bluuebunny/crossref_metadata_2025 huggingface dataset:
The Structuralist Savant
Claude Lévi-Strauss
The Poet in the Laboratory

by Patrick Wilcken

Penguin, New York, 2010. 423 pp. $29.95. ISBN 9781594202735. Bloomsbury, London. 384 pp. £30. ISBN 9780747583622.
Authors: Shankman Paul
Published: November 2010

In this first English-language biography of Lévi-Strauss, Shankman focuses more on the subject's experiences and life than on his writings and ideas.
Cosmic Rays from Cosmic Birth
Authors: Ray Tom
Published: November 2010

Observations of radio emission from young stellar objects provide key information to help us unravel the formation mechanism of astrophysical jets.
Puzzled by PML
Authors: Culjkovic-Kraljacic Bijana , Borden Katherine L. B.
Published: November 2010

A tumor suppressor protein may regulate cell survival by controlling the release of calcium from intracellular stores.
Paul F. Barbara (1953–2010)
Authors: Rossky Peter J. , Walker Gilbert C.
Published: November 2010

A chemical physicist who developed methods to study elementary reactions also explored the dynamics of complex polymers and biomolecules.
New Republicans Could Revise Party Line on Research Funding
Authors: Mervis Jeffrey
Published: November 2010

The new Republican leadership of the House of Representatives is quite different from its predecessors. And that difference could put a damper on hopes that the next Congress will deliver on a long-promised expansion of federal spending on research and education.
Bacteria and Asthma: Untangling the Links
Authors: Couzin-Frankel Jennifer
Published: November 2010

Our guts and airways are awash in bacteria—but people with asthma have a different balance of microbes. Could this be a cause of disease?
Diseases in a Dish Take Off
Authors: Vogel Gretchen
Published: November 2010

Reprogrammed cells from hundreds of patients are giving scientists the chance to model disease in new ways and are catching on among big pharma as well.
Stem Cells for Sale
Authors: Vogel Gretchen
Published: November 2010

Dozens of biotech companies hope to use stem cell technologies to make products that turn a profit, but very few have. Cellular Dynamics International, which sells cardiomyocytes—heart muscle cells—derived from induced pluripotent stem cells, is an exception.
Archaeologists, or Activists?
Authors: Bohannon John
Published: November 2010

Archaeologists who grew up in Africa are often motivated by the need to create jobs for locals and boost national or ethnic pride. At the Preserving African Cultural Heritage meeting, archaeologists called on their colleagues to engage in activist archaeology.
Early Dates For Diepkloof
Authors: Bohannon John
Published: November 2010

For the researchers who study the famed Diepkloof rock shelter in South Africa, the Preserving African Cultural Heritage meeting was both a coming-out party and a defense. The team suggests that sophisticated behavior there stretches more than twice as far back as was previously believed.
Synthetic Double-Stranded RNA Stimulates the Expression of Interferon-Inducible Protein 10 in Human Mesothelial Cells
Authors: Merkle Monika , Sauter Matthias , Ribeiro Andrea , Mussack Thomas , Ladurner Roland , Sitter Thomas , Wörnle Markus
Published: November 2010

Interferon-inducible protein 10 (IP-10) is a chemokine playing an important role in the restriction of viral spread. A time- and dose-dependent increase in IP-10 is found upon activation of viral receptors expressed on mesothelial cells, which provides novel evidence for a link between viral infections and inflammation of serous membranes.
Protective Immunity Induced by
Toxoplasma gondii
Rhoptry Protein 16 against Toxoplasmosis in Mice
Authors: Yuan Zi-Guo , Zhang Xiu-Xiang , He Xian-Hui , Petersen Eskild , Zhou Dong-Hui , He Yong , Lin Rui-Qing , Li Xiu-Zhen , Chen Xu-Li , Shi Xiao-Ru , Zhong Xiu-Ling , Zhang Bing , Zhu Xing-Quan
Published: November 2010

Toxoplasma gondii
can infect a large variety of domestic and wild animals and human beings, sometimes causing severe pathology. Rhoptries are involved in
T. gondii
invasion and host cell interaction and have been implicated as important virulence factors. In this study, we constructed a DNA vaccine expressing rhoptry protein 16 (ROP16) of
T. gondii
and evaluated the immune responses it induced in Kunming mice. The gene sequence encoding ROP16 was inserted into the eukaryotic expression vector pVAX I. We immunized Kunming mice intramuscularly. After immunization, we evaluated the immune response using a lymphoproliferative assay, cytokine and antibody measurements, and the survival times of mice challenged lethally. The results showed that mice immunized with pVAX-ROP16 developed a high level of specific antibody responses against
T. gondii
ROP16 expressed in
Escherichia coli
, a strong lymphoproliferative response, and significant levels of gamma interferon (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-10 production compared with results for other mice immunized with either empty plasmid or phosphate-buffered saline, respectively. The results showed that pVAX-ROP16 induces significant humoral and cellular Th1 immune responses. After lethal challenge, the mice immunized with pVAX-ROP16 showed a significantly (
P
< 0.05) prolonged survival time (21.6 ± 9.9 days) compared with control mice, which died within 7 days of challenge. Our data demonstrate, for the first time, that ROP16 triggers a strong humoral and cellular response against
T. gondii
and that ROP16 is a promising vaccine candidate against toxoplasmosis, worth further development.
Serum Cytokine Responses in Primary Pneumonic Plague Patients
Authors: Wang Xiaoyi , Wang Zuyun , Guo Zhaobiao , Wei Baiqing , Tian Fuzhang , Yu Shouhong , Wang Haoran , Wang Hu , Yang Ruifu
Published: November 2010

The serum levels of interleukin-2 (IL-2), gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, and IL-10 of pneumonic plague patients were determined by enzyme-linked immunosorbent assay. IL-6 was the only elevated cytokine in the patients, and its level increased with a clear time course, indicating that IL-6 might be a prognostic marker for predicting the progression of plague.
Distribution of Borrelia burgdorferi Sensu Lato in China
Authors: Hao Qin , Hou Xuexia , Geng Zhen , Wan Kanglin
Published: November 2010

We genotyped 102
Borrelia burgdorferi
sensu lato strains isolated from ticks, animals, and patients in 11 provinces in China by PCR–restriction fragment length polymorphism (PCR-RFLP) amplification of 5S (
rrf
)-23S (
rrl
) rRNA gene spacer amplicons and multilocus sequence analysis (MLSA). The results showed that
Borrelia garinii
was the main genotype in China (65/102) and that it was distributed mainly in northern China.
Borrelia afzelii
was the second most frequently found species (22/102), and it was distributed in both northern and southern China. All
Borrelia valaisiana
strains were isolated from Guizhou Province. Additionally, one
B. burgdorferi
strain was isolated from Hunan Province. Our results show the diversity and wide distribution of
B. burgdorferi
sensu lato in China.
Estimating Volume of Cervicovaginal Secretions in Cervicovaginal Lavage Fluid Collected for Measurement of Genital HIV-1 RNA Levels in Women
Authors: Mitchell Caroline , Paul Kathleen , Agnew Kathy , Gaussman Reggie , Coombs Robert W. , Hitti Jane
Published: November 2010

To assess the volume of genital fluid collected for measuring the HIV-1 RNA level in cervicovaginal fluid, phosphate-buffered saline containing 10 mM LiCl was used. Thirty-eight women provided 275 cervicovaginal specimens. The estimated median volume of cervicovaginal fluid was 0.51 ml (interquartile range, 0.33, 0.69).
Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry as an Alternative to 16S rRNA Gene Sequencing for Identification of Difficult-To-Identify Bacterial Strains
Authors: Bizzini A. , Jaton K. , Romo D. , Bille J. , Prod'hom G. , Greub G.
Published: November 2010

Conventional methods are sometimes insufficient to identify human bacterial pathogens, and alternative techniques, often molecular, are required. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) identified with a valid score 45.9% of 410 clinical isolates from 207 different difficult-to-identify species having required 16S rRNA gene sequencing. MALDI-TOF MS might represent an alternative to 16S rRNA gene sequencing.
Revealing New Measles Virus Transmission Routes by Use of Sequence Analysis of Phosphoprotein and Hemagglutinin Genes
Authors: Kessler Julia R. , Kremer Jacques R. , Shulga Sergey V. , Tikhonova Nina T. , Santibanez Sabine , Mankertz Annette , Semeiko Galina V. , Samoilovich Elena O. , Tamfum Jean-Jacques Muyembe , Pukuta Elisabeth , Muller Claude P.
Published: November 2010

With improved measles virus (MV) control, the genetic variability of the MV-nucleoprotein hypervariable region (NP-HVR) decreases. Thus, it becomes increasingly difficult to determine the origin of a virus using only this part of the genome. During outbreaks in Europe and Africa, we found MV strains with identical NP-HVR sequences. However, these strains showed considerable diversity within a larger sequencing window based on concatenated MV phosphoprotein and hemagglutinin genes (P/H pseudogenes). In Belarus, Germany, Russia, and the Democratic Republic of Congo, the P/H pseudogenes provided insights into chains of transmission, whereas identical NP-HVR provided none. In Russia, for instance, the P/H pseudogene identified temporal clusters rather than geographical clusters, demonstrating the circulation and importation of independent variants rather than large local outbreaks lasting for several years, as suggested by NP-HVR. Thus, by extending the sequencing window for molecular epidemiology, a more refined picture of MV circulation was obtained with more clearly defined links between outbreaks and transmission chains. Our results also suggested that in contrast to the P gene, the H gene acquired fixed substitutions that continued to be found in subsequent outbreaks, possibly with consequences for its antigenicity. Thus, a longer sequencing window has true benefits both for the epidemiological surveillance of measles and for the better monitoring of viral evolution.
Physician Use of Parasite Tests in the United States from 1997 to 2006 and in a Utah Cryptosporidium Outbreak in 2007
Authors: Polage Christopher R. , Stoddard Gregory J. , Rolfs Robert T. , Petti Cathy A.
Published: November 2010

Parasitic infection is uncommon in the United States, but surveys suggest that physicians test when the presence of parasites is unlikely and fail to order appropriate testing when suspicion is high. Numerous studies confirm that immunoassays are more sensitive for
Giardia
and
Cryptosporidium
detection, but our experience was that physicians preferentially used ovum and parasite examination (O&P). We conducted a retrospective study of fecal parasite testing at a referral laboratory nationally (1997 to 2006) and during a
Cryptosporidium
outbreak (Utah, 2007) to correlate physician use of O&P and enzyme immunoassays (EIAs) with the yield of parasites detected. Nationally, of 170,671 episodes, 76.0% (
n
= 129,732) included O&P, 27.9% (
n
= 47,666) included
Giardia
EIA, and 5.7% (
n
= 9,754) included
Cryptosporidium
EIA. Most pathogens were
Giardia
or
Cryptosporidium
. More episodes were positive when EIA was performed (
n
= 1,860/54,483 [3.4%]) than when O&P only was performed (
n
= 1,667/116,188 [1.4%];
P
< 0.001), and EIA was more sensitive than O&P. However, more O&P results were positive among patients with both O&P and EIA performed (2.5%) than among those with O&P only performed (1.4%;
P
< 0.001), suggesting that patients tested by O&P only may have been at lower risk. During the first 10 weeks of the outbreak, physicians also preferentially used O&P over EIA, but no
Cryptosporidium
cases were detected by O&P. We conclude that clinicians frequently use O&P testing when test performance and epidemiology support the use of immunoassays or no testing. We recommend that stool O&P be limited to patients with negative immunoassay results and persistent symptoms or individuals at increased risk for non-
Giardia
, non-
Cryptosporidium
infection. An evidence-based algorithm for the evaluation of patients with suspected intestinal parasitic infection is proposed.
Bacteremia in Kenyan Children Presenting with Malaria
Authors: Were T. , Davenport G. C. , Hittner J. B. , Ouma C. , Vulule J. M. , Ong'echa J. M. , Perkins D. J.
Published: November 2010

Since the etiologies and clinical outcomes of bacteremia in children with
Plasmodium falciparum
infections, particularly in areas of holoendemic malaria transmission, are largely unexplored, blood cultures and comprehensive clinical, laboratory, hematological, and nutritional parameters for malaria-infected children (aged 1 to 36 months,
n
= 585 patients) were investigated at a rural hospital in western Kenya. After the exclusion of contaminant microorganisms, the prevalence of bacteremia was 11.7% in the cohort (
n
= 506), with nontyphoidal
Salmonella
spp. being the most common isolates (42.4%). Bacteremia was found to occur in a significantly higher proportion of females than males and was associated with elevated blood glucose concentrations and lowered malaria parasite and hemoglobin (Hb) levels compared to those in abacteremic participants. In addition, the incidences of respiratory distress and severe malarial anemia (SMA; Hb level of <6.0g/dl) were nonsignificantly greater in children with bacteremia. Mortality was 8.5-fold higher in children with bacteremia. Multivariate logistic regression analyses revealed that bacteremia was significantly associated with reduced incidences of high-density parasitemia (HDP; ≥10,000/μl) and increased incidences of malnutrition (i.e., underweight; weight-for-age Z score of <−2 using the NCHS system). Since previous studies showed that bacteremia caused by Gram-negative organisms is associated with enhanced anemia and mortality, multivariate logistic regression was also performed separately for randomly age- and gender-matched children with bacteremia caused by Gram-negative organisms (
n
= 37) and for children found to be abacteremic (
n
= 74). These results revealed that the presence of bacteremia caused by Gram-negative organisms was significantly associated with reduced HDP, enhanced susceptibility to respiratory distress, SMA (Hb level of <6.0 g/dl), and being underweight (Z score, <−2). Data presented here from a region of holoendemic
P. falciparum
transmission demonstrate that although bacteremia is associated with reduced malaria parasitemia, a number of unfavorable clinical outcomes, including malnutrition, respiratory distress, anemia, and mortality, are elevated in children with bacteremia, particularly in cases of Gram-negative origin.
Coexpressed RIG-I Agonist Enhances Humoral Immune Response to Influenza Virus DNA Vaccine
Authors: Luke Jeremy M. , Simon Gregory G. , Söderholm Jonas , Errett John S. , August J. Thomas , Gale Michael , Hodgson Clague P. , Williams James A.
Published: November 2010

Increasing levels of plasmid vector-mediated activation of innate immune signaling pathways is an approach to improve DNA vaccine-induced adaptive immunity for infectious disease and cancer applications. Retinoic acid-inducible gene I (RIG-I) is a critical cytoplasmic double-stranded RNA (dsRNA) pattern receptor required for innate immune activation in response to viral infection. Activation of RIG-I leads to type I interferon (IFN) and inflammatory cytokine production through interferon promoter stimulator 1 (IPS-1)-mediated activation of interferon regulatory factor 3 (IRF3) and NF-κB signaling. DNA vaccines coexpressing antigen and an expressed RNA (eRNA) RIG-I agonist were made, and the effect of RIG-I activation on antigen-specific immune responses to the encoded antigen was determined. Plasmid vector backbones expressing various RIG-I ligands from RNA polymerase III promoters were screened in a cell culture assay for RIG-I agonist activity, and optimized, potent RIG-I ligands were developed. One of these, eRNA41H, combines (i) eRNA11a, an immunostimulatory dsRNA expressed by convergent transcription, with (ii) adenovirus VA RNAI. eRNA41H was integrated into the backbone of DNA vaccine vectors expressing H5N1 influenza virus hemagglutinin (HA). The resultant eRNA vectors potently induced type 1 IFN production in cell culture through RIG-I activation and combined high-level HA antigen expression with RNA-mediated type I IFN activation in a single plasmid vector. The eRNA vectors induced increased HA-specific serum antibody binding avidity after naked DNA intramuscular prime and boost delivery in mice. This demonstrates that DNA vaccine potency may be augmented by the incorporation of RIG-I-activating immunostimulatory RNA into the vector backbone.
Dynamics of
In Vitro
Fitness Recovery of HIV-1
Authors: Lorenzo-Redondo Ramón , Bordería Antonio V. , Lopez-Galindez Cecilio
Published: November 2010

The study on the evolutionary consequences of an RNA viral population's fluctuations can be approached by
in vitro
experiments. This work describes the fitness recovery of HIV-1 after 20 large-population passages in 10 debilitated clones. The serial passages promoted an increase in viral fitness. In addition, we detected a significant number of mutations fixed in the complete genome consensus sequence of the final viral populations. Among the mutations, events of convergent evolution with important phenotypic characteristics occurred in several independent clones. One common change, V35I, in the nuclear localization signal of the p17 protein appeared in four viruses of three different lineages. Other common alterations mapped in position E196K of the reverse transcriptase or in position S316K of the V3 loop of the gp120 residue that is associated with the X4/R5 phenotype. Together with this mutational analysis, we studied the quasispecies heterogeneity of the initial and final viruses, revealing that fitness increase correlated with an augmentation in the genetic heterogeneity of viral quasispecies. However, while heterogeneity was mostly composed of synonymous (
dS
) mutations in the first 10 passages performed, at passage 21 it switched to nonsynonymous (
dN
) substitutions, with significant differences in
dN
−
dS
values between passages 11 and 21. In summary, the HIV-1
in vitro
fitness recovery depicts a multiphase process occurring first by generation of mutations followed by fixation of the beneficial ones, depicting a classical Darwinian process.
Nucleoprotein-RNA Orientation in the Measles Virus Nucleocapsid by Three-Dimensional Electron Microscopy
Authors: Desfosses Ambroise , Goret Gaël , Farias Estrozi Leandro , Ruigrok Rob W. H. , Gutsche Irina
Published: November 2010

Recombinant measles virus nucleoprotein-RNA (N-RNA) helices were analyzed by negative-stain electron microscopy. Three-dimensional reconstructions of trypsin-digested and intact nucleocapsids coupled to the docking of the atomic structure of the respiratory syncytial virus (RSV) N-RNA subunit into the electron microscopy density map support a model that places the RNA at the exterior of the helix and the disordered C-terminal domain toward the helix interior, and they suggest the position of the six nucleotides with respect to the measles N protomer.
Seeing the Portal in Herpes Simplex Virus Type 1 B Capsids
Authors: Rochat R. H. , Liu X. , Murata K. , Nagayama K. , Rixon F. J. , Chiu W.
Published: November 2010

Resolving the nonicosahedral components in large icosahedral viruses remains a technical challenge in structural virology. We have used the emerging technique of Zernike phase-contrast electron cryomicroscopy to enhance the image contrast of ice-embedded herpes simplex virus type 1 capsids. Image reconstruction enabled us to retrieve the structure of the unique portal vertex in the context of the icosahedral capsid and, for the first time, show the subunit organization of a portal in a virus infecting eukaryotes. Our map unequivocally resolves the 12-subunit portal situated beneath one of the pentameric vertices, thus removing uncertainty over the location and stoichiometry of the herpesvirus portal.
Nonneutralizing HIV-1 gp41 Envelope Cluster II Human Monoclonal Antibodies Show Polyreactivity for Binding to Phospholipids and Protein Autoantigens
Authors: Dennison S. Moses , Anasti Kara , Scearce Richard M. , Sutherland Laura , Parks Robert , Xia Shi-Mao , Liao Hua-Xin , Gorny Miroslaw K. , Zolla-Pazner Susan , Haynes Barton F. , Alam S. Munir
Published: November 2010

HIV-1 gp41 envelope antibodies, which are frequently induced in HIV-1-infected individuals, are predominantly nonneutralizing. The rare and difficult-to-induce neutralizing antibodies (2F5 and 4E10) that target gp41 membrane-proximal epitopes (MPER) are polyspecific and require lipid binding for HIV-1 neutralization. These results raise the questions of how prevalent polyreactivity is among gp41 antibodies and how the binding properties of gp41-nonneutralizing antibodies differ from those of antibodies that are broadly neutralizing. In this study, we have characterized a panel of human gp41 antibodies with binding specificities within the immunodominant cluster I (gp41 amino acids [aa] 579 to 613) or cluster II (gp41 aa 644 to 667) for reactivity to autoantigens, to the gp140 protein, and with MPER peptide-lipid conjugates. We report that while none of the gp41 cluster I antibodies studied were polyspecific, all three gp41 cluster II antibodies bound either to lipids or autoantigens, thus showing the propensity of cluster II antibodies to manifest polyreactivity. All cluster II gp41 monoclonal antibodies (MAbs), including those that were lipid reactive, failed to bind to gp41 MPER peptide-lipid complexes. Cluster II antibodies bound strongly with nanomolar binding affinity (dissociation constant [Kd]) to oligomeric gp140 proteins, and thus, they recognize conformational epitopes on gp41 that are distinct from those of neutralizing gp41 antibodies. These results demonstrate that lipid-reactive gp41 cluster II antibodies are nonneutralizing due to their inability to bind to the relevant neutralizing epitopes on gp41.
Kaposi's Sarcoma-Associated Herpesvirus ORF57 Interacts with Cellular RNA Export Cofactors RBM15 and OTT3 To Promote Expression of Viral ORF59
Authors: Majerciak Vladimir , Uranishi Hiroaki , Kruhlak Michael , Pilkington Guy R. , Massimelli Maria Julia , Bear Jenifer , Pavlakis George N. , Felber Barbara K. , Zheng Zhi-Ming
Published: November 2010

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes ORF57, which promotes the accumulation of specific KSHV mRNA targets, including ORF59 mRNA. We report that the cellular export NXF1 cofactors RBM15 and OTT3 participate in ORF57-enhanced expression of KSHV ORF59. We also found that ectopic expression of RBM15 or OTT3 augments ORF59 production in the absence of ORF57. While RBM15 promotes the accumulation of ORF59 RNA predominantly in the nucleus compared to the levels in the cytoplasm, we found that ORF57 shifted the nucleocytoplasmic balance by increasing ORF59 RNA accumulation in the cytoplasm more than in the nucleus. By promoting the accumulation of cytoplasmic ORF59 RNA, ORF57 offsets the nuclear RNA accumulation mediated by RBM15 by preventing nuclear ORF59 RNA from hyperpolyadenylation. ORF57 interacts directly with the RBM15 C-terminal portion containing the SPOC domain to reduce RBM15 binding to ORF59 RNA. Although ORF57 homologs Epstein-Barr virus (EBV) EB2, herpes simplex virus (HSV) ICP27, varicella-zoster virus (VZV) IE4/ORF4, and cytomegalovirus (CMV) UL69 also interact with RBM15 and OTT3, EBV EB2, which also promotes ORF59 expression, does not function like KSHV ORF57 to efficiently prevent RBM15-mediated nuclear accumulation of ORF59 RNA and RBM15's association with polyadenylated RNAs. Collectively, our data provide novel insight elucidating a molecular mechanism by which ORF57 promotes the expression of viral intronless genes.
Cell Type-Specific Proteasomal Processing of HIV-1 Gag-p24 Results in an Altered Epitope Repertoire
Authors: Steers Nicholas J. , Currier Jeffrey R. , Kijak Gustavo H. , di Targiani Robert C. , Saxena Ashima , Marovich Mary A. , Kim Jerome H. , Michael Nelson L. , Alving Carl R. , Rao Mangala
Published: November 2010

Proteasomes are critical for the processing of antigens for presentation through the major histocompatibility complex (MHC) class I pathway. HIV-1 Gag protein is a component of several experimental HIV-1 vaccines. Therefore, understanding the processing of HIV-1 Gag protein and the resulting epitope repertoire is essential. Purified proteasomes from mature dendritic cells (DC) and activated CD4
+
T cells from the same volunteer were used to cleave full-length Gag-p24 protein, and the resulting peptide fragments were identified by mass spectrometry. Distinct proteasomal degradation patterns and peptide fragments were unique to either mature DC or activated CD4
+
T cells. Almost half of the peptides generated were cell type specific. Two additional differences were observed in the peptides identified from the two cell types. These were in the HLA-B35-Px epitope and the HLA-B27-KK10 epitope. These epitopes have been linked to HIV-1 disease progression. Our results suggest that the source of generation of precursor MHC class I epitopes may be a critical factor for the induction of relevant epitope-specific cytotoxic T cells.
A Proapoptotic Peptide Derived from Reovirus Outer Capsid Protein μ1 Has Membrane-Destabilizing Activity
Authors: Kim Jae-Won , Lyi Sangbom M. , Parrish Colin R. , Parker John S. L.
Published: November 2010

The reovirus outer capsid protein μ1 is responsible for cell membrane penetration during virus entry and contains determinants necessary for virus-induced apoptosis. Residues 582 to 611 of μ1 are necessary and sufficient for reovirus-induced apoptosis, and residues 594 and 595 independently regulate the efficiency of viral entry and reovirus-induced cell apoptosis, respectively. Two of three α-helices within this region, helix 1 (residues 582 to 611) and helix 3 (residues 644 to 675), play a role in reovirus-induced apoptosis. Here, we chemically synthesized peptides representing helix 1 (H1), H1:K594D, H1:I595K, and helix 3 (H3) and examined their biological properties. We found that H1, but not H3, was able to cause concentration- and size-dependent leakage of molecules from small unilamellar liposomes. We further found that direct application of H1, but not H1:K594D, H1:I595K, or H3, to cells resulted in cytotoxicity. Application of the H1 peptide to L929 cells caused rapid elevations in intracellular calcium concentration that were independent of phospholipase C activation. Cytotoxicity of H1 was not restricted to eukaryotic cells, as the H1 peptide also had bactericidal activity. Based on these findings, we propose that the proapoptotic function of the H1 region of μ1 is dependent on its capacity to destabilize cellular membranes and cause release of molecules from intracellular organelles that ultimately induces cell necrosis or apoptosis, depending on the dose.
High efficacy of bolus methylprednisolone in severe leptospirosis: a descriptive study in Sri Lanka
Authors: Kularatne Senanayake A M , Budagoda B D Sudhara S , de Alwis V Kapila D , Wickramasinghe W M R Sujantha , Bandara J M Ruwanthi P , Pathirage L P Manoji M K , Gamlath G Rohitha R D K , Wijethunga Thusitha J , Jayalath W A Thilak A , Jayasinghe Chandrika , Pinto Vasanthi , Somaratne Praneetha , Kumarasiri P V Ranjith
Published: November 2010

Background

In 2008, an outbreak of leptospirosis caused high mortality in Sri Lanka. The General Hospital, Peradeniya recorded nine deaths in May, which prompted the medical staff to change the treatment protocol. Addition of intravenous methylprednisolone (MP) to the treatment regimen of severely ill patients was implemented on the basis of immune mediated pathogenesis of the disease to reduce mortality.

Methods

The day MP commenced (25 May 2008), the study period was divided into a ‘pre-MP period’ and an ‘MP period’. A clinical score ranging from 0–6 was applied to assess the severity of the infection. A score ≥2 was considered severe. Thus, 62 patients received bolus MP 500 mg intravenously for 3 days, followed by oral 8 mg for 5 days (MP given). Ten patients to whom MP was withheld were included in the MP period severe group (n=72). The same score was applied to pre-MP periods and 60 cases were identified as the historical control group (pre-MP period severe).

Results

There were 78 and 149 cases of leptospirosis in the pre-MP period and MP period, respectively. Of these cases, 17 and 16 patients died, with case death rates of 21.8% and 10.7%, respectively; the difference was significant (p=0.025). The survival rate at score 4 in the MP period severe group was 100% (16 of 16), compared to 38% (5 of 13) in pre-MP period severe group; this difference was highly significant (p<0.001). Six patients who died despite MP therapy had a clinical score of 5 or 6; four were alcohol consumers, and two had heart disease and hypertension.

Conclusion

MP may reduce mortality in patients with severe leptospirosis, except in cases with established multiple organ dysfunction and comorbidities. Therefore, early administration of MP seems advisable.
The effect of rectal administration of insulin on the short-term treatment of alloxan-diabetic dogs
Authors: Yamasaki Yoshimitsu , Shichiri Motoaki , Kawamori Ryuzo , Morishima Toyohiko , Hakui Nobuyoshi , Yagi Toshihiko , Abe Hiroshi
Published: November 2010

Six alloxan-diabetic dogs with fasting plasma glucose levels above 200 mg/100 mL were treated with rectal administration of insulin suppositories twice a day for 6–9 days. The effectiveness was compared with that of subcutaneous insulin injections. In three diabetic dogs with fasting plasma glucose levels below 300 mg/100 mL, both insulin suppository at a dose of 20 U (2.3 U/kg) and subcutaneous insulin at a dose of 0.2 U/kg showed a similar effect in reducing fasting glucose levels and daily urinary glucose amounts. In dogs with higher fasting glucose levels, 0.5 U of subcutaneous insulin/kg is less effective in reducing fasting glucose than 50 U (5.2 U/kg) suppositories, in spite of the same effects on daily urinary glucose output. Postprandial glucose responses were significantly lessened with rectal administration of insulin suppositories. The integrated area of increase in peripheral insulin concentration after subcutaneous injection of 0.2 or 0.5 U insulin/kg was significantly greater than that after rectal administration of an insulin suppository (2.3 or 5.2 U/kg, respectively). These results indicate that diabetes could be controlled by the daily rectal administration of an insulin suppository instead of the conventional subcutaneous injection.
The characterization of cardiac histaminergic chronotropic receptors in the rabbit
Authors: Polanin Alicia , Tenner Jr. Thomas E. , McNeill John H.
Published: November 2010

The effects of selective histamine receptor analogs were studied in spontaneously beating rabbit atria. Atrial rate was increased by histamine (an H1 and H2 agonist), 4-methylhistamine and impromidine (H2 agonists), and 2-pyridylethylamine (PEA, an H1 agonist). The responses to histamine, 4-methylhistamine, and impromidine were not affected by propranolol (1 × 10−7 M) or reserpine pretreatment. However, the response to PEA was nearly abolished upon pretreatment with propranolol or reserpine.Cimetidine pretreatment (H2 receptor blockade) competitively antagonised the positive chronotropic effects of histamine, 4-methylhistamine, and impromidine. Promethazine pretreatment (H1 receptor blockade) competitively blocked the chronotropic effects of histamine but had no effect on the responses to 4-methylhistamine or impromidine. These results suggest that stimulation of H1 and H2 receptors will cause a positive chronotropic response.
Role of the pericardium and intact chest wall in the hemodynamic response to positive end-expiratory pressure ventilation
Authors: Morris Andrew L. , Rabkin Simon W. , Ayotte Brian , Sharma Gyan P.
Published: November 2010

The mechanism for the reduction of both systemic arterial blood pressure and cardiac output (CO) and for the elevation of intravascular pressure which accompanies positive end-expiratory pressure ventilation (PEEP) remains uncertain. The role of the intact pericardium and the chest wall has not been defined. This study examines cardiac transmural pressure with PEEP (0, 4, 8, and 16 cm H2O) administration in nine closed chest, anesthetized, normovolemic dogs utilizing direct measurements of intrapericardial pressure. The experiment was repeated following pericardiectomy and left thoracotomy. The closed chest dogs exhibited significant reductions in blood pressure and CO without detectable changes in transmural pressure. With combined pericardiectomy and left thoracotomy, the responses of both CO and blood pressure to PEEP were similar to those observed with the chest closed. Absolute right atrial pressures were similar at all levels of PEEP and were independent of the presence of the pericardium and the intact chest wall. The rise in absolute left atrial pressure observed with these structures intact was completely abolished by pericardiectomy and left thoracotomy. Thus the major hemodynamic effects of PEEP, namely changes in blood pressure and CO, cannot be accounted for by changes in transmural pressure or influences from the intact chest wall and pericardium.
Fast transit of red cells and plasma in contracted versus relaxed spleens
Authors: Levesque M. J. , Groom A. C.
Published: November 2010

Nine-tenths of the inflowing blood passes through the normal relaxed spleen via a fast arteriovenous pathway whereas the remainder travels slowly via the red pulp. However, flow through this fast pathway diminishes to zero when the organ is distended by perfusion at high venous pressure. The present investigation, in which a slug-injection procedure was used to determine the volumes of distribution of red cells and 125I-labelled albumin in isolated, Ringer-perfused cat spleens during a single transit, has shown that in spleens contracted by noradrenaline the entire inflow passes via the fast arteriovenous pathway. The peak outflow concentration of 125I-labelled albumin occurred much later (factor 2.03) than that of red cells. This difference is too great to be accounted for solely by axial accumulation of red cells within a closed system of vessels in vivo and indicates that albumin was distributed throughout a significantly larger space than red cells. These findings are explained in terms of the classical observations of MacKenzie and co-workers on red cell movement in transilluminated mouse spleens during contraction. Whether the splenic retention of damaged red cells would change as a result of the altered flow pathways is not yet known.
The effect of porcine calcitonin on intestinal calcium and phosphate fluxes in the young piglet
Authors: McKercher H. G. , Radde I. C.
Published: November 2010

The effects of a physiological (3.8 ng∙mL−1) and a pharmacological (120 ng∙mL−1) concentration of porcine calcitonin (CT) on transmucosal calcium and phosphate flux rates were determined in intestinal mucosa from young piglets (4–40 days) mounted in Ussing flux chambers. The physiological concentration of the hormone inhibited net absorptive calcium flux rates in the proximal jejunum and distal ileum but not in the duodenum. No effect of either concentration of CT on phosphate flux rates was observed. The inhibitory effect of the physiological concentration may indicate a role for CT in the maintenance of calcium homeostasis in the young suckling mammal.
Synthesis and assay for activity of a proposed anorexogenic agent, L-pyroglutamyl-L-histidyl-glycine
Authors: Bauce Lorenzo G. , Elliott Crystal , Hughes Rhiannon , Goren H. Joseph
Published: November 2010

L-Pyroglutamyl-L-histidyl-glycine has been reported to be an anorexogenic agent in female mice. In this report the synthesis of this tripeptide is described. The synthetic material was injected into female and male mice and into male rats. In no instance did the animals decrease their food intake. Further, the weights of peptide-treated animals were the same as those of control (saline-treated) animals. The results suggest that L-pyroglutamyl-L-histidyl-glycine is not an anorexogenic agent.
NEW MEASURES FOR COMPARING THE SPECIES DIVERSITY FOUND IN TWO OR MORE HABITATS
Authors: GUIASU RADU CORNEL , GUIASU SILVIU
Published: November 2010

Both the weighted entropy, which generalizes the Shannon entropy, and the weighted quadratic index, which generalizes the Gini-Simpson index, are used for getting a unified treatment of some diversity measures proposed recently in ecology. The weights may reflect the ecological importance, rarity, or economic value of the species from a given habitat. The weighted measures, being concave functions, may be used in the additive partition of diversity. The weighted quadratic index has a special advantage over the weighted entropy because its maximum value has a simple analytical formula which allows us to introduce a normed measure of dissimilarity between habitats. A special case of weighted quadratic index is the Rich-Gini-Simpson index which, unlike the Shannon entropy and the classic Gini-Simpson index, behaves well when the number of species is very large. The weighted entropy and the weighted quadratic index may also be used to measure the global diversity among the subsets of species. In this context, Rao's quadratic index of diversity between the pairs of species, based on the phylogenetic distance between species, is obtained as a particular case and is generalized to measure the diversity among the triads of species as well.
LEARNING AUTOMATA-BASED ALGORITHMS FOR FINDING MINIMUM WEAKLY CONNECTED DOMINATING SET IN STOCHASTIC GRAPHS
Authors: AKBARI TORKESTANI JAVAD , MEYBODI MOHAMMAD REZA
Published: November 2010

A weakly connected dominating set (WCDS) of graph G is a subset of G so that the vertex set of the given subset and all vertices with at least one endpoint in the subset induce a connected sub-graph of G. The minimum WCDS (MWCDS) problem is known to be NP-hard, and several approximation algorithms have been proposed for solving MWCDS in deterministic graphs. However, to the best of our knowledge no work has been done on finding the WCDS in stochastic graphs. In this paper, a definition of the MWCDS problem in a stochastic graph is first presented and then several learning automata-based algorithms are proposed for solving the stochastic MWCDS problem where the probability distribution function of the weight associated with the graph vertices is unknown. The proposed algorithms significantly reduce the number of samples needs to be taken from the vertices of the stochastic graph. It is shown that by a proper choice of the parameters of the proposed algorithms, the probability of finding the MWCDS is as close to unity as possible. Experimental results show the major superiority of the proposed algorithms over the standard sampling method in terms of the sampling rate.
UNCERTAINTY PORTFOLIO MODEL IN CROSS CURRENCY MARKETS
Authors: XU WEIJUN , XU WEIDONG , LI HONGYI , ZHANG WEIGUO
Published: November 2010

Owing to the fluctuations in the financial markets, many financial variables such as expected return, volatility, or exchange rate may occur imprecisely. But many portfolio selection models consider precise input of these values. Therefore, this paper studies a multiobjective international asset allocation problem under fuzzy environment. In our portfolio selection model, both of the return risk and the exchange risk are considered. The coefficient matrices in the objectives and constraints and the decision value are considered as fuzzy variables. The calculation of the portfolio and efficient frontier is derived by considering the exchange risk in the fuzzy environment. An empirical study is performed based on a portfolio of six securities denominated in six different currencies, i.e., USD, EUR, JPY, CNY, HKD, and GBP. The α-level closed interval portfolio [Formula: see text] and the fuzzy efficient frontier are obtained with different values of α ∈ (0, 1]. The empirical results indicate that the fuzzy asset selection method is a useful tool for dealing with the imprecise problem in the real world.
FUZZY BASED GA FOR ENTROPY BIMATRIX GOAL GAME
Authors: DAS CHANDAN BIKASH , ROY SANKAR KUMAR
Published: November 2010

In this paper, we propose a new mathematical model to analyze bimatrix goal game under entropy environment. This new approach incorporates the entropy function of the players as an objective to the bimatrix game. The solution concepts behind this game are based on getting the probability to achieve some specified goals. We consider the solution, not only by the payoff values, but also by the probability to get them. Numerical examples are presented to illustrate the methodology in the paper.
GROUP DECISION MAKING METHODOLOGY BASED ON THE ATANASSOV'S INTUITIONISTIC FUZZY SET GENERALIZED OWA OPERATOR
Authors: LI DENG-FENG , WANG LI-LING , CHEN GUO-HONG
Published: November 2010

The aim of this paper is to develop a new methodology for solving group decision making problems in which preference comparisons between alternatives are expressed with Atanassov's intuitionistic fuzzy (IF) preference relations. In this methodology, the generalized ordered weighted averaging (GOWA) operator is extended to develop the Atanassov's IF set (IFS) generalized ordered weighted averaging (IFSGOWA) operator, which can aggregate vague or imprecise information expressed with the Atanassov's IFSs. The Atanassov's IFSGOWA operator based methodology is further developed to solve group decision making problems with Atanassov's IF preference relations. A real example of the agroecological region assessment problem is used to illustrate the implementation and applicability of the proposed methodology. It is also shown that the obtained decision results could be affected by the choice of the parameter lambda and the nature of the weights.
MODELING (r, Q) POLICY IN A TWO-LEVEL SUPPLY CHAIN SYSTEM WITH FUZZY DEMAND
Authors: PIRAYESH MOHAMMADALI , YAZDI MOHAMMAD MODARRES
Published: November 2010

In this paper a two level supply chain system is studied, in which the final demand is assumed to be fuzzy with triangular membership function. The inventory control policy of (r, Q) is followed for this system and unsatisfied demand is assumed to be back ordered. The objective is to minimize the total cost of the system, including ordering, holding and shortage costs. The model happens to be a nonlinear programming. Considering the complexity arising from the model, we also develop a genetic algorithm to obtain a near-optimal solution. The method is illustrated through some numerical examples.
INTERVAL METHODS IN KNOWLEDGE REPRESENTATION
Authors: Kreinovich Vladik
Published: November 2010

This section is maintained by Vladik Kreinovich. Please send your abstracts (or copies of papers that you want to see reviewed here) to vladik@utep.edu, or by regular mail to: Vladik Kreinovich Department of Computer Science, University of Texas at El Paso, El Paso, TX 79968, USA.
Mitochondrial degradation by autophagy (mitophagy) in GFP-LC3 transgenic hepatocytes during nutrient deprivation
Authors: Kim Insil , Lemasters John J.
Published: November 2010

Fasting in vivo and nutrient deprivation in vitro enhance sequestration of mitochondria and other organelles by autophagy for recycling of essential nutrients. Here our goal was to use a transgenic mouse strain expressing green fluorescent protein (GFP) fused to rat microtubule-associated protein-1 light chain 3 (LC3), a marker protein for autophagy, to characterize the dynamics of mitochondrial turnover by autophagy (mitophagy) in hepatocytes during nutrient deprivation. In complete growth medium, GFP-LC3 fluorescence was distributed diffusely in the cytosol and incorporated in mostly small (0.2–0.3 μm) patches in proximity to mitochondria, which likely represent preautophagic structures (PAS). After nutrient deprivation plus 1 μM glucagon to simulate fasting, PAS grew into green cups (phagophores) and then rings (autophagosomes) that enveloped individual mitochondria, a process that was blocked by 3-methyladenine. Autophagic sequestration of mitochondria took place in 6.5 ± 0.4 min and often occurred coordinately with mitochondrial fission. After ring formation and apparent sequestration, mitochondria depolarized in 11.8 ± 1.4 min, as indicated by loss of tetramethylrhodamine methylester fluorescence. After ring formation, LysoTracker Red uptake, a marker of acidification, occurred gradually, becoming fully evident at 9.9 ± 1.9 min of ring formation. After acidification, GFP-LC3 fluorescence dispersed. PicoGreen labeling of mitochondrial DNA (mtDNA) showed that mtDNA was also sequestered and degraded in autophagosomes. Overall, the results indicate that PAS serve as nucleation sites for mitophagy in hepatocytes during nutrient deprivation. After autophagosome formation, mitochondrial depolarization and vesicular acidification occur, and mitochondrial contents, including mtDNA, are degraded.
Somatostatin stimulates intestinal NHE8 expression via p38 MAPK pathway
Authors: Wang Chunhui , Xu Hua , Chen Huacong , Li Jing , Zhang Bo , Tang Chengwei , Ghishan Fayez K.
Published: November 2010

Diarrhea is a common manifestation of gastrointestinal disorders. Diarrhea-induced losses of fluid and electrolyte could lead to dehydration and electrolyte imbalances, resulting in significant morbidity and mortality, especially in children living in developing countries. Somatostatin, a peptide hormone secreted by D-cells, plays an important role in regulating motility and intestinal Na+ absorption. Although octreotide, a somatostatin analog, is used to treat diarrhea, its mechanisms of action are unclear. Here we showed that octreotide increased brush-border membrane Na+/H+ exchanger 8 (NHE8) expression in the small intestine to the exclusion of other NHEs that participate in Na+ absorption. The same effect also occurred in human intestinal cells (Caco-2). We found that the increase of NHE8 expression by somatostatin required p38 mitogen-activated protein kinase (MAPK) activation. Furthermore, the somatostatin receptor SSTR2 antagonist CYN154806 could abolish somatostatin-induced NHE8 expression and p38 MAPK phosphorylation. Thus our data provided the first concrete evidence indicating that somatostatin stimulates intestinal Na+ absorption by increasing intestinal NHE8 expression through the SSTR2-p38 MAPK pathway.