bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenic cysteine mutations affect progranulin function and production of mature granulins
Authors: Wang Jun , Van Damme Philip , Cruchaga Carlos , Gitcho Michael A. , Vidal Jose Manuel , Seijo‐Martínez Manuel , Wang Lei , Wu Jane Y. , Robberecht Wim , Goate Alison 
Published: December 2009

J. Neurochem. (2010) 112, 1305–1315.AbstractFrontotemporal dementia with ubiquitin‐positive inclusions (FTLD‐U) can be caused by mutations in the progranulin gene (GRN). Progranulin (PGRN) is a cysteine‐rich growth factor, which is proteolytically cleaved by elastase to produce several granulins (GRNs). All FTLD‐U mutations in GRN characterized to date result in reduced secreted PGRN protein. We recently reported a Spanish family with progressive non‐fluent aphasia and dementia in which a novel C521Y mutation segregates with disease. A second cysteine mutation (C139R) has also been reported to be disease specific. Allele‐specific mRNA expression assays in brain reveal that the C521Y mutant allele is expressed at similar levels to the wild‐type allele. Furthermore, plasma PGRN levels in C521Y carriers are comparable with non‐carrier family relatives, suggesting that the mutation does not affect PGRN protein expression and secretion in vivo. Despite normal PGRN levels C521Y and C139R mutant GRNs show reduced neurite growth‐stimulating activity in vitro. Further study revealed that these mutations also cause impaired cleavage of PGRN by elastase. Our data suggest that these mutations affect the function of full‐length PGRN as well as elastase cleavage of PGRN into GRNs, leading to neurodegeneration.
Integrating species life‐history traits and patterns of deforestation in amphibian conservation planning
Authors: Becker C. G. , Loyola R. D. , Haddad C. F. B. , Zamudio K. R. 
Published: December 2009

AbstractAim  To identify priority areas for amphibian conservation in southeastern Brazil, by integrating species life‐history traits and patterns of deforestation.Location  State of São Paulo, Brazil.Methods  We used the software Marxan to evaluate different scenarios of amphibian conservation planning. Our approach differs from previous methods by explicitly including two different landscape metrics; habitat split for species with aquatic larvae, and habitat loss for species with terrestrial development. We evaluated the effect of habitat requirements by classifying species breeding habitats in five categories (flowing water, still water permanent, still water temporary, bromeliad or bamboo, and terrestrial). We performed analyses using two scales, grid cells and watersheds and also considered nature preserves as protected areas.Results  We found contrasting patterns of deforestation between coastal and inland regions. Seventy‐six grid cells and 14 watersheds are capable of representing each species at least once. When accounting for grid cells already protected in state and national parks and considering species habitat requirements we found 16 high‐priority grid cells for species with one or two reproductive habitats, and only one cell representing species with four habitat requirements. Key areas for the conservation of species breeding in flowing and permanent still waters are concentrated in southern state, while those for amphibians breeding in temporary ponds are concentrated in central to eastern zones. Eastern highland zones are key areas for preserving species breeding terrestrially by direct or indirect development. Species breeding in bromeliads and bamboos are already well represented in protected areas.Main conclusions  Our results emphasize the need to integrate information on landscape configuration and species life‐history traits to produce more ecologically relevant conservation strategies.
Ethanol‐Induced Oxidative Stress and Mitochondrial Dysfunction in Rat Placenta: Relevance to Pregnancy Loss
Authors: Gundogan Fusun , Elwood Gwen , Mark Princess , Feijoo Adrian , Longato Lisa , Tong Ming , De La Monte Suzanne M. 
Published: December 2009

Background:  Ethanol consumption during pregnancy increases the risk of early pregnancy loss and causes intrauterine growth restriction. We previously showed that chronic gestational exposure to ethanol impairs placentation, and that this effect is associated with inhibition of insulin and insulin growth factor signaling. Since ethanol also causes oxidative stress and DNA damage, we extended our investigations to assess the role of these pathological processes on placentation and placental gene expression.Methods:  Pregnant Long Evans rats were pair‐fed liquid diets containing 0% or 24% ethanol by caloric content. Placentas harvested on gestation day 16 were used to examine DNA damage, lipid peroxidation, apoptosis, mitochondrial gene/protein and hormonal gene expression in relation to ethanol exposure.Results:  Gestational exposure to ethanol increased fetal resorption, and trophoblast apoptosis/necrosis, oxidative stress, DNA damage, and lipid peroxidation. These adverse effects of ethanol were associated with increased expression of pro‐apoptotic (Bax and Bak) and reduced levels of the anti‐apoptotic Bcl‐2 protein. In addition, increased trophoblast apoptosis proneness was associated with p53‐independent activation of p21, reduced mitochondrial gene and protein expression, and dysregulated expression of prolactin (PRL) family hormones that are required for implantation and pregnancy‐related adaptations.Conclusions:  Chronic gestational exposure to ethanol increases fetal demise due to impaired survival and mitochondrial function, increased oxidative stress, DNA damage and lipid peroxidation, and dysregulated expression of prolactin family hormones in placental trophoblasts.
Betaine Protects Chronic Alcohol and ω‐3 PUFA‐Mediated Down‐Regulations of PON1 Gene, Serum PON1 and Homocysteine Thiolactonase Activities With Restoration of Liver GSH
Authors: Varatharajalu Ravi , Garige Mamatha , Leckey Leslie C. , Gong Maokai , Lakshman M. Raj 
Published: December 2009

Background:  Paraoxonase (PON1) is an antioxidant enzyme that prevents LDL oxidation as well as detoxifies homocysteine thiolactone (HCTL), both of which can cause atherosclerosis. Chronic alcohol (ETOH) and high ω‐3 polyunsaturated fatty acids (ω‐3 PUFA) consumption may affect PON1 status presumably via reactive oxygen species by depleting liver glutathione (GSH), whereas betaine may counter their effects. Therefore, we investigated the influence of ETOH, ω‐3 PUFA, and betaine on liver GSH, PON1 expression, lipid score, as well as serum PON1 and HCTLase activities.Methods:  Experimental rats belonging to various dietary groups were pair‐fed with Lieber‐DeCarli low (2.8% the dietary calories as ω3‐fatty acids) and high (13.8% the dietary calories as ω3‐fatty acids) menhaden fish alcohol‐liquid diets with and without betaine (10 g/l diet) for 8 weeks after which liver PON1 mRNA, GSH, lipid score, and serum PON1, HCTLase, and ALT activities were measured.Results:  High ω‐3 PUFA decreased liver PON1 mRNA expression, serum PON1, and HCTLase activity by 23% (p < 0.01), 20% (p < 0.05), and 28% (p < 0.05), respectively compared to the low ω‐3 PUFA group. ETOH decreased PON1 mRNA expression by 25 and 30% (p < 0.01) with concomitant 27% (p < 0.05) and 38% (p < 0.01), decrease in liver GSH levels in low and high ω‐3 PUFA groups, respectively. Correspondingly, serum PON1 activity decreased by 23% (p < 0.05) and 58% (p < 0.01) while serum HCTLase activity decreased by 25% (p < 0.05) and 59% (p < 0.01) in the low and high ω‐3 PUFA ETOH groups, respectively. Betaine restored liver PON1 mRNA expressions in low and high ω‐3 PUFA ETOH groups with parallel restorations of PON1 activity and liver GSH. Concomitantly, betaine reduced hepatosteatosis accompanied by alleviation of liver injury caused by chronic alcohol and high ω‐3 PUFA.Conclusions:  Based on these results, we conclude that dietary betaine not only atheroprotective by restoring liver GSH that quenches free radicals, but also may alleviate liver injury by reducing hepatosteatosis.
Synergistic action of the novel HSP90 inhibitor NVP‐AUY922 with histone deacetylase inhibitors, melphalan, or doxorubicin in multiple myeloma
Authors: Kaiser Martin , Lamottke Britta , Mieth Maren , Jensen Michael R. , Quadt Cornelia , Garcia‐Echeverria Carlos , Atadja Peter , Heider Ulrike , Von Metzler Ivana , Türkmen Seval , Sezer Orhan 
Published: December 2009

AbstractHeat shock protein 90 (HSP90) is a promising target for tumor therapy. The novel HSP90 inhibitor NVP‐AUY922 has preclinical activity in multiple myeloma, however, little is known about effective combination partners to design clinical studies. Multiple myeloma cell lines, OPM‐2, RPMI‐8226, U‐266, LP‐1, MM1.S, and primary myeloma cells were exposed to NVP‐AUY922 and one of the combination partners histone deacetylase inhibitor NVP‐LBH589, suberoylanilide hydroxamic acid (SAHA), melphalan, or doxorubicin, either simultaneously or in sequential patterns. Effects on cell proliferation and apoptosis were determined. Synergistic effects were evaluated using the method of Chou and Talalay. Combined sequential incubation with NVP‐AUY922 and SAHA showed that best synergistic effects were achieved with 24 h preincubation with SAHA followed by another 48 h of combination treatment. Combination of NVP‐AUY922 with SAHA, NVP‐LBH589, melphalan, or doxorubicin resulted in synergistic inhibition of viability, with strong synergy (combination index < 0.3) in the case of melphalan. Importantly, resistance of the RPMI‐8226 cell line and relative resistance of some primary myeloma cells against NVP‐AUY922 could be overcome by combination treatment. These data show impressive synergistic action of the novel HSP90 inhibitor NVP‐AUY922 with melphalan, doxorubicin, NVP‐LBH589, and SAHA in multiple myeloma and build the frame work for clinical trials.
Dizziness and vertigo in an older population: the Blue Mountains prospective cross‐sectional study
Authors: Gopinath B. , McMahon C.M. , Rochtchina E. , Mitchell P. 
Published: December 2009

Objectives:  We aimed to reassess the prevalence and personal burden of dizziness/vertigo, and to assess the relationship with hearing loss and tinnitus in older adults.Design:  Prospective cross‐sectional study.Setting:  Blue Mountains region, west of Sydney, Australia.Participants:  We examined 2751 of 2956 (aged 50+ years) Blue Mountains Hearing Study participants.Main outcome measures:  Audiologists screened participants for reported dizziness using a single question. Questions from the Dizziness Handicap Inventory were used to assess the impacts of dizziness/vertigo. Hearing impairment was determined as the pure‐tone average of audiometric hearing thresholds at 500, 1000, 2000 and 4000 Hz (PTA0.5–4 KHz), defining any hearing loss as PTA0.5–4 KHz >25 dB HL. Presence of tinnitus was assessed by a positive response to a single question. Quality of life was measured using the Short Form 36‐item Health Survey (SF‐36). Each SF‐36 dimension was scored from 0 (worst possible health state) to 100 (best possible health state).Results:  Prevalences of dizziness/vertigo, vestibular vertigo and non‐vestibular vertigo were 36.2%, 10.0% and 14.2%, respectively. Of the dizziness/vertigo reports, 27.7% and 39.3%, respectively, were attributed to vestibular and non‐vestibular vertigo. Tinnitus was associated with dizziness, odds ratio, OR, 1.99 (95% confidence interval, CI, 1.68–2.35). However, hearing loss was not associated with dizziness/vertigo. Participants reporting dizziness/vertigo had lower quality of life scores (P < 0.0001). Participants reporting vestibular vertigo were more likely than those with non‐vestibular vertigo to report higher DHI scale scores or a greater handicap.Conclusion:  Our findings highlight the burden imposed by dizziness, indicating dizziness/vertigo are important public health care issues. Clin. Otolaryngol. 2009, 34, 552–556.
Flood damage estimation beyond stage–damage functions: an Australian example
Authors: Middelmann‐Fernandes M.H. 
Published: December 2009

AbstractA number of factors influence the direct consequence of flooding. The most important are depth of inundation, velocity, duration of inundation and water quality and the interaction of these factors with human society. Although computer modelling techniques exist that can provide an estimate of these variables, this information is seldom used to estimate the impact of flooding on a community. This work describes the first step to improve this situation using data collected for the Swan River system in Perth, Western Australia. Here, it is shown that residential losses are underestimated when stage–damage functions or the velocity–stage–damage functions are used in isolation. This is because the functions are either limited to assessing partial damage or structural failure resulting from the movement of a house from its foundations. This demonstrates the need to use a combination of techniques to assess the direct cost of flooding.
Infection of Cell Lines with Experimental and Natural Ovine Scrapie Agents
Authors: Neale Michael H. , Mountjoy Susan J. , Edwards Jane C. , Vilette Didier , Laude Hubert , Windl Otto , Saunders Ginny C. 
Published: December 2009

ABSTRACT

Mouse bioassay remains the gold standard for determining proof of infectivity, strain type, and infectious titer estimation in prion disease research. The development of an approach using
ex vivo
cell-based assays remains an attractive alternative, both in order to reduce the use of mice and to hasten results. The main limitation of a cell-based approach is the scarcity of cell lines permissive to infection with natural transmissible spongiform encephalopathy strains. This study combines two advances in this area, namely, the standard scrapie cell assay (SSCA) and the Rov9 and MovS6 cell lines, which both express the ovine PrP VRQ allele, to assess to what extent natural and experimental ovine scrapie can be detected
ex vivo
. Despite the Rov9 and MovS6 cell lines being of different biological origin, they were both permissive and resistant to infection with the same isolates of natural sheep scrapie as detected by SSCA. Rov9 subclones that are 20 times more sensitive than Rov9 to SSBP/1-like scrapie infection were isolated, but all the subclones maintained their resistance to isolates that failed to transmit to the parental line. The most sensitive subclone of the Rov9 cell line was used to estimate the infectious titer of a scrapie brain pool (RBP1) and proved to be more sensitive than the mouse bioassay using wild-type mice. Increasing the sensitivity of the Rov9 cell line to SSBP/1 infection did not correlate with broadening susceptibility, as the specificity of permissiveness and resistance to other scrapie isolates was maintained.
Downregulation of a Chitin Deacetylase-Like Protein in Response to Baculovirus Infection and Its Application for Improving Baculovirus Infectivity
Authors: Jakubowska Agata K. , Caccia Silvia , Gordon Karl H. , Ferré Juan , Herrero Salvador 
Published: December 2009

ABSTRACT

Several expressed sequence tags (ESTs) with homology to chitin deacetylase-like protein (CDA) were selected from a group of
Helicoverpa armigera
genes whose expression changed after infection with
H. armigera
single nucleopolyhedrovirus (HearNPV). Some of these ESTs coded for a midgut protein containing a chitin deacetylase domain (CDAD). The expressed protein, HaCDA5a, did not show chitin deacetylase activity, but it showed a strong affinity for binding to chitin. Sequence analysis showed the lack of any chitin binding domain, described for all currently known peritrophic membrane (PM) proteins. HaCDA5a has previously been detected in the
H. armigera
PM. Such localization, together with its downregulation after pathogen infection, led us to hypothesize that this protein might be responsible for the homeostasis of the PM structure and that, by reduction of its expression, the insect may reduce PM permeability, decreasing the entrance of baculovirus. To test this hypothesis, we constructed a recombinant nucleopolyhedrovirus to express HaCDA5a in insect cells and tested its influence on PM permeability as well as the influence of HaCDA5a expression on the performance of the baculovirus. The experiments showed that HaCDA5a increased PM permeability, in a concentration-dependent manner. Bioassays on
Spodoptera frugiperda
and
Spodoptera exigua
larvae revealed that NPV expressing HaCDA5a was more infective than its parental virus. However, no difference in virulence was observed when the viruses were injected intrahemocoelically. These findings support the downregulation of a midgut-specific CDA-like protein as a possible mechanism used by
H. armigera
to reduce susceptibility to baculovirus by decreasing PM permeability.
Regulation of Porcine Endogenous Retrovirus Release by Porcine and Human Tetherins
Authors: Mattiuzzo Giada , Ivol Sabrina , Takeuchi Yasuhiro 
Published: December 2009

ABSTRACT
The risk of transmission of porcine endogenous retrovirus (PERV) is one of the major safety issues in xenotransplantation. Human tetherin, recently described as an antiviral protein able to inhibit the release of enveloped viruses, and its porcine homologue were shown to inhibit PERV release from producer cells, establishing themselves as candidate molecules to suppress PERV production in porcine xenografts by animal engineering.
Proteomic Analysis of Interactions between a Deep-Sea Thermophilic Bacteriophage and Its Host at High Temperature
Authors: Wei Dahai , Zhang Xiaobo 
Published: December 2009

ABSTRACTThe virus-host interaction is essential to understanding the role that viruses play in ecological and geochemical processes in deep-sea vent ecosystems. Virus-induced changes in cellular gene expression and host physiology have been studied extensively. However, the molecular mechanism of interaction between a bacteriophage and its host at high temperature remains poorly understood. In the present study, the virus-induced gene expression profile ofGeobacillussp. E263, a thermophile isolated from a deep-sea hydrothermal ecosystem, was characterized. Based on proteomic analysis and random arbitrarily primed PCR (RAP-PCR) ofGeobacillussp. E263 cultured under non-bacteriophage GVE2 infection and GVE2 infection conditions, there were two types of protein/gene profiles in response to GVE2 infection. Twenty differentially expressed genes and proteins were revealed that could be grouped into 3 different categories based on cellular function, suggesting a coordinated response to infection. These differentially expressed genes and proteins were further confirmed by Northern blot analysis. To characterize the host proteins in response to virus infection, aspartate aminotransferase (AST) was inactivated to construct the AST mutant ofGeobacillussp. E263. The results showed that the AST protein was essential in virus infection. Thus, transcriptional and proteomic analyses and functional analysis revealed previously unknown host responses to deep-sea thermophilic virus infection.
Where Does the Iberian Peninsula Moisture Come From? An Answer Based on a Lagrangian Approach
Authors: Gimeno Luis , Nieto Raquel , Trigo Ricardo M. , Vicente-Serrano Sergio M. , López-Moreno Juan Ignacio 
Published: December 2009

Abstract
This study investigated the main sources of moisture in the atmosphere over the Iberian Peninsula (IP) at annual and seasonal scales using FLEXPART, a powerful new 3D Lagrangian diagnosis method that identifies the humidity contributions to the moisture budget of a region. This method can identify moisture sources at lower cost and with greater accuracy than standard isotopic content methods. The results are based on back-tracking analysis of all air masses residing over the IP in the 5-yr period from 2000 to 2004. The results show that the two most important moisture source regions affecting the IP are in a tropical–subtropical North Atlantic corridor that extends from the Gulf of Mexico to the IP, and the IP itself and the surrounding Mediterranean. The importance of these two source areas varies throughout the year, and also with respect to different climatic regions inside the IP. The former source region is the dominant moisture source for the entire IP during winter and in western regions throughout the year, whereas the latter source region dominates the moisture supply to the IP in summer and in the eastern Mediterranean region of the IP throughout the year. The results also demonstrate that winter precipitation in the IP is influenced by both atmospheric instability that forces air masses to rise, and the supply of moisture from the tropical–subtropical North Atlantic corridor on a daily scale and a seasonal basis. Thus, a combination of high (low) moisture supply from the North Atlantic corridor and high (low) atmospheric instability appears to be responsible for the most recent wet (dry) winter in the IP.
Teaching Scholarship During The 1990s: A Study of Authorship in Teaching Sociology
Authors: Marx Jonathan , Eckberg Douglas 
Published: December 2009

While the scholarship of teaching has risen in prominence in the past few decades, little is presently known about the structure of knowledge creation and dissemination in that area of scholarship. Such basic facts as the characteristics of programs that perform and publish the research (e.g., B.A., M.A., or Ph.D.), or the identities of specific schools that are leaders in teaching scholarship remain undocumented. This article explores the topic through counts of articles and notes published in a major outlet in the scholarship of teaching, Teaching Sociology, during the decade of the 1990s. We address the following: (1) Does publication of teaching scholarship vary by the type of degree program (e.g., B.A., M.A., and Ph.D.) or by other characteristics? (2) Are some institutions centers of teaching scholarship? (3) How wide is the scope of teaching scholarship across the nation's departments? Overall, we find that a variety of sociology departments have established records of teaching publishing. Yet, some departments are leaders and appear to create a climate favorable to teaching scholarship. Jonathan Marx is professor of sociology at Winthrop University where he teaches courses in research methods, education, sport, organizations, and health. His most recent publications vary from a social history of science fairs to an examination of final gift exchange among the elderly. Douglas Eckberg is professor of sociology and Chair of the Department of Sociology and Anthropology at Winthrop University. He teaches a variety of courses and is convinced that research methods is the most fundamental course for developing critical thinking in students. He will be taking a sabbatical from teaching next year to pursue his strongest research interest–historical (nineteenth-century) southern homicide.
Role of ADAM and ADAMTS metalloproteinases in airway diseases
Authors: Paulissen Genevieve , Rocks Natacha , Gueders Maud M , Crahay Celine , Quesada-Calvo Florence , Bekaert Sandrine , Hacha Jonathan , El Hour Mehdi , Foidart Jean-Michel , Noel Agnes , Cataldo Didier D 
Published: December 2009

Abstract
Lungs are exposed to the outside environment and therefore to toxic and infectious agents or allergens. This may lead to permanent activation of innate immune response elements. A
Disintegrin And Metalloproteinases (ADAMs) and ADAMs with Thrombospondin motifs (ADAMTS) are proteinases closely related to Matrix Metalloproteinases (MMPs). These multifaceted molecules bear metalloproteinase and disintegrin domains endowing them with features of both proteinases and adhesion molecules. Proteinases of the ADAM family are associated to various physiological and pathological processes and display a wide spectrum of biological effects encompassing cell fusion, cell adhesion, "shedding process", cleavage of various substrates from the extracellular matrix, growth factors or cytokines... This review will focus on the putative roles of ADAM/ADAMTS proteinases in airway diseases such as asthma and COPD.