bluuebunny/crossref_metadata_2025 huggingface dataset:
Epitaxial strontium titanate films grown by atomic layer deposition on SrTiO3-buffered Si(001) substrates
Authors: McDaniel Martin D. , Posadas Agham , Ngo Thong Q. , Dhamdhere Ajit , Smith David J. , Demkov Alexander A. , Ekerdt John G.
Published: December 2012

Epitaxial strontium titanate (STO) films have been grown by atomic layer deposition (ALD) on Si(001) substrates with a thin STO buffer layer grown by molecular beam epitaxy (MBE). Four unit cells of STO grown by MBE serve as the surface template for ALD growth. The STO films grown by ALD are crystalline as-deposited with minimal, if any, amorphous SiOx layer at the STO-Si interface. The growth of STO was achieved using bis(triisopropylcyclopentadienyl)-strontium, titanium tetraisopropoxide, and water as the coreactants at a substrate temperature of 250 °C. In situ x-ray photoelectron spectroscopy (XPS) analysis revealed that the ALD process did not induce additional Si–O bonding at the STO-Si interface. Postdeposition XPS analysis also revealed sporadic carbon incorporation in the as-deposited films. However, annealing at a temperature of 250 °C for 30 min in moderate to high vacuum (10−6–10−9 Torr) removed the carbon species. Higher annealing temperatures (>275 °C) gave rise to a small increase in Si–O bonding, as indicated by XPS, but no reduced Ti species were observed. X-ray diffraction revealed that the as-deposited STO films were c-axis oriented and fully crystalline. A rocking curve around the STO(002) reflection gave a full width at half maximum of 0.30° ± 0.06° for film thicknesses ranging from 5 to 25 nm. Cross-sectional transmission electron microscopy revealed that the STO films were continuous with conformal growth to the substrate and smooth interfaces between the ALD- and MBE-grown STO. Overall, the results indicate that thick, crystalline STO can be grown on Si(001) substrates by ALD with minimal formation of an amorphous SiOx layer using a four-unit-cell STO buffer layer grown by MBE to serve as the surface template.
Effect of perceptually irrelevant variance in head-related transfer functions on principal component analysis
Authors: Breebaart Jeroen
Published: December 2012

The significant amount of variance in head-related transfer functions (HRTFs) resulting from source location and subject dependencies have led researchers to use principal components analysis (PCA) to approximate HRTFs with a small set of basis functions. PCA minimizes a mean-square error, and consequently may spend modeling effort on perceptually irrelevant properties. To investigate the extent of this effect, PCA performance was studied before and after removal of perceptually irrelevant variance. The results indicate that from the sixth PCA component onward, a substantial amount of perceptually irrelevant variance is being accounted for.
Identity and Function of a Large Gene Network Underlying Mutagenic Repair of DNA Breaks
Authors: Al Mamun Abu Amar M. , Lombardo Mary-Jane , Shee Chandan , Lisewski Andreas M. , Gonzalez Caleb , Lin Dongxu , Nehring Ralf B. , Saint-Ruf Claude , Gibson Janet L. , Frisch Ryan L. , Lichtarge Olivier , Hastings P. J. , Rosenberg Susan M.
Published: December 2012

Sewing Up DNA Repair

All cells have a battery of DNA-repair pathways to help ensure genome maintenance and stability, including stress-induced DNA break repair in
Escherichia coli.
Similar pathways—which can be mutagenic—are known in yeast and human cells and have the potential to accelerate evolution. Sixteen proteins are known to be required for the pathway in
E. coli.

Al Mamun
et al.

(p.
1344
) analyzed the
E. coli
pathway to determine the full complement of protein contributions to the pathway. Ninety-three genes were found to be required for stress-induced DNA break repair. One-third of the proteins identified in the network were involved in electron transfer, functioning in oxidative phosphorylation, and acting through the σ
s
stress response pathway, which thus represents a critical hub in the network.
Evolution of an MCM Complex in Flies That Promotes Meiotic Crossovers by Blocking BLM Helicase
Authors: Kohl Kathryn P. , Jones Corbin D. , Sekelsky Jeff
Published: December 2012

Swapping Recombination Proteins

Crossing over is a means by which organisms create genetic diversity through the mixing of gene complexes. The primary meiotic crossover pathway in budding yeast, mice, nematodes, and plants requires the Msh4–Msh5 heterodimer, which promotes crossovers by blocking anticrossover activities of the Bloom syndrome helicase. However, some fly species, including members of the genus
Drosophila
, have lost Msh4–Msh5.

Kohl
et al.

(p.
1363
) now show that
Drosophila
have evolved a minichromosome maintenance (MCM)–like protein, dubbed mei-MCM, that performs the same function as Msh4–Msh5. Furthermore, these genes appear to have evolved under positive selection, possibly as a result of their repurposing to this novel function.
Sexually Dimorphic BDNF Signaling Directs Sensory Innervation of the Mammary Gland
Authors: Liu Yin , Rutlin Michael , Huang Siyi , Barrick Colleen A. , Wang Fan , Jones Kevin R. , Tessarollo Lino , Ginty David D.
Published: December 2012

Androgen-Driven Sequestration

Male and female mice differ in the neuronal patterns that serve the mammary glands.

Yin Liu
et al.

(p.
1357
) now describe how gonadal hormones drive development of distinct male and female sensory innervations. Although both male and female mammary glands develop their sensory innervation similarly in early embryogenesis, once the androgens take effect, the developmental trajectories diverge. By birth, the rich network of sensory neurons present in the female is absent in the male. Androgens cause a switch from expression of the full-length neurotrophin receptor TrkB to its truncated form, TrkB.T1, both of which are expressed on the neurons. In males, truncated TrkB.T1 sequesters brain-derived neurotrophic factor (BDNF) from further activity, whereas in females, full-length TrkB binds BDNF and supports neuronal development.
Developmental Progression to Infectivity in
Trypanosoma brucei
Triggered by an RNA-Binding Protein
Authors: Kolev Nikolay G. , Ramey-Butler Kiantra , Cross George A. M. , Ullu Elisabetta , Tschudi Christian
Published: December 2012

Awakening a Life Cycle

Sleeping sickness continues to afflict populations in sub-Saharan Africa, but for the past 100 years, research on the
Trypanosoma brucei
protozoan parasite has been hampered by an inaccessibility of the insect vector stages to modern research tools.

Kolev
et al.

(p.
1352
) have identified an RNA-binding protein (RBP6) as a master regulator that drives the entire developmental program of the trypanosome through all its life-cycle stages. The ability to perform this transformation in vitro will allow study of the many biochemical and morphological changes as parasites change from dividing noninfectious forms to infectious nondividing antigenically variable forms.
Putting a Greenhouse Gas to Work
Authors: Haufe Günter
Published: December 2012

Fluoroform (CHF
3
), a waste product that has been destroyed, can now be used to synthesize a wide variety of fluorinated compounds.
The Utility of Mouse Models in Post-GWAS Research
Authors: Lewis Annabelle , Tomlinson Ian
Published: December 2012

Functional validation of a noncoding genetic variant linked to cancer risk is encouraging for genome-wide association studies.
Ancient Igneous Intrusions and Early Expansion of the Moon Revealed by GRAIL Gravity Gradiometry
Authors: Andrews-Hanna Jeffrey C. , Asmar Sami W. , Head James W. , Kiefer Walter S. , Konopliv Alexander S. , Lemoine Frank G. , Matsuyama Isamu , Mazarico Erwan , McGovern Patrick J. , Melosh H. Jay , Neumann Gregory A. , Nimmo Francis , Phillips Roger J. , Smith David E. , Solomon Sean C. , Taylor G. Jeffrey , Wieczorek Mark A. , Williams James G. , Zuber Maria T.
Published: December 2012

The Holy GRAIL?

The gravity field of a planet provides a view of its interior and thermal history by revealing areas of different density. GRAIL, a pair of satellites that act as a highly sensitive gravimeter, began mapping the Moon's gravity in early 2012. Three papers highlight some of the results from the primary mission.

Zuber
et al.

(p.
668
, published online 6 December) discuss the overall gravity field, which reveals several new tectonic and geologic features of the Moon. Impacts have worked to homogenize the density structure of the Moon's upper crust while fracturing it extensively.

Wieczorek
et al.

(p.
671
, published online 6 December) show that the upper crust is 35 to 40 kilometers thick and less dense—and thus more porous—than previously thought. Finally,

Andrews-Hanna
et al.

(p.
675
, published online 6 December) show that the crust is cut by widespread magmatic dikes that may reflect a period of expansion early in the Moon's history.
The Live Attenuated Actinobacillus pleuropneumoniae Triple-Deletion Mutant Δ
apxIC
Δ
apxIIC
Δ
apxIV
-
ORF1
Strain, SLW05, Immunizes Pigs against Lethal Challenge with Haemophilus parasuis
Authors: Fu Shulin , Ou Jiwen , Zhang Minmin , Xu Juan , Liu Huazhen , Liu Jinlin , Yuan Fangyan , Chen Huanchun , Bei Weicheng
Published: December 2012

Haemophilus parasuis
and
Actinobacillus pleuropneumoniae
both belong to the family
Pasteurellaceae
and are major respiratory pathogens that cause large economic losses in the pig industry worldwide. We previously constructed an attenuated
A. pleuropneumoniae
serovar 1 live vaccine prototype, SLW05 (Δ
apxIC
Δ
apxIIC
Δ
apxIV
-
ORF1
), which is able to produce nontoxic but immunogenic ApxIA, ApxIIA, and ApxIVA. This triple-deletion mutant strain was shown to elicit protective immunity against virulent
A. pleuropneumoniae
. In the present study, we investigated whether immunization with SLW05 could also protect against lethal challenge with virulent
H. parasuis
SH0165 (serovar 5) or MD0322 (serovar 4). The SLW05 strain was found to elicit a strong humoral antibody response in pigs and to confer significant protection against challenge with a lethal dose of
H. parasuis
SH0165 or MD0322. IgG subtype analysis revealed that SLW05 induces a bias toward a Th1-type immune response and stimulates interleukin 2 (IL-2) and gamma interferon (IFN-γ) production. Moreover, antisera from SLW05-vaccinated pigs efficiently inhibited both
A. pleuropneumoniae
and
H. parasuis
growth in a whole-blood assay. This is the first report that a live attenuated
A. pleuropneumoniae
vaccine with SLW05 can protect against lethal
H. parasuis
infection, which provides a novel approach for developing an attenuated
H. parasuis
vaccine.
Hepatitis C Genotype 1 Mosaic Vaccines Are Immunogenic in Mice and Induce Stronger T-Cell Responses than Natural Strains
Authors: Yusim Karina , Dilan Rebecca , Borducchi Erica , Stanley Kelly , Giorgi Elena , Fischer William , Theiler James , Marcotrigiano Joseph , Korber Bette , Barouch Dan H.
Published: December 2012

Despite improved hepatitis C virus (HCV) treatments, vaccines remain an effective and economic option for curtailing the epidemic. Mosaic protein HCV genotype 1 vaccine candidates designed to address HCV diversity were immunogenic in mice. They elicited stronger T-cell responses to NS3-NS4a and E1-E2 proteins than did natural strains, as assessed with vaccine-matched peptides.
Field Evaluation of a Broadly Sensitive HIV-1 In-House Genotyping Assay for Use with both Plasma and Dried Blood Spot Specimens in a Resource-Limited Country
Authors: Inzaule Seth , Yang Chunfu , Kasembeli Alex , Nafisa Lillian , Okonji Jully , Oyaro Boaz , Lando Richard , Mills Lisa A. , Laserson Kayla , Thomas Timothy , Nkengasong John , Zeh Clement
Published: December 2012

HIV-1 drug resistance (HIVDR) assays are important tools in clinical management of HIV-infected patients on antiretroviral therapy (ART) and surveillance of drug-resistant variants at population levels. The high cost associated with commercial assays hinders their use in resource-limited settings. We adopted and validated a low-cost in-house assay using 68 matched plasma and dried blood spot (DBS) samples with a median viral load (VL) of 58,187 copies/ml, ranging from 253 to 3,264,850 against the commercial assay ViroSeq. Results indicated that the in-house assay not only had a higher plasma genotyping rate than did ViroSeq (94% versus 78%) but also was able to genotype 89.5% (51/57) of the matched DBS samples with VLs of ≥1,000 copies/ml. The sensitivity in detecting DR mutations by the in-house assay was 98.29% (95% confidence interval [CI], 97.86 to 98.72) on plasma and 96.54 (95% CI, 95.93 to 97.15) on DBS, and the specificity was 99.97% (95% CI, 99.91 to 100.00) for both sample types compared to ViroSeq. The minor DR mutation differences detected by the in-house assay against ViroSeq did not result in clinical significance. In addition, cost analysis showed that the in-house assay could reduce the genotyping cost by about 60% for both plasma and DBS compared to ViroSeq. This field condition evaluation highlights the potential utility of a cost-effective, subtype-independent, in-house genotyping assay using both plasma and DBS specimens for HIVDR clinical monitoring and population-based surveillance in resource-limited settings.
Zoonotic Cryptosporidium Species and Enterocytozoon bieneusi Genotypes in HIV-Positive Patients on Antiretroviral Therapy
Authors: Wang Lin , Zhang Hongwei , Zhao Xudong , Zhang Longxian , Zhang Guoqing , Guo Meijin , Liu Lili , Feng Yaoyu , Xiao Lihua
Published: December 2012

Molecular diagnostic tools have been used increasingly in the characterization of the transmission of cryptosporidiosis and microsporidiosis in developing countries. However, few studies have examined the distribution of
Cryptosporidium
species and
Enterocytozoon bieneusi
genotypes in AIDS patients receiving antiretroviral therapy. In the present study, 683 HIV-positive patients in the National Free Antiretroviral Therapy Program in China and 683 matched HIV-negative controls were enrolled.
Cryptosporidium
species and subtypes and
Enterocytozoon bieneusi
genotypes were detected and differentiated by PCR and DNA sequencing. The infection rates were 1.5% and 0.15% for
Cryptosporidium
and 5.7% and 4.2% for
E. bieneusi
in HIV-positive and HIV-negative participants, respectively. The majority (8/11) of
Cryptosporidium
cases were infections by zoonotic species, including
Cryptosporidium meleagridis
(5),
Cryptosporidium parvum
(2), and
Cryptosporidium suis
(1). Prevalent
E. bieneusi
genotypes detected, including EbpC (39), D (12), and type IV (7), were also potentially zoonotic. The common occurrence of EbpC was a feature of
E. bieneusi
transmission not seen in other areas. Contact with animals was a risk factor for both cryptosporidiosis and microsporidiosis. The results suggest that zoonotic transmission was significant in the epidemiology of both diseases in rural AIDS patients in China.
Species Shout-Outs From Abdul to Zebra: Encouraging Nonmajors to Communicate in the Biology Classroom
Authors: Colon Christina P.
Published: December 2012

In this learning activity, a simple verbal prompt was employed as a nonthreatening and engaging discussion starter for non-Biology majors in a biology class at a community college. By calling out the name of their favorite species, then relating new content to this organism, these “Species Shout-Outs” fostered enthusiasm among students by promoting engagement and creating relevance, all of which are important to improving higher education. This activity combined the elements of academic and social interaction, as well as active learning, which have been shown to be necessary to foster student retention through college.
Dynamic Model Visualizing the Process of Viral Plaque Formation
Authors: Marintcheva Boriana
Published: December 2012

In Microbiology and Virology courses, viral plaques are often presented to students as the way one can visualize viruses/bacteriophages. While students generally grasp the idea that counting plaques is essentially the same as counting viruses in their sample (assuming that one virus entering the cell is sufficient for productive infection), the process of plaque formation itself remains largely obscure. Many students fail to appreciate that viral plaques are actually a “laboratory-made” phenomenon allowing us to observe and study the growth of lytic viruses. The latter often presents a challenge for the interpretation of experimental data related to viral growth and drug discovery using plaque reduction assay. The hands-on model described here creates an opportunity for students to experience the process of viral plaque formation while engaging multiple senses and creating a lasting impression.
Helping Students Understand Gene Regulation with Online Tools: A Review of MEME and Melina II, Motif Discovery Tools for Active Learning in BiologyReview of:
MEME
, http://meme.sdsc.edu/meme/intro.html, and
Melina II,
http://melina2.hgc.jp/public/index.html.
Authors: Treves David
Published: December 2012

Review of:
MEME and Melina II, which are two free and easy-to-use online motif discovery tools that can be employed to actively engage students in learning about gene regulatory elements.
Virtual Laboratory Meets Case-Based InstructionReview of:
Case It!
website from the University of Wisconsin–River Falls, http://www.caseitproject.org/.
Authors: Best Aaron A. , Harbour Deborah V.
Published: December 2012

Review of:
CaseIt!, which is an NSF sponsored project developed by Mark Berglund and colleagues at the University of Wisconsin-River Falls aimed at bringing active, case-based learning of complex molecular biological techniques and subjects into introductory science classes by freely providing a software simulation environment and supporting instructional resources to educators.
A Holistic View of Emerging Infectious DiseasesReview of:	Emerging Infectious Diseases: A Guide to Diseases, Causative Agents, and Surveillance;	BeltzLisa A.; (	2011).	Jossey-Bass, John Wiley and Sons, Inc.	San Francisco, CA.	700 pages.
Authors: Kulkarni Himgauri K.
Published: December 2012

Review of:
Emerging Infectious Diseases: A Guide to Diseases, Causative Agents, and Surveillance;
Lisa A. Beltz; (2011). Jossey-Bass, John Wiley and Sons, Inc. San Francisco, CA. 700 pages.
Invisible Guide: How Our Understanding of Life Has Been Shaped by
E. coli
Review of:	Microcosm: E. Coli and the New Science of Life;	ZimmerCarl; (	2008).	Pantheon Books,	New York.	243 pages.
Authors: Govindan Brinda
Published: December 2012

Review of:
Microcosm: E. coli and the New Science of Life;
Carl Zimmer; (2008). Pantheon Books, New York. 243 pages.
A Reference Manual for Life Science ResearchersReview of:	Current Protocols Essential Laboratory Techniques,	2nd ed.;	GallagherSeanWileyEmily, eds.; (	2012).	John Wiley and Sons,	Hoboken, NJ.	664 pages.
Authors: Washington Jacqueline
Published: December 2012

Review of:
Current Protocols Essential Laboratory Techniques, 2nd ed.;
Sean Gallagher and Emily Wiley, eds.; (2012). John Wiley and Sons, Hoboken, NJ. 664 pages.
Perspectives on Cholera Pandemics in AfricaReview of:	Africa in the Time of Cholera: A History of Pandemics from 1817 to the Present;	EchenbergMyron; (	2011).	Cambridge University Press,	Cambridge, UK.	232 pages.
Authors: Elder Elisabeth
Published: December 2012

Review of:
Africa in the Time of Cholera: A History of Pandemics from 1817 to the Present;
Myron Echenberg; (2011). Cambridge University Press, Cambridge, UK. 232 pages.
Advancing the Vision: New PubMed Indexing, Creative Commons Licensing, and December Highlights
Authors: Woolverton Christopher J.
Published: December 2012

In the two years since the American Association for the Advancement of Science (AAAS) published the Vision and Change in Undergraduate Biology Education: A Call to Action report, the national momentum to transform undergraduate biology education has driven the Journal of Microbiology & Biology Education (JMBE)’s growth in readership and authorship. Since January 2010, the Journal has more than doubled its registered users and overall submissions have increased by nearly 40%. International presence on the Journal’s Editorial Board is currently at 13%, thanks to Research Editor Kathy M. Takayama’s work to incorporate biology educators on a global scale. The American Society for Microbiology (ASM)’s faculty training programs—such as the ASM/JGI Genomic Sciences Programs and the ASM/ NSF Biology Scholars Program—connect scholars with the Editorial Board and expose them to JMBE’s open access content. After they train and/or present at the annual ASM Conference for Undergraduate Educators (ASMCUE), our readers are poised to submit their work to JMBE. In 2012, 37% of published JMBE authors are alumni of these ASM programs.
Betaretroviral Envelope Subunits Are Noncovalently Associated and Restricted to the Mammalian Class
Authors: Henzy Jamie E. , Coffin John M.
Published: December 2012

The structure of the transmembrane subunit (TM) of the retroviral envelope glycoprotein (Env) is highly conserved among most retrovirus genera and includes a pair of cysteines that forms an intramolecular disulfide loop within the ectodomain. Alpha-, gamma-, and deltaretroviruses have a third cysteine, adjacent to the loop, which forms a disulfide bond between TM and the surface subunit (SU) of Env, while lentiviruses, which have noncovalently associated subunits, lack this third cysteine. The
Betaretrovirus
genus includes Jaagsiekte sheep retrovirus (JSRV) and mouse mammary tumor virus (MMTV), as well as many endogenous retroviruses. Envelope subunit association had not been characterized in the betaretroviruses, but lack of a third cysteine in the TM ectodomain suggested noncovalently associated subunits. We tested the Env proteins of JSRV and MMTV, as well as human endogenous retrovirus K (HERV-K)108—a betaretrovirus-like human endogenous retrovirus—for intersubunit bonding and found that, as in the lentiviruses, the Env subunits lack an intersubunit disulfide bond. Since these results suggest that the number of cysteines in the TM loop region readily distinguishes between covalent and noncovalent structure, we surveyed endogenous retroviral TM sequences in the genomes of vertebrates represented in public databases and found that (i) retroviruses with noncovalently associated subunits have been present during all of anthropoid evolution and (ii) the noncovalent
env
motif is limited to mammals, while the covalent type is found among five vertebrate classes. We discuss implications of these findings for retroviral evolution, cross-species transmissions, and recombination events involving the
env
gene.
Resistance to Two Heterologous Neurotropic Oncolytic Viruses, Semliki Forest Virus and Vaccinia Virus, in Experimental Glioma
Authors: Vähä-Koskela Markus J. V. , Le Boeuf Fabrice , Lemay Chantal , De Silva Naomi , Diallo Jean-Simon , Cox Julie , Becker Michelle , Choi Youngmin , Ananth Abhirami , Sellers Clara , Breton Sophie , Roy Dominic , Falls Theresa , Brun Jan , Hemminki Akseli , Hinkkanen Ari , Bell John C.
Published: December 2012

Attenuated Semliki Forest virus (SFV) may be suitable for targeting malignant glioma due to its natural neurotropism, but its replication in brain tumor cells may be restricted by innate antiviral defenses. We attempted to facilitate SFV replication in glioma cells by combining it with vaccinia virus, which is capable of antagonizing such defenses. Surprisingly, we found parenchymal mouse brain tumors to be refractory to both viruses. Also, vaccinia virus appears to be sensitive to SFV-induced antiviral interference.
MicroRNA miR-155 Affects Antiviral Effector and Effector Memory CD8 T Cell Differentiation
Authors: Tsai Ching-Yi , Allie S. Rameeza , Zhang Weijun , Usherwood Edward J.
Published: December 2012

MicroRNAs are key regulators of the immune response, but their role in CD8 T cell differentiation
in vivo
is not known. We show that miR-155 is important in both effector and memory antiviral CD8 T cell responses. Without miR-155, there was a weaker effector response and a skewing toward memory precursor cells. At the memory stage, miR-155-deficient CD8 T cells preferentially differentiated into central memory cells and were capable of mounting a potent secondary response.
Retroviral DNA Methylation and Epigenetic Repression Are Mediated by the Antiviral Host Protein Daxx
Authors: Shalginskikh Natalia , Poleshko Andrey , Skalka Anna Marie , Katz Richard A.
Published: December 2012

Integrated retroviral DNA is subject to epigenetic transcriptional silencing at different frequencies. This process is mediated by repressive DNA methylation and histone modifications on viral chromatin. However, the detailed mechanisms by which retroviral silencing is initiated and maintained are not well understood. Using a model system in which avian sarcoma virus (ASV) DNA is epigenetically repressed in mammalian cells, we previously found that a cellular scaffolding protein, Daxx, acts as an antiretroviral factor that promotes epigenetic repression through recruitment of histone deacetylases (HDACs). Here we show that human Daxx protein levels are increased in response to retroviral infection and that Daxx acts at the time of infection to initiate epigenetic repression. Consistent with a rapid and active antiviral epigenetic response, we found that repressive histone marks and long terminal repeat (LTR) DNA methylation could be detected within 12 h to 3 days postinfection, respectively. Daxx was also found to be required for long-term ASV silencing maintenance and full viral DNA methylation, and it was physically associated with both viral DNA and DNA methyltransferases (DNMTs). These findings support a model in which incoming retroviral protein-DNA complexes are detected by Daxx, and the integrated provirus is rapidly chromatinized and repressed by DNA methylation and histone modification as part of an antiviral response. These results uncover a possible direct and active antiviral mechanism by which DNMTs can be recruited to retroviral DNA.
Stimulation of NF-κB Activity by the HIV Restriction Factor BST2
Authors: Tokarev Andrey , Suarez Marissa , Kwan Wilson , Fitzpatrick Kathleen , Singh Rajendra , Guatelli John
Published: December 2012

BST2 (HM1.24; CD317; tetherin) is an interferon-inducible transmembrane protein that restricts the release of several enveloped viruses, including HIV, from infected cells. Before its activity as an antiviral factor was described, BST2 was identified as an inducer of NF-κB activity. Here we show that human BST2 induces NF-κB in a dose-dependent manner. This activity is separable from the restriction of virus release: a YxY sequence in the cytoplasmic domain of BST2 is required for the induction of NF-κB but is dispensable for restriction, whereas the glycosylphosphatidylinositol (GPI) addition site in the protein's ectodomain is required for restriction but is largely dispensable for the induction of NF-κB. Mutations predicted to disrupt the coiled-coil structure of the BST2 ectodomain impaired both signaling and restriction, but disruption of the tetramerization interface differentially affected signaling. The induction of NF-κB by BST2 was impaired by inhibition of transforming growth factor β (TGF-β)-activated kinase 1 (TAK1) or by calcium chelation, suggesting potential linkage to the mitogen-activated protein kinase and endoplasmic reticulum (ER) stress response pathways. Consistent with a role for TAK1, BST2 coimmunoprecipitated with TAK1 and the TAK1-associated pseudophosphatase TAB1; these interactions required the YxY sequence in BST2. Moreover, signaling by BST2 was blocked by expression of an IκB-mutant that inhibits the canonical pathway of NF-κB activation. The expression of HIV-1 Vpu inhibited the induction of NF-κB by BST2; this inhibition required Vpu's ability to bind the cellular β-TrCP-E3-ubiquitin ligase complex. The expression of HIV-1 lacking
vpu
augmented the induction of NF-κB activity by BST2, suggesting that BST2 can act as a virus sensor. This augmentation was also inhibited by Vpu in a β-TrCP-dependent manner. The role of BST2 in the host-pathogen relationship is apparently multifaceted: signaling during the innate immune response, sensing of viral gene expression, and direct restriction of virus release. HIV-1 Vpu counteracts each of these functions.
F-Actin Modulates Measles Virus Cell-Cell Fusion and Assembly by Altering the Interaction between the Matrix Protein and the Cytoplasmic Tail of Hemagglutinin
Authors: Wakimoto Hiroshi , Shimodo Masakatsu , Satoh Yuto , Kitagawa Yoshinori , Takeuchi Kaoru , Gotoh Bin , Itoh Masae
Published: December 2012

Actin filament (F-actin) is believed to be involved in measles virus (MV) assembly as a cellular factor, but the precise roles remain unknown. Here we show that Phe at position 50 of the MV matrix (M) protein is important for its association with F-actin, through which the function of the M protein is regulated. In plasmid-expressed or MV-infected cells, a coimmunoprecipitation study revealed that the wild-type M (M-WT) protein associated strongly with F-actin but only weakly with the cytoplasmic tail of the hemagglutinin (H) protein. Since the F50P mutation allowed the M protein the enhanced interaction with the H protein in return for the sharply declined association with F-actin, the mutant M (M-F50P) protein strongly inhibited MV cell-cell fusion and promoted the uptake of the H protein into virus particles. The abundantly incorporated H protein resulted in the increase in infectivity of the F50P virus, although the virus contained a level of genome RNA equal to that of the WT virus. When the structure of F-actin was disrupted with cytochalasin D, the M-WT protein liberated from F-actin interacted with the H protein as tightly as the M-F50P protein, suppressing cell-cell fusion and promoting virus assembly comparably efficiently as the M-F50P protein. The cell-cell fusion activity of the WT virus appeared to be upheld by F-actin, which prevents the M protein interaction with the H protein. Our results indicate that F-actin in association with the M protein alters the interaction between the M and H proteins, thereby modulating MV cell-cell fusion and assembly.
Molecular Mechanism behind Rotavirus NSP1-Mediated PI3 Kinase Activation: Interaction between NSP1 and the p85 Subunit of PI3 Kinase
Authors: Bagchi Parikshit , Nandi Satabdi , Nayak Mukti Kant , Chawla-Sarkar Mamta
Published: December 2012

Our previous study had reported on the interaction of rotavirus NSP1 with cellular phosphoinositide 3-kinase (PI3K) during activation of the PI3K pathway (P. Bagchi et al., J. Virol. 84:6834–6845, 2010). In this study, we have analyzed the molecular mechanism behind this interaction. Results showed that this interaction is direct and that both α and β isomers of the PI3K regulatory subunit p85 and full-length NSP1 are important for this interaction, which results in efficient activation of the PI3K/Akt pathway during rotavirus infection.
N-Terminal Phosphorylation Sites of Herpes Simplex Virus 1 ICP0 Differentially Regulate Its Activities and Enhance Viral Replication
Authors: Mostafa Heba H. , Thompson Thornton W. , Davido David J.
Published: December 2012

The herpes simplex virus 1 (HSV-1) infected cell protein 0 (ICP0) is an immediate-early phosphoprotein that transactivates viral gene expression. Evidence suggests that phosphorylation regulates the functions of ICP0, and three regions (termed regions I, II, and III) in the protein are known to be phosphorylated. Mutation of the putative phosphorylation sites within region I, termed Phos 1, which lies in the N-terminal portion of ICP0, impairs the E3 ubiquitin (Ub) ligase and ND10-disrupting activities of ICP0 in cell culture and diminishes viral replication. To identify the specific phosphorylation site(s) or residues responsible for the phenotypes observed with Phos 1, individual residues within region I were mutated to alanine (S224A, T226A, T231A, and T232A) and one double mutant S224A/T226A was constructed. Tissue culture studies demonstrated that the S224A, S224A/T226A, T231A, and T232A mutants were unable to dissociate the cellular protein PML from ND10 and that the S224/T226A mutant was defective in its ability to dissociate the cellular protein Sp100 from ND10. Additionally, the transactivation activity of ICP0 was impaired in the S224A and S224A/T226A mutants. The S224A and S224A/T226A mutant forms were more stable than wild-type ICP0, suggesting that their ability to autoubiquitinate was limited. Moreover, one ICP0 ubiquitination target, USP-7, was also more stable after infection with these two mutants. Lastly, the replication of the S224A and S224A/T226A mutant viruses was reduced in cell culture and
in vivo
. Overall, our data suggest that specific phosphorylation sites within region I differentially regulate the activities of ICP0, which are required for efficient viral replication.
Pin1 Interacts with the Epstein-Barr Virus DNA Polymerase Catalytic Subunit and Regulates Viral DNA Replication
Authors: Narita Yohei , Murata Takayuki , Ryo Akihide , Kawashima Daisuke , Sugimoto Atsuko , Kanda Teru , Kimura Hiroshi , Tsurumi Tatsuya
Published: December 2012

Peptidyl-prolyl
cis-trans
isomerase NIMA-interacting 1 (Pin1) protein is known as a regulator which recognizes phosphorylated Ser/Thr-Pro motifs and increases the rate of
cis
and
trans
amide isomer interconversion, thereby altering the conformation of its substrates. We found that Pin1 knockdown using short hairpin RNA (shRNA) technology resulted in strong suppression of productive Epstein-Barr virus (EBV) DNA replication. We further identified the EBV DNA polymerase catalytic subunit, BALF5, as a Pin1 substrate in glutathione
S
-transferase (GST) pulldown and immunoprecipitation assays. Lambda protein phosphatase treatment abolished the binding of BALF5 to Pin1, and mutation analysis of BALF5 revealed that replacement of the Thr178 residue by Ala (BALF5 T178A) disrupted the interaction with Pin1. To further test the effects of Pin1 in the context of virus infection, we constructed a BALF5-deficient recombinant virus. Exogenous supply of wild-type BALF5 in HEK293 cells with knockout recombinant EBV allowed efficient synthesis of viral genome DNA, but BALF5 T178A could not provide support as efficiently as wild-type BALF5. In conclusion, we found that EBV DNA polymerase BALF5 subunit interacts with Pin1 through BALF5 Thr178 in a phosphorylation-dependent manner. Pin1 might modulate EBV DNA polymerase conformation for efficient, productive viral DNA replication.
A Hydrogen Peroxide-Inactivated Virus Vaccine Elicits Humoral and Cellular Immunity and Protects against Lethal West Nile Virus Infection in Aged Mice
Authors: Pinto Amelia K. , Richner Justin M. , Poore Elizabeth A. , Patil Pradnya P. , Amanna Ian J. , Slifka Mark K. , Diamond Michael S.
Published: December 2012

West Nile virus (WNV) is an emerging pathogen that is now the leading cause of mosquito-borne and epidemic encephalitis in the United States. In humans, a small percentage of infected individuals develop severe neuroinvasive disease, with the greatest relative risk being in the elderly and immunocompromised, two populations that are difficult to immunize effectively with vaccines. While inactivated and subunit-based veterinary vaccines against WNV exist, currently there is no vaccine or therapy available to prevent or treat human disease. Here, we describe the generation and preclinical efficacy of a hydrogen peroxide (H
2
O
2
)-inactivated WNV Kunjin strain (WNV-KUNV) vaccine as a candidate for further development. Both young and aged mice vaccinated with H
2
O
2
-inactivated WNV-KUNV produced robust adaptive B and T cell immune responses and were protected against stringent and lethal intracranial challenge with a heterologous virulent North American WNV strain. Our studies suggest that the H
2
O
2
-inactivated WNV-KUNV vaccine is safe and immunogenic and may be suitable for protection against WNV infection in vulnerable populations.
Dueling Regulatory Properties of a Transcriptional Activator (MtrA) and Repressor (MtrR) That Control Efflux Pump Gene Expression in Neisseria gonorrhoeae
Authors: Zalucki Yaramah M. , Dhulipala Vijaya , Shafer William M.
Published: December 2012

MtrA is a member of the AraC family of transcriptional regulators and has been shown to play an important role in enhancing transcription of the
mtrCDE
operon, which encodes a tripartite multidrug efflux pump, when gonococci are exposed to a sublethal level of antimicrobials. Heretofore, the DNA-binding properties of MtrA were unknown. In order to understand how MtrA activates
mtrCDE
expression, we successfully purified MtrA and found that it could bind specifically to the
mtrCDE
promoter region. The affinity of MtrA for the
mtrCDE
promoter increased 2-fold in the presence of a known effector and substrate of the MtrCDE pump, the nonionic detergent Triton X-100 (TX-100). When placed in competition with MtrR, the transcriptional repressor of
mtrCDE
, MtrA was found to bind with apparent lower affinity than MtrR to the same region. However, preincubation of MtrA with TX-100 prior to addition of the promoter-containing DNA probe increased MtrA binding and greatly reduced its dissociation from the promoter upon addition of MtrR. Two independent approaches (DNase I footprinting and a screen for bases important in MtrA binding) defined the MtrA-binding site 20–30 bp upstream of the known MtrR-binding site. Collectively, these results suggest that the MtrA and MtrR-binding sites are sterically close and that addition of an effector increases the affinity of MtrA for the
mtrCDE
promoter such that MtrR binding is negatively impacted. Our results provide a mechanism for transcriptional activation of
mtrCDE
by MtrA and highlight the complexity of transcriptional control of drug efflux systems possessed by gonococci.

IMPORTANCE
Antibiotic resistance in
Neisseria gonorrhoeae
has been increasing in recent years, such that in 2007 the Centers for Disease Control and Prevention listed
N. gonorrhoeae
as a “superbug.” One of the major contributors to antibiotic resistance in
N. gonorrhoeae
is the MtrCDE efflux pump. Until now, most work on the regulation of the genes encoding this efflux pump has been done on the transcriptional repressor, MtrR. This study is the first one to purify and define the DNA-binding ability of the transcriptional activator, MtrA. Understanding how levels of the MtrCDE efflux pump are regulated increases our knowledge of gonococcal biology and how the gonococcus can respond to various stresses, including antimicrobials.
Cartilaginous choristoma of the tongue with an immunohistochemical study
Authors: Pereira Gregório Wrublevski , Pereira Volnei David , Pereira Junior José Antonio de Castro , da Silva Rosemeri Maurici
Published: December 2012

By definition, choristomas are normal tissues found in anomalous topography. The cartilaginous features of these lesions are rare in the soft tissues of the oral cavity. The majority of cartilaginous choristomas of the tongue—the primary site of emergence of the oropharynx—are associated with adipose, fibrous or bone tissues—apart from that, only a few of these were confirmed by an immunohistochemical study. The neoplasm exclusively composed of chondromatous tissue is extremely rare in the tongue. This paper reports the clinical, surgical and pathological characteristics of a cartilaginous choristoma of the tongue diagnosed in a 64-year-old woman.
Employment status and the prevalence of poor self-rated health. Findings from UK individual-level repeated cross-sectional data from 1978 to 2004
Authors: Popham Frank , Gray Linsay , Bambra Clare
Published: December 2012

Objectives

To assess, using individual level data, how the proportion of people in different employment statuses may have played a role in the prevalence of poor self-rated health from 1978 to 2004 as there have been major changes in employment patterns in advanced market democracies and employment is an important correlate of health.

Design

Individual-level analysis of repeated cross-sectional surveys.

Setting

UK.

Participants

125 125 men and 139 535 women of working age (25–59).

Outcome measure

Self-rated general health.

Results

Compared to 1978 there was evidence of higher levels of poor health in the subsequent years. For example, in 2004, the prevalence of poor health was 2.8 (95% CI 1.7 to 3.9) and 1.3 (0.1 to 2.5) percentage points higher than 1978 for men and women, respectively, after adjusting for age. After additional adjustment for socio-economic characteristics, annual differences compared to 1978 increased (5.4 (4.2 to 6.5) and 4.4 (3.2 to 5.6) for men and women in 2004). Further adjustment for employment status, however, attenuated the annual differences in poor health (0.7 (−0.3 to 1.7) for men and 1.5 (0.3 to 2.6) for women in 2004).

Conclusions

These results suggest that the proportion of people in different employment statuses, particularly the proportion in sickness- or disability-related economic inactivity, could play an important role in the prevalence of poor self-rated health in the UK. Whether decreasing economic inactivity would enhance population health is an open question that needs further investigation.

Trial registration

This observational study was not registered.
Resistance exercise order does not determine postexercise delivery of testosterone, growth hormone, and IGF-1 to skeletal muscle
Authors: West Daniel W.D. , Cotie Lisa M. , Mitchell Cameron J. , Churchward-Venne Tyler A. , MacDonald Maureen J. , Phillips Stuart M.
Published: December 2012

Does resistance exercise order affect hormone availability? Participants performed arm exercise before and after leg exercise. Hormone delivery was estimated by multiplying brachial artery blood flow and hormone concentrations. Blood flow increased after arm (276%) and leg (193%; both p < 0.001) exercise. Testosterone, growth hormone, and insulin-like growth factor 1 showed with distinct delivery patterns between conditions; however (interactions all p < 0.001), net exposure was similar. The anabolic potential of postexercise hormones was not affected by exercise order.
FERMION PARTICLE PRODUCTION IN DYNAMICAL CASIMIR EFFECT IN A THREE-DIMENSIONAL BOX
Authors: SETARE M. R. , SEYEDZAHEDI A.
Published: December 2012

In this paper, we investigate the problem of fermion creation inside a three-dimensional cubic box. We present an appropriate wave function which satisfies the Dirac equation in this geometry with MIT bag model boundary condition. We consider the box with oscillating walls and introduce the time evolution of the quantized field by expanding it over the instantaneous basis. We explain how we can obtain the average number of particles created. In this regard, we find the Bogoliubov coefficients. We consider an oscillation and determine the coupling conditions between different modes that can be satisfied depending on the cavity's spectrum. Assuming the parametric resonance case we obtain an expression for the mean number of created fermions in each mode of an oscillation and their dynamical Casimir energy.
ACTIONS, LENGTH FUNCTIONS, AND NON-ARCHIMEDEAN WORDS
Authors: KHARLAMPOVICH OLGA , MYASNIKOV ALEXEI , SERBIN DENIS
Published: December 2012

In this paper we survey recent developments in the theory of groups acting on Λ-trees. We are trying to unify all significant methods and techniques, both classical and recently developed, in an attempt to present various faces of the theory and to show how these methods can be used to solve major problems about finitely presented Λ-free groups. Besides surveying results known up to date we draw many new corollaries concerning structural and algorithmic properties of such groups.
ACHIEVING P-TYPE SEMICONDUCTING ZnO NANOWIRES VIA DONOR ADSORPTION
Authors: WU DIHUA , ZHOU ZHEN
Published: December 2012

The difficulty of achieving p-type conductance has severely limited the application of ZnO to electronic devices. In this work, we propose a simple and effective way to achieving p-type semiconducting ZnO nanowires (NWs) through density functional theory computations. Adsorption of tetrathiafulvalene (TTF) during synthetic procedures leads to lower formation energies, and accordingly higher concentration of p-type defects; after the formation of ZnO NWs and the desorption of TTF, p-type ZnO NWs can be achieved. Also, we present a facile synthesis route on basis of previous experiments, which provides some guidance for the realization of p-type ZnO NWs.
BIOMIMETIC SYNTHESIS OF FePt NANOPARTICLES ON MULTI-WALLED CARBON NANOTUBES FOR FUNCTIONAL NANOMATERIALS
Authors: WANG LI , WANG JIKU , LI ZHUANG
Published: December 2012

We present a facile green biomimetic synthesis of FePt nanoparticles (NPs) on the sidewalls of multi-walled carbon nanotubes (CNTs). A core-shell globular protein, ferritin (Fr), was bound onto Z-glycine N-succinimidyl ester (Z-Gly-OSu) modified CNTs and served as precursor to create FePt NPs at the core part of Fr. Biomimetic synthesis of FePt NPs was carried out by chemical reducing of Fe2+ and [Formula: see text] ions that transferred into the core part of Fr molecules. The created one-dimensional CNT- FePt nanohybrids were characterized by transmission electron microscopy and X-ray photoelectron spectroscopy. The synthesized CNT- FePt nanohybrids show multi-properties of high water-solubility, ferromagnetism, and electrocatalytic activity.
NOVEL PREPARATION OF NANO-COMPOSITE CuO-Cr2O3 USING CTAB-TEMPLATE METHOD AND EFFICIENT FOR HYDROGENATION OF BIOMASS-DERIVED FURFURAL
Authors: YAN KAI , WU XU , AN XIA , XIE XIANMEI
Published: December 2012

A simple route to fabricate nano-composite oxides CuO-Cr2O3 using hexadecyltrimethylammonium bromide (CTAB)-templated Cu-Cr hydrotalcite as the precursor is presented. This novel method is based on CTAB-templating effect for mesostructure directing and using the cheap metal nitrate, followed by removal of CTAB. It was indicated that the nano-composite CuO-Cr2O3 was formed during the removal of CTAB. X-ray diffraction (XRD) and transitional electronic microscopy (TEM) revealed nice nano-composite oxides CuO-Cr2O3 were formed with high crystallinity. N2 adsorption and desorption indicated that a high surface area of 170.5 m2/g with a pore size of 2.7 nm of the nano-composite CuO-Cr2O3 was facilely resulted. The as-synthesized nano-composite oxides CuO-Cr2O3 display good catalytic activities for hydrogenation of furfural to furfuryl alcohol, whereas 86% selectivity was achieved at 75% conversion of furfural.
Roles played by 20-HETE, angiotensin II and endothelin in mediating the hypertension in aging female spontaneously hypertensive rats
Authors: Lima Roberta , Yanes Licy L. , Davis Deborah D. , Reckelhoff Jane F.
Published: December 2012

Prevalence of hypertension (HT) increases in women after menopause, and there is evidence that HT is not as well controlled in postmenopausal women as men. The reasons for this are not clear but may be related to the lack of adequate blockade of the systems contributing to HT in women. This study aimed to determine the roles of three of the systems known to contribute to HT in animal studies: angiotensin II (ANG II; enalapril inhibitor), eicosanoids [1-aminobenzotriazole (1-ABT) inhibitor], and endothelin (ETA receptor antagonist), on blood pressure (BP) in three groups of female spontaneously hypertensive rats (SHR), aged 18 mos (postmenopausal rat, PMR). After baseline telemetry BP, three drug periods were performed for 5 days each: single blockade (ABT or enalapril), double blockade (ABT+enalapril or enalapril+ABT), and triple blockade (all 3 drugs). Controls received no treatment until the third period when they received ETA receptor antagonist alone. Single drug blockade reduced BP in PMR to similar levels. Double blockade reduced mean arterial pressure more in ABT+enalapril rats than in the other group (enalapril+ABT). Triple drug blockade reduced BP to similar levels in both groups, but the BP remained ∼110 mmHg. The data suggest that these three systems, ANG II, eicosanoids, and endothelin, contribute together and independently to BP control in old female SHR. However, other systems also contribute to the HT since the BP was not normalized, supporting the notion that HT in postmenopausal women may require complex multidrug therapy to be better controlled and that may require the development of additional drugs.