bluuebunny/crossref_metadata_2025 huggingface dataset:
A Neural Circuit for Memory Specificity and Generalization
Authors: Xu Wei , Südhof Thomas C.
Published: March 2013

The Thalamus in Fear and Memory

The medial prefrontal cortex (mPFC) mediates the cognitive control of many high-level brain functions. However, it is unclear which synaptic projections from the mPFC to subcortical regions are critical for maintaining the proper balance between retention and generalization of fear memory details. Using an array of behavioral, physiological, and anatomical techniques,
Xu and Südhof
(p.
1290
) describe a neural circuit that controls memory generalization and specificity. This circuit involves the nucleus reuniens (NR), a thalamic nucleus of largely unknown function. Optogenetic activation of NR neurons in awake behaving mice revealed the role of the NR in fear memory generalization.
Spin Torque–Generated Magnetic Droplet Solitons
Authors: Mohseni S. M. , Sani S. R. , Persson J. , Nguyen T. N. Anh , Chung S. , Pogoryelov Ye. , Muduli P. K. , Iacocca E. , Eklund A. , Dumas R. K. , Bonetti S. , Deac A. , Hoefer M. A. , Åkerman J.
Published: March 2013

Magnetic Droplet

When a solitary wave travels atop the surface of a fluid, its shape generally changes with time, with some of its components traveling at velocities slightly different than others. In nonlinear media, this spreading effect may be countered by a slimming effect stemming from the non-linearity, which generates an object with perfectly preserved shape, called a soliton. Solitons have been observed in fluids, granular media, and other systems.

Mohseni
et al.

(p.
1295
) detected a dissipative soliton (one that also balances gain and dissipation) in a magnetic system, in the form of a magnetic droplet consisting of a core of spins pointing opposite to the external magnetic field. The droplet exhibited peculiar dynamics and could be controlled by electric current.
Circadian Control of Chloroplast Transcription by a Nuclear-Encoded Timing Signal
Authors: Noordally Zeenat B. , Ishii Kenyu , Atkins Kelly A. , Wetherill Sarah J. , Kusakina Jelena , Walton Eleanor J. , Kato Maiko , Azuma Miyuki , Tanaka Kan , Hanaoka Mitsumasa , Dodd Antony N.
Published: March 2013

Synchronizing Photosynthetic Capacity

Coordination of photosynthetic activity with sunlight benefits plant productivity.

Noordally
et al.

(p.
1316
) analyzed how the
Arabidopsis
circadian clock keeps the chloroplasts working in tune with the Sun. SIGMA FACTOR5 (SIG5) is encoded in the cell nucleus and reflects circadian cycles with changes in its own transcript abundance. SIG5 acts, however, in the chloroplast, where it supports photosystem II production.
Adaptive Evolution of Multiple Traits Through Multiple Mutations at a Single Gene
Authors: Linnen Catherine R. , Poh Yu-Ping , Peterson Brant K. , Barrett Rowan D. H. , Larson Joanna G. , Jensen Jeffrey D. , Hoekstra Hopi E.
Published: March 2013

Additive Effects

Although specific genes involved in animal coloration have been identified, the underlying selection for genetic variation in color-specific adaptation is not well understood. Examining theAgoutigene and other loci in the deer mice of Nebraska, where predation selects for light-colored mice in light environments and dark-colored mice in dark environments,Linnenet al.(p.1312) find evidence of multiple genetic variants under selection affecting coloration. The light color of Sand Hills mice is not the result of a single large-effect mutation, but is because of many accumulated mutations, each with a smaller phenotypic effect.
The SARS Wake-Up Call
Authors: Nuttall Isabelle , Dye Christopher
Published: March 2013

Ten years ago, the SARS outbreak spurred efforts by the World Health Organization to improve global responses to health threats and crises.
Am I Wrong?
Authors: Alberts Bruce
Published: March 2013

I have seven grandchildren, and I worry about their future. The nation that I was raised in, the United States, has clearly lost its way at a time when the world badly needs wise leadership. Nations with a long-term view are making huge investments in their infrastructure—transportation, water, energy, waste, and recreation. And they have a laserlike focus on supporting science and engineering research with government resources. As examples, Germany, China, and South Korea come to mind. Meanwhile, the United States is living off its past. Not only do we face a crumbling infrastructure
*
but our federal investments in fundamental long-term R&D have been stagnant, dropping from 1.25% of the gross domestic product (GDP) in 1985 to 0.87% in 2013.
†
Now, on top of that comes a mindless budget "sequester" that will make the situation considerably worse, causing the U.S. National Science Foundation to announce last week that it may award 1000 fewer research grants in 2013 than it did in 2012.
Anaerobic Digestion: The Rate-Limiting Process and the Nature of Inhibition
Authors: Finney Clifton D. , Evans Robert S.
Published: March 2013

Although attractive as a method for creating preferred fuel from cellulose wastes, the anaerobic digestion process is very slow. A new hypothesis is that phase transfer of products is rate-limiting and product gases inhibit the methanogenic bacteria. In a phase transfer-assisted digester, bacterial reproduction is very rapid.
Albugo
-Like Oogonia from the American Carboniferous
Authors: Stidd B. M. , Cosentino K.
Published: March 2013

Fungal oogonia morphologically similar to those in the extant genus
Albugo
have been discovered in the integumental tissues of the fossil gymnosperm ovule
Nucellangium
. Disease symptoms in the fossil ovule are similar to those produced by
Albugo
in living angiosperm hosts.
Latimeria
, the Living Coelacanth, Is Ovoviviparous
Authors: Smith C. Lavett , Rand Charles S. , Schaeffer Bobb , Atz James W.
Published: March 2013

Dissection of a specimen of
Latimeria chalumnae
in the American Museum of Natural History revealed that it is a gravid female containing five advanced young, averaging 317.8 millimeters long. Each has a large yolk sac with no apparent connection to the surrounding oviducal wall. We conclude that
Latimeria
is ovoviviparous.
Behavioral Taxonomy in Canids by Discriminant Function Analyses
Authors: Bekoff Marc , Hill Harriet L. , Mitton Jeffry B.
Published: March 2013

The technique of linear discriminant function analysis was applied to behavioral data that were collected on infant canids. The method was first tested with a known cross between a wolf and a dog and proved to be valid, indicating that quantitative analyses of behavioral phenotypes can be used in assessing taxonomic relationships. In addition, the controversial New England canid was determined by behavioral analysis to be more closely related to coyotes than to wolves.
Sensitive Cell-Based Assay for Determination of Human Immunodeficiency Virus Type 1 Coreceptor Tropism
Authors: Weber Jan , Vazquez Ana C. , Winner Dane , Gibson Richard M. , Rhea Ariel M. , Rose Justine D. , Wylie Doug , Henry Kenneth , Wright Alison , King Kevin , Archer John , Poveda Eva , Soriano Vicente , Robertson David L. , Olivo Paul D. , Arts Eric J. , Quiñones-Mateu Miguel E.
Published: March 2013

CCR5 antagonists are a powerful new class of antiretroviral drugs that require a companion assay to evaluate the presence of CXCR4-tropic (non-R5) viruses prior to use in human immunodeficiency virus (HIV)-infected individuals. In this study, we have developed, characterized, verified, and prevalidated a novel phenotypic test to determine HIV-1 coreceptor tropism (VERITROP) based on a sensitive cell-to-cell fusion assay. A proprietary vector was constructed containing a near-full-length HIV-1 genome with the yeast uracil biosynthesis (URA3) gene replacing the HIV-1envcoding sequence. Patient-derived HIV-1 PCR products were introduced by homologous recombination using an innovative yeast-based cloning strategy. Theenv-expressing vectors were then used in a cell-to-cell fusion assay to determine the presence of R5 and/or non-R5 HIV-1 variants within the viral population. Results were compared with (i) the original version of Trofile (Monogram Biosciences, San Francisco, CA), (ii) population sequencing, and (iii) 454 pyrosequencing, with the genotypic data analyzed using several bioinformatics tools, i.e., the 11/24/25 rule, Geno2Pheno (2% to 5.75%, 3.5%, or 10% false-positive rate [FPR]), and webPSSM. VERITROP consistently detected minority non-R5 variants from clinical specimens, with an analytical sensitivity of 0.3%, with viral loads of ≥1,000 copies/ml, and from B and non-B subtypes. In a pilot study, a 73.7% (56/76) concordance was observed with the original Trofile assay, with 19 of the 20 discordant results corresponding to non-R5 variants detected using VERITROP and not by the original Trofile assay. The degree of concordance of VERITROP and Trofile with population and deep sequencing results depended on the algorithm used to determine HIV-1 coreceptor tropism. Overall, VERITROP showed better concordance with deep sequencing/Geno2Pheno at a 0.3% detection threshold (67%), whereas Trofile matched better with population sequencing (79%). However, 454 sequencing using Geno2Pheno at a 10% FPR and 0.3% threshold and VERITROP more accurately predicted the success of a maraviroc-based regimen. In conclusion, VERITROP may promote the development of new HIV coreceptor antagonists and aid in the treatment and management of HIV-infected individuals prior to and/or during treatment with this class of drugs.
Neutralization of Antimicrobial Substances in New BacT/Alert FA and FN Plus Blood Culture Bottles
Authors: Mitteregger Dieter , Barousch Wolfgang , Nehr Marion , Kundi Michael , Zeitlinger Markus , Makristathis Athanasios , Hirschl Alexander M.
Published: March 2013

Time to detection (TTD) in automated blood culture systems is delayed for sensitive microorganisms in the presence of antimicrobial substances and has been associated with worse outcomes for sepsis patients on inadequate empirical therapy. While resin addition removes antimicrobial substances to various degrees from blood culture media, media formulations and the blend of resins may influence performance. The BacT/Alert 3D system (bioMérieux) was investigated using the new resin-containing medium types FA Plus (aerobic) and FN Plus (anaerobic). TTD was compared between control and test bottles containing relevant bacteria or
Candida albicans
, with and without defined concentrations of antimicrobials. Failure of neutralization was defined as a negative blood culture on day 3. In general, growth delay was nonlinear, concentration dependent, bottle type specific, and reciprocally associated with MICs. Substance-specific serum drug concentrations corresponding to a predefined, clinically relevant 3-h delay of TTD were calculated. Where appropriate, a time interval allowing for drug elimination below this critical level was obtained by pharmacokinetic modeling. Clarithromycin, clindamycin, gentamicin, linezolid, tigecycline, vancomycin, and fluconazole were neutralized. For ciprofloxacin and piperacillin-tazobactam, which were only incompletely neutralized in combination with the most sensitive test strains, a maximum waiting time for blood draw of 1 h was determined based on pharmacokinetics. One or more test strains did not grow in bottles containing either amoxicillin-clavulanate, cefepime, cefotaxime, meropenem, or metronidazole, and we thus recommend particular caution in timing of blood draws if patients have been pretreated with these agents.
Serial Testing from a 3-Day Collection Period by Use of the Bartonella Alphaproteobacteria Growth Medium Platform May Enhance the Sensitivity of Bartonella Species Detection in Bacteremic Human Patients
Authors: Pultorak Elizabeth L. , Maggi Ricardo G. , Mascarelli Patricia E. , Breitschwerdt Edward B.
Published: March 2013

Patients with infection from bacteremicBartonellaspp., tested usingBartonella Alphaproteobacteriagrowth medium (BAPGM), were retrospectively categorized into one of two groups that included those whose blood was collected once (group 1;n= 55) or three times (group 2;n= 36) within a 1-week period. Overall, 19 patients (20.8%) were PCR positive for one or moreBartonellaspp. using the BAPGM platform. Seven patients (12.7%) in group 1 tested positive, and 12 patients (33.3%) in group 2 tested positive. Detection was improved when the patients were tested three times within a 1-week period (odds ratio, 3.4 [95% confidence interval, 1.2 to 9.8];P= 0.02). Obtaining three sequential blood samples during a 1-week period should be considered a diagnostic approach when bartonellosis is suspected.
Next-Generation Antimicrobial Susceptibility Testing
Authors: van Belkum Alex , Dunne W. Michael
Published: March 2013

Antimicrobial resistance has emerged as one of the most-significant health care problems of the new millennium, and the clinical microbiology laboratory plays a central role in optimizing the therapeutic management of patients with infection. This minireview explores the potential value of innovative methods for antimicrobial susceptibility testing of microorganisms that could provide valuable alternatives to existing methodologies in the very near future.
Comparison of the Abbott
m
2000 RealTi
m
e CT Assay and the Cepheid GeneXpert CT/NG Assay to the Roche Amplicor CT Assay for Detection of Chlamydia trachomatis in Ocular Samples from Tanzania
Authors: Dize Laura , West Sheila , Williams James A. , Van Der Pol Barbara , Quinn Thomas C. , Gaydos Charlotte A.
Published: March 2013

The GeneXpert CT/NG assay (GeneXpert) and the Abbott
m
2000 RealTi
m
e CT (
m
2000) assay were compared to Amplicor for detecting ocular
Chlamydia trachomatis
. Discordant specimens were tested by the Aptima CT assay. The
m
2000 assay sensitivity was 100% (95% confidence interval [CI], 90% to 100%), and specificity was 98.46% (95% CI, 95.2% to 99.2%); GeneXpert sensitivity was 100% (95% CI, 90% to 100%), and specificity was 100% (95% CI, 98.1% to 100%). The
m
2000 and GeneXpert assays appear to perform as well as the Amplicor assay.
Nasopharyngeal Carriage of Klebsiella pneumoniae and Other Gram-Negative Bacilli in Pneumonia-Prone Age Groups in Semarang, Indonesia
Authors: Farida Helmia , Severin Juliëtte A. , Gasem M. Hussein , Keuter Monique , van den Broek Peterhans , Hermans Peter W. M. , Wahyono Hendro , Verbrugh Henri A.
Published: March 2013

Gram-negative bacilli (GNB) cause many cases of pneumonia in Indonesia. We investigated nasopharyngeal carriage of GNB in Semarang, Indonesia.
Klebsiella pneumoniae
carriage in adults (15%) was higher than in children (7%) (
P
= 0.004), while that of other GNB was comparable. Poor food and water hygiene are determinants of carriage of these bacteria.
Multilaboratory Study of the Biomic Automated Well-Reading Instrument versus MicroScan WalkAway for Reading MicroScan Antimicrobial Susceptibility and Identification Panels
Authors: Fader Robert C. , Weaver Emily , Fossett Rhonda , Toyras Michele , Vanderlaan John , Gibbs David , Wang Andrew , Thierjung Nikolaus
Published: March 2013

This study compared the Biomic automated well reader results to the MicroScan WalkAway results for reading MicroScan antimicrobial susceptibility and identification panels at four different sites. Routine fresh clinical isolates and quality control (QC) organisms were tested at each study site. A total of 46,176 MicroScan panel drug-organism combinations were read. The Biomic category agreement for 3,117 Gram-negative bacteria was 98.4%, with 1.4% minor and 0.2% major discrepancies. The Biomic category agreement for 5,233 Gram-positive bacteria was 98.7%, with 0.9% minor, 0.3% major, and 0.1% very major errors. Essential agreement, defined as Biomic results that were within ±1 2-fold dilution of the MicroScan results, was 99.3% for Gram-negative bacteria and 98.3% for Gram-positive bacteria. Biomic reading of MicroScan identification panels provided an overall agreement (first- and second-choice organism match) of 99.5% with 846 Gram-negative isolates and 99.5% with 430 Gram-positive isolates. These results suggest that the Biomic automated reader can provide accurate reading of MicroScan panels and has the capability of a visual panel read for manual adjustment of results.
Comparison of the Biofire FilmArray RP, Genmark eSensor RVP, Luminex xTAG RVPv1, and Luminex xTAG RVP Fast Multiplex Assays for Detection of Respiratory Viruses
Authors: Popowitch Elena B. , O'Neill Stacey S. , Miller Melissa B.
Published: March 2013

There are several U.S. FDA-cleared molecular respiratory virus panels available today, each with advantages and disadvantages. This study compares four multiplex panels, the BioFire Diagnostics FilmArray RP (
r
espiratory
p
anel), the GenMark Dx eSensor RVP (
r
espiratory
v
iral
p
anel), the Luminex xTAG RVPv1, and the Luminex xTAG RVP fast. Three hundred specimens (200 retrospective and 100 consecutive) were tested using all four platforms to determine performance characteristics. The overall sensitivity and specificity, respectively, and 95% confidence interval (CI; in parentheses) for each panel were as follows: FilmArray RP, 84.5% (79.2, 88.6) and 100% (96.2, 100); eSensor RVP, 98.3% (95.5, 99.5) and 99.2% (95.4, 100); xTAG RVPv1, 92.7% (88.5, 95.4) and 99.8% (96.0, 100); and xTAG RVP fast, 84.4% (78.5, 88.9) and 99.9% (96.1, 100). The sensitivity of each assay fluctuated by viral target, with the greatest discrepancies noted for adenovirus and influenza virus B detection. Hands-on time and time to result were recorded and ease of use was assessed to generate a complete profile of each assay.
Comparative Epidemiology of Staphylococcus epidermidis Isolates from Patients with Catheter-Related Bacteremia and from Healthy Volunteers
Authors: Cherifi S. , Byl B. , Deplano A. , Nonhoff C. , Denis O. , Hallin M.
Published: March 2013

Staphylococcus epidermidis
is a major cause of catheter-related bloodstream infections (CRBSIs). Recent studies suggested the existence of well-adapted, highly resistant, hospital-associated
S. epidermidis
clones. The molecular epidemiology of
S. epidermidis
in Belgian hospitals and the Belgian community has not been explored yet. We compared a set of 33
S. epidermidis
isolates causing CRBSI in hospitalized patients with a set of 33 commensal
S. epidermidis
isolates. The factors analyzed included resistance to antibiotics and genetic diversity as determined by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and SCC
mec
typing. Additionally, the presence of virulence-associated mobile genetic elements, the
ica
operon and the arginine catabolic mobile element (ACME), was assessed and compared against clinical data. CRBSI
S. epidermidis
isolates were significantly resistant to more antibiotics than commensal
S. epidermidis
isolates. The two populations studied were very diverse and genetically distinct as only 23% of the 37 PFGE types observed were harbored by both CRBSI and commensal isolates. ACME was found in 76% of
S. epidermidis
strains, regardless of their origin, while the
ica
operon was significantly more prevalent in CRBSI isolates than in commensal isolates (
P
< 0.05). Nine patients presented a clinically severe CRBSI, eight cases of which were due to an
ica
-positive multiresistant isolate belonging to sequence type 2 (ST2) or ST54.
S. epidermidis
isolates causing CRBSI were more resistant and more often
ica
positive than commensal
S. epidermidis
isolates, which were genetically heterogeneous and susceptible to the majority of antibiotics tested. Clinically severe CRBSIs were due to isolates belonging to two closely related MLST types, ST2 and ST54.
Human Cytomegalovirus Inhibits Apoptosis by Proteasome-Mediated Degradation of Bax at Endoplasmic Reticulum-Mitochondrion Contacts
Authors: Zhang Aiping , Hildreth Richard L. , Colberg-Poley Anamaris M.
Published: March 2013

Human cytomegalovirus (HCMV) encodes the UL37 exon 1 protein (pUL37x1), which is the potent viral mitochondrion-localized inhibitor of apoptosis (vMIA), to increase survival of infected cells. HCMV vMIA traffics from the endoplasmic reticulum (ER) to ER subdomains, which are physically linked to mitochondria known as mitochondrion-associated membranes (MAM), and to mitochondria. The antiapoptotic function of vMIA is thought to primarily result from its ability to inhibit Bax-mediated permeabilization of the outer mitochondrial membrane (OMM). Here, we establish that vMIA retargets Bax to the MAM as well as to the OMM from immediate early through late times of infection. However, MAM localization of Bax results in its increased ubiquitination and proteasome-mediated degradation. Surprisingly, HCMV infection does not increase OMM-associated degradation (OMMAD) of Bax, even though the ER and mitochondria are physically connected at the MAM. It was recently found that lipid rafts at the plasma membrane can connect extrinsic and intrinsic apoptotic pathways and can serve as sites of apoptosome assembly. In transfected permissive human fibroblasts, vMIA mediates, through its cholesterol affinity, association of Bax and apoptosome components with MAM lipid rafts. While Bax association with MAM lipid rafts was detected in HCMV-infected cells, association of apoptosome components was not. These results establish that Bax recruitment to the MAM and its MAM-associated degradation (MAMAD) are a newly described antiapoptotic mechanism used by HCMV infection to increase cell survival for its growth.
Pathogenesis, Transmissibility, and Ocular Tropism of a Highly Pathogenic Avian Influenza A (H7N3) Virus Associated with Human Conjunctivitis
Authors: Belser Jessica A. , Davis C. Todd , Balish Amanda , Edwards Lindsay E. , Zeng Hui , Maines Taronna R. , Gustin Kortney M. , Martínez Irma López , Fasce Rodrigo , Cox Nancy J. , Katz Jacqueline M. , Tumpey Terrence M.
Published: March 2013

H7 subtype influenza A viruses, responsible for numerous outbreaks in land-based poultry in Europe and the Americas, have caused over 100 cases of confirmed or presumed human infection over the last decade. The emergence of a highly pathogenic avian influenza H7N3 virus in poultry throughout the state of Jalisco, Mexico, resulting in two cases of human infection, prompted us to examine the virulence of this virus (A/Mexico/InDRE7218/2012 [MX/7218]) and related avian H7 subtype viruses in mouse and ferret models. Several high- and low-pathogenicity H7N3 and H7N9 viruses replicated efficiently in the respiratory tract of mice without prior adaptation following intranasal inoculation, but only MX/7218 virus caused lethal disease in this species. H7N3 and H7N9 viruses were also detected in the mouse eye following ocular inoculation. Virus from both H7N3 and H7N9 subtypes replicated efficiently in the upper and lower respiratory tracts of ferrets; however, only MX/7218 virus infection caused clinical signs and symptoms and was capable of transmission to naive ferrets in a direct-contact model. Similar to other highly pathogenic H7 viruses, MX/7218 replicated to high titers in human bronchial epithelial cells, yet it downregulated numerous genes related to NF-κB-mediated signaling transduction. These findings indicate that the recently isolated North American lineage H7 subtype virus associated with human conjunctivitis is capable of causing severe disease in mice and spreading to naive-contact ferrets, while concurrently retaining the ability to replicate within ocular tissue and allowing the eye to serve as a portal of entry.
Hepatitis C Virus Suppresses C9 Complement Synthesis and Impairs Membrane Attack Complex Function
Authors: Kim Hangeun , Meyer Keith , Di Bisceglie Adrian M. , Ray Ranjit
Published: March 2013

Hepatitis C virus (HCV) proteins inhibit complement component expression, which may attenuate immunity against infection. In this study, we examined whether HCV regulates the membrane attack complex (MAC) via complement component C9. MAC is composed of C5b to C9 (C5b-9) and mediates cell lysis of invaded pathogens. Liver biopsy specimens from chronically HCV-infected patients exhibited a lower level of C9 mRNA expression than liver biopsy specimens from unrelated disease or healthy control human liver RNA. Hepatocytes infected with cell culture-grown HCV or expressing HCV core protein also displayed significant repression of C9 mRNA and protein levels. Promoter analysis suggested that the T cell factor-4 (TCF-4E) transcription factor is responsible for HCV core-mediated C9 promoter regulation. Sera from chronically HCV-infected patients displayed a lower level of C5b-9 and a reduced antimicrobial effect on model organisms compared to unrelated patient sera or sera from healthy volunteers. Together, these results for C9 regulation by HCV core protein coupled with functional impairment of the membrane attack complex underscore HCV-mediated attenuation of immune mechanisms.
Directed Evolution of Mutator Adenoviruses Resistant to Antibody Neutralization
Authors: Myers Nicolle D. , Skorohodova Ksenia V. , Gounder Anshu P. , Smith Jason G.
Published: March 2013

We incorporated a previously identified mutation that reduces the fidelity of the DNA polymerase into a human adenovirus vector. Using this mutator vector, we demonstrate rapid selection of resistance to a neutralizing anti-hexon monoclonal antibody due to a G434D mutation in hexon that precludes antibody binding. Since mutator adenoviruses can accumulate compound mutations that are unattainable using traditional random mutagenesis techniques, this approach will be valuable to the study of antivirals and host factor interactions.
Herpes Simplex Virus 2 Expresses a Novel Form of ICP34.5, a Major Viral Neurovirulence Factor, through Regulated Alternative Splicing
Authors: Tang Shuang , Guo Nini , Patel Amita , Krause Philip R.
Published: March 2013

Herpes simplex virus 1 (HSV-1) and HSV-2, two closely related neurotropic human herpesviruses, achieve neurotropism through ICP34.5, a major viral neurovirulence factor. In this report, in addition to the full-length 38-kDa protein (ICP34.5α), we identified a 28-kDa novel form of ICP34.5 (ICP34.5β) in HSV-2-infected cells. ICP34.5β is translated from unspliced ICP34.5 mRNA, with the retained intron introducing a premature stop codon. Thus, ICP34.5β lacks the C-terminal conserved GADD34 domain but includes 19 additional amino acids encoded by the intron. Although a fraction of both HSV-2 ICP34.5 proteins are detected in the nucleolus, ICP34.5α is predominantly located in cytoplasm, and ICP34.5β is mainly detected more diffusely in the nucleus. ICP34.5β is unable to counteract PKR-mediated eIF2 phosphorylation but does not interfere with ICP34.5α's function in this process. Efficient expression of ICP34.5β in cell culture assays is dependent on viral infection or expression of ICP27, a multifunctional immediate-early gene. The effect of ICP27 on the ICP34.5β protein level is attributed to its selective inhibition of ICP34.5 splicing, which results in increased expression of ICP34.5β but a reduced level of ICP34.5α. The C- terminal KH3 domain but not the RNA binding domain of ICP27 is required for its specific inhibition of ICP34.5 splicing and promotion of ICP34.5β expression. Our results suggest that the expression of ICP34.5α and ICP34.5β is tightly regulated in HSV-2 and likely contributes to viral pathogenesis.
Oxylipin Biosynthesis Genes Positively Regulate Programmed Cell Death during Compatible Infections with the Synergistic Pair
Potato Virus X-Potato Virus Y
and Tomato Spotted Wilt Virus
Authors: García-Marcos Alberto , Pacheco Remedios , Manzano Aranzazu , Aguilar Emmanuel , Tenllado Francisco
Published: March 2013

One of the most severe symptoms caused by compatible plant-virus interactions is systemic necrosis, which shares common attributes with the hypersensitive response to incompatible pathogens. Although several studies have identified viral symptom determinants responsible for systemic necrosis, mechanistic models of how they contribute to necrosis in infected plants remain scarce. Here, we examined the involvement of different branches of the oxylipin biosynthesis pathway in the systemic necrosis response caused either by the synergistic interaction of
Potato virus X
with
Potato virus Y
(PVX-PVY) or by
Tomato spotted wilt virus
(TSWV) in
Nicotiana benthamiana
. Silencing either
9-lipoxygenase
(
LOX
),
13-LOX
, or α-
dioxygenase-1
(α-
DOX-1
) attenuated the programmed cell death (PCD)-associated symptoms caused by infection with either PVX-PVY or TSWV. In contrast, silencing of the jasmonic acid perception gene,
COI1
(Coronatine insensitive 1), expedited cell death during infection with compatible viruses. This correlated with an enhanced expression of oxylipin biosynthesis genes and dioxygenase activity in PVX-PVY-infected plants. Moreover, the
Arabidopsis thaliana
double
lox1
α-
dox-1
mutant became less susceptible to TSWV infection. We conclude that oxylipin metabolism is a critical component that positively regulates the process of PCD during compatible plant-virus interactions but does not play a role in restraining virus accumulation
in planta
.
PARP expression in germ cell tumours
Authors: Mego Michal , Cierna Zuzana , Svetlovska Daniela , Macak Dusan , Machalekova Katarina , Miskovska Viera , Chovanec Michal , Usakova Vanda , Obertova Jana , Babal Pavel , Mardiak Jozef
Published: March 2013

Background

Poly(ADP-ribose)polymerase (PARP) inhibitors represent a new class of promising drugs in anticancer therapy.

Aims

To evaluate PARP expression in testicular germ cell tumours (GCTs) and to correlate expression patterns with clinicopathological variables.

Methods

In this translational study, tumour specimens from 124 patients with GCTs (114 patients with testicular primary tumours and 10 with extragonadal GCTs) were identified. PARP expression was detected by immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method and compared to PARP expression in normal testicular tissue.

Results

We observed higher expression of PARP in testicular tumours compared to normal testicular tissue (mean QS=10.04 vs 3.31, p<0.0000001). Mean QS±SD for each histological subtype was as follows: intratubular germ cell neoplasia unclassified (IGCNU)=18.00±0.00, embryonal carcinoma=9.62±5.64, seminoma=9.74±6.51, yolk sac tumour=7.8±7.20, teratoma=5.87±5.34, and choriocarcinoma=4.50±8.33. The PARP overexpression (QS>9) was most often detected in IGCNU (100% of specimen with PARP overexpression), seminona (52.6%), embryonal carcinoma (47.0%), yolk sac tumour (33.3%), teratoma (26.7%) and choriocarcinoma (25.0%), compared to 1.9% of normal testicular tissue specimens. There was no association between PARP expression and clinical variables.

Conclusions

In this pilot study, we showed for the first time, that PARP is overexpressed in testicular germ cell tumours compared to normal testis.
Living into the imagined body: how the diagnostic image confronts the lived body
Authors: Stahl Devan
Published: March 2013

In this paper I will show how the medical image, presented to the patient by the physician, participates in medicine's cold culture of abstraction, objectification and mandated normativity. I begin by giving a brief account of the use of anatomical imaging since the Renaissance to show how images have historically functioned in contrast to how they are currently used in medical practice. Next, I examine how contemporary medical imaging techniques participate in a kind of knowledge production that objectifies the human body. Finally, I elucidate how physicians ought to place the medical image within the context of thelivedbody so as to create a healing relationship with the patient. In all this I hope to show that the medical image, far from a piece of objective data, testifies to the interplay of particular beliefs, practices and doctrines contemporary medicine holds dear. To best treat her patient, the physician must appreciate the influence of these images and appropriately place them within the context of the patient's lived experience.
Density functional theory study of allopurinol
Authors: Chong Delano P.
Published: March 2013

Allopurinol vapour is studied with density functional theory. Using the best method from past experience for each property, we predict the equilibrium geometry, vibrational spectrum, dipole moment, average dipole polarizability, UV absorption spectrum, vertical ionization energies of valence electrons, and core-electron binding energies.
Coupled quantum oscillators within independent quantum reservoirs
Authors: Dorofeyev Illarion
Published: March 2013

This paper addresses the problem of open quantum systems. The energy of interaction of coupled dissipative systems is the main focus of the study. Quantum Langevin equations for two quantum coupling oscillators within independent heat baths of quantum oscillators are obtained using a model Hamiltonian and corresponding Heisenberg equations of motion. Analytical expressions for mean energy of coupled oscillators and their mean energy of interaction are derived and analyzed. Nonmonotonic dependence of the interaction energy versus a coupling constant is demonstrated and an explanation is suggested.
JUST-IN-TIME SCHEDULING UNDER SCENARIO-BASED UNCERTAINTY
Authors: CHUNG DAE-YOUNG , CHOI BYUNG-CHEON
Published: March 2013

This paper considers the single-machine scheduling problem, where job parameters are uncertain and the performance measure is to maximize the weighted number of just-in-time jobs, defined as jobs completed exactly on their due dates. Uncertainty is described through a finite set of well-defined scenarios. The criteria for this environment is to minimize the maximum deviation from optimality for all scenarios. We present the computational complexity results for several cases.
NEXT-TO-LEADING ORDER TESTS OF NON-RELATIVISTIC-QCD FACTORIZATION WITH J/ψ YIELD AND POLARIZATION
Authors: BUTENSCHOEN MATHIAS , KNIEHL BERND A.
Published: March 2013

We report on recent progress in testing the factorization formalism of non-relativistic quantum chromodynamics (NRQCD) at next-to-leading order (NLO) for J/ψ yield and polarization. We demonstrate that it is possible to unambiguously determine the leading color-octet (CO) long-distance matrix elements (LDMEs) in compliance with the velocity scaling rules through a global fit to experimental data of unpolarized J/ψ production in pp, [Formula: see text], ep, γγ, and e+e-collisions. Three data sets not included in the fit, from hadro-production and from photo-production in the fixed-target and colliding-beam modes, are nicely reproduced. The polarization observables measured in different frames at DESY HERA and CERN LHC reasonably agree with NLO NRQCD predictions obtained using the LDMEs extracted from the global fit, while measurements at the FNAL Tevatron exhibit severe disagreement. We demonstrate that the alternative LDME sets recently obtained, with different philosophies, in two other NLO NRQCD analyses of J/ψ yield and polarization also fail to reconcile the Tevatron polarization data with the other available world data.
QUANTUM KALB–RAMOND FIELD IN D-DIMENSIONAL DE SITTER SPACE–TIMES
Authors: ALENCAR G. , GUEDES I. , LANDIM R. R. , COSTA FILHO R. N.
Published: March 2013

In this work, we investigate the quantum theory of the Kalb–Ramond fields propagating in D-dimensional de Sitter space–times using the dynamic invariant method developed by Lewis and Riesenfeld [J. Math. Phys.10, 1458 (1969)] to obtain the solution of the time-dependent Schrödinger equation. The wave function is written in terms of a c-number quantity satisfying the Milne–Pinney equation, whose solution can be expressed in terms of two independent solutions of the respective equation of motion. We obtain the exact solution for the quantum Kalb–Ramond field in the de Sitter background and discuss its relation with the Cremmer–Scherk–Kalb–Ramond model.
PREDICTING THE VARIANCE OF A MEASUREMENT WITH 1/f NOISE
Authors: LENOIR BENJAMIN
Published: March 2013

Measurement devices always add noise to the signal of interest and it is necessary to evaluate the variance of the results. This article focuses on stationary random processes whose power spectrum density is a power law of frequency. For flicker noise, behaving as 1/f and which is present in many different phenomena, the usual way to compute the variance leads to infinite values. This article proposes an alternative definition of the variance which takes into account the fact that measurement devises need to be calibrated. This new variance, which depends on the calibration duration, the measurement duration and the duration between the calibration and the measurement, allows avoiding infinite values when computing the variance of a measurement.
MECHANICS IN MECHANOSENSITIVITY OF CELL ADHESION AND ITS ROLES IN CELL MIGRATION
Authors: ZHONG YUAN , HE SHIJIE , JI BAOHUA
Published: March 2013

Cells sense and respond to external stimuli and properties of their environment through focal adhesion complexes (FACs) to regulate a broad range of physiological and pathological processes, including cell migration. Currently, the basic principles in mechanics of the mechanosensitivity of cell adhesion and migration have not been fully understood. In this paper, an FEM-based mechano-chemical coupling model is proposed for studying the cell migration behaviors in which the dynamics of stability of FACs and the effect of cell shape on cell traction force distribution are considered. We find that the driving force of cell migration is produced by the competition of stability of cell adhesion between the cell front and cell rear, which consequently controls the speed of cell migration. We show that the rigidity gradient of matrix can bias this competition which allows cell to exhibit a durotaxis behavior, i.e. the larger the gradient, the higher the cell speed.
The multi-diffusion domain model: past, present and future
Authors: Harrison T. Mark , Lovera Oscar M.
Published: March 2013

It is axiomatic that application of closure theory – the foundation of isotope-based thermochronology – requires an empirical diffusion model. It is therefore surprising that the majority of thermochronological studies have not met this requirement. The advent of the multi-diffusion domain (MDD) model transcended this limitation yielding both diffusion and age information via routine
40
Ar/
39
Ar step-heating of K-feldspar. Observed correlations between age and Arrhenius spectra show that Ar diffusion occurs by the same mechanisms in nature as in the laboratory. Under certain conditions, these data permit the recovery of a unique, cooling history. The community reaction included some unproductive lines of argument but some stimulated refinements of the MDD model that benefited the development of thermochronology. The MDD model was recently applied to muscovite upon recognition that the same diffusion mechanism operates in vacuum step-heating as in nature. The advent of
40
K–
40
Ca closure profile dating opens up a new thermochronological approach. Initial results confirm that muscovite intragrain defects can restrict effective diffusion length scales in white micas from 10–100 s of microns. Our hope for the future of the MDD model is that it be subject to aggressive and sceptical testing by the community in which quantification is valued over assertion.
On the role of ATP release, ectoATPase activity, and extracellular ADP in the regulatory volume decrease of Huh-7 human hepatoma cells
Authors: Espelt María V. , de Tezanos Pinto Felicitas , Alvarez Cora L. , Alberti Germán Sanchez , Incicco Jeremías , Denis María F. Leal , Davio Carlos , Schwarzbaum Pablo J.
Published: March 2013

Hypotonicity triggered in human hepatoma cells (Huh-7) the release of ATP and cell swelling, followed by volume regulatory decrease (RVD). We analyzed how the interaction between those processes modulates cell volume. Cells exposed to hypotonic medium swelled 1.5 times their basal volume. Swelling was followed by 41% RVD40 (extent of RVD after 40 min of maximum), whereas the concentration of extracellular ATP (ATPe) increased 10 times to a maximum value at 15 min. Exogenous apyrase (which removes di- and trinucleotides) did not alter RVD, whereas exogenous Na+-K+-ATPase (which converts ATP to ADP in the extracellular medium) enhanced RVD40 by 2.6 times, suggesting that hypotonic treatment alone produced a basal RVD, whereas extracellular ADP activated RVD to achieve complete volume regulation (i.e., RVD40 ≈100%). Under hypotonicity, addition of 2-(methylthio)adenosine 5′-diphosphate (2MetSADP; ADP analog) increased RVD to the same extent as exposure to Na+-K+-ATPase and the same analog did not stimulate RVD when coincubated with MRS2211, a blocker of ADP receptor P2Y13. RT-PCR and Western blot analysis confirmed the presence of P2Y13. Cells exhibited significant ectoATPase activity, which according to RT-PCR analysis can be assigned to ENTPDase2. Both carbenoxolone, a blocker of conductive ATP release, and brefeldin A, an inhibitor of exocytosis, were able to partially decrease ATPe accumulation, pointing to the presence of at least two mechanisms for ATP release. Thus, in Huh-7 cells, hypotonic treatment triggered the release of ATP. Conversion of ATPe to ADPe by ENTPDase 2 activity facilitates the accumulated ADPe to activate P2Y13 receptors, which mediate complete RVD.
Expression of a novel isoform of Na+/H+exchanger 3 in the kidney and intestine of banded houndshark,Triakis scyllium
Authors: Li Shanshan , Kato Akira , Takabe Souichirou , Chen An-Ping , Romero Michael F. , Umezawa Takahiro , Nakada Tsutomu , Hyodo Susumu , Hirose Shigehisa
Published: March 2013

Na+/H+exchanger 3 (NHE3) provides one of the major Na+absorptive pathways of the intestine and kidney in mammals, and recent studies of aquatic vertebrates (teleosts and elasmobranchs) have demonstrated that NHE3 is expressed in the gill and plays important roles in ion and acid-base regulation. To understand the role of NHE3 in elasmobranch osmoregulatory organs, we analyzed renal and intestinal expressions and localizations of NHE3 in a marine elasmobranch, Japanese banded houndshark ( Triakis scyllium). mRNA for Triakis NHE3 was most highly expressed in the gill, kidney, spiral intestine, and rectum. The kidney and intestine expressed a transcriptional isoform of NHE3 (NHE3k/i), which has a different amino terminus compared with that of NHE3 isolated from the gill (NHE3g), suggesting that NHE3k/i and NHE3g arise from a single gene by alternative promoter usage. Immunohistochemical analyses of the Triakis kidney demonstrated that NHE3k/i is expressed in the apical membrane of a part of the proximal and late distal tubules in the sinus zone. In the bundle zone of the kidney, NHE3k/i was expressed in the apical membrane of the early distal tubules known as the diluting segment. In the spiral intestine and rectum, NHE3k/i was localized toward the apical membrane of the epithelial cells. The transcriptional levels of NHE3k/i were increased in the kidney when Triakis was acclimated in 130% seawater, whereas those in the spiral intestine were increased in fish acclimated in diluted seawater. These results suggest that NHE3 is involved in renal Na+reabsorption, urine acidification, and intestinal Na+absorption in elasmobranchs.
Nitro-oleic acid protects against adriamycin-induced nephropathy in mice
Authors: Liu Shanshan , Jia Zhanjun , Zhou Li , Liu Ying , Ling Hong , Zhou Shu-Feng , Zhang Aihua , Du Yaomin , Guan Guangju , Yang Tianxin
Published: March 2013

Adriamycin (ADR) administration in susceptible rodents such as the BALB/c mouse strain produces injury to the glomerulus mimicking human focal glomerular sclerosis. The goal of the present study was to use this model to investigate antiproteinuric action of nitro-oleic acid (OA-NO2), a nitric oxide-derived endogenous lipid product, which has exhibited multiple attractive signaling properties particularly in the kidney. BALB/c mice were pretreated for 2 days with OA-NO2 at 5 mg·kg−1·day−1 via an osmotic minipump, followed by a single injection of vehicle or adriamycin (10 mg/kg) via the tail vein. Albuminuria and renal function were analyzed at 1 wk post-ADR treatment. ADR mice developed prominent albuminuria, hypoalbuminemia, hyperlipidemia, and severe ascites. In contrast, the symptoms of nephrotic syndrome were greatly improved by OA-NO2 treatment. In parallel, plasma creatinine and plasma urea nitrogen were elevated in the ADR group, and the severity was less in the ADR+OA-NO2 group. OA-NO2 attenuates ADR-induced glomerulosclerosis, podocyte loss, and tubulointerstitial fibrosis. Indices of oxidative stress, including plasma and urinary thiobarbituric acid-reactive substances and renal expression of NAD(P)H oxidase p47phox and gp91phox, and inflammation, including renal expression of TNF-α, IL-1β, and MCP-1 in response to ADR, were all similarly suppressed. Together, these findings suggest that OA-NO2 exerts renoprotective action against ADR nephropathy likely via its anti-inflammatory and antioxidant properties.
Mutant SOD1-expressing astrocytes release toxic factors that trigger motoneuron death by inducing hyperexcitability
Authors: Fritz Elsa , Izaurieta Pamela , Weiss Alexandra , Mir Franco R. , Rojas Patricio , Gonzalez David , Rojas Fabiola , Brown Robert H. , Madrid Rodolfo , van Zundert Brigitte
Published: March 2013

Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by dysfunction and degeneration of motoneurons starting in adulthood. Recent studies using cell or animal models document that astrocytes expressing disease-causing mutations of human superoxide dismutase 1 (hSOD1) contribute to the pathogenesis of ALS by releasing a neurotoxic factor(s). Neither the mechanism by which this neurotoxic factor induces motoneuron death nor its cellular site of action has been elucidated. Here we show that acute exposure of primary wild-type spinal cord cultures to conditioned medium derived from astrocytes expressing mutant SOD1 (ACM-hSOD1G93A) increases persistent sodium inward currents (PCNa), repetitive firing, and intracellular calcium transients, leading to specific motoneuron death days later. In contrast to TTX, which paradoxically increased twofold the amplitude of calcium transients and killed motoneurons, reduction of hyperexcitability by other specific (mexiletine) and nonspecific (spermidine and riluzole) blockers of voltage-sensitive sodium (Nav) channels restored basal calcium transients and prevented motoneuron death induced by ACM-hSOD1G93A. These findings suggest that riluzole, the only FDA-approved drug with known benefits for ALS patients, acts by inhibiting hyperexcitability. Together, our data document that a critical element mediating the non-cell-autonomous toxicity of ACM-hSOD1G93A on motoneurons is increased excitability, an observation with direct implications for therapy of ALS.
Repeated cocaine exposure increases fast-spiking interneuron excitability in the rat medial prefrontal cortex
Authors: Campanac Emilie , Hoffman Dax A.
Published: March 2013

The medial prefrontal cortex plays a key role in cocaine addiction. However, how chronic cocaine exposure affects cortical networks remains unclear. Most studies have focused on layer 5 pyramidal neurons (the circuit output), while the response of local GABAergic interneurons to cocaine remains poorly understood. Here, we recorded from fast-spiking interneurons (FS-IN) after repeated cocaine exposure and found altered membrane excitability. After cocaine withdrawal, FS-IN showed an increase in the number of spikes evoked by positive current injection, increased input resistance, and decreased hyperpolarization-activated current. We also observed a reduction in miniature excitatory postsynaptic currents, whereas miniature inhibitory postsynaptic current activity was unaffected. We show that, in animals with cocaine history, dopamine receptor D2 activation is less effective in increasing FS-IN intrinsic excitability. Interestingly, these alterations are only observed 1 wk or more after the last cocaine exposure. This suggests that the dampening of D2-receptor-mediated response may be a compensatory mechanism to rein down the excitability of FS-IN.