bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic drainage and endoscopic necrosectomy in the management of symptomatic pancreatic collections
Authors: ANG Tiing Leong , TEO Eng Kiong , FOCK Kwong Ming
Published: July 2009

OBJECTIVE:  To evaluate the role of endoscopic drainage and endoscopic necrosectomy in the management of symptomatic pancreatic fluid collection.

METHODS:  The clinical data of patients with symptomatic pancreatic fluid collection referred for endoscopic drainage were captured prospectively and analyzed. Pancreatic duct disruption was treated with stenting. Endosonography‐guided transmural drainage and endoscopic necrosectomy were performed when indicated.

RESULTS:  Fifteen consecutive patients (mean age 53.7 years; range 23–82 years) underwent endoscopic management of pancreatic fluid collections (pseudocysts: six; abscesses: six; infected walled‐off necrosis: three). Pancreatic duct fistulas were present in 13 patients. The drainage techniques used were: (i) transpapillary drainage; five; (ii) transmural drainage; two (these two patients had no pancreatic duct fistulas); and (iii) combined transpapillary and transmural drainage; eight. An additional transgastric endoscopic necrosectomy was performed in five patients. The endoscopic treatment was successful in all cases. The only complication was asymptomatic pneumo‐peritoneum that occurred in one patient. Combined transpapillary and transmural drainage led to the faster resolution of the fluid collection compared to transpapillary drainage (75.6 vs 147 days, P = 0.03). No recurrence occurred over a mean follow up of 486 days.

CONCLUSION:  Endoscopic drainage and endoscopic necrosectomy are safe and effective techniques for the treatment of symptomatic pancreatic fluid collection.
Spatial and Temporal Epidemiology of Sporadic Human Cryptosporidiosis in Scotland
Authors: Pollock K. G. J. , Ternent H. E. , Mellor D. J. , Chalmers R. M. , Smith H. V. , Ramsay C. N. , Innocent G. T.
Published: July 2009

The spatial and temporal epidemiology of human cryptosporidiosis was described by analysing sporadic cases reported in Scotland from 2005 to 2007. Measures of livestock density and human population density were explored as indicators of the geographical variation in prevalence. Cryptosporidium parvum was more common in areas with lower human population densities, with a higher ratio of the number of farms to human inhabitants and with a higher ratio of the number of private water supplies to human inhabitants. Cryptosporidium parvum caused disease in humans in rural areas and in areas with high ruminant livestock density, whereas Cryptosporidium hominis was more common in the more densely human populated areas of Scotland. The association of private water supplies and increased Cryptosporidium reports merits further public health efforts.
Screening for Nipah Virus Infection in West Kalimantan Province, Indonesia
Authors: Sendow I. , Field H. E. , Adjid A. , Ratnawati A. , Breed A. C. , Darminto  , Morrissy C. , Daniels P.
Published: July 2009

Compared to other viruses, research on Nipah virus has been limited in Indonesia because attributable disease outbreaks have not been reported. However, Nipah virus is a zoonotic Biosafety Level 4 (BSL4) agent, so strategic monitoring is prudent. Farmer interviews and a serologic survey of 610 pig sera and 99 bat sera from West Kalimantan province were conducted. Farmers reported no recent or historic encephalitic or respiratory disease in themselves, their families, workers or pigs. The survey found no evidence of exposure to Nipah virus in pigs. In contrast, 19% of the 84 Pteropus vampyrus bat sera reacted in the ELISA, but none of 15 Cynopterus brachyotis bats reacted.
Helical Nanofilament Phases
Authors: Hough L. E. , Jung H. T. , Krüerke D. , Heberling M. S. , Nakata M. , Jones C. D. , Chen D. , Link D. R. , Zasadzinski J. , Heppke G. , Rabe J. P. , Stocker W. , Körblova E. , Walba D. M. , Glaser M. A. , Clark N. A.
Published: July 2009

Packing Bananas and Boomerangs

Assembling achiral molecules typically generates achiral domains. However, odd things can happen when the molecules are banana-or boomerang-shaped—their cores can twist out of plain to form left- or right-handed helices, which can then pack into chiral domains that will polarize light (see the Perspective by
Amabilino
).

Hough
et al.

(p.
452
) show that if you make the situation even more complex by frustrating the packing of adjacent layers, you can create a material that appears to be macroscopically isotropic with only very local positional and orientational ordering of the molecules but still shows an overall chirality. In a second paper,

Hough
et al.

(p.
456
) also show that if you change the chemistry of the molecules to allow for better overall packing, you can create a situation where helical filaments form that also tend to pack in layered structures. However, the frustration between the two types of packing leads to macroscopically chiral and mesoporous structures.
Disentangling the Web of Life
Authors: Bascompte Jordi
Published: July 2009

Biodiversity research typically focuses on species richness and has often neglected interactions, either by assuming that such interactions are homogeneously distributed or by addressing only the interactions between a pair of species or a few species at a time. In contrast, a network approach provides a powerful representation of the ecological interactions among species and highlights their global interdependence. Understanding how the responses of pairwise interactions scale to entire assemblages remains one of the great challenges that must be met as society faces global ecosystem change.
A General Framework for Analyzing Sustainability of Social-Ecological Systems
Authors: Ostrom Elinor
Published: July 2009

A major problem worldwide is the potential loss of fisheries, forests, and water resources. Understanding of the processes that lead to improvements in or deterioration of natural resources is limited, because scientific disciplines use different concepts and languages to describe and explain complex social-ecological systems (SESs). Without a common framework to organize findings, isolated knowledge does not cumulate. Until recently, accepted theory has assumed that resource users will never self-organize to maintain their resources and that governments must impose solutions. Research in multiple disciplines, however, has found that some government policies accelerate resource destruction, whereas some resource users have invested their time and energy to achieve sustainability. A general framework is used to identify 10 subsystem variables that affect the likelihood of self-organization in efforts to achieve a sustainable SES.
Knockout Rats via Embryo Microinjection of Zinc-Finger Nucleases
Authors: Geurts Aron M. , Cost Gregory J. , Freyvert Yevgeniy , Zeitler Bryan , Miller Jeffrey C. , Choi Vivian M. , Jenkins Shirin S. , Wood Adam , Cui Xiaoxia , Meng Xiangdong , Vincent Anna , Lam Stephen , Michalkiewicz Mieczyslaw , Schilling Rebecca , Foeckler Jamie , Kalloway Shawn , Weiler Hartmut , Ménoret Séverine , Anegon Ignacio , Davis Gregory D. , Zhang Lei , Rebar Edward J. , Gregory Philip D. , Urnov Fyodor D. , Jacob Howard J. , Buelow Roland
Published: July 2009

Targeted gene disruption in rats paves the way for new human disease models.
Neglecting the Crucial “Why?”
Plastic Fantastic
How the Biggest Fraud in Physics Shook the Scientific World

by Eugenie Samuel Reich

Palgrave Macmillan, London, 2009. 270 pp. $26.95, C$29.95, £15.99. ISBN 9780230224674.
Authors: Eigler Donald
Published: July 2009

Reich discusses the Schön case and how it was handled by the journals that had been publishing his high-impact papers and by scientists in the affected fields.
Heat Exchange from the Toucan Bill Reveals a Controllable Vascular Thermal Radiator
Authors: Tattersall Glenn J. , Andrade Denis V. , Abe Augusto S.
Published: July 2009

Toucan Heat Exchanger

Toucans are instantly recognizable by their large bills, which in the toco toucan (
Ramphastos toco
) accounts for about one-third of the total body length. The toucan's bill has been interpreted as a sexual ornament and as an adaptation for handling fruit.

Tattersall
et al.

(p.
468
) explore an alternative explanation in which the bill serves primarily as a thermoregulator. Infrared thermography techniques, which allow detailed observations with minimal disturbance to the birds, show that the birds alter blood flow to the bill according to ambient conditions, effectively using it as a radiator to “dump heat.”
Connecting Organelles
Authors: Wiedemann Nils , Meisinger Chris , Pfanner Nikolaus
Published: July 2009

Protein contacts between mitochondria and the endoplasmic reticulum allow metabolic exchange and communication.
Spy Satellites Give Scientists A Sharper Image of Field Sites
Authors: Bhattacharjee Yudhijit
Published: July 2009

Last week, thanks to the U.S. intelligence community, researchers saw pictures that will allow them to model the breakup of sea ice at a level of detail they never imagined.
With ‘Phenomics,’ Plant Scientists Hope to Shift Breeding Into Overdrive
Authors: Finkel Elizabeth
Published: July 2009

Institutes worldwide are racing to build facilities with instrument arrays that can scan thousands of plants a day in an approach to science akin to high-throughput DNA sequencing.
Ourselves and Our Interactions: The Ultimate Physics Problem?
Authors: Cho Adrian
Published: July 2009

In the field of complex socioeconomic systems, physicists and others analyze people almost as if they were interchangeable electrons. Can that approach decipher society and what ails it?
Counterterrorism's New Tool: ‘Metanetwork’ Analysis
Authors: Bohannon John
Published: July 2009

Researchers have created sophisticated new programs to probe beneath the surface of social interactions. How well do they work against terrorists?
Census and Analysis of Persistent False-Negative Results in Serological Diagnosis of Human Immunodeficiency Virus Type 1 Group O Infections
Authors: Plantier J.-C. , Djemai M. , Lemée V. , Reggiani A. , Leoz M. , Burc L. , Vessière A. , Rousset D. , Poveda J.-D. , Henquell C. , Gautheret-Dejean A. , Barin F.
Published: July 2009

Human immunodeficiency viruses (HIV) have a high level of genetic diversity. The outlier variants of HIV type 1 (HIV-1) group O are distantly related to HIV-1 group M. Their divergence has an impact on serological diagnosis, with a risk of false-negative results. In this study, we report 20 failure cases, involving patients with primary or chronic infection, in France and Cameroon between 2001 and 2008. Our results indicate that some assays detected group O infection much less efficiently than others. Two major reasons for these false-negative results were identified: the presence or absence of a group O-specific antigen (and the designed sequence) for the detection of antibodies and the greater envelope variability of group O than of group M strains. This study highlights the complexity of screening for these divergent variants and the need to evaluate test performance with a large panel of strains, due to the extensive diversity of group O variants.
Variable-Number Tandem Repeat Analysis and Multilocus Sequence Typing Data Confirm the Epidemiological Changes Observed with
Staphylococcus aureus
Strains Isolated from Bloodstream Infections
Authors: van der Mee-Marquet Nathalie , François Patrice , Domelier Anne-Sophie , Arnault Laurence , Girard Nicole , Schrenzel Jacques , Quentin Roland
Published: July 2009

Since 2000, our geographical region in France systematically surveys bloodstream infections (BSI) due to
Staphylococcus aureus
. This survey involves 39 health care institutions (HCIs) encompassing 6,888 short-stay beds and was performed during two 3-month periods during 2007 and 2008. The study periods of this survey identified 292
S. aureus
isolates causing BSI. Extensive molecular characterization, including genotyping as well as toxin,
agr
, and staphylococcal cassette chromosome content determinations, allowed us to describe epidemiological evolution in comparison to that discussed in our previous study. Our main epidemiological observation shows that the incidence of BSI remained constant but that methicillin (meticillin)-resistant
S. aureus
strains with a wider variety of genetic backgrounds now harbor
pyl
, as has already been reported in different European countries. We noticed stable numbers of BSI episodes involving community-acquired methicillin-sensitive
S. aureus
(MSSA), whereas a drastic increase in the number of strains harboring the
tst
gene was recorded. The increase in the number of
tst
gene-harboring strains is related to known hospital-acquired MSSA isolates and appears related to epidemic episodes in specific HCIs. Monitoring the increase in prevalence of specific strains helps us understand where the standard precautions are not satisfactorily applied or do not efficiently prevent the spread of epidemic MSSA strains in these HCIs. The recent increases in incidence of these strains call for particular vigilance to avoid the spread of potentially virulent MSSA strains harboring the
tst
gene and for continuance of this strategy of BSI surveillance.
Performance of the RealStar Chikungunya Virus Real-Time Reverse Transcription-PCR Kit
Authors: Panning Marcus , Hess Markus , Fischer Waldemar , Grywna Klaus , Pfeffer Martin , Drosten Christian
Published: July 2009

A novel commercial Chikungunya virus real-time reverse transcription-PCR (RT-PCR) kit was evaluated on a comprehensive panel of original patient samples. The assay was 100% sensitive and specific in comparison to a published real-time RT-PCR. Viral loads from both assays were highly correlated. The kit proved to be suitable for routine use in patient care.
The Six-Helix Bundle of Human Immunodeficiency Virus Env Controls Pore Formation and Enlargement and Is Initiated at Residues Proximal to the Hairpin Turn
Authors: Markosyan Ruben M. , Leung Michael Y. , Cohen Fredric S.
Published: July 2009

Residues that create the grooves of the human immunodeficiency virus type 1 (HIV-1) Env triple-stranded coiled coil (HR1) and the residues that pack into the grooves (HR2) to complete the formation of the six-helix bundle (6HB) were mutated. The extent and kinetics of fusion as well as pore enlargement were measured for each mutant. Mutations near the hairpin turns of each monomer of the 6HB were more important than those far from the turn, for both HR1 and HR2. This result is consistent with the idea that binding of HR2 to the HR1 grooves is initiated near the hairpin turn of each monomer. Mutations at the distal portions also reduced fusion, albeit to a smaller extent. An intermediate of fusion (temperature-arrested state [TAS]) was formed, and the consequences of mutation were compared; a mutant that exhibited less fusion also showed slower kinetics from TAS. This suggests that formation of the bundle is a rate-limiting step downstream of the intermediate state. The rate of enlargement of a fusion pore also correlated with the extent and kinetics of fusion. The rate of pore enlargement was severely reduced by mutation. This supports our prior conclusion that formation of the 6HB occurs after pore creation and strongly suggests that the free energy released by bundle formation is directly used to promote pore growth.
Development of a Human Immunodeficiency Virus Type 1-Based Lentiviral Vector That Allows Efficient Transduction of both Human and Rhesus Blood Cells
Authors: Uchida Naoya , Washington Kareem N. , Hayakawa Jun , Hsieh Matthew M. , Bonifacino Aylin C. , Krouse Allen E. , Metzger Mark E. , Donahue Robert E. , Tisdale John F.
Published: July 2009

Human immunodeficiency virus type 1 (HIV-1) vectors transduce rhesus blood cells poorly due to a species-specific block by TRIM5α and APOBEC3G, which target HIV-1 capsid and viral infectivity factor (Vif), respectively. We sought to develop a lentiviral vector capable of transducing both human and rhesus blood cells by combining components of both HIV-1 and simian immunodeficiency virus (SIV), including SIV capsid (sCA) and SIV Vif. A chimeric HIV-1 vector including sCA (χHIV) was superior to the conventional SIV in transducing a human blood cell line and superior to the conventional HIV-1 vector in transducing a rhesus blood cell line. Among human CD34
+
hematopoietic stem cells (HSCs), the χHIV and HIV-1 vectors showed similar transduction efficiencies; in rhesus CD34
+
HSCs, the χHIV vector yielded superior transduction rates. In in vivo competitive repopulation experiments with two rhesus macaques, the χHIV vector demonstrated superior marking levels over the conventional HIV-1 vector in all blood lineages (first rhesus, 15 to 30% versus 1 to 5%; second rhesus, 7 to 15% versus 0.5 to 2%, respectively) 3 to 7 months postinfusion. In summary, we have developed an HIV-1-based lentiviral vector system that should allow comprehensive preclinical testing of HIV-1-based therapeutic vectors in the rhesus macaque model with eventual clinical application.
Prime-Boost Vaccination with Recombinant Mumps Virus and Recombinant Vesicular Stomatitis Virus Vectors Elicits an Enhanced Human Immunodeficiency Virus Type 1 Gag-Specific Cellular Immune Response in Rhesus Macaques
Authors: Xu R. , Nasar F. , Megati S. , Luckay A. , Lee M. , Udem S. A. , Eldridge J. H. , Egan M. A. , Emini E. , Clarke D. K.
Published: July 2009

Intramuscular inoculation of rhesus macaques with one or more doses of recombinant vesicular stomatitis virus (rVSV) expressing human immunodeficiency virus type 1 (HIV-1) Gag (rVSVgag) typically elicits peak cellular immune responses of 500 to 1,000 gamma interferon (IFN-γ) enzyme-linked immunospots (ELISPOTS)/10
6
peripheral blood lymphocytes (PBL). Here, we describe the generation of a novel recombinant mumps virus (rMuV) expressing HIV-1 Gag (rMuVgag) and measure the Gag-specific cellular immune responses detected in rhesus macaques following vaccination with a highly attenuated form of rVSV expressing HIV-1 Gag (rVSVN4CT1gag1) and rMuVgag in various prime-boost combinations. Notably, peak Gag-specific cellular immune responses of 3,000 to 3,500 ELISPOTS/10
6
PBL were detected in macaques that were primed with rMuVgag and boosted with rVSVN4CT1gag1. Lower peak cellular immune responses were detected in macaques that were primed with rVSVN4CT1gag1 and boosted with rMuVgag, although longer-term gag-specific responses appeared to remain higher in this group of macaques. These findings indicate that rMuVgag may significantly enhance Gag-specific cellular immune responses when administered with rVSVN4CT1gag1 in heterologous prime-boost regimens.
Detection of Mammalian Virulence Determinants in Highly Pathogenic Avian Influenza H5N1 Viruses: Multivariate Analysis of Published Data
Authors: Lycett S. J. , Ward M. J. , Lewis F. I. , Poon A. F. Y. , Kosakovsky Pond S. L. , Brown A. J. Leigh
Published: July 2009

Highly pathogenic avian influenza (HPAI) virus H5N1 infects water and land fowl and can infect and cause mortality in mammals, including humans. However, HPAI H5N1 strains are not equally virulent in mammals, and some strains have been shown to cause only mild symptoms in experimental infections. Since most experimental studies of the basis of virulence in mammals have been small in scale, we undertook a meta-analysis of available experimental studies and used Bayesian graphical models (BGM) to increase the power of inference. We applied text-mining techniques to identify 27 individual studies that experimentally determined pathogenicity in HPAI H5N1 strains comprising 69 complete genome sequences. Amino acid sequence data in all 11 genes were coded as binary data for the presence or absence of mutations related to virulence in mammals or nonconsensus residues. Sites previously implicated as virulence determinants were examined for association with virulence in mammals in this data set, and the sites with the most significant association were selected for further BGM analysis. The analyses show that virulence in mammals is a complex genetic trait directly influenced by mutations in polymerase basic 1 (PB1) and PB2, nonstructural 1 (NS1), and hemagglutinin (HA) genes. Several intra- and intersegment correlations were also found, and we postulate that there may be two separate virulence mechanisms involving particular combinations of polymerase and NS1 mutations or of NS1 and HA mutations.
Bypass Suppression of Small-Plaque Phenotypes by a Mutation in Poliovirus 2A That Enhances Apoptosis
Authors: Burgon Trever B. , Jenkins Jomaquai A. , Deitz Stephen B. , Spagnolo Jeannie F. , Kirkegaard Karla
Published: July 2009

The rate of protein secretion in host cells is inhibited during infection with several different picornaviruses, with consequences likely to have significant effects on viral growth, spread, and pathogenesis. This
Sin

+

(secretion inhibition) phenotype has been documented for poliovirus, foot-and-mouth disease virus, and coxsackievirus B3 and can lead to reduced cell surface expression of major histocompatibility complex class I and tumor necrosis factor receptor as well as reduced extracellular secretion of induced cytokines such as interleukin-6 (IL-6), IL-8, and beta interferon. The inhibition of protein secretion is global, affecting the movement of all tested cargo proteins through the cellular secretion apparatus. To test the physiological significance of the
Sin
−
and
Sin

+

phenotypes in animal models,
Sin
−
mutant viruses are needed that fail to inhibit host protein secretion and also exhibit robust growth properties. To identify such
Sin
−
mutant polioviruses, we devised a fluorescence-activated cell sorter-based screen to select virus-infected cells that nevertheless expressed newly synthesized surface proteins. After multiple rounds of selection, candidate
Sin
−
mutant viruses were screened for genetic stability, increased secretion of cargo molecules and wild-type translation and growth properties. A newly identified
Sin
−
mutant poliovirus that contained coding changes in nonstructural proteins 2A (N32D) and 2C (E253G) was characterized. In this virus, the 2C mutation is responsible for the
Sin
−
phenotype and the 2A mutation suppresses a resulting growth defect by increasing the rate of cell death and therefore the rate of viral spread. The 2A-N32D suppressor mutation was not allele specific and, by increasing the rate of cellular apoptosis, affected a completely different pathway than the 2C-E253G
Sin
−
mutation. Therefore, the 2A mutation suppresses the 2C-E253G mutant phenotype by a bypass suppression mechanism.
Cellular Restriction Targeting Viral Capsids Perturbs Human Immunodeficiency Virus Type 1 Infection of Nondividing Cells
Authors: Yamashita Masahiro , Emerman Michael
Published: July 2009

The ability of human immunodeficiency virus (HIV) to infect nondividing cells is a fundamental property by which HIV replicates in critical target cells, such as macrophages and resting CD4
+
T cells. Recent studies have revealed that the capsid (CA) protein is a dominant factor that determines retrovirus infectivity in nondividing cells, and several mutations in HIV type 1 (HIV-1) CA abrogate the ability of HIV-1 to infect nondividing cells. We present evidence for a connection between cellular restriction against viral capsids and the resistance of nondividing cells to retrovirus infection. TRIM proteins that are able to target incoming viral capsids restrict HIV-1 more potently in nondividing cells than in dividing cells, thus rendering HIV-1 infection dependent on cell division. Moreover, cyclophilin A, another cellular protein that binds to HIV-1 CA, regulates HIV-1 infection of nondividing cells. Together, these data demonstrate the importance of capsid-binding cellular proteins in the control of the cell cycle independence of HIV-1. We propose that cellular restrictions to retroviral infections are themselves cell cycle dependent.
Human Immunodeficiency Virus Type 1 Vpr Modulates Cellular Expression of UNG2 via a Negative Transcriptional Effect
Authors: Langevin Christelle , Maidou-Peindara Priscilla , Aas Per Arne , Jacquot Guillaume , Otterlei Marit , Slupphaug Geir , Benichou Serge
Published: July 2009

It was recently reported that human immunodeficiency virus type 1 (HIV-1) Vpr induced the proteasomal degradation of the nuclear UNG2 enzyme for efficient virus replication. We confirm here that HIV-1 infection and Vpr expression reduce the level of endogenous UNG2, but this effect is not reverted by treatment with the proteasome inhibitor MG132. Moreover, this reduction is not mediated by Vpr binding to UNG2 and is independent of the Vpr-induced G
2
arrest. Finally, we show that Vpr influences the
UNG2
promoter without affecting
UNG1
gene expression. These data indicate that the Vpr-induced decrease of UNG2 level is mainly related to a transcriptional effect.
Clinical evaluation of NucliSENS magnetic extraction and NucliSENS analytical specific reagents for the real-time detection of respiratory syncytial virus (RSV) in paediatric respiratory specimens
Authors: Manji R , Lotlikar M , Zhang F , Ginocchio C C
Published: July 2009

Aims:

To evaluate the combination of NucliSENS magnetic extraction and NucliSENS analytical specific reagents (bioMérieux, Marcy L’Etoile, France) for the detection of respiratory syncytial virus (RSV) from a variety of respiratory samples.

Methods:

Nucleic acids (NA) from paediatric samples (n = 603) and an RSV-specific inhibition control (R-IC) were coextracted using the miniMAG and/or the easyMAG. Nucleic-acid-sequence-based amplification (NASBA) and molecular beacon detection of RSV and R-IC were performed using NucliSENS analyte-specific reagents (NRSVA) and the NucliSENS EasyQ Analyzer. NRSVA results were compared with R-Mix culture and direct fluorescent antibody detection (DFA).

Results:

The NRSVA analytical specificity was 100%, and the NRSVA limit of detection was 5–20 RNA copies/reaction. The prediscordant analysis, sensitivity, specificity, PPV and NPV were, respectively, for R-Mix (64.7%, 100%, 100%, 94.5%); DFA (98.8%, 99.0%, 94.4%, 99.8%); NRSVA (94.1%, 95%, 75.5%, 99%). After discordant analysis, sensitivity, specificity, PPV and NPV were, respectively, for R-Mix (56.7%, 100%, 100%, 92.3%); DFA (87.6%, 99.2%, 95.5%, 97.7%); NRSVA (93.8%, 97%, 85.9%, 99%). RSV was detected in 17.8% of the samples and in seven coinfections. Children with proven RSV infection, compared with children without a pathogen identified, had shorter median hospitalisation stays (2 days vs 3 days, p = 0.035), used fewer antibiotics (54% vs 69%) and had shorter durations of antibiotic therapy (6.2 days vs 9.3 days, p = 0.021), respectively.

Conclusions:

NRSVA is sensitive and specific for RSV detection in respiratory samples. The R-IC monitored the test process, including NA extraction, target amplification and detection. The rapid detection of respiratory pathogens can foster appropriate patient management.
Occupational risk of lung cancer among lifetime non-smoking women in Shanghai, China
Authors: Pronk A , Coble J , Ji B-T , Shu X-O , Rothman N , Yang G , Gao Y-T , Zheng W , Chow W-H
Published: July 2009

Objectives:

Occupational lung carcinogens have been primarily studied in men. The aim of this study was to investigate occupational lung cancer risk in a cohort of Chinese non-smoking women.

Methods:

In 1996–2000, 71 067 non-smoking women who had held a job outside the home were interviewed for the prospective Shanghai Women’s Health Study in China. Exposure to lung carcinogens was assessed by matching occupation and industry titles from lifetime occupational histories with lists of jobs identified by the International Agency for Research on Cancer to have potential exposure to: (1) known (A-list); or (2) suspected (B-list) carcinogens. In addition, similar occupational titles were grouped independent of the a priori defined lists. Relative risks (RRs) were calculated using Cox proportional hazards regression.

Results:

During follow-up through 2005, 219 incident lung cancer cases were diagnosed. Jobs on the A-list and B-list were held by 0.8–6.7% and 2.7–9.4% of the cohort, respectively. Overall, ever holding any job on the A-list or B-list was not associated with lung cancer incidence. Indications of excess risk were found for two subgroups: painters (A-list) and rubber workers (B-list) (RR  =  2.0 and 1.7, respectively, p⩽0.1). An exploratory analysis of 35 occupational categories independent of the lists showed significantly increased risks for leather products/shoes, wood/paper products and miscellaneous production/transportation. The former two of these categories were similar to subgroups of the B-list, but broader than the specific a priori defined jobs.

Conclusions:

Significantly elevated lung cancer risk was associated with employment in some broad occupational categories that also included jobs with potential exposure to suspected carcinogens (B-list). The results suggest that although similar exposures to those described on the B-list may play a role in this cohort of Chinese women, carcinogenic exposure may not be restricted only to the jobs on the B-list.
UNIQUENESS, INTRACTABILITY AND EXACT ALGORITHMS: REFLECTIONS ON LEVEL-K PHYLOGENETIC NETWORKS
Authors: VAN IERSEL LEO , KELK STEVEN , MNICH MATTHIAS
Published: July 2009

Phylogenetic networks provide a way to describe and visualize evolutionary histories that have undergone so-called reticulate evolutionary events such as recombination, hybridization or horizontal gene transfer. The level k of a network determines how non-treelike the evolution can be, with level-0 networks being trees. We study the problem of constructing level-k phylogenetic networks from triplets, i.e. phylogenetic trees for three leaves (taxa). We give, for each k, a level-k network that is uniquely defined by its triplets. We demonstrate the applicability of this result by using it to prove that (1) for all k ≥ 1 it is NP-hard to construct a level-k network consistent with all input triplets, and (2) for all k ≥ 0 it is NP-hard to construct a level-k network consistent with a maximum number of input triplets, even when the input is dense. As a response to this intractability, we give an exact algorithm for constructing level-1 networks consistent with a maximum number of input triplets.
Acute molecular response of mouse hindlimb muscles to chronic stimulation
Authors: LaFramboise W. A. , Jayaraman R. C. , Bombach K. L. , Ankrapp D. P. , Krill-Burger J. M. , Sciulli C. M. , Petrosko P. , Wiseman R. W.
Published: July 2009

Stimulation of the mouse hindlimb via the sciatic nerve was performed for a 4-h period to investigate acute muscle gene activation in a model of muscle phenotype conversion. Initial force production (1.6 ± 0.1 g/g body wt) declined 45% within 10 min and was maintained for the remainder of the experiment. Force returned to initial levels upon study completion. An immediate-early growth response was present in the extensor digitorum longus (EDL) muscle (FOS, JUN, activating transcription factor 3, and musculoaponeurotic fibrosarcoma oncogene) with a similar but attenuated pattern in the soleus muscle. Transcript profiles showed decreased fast fiber-specific mRNA (myosin heavy chains 2A and 2B, fast troponins T3 and I, α-tropomyosin, muscle creatine kinase, and parvalbumin) and increased slow transcripts (myosin heavy chain-1β/slow, troponin C slow, and tropomyosin 3y) in the EDL versus soleus muscles. Histological analysis of the EDL revealed glycogen depletion without inflammatory cell infiltration in stimulated versus control muscles, whereas ultrastructural analysis showed no evidence of myofiber damage after stimulation. Multiple fiber type-specific transcription factors (tea domain family member 1, nuclear factor of activated T cells 1, peroxisome proliferator-activated receptor-γ coactivator-1α and -β, circadian locomotor output cycles kaput, and hypoxia-inducible factor-1α) increased in the EDL along with transcription factors characteristic of embryogenesis (Kruppel-like factor 4; SRY box containing 17; transcription factor 15; PBX/knotted 1 homeobox 1; and embryonic lethal, abnormal vision). No established in vivo satellite cell markers or genes activated in our parallel experiments of satellite cell proliferation in vitro (cyclins A2, B2, C, and E1 and MyoD) were differentially increased in the stimulated muscles. These results indicated that the molecular onset of fast to slow phenotype conversion occurred in the EDL within 4 h of stimulation without injury or satellite cell recruitment. This conversion was associated with the expression of phenotype-specific transcription factors from resident fiber myonuclei, including the activation of nascent developmental transcriptional programs.
Hypochlorous acid-induced heme oxygenase-1 gene expression promotes human endothelial cell survival
Authors: Wei Yong , Liu Xiao-ming , Peyton Kelly J. , Wang Hong , Johnson Fruzsina K. , Johnson Robert A. , Durante William
Published: July 2009

Hypochlorous acid (HOCl) is a unique oxidant generated by the enzyme myeloperoxidase that contributes to endothelial cell dysfunction and death in atherosclerosis. Since myeloperoxidase localizes with heme oxygenase-1 (HO-1) in and around endothelial cells of atherosclerotic lesions, the present study investigated whether there was an interaction between these two enzymes in vascular endothelium. Treatment of human endothelial cells with the myeloperoxidase product HOCl stimulated a concentration- and time-dependent increase in HO-1 protein that resulted in a significant rise in carbon monoxide (CO) production. The induction of HO-1 protein was preceded by a prominent increase in HO-1 mRNA and total and nuclear factor-erythroid 2-related factor 2 (Nrf2). In addition, HOCl induced a significant rise in HO-1 promoter activity that was blocked by mutating the antioxidant response element (ARE) in the promoter or by overexpressing a dominant-negative mutant of Nrf2. The HOCl-mediated induction of Nrf2 or HO-1 was blocked by the glutathione donor N-acetyl-l-cysteine but was unaffected by ascorbic or uric acid. Finally, treatment of endothelial cells with HOCl stimulated mitochondrial dysfunction, caspase-3 activation, and cell death that was potentiated by the HO inhibitor, tin protoporphyrin-IX, or by the knockdown of HO-1, and reversed by the exogenous administration of biliverdin, bilirubin, or CO. These results demonstrate that HOCl induces HO-1 gene transcription via the activation of the Nrf2/ARE pathway to counteract HOCl-mediated mitochondrial dysfunction and cell death. The ability of HOCl to activate HO-1 gene expression may represent a critical adaptive response to maintain endothelial cell viability at sites of vascular inflammation and atherosclerosis.
Different roles of H-ras for regulation of myosin heavy chain promoters in satellite cell-derived muscle cell culture during proliferation and differentiation
Authors: Scholz Michael E. , Meissner Joachim D. , Scheibe Renate J. , Umeda Patrick K. , Chang Kin-Chow , Gros Gerolf , Kubis Hans-Peter
Published: July 2009

The effect of constitutively activated proto-oncogene H-ras (H-rasQ61L) on the regulation of myosin heavy chain (MHC) promoter activities was investigated in rabbit satellite cell-derived muscle cell culture during the proliferation stage and early and later stages of differentiation, respectively. During proliferation, overexpression of H-rasQ61L did not affect basal level of activity of the slow MHCI/β or the fast MHCIId/x promoter luciferase reporter gene construct in transient transfection assays. By contrast, H-rasQ61L affected both MHC promoter activities during differentiation, and this effect changes from inactivation after 2 days to activation after 4 days of differentiation. The activating effect of H-rasQ61L on both MHC promoters after 4 days of differentiation was significantly reduced by LY-294002, a specific inhibitor of the phosphoinositol-3-kinase (PI3K), a downstream target of Ras. Furthermore, the protein kinase Akt (protein kinase B), a downstream target of PI3k, was activated 4 days after initiation of differentiation in myotubes overexpressing H-rasQ61L. By contrast, inhibition of another Ras downstream pathway, mitogen-activated protein kinase kinase 1/2-extracellular signal-regulated protein kinase 1/2 (MKK1/2-ERK1/2-MAPK), increased activities of both MHC promoters, indicating a suppressive role of this pathway. Moreover, the Ras-PI3K-Akt signaling pathway is involved in the activation of MHCI/β and IId/x promoters in a later stage of differentiation of muscle cells, presumably by a known inhibiting effect of activated Akt on the MKK1/2-ERK1/2-MAPK pathway. The experiments demonstrate that during differentiation of muscle cells activated H-ras is an important regulator of MHC isoform promoter function with opposite effects during early and later stages.
Lipopolysaccharide directly alters renal tubule transport through distinct TLR4-dependent pathways in basolateral and apical membranes
Authors: Good David W. , George Thampi , Watts Bruns A.
Published: July 2009

Bacterial infection of the kidney is associated with renal tubule dysfunction and dysregulation of systemic electrolyte balance. Whether bacterial molecules directly affect renal tubule transport is unknown. We examined the effects of LPS on HCO3−absorption in the isolated rat and mouse medullary thick ascending limb (MTAL). LPS decreased HCO3−absorption when added to bath or lumen. The MEK/ERK inhibitor U0126 eliminated inhibition by bath LPS but had no effect on inhibition by lumen LPS. Conversely, the mammalian target of rapamycin (mTOR) inhibitor rapamycin eliminated inhibition by lumen LPS but had no effect on inhibition by bath LPS. Inhibiting basolateral Na+/H+exchange with amiloride eliminated inhibition of HCO3−absorption by lumen but not bath LPS. Confocal immunofluorescence showed expression of TLR4 in basolateral and apical membrane domains. Inhibition of HCO3−absorption by bath and lumen LPS was eliminated in MTALs from TLR4−/−mice. Thus LPS inhibits HCO3−absorption through distinct TLR4-dependent pathways in basolateral and apical membranes. These results establish that bacterial molecules can directly impair the transport function of renal tubules, identifying a new mechanism contributing to tubule dysfunction during bacterial infection. The LPS-induced reduction in luminal acidification may contribute to Gram-negative pathogenicity by promoting bacterial adherence and growth and impairing correction of infection-induced systemic acid-base disorders.
Rapid muscle atrophy response to unloading: pretranslational processes involving MHC and actin
Authors: Giger Julia M. , Bodell Paul W. , Zeng Ming , Baldwin Kenneth M. , Haddad Fadia
Published: July 2009

Skeletal muscles, especially weight-bearing muscles, are very sensitive to changes in loading state. The aim of this paper was to characterize the dynamic changes in the unloaded soleus muscle in vivo following a short bout of hindlimb suspension (HS), testing the hypothesis that transcriptional events respond early to the atrophic stimulus. In fact, we observed that after only 1 day of HS, primary transcript levels of skeletal α-actin and type I myosin heavy chain (MHC) genes were significantly reduced by more than 50% compared with ground control levels. The degree of the decline for the mRNA expression of actin and type I MHC lagged behind that of the pre-mRNA levels after 1 day of HS, but by 2 and 7 days of HS, large decreases were observed. Although the faster MHC isoforms, IIx and IIb, began to be expressed in soleus after 1 day of HS, a relatively significant shift in mRNA expression from the slow MHC isoform type I toward these fast MHC isoforms did not emerge until 7 days of HS. One day of HS was sufficient to show significant decreases in mRNA levels of putative signaling factors serum response factor (SRF), suppressor of cytokine signaling-3 (SOCS3), and striated muscle activator of Rho signaling (STARS), although transcription factors yin-yang-1 (YY1) and transcriptional enhancing factor-1 (TEF-1) were not significantly affected by HS. The protein levels of actin and type I MHC were significantly decreased after 2 days of HS, and SRF protein was significantly decreased after 7 days HS. Our results show that after only 1 day of unloading, pre-mRNA and mRNA expression of muscle proteins and muscle-specific signaling factors are significantly reduced, suggesting that the downregulation of the synthesis side of the protein balance equation that occurs in atrophying muscle is initiated rapidly.
Motion Perception During Variable-Radius Swing Motion in Darkness
Authors: Rader A. A. , Oman C. M. , Merfeld D. M.
Published: July 2009

Using a variable-radius roll swing motion paradigm, we examined the influence of interaural ( y-axis) and dorsoventral ( z-axis) force modulation on perceived tilt and translation by measuring perception of horizontal translation, roll tilt, and distance from center of rotation (radius) at 0.45 and 0.8 Hz using standard magnitude estimation techniques (primarily verbal reports) in darkness. Results show that motion perception was significantly influenced by both y- and z-axis forces. During constant radius trials, subjects' perceptions of tilt and translation were generally almost veridical. By selectively pairing radius (1.22 and 0.38 m) and frequency (0.45 and 0.8 Hz, respectively), the y-axis acceleration could be tailored in opposition to gravity so that the combined y-axis gravitoinertial force (GIF) variation at the subject's ears was reduced to ∼0.035 m/s2– in effect, the y-axis GIF was “nulled” below putative perceptual threshold levels. With y-axis force nulling, subjects overestimated their tilt angle and underestimated their horizontal translation and radius. For some y-axis nulling trials, a radial linear acceleration at twice the tilt frequency (0.25 m/s2at 0.9 Hz, 0.13 m/s2at 1.6 Hz) was simultaneously applied to reduce the z-axis force variations caused by centripetal acceleration and by changes in the z-axis component of gravity during tilt. For other trials, the phase of this radial linear acceleration was altered to double the magnitude of the z-axis force variations. z-axis force nulling further increased the perceived tilt angle and further decreased perceived horizontal translation and radius relative to the y-axis nulling trials, while z-axis force doubling had the opposite effect. Subject reports were remarkably geometrically consistent; an observer model-based analysis suggests that perception was influenced by knowledge of swing geometry.
Inhibitory Transmission inLocus CoeruleusNeurons Expressing GABAAReceptor Epsilon Subunit Has a Number of Unique Properties
Authors: Belujon P. , Baufreton J. , Grandoso L. , Boué-Grabot E. , Batten T.F.C. , Ugedo L. , Garret M. , Taupignon A. I.
Published: July 2009

Fast inhibitory synaptic transmission in the brain relies on ionotropic GABAAreceptors (GABAAR). Eighteen genes code for GABAAR subunits, but little is known about the ε subunit. Our aim was to identify the synaptic transmission properties displayed by native receptors incorporating ε. Immunogold localization detected ε at synaptic sites on locus coeruleus (LC) neurons. In situ hybridization revealed prominent signals from ε, and θ mRNAs, some low β1 and β3 signals, and no γ signal. Using in vivo extracellular and in vitro patch-clamp recordings in LC, we established that neuron firing rates, GABA-activated currents, and mIPSC charge were insensitive to the benzodiazepine flunitrazepam (FLU), in agreement with the characteristics of recombinant receptors including an ε subunit. Surprisingly, LC provided binding sites for benzodiazepines, and GABA-induced currents were potentiated by diazepam (DZP) in the micromolar range. A number of GABAAR ligands significantly potentiated GABA-induced currents, and zinc ions were only active at concentrations above 1 μM, further indicating that receptors were not composed of only α and β subunits, but included an ε subunit. In contrast to recombinant receptors including an ε subunit, GABAAR in LC showed no agonist-independent opening. Finally, we determined that mIPSCs, as well as ensemble currents induced by ultra-fast GABA application, exhibited surprisingly slow rise times. Our work thus defines the signature of native GABAAR with a subunit composition including ε: differential sensitivity to FLU and DZP and slow rise time of currents. We further propose that α3,β1/3,θ and ε subunits compose GABAAR in LC.
Fast Responses to Stepping on an Unexpected Surface Height Depend on Intact Large-Diameter Nerve Fibers: A Study on Charcot–Marie–Tooth Type 1A Disease
Authors: van der Linden Marleen H. , de Kam Digna , van Engelen Baziel G. M. , Hendricks Henk T. , Duysens Jacques
Published: July 2009

The contribution of reflexes from the large myelinated afferents in the control of normal and perturbed gait in humans is a highly debated issue. One way to investigate this topic is by studying normal and perturbed gait in patients lacking large myelinated fibers in the distal limb (Charcot–Marie–Tooth [CMT] type 1A disease). Such patients should have delayed and decreased reflexes if the latter depend on these large myelinated fibers. To elicit the reflexes, both patients and controls had to step on a platform that was either at the same level or lowered by 5 cm. In control subjects, landing on a level surface induced short-latency responses in the biceps femoris and tibialis anterior muscles, whereas such responses were largely absent in the patients. Similarly, stepping down unexpectedly induced a very fast muscle synergy, leading to a brake of the forward propulsion in the controls, which was significantly reduced and delayed (on average 32 ms) in the patients. The observed changes correlated with both sensory and motor deficits. Nevertheless, it is concluded that the results are primarily related to the sensory deficits, since the delayed or absent responses appeared in both upper and lower leg muscles, whereas only the latter showed motor deficits. The data are taken as evidence that large-diameter afferents from the distal leg are essential for fast reflex activations induced by stepping on a level or lowered surface unexpectedly.
Psychoanalytic Perspectives On Early Trauma: Interviews With Thirty Analysts Who Treated an Adult Victim of a Circumscribed Trauma in Early Childhood
Authors: Gaensbauer Theodore J. , Jordan Leslie
Published: July 2009

Information on the long-term effects of early trauma and how such effects are manifested in treatment was obtained through interviews with thirty analysts who had treated an adult patient with a circumscribed trauma in the first four years of life. Childhood traumas fell into four categories: medical/accidental; separation/loss; witnessing a traumatic event; and physical/sexual abuse. Traumatic carryover was recorded in terms of explicit memories, implicit memories (somatic reliving, traumatic dreams, affective memories, behavioral reenactments, and transference phenomena), and global carryover effects (generalized traumatic affective states, defensive styles, patterns of object relating, and developmental disruptions). Linkages between the early trauma and adult symptomatology could be posited in almost every case, yet the clinical data supporting such linkages was often fragmented and ambiguous. Elements of patients’ traumas appeared to be dispersed along variable avenues of expression and did not appear amenable to holistic, regressive reworking in treatment. The data did not support linear models of traumatic carryover or the idea that early traumatic experiences will be directly accessible in the course of an analysis. Factors that we believe help explain why traumatic aftereffects in our sample were so heterogeneous and difficult to track over the long term are discussed.