated CREB conditional mutants in DA neurons by using a newly generated transgenic Cre line targeting the dopaminergic system (DATCre). Here we report the generation and analysis of mutant mice lacking CREB in DA neurons (CREBDATCre mutants). During adulthood, lack of CREB leads to a partial loss of DA neurons. Since CREM is upregulated in absence of CREB, we have introduced this mutation in a CREM−/− genetic background to assess a compensatory role of CREM. Additional inactivation of CREM does not lead to a more severe phenotype. genesis 44:454–464, 2006. © 2006 Wiley‐Liss, Inc.
Site‐specific recombination systems for the genetic manipulation of eukaryotic genomes
Authors: Thomson James G. , Ow David W.
Published: September 2006

Site‐specific recombination systems, such as the bacteriophage Cre‐lox and yeast FLP‐FRT systems, have become valuable tools for the rearrangement of DNA in higher eukaryotes. As a first step to expanding the repertoire of recombination tools, we screened recombination systems derived from the resolvase/invertase family for site‐specific recombinase activity in the fission yeast Schizosaccharomyces pombe. Here, we report that seven recombination systems, four from the small serine resolvase subfamily (CinH, ParA, Tn1721, and Tn5053) and three from the large serine resolvase subfamily (Bxb1, TP901‐1, and U153), can catalyze site‐specific deletion in S. pombe. Those from the large serine resolvase subfamily were also capable of site‐specific integration and inversion. In all cases, the recombination events were precise. Functional operation of these recombination systems in the fission yeast holds promise that they may be further developed as recombination tools for the site‐specific rearrangement of plant and animal genomes. genesis 44:465–476, 2006. Published 2006 Wiley‐Liss, Inc.
IL‐15 protects intestinal epithelial cells
Authors: Obermeier Florian , Hausmann Martin , Kellermeier Silvia , Kiessling Stefan , Strauch Ulrike G. , Duitman Erwin , Bulfone‐Paus Silvia , Herfarth Hans , Bock Jürgen , Dunger Nadja , Stoeck Michael , Schölmerich Jürgen , Falk Werner , Rogler Gerhard
Published: September 2006

IL‐15, a T‐cell growth factor, has been shown to be increased in inflammatory bowel disease (IBD). It has been suggested that neutralization of IL‐15 could protect from T cell‐dependent autoimmune inflammation. On the other hand, an anti‐apoptotic effect of IL‐15 has been demonstrated in kidney epithelial cells during nephritis. We therefore tested the role of IL‐15 in two different experimental models of colitisin vivo, and in models of intestinal epithelial cell (IEC) apoptosisin vitro. IL‐15 blockade in chronic dextran sulphate sodium‐induced colitis resulted in aggravation of the disease with a significantly 2.1‐fold increased epithelial damage score compared to controls. TUNEL staining clearly revealed increased apoptosis. IL‐6, TNF and IFN‐γ secretion by mesenteric lymph node cells were increased. In the T cell‐dependent SCID transfer model of colitis IL‐15 neutralization reduced the inflammatory infiltration and proinflammatory cytokine production. Despite that, the intestinal epithelial damage was not reduced.In vitro,IL‐15 pre‐incubation prevented up to 75% of CH11 antibody‐induced apoptosis in SW‐480 cells and reduced caspase‐3 activity. According to this, endogenously produced IL‐15 in chronic colitis does not only act as a proinflammatory cytokine but has at the same time the potential to reduce mucosal damage by preventing IEC apoptosis.
Structural requirements for initiation of cross‐reactivity and CNS autoimmunity with a PLP139–151 mimic peptide derived from murine hepatitis virus
Authors: Croxford J. Ludovic , Ercolini Anne M. , DeGutes Mathew , Miller Stephen D.
Published: September 2006

MS is an autoimmune CNS demyelinating disease in which infection appears to be an important pathogenic factor. Molecular mimicry, the cross‐activation of autoreactive T cells by mimic peptides from infectious agents, is a possible explanation for infection‐induced autoimmunity. Infection of mice with a non‐pathogenic strain of Theiler's murine encephalomyelitis virus (TMEV) engineered to express an epitope from Haemophilus influenzae (HI) sharing 6/13 amino acids with the dominant proteolipid protein (PLP) epitope, PLP139–151, can induce CNS autoimmune disease. Here we demonstrate that another PLP139–151 mimic sequence derived from murine hepatitis virus (MHV) which shares only 3/13 amino acids with PLP139–151 can also induce CNS autoimmune disease, but only when delivered by genetically engineered TMEV, not by immunization with the MHV peptide. Further, we demonstrate the importance of proline at the secondary MHC class II contact residue for effective cross‐reactivity, as addition of this amino acid to the native MHV sequence increases its ability to cross‐activate PLP139–151‐specific autoreactive T cells, while substitution of proline in the HI mimic peptide has the opposite effect. This study describes a structural requirement for potential PLP139–151 mimic peptides, and provides further evidence for infection‐induced molecular mimicry in the pathogenesis of autoimmune disease.
Inhibition of CD1d1‐mediated antigen presentation by the vaccinia virus B1R and H5R molecules
Authors: Webb Tonya J. Roberts , Litavecz Roberta A. , Khan Masood A. , Du Wenjun , Gervay‐Hague Jacquelyn , Renukaradhya Gourapura J. , Brutkiewicz Randy R.
Published: September 2006

Vaccinia virus (VV) has been most commonly used as the vaccine to protect individuals against the causative agent of smallpox (variola virus), but it also uses a number of strategies meant to evade or blunt the host's antiviral immune response. Natural killer T (NKT) cells are a subset of immunoregulatory CD1d‐restricted T lymphocytes believed to bridge the innate and adaptive immune responses. It is shown here that the VV‐encoded molecules, B1R and H5R, play a role in the ability of VV to inhibit CD1d‐mediated antigen presentation to NKT cells. These are the first poxvirus‐encoded molecules identified that can play such a role in the evasion of an important component of the innate immune response.
Kinetics of CD8+ effector T cell responses and induced CD4+ regulatory T cell responses during Friend retrovirus infection
Authors: Zelinskyy Gennadiy , Kraft Anke R. M. , Schimmer Simone , Arndt Tanja , Dittmer Ulf
Published: September 2006

Cytolytic CD8+ T cells are critical for the control of acute Friend virus (FV) infection yet they fail to completely eliminate the virus during chronic infection because they are functionally impaired by regulatory T cells (Treg). We performed a kinetic analysis of T cell responses during FV infection to determine when dysfunction of CD8+ T cells and suppressive activity of CD4+ regulatory T cells develops. At 1 week post infection, virus‐specific CD8+ T cells with effector phenotype and cytolytic potential expanded. Peak expansion was found at 12 days post infection, correlating with peak viral loads. After 2 weeks when viral loads dropped, numbers of activated CD8+ T cells started to decline. However, a population of virus‐specific CD8+ T cells with effector phenotype was still detectable subsequently, but these cells had lost their ability to produce granzymes and to degranulate cytotoxic molecules. Contemporaneous with the development of CD8+ T cell dysfunction, different CD4+ T cell populations expressing cell surface markers for Treg and the Treg‐associated transcription factor Foxp3 expanded. Transfer as well as depletion experiments indicated that regulatory CD4+ cells developed during the second week of FV infection and subsequently suppressed CD8+ T cell functions, which was associated with impaired virus clearance.
Direct Heterogeneous Electron Transfer Reactions of Trametes hirsuta Laccase at Bare and Thiol‐Modified Gold Electrodes
Authors: Shleev Sergey , Pita Marcos , Yaropolov Alexander I. , Ruzgas Tautgirdas , Gorton Lo
Published: September 2006

Direct electron transfer reactions of high redox potential Trametes hirsuta laccase on bare and 15 different thiol‐modified gold electrodes were studied using cyclic voltammetry and potentiometry. Well‐pronounced Faradaic processes were obtained for the enzyme adsorbed on bare gold, whereas reproducible and stable electrochemistry was obtained only when 4‐aminothiophenol was used for gold modification. Moreover, the laccase‐4‐aminothiophenol‐modified gold electrode showed the highest value of the steady‐state potential under aerobic conditions equal to 660 mV vs. NHE compared with the other 15 different thiol modified electrodes and also the bare electrodes with immobilized enzyme. However, this value is still too far away from the equilibrium potential of the oxygen electrode and Trametes hirsuta laccase‐modified graphite electrode, for which a well‐pronounced high potential process of oxygen bioelectroreduction is shown at 800 mV vs. NHE. Possible mechanisms of the enzyme function on bare and thiol‐modified gold electrodes are discussed in correlation with the structure and orientation of the enzyme on the surface of the various electrodes.
Nonfaradaic Impedance Probing of Potato Glycoalkaloids Interaction with Butyrylcholinesterase Immobilized onto Gold Electrode
Authors: Benilova Iryna V. , Soldatkin Alexey P. , Martelet Claude , Jaffrezic‐Renault Nicole
Published: September 2006

In this paper, we report the development of enzyme‐based nonfaradaic impedimetric biosensor for direct detection of potato glycoalkaloids α‐chaconine and α‐solanine. The sensors were prepared by cross‐linking of horse butyrylcholinesterase (BuChE) onto gold electrodes. Affinity interaction of both glycoalkaloids with immobilized BuChE caused an essential decrease of the total impedance and of the interfacial polarization resistance as well. No effect was observed after α‐chaconine contact with bovine serum albumin and bacterial carboxylesterase immobilized onto gold. BuChE‐modified electrodes were more sensitive to α‐chaconine, and found I50 values were in quite good agreement with those measured by biocatalytic ISFET‐based sensors.
SDS‐CGE of proteins in microchannels made of SU‐8 films
Authors: Agirregabiria Maria , Blanco Francisco Javier , Berganzo Javier , Fullaondo Asier , Zubiaga Ana María , Mayora Kepa , Ruano‐López Jesús M.
Published: September 2006

This work describes the SDS‐CGE of proteins carried out in microchannels made of the negative photoresist EPON SU‐8. Embedded electrophoretic microchannels have been fabricated with a multilayer technology based on bonding and releasing steps of stacked SU‐8 films. This technology allows the monolithic integration of the electrodes in the device. A high wafer fabrication yield and mass production compatibility guarantees low costs and high reliability. A poly(methyl methacrylate) (PMMA) packaging allows an easy setup and replacement of the device for electrophoresis experiments. In addition, the wire‐bonding step is avoided. The electrophoretic mobilities of four proteins have been measured in microchannels filled with polyacrylamide. Different pore sizes have been tested obtaining their Ferguson plots. Finally, a separation of two proteins (20 and 36 kDa) has been carried out confirming that this novel device is suitable for protein separation. A resolution of 2.75 is obtained. This is the first time that this SU‐8 microfluidic technology has been validated for SDS‐CGE of proteins. This technology offers better separation performance than glass channels, at lower costs and with an easy packaging procedure.
Microchannel‐Based Methods for Proteomics
Authors: Lee Cheng S.
Published: September 2006

No abstracts.
Glioblastoma‐derived tumorospheres identify a population of tumor stem‐like cells with angiogenic potential and enhanced multidrug resistance phenotype
Authors: Salmaggi Andrea , Boiardi Amerigo , Gelati Maurizio , Russo Annamaria , Calatozzolo Chiara , Ciusani Emilio , Sciacca Francesca Luisa , Ottolina Arianna , Parati Eugenio Agostino , La Porta Caterina , Alessandri Giulio , Marras Carlo , Croci Danilo , De Rossi Marco
Published: September 2006

We investigated in vitro the properties of selected populations of cancer stem‐like cells defined as tumorospheres that were obtained from human glioblastoma. We also assessed their potential and capability of differentiating into mature cells of the central nervous system. In vivo, their tumorigenicity was confirmed after transplantation into the brain of non‐obese diabetic/severe combined immunodeficient (NOD‐SCID) mice. The angiogenic potential of tumorospheres and glioblastoma‐derived cells grown as adherent cells was revealed by evaluating the release of angiogenic factors such as vascular endothelial growth factor and CXCL12 by ELISA, as well as by rat aortic ring assay. The proliferative response of tumorospheres in the presence of CXCL12 was observed for the first time. Multidrug resistance‐associated proteins 1 and 3 as well as other molecules conferring multidrug resistance were higher when compared with primary adherent cells derived from the same tumor. Finally, we obtained cells from the tumor developing after grafting that clearly expressed the putative neural stem cell marker CD133 as shown by FACS analysis and also nestin and CXCR4. The cells' positivity for glial fibrillary acidic protein was very low. Moreover these cells preserved their angiogenic potential. We conclude that human glioblastoma could contain tumor cell subsets with angiogenic and chemoresistance properties and that this chemoresistance potential is highly preserved by immature cells whereas the angiogenic potential is, to a higher extent, a property of mature cells. A better understanding of the features of these cell subsets may favor the development of more specifically targeted therapies. © 2006 Wiley‐Liss, Inc.
The Addenbrooke's Cognitive Examination Revised (ACE‐R): a brief cognitive test battery for dementia screening
Authors: Mioshi Eneida , Dawson Kate , Mitchell Joanna , Arnold Robert , Hodges John R.
Published: September 2006

There is a clear need for brief, but sensitive and specific, cognitive screening instruments as evidenced by the popularity of the Addenbrooke's Cognitive Examination (ACE).

Objectives

We aimed to validate an improved revision (the ACE‐R) which incorporates five sub‐domain scores (orientation/attention, memory, verbal fluency, language and visuo‐spatial).

Methods

Standard tests for evaluating dementia screening tests were applied. A total of 241 subjects participated in this study (Alzheimer's disease = 67, frontotemporal dementia = 55, dementia of Lewy Bodies = 20; mild cognitive impairment–MCI = 36; controls = 63).

Results

Reliability of the ACE‐R was very good (alpha coefficient = 0.8). Correlation with the Clinical Dementia Scale was significant (r = −0.321, p < 0.001). Two cut‐offs were defined (88: sensitivity = 0.94, specificity = 0.89; 82: sensitivity = 0.84, specificity = 1.0). Likelihood ratios of dementia were generated for scores between 88 and 82: at a cut‐off of 82 the likelihood of dementia is 100:1. A comparison of individual age and education matched groups of MCI, AD and controls placed the MCI group performance between controls and AD and revealed MCI patients to be impaired in areas other than memory (attention/orientation, verbal fluency and language).

Conclusions

The ACE‐R accomplishes standards of a valid dementia screening test, sensitive to early cognitive dysfunction. Copyright © 2006 John Wiley & Sons, Ltd.
Humour therapy in patients with late‐life depression or Alzheimer's disease: a pilot study
Authors: Walter Marc , Hänni Beat , Haug Myriam , Amrhein Isabelle , Krebs‐Roubicek Eva , Müller‐Spahn Franz , Savaskan Egemen
Published: September 2006

Background

Of the disabling disorders of the elderly, depression is the most common affective disorder and Alzheimer's disease (AD) the most common neurodegenerative disorder. Pharmacological treatment strategies for these disorders are often accompanied with severe side effects. Therefore non‐pharmacological treatment strategies are of great importance. The aim of the present study was to investigate the impact of humour therapy on quality of life in patients with depression or AD.

Methods

Twenty patients with late‐life depression and 20 patients with AD were evaluated. Ten patients in each group underwent a humour therapy group (HT) once in two weeks for 60 min in addition to standard pharmacotherapy, which was given as usual to the other group as standard therapy (ST). All patients completed a psychometric test battery at admission and before discharge from the clinic.

Results

The quality of life scores improved both in HT and ST groups for depressive patients but not for patients with AD irrespective of the therapy group. Depressive patients receiving HT showed the highest quality of life after treatment. In addition, patients with depression in both therapy groups showed improvements in mood, depression score, and instrumental activities of daily living.

Conclusions

Although there was no significant effect of humour therapy comparing with standard therapy on quality of life, these findings suggest that humour therapy can provide an additional therapeutic tool. Further studies with higher frequently humour groups are required in order to investigate the impact of humour therapy in gerontopsychiatric treatment. Copyright © 2006 John Wiley & Sons, Ltd.
Dementia and depression among nursing home residents in Lebanon: a pilot study
Authors: Chahine L. M. , Bijlsma A. , Hospers A. P. N. , Chemali Z.
Published: September 2006

Background

The proportion of elderly in the Lebanese population is 7.1% and this is expected to increase to 10.2% by the year 2025. The nursing home (NH) population in Lebanon has not been studied. The aim of this study was to investigate the prevalence of dementia and depression among a portion of nursing home residents (NHR) in Lebanon and describe the characteristics of NHR afflicted with dementia and depression.

Method

Of 200 NHR from three NH in Lebanon, 117 were selected by random sampling. Data on demographics and medical history were collected. An Arabic version of the Mini‐Mental Status Examination and Geriatric Depression Scale (GDS) were administered.

Results

Our final sample consisted of 102 NHR. Sixty‐one (59.8%) had dementia of some kind. Seventeen (27.9%) had mild dementia, 14 (22.9%) had moderate dementia, and 30 (49.2%) had severe dementia. Forty‐five (57.7%) of the NHR tested had depression as measured by a GDS score of more than 10.

Conclusions

Dementia and depression were present in more than half of the NHR in our sample. Our results have important implications, being the first to be collected in the Lebanese community. Screening NHR for dementia and depression on admission and at regular time intervals is a must. More studies targeting all aspects of the elderly population in Lebanon are needed. Copyright © 2006 John Wiley & Sons, Ltd.
Public health expenditure and spatial interactions in a decentralized national health system
Authors: Costa‐Font Joan , Pons‐Novell Jordi
Published: September 2006

One of the limitations of cross‐country health expenditure analysis refers to the fact that the financing, the internal organization and political restraints of health care decision‐making are country‐specific and heterogeneous. Yet, a way through is to examine the influence of such effects in those countries that have undertaken decentralization processes. In such a setting, it is possible to examine potential expenditure spillovers across the geography of a country as well as the influence of the political ideology of regional incumbents and institutional factors on public health expenditure. This paper examines the determinants of public health expenditure within Spanish region‐states (Autonomous Communities, ACs), most of them subject to similar financing structures although exhibiting significant heterogeneity as a result of the increasing decentralization, region‐specific political factors along with different use of health care inputs, economic dimension and spatial interactions. Copyright © 2006 John Wiley & Sons, Ltd.
Expected value of information and decision making in HTA
Authors: Eckermann Simon , Willan Andrew R.
Published: September 2006

Decision makers within a jurisdiction facing evidence of positive but uncertain incremental net benefit of a new health care intervention have viable options where no further evidence is anticipated to:

adopt the new intervention without further evidence;

adopt the new intervention and undertake a trial; or

delay the decision and undertake a trial.

Value of information methods have been shown previously to allow optimal design of clinical trials in comparing option (2) against option (1), by trading off the expected value and cost of sample information. However, this previous research has not considered the effect of cost of reversal on expected value of information in comparing these options. This paper demonstrates that, where a new intervention is adopted, the expected value of information is reduced under optimal decision making with costs of reversing decisions. Further, the paper shows that comparing expected net gain of optimally designed trials for option (2) vs (1) conditional on cost of reversal, and (3) vs (1) conditional on opportunity cost of delay allow systematic identification of an optimal decision strategy and trial design. Copyright © 2006 John Wiley & Sons, Ltd.
Elasticities of market shares and social health insurance choice in germany: a dynamic panel data approach
Authors: Tamm Marcus , Tauchmann Harald , Wasem Jürgen , Greß Stefan
Published: September 2006

In 1996, free choice of health insurers was introduced to the German social health insurance system. One objective was to increase efficiency through competition. A crucial precondition for effective competition among health insurers is that consumers search for lower‐priced health insurers. We test this hypothesis by estimating the price elasticities of insurers' market shares. We use unique panel data and specify a dynamic panel model to explain changes in market shares. Estimation results suggest that short‐run price elasticities are smaller than previously found by other studies. In the long‐run, however, estimation results suggest substantial price effects. Copyright © 2006 John Wiley & Sons, Ltd.
Are low ultraviolet B and high animal protein intake associated with risk of renal cancer?
Authors: Mohr Sharif B. , Gorham Edward D. , Garland Cedric F. , Grant William B. , Garland Frank C.
Published: September 2006

Incidence rates of kidney cancer are thought to be highest in places situated at high latitudes and in populations with high intake of energy from animal sources. This suggests that low 25‐hydroxyvitamin D status, due to lower levels of UVB irradiance, and energy from animal sources might be involved in etiology. The association of latitude with age‐adjusted incidence rates was determined for all 175 countries in a UN cancer database, GLOBOCAN. The independent association of UVB irradiance, cloud cover and intake of calories from animal sources with age‐adjusted incidence rates was assessed using multiple regression in 139 countries that provided dietary data. Renal cancer incidence rates were highest in countries situated at the highest latitudes, in men (R2 = 0.64, p < 0.01) and women (R2 = 0.63, p < 0.01). According to multivariate analysis in men, UVB irradiance was inversely associated with renal cancer incidence rates (p = 0.0003), while cloud cover (p = 0.003) and intake of calories from animal sources (p < 0.0001) were independently positively associated (R2 for model = 0.73, p < 0.0001). In women, UVB irradiance was inversely associated with incidence rates (p = 0.04), while total cloud cover (p = 0.0008) and calories from animal sources (p < 0.0001) were positively associated (R2 = 0.68, p < 0.0001). Lower levels of UVB irradiance and higher intakes of calories from animal sources were independently associated with higher incidence rates of kidney cancer. © 2006 Wiley‐Liss, Inc.
APC gene methylation is inversely correlated with features of the CpG island methylator phenotype in colorectal cancer
Authors: Iacopetta Barry , Grieu Fabienne , Li Wei , Ruszkiewicz Andrew , Caruso Maria , Moore James , Watanabe Goh , Kawakami Kazuyuki
Published: September 2006

The notion of a CpG island methylator phenotype (CIMP) was proposed to describe a subset of colorectal cancers (CRC) displaying frequent and concordant methylation of CpG islands located within gene promoter regions. Some workers have failed to observe associations between CIMP and specific clinicopathological features of CRC, possibly because of the choice of genes used to define this phenotype. The aim of the current study was to determine whether the aberrant methylation of 6 genes implicated in CRC development was associated with the same phenotypic features of this tumour type. The MethyLight assay was used to provide quantitative estimates of MLH1, P16, TIMP3, P14, DAPK and APC methylation levels in 199 unselected colorectal tumours. The methylation of MLH1, P16, TIMP3 and P14 was highly concordant (p < 0.0001 for each pair) but that of DAPK and APC was not. An inverse association was observed between the methylation of APC and TIMP3 (p = 0.004). Methylation of the MLH1, P16, TIMP3 and P14 genes was associated with tumour infiltrating lymphocytes (p < 0.05), microsatellite instability (p < 0.001), BRAF mutation (p < 0.0001) and elevated concentrations of the methyl group carriers tetrahydrofolate (THF) and 5,10‐methylene THF (p < 0.05). In contrast, APC methylation was associated with wildtype BRAF (p = 0.003) and with lower concentrations of methyl group carriers (p < 0.05). These findings highlight the importance of gene selection in studies that aim to characterize the biological features and clinical behaviour of CIMP+ tumours. © 2006 Wiley‐Liss, Inc.
The late Quaternary tephrostratigraphical record of the San Gregorio Magno basin (southern Italy)
Authors: Munno R. , Petrosino P.
Published: September 2006

Twenty‐one primary pyroclastic layers were found embedded in the lacustrine sediments of the San Gregorio Magno basin (Southern Apennines). These sand‐sized layers were characterised by a noticeable juvenile fragments content and by a sharp basal contact with the underlying clay and silt sediments. The tephra layers have been correlated with terrestrial counterparts from well‐known eruptive events of the Campanian volcanic area, or with reference layers from deep sea sediment cores and from the Monticchio maar sequence. The investigation of the San Gregorio Magno tephra layers made it possible to deduce that lacustrine sedimentation at San Gregorio Magno basin began before 170k yr BP and lasted at least until the emplacement of the Neapolitan Yellow Tuff, which occurred about 15k yr BP. The tephrochronology allowed determination of the varying sedimentation rate that occurred in the basin. Correlation of the lacustrine record with marine sequences has allowed development of a late Quaternary tephrostratotype for southern Italy. Copyright © 2006 John Wiley & Sons, Ltd.
Discrepancies in the characterization of the glass transition in thin films of hyperbranched polyesters
Authors: Serghei A. , Mikhailova Y. , Eichhorn K.‐J. , Voit B. , Kremer F.
Published: September 2006

The dynamic glass transition and the dilatometric glass transition temperature are simultaneously characterized in thin films of hyperbranched aromatic polyesters by broadband dielectric spectroscopy and capacitive scanning dilatometry. A diverging thickness dependence is detected: while the temperature position of the alpha relaxation peak Tα decreases by ∼30 K, the dilatometric Tg increases by ∼10 K with decreasing film thickness. This emphasizes the subtle character of the glass transition phenomenon—as manifested in the molecular dynamics and in the (structural) thermal expansion—and proves that, in contrast to the bulk, different experimental techniques do not necessarily deliver similar results in confinement. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 3006–3010, 2006
Comparison of multiple Amber force fields and development of improved protein backbone parameters
Authors: Hornak Viktor , Abel Robert , Okur Asim , Strockbine Bentley , Roitberg Adrian , Simmerling Carlos
Published: September 2006

The ff94 force field that is commonly associated with the Amber simulation package is one of the most widely used parameter sets for biomolecular simulation. After a decade of extensive use and testing, limitations in this force field, such as over‐stabilization of α‐helices, were reported by us and other researchers. This led to a number of attempts to improve these parameters, resulting in a variety of “Amber” force fields and significant difficulty in determining which should be used for a particular application. We show that several of these continue to suffer from inadequate balance between different secondary structure elements. In addition, the approach used in most of these studies neglected to account for the existence in Amber of two sets of backbone φ/ψ dihedral terms. This led to parameter sets that provide unreasonable conformational preferences for glycine. We report here an effort to improve the φ/ψ dihedral terms in the ff99 energy function. Dihedral term parameters are based on fitting the energies of multiple conformations of glycine and alanine tetrapeptides from high level ab initio quantum mechanical calculations. The new parameters for backbone dihedrals replace those in the existing ff99 force field. This parameter set, which we denote ff99SB, achieves a better balance of secondary structure elements as judged by improved distribution of backbone dihedrals for glycine and alanine with respect to PDB survey data. It also accomplishes improved agreement with published experimental data for conformational preferences of short alanine peptides and better accord with experimental NMR relaxation data of test protein systems. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Stereochemistry of guanidine–metal interactions: Implications for L‐arginine–metal interactions in protein structure and function
Authors: Di Costanzo Luigi , Flores Lloyd V. , Christianson David W.
Published: September 2006

The geometries of 150 guanidine–metal ion interactions retrieved from crystal structures deposited in the Cambridge Structural Database have been analyzed. Metal ions exhibit a preference for anti coordination stereochemistry in the plane of the unprotonated guanidine group, usually in chelate complexes with a diguanidine moiety, but syn‐oriented interactions are occasionally found for single guanidine–metal interactions. Three L‐arginine‐metal coordination interactions are found in metalloenzyme structures deposited in the Protein Data Bank: biotin synthase from E. coli, His‐67 → Arg human carbonic anhydrase I, and inactivated B. caldovelox arginase complexed with L‐arginine. In these proteins, L‐arginine‐metal coordination adopts syn/out‐of‐plane and anti/in‐plane coordination stereochemistry. The implications of these results for L‐arginine‐metal interactions in protein structure and function are discussed. Although such interactions are rare, this analysis serves as a useful reference point for the growing interest in enzymes containing L‐arginine residues that function as general bases or metal ligands. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Prediction of EF‐hand calcium‐binding proteins and analysis of bacterial EF‐hand proteins
Authors: Zhou Yubin , Yang Wei , Kirberger Michael , Lee Hsiau‐Wei , Ayalasomayajula Gayatri , Yang Jenny J.
Published: September 2006

The EF‐hand protein with a helix–loop–helix Ca2+ binding motif constitutes one of the largest protein families and is involved in numerous biological processes. To facilitate the understanding of the role of Ca2+ in biological systems using genomic information, we report, herein, our improvement on the pattern search method for the identification of EF‐hand and EF‐like Ca2+‐binding proteins. The canonical EF‐hand patterns are modified to cater to different flanking structural elements. In addition, on the basis of the conserved sequence of both the N‐ and C‐terminal EF‐hands within S100 and S100‐like proteins, a new signature profile has been established to allow for the identification of pseudo EF‐hand and S100 proteins from genomic information. The new patterns have a positive predictive value of 99% and a sensitivity of 96% for pseudo EF‐hands. Furthermore, using the developed patterns, we have identified zero pseudo EF‐hand motif and 467 canonical EF‐hand Ca2+ binding motifs with diverse cellular functions in the bacteria genome. The prediction results imply that pseudo EF‐hand motifs are phylogenetically younger than canonical EF‐hand motifs. Our prediction of Ca2+ binding motifs provides not only an insight into the role of Ca2+ and Ca2+‐binding proteins in bacterial systems, but also a way to explore and define the role of Ca2+ in other biological systems (calciomics). Proteins 2006. © 2006 Wiley‐Liss, Inc.
Molecular dynamics simulations of Hydrogenobacter thermophilus cytochrome c552: Comparisons of the wild‐type protein, a b‐type variant, and the apo state
Authors: Smith Lorna J. , Davies Robert J. , van Gunsteren Wilfred F.
Published: September 2006

Molecular dynamic simulations have been performed for wild‐type Hydrogenobacter thermophilus cytochrome c552, a b‐type variant of the protein, and the apo state with the heme prosthetic group removed. In the b‐type variant, Cys 10 and Cys 13 were mutated to alanine residues, and so the heme group was no longer covalently bound to the protein. Two 8‐ns simulations have been performed for each system at 298 and 360 K. The simulations of the wild‐type protein at 298 K show a very close agreement with experimental NMR data. A fluxional process involving the side chain of Met 59, which coordinates to the heme iron, is observed in accord with proposals from NMR studies. Overall, the structure and dynamical behavior of the protein during the simulations of the b‐type variant is closely similar to that of the wild‐type protein. However, side chains in the heme‐binding site show larger fluctuations in the b‐type variant simulation at 360 K. In addition, structural changes are seen for a number of residues close to the heme group, particularly Gly 22 and Ser 51. The simulations of the apo state show significant conformational changes for residues 50–59. These residues form a loop region, which packs over the heme group in the wild‐type protein and hydrogen bonds to the heme propionate groups. In the absence of heme, in the apo state simulations, these residues form short but persistent regions of β‐sheet secondary structure. These could provide nucleation sites for the conversion to amyloid fibrils. Proteins 2006. © 2006 Wiley‐Liss, Inc.
A novel high resolution CαCα distance dependent force field based on a high quality decoy set
Authors: Rajgaria R. , McAllister S. R. , Floudas C. A.
Published: September 2006

This work presents a novel CαCα distance dependent force field which is successful in selecting native structures from an ensemble of high resolution near‐native conformers. An enhanced and diverse protein set, along with an improved decoy generation technique, contributes to the effectiveness of this potential. High quality decoys were generated for 1489 nonhomologous proteins and used to train an optimization based linear programming formulation. The goal in developing a set of high resolution decoys was to develop a simple, distance‐dependent force field that yields the native structure as the lowest energy structure and assigns higher energies to decoy structures that are quite similar as well as those that are less similar. The model also includes a set of physical constraints that were based on experimentally observed physical behavior of the amino acids. The force field was tested on two sets of test decoys not in the training set and was found to excel on all the metrics that are widely used to measure the effectiveness of a force field. The high resolution force field was successful in correctly identifying 113 native structures out of 150 test cases and the average rank obtained for this test was 1.87. All the high resolution structures (training and testing) used for this work are available online and can be downloaded from http://titan.princeton.edu/HRDecoys. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Aggregation of small peptides studied by molecular dynamics simulations
Authors: Flöck Dagmar , Rossetti Giulia , Daidone Isabella , Amadei Andrea , Nola Alfredo Di
Published: September 2006

Peptides and proteins tend to aggregate under appropriate conditions. The amyloid fibrils that are ubiquitously found among these structures are associated with major human diseases like Alzheimer's disease, type II diabetes, and various prion diseases. Lately, it has been observed that even very short peptides like tetra and pentapeptides can form ordered amyloid structures. Here, we present aggregation studies of three such small polypeptide systems, namely, the two amyloidogenic peptides DFNKF and FF, and a control (nonamyloidogenic) one, the AGAIL. The respective aggregation process is studied by all‐atom Molecular Dynamics simulations, which allow to shed light on the fine details of the association and aggregation process. Our analysis suggests that naturally aggregating systems exhibit significantly diverse overall cluster shape properties and specific intermolecular interactions. Additional analysis was also performed on the previously studied NFGAIL system. Proteins 2006. © 2006 Wiley‐Liss, Inc.