bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Outcome of Henipavirus Infection in Hamsters Is Determined by the Route and Dose of Infection
Authors: Rockx Barry , Brining Douglas , Kramer Joshua , Callison Julie , Ebihara Hideki , Mansfield Keith , Feldmann Heinz
Published: May 2011

Nipah virus (NiV) and Hendra virus (HeV) are emerging zoonotic viruses and the causative agents of severe respiratory disease and encephalitis in humans. Little is known about the mechanisms that govern the development of respiratory and neurological disease. Using a hamster model of lethal NiV and HeV infection, we describe the role of the route and dose of infection on the clinical outcome and determine virus tropism and host responses following infection. Infection of hamster with a high dose of NiV or HeV resulted in acute respiratory distress. NiV initially replicated in the upper respiratory tract epithelium, whereas HeV initiated infection primarily in the interstitium. In contrast, infection with a low dose of NiV or HeV resulted in the development of neurological signs and more systemic spread of the virus through involvement of the endothelium. The development of neurological signs coincided with disruption of the blood-brain barrier (BBB) and expression of tumor necrosis alpha (TNF-α) and interleukin 1 β (IL-1β). In addition, interferon-inducible protein 10 (IP-10) was identified as playing an important role in NiV and HeV pathogenesis. These studies reveal novel information on the development and progression of NiV and HeV clinical disease, provide a mechanism for the differences in transmission observed between NiV and HeV outbreaks, and identify specific cytokines and chemokines that serve as important targets for treatment.
A Tyr Residue in the Reverse Transcriptase Domain Can Mimic the Protein-Priming Tyr Residue in the Terminal Protein Domain of a Hepadnavirus P Protein
Authors: Beck Jürgen , Nassal Michael
Published: May 2011

Hepadnaviruses are the only known viruses that replicate by protein-primed reverse transcription. Beyond the conserved reverse transcriptase (RT) and RNase H domains, their polymerases (P proteins) carry a unique terminal protein (TP) domain that provides a specific Tyr residue, Tyr96 in duck hepatitis B virus (DHBV), to which the first nucleotide of minus-strand DNA is autocatalytically attached and extended by three more nucleotides.In vitroreconstitution of this priming reaction with DHBV P protein and cellular chaperones had revealed strict requirements for the Dε RNA stem-loop as a template and for catalytic activity of the RT domain plus RNA-binding competence of the TP domain. Chaperone dependence can be obviated by using a truncated P protein (miniP). Here, we found that miniP with a tobacco etch virus (TEV) protease cleavage site between TP and RT (miniPTEV) displayed authentic priming activity when supplied with α-32P-labeled deoxynucleoside triphosphates; however, protease cleavage revealed, surprisingly, that the RT domain was also labeled. RT labeling had identical requirements as priming at Tyr96 and originated from dNMP transfer to a unique Tyr residue identified as Tyr561 in the presumed RT primer grip motif. Mutating Tyr561 did not affect Tyr96 primingin vitroand only modestly reduced replication competence of an intact DHBV genome; hence, deoxynucleotidylated Tyr561 is not an obligate intermediate in TP priming. However, as a first alternative substrate for the exquisitely complex protein-priming reaction, dNMP transfer to Tyr561 is a novel tool to further clarify the mechanism of hepadnaviral replication initiation and suggests that specific priming inhibitors can be found.
Cryptic Protein Priming Sites in Two Different Domains of Duck Hepatitis B Virus Reverse Transcriptase for Initiating DNA Synthesis
In Vitro
Authors: Boregowda Rajeev K. , Lin Li , Zhu Qin , Tian Fang , Hu Jianming
Published: May 2011

Initiation of reverse transcription in hepadnaviruses is accomplished by a unique protein-priming mechanism whereby a specific Y residue in the terminal protein (TP) domain of the viral reverse transcriptase (RT) acts as a primer to initiate DNA synthesis, which is carried out by the RT domain of the same protein. When separate TP and RT domains from the duck hepatitis B virus (DHBV) RT protein were tested in a
trans
-complementation assay
in vitro
, the RT domain could also serve, unexpectedly, as a protein primer for DNA synthesis, as could a TP mutant lacking the authentic primer Y (Y96) residue. Priming at these other, so-called cryptic, priming sites in both the RT and TP domains shared the same requirements as those at Y96. A mini RT protein with both the TP and RT domains linked in
cis
, as well as the full-length RT protein, could also initiate DNA synthesis using cryptic priming sites. The cryptic priming site(s) in TP was found to be S/T, while those in the RT domain were Y and S/T. As with the authentic TP Y96 priming site, the cryptic priming sites in the TP and RT domains could support DNA polymerization subsequent to the initial covalent linkage of the first nucleotide to the priming amino acid residue. These results provide new insights into the complex mechanisms of protein priming in hepadnaviruses, including the selection of the primer residue and the interactions between the TP and RT domains that is essential for protein priming.
Virally Expressed Interleukin-10 Ameliorates Acute Encephalomyelitis and Chronic Demyelination in Coronavirus-Infected Mice
Authors: Trandem Kathryn , Jin Qiushuang , Weiss Kayla A. , James Britnie R. , Zhao Jingxian , Perlman Stanley
Published: May 2011

The absence of interleukin-10 (IL-10), a potent anti-inflammatory cytokine results in increased immune-mediated demyelination in mice infected with a neurotropic coronavirus (recombinant J2.2-V-1 [rJ2.2]). Here, we examined the therapeutic effects of increased levels of IL-10 at early times after infection by engineering a recombinant J2.2 virus to produce IL-10. We demonstrate that viral expression of IL-10, which occurs during the peak of virus replication and at the site of disease, enhanced survival and diminished morbidity in rJ2.2-infected wild-type B6 and IL-10−/−mice. The protective effects of increased IL-10 levels were associated with reductions in microglial activation, inflammatory cell infiltration into the brain, and proinflammatory cytokine and chemokine production. Additionally, IL-10 increased both the frequency and number of Foxp3+regulatory CD4 T cells in the infected central nervous system. Most strikingly, the ameliorating effects of IL-10 produced during the first 5 days after infection were long acting, resulting in decreased demyelination during the resolution phase of the infection. Collectively, these results suggest that the pathogenic processes that result in demyelination are initiated early during infection and that they can be diminished by exogenous IL-10 delivered soon after disease onset. IL-10 functions by dampening the innate or very early T cell immune response. Further, they suggest that early treatment with IL-10 may be useful adjunct therapy in some types of viral encephalitis.
Nipah Virus Uses Leukocytes for Efficient Dissemination within a Host
Authors: Mathieu Cyrille , Pohl Christine , Szecsi Judit , Trajkovic-Bodennec Selena , Devergnas Séverine , Raoul Hervé , Cosset François-Loïc , Gerlier Denis , Wild T. Fabian , Horvat Branka
Published: May 2011

Nipah virus (NiV) is a recently emerged zoonotic paramyxovirus whose natural reservoirs are several species of
Pteropus
fruit bats. NiV provokes a widespread vasculitis often associated with severe encephalitis, with up to 75% mortality in humans. We have analyzed the pathogenesis of NiV infection, using human leukocyte cultures and the hamster animal model, which closely reproduces human NiV infection. We report that human lymphocytes and monocytes are not permissive for NiV and a low level of virus replication is detected only in dendritic cells. Interestingly, despite the absence of infection, lymphocytes could efficiently bind NiV and transfer infection to endothelial and Vero cells. This lymphocyte-mediated transinfection was inhibited after proteolytic digestion and neutralization by NiV-specific antibodies, suggesting that cells could transfer infectious virus to other permissive cells without the requirement for NiV internalization. In NiV-infected hamsters, leukocytes captured and carried NiV after intraperitoneal infection without themselves being productively infected. Such NiV-loaded mononuclear leukocytes transfer lethal NiV infection into naïve animals, demonstrating efficient virus transinfection
in vivo
. Altogether, these results reveal a remarkable capacity of NiV to hijack leukocytes as vehicles to transinfect host cells and spread the virus throughout the organism. This mode of virus transmission represents a rapid and potent method of NiV dissemination, which may contribute to its high pathogenicity.
Virion Structure of Baboon Reovirus, a Fusogenic Orthoreovirus That Lacks an Adhesion Fiber
Authors: Yan Xiaodong , Parent Kristin N. , Goodman Russell P. , Tang Jinghua , Shou Jingyun , Nibert Max L. , Duncan Roy , Baker Timothy S.
Published: May 2011

Baboon reovirus (BRV) is a member of the fusogenic subgroup of orthoreoviruses. Unlike most other members of its genus, BRV lacks S-segment coding sequences for the outer fiber protein that binds to cell surface receptors. It shares this lack with aquareoviruses, which constitute a related genus and are also fusogenic. We used electron cryomicroscopy and three-dimensional image reconstruction to determine the BRV virion structure at 9.0-Å resolution. The results show that BRV lacks a protruding fiber at its icosahedral 5-fold axes or elsewhere. The results also show that BRV is like nonfusogenic mammalian and fusogenic avian orthoreoviruses in having 150 copies of the core clamp protein, not 120 as in aquareoviruses. On the other hand, there are no hub-and-spoke complexes attributable to the outer shell protein in the P2 and P3 solvent channels of BRV, which makes BRV like fusogenic avian orthoreoviruses and aquareoviruses but unlike nonfusogenic mammalian orthoreoviruses. The outermost “flap” domains of the BRV core turret protein appear capable of conformational variability within the virion, a trait previously unseen among other ortho- and aquareoviruses. New cDNA sequence determinations for the BRV L1 and M2 genome segments, encoding the core turret and outer shell proteins, were helpful for interpreting the structural features of those proteins. Based on these findings, we conclude that the evolution of ortho- and aquareoviruses has included a series of discrete gains or losses of particular components, several of which cross taxonomic boundaries. Gain or loss of adhesion fibers is one of several common themes in double-stranded RNA virus evolution.
Immune Mediators of Rotavirus Antigenemia Clearance in Mice
Authors: Marcelin Glendie , Miller Amber D. , Blutt Sarah E. , Conner Margaret E.
Published: May 2011

The immunological mediators that clear rotavirus antigenemia or viremia remain undefined. Immunodeficient mice and antibody transfer were used to test whether lymphocytes or rotavirus-specific serum antibodies are essential for resolving antigenemia. Clearance of antigenemia required lymphocytes, but neither T nor B lymphocytes were absolutely required. Transfer of convalescent-phase or nonneutralizing rotavirus-specific serum antibodies to the systemic compartment of severe-combined-immunodeficient (SCID) mice temporarily suppressed the onset or level of chronic rotavirus antigenemia. Our findings provide the first report demonstrating that clearance of rotavirus antigenemia and possibly viremia are mediated by multiple effector lymphocyte subsets and serum antibodies.
Transforming Growth Factor β-Induced Reactivation of Epstein-Barr Virus Involves Multiple Smad-Binding Elements Cooperatively Activating Expression of the Latent-Lytic SwitchBZLF1Gene
Authors: Iempridee Tawin , Das Shreyasi , Xu Iris , Mertz Janet E.
Published: May 2011

Transforming growth factor β (TGF-β) physiologically induces Epstein-Barr virus (EBV) lytic infection by activating the expression of EBV's latent-lytic switchBZLF1gene. Liang et al. (J. Biol. Chem.277:23345–23357, 2002) previously identified a Smad-binding element (SBE) within theBZLF1promoter, Zp; however, it accounts for only 20 to 30% of TGF-β-mediated activation of transcription from Zp. Here, we identified additional factors responsible for the rest of this activation. The incubation of EBV-positive MutuI cells with a TGF-β neutralizing antibody or inhibitors of the TGF-β type I receptor (TβRI) or Smad3 eliminated the TGF-β-induced reactivation of EBV. The coexpression of Smad2, Smad3, and Smad4 together with a constitutively active form of TβRI induced 15- to 25-fold transcription from Zp in gastric carcinoma AGS cells. By electrophoretic mobility shift assays, we identified four additional Smad-binding elements, named SBE2 to SBE5. Substitution mutations in individual SBEs reduced Smad-mediated activation of Zp by 20 to 60%; together, these mutations essentially eliminated it. Chromatin immunoprecipitation assays confirmed that Smad4 newly bound the Zp region of the EBV genome following the incubation of MutuI cells with TGF-β. SBE2 overlaps the ZEB-binding ZV silencing element of Zp. Depending upon posttranslational modifications, Smad4 either competed with ZEB1 for binding or formed a complex with ZEB1 on the Zp ZV element in a cell-free assay system. In transiently transfected cells, exogenously expressed ZEB1 inhibited Smad-mediated transcriptional activation from Zp. We conclude that TGF-β induces EBV lytic reactivation via the canonical Smad pathway by activatingBZLF1gene expression through multiple SBEs acting in concert.
Molecular Epidemiology and Phylogeny Reveal Complex Spatial Dynamics in Areas Where Canine Parvovirus Is Endemic
Authors: Clegg S. R. , Coyne K. P. , Parker J. , Dawson S. , Godsall S. A. , Pinchbeck G. , Cripps P. J. , Gaskell R. M. , Radford A. D.
Published: May 2011

Canine parvovirus type 2 (CPV-2) is a severe enteric pathogen of dogs, causing high mortality in unvaccinated dogs. After emerging, CPV-2 spread rapidly worldwide. However, there is now some evidence to suggest that international transmission appears to be more restricted. In order to investigate the transmission and evolution of CPV-2 both nationally and in relation to the global situation, we have used a long-range PCR to amplify and sequence the full VP2 gene of 150 canine parvoviruses obtained from a large cross-sectional sample of dogs presenting with severe diarrhea to veterinarians in the United Kingdom, over a 2-year period. Among these 150 strains, 50 different DNA sequence types (S) were identified, and apart from one case, all appeared unique to the United Kingdom. Phylogenetic analysis provided clear evidence for spatial clustering at the international level and for the first time also at the national level, with the geographical range of some sequence types appearing to be highly restricted within the United Kingdom. Evolution of the VP2 gene in this data set was associated with a lack of positive selection. In addition, the majority of predicted amino acid sequences were identical to those found elsewhere in the world, suggesting that CPV VP2 has evolved a highly fit conformation. Based on typing systems using key amino acid mutations, 43% of viruses were CPV-2a, and 57% CPV-2b, with no type 2 or 2c found. However, phylogenetic analysis suggested complex antigenic evolution of this virus, with both type 2a and 2b viruses appearing polyphyletic. As such, typing based on specific amino acid mutations may not reflect the true epidemiology of this virus. The geographical restriction that we observed both within the United Kingdom and between the United Kingdom and other countries, together with the lack of CPV-2c in this population, strongly suggests the spread of CPV within its population may be heterogeneously subject to limiting factors. This cross-sectional study of national and global CPV phylogeographic segregation reveals a substantially more complex epidemic structure than previously described.
The Diversity of Torque Teno Viruses:
In Vitro
Replication Leads to the Formation of Additional Replication-Competent Subviral Molecules
Authors: de Villiers Ethel-Michele , Borkosky Silvia S. , Kimmel Romana , Gunst Karin , Fei Jian-Wei
Published: May 2011

The family
Anelloviridae
comprises torque teno viruses (TTVs) diverse in genome structure and organization. The isolation of a large number of TTV genomes (TTV Heidelberg [TTV-HD]) of 26 TTV types is reported. Several isolates from the same type indicate sequence variation within open reading frame 1 (ORF1), resulting in considerably modified open reading frames. We demonstrate
in vitro
replication of 12 full-length genomes of TTV-HD in 293TT cells. Propagation of virus was achieved by several rounds of infections using supernatant and frozen whole cells of initially infected cells. Replication of virus was measured by PCR amplification and transcription analyses. Subgenomic molecules (μTTV), arising early during propagation and ranging in size from 401 to 913 bases, were cloned and characterized. Propagation of these μTTV in
in vitro
cultures was demonstrated in the absence of full-length genomes.
Fluorescence in situ hybridisation analysis of formalin-fixed paraffin-embedded tissue sections in the diagnostic work-up of non-Burkitt high grade B-cell non-Hodgkin's lymphoma: a single centre's experience
Authors: Foot Nicola J , Dunn Robert G , Geoghegan Helen , Wilkins Bridget S , Neat Michael J
Published: May 2011

Aims

In recent years the genetic aberrations associated with diffuse large B-cell lymphoma and the new subtype described in the 2008 revision of the WHO classification, ‘B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma’ have been increasingly well defined. Recurrent genetic abnormalities include rearrangements involvingMYC(8q24),BCL2(18q21) andBCL6(3q27); as the prognostic and therapeutic implications associated with these abnormalities are clarified their accurate identification at diagnosis is becoming increasingly critical. We describe our experience of using a panel of fluorescence in situ hybridisation (FISH) probes on formalin-fixed paraffin-embedded tissue sections in the diagnostic work-up of 162 patients with non-Burkitt high grade B-cell non-Hodgkin's lymphomas (HG-BNHL).

Methods

BCL6, IGH-BCL2andMYCstatus were determined prospectively in sequential patients presenting with HG-BNHL, with respect to the presence of rearrangements and copy number changes. Small numbers of samples were analysed retrospectively or were studied at relapse in previously untested patients.

Results

FISH analysis was successful in 160/162 (99%) cases, with abnormalities detected in 118/160 (74%).

Conclusions

FISH analysis of formalin-fixed paraffin-embedded tissue sections is a highly reproducible technique with an excellent success rate for the detection of genetic abnormalities which will play an increasingly important role in improving risk stratification of patients with HG-BNHL.
Resident education and quality of gross tissue examination practices of benign uteri
Authors: Ryan Margaret S , Smith Maxwell L , Grzybicki Dana M , Raab Stephen S
Published: May 2011

Introduction

In the USA, most anatomical pathology residency training is based on an apprenticeship model in which residents learn directly by watching more senior personnel and then performing the examination. The level and the effect of the standardisation of resident trainee gross tissue examination practices have not been extensively evaluated.

Methods

In this apprenticeship-based training programme, a retrospective report review was performed to measure the level of standardisation of gross description (for 11 mandatory descriptors) and tissue submission (for four mandatory sections) practices for uterine specimens removed for benign conditions (n=78). Practices were examined for significant relationships with error, turnaround time (TAT), resource utilisation and postgraduate year of resident (n=25) training.

Results

Residents provided mandatory descriptors from 23.1% to 93.6% of the time and submitted mandatory sections from 82.1% to 96.2% of the time. Cases submitted by less experienced residents had a longer TAT and were associated with more errors, measured by the necessity to submit additional tissues. Less experienced residents used greater resources (submitting 9.5 tissue cassettes per case) compared with more experienced residents (7.3 cassettes per case), and a statistically significant correlation was found between the number of cassettes submitted and TAT.

Conclusions

In this training programme, the model of apprenticeship training leads to less than optimal standardisation of gross examination practices, inefficiency, active errors and a high frequency of latent conditions leading to error.
The biology of micrometastases from uveal melanoma
Authors: Borthwick Nicola J , Thombs Jasmine , Polak Marta , Gabriel F Guy , Hungerford John L , Damato Bertil , Rennie Ian G , Jager Martine J , Cree Ian A
Published: May 2011

Background

The aim of this study was to investigate the possible causes of tumour latency in uveal melanoma primarily through the analysis of micrometastases in tissue obtained from donors postmortem. Various explanations have been proposed but there is no clear answer from animal studies and few human data. The main hypotheses may be divided into several areas—immunological control of metastatic cells, lack of angiogenesis within micrometastases and reduced cell turnover.

Methods

196 patients were recruited to the study between 2003 and 2007. Patients were invited to take part and their relatives agreed to postmortem examination of their liver and lungs in the event of their death, including tissue sampling to assess the presence of micrometastases and their biology. Metastatic cells were detected by immunohistochemistry using a pan-melanoma antibody reagent, and by quantitative reverse transcriptase (qRT)–PCR for three melanoma-associated genes (tyrosinase Melan-A, andgp100) and a housekeeping gene (HMBS/PBGD) in samples stored in RNAlater or as formalin-fixed paraffin-embedded tissue.

Results

22 deaths were investigated at autopsy as part of the study. Sixteen patients died with large deposits of metastatic melanoma, while six patients died of other causes. In addition, a liver resection for hepatic adenoma provided further tissue from a case without clinical evidence of metastasis. Metastatic melanoma cells were identified by immunohistochemistry of the liver samples in one case and by qRT–PCR in two further cases without macrometastases. There was no evidence of multicellular micrometastases sufficiently large to require angiogenesis and no associated inflammation was observed.

Conclusion

The most likely explanation for latency in this setting is the inability of uveal melanoma cells in metastatic sites to grow.
A Pilot Study of Qigong Practice and Upper Respiratory Illness in Elite Swimmers
Authors: Wright Peggy A. , Innes Kim E. , Alton John , Bovbjerg Viktor E. , Owens Justine E.
Published: May 2011

Upper respiratory tract infections (URIs) are a common complaint in competitive swimmers and can adversely affect performance. No intervention has yet been shown to reduce URI incidence in intensively trained athletes. The University of Virginia varsity swim team received three weeks of training in qigong for the purpose of reducing stress and improving health. Our primary objective was to assess the relationship between qigong practice and symptoms of URI during a time when swimmers would be at high URI risk. Secondary objectives were to assess degree of compliance with a qigong practice regimen, to evaluate differences between qigong practitioners and non-practitioners, and to determine the response-rate and reliability of a newly developed internet-based, self-report survey. The design was observational, cross-sectional, and prospective. Weekly data on cold and flu symptoms, concurrent health problems and medication use, and qigong practice were gathered for seven weeks. Retrospective information on health and qigong training response was also collected. Participants were 27 of the 55 members of the University of Virginia Swim Team in the Virginia Athletic Department. Main outcomes were measures of aggregated cold/flu symptoms and Qigong practice. Survey completion was 100%, with no missing data, and reliability of the instrument was acceptable. Cold and flu symptoms showed a significant non-linear association with frequency of qigong practice (R2 = 0.33, p < 0.01), with a strong, inverse relationship between practice frequency and symptom scores in swimmers who practised qigong at least once per week (R2 = 0.70, p < 0.01). Qigong practitioners did not differ from non-practitioners in demographic or lifestyle characteristics, medical history, supplement or medication use, or belief in qigong. These preliminary findings suggest that qigong practice may be protective against URIs among elite swimmers who practice at least once per week.
Diosgenin Ameliorates Cognition Deficit and Attenuates Oxidative Damage in Senescent Mice Induced by D-Galactose
Authors: Chiu Chuan-Sung , Chiu Yung-Jia , Wu Lung-Yuan , Lu Tsung-Chun , Huang Tai-Hung , Hsieh Ming-Tsuen , Lu Chung-Yen , Peng Wen-Huang
Published: May 2011

This study attempted to access the neuroprotective effect of diosgenin on the senescent mice induced by d-galactose (D-gal). The mice in the experiments were orally administered with diosgenin (1, 5, 25 and 125 mg/kg), for four weeks from the sixth week. The learning and memory abilities of the mice in Morris water maze test and the mechanism involved in the neuroprotective effect of diosgenin on the mice brain tissue were investigated.

Diosgenin (5, 25 and 125 mg/kg, p.o.) showed significantly improved learning and memory abilities in Morris water maze test compared to D-gal treated mice (200 mg/kg, ten weeks). Diosgenin also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the malondialdehyde (MDA) level in the brain of D-gal treated mice.

These results indicated that diosgenin has the potential to be a useful treatment for cognitive impairment. In addition, the memory enhancing effect of diosgenin may be partly mediated via enhancing endogenous antioxidant enzymatic activities.
The Protective Effect of Cassia obtusifolia on DSS-Induced Colitis
Authors: Kim Su-Jin , Kim Koh-Woon , Kim Dae-Seung , Kim Min-Cheol , Jeon Yong-Deok , Kim Se-Gun , Jung Hyun-Ju , Jang Hyeung-Jin , Lee Byung-Cheol , Chung Won-Seok , Hong Seung-Heon , Chung Seok-Hee , Um Jae-Young
Published: May 2011

Cassia obtusifolia (CO) has been traditionally used in Korea to treat eye inflammation, photophobia, and lacrimation. However, the regulatory effect and molecular mechanism of CO in intestinal inflammation has not been understood. In this study, we investigate the protective effect of CO in dextran sulfate sodium (DSS)-induced colitis. CO reduced clinical signs of DSS-induced colitis, including body weight loss, shortened colon length, and increased disease activity index. The results show that CO significantly suppressed the levels of interleukin (IL)-6 and expression of cyclooxygenase-2 in DSS-treated colon tissues. Additionally, we observed that CO reduced the activation of transcription nuclear factor-κB p65 in DSS-treated colon tissues. Taken together, these findings suggest that CO has improving effects on DSS-induced ulcerative colitis, which may explain its beneficial effect in the regulation of chronic intestinal inflammation.
Protective Effect of a Chrysanthemum indicum containing Formulation in Cadmium-Induced Ototoxicity
Authors: Kim Su-Jin , Myung Noh-Yil , Shin Bong-Gi , Lee Jeong-Han , So Hong-Seob , Park Rae-Kil , Um Jae-Young , Hong Seung-Heon
Published: May 2011

Chungshinchongyitang (CSCYT) is an herbal drug formula containing Chrysanthemum indicum and 13 other herbs used for treating auditory diseases. Irreversible hearing loss is a characteristic effect of a number of heavy metals. Cadmium ( Cd2+ ) is an environmental contaminant that causes a variety of adverse effects. In the present study, we investigate the protective effects of CSCYT against Cd2+ induced ototoxicity in vitro and ex vivo. The findings of this study show that CSCYT prevents the destruction of hair cell arrays induced by Cd2+ in the rat organ of Corti primary explants. CSCYT inhibited cell death, release of cytochrome c and generation of reactive oxygen species induced by Cd2+ in HEI-OC1 auditory cell line. In addition, we also demonstrated that CSCYT exerted its effect by modulating of apoptosis via the caspase-3 activation and extracellular signal-regulated kinase activation. These results are expected to improve the understanding of the pharmacological mechanism of CSCYT and aid in the development of potential therapeutic strategies against ototoxicity.
WAVES FOR A HYPERBOLIC KELLER–SEGEL MODEL AND BRANCHING INSTABILITIES
Authors: CERRETI FIAMMETTA , PERTHAME BENOÎT , SCHMEISER CHRISTIAN , TANG MIN , VAUCHELET NICOLAS
Published: May 2011

Recent experiments for swarming of the bacteria Bacillus subtilis on nutrient-rich media show that these cells are able to proliferate and spread out in colonies exhibiting complex patterns as dendritic ramifications. Is it possible to explain this process with a model that does not use local nutrient depletion?

We present a new class of models which is compatible with the experimental observations and which predict branching instabilities and does not use nutrient limitation. These conclusions are based on numerical simulations. The most complex of these models is also the biologically most accurate but the essential effects can also be obtained in simplified versions which are amenable to analysis. An example of instability mechanism is the transition from a shock wave to a rarefaction wave in a reduced two by two hyperbolic system.
AN IN VITRO CELL POPULATION DYNAMICS MODEL INCORPORATING CELL SIZE, QUIESCENCE, AND CONTACT INHIBITION
Authors: DUCROT ARNAUD , LE FOLL FRANK , MAGAL PIERRE , MURAKAWA HIDEKI , PASQUIER JENNIFER , WEBB GLENN F.
Published: May 2011

In this paper, we construct a model to describe the spatial motion of a monolayer of cells occupying a two-dimensional dish. By taking care of nonlocal contact inhibition, quiescence phenomenon, and the cell cycle, we derive porous media-like equation with nonlocal reaction terms. The first part of this paper is devoted to the construction of the model. In the second part we study the well-posedness of the model. We conclude the paper by presenting some numerical simulations of the model and we observe the formation of colonies.
QUALITATIVE PROPERTIES OF THE SOLUTIONS OF A NONLINEAR FLUX-LIMITED EQUATION ARISING IN THE TRANSPORT OF MORPHOGENS
Authors: CALVO JUAN , MAZÓN JOSÉ , SOLER JUAN , VERBENI MICHELA
Published: May 2011

In this paper we study some qualitative properties of the solutions of a nonlinear flux-limited equation arising in the transport of morphogens in biological systems. Questions related to the existence of steady states, the finite speed of propagating fronts or the regularization in the interior of the support are studied from analytical and numerical points of view.
MULTISCALE MODELING OF PSEUDOMONAS AERUGINOSA SWARMING
Authors: DU HUIJING , XU ZHILIANG , SHROUT JOSHUA D. , ALBER MARK
Published: May 2011

Experiments have shown that wild type P. aeruginosa swarms much faster than rhlAB mutants on 0.4% agar concentration surface. These observations imply that development of a liquid thin film is an important component of the self-organized swarming process. A multiscale model is presented in this paper for studying interplay of key hydrodynamical and biological mechanisms involved in the swarming process of P. aeruginosa. This model combines a liquid thin film equation, convection–reaction–diffusion equations and a cell-based stochastic discrete model. Simulations demonstrate how self-organized swarming process based on the microscopic individual bacterial behavior results in complicated fractal type patterns at macroscopic level. It is also shown that quorum sensing mechanism causing rhamnolipid synthesis and resulting liquid extraction from the substrate lead to the fast swarm expansion. Simulations also demonstrate formation of fingers (tendrils) at the edge of a swarm which have been earlier observed in experiments.
SHORT RANGE POTENTIAL SCHRÖDINGER SCATTERING
Authors: BOHM ARNO , GADELLA MANUEL , GOMEZ-CUBILLO FERNANDO , WICKRAMASEKARA SUJEEV
Published: May 2011

We review certain general properties of short range potential scattering and discuss eigenfunction expansions related to short range and spherically symmetric potentials. In the case of a square barrier potential with a hard core at the origin, we study resonance phenomena and construct Gamow vectors in the radial representation.
REMARKS ON THE MYERS-PERRY AND EINSTEIN–GAUSS–BONNET ROTATING SOLUTIONS
Authors: ANABALÓN ANDRES , DERUELLE NATHALIE , TEMPO DAVID , TRONCOSO RICARDO
Published: May 2011

The Kerr-type solutions of the five-dimensional Einstein and Einstein–Gauss–Bonnet equations look pretty similar when written in Kerr–Schild form. However the Myers-Perry spacetime is circular whereas the rotating solution of the Einstein–Gauss–Bonnet theory is not. We explore some consequences of this difference in particular regarding the (non)existence of Boyer–Lindquist-type coordinates and the extension of the manifold.
THE LOGIC BEHIND FEYNMAN'S PATHS
Authors: GARCÍA ÁLVAREZ EDGARDO T.
Published: May 2011

The classical notions of continuity and mechanical causality are left in order to reformulate the Quantum Theory starting from two principles: (I) the intrinsic randomness of quantum process at microphysical level, (II) the projective representations of symmetries of the system. The second principle determines the geometry and then a new logic for describing the history of events (Feynman's paths) that modifies the rules of classical probabilistic calculus. The notion of classical trajectory is replaced by a history of spontaneous, random and discontinuous events. So the theory is reduced to determining the probability distribution for such histories accordingly with the symmetries of the system. The representation of the logic in terms of amplitudes leads to Feynman rules and, alternatively, its representation in terms of projectors results in the Schwinger trace formula.
CHARACTERIZING SMOOTH ISOLATED BLACK HOLES
Authors: KOZAMEH CARLOS , MORESCHI OSVALDO M. , PÉREZ ALEJANDRO
Published: May 2011

We study the characterization and the main basic properties of smooth isolated black holes, which are defined below.
VARIABLE SPEED OF LIGHT THEORIES: A THERMODYNAMIC ANALYSIS OF PLANETARY AND WHITE DWARF PHENOMENA
Authors: SISTERNA PABLO D.
Published: May 2011

The thermodynamics of a scalar field interacting with a perfect fluid is studied, and observable consequences of the covariant variable speed of light (VSL) theory proposed by J. Magueijo are obtained. The first law of thermodyamics is modified as the scalar field becomes an additional thermodynamical variable. A recipe to obtain the modified equations of state is also obtained. After discussing the Newtonian limit and the non-relativistic hydrostatic equilibrium equation for the theory, the time-variation of the radius of Mercury induced by the variability of the speed of light (c), and the scalar contribution to the luminosity of white dwarfs are found. Using a bound for the change of that radius and combining it with an upper limit for the variation of the fine-structure constant, a bound on the time-variation of c is set. An independent bound is obtained from luminosity estimates for Stein 2015B.
SEISMIC BEHAVIOR OF A NEW TYPE OF STEEL–CONCRETE COMPOSITE RIGID CONNECTION
Authors: NIE X. , FAN J. S. , SHI Y. J.
Published: May 2011

The composite steel–concrete rigid frame bridge is composed of steel or composite girders connecting rigidly to RC piers, and has advantages of lower maintenance costs, faster construction, and higher resistance and ductility during an earthquake. In this paper, a new type of steel–concrete composite rigid connection is developed and studied by finite element analysis. The comparison with other types of connections shows that this new type of connection has a good structural performance from the confining of concrete by steel and preventing the buckling of steel by concrete.
EVACUATION BEHAVIOR IN THE 29 SEPTEMBER 2009 SAMOA ISLANDS REGION EARTHQUAKE TSUNAMI
Authors: OKUMURA YOSHIHIRO , HARADA KENJI , KAWATA YOSHIAKI
Published: May 2011

A large earthquake of Mw 8.0 occurred in Samoa Islands region in the early morning of 29 September 2009 (local time). A large tsunami generated by the earthquake hit Samoa, American Samoa, and Tonga. The field investigation on evacuation behavior was carried out in Tutuila Island, American Samoa. The death ratio was low against the tsunami magnitude. This feature of this disaster resulted from waveform of tsunami, land use, residents' call, mayor's call, and so on.
A DUAL-MODALITY OPTICAL BIOPSY APPROACH FOR IN VIVO DETECTION OF PROSTATE CANCER IN RAT MODEL
Authors: SHARMA VIKRANT , PATEL NIMIT , SHEN JINHUI , TANG LIPING , ALEXANDRAKIS GEORGE , LIU HANLI
Published: May 2011

Ultrasound-guided biopsy procedure for prostate cancer diagnosis, which is the current gold standard, involves quasi-random sampling of prostate tissue without any functional guidance. In this study, we discuss the possibility to augment the detection of prostate cancer using a dual-modality optical approach, which can be coupled with the current needle biopsy setup. Two techniques are light reflectance spectroscopy (LRS) that uses a broadband light source and a CCD array spectrometer, and auto-fluorescence lifetime measurement (AFLM) that uses a custom-designed, time-correlated single photon counting (TCSPC) system. Both LRS and AFLM were employed sequentially in this study to measure cancer tissue along with control tissue on a rat prostate tumor model. At an excitation wavelength of 447 nm, we investigated auto-fluorescence decay curves at the emission wavelengths of 532, 562, 632 and 684 nm for in vivo and ex vivo AFLM. These results show that auto-fluorescence lifetimes at all measured emission wavelengths differ between control and cancerous tissues with 100% specificity and sensitivity. Moreover, absolute values of hemoglobin derivatives and scattering coefficient were quantified using in vivo LRS. This part of study also demonstrates that light scattering and absorption are significantly different between the control and cancerous tissue. Overall, the study demonstrates that both LRS and AFLM may provide several intrinsic biomarkers for in vivo detection of prostate cancer.
MINIMIZING EXCITATION LIGHT LEAKAGE AND MAXIMIZING MEASUREMENT SENSITIVITY FOR MOLECULAR IMAGING WITH NEAR-INFRARED FLUORESCENCE
Authors: ZHU BANGHE , SEVICK-MURACA EVA M.
Published: May 2011

Near-infrared fluorescence (NIRF) imaging involves the separation of weak fluorescence signals from backscattered excitation light. The measurement sensitivity of current NIRF imaging systems is limited by the excitation light leakage through rejection filters. In this contribution, the authors demonstrate that the excitation light leakage can be suppressed upon using appropriate filter combination and permutations. The excitation light leakage and measurement sensitivity were assessed and compared in this study by computing the transmission ratios of excitation to emission light collected and the signal-to-noise ratios in well-controlled phantom studies with different filter combinations and permutations. Using appropriate filter combinations and permutations, we observe as much as two orders of magnitude reduction in the transmission ratio and higher signal-to-noise ratio.
POWER OF DUAL-WAVELENGTH APPROACHES IN STUDYING PHYSIOLOGICAL AND FUNCTIONAL CHANGES OF INTACT HEART ANDIN VIVOBRAIN
Authors: LUO ZHONGCHI , DU CONGWU
Published: May 2011

Since the dual-wavelength spectrophotometer was developed, it has been widely used for studying biological samples and applied to extensive investigations of the electron transport in respiration and redox cofactors, redox state, metabolic control, and the generation of reactive oxygen species in mitochondria. Here, we discuss some extension of dual-wavelength approaches in our research to study the physiological and functional changes in intact hearts and in vivo brain. Specifically, we aimed at (1) making nonratiometric fluorescent indicator become ratiometric fluorescence function for investigation of Ca2+dynamics in live tissue; (2) eliminating the effects of physiological changes on measurement of intracellular calcium; (3) permitting simultaneous imaging of multiple physiological parameters. The animal models of the perfused heart and transiently ischemic insult of brain are used to validate these approaches for physiological applications.
THE EVOLUTION OF FIELD DEPLOYABLE fNIR SPECTROSCOPY FROM BENCH TO CLINICAL SETTINGS
Authors: IZZETOGLU KURTULUS , AYAZ HASAN , MERZAGORA ANNA , IZZETOGLU MELTEM , SHEWOKIS PATRICIA A. , BUNCE SCOTT C. , POURREZAEI KAMBIZ , ROSEN ARYE , ONARAL BANU
Published: May 2011

In the late 1980s and early 1990s, Dr. Britton Chance and his colleagues, using picosecond-long laser pulses, spearheaded the development of time-resolved spectroscopy techniques in an effort to obtain quantitative information about the optical characteristics of the tissue. These efforts by Chance and colleagues expedited the translation of near-infrared spectroscopy (NIRS)-based techniques into a neuroimaging modality for various cognitive studies. Beginning in the early 2000s, Dr. Britton Chance guided and steered the collaboration with the Optical Brain Imaging team at Drexel University toward the development and application of a field deployable continuous wave functional near-infrared spectroscopy (fNIR) system as a means to monitor cognitive functions, particularly during attention and working memory tasks as well as for complex tasks such as war games and air traffic control scenarios performed by healthy volunteers under operational conditions. Further, these collaborative efforts led to various clinical applications, including traumatic brain injury, depth of anesthesia monitoring, pediatric pain assessment, and brain–computer interface in neurology. In this paper, we introduce how these collaborative studies have made fNIR an excellent candidate for specified clinical and research applications, including repeated cortical neuroimaging, bedside or home monitoring, the elicitation of a positive effect, and protocols requiring ecological validity. This paper represents a token of our gratitude to Dr. Britton Chance for his influence and leadership. Through this manuscript we show our appreciation by contributing to his commemoration and through our work we will strive to advance the field of optical brain imaging and promote his legacy.
HIGH-SPEED SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY SIGNAL PROCESSING WITH TIME-DOMAIN INTERPOLATION USING GRAPHICS PROCESSING UNIT
Authors: LI XIQI , SHI GUOHUA , WEI LING , DING ZHIHUA , ZHANG YUDONG
Published: May 2011

Sensitivity and data processing speed are important in spectral domain Optical Coherence Tomography (SD-OCT) system. To get a higher sensitivity, zero-padding interpolation together with linear interpolation is commonly used to re-sample the interference data in SD-OCT, which limits the data processing speed. Recently, a time-domain interpolation for SD-OCT was proposed. By eliminating the huge Fast Fourier Transform Algorithm (FFT) operations, the operation number of the time-domain interpolation is much less than that of the zero-padding interpolation. In this paper, a numerical simulation is performed to evaluate the computational complexity and the interpolation accuracy. More than six times acceleration is obtained. At the same time, the normalized mean square error (NMSE) results show that the time-domain interpolation method with cut-off length L = 21 and L = 31 can improve about 1.7 dB and 2.1 dB when the distance mismatch is 2.4 mm than that of zero-padding interpolation method with padding times M = 4, respectively. Furthermore, this method can be applied the parallel arithmetic processing because only the data in the cut-off window is processed. By using Graphics Processing Unit (GPU) with compute unified device architecture (CUDA) program model, a frame (400 A-lines × 2048 pixels × 12 bits) data can be processed in 6 ms and the processing capability can be achieved 164,000 line/s for 1024-OCT and 71,000 line/s for 2048-OCT when the cut-off length is 21. Thus, a high-sensitivity and ultra-high data processing SD-OCT is realized.
COOH-terminal truncation of flightin decreases myofilament lattice organization, cross-bridge binding, and power output in Drosophila indirect flight muscle
Authors: Tanner Bertrand C. W. , Miller Mark S. , Miller Becky M. , Lekkas Panagiotis , Irving Thomas C. , Maughan David W. , Vigoreaux Jim O.
Published: May 2011

The indirect flight muscle (IFM) of insects is characterized by a near crystalline myofilament lattice structure that likely evolved to achieve high power output. In Drosophila IFM, the myosin rod binding protein flightin plays a crucial role in thick filament organization and sarcomere integrity. Here we investigate the extent to which the COOH terminus of flightin contributes to IFM structure and mechanical performance using transgenic Drosophila expressing a truncated flightin lacking the 44 COOH-terminal amino acids ( flnΔ C44). Electron microscopy and X-ray diffraction measurements show decreased myofilament lattice order in the flnΔ C44 line compared with control, a transgenic flightin-null rescued line ( fln +). flnΔ C44 fibers produced roughly 1/3 the oscillatory work and power of fln +, with reduced frequencies of maximum work (123 Hz vs. 154 Hz) and power (139 Hz vs. 187 Hz) output, indicating slower myosin cycling kinetics. These reductions in work and power stem from a slower rate of cross-bridge recruitment and decreased cross-bridge binding in flnΔ C44 fibers, although the mean duration of cross-bridge attachment was not different between both lines. The decreases in lattice order and myosin kinetics resulted in flnΔ C44 flies being unable to beat their wings. These results indicate that the COOH terminus of flightin is necessary for normal myofilament lattice organization, thereby facilitating the cross-bridge binding required to achieve high power output for flight.