bluuebunny/crossref_metadata_2025 huggingface dataset:
The Shortfall in Development Investment: a comment on Jayawardena's proposal
Authors: Dangeard Alain
Published: August 2010

SUMMARY The spirit behind Jayawardena's proposal for a new recycling mechanism is more important than the details, which can be faulted on several counts. It emphasises interdependence, the need for a unilateral gesture by the EEC during a period of soft oil prices, and the need for reciprocal action from the oil surplus countries. However, these three elements can be woven together into a different, more viable pattern. An alternative approach would be for developing countries to set up sectoral priority programmes, designed in consultation with surplus countries. These would then form a framework for private, decentralised initiatives in which risk capital from both developed and OPEC states would enter into joint ventures with local interests.

RESUMEN El déficit en la inversión para el desarrollo. Un comentaio sobre la proposición de Jayawardena

El espíritu que sustenta la proposición de Jayawardena, para un nuevo mecanismo de reciclaje, es más importante que los detalles, los cuales pueden ser defectuosos en varios aspectos. La proposición enfatiza la interdependencia, la necesidad de un gesto unilateral de la CEE durante un período de bajos precios del petróleo y de una acción reciproca de los países excedentarios de petróleo. Sin embargo, estos tres elementos pueden entrelazarse en un modelo diferente, con mayor viabilidad. Un enfoque alternativo para los países en desarrollo, podría consistir eestablecer programas sectoriales prioritarios, diseñados en consulta con los países excedentarios. A su vez, éstos formarían un sistema para iniciativas privadas descentralizadas, en et cual el capital invertido, tanto de los estados desarrollados como de los de la OPEP, entraría en empresas conjuntas con intereses locales.

RÉSUMÉ L'Insuffisance de l'Investìssement dans le Développement: un commentaire sur la proposition de Jayawardena

L'idée derrière la proposition de Jayawardena d'un nouveau mécanisme de recyclage est plus importante que les détails, qui peuvent s'avérer faux sur plusieurs points. Elle souligne l'importance de l'interdépendance, le besoin d'une action unilatérale de la part de la CEE à une période où les prix du pétrole sont modérés, et le besoin d'une action réciproque de la part des pays excédentaires de pétrole. Toutefois, ces trois éléments peuvent être regroupés et ainsi créer un plan différent et plus viable. Une autre approche serait une mise en place par les pays en voie de développement de programmes prioritaires par secteur, élaborés en collaboration avec les pays excédentaires. Ils formeraient ainsi un encadrement pour des initiatives privées et décentralisées où les capitaux risqués à la fois par les pays développés et les pays del'OPEPseraient investis dans des projets liés aux intérêts locaux
An Emerging Disease Causes Regional Population Collapse of a Common North American Bat Species
Authors: Frick Winifred F. , Pollock Jacob F. , Hicks Alan C. , Langwig Kate E. , Reynolds D. Scott , Turner Gregory G. , Butchkoski Calvin M. , Kunz Thomas H.
Published: August 2010

Threats to and from Bats

Bats appear to be able to host an assortment of alarming pathogens, which, if they do not extirpate the bats, have implications for human health (see the Perspective by

Daszak

). For example, exposure to bats is the main source of human rabies in the Americas. But rabies is not generally transmitted among people; humans are a dead end for the virus.

Streicker
et al.

(p.
676
, see the cover) show that rabies virus lineages tend to be specific for bat lineages. It seems that although rabies viruses have the potential for rapid evolution, this property alone is not enough to overcome genetic barriers, which inhibit the onward transmission of rabies virus into a new species. White-nose syndrome, an exotic fungal infection of bats, has, over the past 3 years, spread from upstate New York to West Virginia, killing on average 70% of the animals in a hibernating colony. The infection makes bats restless over winter when they should be dormant, which makes them exhaust their fat reserves, resulting in the death of over a million bats.

Frick
et al.

(p.
679
) have analyzed population data collected on bats in the northeastern United States for the past 30 years and show that, mainly owing to white-nose syndrome, the once abundant little brown bat is heading for regional extinction in the next 16 years or so. This scale of loss of an insectivorous mammal is expected to have repercussions for ecosystem integrity and for the economic costs of agricultural pest control.
Host Phylogeny Constrains Cross-Species Emergence and Establishment of Rabies Virus in Bats
Authors: Streicker Daniel G. , Turmelle Amy S. , Vonhof Maarten J. , Kuzmin Ivan V. , McCracken Gary F. , Rupprecht Charles E.
Published: August 2010

Threats to and from Bats

Bats appear to be able to host an assortment of alarming pathogens, which, if they do not extirpate the bats, have implications for human health (see the Perspective by

Daszak

). For example, exposure to bats is the main source of human rabies in the Americas. But rabies is not generally transmitted among people; humans are a dead end for the virus.

Streicker
et al.

(p.
676
, see the cover) show that rabies virus lineages tend to be specific for bat lineages. It seems that although rabies viruses have the potential for rapid evolution, this property alone is not enough to overcome genetic barriers, which inhibit the onward transmission of rabies virus into a new species. White-nose syndrome, an exotic fungal infection of bats, has, over the past 3 years, spread from upstate New York to West Virginia, killing on average 70% of the animals in a hibernating colony. The infection makes bats restless over winter when they should be dormant, which makes them exhaust their fat reserves, resulting in the death of over a million bats.

Frick
et al.

(p.
679
) have analyzed population data collected on bats in the northeastern United States for the past 30 years and show that, mainly owing to white-nose syndrome, the once abundant little brown bat is heading for regional extinction in the next 16 years or so. This scale of loss of an insectivorous mammal is expected to have repercussions for ecosystem integrity and for the economic costs of agricultural pest control.
China's Innovation Landscape
Authors: Huang Kenneth G.
Published: August 2010

A growing, domestic, private-sector and geographic diffusion of capacity mark the first two decades of China's patent system.
Vanadium Nitrogenase Reduces CO
Authors: Lee Chi Chung , Hu Yilin , Ribbe Markus W.
Published: August 2010

An enzyme that reduces nitrogen to ammonia can also reduce carbon monoxide to hydrocarbons.
As Questions Grow, Duke Halts Trials, Launches Investigation
Authors: Couzin-Frankel Jennifer
Published: August 2010

A pair of biostatisticians' questions about a prominent genetics group at Duke University have led Duke to investigate the researcher in question, and there are calls for a general review of the field.
Unique Th1/Th2 Phenotypes Induced during Priming and Memory Phases by Use of Interleukin-12 (IL-12) or IL-28B Vaccine Adjuvants in Rhesus Macaques
Authors: Morrow Matthew P. , Yan Jian , Pankhong Panyupa , Ferraro Bernadette , Lewis Mark G. , Khan Amir S. , Sardesai Niranjan Y. , Weiner David B.
Published: August 2010

Adjuvant compounds are usually included in vaccinations in order to bolster total vaccine-specific responses or to tailor an immune response toward a desired endpoint, such as the production of gamma interferon or an increase in antibody titers. While most adjuvants are studied in regard to their impact on vaccine-specific responses during and just after the vaccination period, a detailed analysis of how adjuvants skew the Th1/Th2 axis at more distant time points is not often undertaken. In the current study, we present data that suggests that adjuvants differ in their relative abilities to bolster and skew immune responses in the short term compared with more distant time points. To that end, we have employed interleukin-12 (IL-12) and IL-28B as adjuvants for DNA vaccination of rhesus macaques. While both adjuvants were able to bolster Th1-biased responses, our analysis shows that this skewing was achieved through different mechanisms. Moreover, analysis 3 months after the final immunization revealed the activity of the IL-12 adjuvant to be short lived, while the IL-28B adjuvant continued to exert its influence on the immune system. Taken together, these data suggest that the scientific and medical communities would benefit from a more detailed analysis of adjuvant function, including the determination of long-term influences of administered adjuvants.
Biochip System for Rapid and Accurate Identification of Mycobacterial Species from Isolates and Sputum
Authors: Zhu Lingxiang , Jiang Guanglu , Wang Shengfen , Wang Can , Li Qiang , Yu Hao , Zhou Yang , Zhao Bing , Huang Hairong , Xing Wanli , Mitchelson Keith , Cheng Jing , Zhao Yanlin , Guo Yong
Published: August 2010

The accurate detection of mycobacterial species from isolates and clinical samples is important for pathogenic diagnosis and treatment and for disease control. There is an urgent need for the development of a rapid, simple, and accurate detection method. We established a biochip assay system, including a biochip, sample preparation apparatus, hybridization instrument, chip washing machine, and laser confocal scanner equipped with interpretation software for automatic diagnosis. The biochip simultaneously identified 17 common mycobacterial species by targeting the differences in the 16S rRNA. The system was assessed with 64 reference strains and 296
Mycobacterium tuberculosis
and 243 nontuberculous mycobacterial isolates, as well as 138 other bacteria and 195 sputum samples, and then compared to DNA sequencing. The entire biochip assay took 6 h. The concordance rate between the biochip assay and the DNA sequencing results was 100%. In conclusion, the biochip system provides a simple, rapid, reliable, and highly accurate clinical assay for determination of mycobacterial species in a 6-h procedure, from either culture isolates or sputum samples, allowing earlier pathogen-adapted antimicrobial therapy in patients.
Unusual “Flesh-Eating” Strain ofEscherichia coli
Authors: Grimaldi David , Bonacorsi Stéphane , Roussel Hélène , Zuber Benjamin , Poupet Hélène , Chiche Jean-Daniel , Poyart Claire , Mira Jean-Paul
Published: August 2010

We report an exceptional case of life-threateningEscherichia coli-induced necrotizing fasciitis. A combined host-pathogen genetic analysis explained the phenotype: the host displayed a susceptibility to intravascular coagulation, and the strain was capable of producing a necrotic toxin (cytotoxic necrotizing factor 1), showing howE. colican be a dermonecrotic pathogen.
PCR-Based Pooling of Dried Blood Spots for Detection of Malaria Parasites: Optimization and Application to a Cohort of Ugandan Children
Authors: Hsiang Michelle S. , Lin Michael , Dokomajilar Christian , Kemere Jordan , Pilcher Christopher D. , Dorsey Grant , Greenhouse Bryan
Published: August 2010

Sensitive, high-throughput methods to detect malaria parasites in low-transmission settings are needed. PCR-based pooling strategies may offer a solution. We first used laboratory-prepared samples to compare 2 DNA extraction and 4 PCR detection methods across a range of pool sizes and parasite densities. Pooled Chelex extraction of DNA, followed by nested PCR of cytochromeb, was the optimal strategy, allowing reliable detection of a single low-parasitemic sample (100 parasites/μl) in pool sizes up to 50. This PCR-based pooling strategy was then compared with microscopy using 891 dried blood spots from a cohort of 77 Ugandan children followed for 2 years in an urban setting of low endemicity. Among 419 febrile episodes, 35 cases of malaria were detected using the PCR-based pooling strategy and 40 cases using microscopy. All five cases of malaria not detected by PCR were from samples stored for >2 years with parasitemia of <6,000/μl, highlighting the issue of possible DNA degradation with long-term storage of samples. Among 472 samples collected from asymptomatic children as part of routine surveillance, 15 (3.2%) were positive by PCR-based pooling compared to 4 (0.8%) by microscopy (P= 0.01). Thus, this PCR-based pooling strategy for detection of malaria parasites using dried blood spots offers a sensitive and efficient approach for malaria surveillance in low-transmission settings, enabling improved detection of asymptomatic submicroscopic infections and dramatic savings in labor and costs.
Monascus ruber
: Invasive Gastric Infection Caused by Dried and Salted Fish Consumption
Authors: Iriart Xavier , Fior Angela , Blanchet Denis , Berry Antoine , Neron Paul , Aznar Christine
Published: August 2010

We report a case of invasive gastric infection caused by
Monascus ruber
observed in a patient from French Guiana with gastric adenocarcinoma. The originality of this case is that, first, this invasive mycosis is extremely rare and, second, the probable mode of infection was by the consumption of
Monascus ruber
-contaminated food.
Trends in Methicillin-Resistant
Staphylococcus aureus
Anovaginal Colonization in Pregnant Women in 2005 versus 2009
Authors: Top Karina A. , Huard Richard C. , Fox Zachary , Wu Fann , Whittier Susan , Della-Latta Phyllis , Saiman Lisa , Ratner Adam J.
Published: August 2010

In 2005, the prevalence of methicillin-resistant
Staphylococcus aureus
(MRSA) anovaginal colonization in pregnant women at our center (Columbia University Medical Center) was 0.5%, and MRSA-colonized women were less likely to carry group B streptococcus (GBS). In this study, our objectives were to identify changing trends in the prevalence of MRSA and methicillin-susceptible
S. aureus
(MSSA) anovaginal colonization in pregnant women, to assess the association between MRSA and GBS colonization, and to characterize the MRSA strains. From February to July 2009, Lim broths from GBS surveillance samples were cultured for
S. aureus
. MRSA strains were identified by resistance to cefoxitin and characterized by MicroScan, staphylococcal cassette chromosome
mec
(SCC
mec
) typing, pulsed-field gel electrophoresis (PFGE),
spa
typing, and Panton-Valentine leukocidin PCR. A total of 2,921 specimens from different patients were analyzed. The prevalences of MSSA, MRSA, and GBS colonization were 11.8%, 0.6% and 23.3%, respectively. GBS colonization was associated with
S. aureus
colonization (odds ratio [OR], 1.9; 95% confidence interval [95% CI], 1.5 to 2.4). The frequencies of GBS colonization were similar in MRSA-positive (34.2%) versus MRSA-negative patients (21.8%) (
P
= 0.4). All MRSA isolates from 2009 and 13/14 isolates from 2005 were SCC
mec
type IV or V, consistent with community-associated MRSA; 12/18 (2009) and 0/14 (2005) isolates were the USA300 clone. Levofloxacin resistance increased from 14.3% (2005) to 55.6% (2009) (
P
= 0.028). In conclusion, the prevalence of MRSA anovaginal colonization in pregnant women in New York City, NY, remained stable from 2005 to 2009, and USA300 emerged as the predominant clone with a significant increase in levofloxacin-resistant isolates.
Herpes Simplex Virus Immediate-Early ICP0 Protein Inhibits Toll-Like Receptor 2-Dependent Inflammatory Responses and NF-κB Signaling
Authors: van Lint Allison L. , Murawski Matthew R. , Goodbody Rory E. , Severa Martina , Fitzgerald Katherine A. , Finberg Robert W. , Knipe David M. , Kurt-Jones Evelyn A.
Published: August 2010

The discovery of the Toll-like receptors (TLRs) and their importance in the regulation of host responses to infection raised attention to the complex interplay between viral gene products and the host innate immune responses in determining the outcome of virus infection. Robust inflammatory cytokine responses are observed in herpes simplex virus (HSV)-infected animals and cells. Our studies have demonstrated that Toll-like receptor 2 (TLR2) activation by HSV results in NF-κB activation with concomitant inflammatory cytokine production and that TLR2 activation plays a critical role in HSV-induced pathology and mortality. Here we demonstrate that the HSV-1 immediate-early ICP0 protein reduces the TLR2-mediated inflammatory response to HSV 1 (HSV-1) infection. Expression of ICP0 alone is sufficient to block TLR2-driven responses to both viral and nonviral ligands at or downstream of the MyD88 adaptor and upstream of p65. ICP0 alone can also reduce the levels of MyD88 and Mal (TIRAP). In HSV-infected cells, the E3 ligase function of ICP0 and cellular proteasomal activity are required for the inhibitory activity. Our results argue for a model in which ICP0 promotes the degradation of TLR adaptor molecules and inhibition of the inflammatory response, much as it inhibits the interferon response by sequestration and degradation of interferon regulatory factor 3 (IRF-3).
Adenovirus-Based Vaccines: Comparison of Vectors from Three Species of
Adenoviridae
Authors: Chen H. , Xiang Z. Q. , Li Y. , Kurupati R. K. , Jia B. , Bian A. , Zhou D. M. , Hutnick N. , Yuan S. , Gray C. , Serwanga J. , Auma B. , Kaleebu P. , Zhou X. , Betts M. R. , Ertl H. C. J.
Published: August 2010

In order to better understand the broad applicability of adenovirus (Ad) as a vector for human vaccine studies, we compared four adenovirus (Ad) vectors from families C (Ad human serotype 5 [HAdV-5; here referred to as AdHu5]), D (HAdV-26; here referred to as AdHu26), and E (simian serotypes SAdV-23 and SAdV-24; here referred to as chimpanzee serotypes 6 and 7 [AdC6 and AdC7, respectively]) of the
Adenoviridae
. Seroprevalence rates and titers of neutralizing antibodies to the two human-origin Ads were found to be higher than those reported previously, especially in countries of sub-Saharan Africa. Conversely, prevalence rates and titers to AdC6 and AdC7 were markedly lower. Healthy human adults from the United States had readily detectable circulating T cells recognizing Ad viruses, the levels of which in some individuals were unexpectedly high in response to AdHu26. The magnitude of T-cell responses to AdHu5 correlated with those to AdHu26, suggesting T-cell recognition of conserved epitopes. In mice, all of the different Ad vectors induced CD8
+
T-cell responses that were comparable in their magnitudes and cytokine production profiles. Prime-boost regimens comparing different combinations of Ad vectors failed to indicate that the sequential use of Ad vectors from distinct families resulted in higher immune responses than the use of serologically distinct Ad vectors from the same family. Moreover, the transgene product-specific antibody responses induced by the AdHu26 and AdC vectors were markedly lower than those induced by the AdHu5 vector. AdHu26 vectors and, to a lesser extent, AdC vectors induced more potent Ad-neutralizing antibody responses. These results suggest that the potential of AdHu26 as a vaccine vector may suffer from limitations similar to those found for vectors based on other prevalent human Ads.
Ultrastructural and Biophysical Characterization of Hepatitis C Virus Particles Produced in Cell Culture
Authors: Gastaminza Pablo , Dryden Kelly A. , Boyd Bryan , Wood Malcolm R. , Law Mansun , Yeager Mark , Chisari Francis V.
Published: August 2010

We analyzed the biochemical and ultrastructural properties of hepatitis C virus (HCV) particles produced in cell culture. Negative-stain electron microscopy revealed that the particles were spherical (∼40- to 75-nm diameter) and pleomorphic and that some of them contain HCV E2 protein and apolipoprotein E on their surfaces. Electron cryomicroscopy revealed two major particle populations of ∼60 and ∼45 nm in diameter. The ∼60-nm particles were characterized by a membrane bilayer (presumably an envelope) that is spatially separated from an internal structure (presumably a capsid), and they were enriched in fractions that displayed a high infectivity-to-HCV RNA ratio. The ∼45-nm particles lacked a membrane bilayer and displayed a higher buoyant density and a lower infectivity-to-HCV RNA ratio. We also observed a minor population of very-low-density, >100-nm-diameter vesicular particles that resemble exosomes. This study provides low-resolution ultrastructural information of particle populations displaying differential biophysical properties and specific infectivity. Correlative analysis of the abundance of the different particle populations with infectivity, HCV RNA, and viral antigens suggests that infectious particles are likely to be present in the large ∼60-nm HCV particle populations displaying a visible bilayer. Our study constitutes an initial approach toward understanding the structural characteristics of infectious HCV particles.
Rearranged JC Virus Noncoding Control Regions Found in Progressive Multifocal Leukoencephalopathy Patient Samples Increase Virus Early Gene Expression and Replication Rate
Authors: Gosert Rainer , Kardas Piotr , Major Eugene O. , Hirsch Hans H.
Published: August 2010

Polyomavirus JC (JCV) infects ∼60% of the general population, followed by asymptomatic urinary shedding in ∼20%. In patients with pronounced immunodeficiency, including HIV/AIDS, JCV can cause progressive multifocal leukoencephalopathy (PML), a devastating brain disease of high mortality. While JCV in the urine of healthy people has a linear noncoding control region called the archetype NCCR (
at
-NCCR), JCV in brain and cerebrospinal fluid (CSF) of PML patients bear rearranged NCCRs (
rr
-NCCRs). Although JCV NCCR rearrangements are deemed pathognomonic for PML, their role as a viral determinant is unclear. We sequenced JCV NCCRs found in CSF of eight HIV/AIDS patients newly diagnosed with PML and analyzed their effect on early and late gene expression using a bidirectional reporter vector recapitulating the circular polyomavirus early and late gene organization. The
rr
-NCCR sequences were highly diverse, but all increased viral early reporter gene expression in progenitor-derived astrocytes, glia-derived cells, and human kidney compared to the expression levels with the
at
-NCCR. The expression of simian virus 40 (SV40) large T antigen or HIV Tat expression in
trans
was associated with a strong increase of
at
-NCCR-controlled early gene expression, while
rr
-NCCRs were less responsive. The insertion of
rr-
NCCRs into the JCV genome backbone revealed higher viral replication rates for
rr
-NCCR compared to those of the
at
-NCCR JCV in human progenitor-derived astrocytes or glia cells, which was abrogated in SV40 large T-expressing COS-7 cells. We conclude that naturally occurring JCV
rr
-NCCR variants from PML patients confer increased early gene expression and higher replication rates compared to those of
at-
NCCR JCV and thereby increase cytopathology.
Genomic Characterization of Severe Acute Respiratory Syndrome-Related Coronavirus in European Bats and Classification of Coronaviruses Based on Partial RNA-Dependent RNA Polymerase Gene Sequences
Authors: Drexler Jan Felix , Gloza-Rausch Florian , Glende Jörg , Corman Victor Max , Muth Doreen , Goettsche Matthias , Seebens Antje , Niedrig Matthias , Pfefferle Susanne , Yordanov Stoian , Zhelyazkov Lyubomir , Hermanns Uwe , Vallo Peter , Lukashev Alexander , Müller Marcel Alexander , Deng Hongkui , Herrler Georg , Drosten Christian
Published: August 2010

Bats may host emerging viruses, including coronaviruses (CoV). We conducted an evaluation of CoV in rhinolophid and vespertilionid bat species common in Europe. Rhinolophids carried severe acute respiratory syndrome (SARS)-related CoV at high frequencies and concentrations (26% of animals are positive; up to 2.4 × 10
8
copies per gram of feces), as well as two
Alphacoronavirus
clades, one novel and one related to the HKU2 clade. All three clades present in
Miniopterus
bats in China (HKU7, HKU8, and 1A related) were also present in European
Miniopterus
bats. An additional novel
Alphacoronavirus
clade (bat CoV [BtCoV]/BNM98-30) was detected in
Nyctalus leisleri
. A CoV grouping criterion was developed by comparing amino acid identities across an 816-bp fragment of the RNA-dependent RNA polymerases (RdRp) of all accepted mammalian CoV species (RdRp-based grouping units [RGU]). Criteria for defining separate RGU in mammalian CoV were a >4.8% amino acid distance for alphacoronaviruses and a >6.3% distance for betacoronaviruses. All the above-mentioned novel clades represented independent RGU. Strict associations between CoV RGU and host bat genera were confirmed for six independent RGU represented simultaneously in China and Europe. A SARS-related virus (BtCoV/BM48-31/Bulgaria/2008) from a
Rhinolophus blasii
(Rhi bla) bat was fully sequenced. It is predicted that proteins 3b and 6 were highly divergent from those proteins in all known SARS-related CoV. Open reading frame 8 (ORF8) was surprisingly absent. Surface expression of spike and staining with sera of SARS survivors suggested low antigenic overlap with SARS CoV. However, the receptor binding domain of SARS CoV showed higher similarity with that of BtCoV/BM48-31/Bulgaria/2008 than with that of any Chinese bat-borne CoV. Critical spike domains 472 and 487 were identical and similar, respectively. This study underlines the importance of assessments of the zoonotic potential of widely distributed bat-borne CoV.
Efficacious Early Antiviral Activity of HIV Gag- and Pol-Specific HLA-B*2705-Restricted CD8
+
T Cells
Authors: Payne Rebecca P. , Kløverpris Henrik , Sacha Jonah B. , Brumme Zabrina , Brumme Chanson , Buus Søren , Sims Stuart , Hickling Stephen , Riddell Lynn , Chen Fabian , Luzzi Graz , Edwards Anne , Phillips Rodney , Prado Julia G. , Goulder Philip J. R.
Published: August 2010

The association between HLA-B*2705 and the immune control of human immunodeficiency virus type 1 (HIV-1) has previously been linked to the targeting of the HLA-B*2705-restricted Gag epitope KRWIILGLNK (KK10) by CD8
+
T cells. In order to better define the mechanisms of the HLA-B*2705 immune control of HIV, we first characterized the CD8
+
T-cell responses of nine highly active antiretroviral therapy (HAART)-naïve B*2705-positive subjects. Unexpectedly, we observed a strong response to an HLA-B*2705-restricted Pol epitope, KRKGGIGGY (KY9), in 8/9 subjects. The magnitude of the KY9 response was only marginally lower than that of the KK10-specific response (median, 695 versus 867 spot-forming cells [SFC]/million peripheral blood mononuclear cells [PBMCs]; not significant [NS]), and viral escape mutants were observed in both KY9 and KK10, resulting from selection pressure driven by the respective CD8
+
T-cell response. By comparing inhibitions of viral replication by CD8
+
T cells specific for the Gag KK10, Pol KY9, and Vpr VL9 HLA-B*2705-restricted epitopes, we observed a consistent hierarchy of antiviral efficacy (Gag KK10 > Pol KY9 > Vpr VL9). This hierarchy was associated with early recognition of HIV-1-infected cells, within 6 h of infection, by KK10- and KY9-specific CD8
+
T cells but not until 18 h postinfection by VL9-specific CD8
+
T cells. There was no association between antiviral efficacy and proliferative capacity, cytotoxicity, polyfunctionality, or T-cell receptor (TCR) avidity. These data are consistent with previous studies indicating an important role for the B*2705-Gag KK10 response in the control of HIV but also suggest a previously unrecognized role played by the subdominant Pol-specific KY9 response in HLA-B*2705-mediated control of HIV and that the recognition of HIV-infected cells by CD8
+
T cells early in the viral life cycle may be important for viral containment in HIV-infected individuals.
Epitope-Specific Regulatory CD4 T Cells Reduce Virus-Induced Illness while Preserving CD8 T-Cell Effector Function at the Site of Infection
Authors: Liu Jie , Ruckwardt Tracy J. , Chen Man , Nicewonger John D. , Johnson Teresa R. , Graham Barney S.
Published: August 2010

The role of epitope-specific regulatory CD4 T cells in modulating CD8 T-cell-mediated immunopathology during acute viral infection has not been well defined. In the murine model of respiratory syncytial virus (RSV) infection, CD8 T cells play an important role in both viral clearance and immunopathology. We have previously characterized two RSV epitope-specific CD4 T-cell responses with distinct phenotypic properties. One of them, the IAbM209-specific subset, constitutively expresses FoxP3 and modulates CD8 T-cell functionin vitro. We show here that the IAbM209-specific CD4 T-cell response regulates CD8 T-cell functionin vivoand is associated with diminished RSV-induced illness without affecting viral clearance at the site of infection. Achieving the optimal balance of regulatory and effector T-cell function is an important consideration for designing future vaccines.
The Endoplasmic Reticulum Provides the Membrane Platform for Biogenesis of the Flavivirus Replication Complex
Authors: Gillespie Leah K. , Hoenen Antje , Morgan Gary , Mackenzie Jason M.
Published: August 2010

The cytoplasmic replication of positive-sense RNA viruses is associated with a dramatic rearrangement of host cellular membranes. These virus-induced changes result in the induction of vesicular structures that envelop the virus replication complex (RC). In this study, we have extended our previous observations on the intracellular location of West Nile virus strain Kunjin virus (WNV
KUN
) to show that the virus-induced recruitment of host proteins and membrane appears to occur at a pre-Golgi step. To visualize the WNV
KUN
replication complex, we performed three-dimensional (3D) modeling on tomograms from WNV
KUN
replicon-transfected cells. These analyses have provided a 3D representation of the replication complex, revealing the open access of the replication complex with the cytoplasm and the fluidity of the complex to the rough endoplasmic reticulum. In addition, we provide data that indicate that a majority of the viral RNA species housed within the RC is in a double-stranded RNA (dsRNA) form.
High Level of Genetic Compatibility between Swine-Origin H1N1 and Highly Pathogenic Avian H5N1 Influenza Viruses
Authors: Octaviani Cássio Pontes , Ozawa Makoto , Yamada Shinya , Goto Hideo , Kawaoka Yoshihiro
Published: August 2010

Reassortment is an important mechanism for the evolution of influenza viruses. Here, we coinfected cultured cells with the pandemic swine-origin influenza virus (S-OIV) and a contemporary H5N1 virus and found that these two viruses have high genetic compatibility. Studies of human lung cell lines indicated that some reassortants had better growth kinetics than their parental viruses. We conclude that reassortment between these two viruses can occur and could create pandemic H5N1 viruses.
Small Peptide Inhibitors Disrupt a High-Affinity Interaction between Cytoplasmic Dynein and a Viral Cargo Protein
Authors: Hernáez Bruno , Tarragó Teresa , Giralt Ernest , Escribano Jose M. , Alonso Covadonga
Published: August 2010

Several viruses target the microtubular motor system in early stages of the viral life cycle. African swine fever virus (ASFV) protein p54 hijacks the microtubule-dependent transport by interaction with a dynein light chain (DYNLL1/DLC8). This was shown to be a high-affinity interaction, and the residues gradually disappearing were mapped on DLC8 to define a putative p54 binding surface by nuclear magnetic resonance (NMR) spectroscopy. The potential of short peptides targeting the binding domain to disrupt this high-affinity protein-protein interaction was assayed, and a short peptide sequence was shown to bind and compete with viral protein binding to dynein. Given the complexity and number of proteins involved in cellular transport, the prevention of this viral-DLC8 interaction might not be relevant for successful viral infection. Thus, we tested the capacity of these peptides to interfere with viral infection by disrupting dynein interaction with viral p54. Using this approach, we report on short peptides that inhibit viral growth.
STATIC ENDURANCE OF THE BACK EXTENSOR MUSCLES: ASSOCIATION BETWEEN PERFORMANCE AND REPORTED REASONS FOR TEST TERMINATION
Authors: Mbada Chidozie E. , Ayanniyi Olusola , Adedoyin Rufus A. , Johnson Olubusola E.
Published: August 2010

Purpose: Quite a few studies have reported previously on reasons for terminating tests of back muscles endurance. This study investigated the association between endurance performance and reported reasons for terminating back extensor muscle endurance test in apparently healthy adults. Methods: Three-hundred-and-seventy-six volunteers with the mean age of 38.9 ± 13.5 years participated in this study. All participants underwent modified Biering–Sørensen test of Static Muscular Endurance. Descriptive statistics of mean and standard deviation, Pearson's correlation and Chi-square, ANOVA and ANCOVA were used to analyze the data. The α level was set at 0.05. Results: It is found that 76.1% of the participants terminated the test due to fatigue in the low back, followed by low-back pain (LBP) (12.8%) and fatigue in the gluteal or hamstring muscles (7.4%) respectively. The magnitudes of the endurance time for each reason of termination — fatigue in the low back (121 ± 49.3 sec), fatigue in the gluteal or hamstring muscles (102 ± 44.0 sec), LBP (59 ± 27.4 sec), and behavioral factors (92 ± 34.7 sec) were found to be significantly different (p = 0.001). Test termination due to fatigue in the low back was on the average 62 seconds longer than that due to LBP. Conclusions: Fatigue was the most commonly reported reason for back extensor muscles' endurance test termination. Endurance time was least in those individuals who terminate the test due to complaints of LBP and greatest in those who end the task for fatigue only.
EOS: A NEW IMAGING SYSTEM WITH LOW DOSE RADIATION IN STANDING POSITION FOR SPINE AND BONE & JOINT DISORDERS
Authors: Dubousset Jean , Charpak Georges , Skalli Wafa , Deguise Jacques , Kalifa Gabriel
Published: August 2010

Very precise combined work between multidisciplinary partners (radiation engineers in physics, engineers in biomechanics, medical radiologists and orthopedic pediatric surgeons) has led to the concept and development of a new low-dose radiation device named EOS. This device has three main advantages: (1) Thanks to the invention of Georges Charpak who designed gaseous detectors for X-rays, the reduction of dose necessary to obtain a good image of skeletal system was 8 to 10 times less for 2D imaging; compared to the dose necessary to obtain a 3D reconstruction from CT scan cuts, the reduction factor was 800 to 1000. (2) The accuracy of 3D reconstruction obtained is better than that of 3D reconstruction from CT scan cuts. (3) The patient in addition gets imaged in a standing functional position, thanks to the AP and lateral X-rays obtained from head to feet simultaneously. This is a big advantage compared to CT scans which are used only in lying position. From the simultaneous AP and lateral X-rays of the whole body obtained via the 3D bone external envelop technique, the biomechanics engineers obtain 3D reconstruction of every level of osteo-articular system, especially for spine, in standing position with an acceptable period of time for reconstruction. This (in spite of the evolution of standing MRI) allows more precise bone reconstruction in orthopedics, especially at the level of the entire skeleton, including the head, spine, pelvis, lower limbs, giving new consideration for physiology, physiopathology and therapeutics.
CERVICAL INTRAMEDULLARY GLIOBLASTOMA WITH INTRACRANIAL DISSEMINATION: DESCRIPTION OF A RAPIDLY PROGRESSING CASE AND A LITERATURE REVIEW
Authors: Ando Kei , Matsuyama Yukihiro , Sakai Yoshito , Imagama Shiro , Ito Zenya , Wakao Norimitsu , Ishiguro Naoki
Published: August 2010

We present a case of a 65-year-old female with glioblastoma of the spinal cord, which disseminated to an intracranial lesion. Magnetic resonance imaging revealed diffuse swelling at levels C1 to 4, which was pathologically consistent with glioblastoma, and right side pontine parenchyma mass. The patient died after seven weeks of hospitalization. The confirmed diagnosis of glioblastomas was obtained as a result of autopsy. Spinal glioblastomas are rare lesions of the central nervous system with a prognosis as poor as that of their intracranial counterpart. There have been only nine reports in English since 1990, including this case in Japan.
Phase Change Memory Cell Using Si2Sb2Te3 Material
Authors: Ren Kun , Rao Feng , Song Zhitang , Wu Liangcai , Zhou Xilin , Liu Bo , Feng Songlin , Xi Wei , Chen Bomy
Published: August 2010

Phase memory cell based on Si2Sb2Te3 film shows reversible phase change ability between low and high resistance states. Crystalline Si2Sb2Te3 is a nano composite material consisted of amorphous Si and crystalline Sb2Te3, without separated Te phase. The thermally stable Si2Sb2Te3 material has a better data retention ability (10 years at 407 K) than that of Ge2Sb2Te5 material (10 years at 383 K). Moreover, the Si2Sb2Te3 based phase change memory cell shows good properties including faster operation speed and lower power consumption than those of the Ge2Sb2Te5 based cell.
Cellular Remodeling During Plant Virus Infection
Authors: Laliberté Jean-François , Sanfaçon Hélène
Published: August 2010

This review focuses on the extensive membrane and organelle rearrangements that have been observed in plant cells infected with RNA viruses. The modifications generally involve the formation of spherules, vesicles, and/or multivesicular bodies associated with various organelles such as the endoplasmic reticulum and peroxisomes. These virus-induced organelles house the viral RNA replication complex and are known as virus factories or viroplasms. Membrane and organelle alterations are attributed to the action of one or two viral proteins, which additionally act as a scaffold for the assembly of a large complex of proteins of both viral and host origin and viral RNA. Some virus factories have been shown to align with and traffic along microfilaments. In addition to viral RNA replication, the factories may be involved in other processes such as viral RNA translation and cell-to-cell virus transport. Confining the process of RNA replication to a specific location may also prevent the activation of certain host defense functions.
Studying Plant-Pathogen Interactions in the Genomics Era: Beyond Molecular Koch's Postulates to Systems Biology
Authors: Schneider David J. , Collmer Alan
Published: August 2010

Molecular factors enabling microbial pathogens to cause plant diseases have been sought with increasing efficacy over three research eras that successively introduced the tools of disease physiology, single-gene molecular genetics, and genomics. From this work emerged a unified model of the interactions of biotrophic and hemibiotrophic pathogens, which posits that successful pathogens typically defeat two levels of plant defense by translocating cytoplasmic effectors that suppress the first defense (surface arrayed against microbial signatures) while evading the second defense (internally arrayed against effectors). As is predicted from this model and confirmed by sequence pattern–driven discovery of large repertoires of cytoplasmic effectors in the genomes of many pathogens, the coevolution of (hemi)biotrophic pathogens and their hosts has generated pathosystems featuring extreme complexity and apparent robustness. These findings highlight the need for a fourth research era of systems biology in which virulence factors are studied as pathosystem components, and pathosystems are studied for their emergent properties.
Xanthomonas AvrBs3 Family-Type III Effectors: Discovery and Function
Authors: Boch Jens , Bonas Ulla
Published: August 2010

Xanthomonads are bacterial plant pathogens that cause diseases on many plant species, including important crops. Key to pathogenicity of most Xanthomonas pathovars is a Hrp-type III secretion (T3S) system that translocates effector proteins into plant cells. Within the eukaryotic cell, the effectors are thought to perform a variety of tasks to support bacterial virulence, proliferation, and dissemination. We are only beginning to understand the host targets of different effectors. The largest effector family found in Xanthomonas spp. is the AvrBs3/PthA or TAL (transcription activator-like) family. TAL effectors act as transcriptional activators in the plant cell nucleus. Specificity of TAL effectors is determined by a novel modular DNA-binding domain. Here, we describe the discovery of TAL effectors and their structure, activity, and host targets.
S100A1 promotes action potential-initiated calcium release flux and force production in skeletal muscle
Authors: Prosser Benjamin L. , Hernández-Ochoa Erick O. , Lovering Richard M. , Andronache Zoita , Zimmer Danna B. , Melzer Werner , Schneider Martin F.
Published: August 2010

The role of S100A1 in skeletal muscle is just beginning to be elucidated. We have previously shown that skeletal muscle fibers from S100A1 knockout (KO) mice exhibit decreased action potential (AP)-evoked Ca2+ transients, and that S100A1 binds competitively with calmodulin to a canonical S100 binding sequence within the calmodulin-binding domain of the skeletal muscle ryanodine receptor. Using voltage clamped fibers, we found that Ca2+ release was suppressed at all test membrane potentials in S100A1−/− fibers. Here we examine the role of S100A1 during physiological AP-induced muscle activity, using an integrative approach spanning AP propagation to muscle force production. With the voltage-sensitive indicator di-8-aminonaphthylethenylpyridinium, we first demonstrate that the AP waveform is not altered in flexor digitorum brevis muscle fibers isolated from S100A1 KO mice. We then use a model for myoplasmic Ca2+ binding and transport processes to calculate sarcoplasmic reticulum Ca2+ release flux initiated by APs and demonstrate decreased release flux and greater inactivation of flux in KO fibers. Using in vivo stimulation of tibialis anterior muscles in anesthetized mice, we show that the maximal isometric force response to twitch and tetanic stimulation is decreased in S100A1−/− muscles. KO muscles also fatigue more rapidly upon repetitive stimulation than those of wild-type counterparts. We additionally show that fiber diameter, type, and expression of key excitation-contraction coupling proteins are unchanged in S100A1 KO muscle. We conclude that the absence of S100A1 suppresses physiological AP-induced Ca2+ release flux, resulting in impaired contractile activation and force production in skeletal muscle.
Dact2 is expressed in the developing ureteric bud/collecting duct system of the kidney and controls morphogenetic behavior of collecting duct cells
Authors: Lee Wen-Chin , Hough Melinda T. , Liu Weijia , Ekiert Robert , Lindström Nils O. , Hohenstein Peter , Davies Jamie A.
Published: August 2010

The overall pattern of the developing kidney is set in large part by the developing ureteric bud/collecting duct system, and dysgenesis of this system accounts for a variety of clinically significant renal diseases. Understanding how the behavior of cells in the developing ureteric bud/collecting duct is controlled is therefore important to understanding the normal and abnormal kidney. Dact proteins have recently been identified as cytoplasmic regulators of intracellular signaling. Dact1 inhibits Wnt signaling, and Dact2 inhibits transforming growth factor (TGF)-β signaling. Here, we report that Dact2 is expressed in developing and adult mouse kidneys, specifically in the ureteric bud/collecting duct epithelium, a structure whose morphogenesis is controlled partially by TGF-β. When small interfering RNA is used to knock down Dact2 expression in collecting duct cells, they show some constitutive phospho-Smad2, undetectable in controls, and elevated phospho-Smad2 in response to TGF-β. They also show defective migration and, in a monolayer wound-healing assay, they fail to assemble a leading edge “cable” of actomyosin and advance instead as a disorganized mass of lamellipodium-bearing cells. This effect is seriously exacerbated by exogenous TGF-β, although control cells tolerate it well. In three-dimensional culture, Dact2 knockdown cells form cysts and branching tubules, but the outlines of the cysts made by knockdown cells are ragged rather than smooth and the branching tubules are decorated with many fine spikes not seen in controls. These data suggest Dact2 plays a role in regulating morphogenesis by renal collecting duct cells, probably by protecting cells from overly strong TGF-β pathway activation.
Context-Dependent Partitioning of Motor Learning in Bimanual Movements
Authors: Howard Ian S. , Ingram James N. , Wolpert Daniel M.
Published: August 2010

Human subjects easily adapt to single dynamic or visuomotor perturbations. In contrast, when two opposing dynamic or visuomotor perturbations are presented sequentially, interference is often observed. We examined the effect of bimanual movement context on interference between opposing perturbations using pairs of contexts, in which the relative direction of movement between the two arms was different across the pair. When each perturbation direction was associated with a different bimanual context, such as movement of the arms in the same direction versus movement in the opposite direction, interference was dramatically reduced. This occurred over a short period of training and was seen for both dynamic and visuomotor perturbations, suggesting a partitioning of motor learning for the different bimanual contexts. Further support for this was found in a series of transfer experiments. Having learned a single dynamic or visuomotor perturbation in one bimanual context, subjects showed incomplete transfer of this learning when the context changed, even though the perturbation remained the same. In addition, we examined a bimanual context in which one arm was moved passively and show that the reduction in interference requires active movement. The sensory consequences of movement are thus insufficient to allow opposing perturbations to be co-represented. Our results suggest different bimanual movement contexts engage at least partially separate representations of dynamics and kinematics in the motor system.
Optogenetic fMRI Sheds Light on the Neural Basis of the BOLD Signal
Authors: Palmer Helen. S.
Published: August 2010

Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used as a measure of neuronal activity, despite an incomplete understanding of the hemodynamic and neural bases for BOLD signals. Recent work by Lee and colleagues investigated whether activating genetically specified neurons elicits BOLD responses. Integrating optogenetic control of specific cells and fMRI showed that stimulating excitatory neurons triggers a positive BOLD signal with conventional kinetics locally and delayed weaker BOLD signals distally.
Extensive Lysine Methylation in Hyperthermophilic Crenarchaea: Potential Implications for Protein Stability and Recombinant Enzymes
Authors: Botting Catherine H. , Talbot Paul , Paytubi Sonia , White Malcolm F.
Published: August 2010

In eukarya and bacteria, lysine methylation is relatively rare and is catalysed by sequence-specific lysine methyltransferases that typically have only a single-protein target. Using RNA polymerase purified from the thermophilic crenarchaeumSulfolobus solfataricus, we identified 21 methyllysines distributed across 9 subunits of the enzyme. The modified lysines were predominantly inα-helices and showed no conserved sequence context. A limited survey of theThermoproteus tenaxproteome revealed widespread modification with 52 methyllysines in 30 different proteins. These observations suggest the presence of an unusual lysine methyltransferase with relaxed specificity in the crenarchaea. Since lysine methylation is known to enhance protein thermostability, this may be an adaptation to a thermophilic lifestyle. The implications of this modification for studies and applications of recombinant crenarchaeal enzymes are discussed.