bluuebunny/crossref_metadata_2025 huggingface dataset:
Peristaltic pumping and irreversibility of a Stokesian viscoelastic fluid
Authors: Teran Joseph , Fauci Lisa , Shelley Michael
Published: July 2008

Peristaltic pumping by wavelike contractions is a fundamental biomechanical mechanism for fluid and material transport and is used in the esophagus, intestine, oviduct, and ureter. While peristaltic pumping of a Newtonian fluid is well understood, in many important settings, as in the fluid dynamics of reproduction, the fluids have non-Newtonian responses. Here, we present a numerical method for simulating an Oldroyd-B fluid coupled to contractile, moving walls. A marker and cell grid-based projection method is used for the fluid equations and an immersed boundary method is used for coupling to a Lagrangian representation of the deforming walls. We examine numerically the peristaltic transport of a highly viscous Oldroyd-B fluid over a range of Weissenberg numbers and peristalsis wavelengths and amplitudes.
Measurement and validation of PbS nanocrystal energy levels
Authors: Dissanayake D. M. N. M. , Lutz T. , Curry R. J. , Silva S. R. P.
Published: July 2008

Cyclic voltammetry was used to measure PbS nanocrystal (PbS-NC) energy levels. Accuracy of these measurements was justified by electron transfer experiments, with well known fullerene derivatives, which included photoluminescence quenching experiments and current density-voltage measurements of hybrid photovoltaic devices. It is believed that these energy level measurements, carried out on PbS-NCs under ambient conditions, would provide valuable information for the design and fabrication of optimized hybrid nanoelectronic devices.
Photoinduced reentrant insulator-metal-insulator transitions in vanadium oxide nanotubes
Authors: Kweon Hyocheon , Lee Kyu Won , Lee Cheol Eui
Published: July 2008

We report photoinduced reentrant insulator-metal-insulator transitions in a low-dimensional nanoscale system of vanadium oxide nanotubes, a Mott insulator in the dark with no metal-insulator transitions. The nature of the spatially inhomogeneous intermediate metallic phase was elucidated by the photocurrent decay analysis of the system.
Design and integration of an all-in-one biomicrofluidic chip
Authors: Liu Liyu , Cao Wenbin , Wu Jinbo , Wen Weijia , Chang Donald Choy , Sheng Ping
Published: July 2008

We demonstrate a highly integrated microfluidic chip with the function of DNA amplification. The integrated chip combines giant electrorheological-fluid actuated micromixer and micropump with a microheater array, all formed using soft lithography. Internal functional components are based on polydimethylsiloxane (PDMS) and silver/carbon black-PDMS composites. The system has the advantages of small size with a high degree of integration, high polymerase chain reaction efficiency, digital control and simple fabrication at low cost. This integration approach shows promise for a broad range of applications in chemical synthesis and biological sensing/analysis, as different components can be combined to target desired functionalities, with flexible designs of different microchips easily realizable through soft lithography.
Production of Helicoverpa spp. (Lepidoptera, Noctuidae) from different refuge crops to accompany transgenic cotton plantings in eastern Australia
Authors: Baker Geoff H. , Tann Colin. R. , Fitt Gary P.
Published: July 2008

The adoption of transgenic (Bt) cotton varieties has markedly reduced feeding damage by noctuid pests, Helicoverpa armigera and H. punctigera, in Australian cotton crops. However, the potential for Bt resistance to evolve within these insect pests is a major concern. To reduce the likelihood of Bt resistance occurring, it is mandatory for growers of Bt cotton to also grow refuge crops which produce large numbers of Bt-susceptible moths. We present here findings from a series of field studies which sought to identify the relative Helicoverpa productivity of different refuge crop options. The abundance of Helicoverpa pupae (during the cotton season) was compared under crops of Ingard® (transgenic, single Bt gene) cotton, sprayed conventional cotton, and various unsprayed refuge crops (cotton, sorghum, maize, pigeon pea) from 1996 to 2003 in the major cotton-producing regions of northern New South Wales, plus St George and Dirranbandi in southern Queensland. Unsprayed, conventional cotton was used as the ‘control’ refuge in these studies. Productivity of adult Helicoverpa was estimated by surveying for pupae and discounting those that were parasitised and dead. Some supplementary experiments were also conducted to evaluate specific issues, in particular the value of additional refuge crops sown late in 2000–01 (due to accidental over-planting of Ingard® cotton that year) and the potential productivity of mixed plantings of various refuge crops which individually flowered at different times throughout the cotton season. Unsprayed refuges generally produced many more pupae than sprayed, conventional cotton and Ingard® cotton. Overall, pigeon pea, which has the advantage of prolonged flowering and thus on-going attractiveness to Helicoverpa, was the most reliable and productive refuge option, producing about twice as many pupae as unsprayed cotton. The seed mix refuge is perhaps a viable alternative option, although logistically more difficult for growers to adopt. Laboratory rearing of live pupae until moth emergence indicated that parasitism can be a substantial source of mortality in some refuge crops, especially sorghum. The most common parasitoid of Helicoverpa pupae was the ichneumonid wasp, Heteropelma scaposum. Such parasitism can greatly reduce productivity of adult Helicoverpa from refuges and needs to be taken into account when assessing relative refuge ‘value’, although such refuges will obviously contribute to the abundance of these beneficial species across the landscape.
Adaptation of sulla cultivars to contrasting Mediterranean environments
Authors: Annicchiarico P. , Abdelguerfi A. , Ben Younes M. , Bouzerzour H. , Carroni A. M. , Pecetti L. , Tibaoui G.
Published: July 2008

Sulla coronaria (L.) Choi & Ohashi (syn. Hedysarum coronarium L.) may become a major forage species in various Mediterranean-climate areas. This study aimed to assess the extent of genotype × environment (GE) interaction in the western Mediterranean region and its implications for breeding programmes. The milestone Italian varieties Grimaldi and Sparacia, one recent Italian variety, and the Tunisian cv. D’Italie (evolved under moderately favourable conditions from Italian germplasm introduced about 40 years ago) were evaluated in three environments of Tunisia (of which two were irrigated), two of Algeria, and one of Sardinia (Italy). Water available over the crop cycle (rainfall + possible irrigation from October 2004 to June 2006), ranging from 881 to 1906 mm, accounted for 85% of the variation among environments and 72% of the GE interaction variation for dry matter yield. The latter was adequately described by one-covariate factorial regression, which was preferable to joint regression and additive main effects and multiplicative interaction modelling. D’Italie was specifically adapted to environments with available water exceeding 1200 mm, Grimaldi was top-ranking between 950 and 1200 mm, and Sparacia below 950 mm. The crossover GE interaction between top-yielding material (P < 0.05) has implications for adaptation targets, genetic resources, selection environments, and opportunities for international co-operation between breeding programmes. It suggests breeding either for rainfed cropping in semi-arid or near semi-arid environments, or for definitely subhumid or irrigated environments.
Endothelial nitric oxide synthase regulates N-Ras activation on the Golgi complex of antigen-stimulated T cells
Authors: Ibiza Sales , Pérez-Rodríguez Andrea , Ortega Ángel , Martínez-Ruiz Antonio , Barreiro Olga , García-Domínguez Carlota A. , Víctor Víctor M. , Esplugues Juan V. , Rojas José M. , Sánchez-Madrid Francisco , Serrador Juan M.
Published: July 2008

Ras/ERK signaling plays an important role in T cell activation and development. We recently reported that endothelial nitric oxide synthase (eNOS)-derived NO regulates T cell receptor (TCR)-dependent ERK activation by a cGMP-independent mechanism. Here, we explore the mechanisms through which eNOS exerts this regulation. We have found that eNOS-derived NO positively regulates Ras/ERK activation in T cells stimulated with antigen on antigen-presenting cells (APCs). Intracellular activation of N-, H-, and K-Ras was monitored with fluorescent probes in T cells stably transfected with eNOS-GFP or its G2A point mutant, which is defective in activity and cellular localization. Using this system, we demonstrate that eNOS selectively activates N-Ras but not K-Ras on the Golgi complex of T cells engaged with APC, even though Ras isoforms are activated in response to NO from donors. We further show that activation of N-Ras involves eNOS-dependent
S
-nitrosylation on Cys
118
, suggesting that upon TCR engagement, eNOS-derived NO directly activates N-Ras on the Golgi. Moreover, wild-type but not C118S N-Ras increased TCR-dependent apoptosis, suggesting that
S
-nitrosylation of Cys
118
contributes to activation-induced T cell death. Our data define a signaling mechanism for the regulation of the Ras/ERK pathway based on the eNOS-dependent differential activation of N-Ras and K-Ras at specific cell compartments.
Calculation of site-specific carbon-isotope fractionation in pedogenic oxide minerals
Authors: Rustad James R. , Zarzycki Piotr
Published: July 2008

Ab initio
molecular dynamics and quantum chemistry techniques are used to calculate the structure, vibrational frequencies, and carbon-isotope fractionation factors of the carbon dioxide component [CO
2
(m)] of soil (oxy)hydroxide minerals goethite, diaspore, and gibbsite. We have identified two possible pathways of incorporation of CO
2
(m) into (oxy)hydroxide crystal structures: one in which the C
4+
substitutes for four H
+
[CO
2
(m)
A
] and another in which C
4+
substitutes for (Al
3+
,Fe
3+
) + H
+
[CO
2
(m)
B
]. Calculations of isotope fractionation factors give large differences between the two structures, with the CO
2
(m)
A
being isotopically lighter than CO
2
(m)
B
by ≈10 per mil in the case of gibbsite and nearly 20 per mil in the case of goethite. The reduced partition function ratio of CO
2
(m)
B
structure in goethite differs from CO
2
(g) by <1 per mil. The predicted fractionation for gibbsite is >10 per mil higher, close to those measured for calcite and aragonite. The surprisingly large difference in the carbon-isotope fractionation factor between the CO
2
(m)
A
and CO
2
(m)
B
structures within a given mineral suggests that the isotopic signatures of soil (oxy)hydroxide could be heterogeneous.
Lévy strategies in intermittent search processes are advantageous
Authors: Lomholt Michael A. , Tal Koren , Metzler Ralf , Joseph Klafter
Published: July 2008

Intermittent search processes switch between local Brownian search events and ballistic relocation phases. We demonstrate analytically and numerically in one dimension that when relocation times are Lévy distributed, resulting in a Lévy walk dynamics, the search process significantly outperforms the previously investigated case of exponentially distributed relocation times: The resulting Lévy walks reduce oversampling and thus further optimize the intermittent search strategy in the critical situation of rare targets. We also show that a searching agent that uses the Lévy strategy is much less sensitive to the target density, which would require considerably less adaptation by the searcher.
High-field fMRI unveils orientation columns in humans
Authors: Yacoub Essa , Harel Noam , Uğurbil Kâmil
Published: July 2008

Functional (f)MRI has revolutionized the field of human brain research. fMRI can noninvasively map the spatial architecture of brain function via localized increases in blood flow after sensory or cognitive stimulation. Recent advances in fMRI have led to enhanced sensitivity and spatial accuracy of the measured signals, indicating the possibility of detecting small neuronal ensembles that constitute fundamental computational units in the brain, such as cortical columns. Orientation columns in visual cortex are perhaps the best known example of such a functional organization in the brain. They cannot be discerned via anatomical characteristics, as with ocular dominance columns. Instead, the elucidation of their organization requires functional imaging methods. However, because of insufficient sensitivity, spatial accuracy, and image resolution of the available mapping techniques, thus far, they have not been detected in humans. Here, we demonstrate, by using high-field (7-T) fMRI, the existence and spatial features of orientation- selective columns in humans. Striking similarities were found with the known spatial features of these columns in monkeys. In addition, we found that a larger number of orientation columns are devoted to processing orientations around 90° (vertical stimuli with horizontal motion), whereas relatively similar fMRI signal changes were observed across any given active column. With the current proliferation of high-field MRI systems and constant evolution of fMRI techniques, this study heralds the exciting prospect of exploring unmapped and/or unknown columnar level functional organizations in the human brain.
Loss of p53 synthesis in zebrafish tumors with ribosomal protein gene mutations
Authors: MacInnes Alyson W. , Amsterdam Adam , Whittaker Charles A. , Hopkins Nancy , Lees Jacqueline A.
Published: July 2008

Zebrafish carrying heterozygous mutations for 17 different ribosomal protein (
rp
) genes are prone to developing malignant peripheral nerve sheath tumors (MPNSTs), a tumor type that is seldom seen in laboratory strains of zebrafish. Interestingly, the same rare tumor type arises in zebrafish that are homozygous for a loss-of-function point mutation in the tumor suppressor gene
p53
. For these reasons, and because
p53
is widely known to be mutated in the majority of human cancers, we investigated the status of p53 in the
rp
+/−
MPNSTs. Using monoclonal antibodies that we raised to zebrafish p53, we found that cells derived from
rp
+/−
MPNSTs are significantly impaired in their ability to produce p53 protein even in the presence of a proteasome inhibitor and γ-irradiation. Although the coding regions of the
p53
gene remain wild type, the gene is transcribed, and overall protein production rates appear normal in
rp
+/−
MPNST cells, p53 protein does not get synthesized. This defect is observed in all MPNSTs we examined that were derived from our 17 zebrafish lines with
rp
gene mutations. To date, studies of
p53
in malignancies have focused predominantly on either
p53
gene mutations or the aberrant posttranslational regulation of the p53 protein. Our results show that the appropriate amount of numerous ribosomal proteins is required for p53 protein production
in vivo
and that disruption of this regulation most likely contributes to tumorigenesis.
Estimating the Economic Impact of Natural and Social Disasters, with an Application to Hurricane Katrina
Authors: Baade Robert A. , Baumann Robert , Matheson Victor
Published: July 2008

This paper examines taxable sales in the Los Angeles and Miami metropolitan areas to find evidence of the short- and long-run effects of the Rodney King riots and Hurricane Andrew on their respective economies. The comparison of these two events shows that the King riots had a long-term negative effect on Los Angeles' economy while Hurricane Andrew had a short-term positive effect on the Miami economy. The paper also applies the contrasting experiences of Los Angeles and Miami to New Orleans following Hurricane Katrina. In some ways, Katrina is a hybrid of these two events since it combines elements of both a natural disaster and a social disaster. The paper examines how Katrina is similar to each of the previous incidents and how these similarities might affect the recovery of New Orleans following the storm.
Residents' Perceptions of their Neighbourhood: Disentangling Dissatisfaction, a French Survey
Authors: Pan Ké Shon Jean-Louis
Published: July 2008

To avoid the conventional and normative pitfalls of neighbourhood satisfaction scales, the responses to a non-inductive open question identified six statistical types of resident in France. The reasons for their satisfaction or dissatisfaction reflect both personal inclinations and characteristics of the neighbourhood. By controlling for these characteristics, for the local network of relationships, for the socio-demographic characteristics of the respondents and the social type of the neighbourhood, poor neighbourhoods stand apart in all six types of resident. The few reasons for contentment stem mainly from relationships with relatives and friends in the neighbourhood. The introduction of a socio-residential variable to categorise the neighbourhood socially clarifies residents' perceptions in terms of their social grade.
Modalities of the New Middle Class: Ideology and Behaviour in the Journey to Work from Gentrified Neighbourhoods in Canada
Authors: Danyluk Martin , Ley David
Published: July 2008

This study examines the relationship between gentrification and the transport mode selected for the journey to work. A review of surveys, ethnographies and electoral records shows a liberal and anti-suburban ideology associated with gentrification, including endorsement of sustainability and the public household. Consequently, one would expect to find non-automobile transport prevailing in gentrified districts. Data secured from the Census of Canada permit this proposition to be examined for the central cities of Toronto, Montreal and Vancouver. The results show some complexity, due in part to divisions internal to gentrified neighbourhoods. The most robust results reveal an overrepresentation of cycling to work in gentrified districts and, surprisingly in light of a putative left-liberal ideology, an underutilisation of public transport compared with other districts.
Sulfur Mustard-Induced Apoptosis in Hairless Guinea Pig Skin
Authors: Kan Robert K. , Pleva Christina M. , Hamilton Tracey A. , Anderson Dana R. , Petrali John P.
Published: July 2008

The present study was aimed to examine whether apoptosis is involved in the pathogenesis of sulfur mustard (SM)-induced basal cell death. Skin sites of the hairless guinea pig exposed to SM vapor for 8 minutes were harvested at 3, 6, 12, 24, and 48 hours postexposure. Immunohistochemical detection of basal cell apoptosis was performed using the ApopTag in situ apoptosis labeling kit. Only occasional apoptotic basal cells (BC) were observed in nonexposed and perilesional control sites. At lesional sites, apoptosis of BC was not detected at 3 hours postexposure. However, at 6 hours and 12 hours postexposure, 18% and 59% of BC were apoptotic, respectively. At 24 and 48 hours postexposure, individual apoptotic basal cells were not clearly recognizable due to necrosis. At the ultrastructural level, degenerating BC exhibited typical apoptotic morphology including nuclear condensation and chromatin margination. The results suggest that apoptotic cell death is a cytotoxic mechanism with the number of BC undergoing apoptosis significantly increasing from 6 to 12 hours postexposure. In addition, because necrosis is preferential at 24 hours postexposure, we believe that SM-induced cell death involves early apoptosis and late necrosis, which temporally overlap to produce a single cell death pathway along an apoptotic-necrotic continuum.
Involvement of bcl-2 and Caspase-3 in Apoptosis Induced by Cigarette Smoke Extract in the Gastric Epithelial Cell
Authors: Wang Hong Y. , Shin Vivian Y. , Leung Suet Y. , Yuen Siu T. , Cho Cho H.
Published: July 2008

Previous studies have shown that short-term passive cigarette smoking can increase apoptosis in rat gastric mucosa. However, the mechanism is not yet defined. Chloroform and ethanol extracts were used to investigate whether cigarette smoke could induce apoptosis in a human gastric epithelial cell line (AGS) as well as the roles of bcl-2, caspase-3, and cytochrome c in this process. AGS cell lines were treated with either chloroform extract (CE) or ethanol extract (EE) for 5 hours, and the level of bcl-2, the activity of caspase-3, and the level of cytosolic cytochrome c in these cells were determined. Time course studies on the effects of cigarette smoke extracts (CSEs) on DNA fragmentation and cytochrome c relocalization were also performed. Data showed that only CE induced apoptosis in a dose- and time-dependent manner in AGS cells, along with a decrease of bcl-2 and an increase of caspase-3 activity. Pretreatment with Z-DEVD-FMK (specific inhibitor of caspase-3) dose-dependently blocked the DNA fragmentation induced by the CE. Moreover, CE could time- and dose-dependently increase the level of cytochrome c in the cytoplasm, which might activate caspase-3. In conclusion, CSE triggers apoptosis in AGS cells through the inhibition of bcl-2 and the activation of a mitochondria-related pathway.
Murine Lethal Toxic Shock Caused by Intranasal Administration of Staphylococcal Enterotoxin B
Authors: Savransky Vladimir , Rostapshov Victor , Pinelis Dmitriy , Polotsky Yury , Korolev Sergey , Komisar Jack , Fegeding Konstantin
Published: July 2008

Currently available murine staphylococcal enterotoxin B (SEB) shock models require pretreatment with various agents to increase mouse sensitivity to SEB. This study was performed to show that C3H/HeJ mice are highly susceptible to intranasal SEB inoculation, which caused toxic shock without using pretreatment agents. For this purpose, mice were injected intranasally with different doses of SEB and observed for up to 1 month. The median lethal dose of SEB was determined using the probit procedure. Tissue samples were taken at different time points for histopathological examination. The LD50 was found at 1.6 μg/g (95% fiducial limit (f.l.) 0.7 to 2.2), the LD80 at 2.7 μg/g (95% f.l. 1.9 to 4.0) and the LD90 at 3.6 μg/g (95% f.l. 2.7 to 6.4). Histopathologic examination revealed pulmonary edema and bronchopneumonia. Mucosal-associated lymphoid tissue first became activated, followed by increasing lymphocyte apoptosis and depletion. In the liver there were intralobular and portal inflammatory foci with increasing lymphocyte apoptosis and degenerative necrosis. The splenic white pulp was characterized by early activation and subsequent depletion of lymphoid follicle germinal centers. The thymus initially was activated, followed by increasing apoptosis and migration of lymphoid cells from the cortex to the medulla. The pathological features detected in the mice were similar to those of rhesus monkeys treated with SEB aerosol challenge.
Microarray Analysis Using Amplified mRNA from Laser Capture Microdissection of Microscopic Hepatocellular Precancerous Lesions and Frozen Hepatocellular Carcinomas Reveals Unique and Consistent Gene Expression Profiles
Authors: Sun Hee Yim  , Ward Jerrold M. , Dragan Yvonne , Yamada Atsushi , Scacheri Peter C. , Kimura Shioko , Gonzalez Frank J.
Published: July 2008

The indirect labeling cDNA microarray technique was used to evaluate gene expression profiles of pure cell populations from frozen sections of carcinomas and adenomas harvested from precancerous hepatocellular lesions by using laser capture microdissection (LCM). The levels of differentially expressed genes were investigated using a cDNA microarray with 9,984 features with only 2 ug of two-round amplified aRNA, equivalent to 35 cells from LCM-adenomas and frozen samples of carcinomas from simian virus 40 (SV40) large T antigen transgenic rats. A total of 855 genes were identified as being 3-fold or more differentially expressed in carcinomas or adenomas as compared to normal tissue controls. Among these 855 genes, 71 genes were differentially expressed in both carcinomas and adenomas. Commonly up-regulated genes in both carcinoma and adenomas were 28 while 41 of the 71 genes were commonly down-regulated. Two genes, Igh1 (immunoglobulin heavy chain 1(Serum IgG2a), Image clone ID: 875880) and EST clone (AI893585, Image clone ID: 596604) were more than 7-fold up-regulated in carcinomas and 6-fold down-regulated in adenomas. In Cy5 and Cy3 reciprocal experiments for screening out false positive signals, the amplified carcinomas showed higher Pearson Correlation Coefficient values (-0.94 and -0.92) than the LCM-amplified adenoma samples (-0.79 and -0.84). LCM-amplified samples provided higher signal intensities over backgrounds and a greater average of Cy5:Cy3 ratios. Expression levels of mRNAs from selected genes, determined by using traditional dot blot analysis, revealed that 36 of 40 tested expression profiles were consistent with the microarray data. Thus, amplified aRNA harvested from homogeneous cell types using LCM can be applied to study gene expression profiles by use of microarray analysis.
Frequent Sampling Reveals Dynamic Responses by the Transcriptome to Routine Media Replacement in HepG2 Cells
Authors: Morgan Kevin T. , Casey Warren , Easton Marilyn , Creech Don , Hong Ni  , Yoon Lawrence , Anderson Steve , Qualls Charles W. , Crosby Lynn M. , Macpherson Alistair , Bloomfield Peter , Elston Timothy C.
Published: July 2008

Cultured cell lines are employed extensively for biological research. Large-scale differential gene expression (LSDGE) is being used to study mechanisms of toxicity in such cultures. `Normal' gene expression dynamics could have a major impact on the design and interpretation of these studies. In order to provide understanding of such dynamics, we investigated LSDGE responses to media replacement in human hepatoblastoma cells (HepG2) using 5-minute sampling frequencies for 6 hours post routine media replacement. Each mRNA transcript was found to exhibit a characteristic `operating range' based on signal intensity. Following media replacement, which replenishes nutrients (eg, glucose and glutamate) and removes excretory products (eg, lactate), a complex set of gene expression changes was observed. Some transcripts appeared to switch on from a quiescent state to a very active one (eg, CYP1A1), others exhibited `clocklike' oscillations (eg, asparagine synthetase), or a synchronous burst (chirp) of expression up regulation (eg, timeless). Mathematical analysis (Fourier Transform, Singular Value Decomposition, Wavelets, Phase Analysis) of oscillating expression patterns identified cycle lengths ranging from 11.8 to 210 minutes. There were prominent 36.5- and 17.4-minute cycles, for subsets of genes, and transcript-specific differences in phase angle with respect to these cycles. The functional consequences of these novel observations remain to be determined. It is clear that dense time-course studies provide a valuable approach to the investigation of physiological responses to nutrients, toxicants, and other environmental variables. This research also highlights the need for an understanding of biological dynamics when using cell culture systems.

An Excel data file representing individual transcripts from the respective Clontech cDNA arrays referred to in this article is available at http://taylorandfrancis.metapress.com/openurl.asp?genre=journal&issn=0192-6233. Rows represent data for individual transcripts and columns represent the time-points from 0 to 360 minutes. To access this file, click on the issue link for 31(4), then select this article. In order to access the full article online, you must either have an individual subscription or a member subscription accessed through www.toxpath.org.
Mono-Iodoacetate-Induced Histologic Changes in Subchondral Bone and Articular Cartilage of Rat Femorotibial Joints: An Animal Model of Osteoarthritis
Authors: Guzman Roberto E. , Evans Mark G. , Bove Susan , Morenko Brandy , Kilgore Kenneth
Published: July 2008

Osteoarthritis (OA) is a degenerative joint disease characterized by joint pain and a progressive loss of articular cartilage. Studies to elucidate the pathophysiology of OA have been hampered by the lack of a rapid, reproducible animal model that mimics both the histopathology and symptoms associated with the disease. Injection of mono-iodoacetate (MIA), an inhibitor of glycolysis, into the femorotibial joint of rodents promotes loss of articular cartilage similar to that noted in human OA. Here, we describe the histopathology in the subchondral bone and cartilage of rat (Wistar) knee joints treated with a single intra articular injection of MIA (1 mg) and sacrificed at 1, 3, 5, 7, 14, 28, and 56 days postinjection. Histologically, the early time points (days 1—7) were characterized by areas of chondrocyte degeneration/necrosis sometimes involving the entire thickness of the articular cartilage in the tibial plateaus and femoral condyles. Changes to the subchondral bone, as evidenced by increased numbers of osteoclasts and osteoblasts, were noted at by day 7. By 28 days, there was focal fragmentation and collapse of bony trabeculae with fibrosis and increased osteoclastic activity. By 56 days there were large areas of bone remodeling evidenced by osteoclastic bone resorption and newly formed trabeculae with loss of marrow hematopoietic cells. Subchondral cysts and subchondral sclerosis were present in some rats. In conclusion, intra-articular injection of MIA induces loss of articular cartilage with progression of subchondral bone lesions that mimic those of OA. This model offers a rapid and minimally invasive method to reproduce OA-like lesions in a rodent species.
Molecular Mechanisms of Renal Tissue Repair in Survival from Acute Renal Tubule Necrosis: Role of ERK1/2 Pathway
Authors: Vaidya Vishal S. , Shankar Kartik , Lock Edward A. , Dixon Darlene , Mehendale Harihara M.
Published: July 2008

Our earlier studies with S-(1,2-dichlorovinyl)-L-cysteine (DCVC) showed that prior administration of a low priming dose of 15 mg/kg, IP to mice, given 72 hours before administration of a normally lethal dose of DCVC (75 mg/kg, IP) led to renal tubule necrosis, however sustained renal tubule regeneration was observed and these mice recovered from renal failure and survived. The objective of the present study was to investigate the role of extracellular signal-regulated kinase (ERK) pathway in this autoprotection model. Following the priming dose of DCVC, IL-6 protein and mRNA increased markedly as early as 1 hour after dosing, peaking at 3 hours with a 1.5-fold increase in plasma. Immunocytochemistry on kidney sections using specific antibodies against TGF- α, HB-EGF, EGFr, IGF-1R β, Grb-2, and phospho-p44/42 MAP kinase (ERK1/2) revealed a significantly higher staining of these molecules 3 to 72 hours after dosing, indicating up regulation of the ERK pathway. Following a lethal dose of DCVC (75 mg/kg) the early increase in these signaling molecules was not sustained, being markedly reduced 24 and 36 hours after dosing, leading to inhibition of S-phase DNA synthesis, cell division and renal tubule repair. In contrast, prior treatment with a low dose of DCVC, followed by a high dose led to a sustained stimulation of the renal ERK pathway, renal tubule regeneration and recovery from acute renal failure. These results suggest that a sustained activation of the ERK1/2 pathway may be a key factor in enabling a continued renal tubule repair and hence protection from the progressive phase of DCVC-induced acute renal tubular necrosis in the mouse.
Carcinogenicity Evaluation: Comparison of Tumor Data from Dual Control Groups in the Sprague–Dawley Rat
Authors: Baldrick Paul
Published: July 2008

Following recent clarification in Europe that a single control group is now acceptable for rodent carcinogenicity studies, the use of dual controls may be reduced or disappear. To date, virtually nothing has been published on whether this latter situation has improved the identification of tumorigenic risk potential in these studies. In this paper, the results of 13 rat carcinogenicity studies, performed between 1991 and 2002, with 2 control groups, are presented. Although no major differences in tumor incidences between these dual control groups were found, some interstudy variation occurred. In cases where a notable difference was seen, the use of 2 control groups, as well as robust, contemporary background data, allowed an easier interpretation of findings in drug-treated groups. Thus, the continued use of dual control groups has a vital role in the assessment of tumoriogenic risk. The paper also presents an update on survival, on the range and extent of background spontaneous neoplasms, and comments on genetic drift in this commonly used rat strain.
Actin disassembly by cofilin, coronin, and Aip1 occurs in bursts and is inhibited by barbed-end cappers
Authors: Kueh Hao Yuan , Charras Guillaume T. , Mitchison Timothy J. , Brieher William M.
Published: July 2008

Turnover of actin filaments in cells requires rapid actin disassembly in a cytoplasmic environment that thermodynamically favors assembly because of high concentrations of polymerizable monomers. We here image the disassembly of single actin filaments by cofilin, coronin, and actin-interacting protein 1, a purified protein system that reconstitutes rapid, monomer-insensitive disassembly (Brieher, W.M., H.Y. Kueh, B.A. Ballif, and T.J. Mitchison. 2006. J. Cell Biol. 175:315–324). In this three-component system, filaments disassemble in abrupt bursts that initiate preferentially, but not exclusively, from both filament ends. Bursting disassembly generates unstable reaction intermediates with lowered affinity for CapZ at barbed ends. CapZ and cytochalasin D (CytoD), a barbed-end capping drug, strongly inhibit bursting disassembly. CytoD also inhibits actin disassembly in mammalian cells, whereas latrunculin B, a monomer sequestering drug, does not. We propose that bursts of disassembly arise from cooperative separation of the two filament strands near an end. The differential effects of drugs in cells argue for physiological relevance of this new disassembly pathway and potentially explain discordant results previously found with these drugs.
PIGS: automatic prediction of antibody structures
Authors: Marcatili Paolo , Rosi Alessandra , Tramontano Anna
Published: July 2008

Summary: We describe a web server for the automatic prediction of immunoglobulin variable domains based on the canonical structure model. The server is user-friendly and flexible. It allows the user to select the templates for the frameworks and the loops using different strategies. The final output is a full-fledged 3D model of the variable domains of the target immunoglobulin.

Availability: The server is openly accessible to academic users at the address: http://arianna.bio.uniroma1.it/pigs. It does not require registration and there is no limit to the number of sequences that can be submitted.

Contact:  anna.tramontano@uniroma1.it
Data-driven extraction of relative reasoning rules to limit combinatorial explosion in biodegradation pathway prediction
Authors: Fenner Kathrin , Gao Junfeng , Kramer Stefan , Ellis Lynda , Wackett Larry
Published: July 2008

Motivation: The University of Minnesota Pathway Prediction System (UM-PPS) is a rule-based expert system to predict plausible biodegradation pathways for organic compounds. However, iterative application of these rules to generate biodegradation pathways leads to combinatorial explosion. We use data from known biotransformation pathways to rationally determine biotransformation priorities (relative reasoning rules) to limit this explosion.

Results: A total of 112 relative reasoning rules were identified and implemented. In one prediction step, i.e. as per one generation predicted, the use of relative reasoning decreases the predicted biotransformations by over 25% for 50 compounds used to generate the rules and by about 15% for an external validation set of 47 xenobiotics, including pesticides, biocides and pharmaceuticals. The percentage of correctly predicted, experimentally known products remains at 75% when relative reasoning is used. The set of relative reasoning rules identified, therefore, effectively reduces the number of predicted transformation products without compromising the quality of the predictions.

Availability: The UM-PPS server is freely available on the web to all users at the time of submission of this manuscript and will be available following publication at http://umbbd.msi.umn.edu/predict/.

Contact:  kathrin.fenner@eawag.ch

Supplementary information:  Supplementary data are available at Bioinformatics online.
Sensitivity of predicted cohort size and catches to errors in estimates of fishing mortality in the terminal year
Authors: Horbowy Jan
Published: July 2008

Horbowy, J. 2008. Sensitivity of predicted cohort size and catches to errors in estimates of fishing mortality in the terminal year. – ICES Journal of Marine Science, 65: 1227–1234. Formulae for the sensitivity of projected cohort size and catches to errors (bias) in estimates of fishing mortality in the terminal year were developed. Assessment models allowing for random errors in the observed catches as well as models in which catches are treated as exact were considered. The formulae were applied to a Gulf of Riga (Baltic Sea) herring assessment to show how well they estimated prediction errors and to evaluate the effect of assessment errors on predictions. The errors propagate quickly with time, and the higher the fishing mortality, the bigger the projection error. The errors in predicted catches are somewhat lower than the errors in predicted cohort sizes. The formulae developed show that with moderate error in estimated fishing mortality (20%), the errors in predicted cohort size can reach 100%, and the errors in predicted catches may be 50% for fishing mortality estimated at 1.0 in the terminal year and the status quo prediction. As the Gulf of Riga herring case demonstrates, the overall error in predicted stock size and catches may be lower when terminal fishing mortality is underestimated at some ages and overestimated at others (cancelling effect).
The Evolution of DNA Regulatory Regions for Proteo-Gamma Bacteria by Interspecies Comparisons
Authors: Rajewsky Nikolaus , Socci Nicholas D. , Zapotocky Martin , Siggia Eric D.
Published: July 2008

The comparison of homologous noncoding DNA for organisms a suitable evolutionary distance apart is a powerful tool for the identification of cis regulatory elements for transcription and translation and for the study of how they assemble into functional modules. We have fit the three parameters of an affine global probabilistic alignment algorithm to establish the background mutation rate of noncoding seqeunce betweenE. coli and a series of gamma proteobacteria ranging from Salmonella to Vibrio. The lower bound we find to the neutral mutation rate is sufficiently high, even for Salmonella, that most of the conservation of noncoding sequence is indicative of selective pressures rather than of insufficient time to evolve. We then use a local version of the alignment algorithm combined with our inferred background mutation rate to assign a significance to the degree of local sequence conservation between orthologous genes, and thereby deduce a probability profile for the upstream regulatory region of all E. coli protein-coding genes. We recover 75%–85% (depending on significance level) of all regulatory sites from a standard compilation for E. coli, and 66%–85% of sigma sites.

We also trace the evolution of known regulatory sites and the groups associated with a given transcription factor. Furthermore, we find that approximately one-third of paralogous gene pairs in E. coli have a significant degree of correlation in their regulatory sequence. Finally, we demonstrate an inverse correlation between the rate of evolution of transcription factors and the number of genes they regulate. Our predictions are available athttp://www.physics.rockefeller.edu/∼siggia. [Online supplemental material available at http://www.genome.org.]
Recombination Rate and the Distribution of Transposable Elements in the Drosophila melanogaster Genome
Authors: Rizzon Carène , Marais Gabriel , Gouy Manolo , Biémont Christian
Published: July 2008

We analyzed the distribution of 54 families of transposable elements (TEs; transposons, LTR retrotransposons, and non-LTR retrotransposons) in the chromosomes of Drosophila melanogaster, using data from the sequenced genome. The density of LTR and non-LTR retrotransposons (RNA-based elements) was high in regions with low recombination rates, but there was no clear tendency to parallel the recombination rate. However, the density of transposons (DNA-based elements) was significantly negatively correlated with recombination rate. The accumulation of TEs in regions of reduced recombination rate is compatible with selection acting against TEs, as selection is expected to be weaker in regions with lower recombination. The differences in the relationship between recombination rate and TE density that exist between chromosome arms suggest that TE distribution depends on specific characteristics of the chromosomes (chromatin structure, distribution of other sequences), the TEs themselves (transposition mechanism), and the species (reproductive system, effective population size, etc.), that have differing influences on the effect of natural selection acting against the TE insertions.
Processed Pseudogenes of Human Endogenous Retroviruses Generated by LINEs: Their Integration, Stability, and Distribution
Authors: Pavlíček Adam , Pačes Jan , Elleder Daniel , Hejnar Jiří
Published: July 2008

We report here the presence of numerous processed pseudogenes derived from the W family of endogenous retroviruses in the human genome. These pseudogenes are structurally colinear with the retroviral mRNA followed by a poly(A) tail. Our analysis of insertion sites of HERV-W processed pseudogenes shows a strong preference for the insertion motif of long interspersed nuclear element (LINE) retrotransposons. The genomic distribution, stability during evolution, and frequent truncations at the 5′ end resemble those of the pseudogenes generated by LINEs. We therefore suggest that HERV-W processed pseudogenes arose by multiple and independent LINE-mediated retrotransposition of retroviral mRNA. These data document that the majority of HERV-W copies are actually nontranscribed promoterless pseudogenes. The current search for HERV-Ws associated with several human diseases should concentrate on a small subset of transcriptionally competent elements.

[Online supplementary material available at http://www.genome.org]
Determination of Redundancy and Systems Properties of the Metabolic Network of Helicobacter pylori Using Genome-Scale Extreme Pathway Analysis
Authors: Price Nathan D. , Papin Jason A. , Palsson Bernhard Ø.
Published: July 2008

The capabilities of genome-scale metabolic networks can be described through the determination of a set of systemically independent and unique flux maps called extreme pathways. The first study of genome-scale extreme pathways for the simultaneous formation of all nonessential amino acids or ribonucleotides in Helicobacter pylori is presented. Three key results were obtained. First, the extreme pathways for the production of individual amino acids inH. pylori showed far fewer internal states per external state than previously found in Haemophilus influenzae, indicating a more rigid metabolic network. Second, the degree of pathway redundancy in H. pylori was essentially the same for the production of individual amino acids and linked amino acid sets, but was approximately twice that of the production of the ribonucleotides. Third, the metabolic network of H. pyloriwas unable to achieve extensive conversion of amino acids consumed to the set of either nonessential amino acids or ribonucleotides and thus diverted a large portion of its nitrogen to ammonia production, a potentially important result for pH regulation in its acidic habitat. Genome-scale extreme pathways elucidate emergent system-wide properties. Extreme pathway analysis is emerging as a potentially important method to analyze the link between the metabolic genotype and its phenotypes.
A Genome-Wide Screen for Normally Methylated Human CpG Islands That Can Identify Novel Imprinted Genes
Authors: Strichman-Almashanu Liora Z. , Lee Richard S. , Onyango Patrick O. , Perlman Elizabeth , Flam Folke , Frieman Matthew B. , Feinberg Andrew P.
Published: July 2008

DNA methylation is a covalent modification of the nucleotide cytosine that is stably inherited at the dinucleotide CpG by somatic cells, and 70% of CpG dinucleotides in the genome are methylated. The exception to this pattern of methylation are CpG islands, CpG-rich sequences that are protected from methylation, and generally are thought to be methylated only on the inactive X-chromosome and in tumors, as well as differentially methylated regions (DMRs) in the vicinity of imprinted genes. To identify chromosomal regions that might harbor imprinted genes, we devised a strategy for isolating a library of normally methylated CpG islands. Most of the methylated CpG islands represented high copy number dispersed repeats. However, 62 unique clones in the library were characterized, all of which were methylated and GC-rich, with a GC content >50%. Of these, 43 clones also showed a CpGobs/CpGexp >0.6, of which 30 were studied in detail. These unique methylated CpG islands mapped to 23 chromosomal regions, and 12 were differentially methylated regions in uniparental tissues of germline origin, i.e., hydatidiform moles (paternal origin) and complete ovarian teratomas (maternal origin), even though many apparently were methylated in somatic tissues. We term these sequences gDMRs, for germline differentially methylated regions. At least two gDMRs mapped near imprinted genes, HYMA1 and a novel homolog of Elongin A and Elongin A2, which we termElongin A3. Surprisingly, 18 of the methylated CpG islands were methylated in germline tissues of both parental origins, representing a previously uncharacterized class of normally methylated CpG islands in the genome, and which we term similarly methylated regions (SMRs). These SMRs, in contrast to the gDMRs, were significantly associated with telomeric band locations (P = .0008), suggesting a potential role for SMRs in chromosome organization. At least 10 of the methylated CpG islands were on average 85% conserved between mouse and human. These sequences will provide a valuable resource in the search for novel imprinted genes, for defining the molecular substrates of the normal methylome, and for identifying novel targets for mammalian chromatin formation.

[The sequence data described in this paper have been submitted to the GenBank data library under accession nos.AF484557–AF484583.]
Damage Tolerance of Notched Composite Laminates with Reinforcing Strips
Authors: Qing Xinlin , Chang Fu-Kuo , Starnes James
Published: July 2008

An investigation was performed to study the effects of reinforcing strips on the notch strength and failure response of laminated composites. A three-dimensional finite element method 3DPDCOM which combined the commercial ABAQUS code with a progressive failure analysis was developed for the study. Composite specimens containing a cutout with or without unidirectional reinforcing strips were tested to verify the model predictions. The test data and numerical simulations proved to be in agreement with each other. Results showed that the notch strength and damage progression of composite laminates could be affected significantly by adding reinforcing strips in front of notches such as crack tips and cutouts. The change in notch strength strongly depended upon the geometry, properties, and bond strength of the reinforcing strips. The strips could significantly alter the failure progression and failure modes in composite plates.