bluuebunny/crossref_metadata_2025 huggingface dataset:
Watch Water Flow
Authors: Abramson Jeff , Vartanian Armand S.
Published: June 2013

A high-resolution structure elucidates how water flows through aquaporin into and out of biological cells.

[Also see Report by

Kosinska Eriksson
et al.

]
Cold-Atom Magnetism
Authors: Porto J. V.
Published: June 2013

A trapped cloud of cold atoms can be used to simulate magnetism found in condensed matter systems.

[Also see Report by

Greif
et al.

]
Network Science at Center of Surveillance Dispute
Authors: Cho Adrian
Published: June 2013

Last week's disclosures that the U.S. National Security Agency (NSA) is collecting cell phone records and Internet data came as no surprise to experts in network analysis, who say that the type of data crunching NSA is engaged in—identifying social groups from connections among people—is business as usual at several private companies.
Educators, Lawmakers Question Proposed Reorganization
Authors: Mervis Jeffrey
Published: June 2013

President Barack Obama's plan to reorganize U.S. STEM education is drawing congressional opposition.
On the Trail of Ancient Killers
Authors: Gibbons Ann
Published: June 2013

Armed with new methods, researchers are interrogating the DNA of centuries-old pathogens extracted from the bones and teeth of victims.
Cellular Immune Responses to Recombinant Mycobacterium bovis BCG Constructs Expressing Major Antigens of Region of Difference 1 of Mycobacterium tuberculosis
Authors: Shaban Kholoud , Amoudy Hanady A. , Mustafa Abu S.
Published: June 2013

Besides being the most widely used vaccine directed against tuberculosis (TB) worldwide,
Mycobacterium bovis
BCG is also the most controversial vaccine in current use. Its protective efficacy varies widely in different parts of the world. One approach to improving the current BCG vaccine might be to produce recombinant BCG strains that express major antigens encoded by genes that are present in the
M. tuberculosis
-specific region of difference 1 (RD1), such as
pe35
,
cfp10
, and
esat6
. In this study,
pe35
,
cfp10
, and
esat6
genes were cloned into shuttle plasmid pDE22 to generate the recombinant plasmids PDE22-PE35, PDE22-CFP10, and PDE22-ESAT6, which were electroporated into BCG to generate recombinant BCGs (rBCGs). The cellular immune responses (antigen-induced proliferation and secretion of selected T helper 1 [Th1], Th2, and anti-inflammatory cytokines, i.e., gamma interferon [IFN-γ], interleukin 5 [IL-5], and IL-10, respectively) that are specific to the proteins of cloned genes were studied by using spleen cells from mice immunized with native BCGs and rBCGs and synthetic peptides covering the protein sequence of the cloned genes. The results showed that the spleen cells did not secrete IL-5, whereas IL-10 was secreted in response to peptides of all three proteins from mice immunized with rBCGs only, suggesting expression of the cloned genes and
in vivo
priming of spleen cells to the expressed proteins. However, in Th1 cell assays that correlate with protective cellular immune responses, i.e., antigen-induced proliferation and IFN-γ secretion, only mice immunized with rBCG-pDE22-PE35 yielded positive responses to the peptides of PE35. These results suggest that rBCG-PDE22-PE35 is the only one of the three vaccines used in this work that is worthy of consideration as a new vaccine candidate against TB.
Development of a Highly Sensitive Bioluminescent Enzyme Immunoassay for Hepatitis B Virus Surface Antigen Capable of Detecting Divergent Mutants
Authors: Minekawa Takayuki , Takehara Shizuka , Takahashi Masaharu , Okamoto Hiroaki
Published: June 2013

Hepatitis B virus (HBV) infections are sometimes overlooked when using commercial kits to measure hepatitis B virus surface antigen (HBsAg) due to their low sensitivities and reactivities to mutant strains of various genotypes. We developed an ultrasensitive bioluminescent enzyme immunoassay (BLEIA) for HBsAg using firefly luciferase, which is adaptable to a variety of HBsAg mutants, by combining four monoclonal antibodies with a polyclonal antibody against HBsAg. The measurement of seroconversion panels showed trace amounts of HBsAg during the early infection phase by the BLEIA because of its high sensitivity of 5 mIU/ml. The BLEIA detected HBsAg as early as did PCR in five of seven series and from 2.1 to 9.4 days earlier than commercial immunoassay methods. During the late infection phase, the BLEIA successfully detected HBsAg even 40 days after the disappearance of HBV DNA and the emergence of antibodies against HBsAg. The HBsAg BLEIA successfully detected all 13 recombinant HBsAg and 45 types of HBsAg mutants with various mutations within amino acids 90 to 164 in the S gene product. Some specimens had higher values determined by the BLEIA than those by a commercial chemiluminescent immunoassay; this suggests that such discrepancies were caused by the dissociation of preS1/preS2 peptides from the particle surface. With its highly sensitive detection of low-titer HBsAg, including various mutants, the HBsAg BLEIA is considered to be useful for the early diagnosis and prevention of HBV infection because of the shorter window of infection prior to detection, which facilitates early prediction of recurrence in HBV-infected individuals.
Clinical Disease Upregulates Expression of CD40 and CD40 Ligand on Peripheral Blood Mononuclear Cells from Cattle Naturally Infected with Mycobacterium avium subsp. paratuberculosis
Authors: Khalifeh M. S. , Stabel J. R.
Published: June 2013

CD40 and CD40 ligand (CD40L) have costimulatory effects as part of a complex series of events in host immunity. In this study, the expression of CD40 and CD40L on peripheral blood mononuclear cells (PBMCs) isolated from cattle with Johne's disease were measured on freshly isolated PBMCs and on cells cultured for 8, 24, and 72 h in the presence or absence of liveMycobacterium aviumsubsp.paratuberculosisand exogenous gamma interferon, interleukin 10, and transforming growth factor β. Results demonstrated greater CD40 and CD40L expression on fresh PBMCs obtained from animals in the clinical stage of disease (symptomatic) than those from healthy control animals or cows in the subclinical stage of disease (asymptomatic). A similar expression profile with greater magnitude was noted for cultured PBMCs, with increased CD40 expression after 8 and 24 h of culture and increased CD40L expression between 24 and 72 h on PBMCs obtained from clinically infected animals. The addition of liveM. aviumsubsp.paratuberculosisto cell cultures resulted in downregulation of CD40L expression in naturally infected cows, regardless of the disease stage. In contrast, the addition of liveM. aviumsubsp.paratuberculosisto cultures resulted in upregulation of CD40 expression on cells obtained from clinically infected animals, while a decrease in expression was noted for healthy and subclinically infected cows. No effects of exogenous cytokines on CD40 or CD40L expression were observed. These results clearly point for the first time to a disparity in the expression of these costimulatory molecules on immune cells from cattle in different stages of Johne's disease and suggest further investigation into their roles in paratuberculosis pathogenesis.
In VitroAssessment of the Immunological Significance of a Human Monoclonal Antibody Directed to the Influenza A Virus Nucleoprotein
Authors: Bodewes Rogier , Geelhoed-Mieras Martina M. , Wrammert Jens , Ahmed Rafi , Wilson Patrick C. , Fouchier Ron A. M. , Osterhaus Albert D. M. E. , Rimmelzwaan Guus F.
Published: June 2013

Influenza A viruses cause annual epidemics and occasionally pandemics. Antibodies directed to the conserved viral nucleoprotein (NP) may play a role in immunity against various influenza A virus subtypes. Here, we assessed the immunological significance of a human monoclonal antibody directed to NPin vitro. This antibody bound to virus-infected cells but did not display virus-neutralizing activity, complement-dependent cell cytotoxicity, or opsonization of viral antigen for improved antigen presentation to CD8+T cells by dendritic cells.
Development of a Sensitive Loop-Mediated Isothermal Amplification Assay That Provides Specimen-to-Result Diagnosis of Respiratory Syncytial Virus Infection in 30 Minutes
Authors: Mahony James , Chong Sylvia , Bulir David , Ruyter Alexandra , Mwawasi Ken , Waltho Daniel
Published: June 2013

Rapid isothermal amplification methods have recently been introduced, and some of these methods offer significant advantages over PCR. The objective of this study was to develop a rapid and sensitive multiplex loop-mediated isothermal amplification (M-LAMP) assay for the detection of respiratory syncytial virus subgroups A and B (RSV A and B). We designed six primers each for the matrix gene of RSV A and the polymerase gene of RSV B and developed an M-LAMP assay by using a commercially available master mix and a real-time fluorometer (Genie II; Optigene, United Kingdom) that displays real-time amplification, time to positivity, and amplicon annealing temperature (

T
m

). The M-LAMP was evaluated against PCR by testing 275 nasopharyngeal (NP) specimens. The final optimized M-LAMP assay had a mean amplification time of 14.2 min (compared with 90 to 120 min for PCR) and had an analytical sensitivity of 1 genome equivalent (ge) for both RSV A and B. Using PCR as a comparator, M-LAMP had a sensitivity of 100% (81/81) and specificity of 100% (194/194). We also evaluated a 3- to 10-min specimen processing method involving vortexing with glass beads and heating to 98°C in M-swab medium (Copan Italia, Brescia, Italy) and found that this rapid processing method allowed detection of 37/41 (90.2%) of positives when we used extracted nucleic acid. In summary, the M-LAMP assay had excellent sensitivity and specificity for detecting RSV A and B in NP specimens and, when coupled with a rapid specimen preparation method, could provide a specimen-to-result diagnosis time of 30 min.
RECall for Automated Genotypic Tropism Testing
Authors: Pou Christian , Bellido Rocío , Casadellà Maria , Puig Teresa , Clotet Bonaventura , Harrigan Richard , Paredes Roger
Published: June 2013

Standardization of sequence chromatogram analysis is required for consistent genotypic tropism determination across laboratories. A freely available, fast, and automated chromatogram analysis tool (RECall) provided tropism interpretations equivalent to those of manual sequence editing of 521 V3 loop HIV-1 population sequences, suggesting that RECall can be useful in standardizing genotypic tropism testing across laboratories.
Multiplex Real-Time PCR for Detection of Campylobacter, Salmonella, and Shigella
Authors: Barletta F. , Mercado E. H. , Lluque A. , Ruiz J. , Cleary T. G. , Ochoa T. J.
Published: June 2013

Infectious diarrhea can be classified based on its clinical presentation as noninflammatory or inflammatory disease. In developing countries, among inflammatory diarrhea cases,
Shigella
is the most common cause, followed by
Campylobacter
and
Salmonella
. Because the time frame in which treatment choices must be made is short and conventional stool cultures lack good sensitivity, there is a need for a rapid, sensitive, and inexpensive detection technique. The purpose of our study was to develop a multiplex real-time PCR procedure to simultaneously identify
Campylobacter
spp.,
Salmonella
spp., and
Shigella
spp. Primers were designed to amplify the
invA
,
ipaH
, and 16S rRNA genes simultaneously in a single reaction to detect
Salmonella
,
Shigella
, and
Campylobacter
, respectively. Using this approach, we correctly identified 102 of 103 strains of the targeted enteropathogens and 34 of 34 other pathogens. The melting temperatures were 82.96 ± 0.05°C for
invA
, 85.56 ± 0.28°C for
ipaH
, and 89.21 ± 0.24°C for 16S rRNA. The limit of accurate quantification for the assay in stool samples was 10
4
CFU g
−1
; however, the limit of detection was 10
3
CFU g
−1
. This assay is a simple, rapid, inexpensive, and reliable system for the practical detection of these three enteropathogens in clinical specimens.
Frog Virus 3 Open Reading Frame 97R Localizes to the Endoplasmic Reticulum and Induces Nuclear Invaginations
Authors: Ring Brooke A. , Ferreira Lacerda Andressa , Drummond Dylan J. , Wangen Christina , Eaton Heather E. , Brunetti Craig R.
Published: June 2013

Frog virus 3 (FV3) is the type species of the genus
Ranavirus
, family
Iridoviridae
. The genome of FV3 is 105,903 bases in length and encodes 97 open reading frames (ORFs). The FV3 ORF 97R contains a B-cell lymphoma 2 (Bcl-2) homology 1 (BH1) domain and has sequence similarity to the myeloid cell leukemia-1 (Mcl-1) protein, suggesting a potential role in apoptosis. To begin to understand the role of 97R, we characterized 97R through immunofluorescence and mutagenesis. Here we demonstrated that 97R localized to the endoplasmic reticulum (ER) at 24 h posttransfection. However, at 35 h posttransfection, 97R localized to the ER but also began to form concentrated pockets continuous with the nuclear membrane. After 48 h posttransfection, 97R was still localized to the ER, but we began to observe the ER and the outer nuclear membrane invaginating into the nucleus. To further explore 97R targeting to the ER, we created a series of C-terminal transmembrane domain deletion mutants. We found that deletion of 29 amino acids from the C terminus of 97R abolished localization to the ER. In contrast, deletion of 12 amino acids from the C terminus of 97R did not affect 97R localization to the ER. In addition, a hybrid protein containing the 97R C-terminal 33 amino acids was similarly targeted to the ER. These data indicate that the C-terminal 33 amino acids of 97R are necessary and sufficient for ER targeting.
NS1′ Colocalizes with NS1 and Can Substitute for NS1 in West Nile Virus Replication
Authors: Young Lucy B. , Balmori Melian Ezequiel , Khromykh Alexander A.
Published: June 2013

NS1′ is a C-terminally extended form of the NS1 protein produced only by encephalitic flaviviruses from the Japanese encephalitis virus serogroup. Here we show that West Nile virus (WNV) NS1′ and NS1 localize to the same cellular compartments when expressed from plasmid DNAs and also colocalize to viral RNA replication sites in infected cells. Using complementation analysis with NS1-deleted WNV cDNA, we demonstrated that NS1′ is able to substitute for the crucial function of NS1 in virus replication.
The effect of field condition and shoe type on lower extremity injuries in American Football
Authors: Iacovelli Jaclyn Nicole , Yang Jingzhen , Thomas Geb , Wu Hongqian , Schiltz Trisha , Foster Danny T
Published: June 2013

Background/aim

Considerable improvement has been made in football field surfaces and types of shoe, yet relatively few epidemiological studies have investigated their roles in the risk of football injuries. This study examined the effects of field surface, surface condition and shoe type on the likelihood of lower extremity football injuries.

Methods

Deidentified data from 188 players from one division I university football team during the 2007–2010 seasons were analysed. Lower extremity injury rate and rate ratio, along with 95% confidence limits, were calculated by football activity, playing surface condition and shoe type.

Results

A total of 130 lower extremity injuries were sustained, with an overall lower extremity injury rate of 33.5/10 000 athlete-sessions. The lower extremity injury rate was 2.61 times higher when the surface condition was abnormal compared with when the surface condition was normal. During games, the risk for lower extremity injury was 3.34 times higher (95% CI 1.70 to 6.56) on artificial turf compared with natural grass. However, this trend was not statistically significant in practice sessions. Furthermore, neither the number of shoe cleats nor the height of the shoe top was statistically associated with risk of lower extremity injuries.

Conclusions

Football players who played on artificial turf or when the surface condition was abnormal were susceptible to lower extremity injuries. Evidence from this study suggests that further research into playing surfaces and shoe types may provide fruitful opportunities to reduce injuries to collegiate football players.
The Nordic Football Injury Audit: higher injury rates for professional football clubs with third-generation artificial turf at their home venue
Authors: Kristenson Karolina , Bjørneboe John , Waldén Markus , Andersen Thor Einar , Ekstrand Jan , Hägglund Martin
Published: June 2013

Background

Previously, no difference in acute injury rate has been found when playing football on artificial turf (AT) compared with natural grass (NG).

Aim

To compare acute injury rates in professional football played on AT and NG at the individual player level; and to compare, at club level, acute and overuse injury rates between clubs that have AT at their home venue (AT clubs) and clubs that have NG (NG clubs).

Methods

32 clubs (AT, n=11; NG, n=21) in the male Swedish and Norwegian premier leagues were followed prospectively during the 2010 and 2011 seasons. Injury rate was expressed as the number of time loss injuries/1000 h and compared with rate ratio (RR) and 99% CI.

Results

No statistically significant differences were found in acute injury rates on AT compared with NG during match play (RR 0.98, 99% CI 0.79 to 1.22) or training (RR 1.14, 99% CI 0.86 to 1.50) when analysing at the individual player level. When analysing at the club level, however, AT clubs had a significantly higher acute training injury rate (RR 1.31, 99% CI 1.04 to 1.63) and overuse injury rate (RR 1.38, 99% CI 1.14 to 1.65) compared with NG clubs.

Conclusions

At the individual player level, no significant differences were found in acute injury rates when playing on AT compared with NG. However, clubs with AT at their home venue had higher rates of acute training injuries and overuse injuries compared with clubs that played home matches on NG.
Economic determinants of diet in older adults: systematic review
Authors: Conklin Annalijn I , Maguire Eva R , Monsivais Pablo
Published: June 2013

Background and aims

Many economic factors are associated with diet, yet the evidence is generally cross-sectional. Older people are considered especially vulnerable to poor diets from negative changes to varied economic factors. This review extends current knowledge on known correlates to decipher actual economic determinants of diet in older adults.

Methods

Eight bibliometric databases were searched between May and December 2012, supplemented by hand-searches, with no restrictions on publication date or country. Longitudinal studies, or reviews, were eligible when examining diet as a function of change in an economic factor in non-institutionalised adults ≥60 years. Data were extracted using a standardised evidence table and quality assessed before narrative synthesis.

Results

We found nine original studies for inclusion, of which eight examined change from work to retirement and one evaluated a food price intervention. Designs were generally pre-post without controls and varying in follow-up. Studies reported mixed impact on food spending and/or food intake. Retirement was shown to both reduce and have no impact on food spending and to have either positive and negative, or positive and no impact on food intake. Subgroup differences were observed, especially between men and women.

Conclusions

Despite ample research on economic correlates of older adults' diets, little is still known about actual economic determinants of diet in this population. Studies of retirement suggest divergent effects in some but not all older people. Robust high-quality longitudinal studies to decipher economic drivers of diet must be prioritised in research and policy as firm conclusions remain elusive.
Improvement of working memory after stenting for cervicocerebral artery stenosis
Authors: He Zi-Jun , Qin Bin , Cui Zhuang , Liu Fang , Qi Peng , Lu Jun , Liu Jia-Chun , Wang Li-Jun , Zeng Ping , Wang Da-Ming
Published: June 2013

Objective

To investigate the working memory of patients with cervicocerebral artery stenosis and its change after stenting.

Methods

35 patients with cervicocerebral artery stenosis (≥50% with related symptoms of cerebral ischemia, or ≥70% with or without related symptoms of cerebral ischemia) underwent endovascular stenting. Working memory of all 35 patients before and within 3 weeks of stenting was evaluated by memory quotient (MQ) scores. Change in regional cerebral blood flow (rCBF) was assessed by single photon emission CT (SPECT) for 13 of the patients. MQ scores were compared according to location and degree of stenosis for all patients, as well as changes in rCBF for the 13 patients.

Results

Mean MQ scores were significantly lower than normal for patients with carotid artery stenosis alone and for patients with carotid stenosis in addition to vertebrobasilar and/or subclavical stenosis, but not for patients with vertebrobasilar and/or subclavical stenosis. MQ scores were significantly increased after stenting for all patients, especially those with carotid stenosis. There was no significant difference between patients with moderate stenosis and those with severe (>70%) stenosis in MQ increments pre- and post-stenting (p=0.085). Nine of the 13 patients who received SPECT showed an improvement in rCBF after stenting, and their MQ increments were significantly higher than those without an improvement in rCBF (p=0.020).

Conclusions

Working memory impairment can be observed in patients with cervicocerebral artery stenosis, especially those with carotid stenosis. Endovascular stenting of stenosis might improve the impairment by alleviating cerebral perfusion deficit.
Association of genital human papillomavirus infection with HIV acquisition: a systematic review and meta-analysis
Authors: Lissouba Pascale , Van de Perre Philippe , Auvert Bertran
Published: June 2013

Objectives

To conduct a systematic review and a meta-analysis of epidemiological studies investigating the association of genital human papillomavirus (HPV) infection and HIV acquisition.

Design

Systematic review and meta-analysis.

Data Sources

Scientific databases and conference abstracts were systematically searched to identify all relevant studies published up to 31 January 2012. Search terms included ‘HIV’, ‘HPV’, ‘human papillomavirus’ and ‘papillomaviridae’ as keywords or text, in the title or abstract.

Methods

To be eligible for inclusion, a study had to be conducted among humans, report data on HIV incidence, and assess genital HPV infection. Summary ORs and 95% CIs were estimated from the extracted data using random-effect meta-analysis. Subgroup analyses were conducted for high-risk (HR) and low-risk (LR) HPV oncogenic risk groups. Between-study heterogeneity and publication bias were assessed.

Results

Of 2601 identified abstracts, six observational studies, comprising 6567 participants were retained for the systematic review and the meta-analysis. HIV acquisition was significantly associated with HPV infection (summary OR=1.96; 95% CI 1.55 to 2.49). HIV incident infection was significantly associated with HR-HPV in five of six studies and with LR-HPV in two out of five. The association was significant for HR-HPV (summary OR=1.92; 95% CI 1.49 to 2.46) and borderline for LR-HPV. No between-study heterogeneity was detected. There was a borderline indication of publication bias.

Conclusions

Further research is needed to elucidate the biological mechanisms involved, and assess the effect of HPV vaccination on HIV acquisition, using vaccines with broad coverage of HPV genotypes. Such research could have important public health implications for HIV prevention.
A statistical model for presence of late-season frozen ground in discontinuous permafrost at Dublin Gulch, Yukon
Authors: Quinn P.E.
Published: June 2013

This paper describes geostatistical analyses completed at a discontinuous permafrost site in central Yukon to develop a predictive model for the presence of late-season frozen ground in support of planning and design for potential site development. The most important factors in the bivariate statistical model were soil type, as determined through terrain analysis, and slope aspect, as inferred from available topographic data. The other three factors included in the final model were profile curvature, slope angle, and ground elevation, each interpreted from available topographic data. The resulting model subdivides the site into three broad classes of frozen ground likelihood: low, where frozen ground can be expected to be encountered in late summer at 15% of observation locations; medium, where 50% of the ground is expected to remain frozen; and high, where 85% of the ground is expected to remain frozen. New test pit and borehole data from the summer of 2012 were used to verify model performance. The inferred correlations between frozen ground and soil type, aspect, curvature, slope, and elevation obtained in this case study may provide useful information relative to expected permafrost occurrence at sites in central Yukon with similar geology and physiography.
High-fat diet stimulates hepatic cystathionine β-synthase and cystathionine γ-lyase expression
Authors: Hwang Sun-Young , Sarna Lindsei K. , Siow Yaw L. , O Karmin
Published: June 2013

Cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) catalyze homocysteine (Hcy) metabolism via the trans-sulfuration pathway. They are also responsible for hydrogen sulfide (H2S) production via desulfuration reactions. The liver contributes significantly to the regulation of Hcy and H2S homeostasis, which might participate in many physiological and pathological processes. The aim of this study was to investigate the effect of a high-fat diet (HFD) on hepatic CBS and CSE expression and its impact on Hcy and H2S metabolism. Mice (C57BL/6) fed a HFD (60% kcal fat) for 5 weeks developed fatty liver. The mRNA and protein levels of CBS and CSE in the liver were significantly elevated in mice fed a HFD. Subsequently the metabolism of Hcy by CBS and CSE was increased in the liver, and its level decreased in the circulation. Increased CBS and CSE expression also caused a significant elevation in H2S production in the liver. The level of lipid peroxides was elevated, indicating oxidative stress, while the level of total glutathione remained unchanged in the liver of HFD-fed mice. Upregulation of the trans-sulfuration pathway might play an adaptive role against oxidative stress by maintaining total glutathione levels in the liver.
LANDAU–ZENER TRANSITIONS IN THE PRESENCE OF HARMONIC NOISE
Authors: KRAFT MATTHIAS , BURKHARDT STEPHAN , MANNELLA RICCARDO , WIMBERGER SANDRO
Published: June 2013

We study the influence of off-diagonal harmonic noise on transitions in a Landau–Zener model. We demonstrate that the harmonic noise can change the transition probabilities substantially and that its impact depends strongly on the characteristic frequency of the noise. In the underdamped regime of the noise process, its effect is compared with the one of a deterministic sinusoidally oscillating function. While altering the properties of the noise process allows one to engineer the transitions probabilities, driving the system with a deterministic sinusoidal function can result in larger and more controlled changes of the transition probability. This may be relevant for realistic implementations of our model with Bose–Einstein condensates in noise-driven optical lattices.
FIFTH GRADE STUDENTS ENGAGED IN A COOPERATIVE LEARNING ENVIRONMENT: EVALUATING THEIR ABILITY TO DETERMINE THE STATUS OF THEIR OWN CONCEPTIONS ABOUT MATTER
Authors: LEWIS DONNA M. , TREAGUST DAVID F. , CHANDRASEGARAN A. L.
Published: June 2013

This study integrated cooperative learning methods in classroom instruction to investigate the effects on achievement and conceptual change in matter concepts involving 70 fifth grade students after 10 weeks of instruction. Data obtained from the administration of two achievement tests indicated that there were significant differences between the pre-test and post-test mean scores on the Matter Unit Test as well as on the Matter Diagnostic Test. Since the notion of status is fundamental to the Conceptual Change Model (Posner, Hewson, Strike & Gertzog, 1982) this study also investigated the students' ability to determine the status of their own conceptions. Analysis of the students' use of written descriptors provided varied evidence of their ability to use technical language (intelligible, plausible, or fruitful) and effectively determine the status of their own conceptions.
PHYSICS TEACHERS' PROFESSIONAL DEVELOPMENT IN THE PROJECT "PHYSICS IN CONTEXT"
Authors: MIKELSKIS-SEIFERT SILKE , DUIT REINDERS
Published: June 2013

Developing teachers' ways of thinking about "good" instruction as well as their views of the teaching and learning process is generally seen as essential for improving teaching behaviour and implementation of more efficient teaching and learning settings. Major deficiencies of German physics instruction as revealed by a nationwide video-study on the practice of physics instruction are addressed. Teachers participating in the project are made familiar with recent views of efficient instruction on the one hand and develop context-based instructional settings on the other. The evaluation resulted in partly encouraging findings. However, it also turned out that a number of teachers' ways of thinking about good instruction did only develop to a somewhat limited degree. The most impressive changes occurred for teachers who enjoyed the most intensive coaching.
BAYESIAN OPTIMAL BLENDING AND CREDIBLE INTERVAL ESTIMATION FOR SATELLITE AND GROUND RAINFALL OBSERVATIONS
Authors: SHEN SAMUEL S. P. , LEE JUNE-YI , LAU WILLIAM K.M.
Published: June 2013

This paper introduces a Bayesian approach to blending rainfall observations from both satellite remote sensing and ground rain gauges and to estimating errors of the blended data in terms of credible interval. The Bayesian posterior estimate (BPE) approach treats one observation as prior information and uses another observation as likelihood function information and as a correction. The BPE is an alternative to the minimum mean square estimate (MMSE) approach, also known as the least square approach. The posterior estimate outputs a probability density function (PDF), while the MMSE approach yields only an estimated mean and mean square error (MSE). When a diffusive rain rate model is assumed, the sampling errors of the Tropical Rainfall Measuring Mission (TRMM) satellite and a regular array of ground rain gauges are calculated under assumptions of idealized conditions: homogenous statistical properties of the rain rate, and flush visits of TRMM approximately twice a day. The optimal blend of the TRMM and ground gauges is determined by the optimal weight for each. The weight for the rain gauges wgis a nonlinear function of the ratio of the space gap to the time gap. The error of the blended product increases as the gaps of time and space samplings expand, and the increase is almost linear when neither time gap nor space gap is small, but becomes strongly nonlinear when the space gap is very small. Our results are helpful in the design of appropriate sampling strategies for rainfall measurements.
Cellular Mechanisms of Tissue Fibrosis. 4. Structural and functional consequences of skeletal muscle fibrosis
Authors: Lieber Richard L. , Ward Samuel R.
Published: June 2013

Skeletal muscle fibrosis can be a devastating clinical problem that arises from many causes, including primary skeletal muscle tissue diseases, as seen in the muscular dystrophies, or it can be secondary to events that include trauma to muscle or brain injury. The cellular source of activated fibroblasts (myofibroblasts) may include resident fibroblasts, adult muscle stem cells, or inflammatory or perivascular cells, depending on the model studied. Even though it is likely that there is no single source for all myofibroblasts, a common mechanism for the production of fibrosis is via the transforming growth factor-β/phosphorylated Smad3 pathway. This pathway and its downstream targets thus provide loci for antifibrotic therapies, as do methods for blocking the transdifferentiation of progenitors into activated fibroblasts. A structural model for the extracellular collagen network of skeletal muscle is needed so that measurements of collagen content, morphology, and gene expression can be related to mechanical properties. Approaches used to study fibrosis in tissues, such as lung, kidney, and liver, need to be applied to studies of skeletal muscle to identify ways to prevent or even cure the devastating maladies of skeletal muscle.
Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults
Authors: Drummond Micah J. , Timmerman Kyle L. , Markofski Melissa M. , Walker Dillon K. , Dickinson Jared M. , Jamaluddin Mohammad , Brasier Allan R. , Rasmussen Blake B. , Volpi Elena
Published: June 2013

Bed rest induces significant loss of leg lean mass in older adults. Systemic and tissue inflammation also accelerates skeletal muscle loss, but it is unknown whether inflammation is associated to inactivity-induced muscle atrophy in healthy older adults. We determined if short-term bed rest increases toll-like receptor 4 (TLR4) signaling and pro-inflammatory markers in older adult skeletal muscle biopsy samples. Six healthy, older adults underwent seven consecutive days of bed rest. Muscle biopsies (vastus lateralis) were taken after an overnight fast before and at the end of bed rest. Serum cytokine expression was measured before and during bed rest. TLR4 signaling and cytokine mRNAs associated with pro- and anti-inflammation and anabolism were measured in muscle biopsy samples using Western blot analysis and qPCR. Participants lost ∼4% leg lean mass with bed rest. We found that after bed rest, muscle levels of TLR4 protein expression and interleukin-6 (IL-6), nuclear factor-κB1, interleukin-10, and 15 mRNA expression were increased after bed rest ( P < 0.05). Additionally, the cytokines interferon-γ, and macrophage inflammatory protein-1β, were elevated in serum samples following bed rest ( P < 0.05). We conclude that short-term bed rest in older adults modestly increased some pro- and anti-inflammatory cytokines in muscle samples while systemic changes in pro-inflammatory cytokines were mostly absent. Upregulation of TLR4 protein content suggests that bed rest in older adults increases the capacity to mount an exaggerated, and perhaps unnecessary, inflammatory response in the presence of specific TLR4 ligands, e.g., during acute illness.
Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle: implications for exercise hyperemia
Authors: Nyberg Michael , Al-Khazraji Baraa K. , Mortensen Stefan P. , Jackson Dwayne N. , Ellis Christopher G. , Hellsten Ylva
Published: June 2013

During skeletal muscle contractions, the concentration of ATP increases in muscle interstitial fluid as measured by microdialysis probes. This increase is associated with the magnitude of blood flow, suggesting that interstitial ATP may be important for contraction-induced vasodilation. However, interstitial ATP has solely been described to induce vasoconstriction in skeletal muscle. To examine whether interstitial ATP induces vasodilation in skeletal muscle and to what extent this vasoactive effect is mediated by formation of nitric oxide (NO) and prostanoids, three different experimental models were studied. The rat gluteus maximus skeletal muscle model was used to study changes in local skeletal muscle hemodynamics. Superfused ATP at concentrations found during muscle contractions (1–10 μM) increased blood flow by up to 400%. In this model, the underlying mechanism was also examined by inhibition of NO and prostanoid formation. Inhibition of these systems abolished the vasodilator effect of ATP. Cell-culture experiments verified ATP-induced formation of NO and prostacyclin in rat skeletal muscle microvascular endothelial cells, and ATP-induced formation of NO in rat skeletal muscle cells. To confirm these findings in humans, ATP was infused into skeletal muscle interstitium of healthy subjects via microdialysis probes and found to increase muscle interstitial concentrations of NO and prostacyclin by ∼60% and ∼40%, respectively. Collectively, these data suggest that a physiologically relevant elevation in interstitial ATP concentrations increases muscle blood flow, indicating that the contraction-induced increase in skeletal muscle interstitial [ATP] is important for exercise hyperemia. The vasodilator effect of ATP application is mediated by NO and prostanoid formation.
Identification and proximal tubular localization of the Mg2+transporter, Slc41a1, in a seawater fish
Authors: Islam Zinia , Hayashi Naoko , Yamamoto Yoko , Doi Hiroyuki , Romero Michael F. , Hirose Shigehisa , Kato Akira
Published: June 2013

The second most abundant cation in seawater (SW), Mg2+, is present at concentrations of ∼53 mM. Marine teleosts maintain plasma Mg2+concentration at 1–2 mM by excreting Mg2+into the urine. Urine Mg2+concentrations of SW teleosts exceed 70 mM, most of which is secreted by the renal tubular epithelial cells. However, molecular mechanisms of the Mg2+secretion have yet to be clarified. To identify transporters involved in Mg2+secretion, we analyzed the expression of fish homologs of the Slc41 Mg2+transporter family in various tissues of SW pufferfish torafugu ( Takifugu rubripes) and its closely related euryhaline species mefugu ( Takifugu obscurus). Takifugu genome contained five members of Slc41 genes, and only Slc41a1 was highly expressed in the kidney. Renal expression of Slc41a1 was markedly elevated when mefugu were transferred from fresh water (FW) to SW. In situ hybridization analysis and immunohistochemistry at the light and electron microscopic levels revealed that Slc41a1 is localized to vacuoles in the apical cytoplasm of the proximal tubules. These results suggest that pufferfish Slc41a1 is a Mg2+transporter involved in renal tubular transepithelial Mg2+secretion by mediating Mg2+transport from the cytosol to the vacuolar lumen, and support the hypothesis that Mg2+secretion is mediated by exocytosis of Mg2+-rich vacuoles to the lumen.
Novel role of ouabain as a cystogenic factor in autosomal dominant polycystic kidney disease
Authors: Blanco Gustavo , Wallace Darren P.
Published: June 2013

The classic role of the Na-K-ATPase is that of a primary active transporter that utilizes cell energy to establish and maintain transmembrane Na+and K+gradients to preserve cell osmotic stability, support cell excitability, and drive secondary active transport. Recent studies have revealed that Na-K-ATPase located within cholesterol-containing lipid rafts serves as a receptor for cardiotonic steroids, including ouabain. Traditionally, ouabain was viewed as a toxin produced only in plants, and it was used in relatively high concentrations to experimentally block the pumping action of the Na-K-ATPase. However, the new and unexpected role of the Na-K-ATPase as a signal transducer revealed a novel facet for ouabain in the regulation of a myriad of cell functions, including cell proliferation, hypertrophy, apoptosis, mobility, and metabolism. The seminal discovery that ouabain is endogenously produced in mammals and circulates in plasma has fueled the interest in this endogenous molecule as a potentially important hormone in normal physiology and disease. In this article, we review the role of the Na-K-ATPase as an ion transporter in the kidney, the experimental evidence for ouabain as a circulating hormone, the function of the Na-K-ATPase as a signal transducer that mediates ouabain's effects, and novel results for ouabain-induced Na-K-ATPase signaling in cystogenesis of autosomal dominant polycystic kidney disease.
New Molecular Tools for Efficient Screening of Cervical Cancer
Authors: Doeberitz Magnus von Knebel
Published: June 2013

Cytological screening using the Pap‐smear led to a remarkable reduction of the mortality of cervical cancer. However, due to subjective test criteria it is hampered by poor inter‐ and intra‐observer agreement. More reproducible assays are expected to improve the current screening and avoid unnecessary medical intervention and psychological distress for the affected women. Cervical cancer arises as consequence of persistent high risk papillomavirus (HR‐HPV) infections. Expression of two viral oncogenes, E6 and E7, in epithelial stem cells is required to initiate and maintain cervical carcinogenesis and results in significant overexpression of the cellular p16INK4a protein. Since this protein is not expressed in normal cervical squamous epithelia, screening for p16INK4a over‐expressing cells allows to specifically identify dysplastic lesions, and significantly reduces the inter‐observer disagreement of the conventional cytological or histological tests. Progression of preneoplastic lesions to invasive cancers is associated with extensive recombination of viral and cellular genomes which can be monitored by detection of papillomavirus oncogene transcripts (APOT assay) derived from integrated viral genome copies. Detection of integrated type oncogene transcripts points to far advanced dysplasia or invasive cancers and thus represents a progression marker for cervical lesions. These new assays discussed here will help to improve current limitations in cervical cancer screening, diagnosis, and therapy control.
SV40: A Human Pathogen?
Authors: Garcea Robert L.
Published: June 2013

Over the past eight years an increasing number of investigators have found SV40 genomic sequences in a variety of human samples, both malignant and normal. Tumor types recurrently reported as SV40‐positive include choroid plexus neoplasms, ependymomas, osteosarcomas, and mesotheliomas. Nonetheless, considerable skepticism that SV40 is a human pathogen still prevails. More constructively, the study of SV40 in humans has renewed interest in the related BK and JC viruses and their role in human disease. New questions now must be addressed. In particular, seroepidemiologic studies utilizing reagents that distinguish SV40, BKV, and JCV immune responses would be a logical next step for independently assessing viral prevalence. Also, prospective studies of select patient groups using optimized detection methods might determine whether SV40 is associated with human oncogenesis in particular circumstances. The importance of such research is underscored by the potential to prevent human polyomavirus infections, and possible associated malignancy, through immunization of high risk populations.
Increasing Evidence for Involvement of SV40 in Human Cancer
Authors: Butel Janet S.
Published: June 2013

SV40, a small DNA virus, is known to possess strong oncogenic potential. Millions of people were exposed to SV40 as an unknown contaminant of some early poliovaccines. This article briefly summarizes the increasing evidence of the association of SV40 with certain types of human cancer, including mesotheliomas and brain tumors. Unanswered questions pertaining to the pathogenesis of human infections by SV40 and the functional role of the virus in tumor development are noted. It is concluded that SV40 should be considered a candidate human tumor virus and that vigorous efforts to clarify the role of the virus in human disease should be supported.
Potential Cellular Signatures of Viral Infections in Human Hematopoietic Cells
Authors: Mikovits J. , Ruscetti F. , Zhu W. , Bagni R. , Dorjsuren D. , Shoemaker R.
Published: June 2013

Expression profiling of cellular genes was performed using a 10,000 cDNA human gene array in order to identify expression changes following chronic infection of human hematopoietic cells with Kapsosi’s Sarcoma ‐associated Virus (KSHV) also known as Human Herpesvirus 8 (HHV8) and Human T cell leukemia virus‐1 (HTLV‐1). We performed cell‐free {\it in vitro} infection of primary bone marrow derived CD34+ cells using semi‐purified HHV8 and a mature IL‐2 dependent T cell line, KIT 225, using highly concentrated viral stocks prepared from an infectious molecular clone of HTLV‐1. Thirty days post infection, mRNA was isolated from infected cultures and uninfected controls and submitted for microarray analysis. More than 400 genes were differentially expressed more than two‐fold following HHV8 infection of primary bone marrow derived CD34+ cells. Of these 400, interferon regulatory factor 4 (IRF4), cyclin B2, TBP‐associated factor, eukaryotic elongation factor and pim 2 were up‐regulated more than 3.5 fold. In contrast, less than 100 genes were differentially expressed more than two‐fold following chronic infection of a mature T cell line with HTLV‐1. Of these, only cdc7 was up‐regulated more than 3.5 fold. These data may provide insight into cellular signatures of infection useful for diagnosis of infection as well as potential targets for therapeutic intervention.
Comprehensive phenotyping and biological marker discovery
Authors: Kantor Aaron B.
Published: June 2013

There is an enormous unmet need for biological markers to characterize disease type, status, progression, and response to therapy. We are developing and applying an integrated bioanalytical platform and clinical research program to facilitate comprehensive differential phenotyping of patient samples and enable the discovery of biomarkers. The platform employs high‐throughput, quantitative analysis for the characterization of thousands of parameters including cell populations, cell‐surface antigen density, soluble proteins and soluble low molecular weight biomolecules, from small‐volume biological samples in a clinical research laboratory‐like setting.
Biomarkers and Surrogate Endpoints: How and When might They Impact Drug Development?
Authors: Lathia Chetan D.
Published: June 2013

As the pharmaceutical industry starts developing novel molecules developed based on molecular biology principles and a better understanding of the human genome, it becomes increasingly important to develop early indicators of activity and/or toxicity. Biomarkers are measurements based on molecular pharmacology and/or pathophysiology of the disease being evaluated that may assist with decision‐making in various phases of drug development. The utility of biomarkers in the development of drugs is described in this review. Additionally, the utility of pharmacokinetic data in drug development is described. Development of biomarkers may help reduce the cost of drug development by allowing key decisions earlier in the drug development process. Additionally, biomarkers may be used to select patients who have a high likelihood of benefit or they could be used by clinicians to evaluate the potential for efficacy after start of treatment.