bluuebunny/crossref_metadata_2025 huggingface dataset:
Down‐regulation of CBP80 gene expression as a strategy to engineer a drought‐tolerant potato
Authors: Pieczynski Marcin , Marczewski Waldemar , Hennig Jacek , Dolata Jakub , Bielewicz Dawid , Piontek Paulina , Wyrzykowska Anna , Krusiewicz Dominika , Strzelczyk‐Zyta Danuta , Konopka‐Postupolska Dorota , Krzeslowska Magdalena , Jarmolowski Artur , Szweykowska‐Kulinska Zofia
Published: December 2012

Developing new strategies for crop plants to respond to drought is crucial for their innovative breeding. The down‐regulation of nuclear cap‐binding proteins in Arabidopsis renders plants drought tolerant. The CBP80 gene in the potato cultivar Desiree was silenced using artificial microRNAs. Transgenic plants displayed a higher tolerance to drought, ABA‐hypersensitive stomatal closing, an increase in leaf stomata and trichome density, and compact cuticle structures with a lower number of microchannels. These findings were correlated with a higher tolerance to water stress. The level of miR159 was decreased, and the levels of its target mRNAs MYB33 and MYB101 increased in the transgenic plants subjected to drought. Similar trends were observed in an Arabidopsis cbp80 mutant. The evolutionary conservation of CBP80, a gene that plays a role in the response to drought, suggests that it is a candidate for genetic manipulations that aim to obtain improved water‐deficit tolerance of crop plants.
Localization of reactive oxygen species and change of antioxidant capacities in mesophyll and bundle sheath chloroplasts of maize under salinity
Authors: Omoto Eiji , Nagao Haruto , Taniguchi Mitsutaka , Miyake Hiroshi
Published: December 2012

In maize, the structure of bundle sheath cell (BSC) chloroplasts is less subject to salinity stress than that of mesophyll cell (MC) chloroplasts. To elucidate the difference in sensitivity to salinity, antioxidant capacities and localization of reactive oxygen species were investigated in both chloroplasts. Transmission electron microscopic observation showed that O2− localization was found in both chloroplasts under salinity, but the accumulation was much greater in MC chloroplasts. H2O2 localization was observed only in MC chloroplasts of salt‐treated plants. In isolated chloroplasts, the activities of superoxide dismutase (SOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11) and dehydroascorbate reductase (DHAR, EC 1.8.5.1) were increased by salinity. While the enhancement of SOD activity was similar in both chloroplasts, the increase of APX and DHAR activities were more pronounced in BSC chloroplasts than in MC chloroplasts. Monodehydroascorbate reductase (MDHAR, EC 1.6.5.4) and glutathione reductase (GR, EC 1.6.4.2) were undetectable in BSC chloroplasts, while they increased in MC chloroplasts under salinity. Although ascorbate content increased by salinity only in BSC chloroplasts, glutathione content increased significantly in both chloroplasts, and was higher in MC chloroplasts than in BSC chloroplasts. The content of thiobarbituric acid‐reactive substances, which is an indicator of lipid peroxidation, was significantly increased by salinity in both chloroplasts. These results suggested O2−‐scavenging capacity was comparable between both chloroplasts, whereas H2O2‐scavenging capacity was lower in MC chloroplasts than in BSC chloroplasts. Moreover, the increased lipid peroxidation under salinity was associated with the structural alteration in MC chloroplasts, while it had less impact on the structure of BSC chloroplasts.
Political Representation and Imagined Community: The Case of Luxembourg
Authors: Dormal Michel
Published: December 2012

Discussions of nation‐building often focus on political elites, who are considered the makers of new communities. This article seeks to sketch out a different approach. It suggests thinking of representative relations as the site of a negotiation of collective identity. Drawing on recent discussions in political theory, the first part of the article discusses conceptual implications of this assumption, arguing that representation should be analysed in terms of its symbolic structure. The second part offers a historical case study of the Grand‐Duchy of Luxembourg. It explores how processes of political democratisation and imagination of national community were deeply interconnected in the period from 1890 to 1939. The article illustrates how the representative politisation of social conflict may trigger nation‐building.
Auto‐Ironic Dissidence: Imagined Exile, Histories, and Communities in 1970s English Canada and Romania
Authors: Manole Diana
Published: December 2012

This article analyses and compares the treatment of history in two dramatic re‐enactments: the English Canadian 1837: The Farmers' Revolt, a collective creation of Theatre Passe Muraille with Rick Salutin as dramaturge, and the Romanian A Cold, by Marin Sorescu. Both plays re‐enact past events as a form of anti‐colonial and respectively anti‐communist resistance and as a way to enable imagined exile, but their dramaturgical strategies and substance are necessarily different as each deals with a specific order of history.
Two Nigerian Ethnonationalist Movements: A Comparison of the OPC and MASSOB
Authors: Duruji Moses Metumara
Published: December 2012

The proliferation of ethnic militia organisations in Nigeria raises questions about the factors responsible for the development. Although reasons adduced from the rhetoric of these organisations point to the politics of exclusion and marginalisation in Nigeria, this form of ethnicity is a new phenomenon. The growth of these militant formations pervading the length and breadth of the country is attributable to the nature and character of the Nigerian state. Perceptions of marginalisation in the distribution of power and resources, and the repressive tactics of the state to sub‐national dissent, have encouraged their growth. The Movement for the Actualization of the Sovereign State of Biafra (MASSOB) and the Oodua Peoples Congress (OPC) are prominent ethnic militia groups that draw membership from major ethnic groups in southern Nigeria. Rivalry and hegemonic competition for the control of the state among the major ethnic groups led to a civil war in the late 1960s, but wartime experiences were not harnessed for a nation‐building project. The result was the systematic perversion of the state, which has resulted in throwing up new forms of ethnicity in Nigeria as reflected in the emergence of these organisations.
Extending Social Theory to Farm Animals: Addressing Alienation in the Dairy Sector
Authors: Stuart Diana , Schewe Rebecca L. , Gunderson Ryan
Published: December 2012

We extend social theory to farm animals in an attempt to illustrate how non‐human animals embedded in social systems can be examined using sociological concepts. Inspired by efforts to include the freedom to express natural behaviour in farm animal welfare standards, we apply Marx's conception of alienation to dairy cows. We first examine industrial dairy farm conditions and find that these systems result in the distortion of life and the suppression of physical and social needs. We then explore alienation in an alternative production system where cows graze on pasture and choose when to be milked by robotic milking machines. Based on farm visits and interviews with farmers, we find that this alternative system addresses several aspects of alienation found in industrial dairy farms. However, despite the benefits associated with alternative production systems, forms of alienation will persist in all systems where maximising profits remains prioritised over life and wellbeing.
Ground‐based InSAR reveals conduit pressurization pulses at Stromboli volcano
Authors: Di Traglia Federico , Del Ventisette Chiara , Rosi Mauro , Mugnai Francesco , Intrieri Emanuele , Moretti Sandro , Casagli Nicola
Published: December 2012

At Stromboli volcano (Southern Italy), only few minor precursors (gas output) have been identified for ‘major’ Strombolian explosions. We use ground‐based interferometric synthetic aperture radar (GBInSAR) technology to monitor the displacement rate of the summit area of Stromboli. We analysed the 2009–2011 period. The analysis of the displacement rate has been performed by dividing the summit zone monitored by the GBInSAR into three regions, corresponding to the edge of the crater area (1 and 2), and to the slope of the NE crater (3). Pulses of rapid expansion of sector 3, of variable duration and amplitude, appear in coincidence with periods of intense activity that include lava flows and major explosions. We associate this expansion with the pressurization of the magma column that is recharged by deep‐derived gas, promoting the onset of ‘major explosion‐dominated’ activity.
Avoiding room temperature storage and delayed cryopreservation provide better postthaw potency in hematopoietic progenitor cell grafts
Authors: Fry Laura Jayne , Giner Sergio Querol , Gomez Susana G. , Green Melanie , Anderson Sally , Horder Jackie , McArdle Stephanie , Rees Robert , Madrigal Jose Alejandro
Published: December 2012

Background

Conditions for maintaining hematopoietic progenitor cells (HPCs) before cryopreservation remain controversial. An understanding of the impact of time and temperature during nonfrozen storage can contribute to the maintenance of the quality of products, improving transplantation outcomes. The objective of this study was to determine the influence on cell potency of thawed products from three sources of HPCs after prolonged storage at different temperatures before cryopreservation.

Study Design and Methods

Viable cell counts by flow cytometry and colony‐forming unit (CFU) recoveries were assessed on cord blood (CB), mobilized peripheral blood stem cell (PBSC), and bone marrow (BM) samples over 72 hours using two different storage conditions, refrigerated (4‐8°C) or room temperature (19‐22°C). To determine the effects of delayed freezing on progenitor recoveries, paired samples were evaluated before and after cryopreservation.

Results

All samples maintained at refrigerated temperatures resulted in higher recoveries than those at room temperature in all variables assessed. Specifically, when assessing for CFU yields after thawing, the impact of time on BM resulted in a significant loss as soon as 24 hours (n = 10, 36.4 ± 28.0%, p = 0.003). This decrease was also observed for PBSCs and CB but at 48 hours of fresh storage (PBSCs n = 11, 32.7 ± 26.2%, p = 0.006; CB n = 10, 39.6 ± 26.4%, p = 0.001).

Conclusion

Our data suggest that HPC products are better maintained at refrigerated temperatures before cryopreservation. Delaying cryopreservation should be minimized to avoid significant losses in cell potency.
Red blood cell–derived microparticles isolated from blood units initiate and propagate thrombin generation
Authors: Rubin Olivier , Delobel Julien , Prudent Michel , Lion Niels , Kohl Kid , Tucker Erik I. , Tissot Jean‐Daniel , Angelillo‐Scherrer Anne
Published: December 2012

Background

Red blood cell–derived microparticles (RMPs) are small phospholipid vesicles shed from RBCs in blood units, where they accumulate during storage. Because microparticles are bioactive, it could be suggested that RMPs are mediators of posttransfusion complications or, on the contrary, constitute a potential hemostatic agent.

Study Design and Methods

This study was performed to establish the impact on coagulation of RMPs isolated from blood units. Using calibrated automated thrombography, we investigated whether RMPs affect thrombin generation (TG) in plasma.

Results

We found that RMPs were not only able to increase TG in plasma in the presence of a low exogenous tissue factor (TF) concentration, but also to initiate TG in plasma in absence of exogenous TF. TG induced by RMPs in the absence of exogenous TF was neither affected by the presence of blocking anti‐TF nor by the absence of Factor (F)VII. It was significantly reduced in plasma deficient in FVIII or F IX and abolished in FII‐, FV‐, FX‐, or FXI‐deficient plasma. TG was also totally abolished when anti‐XI 01A6 was added in the sample. Finally, neither Western blotting, flow cytometry, nor immunogold labeling allowed the detection of traces of TF antigen. In addition, RMPs did not comprise polyphosphate, an important modulator of coagulation.

Conclusions

Taken together, our data show that RMPs have FXI‐dependent procoagulant properties and are able to initiate and propagate TG. The anionic surface of RMPs might be the site of FXI‐mediated TG amplification and intrinsic tenase and prothrombinase complex assembly.
Establishment of a medium‐throughput approach for the genotyping of RHD variants and report of nine novel rare alleles
Authors: Fichou Yann , Le Maréchal Cédric , Jamet Déborah , Bryckaert Laurence , Ka Chandran , Audrézet Marie‐Pierre , Le Gac Gérald , Dupont Isabelle , Chen Jian‐Min , Férec Claude
Published: December 2012

Background

The routinely used serologic methods are robust in accurately typing standard D− or D+ blood. However, they result in discrepancy in weak or partial D blood, which requires genetic analysis. We have previously used denaturing high‐performance liquid chromatography (DHPLC) to screen the entire RHD‐coding sequence. However, DHPLC is technically challenging, labor‐intensive, and time‐consuming. To overcome these inconveniences, we sought to develop a new two‐step approach.

Study Design and Methods

A total of 430 blood samples with D phenotype ambiguity were recruited for this study. The three most frequent weak D alleles (i.e., weak D, Type 1; weak D, Type 2; and weak D, Type 3), which altogether account for 60% to 90% of the atypical RHD alleles in the Caucasian population, were first identified by Tm‐shift genotyping. The remaining unidentified samples were then subjected to a single‐tube multiplex polymerase chain reaction (PCR) amplification of all 10 RHD exons followed by direct sequencing.

Results

Optimal conditions for efficient and reliable identification of the three most common weak D variants by Tm‐shift genotyping were established. All 10 RHD exons were successfully amplified in a single‐multiplex PCR procedure. Employment of the two‐step analysis identified RHD variants in 91.6% of the 430 studied samples. Two of the nine previously undescribed variants, c.335G>T and c.939G>A, were found to cause aberrant mRNA splicing by means of a splicing minigene assay.

Conclusion

The new two‐step analysis proved to be much easier and cheaper than the DHPLC method and therefore is convenient to be used as a routine, medium‐throughput approach for RHD genotyping.
Frequency and risk factors for donor reactions in an anonymous blood donor survey
Authors: Goldman Mindy , Osmond Lori , Yi Qi‐Long , Cameron‐Choi Keltie , O'Brien Sheila F.
Published: December 2012

Background

Adverse donor reactions can result in injury and decrease the likelihood of donor return. Reaction reports captured in the blood center's database provide an incomplete picture of reaction rates and risk factors.

Study Design and Methods

We performed an anonymous survey, mailed to 40,000 donors in 2008, including questions about symptoms, height, weight, sex, and donation status. Reaction rates were compared to those recorded in our database. Possible risk factors were assessed for various reactions.

Results

The response rate was 45.5%. A total of 32% of first‐time and 14% of repeat donors reported having any adverse symptom, most frequently bruising (84.9 per 1000 donors) or feeling faint or weak (66.2 per 1000). Faint reactions were two to eight times higher than reported in our database, although direct comparison was difficult. Younger age, female sex, and first‐time donation status were risk factors for systemic and arm symptoms. In females, low estimated blood volume (EBV) was a risk factor for systemic symptoms. Only 51% of donors who consulted an outside physician also called Canadian Blood Services. A total of 10% of first‐time donors with reactions found adverse effects information inadequate.

Conclusion

This study allowed us to collect more information about adverse reactions, including minor symptoms and delayed reactions. Based on our findings of the risk factors and frequency of adverse reactions, we are implementing more stringent EBV criteria for younger donors and providing more detailed information to donors about possible adverse effects and their management.
China and the World Trading System
Authors: Mattoo Aaditya , Subramanian Arvind
Published: December 2012

The WTO has been until recently an effective framework for cooperation because it has continually adapted to changing economic realities. The current Doha Agenda is an aberration because it does not reflect one of the biggest shifts in the international economic and trading system: the rise of China. Even though China will have a stake in maintaining trade openness, an initiative that builds on but redefines the Doha Agenda would anchor China more fully in the multilateral trading system. Such an initiative would have two pillars. First, a new negotiating agenda that would include the major issues of interest to China and its trading partners and thus unleash the powerful reciprocal liberalisation mechanism that has driven the WTO process to previous successes. Second, new restraints on bilateralism and regionalism that would help preserve incentives for maintaining the current broadly non‐discriminatory trading order.
The André–Oort conjecture for the moduli space of abelian surfaces
Authors: Pila Jonathan , Tsimerman Jacob
Published: December 2012

We provide an unconditional proof of the André–Oort conjecture for the coarse moduli space 𝒜2,1 of principally polarized abelian surfaces, following the strategy outlined by Pila–Zannier.
Supersonic Jump
Authors: Müller Andreas
Published: December 2012

On October 14,2012, Felix Baumgartner, an Austrian sky-diver, set some new world records for his discipline. Jumping from a height of about 39 km, he reached a top speed of 1342 km/h, becoming the first human being to break the sound barrier in free fall. In order to understand some essential physics aspects of this remarkable feat, we wonder why his start height had to be that high (when the tremendous effort that was necessary for leaping from such a height required $50 million, as reported in the press). More precisely, can you give an estimate for the minimal start height—which we will call the Baumgartner limit, zB—of a sky diver who wants to break the sound barrier in free fall?
A Fresh Look at Longitudinal Standing Waves on a Spring
Authors: Rutherford Casey
Published: December 2012

Transverse standing waves produced on a string, as shown in Fig. 1, are a common demonstration of standing wave patterns that have nodes at both ends. Longitudinal standing waves can be produced on a helical spring that is mounted vertically and attached to a speaker, as shown in Fig. 2, and used to produce both node-node (NN) and node-antinode (NA) standing waves. The resonant frequencies of the two standing wave patterns are related with theory that is accessible to students in algebra-based introductory physics courses, and actual measurements show good agreement with theoretical predictions.
A Remote Radioactivity Experiment
Authors: Jona Kemi , Vondracek Mark
Published: December 2012

Imagine a high school with very few experimental resources and limited budgets that prevent the purchase of even basic laboratory equipment. For example, many high schools do not have the means of experimentally studying radioactivity because they lack Geiger counters and/or good radioactive sources. This was the case at the first high school one of us (MV) worked at, and after talking with numerous colleagues we know this is still the case at many schools. What options are there then for physics teachers to allow their students to experimentally investigate certain characteristics of radioactivity, such as how distance affects the intensity of radiation coming from a radioactive source? There are computer simulations that can be run, or perhaps the teacher has a light sensor and tries to make an analogy between the intensity of light from a light bulb and the intensity of radiation from a radioactive source based on geometric arguments to get an inverse-square law. But for many there is no direct experimental option if one does not possess a Geiger counter and good radioactive sample. It is for that teacher and class of students that an online, remote radioactivity experiment was created.
Learning About Non-Newtonian Fluids in a Student-Driven Classroom
Authors: Dounas-Frazer D. R. , Lynn J. , Zaniewski A. M. , Roth N.
Published: December 2012

We describe a simple, low-cost experiment and corresponding pedagogical strategies for studying fluids whose viscosities depend on shear rate, referred to as “non-Newtonian fluids.” We developed these materials teaching for the Compass Project,1 an organization that fosters a creative, diverse, and collaborative community of science students at UC Berkeley. Incoming freshmen worked together in a week-long residential program to explore physical phenomena through a combination of conceptual model-building and hands-on experimentation. During the program, students were exposed to three major aspects of scientific discovery: developing a model, testing the model, and investigating deviations from the model.
Using iPads to illustrate the impulse-momentum relationship
Authors: Streepey Jefferson W.
Published: December 2012

One of the fundamental challenges in teaching is making the students able to transform course material in ways that help them solve “real world” problems.1 Sophisticated mobile technology (such as smartphones, iPads, or iTouches) offers students an opportunity to apply physics content to a broad range of scenarios to enhance their understanding and improve their class engagement. For the outlined example, students in an upper-level biomechanics class used the native accelerometers in iPads to record and analyze human movement. This activity allowed the students to experiment with the impulse-momentum relationship.
Those ever-present lab reports
Authors: Chesick Elizabeth
Published: December 2012

When I started teaching, I was totally green. I had a BA and an MA in physics, but I had taught only quiz sections in graduate school. Whatever possessed me to think I might be able to teach? However, I have retired after 45 years of teaching high school physics.
Celebrating 30 Years of Wnt Signaling
Meeting Information:
EMBO Conference—30 Years of Wnt Signalling, 27 June to 1 July 2012, Egmond aan Zee, Netherlands
Authors: Verkaar Folkert , Cadigan Ken M. , van Amerongen Renée
Published: December 2012

Researchers gathered to share the latest findings on Wnt signaling in development and disease.
Dissecting Wnt Signaling
Authors: Ray L. Bryan
Published: December 2012

Reducing the rate of phosphorylation of β-catenin leads to an increase in the steady-state level of the unmodified form.
Platelets Poison Parasites
Authors: Ash Caroline
Published: December 2012

Interaction of a platelet protein and a red cell protein enables platelets to attack malarial parasites inside red cells.
Androgen-Driven Sequestration
Authors: Hines Pamela J.
Published: December 2012

Androgen-driven changes in receptor expression disrupt a neuronal signaling pathway and deinnervation.
Bacterial Cooperation
Authors: Gough Nancy R.
Published: December 2012

The pathogenic bacterium EHEC relies on fucose produced by a commensal bacterium to regulate its metabolism to maximize effective intestinal colonization.
Rapid Antimicrobial Susceptibility Testing by Sensitive Detection of Precursor rRNA Using a Novel Electrochemical Biosensing Platform
Authors: Halford Colin , Gonzalez Rodrigo , Campuzano Susana , Hu Bo , Babbitt Jane T. , Liu Jun , Wang Joseph , Churchill Bernard M. , Haake David A.
Published: December 2012

Precursor rRNA (pre-rRNA) is an intermediate stage in the formation of mature rRNA and is a useful marker for cellular metabolism and growth rate. We developed an electrochemical sensor assay for
Escherichia coli
pre-rRNA involving hybridization of capture and detector probes with tail sections that are spliced away during rRNA maturation. A ternary self-assembled monolayer (SAM) prepared on gold electrode surfaces by coassembly of thiolated capture probes with hexanedithiol and posttreatment with 6-mercapto-1-hexanol minimized the background signal and maximized the signal-to-noise ratio. Inclusion of internal calibration controls allowed accurate estimation of the pre-rRNA copy number per cell. As expected, the ratio of pre-rRNA to mature rRNA was low during stationary phase and high during log phase. Pre-rRNA levels were highly dynamic, ranging from 2 copies per cell during stationary phase to ∼1,200 copies per cell within 60 min of inoculation into fresh growth medium. Specificity of the assay for pre-rRNA was validated using rifampin and chloramphenicol, which are known inhibitors of pre-rRNA synthesis and processing, respectively. The DNA gyrase inhibitor, ciprofloxacin, was found to act similarly to rifampin; a decline in pre-rRNA was detectable within 15 min in ciprofloxacin-susceptible bacteria. Assays for pre-rRNA provide insight into cellular metabolism and are promising predictors of antibiotic susceptibility.
Effect of Combined Fluoroquinolone and Azole Use on QT Prolongation in Hematology Patients
Authors: Zeuli John D. , Wilson John W. , Estes Lynn L.
Published: December 2012

QTc prolongation is a risk factor for development of torsades de pointes (TdP). Combination therapy with fluoroquinolones and azoles is used in patients with hematologic malignancies for prophylaxis and treatment of infection. Both drug classes are implicated as risk factors for QTc prolongation. The cumulative effect on and incidence of QTc prolongation for this combination have not been previously described. A retrospective chart review was performed with hospitalized inpatients from 1 September 2008 to 31 January 2010 comparing QTc interval data from electrocardiogram (ECG) assessment at baseline and after the initiation of combination therapy. Ninety-four patients were eligible for inclusion. The majority, 88 patients (93.6%), received quinolone therapy with levofloxacin. Fifty-three patients (56.4%) received voriconazole; 40 (42.6%) received fluconazole. The overall mean QTc change from baseline was 6.1 (95% confidence interval [CI], 0.2 to 11.9) ms. Twenty-one (22.3%) of the studied patients had clinically significant changes in the QTc while receiving combination fluoroquinolone-azole therapy. Statistically significant risk factors for clinically significant changes in QTc were hypokalemia (
P
= 0.03) and a left-ventricular ejection fraction of <55% (
P
= 0.02). Low magnesium (
P
= 0.11), exposure to 2 or more drugs with the potential to prolong the QTc interval (
P
= 0.17), and female sex (
P
= 0.21) trended toward significance. Combination therapy with fluoroquinolone and azole antifungals is associated with increased QTc from baseline in hospitalized patients with hematologic malignancies. One in five patients had a clinically significant change in the QTc, warranting close monitoring and risk factor modification to prevent the possibility of further QTc prolongation and risk of TdP.
In Vitro
Pharmacodynamics of AZD5206 against Staphylococcus aureus
Authors: Tam Vincent H. , Chang Kai-Tai , Yang Zhen , Newman Joseph , Hu Ming
Published: December 2012

AZD5206 is a novel antimicrobial agent with potent
in vitro
activity against
Staphylococcus aureus
. We evaluated the
in vitro
pharmacodynamics of AZD5206 against a standard wild-type methicillin-susceptible strain (ATCC 29213) and a clinical strain of methicillin-resistant
S. aureus
(SA62). Overall, bacterial killing against a low baseline inoculum was more remarkable. Low dosing exposures and/or high baseline inoculum resulted in early reduction in bacterial burden, followed by regrowth and selective amplification of the resistant population.
STB5
Is a Negative Regulator of Azole Resistance in Candida glabrata
Authors: Noble Jason A. , Tsai Huei-Fung , Suffis Sara D. , Su Qin , Myers Timothy G. , Bennett John E.
Published: December 2012

The opportunistic yeast pathogen
Candida glabrata
is recognized for its ability to acquire resistance during prolonged treatment with azole antifungals (J. E. Bennett, K. Izumikawa, and K. A. Marr. Antimicrob. Agents Chemother. 48:1773–1777, 2004). Resistance to azoles is largely mediated by the transcription factor
PDR1
, resulting in the upregulation of ATP-binding cassette (ABC) transporter proteins and drug efflux. Studies in the related yeast
Saccharomyces cerevisiae
have shown that Pdr1p forms a heterodimer with another transcription factor, Stb5p. In
C. glabrata
, the open reading frame (ORF) designated CAGL0I02552g has 38.8% amino acid identity with
STB5
(YHR178w) and shares an N-terminal Zn
2
Cys
6
binuclear cluster domain and a fungus-specific transcriptional factor domain, prompting us to test for homologous function and a possible role in azole resistance. Complementation of a Δyhr178w (Δ
stb5
) mutant with CAGL0I02552g resolved the increased sensitivity to cold, hydrogen peroxide, and caffeine of the mutant, for which reason we designated CAGl0I02552g
CgSTB5
. Overexpression of
CgSTB5
in
C. glabrata
repressed azole resistance, whereas deletion of
CgSTB5
caused a modest increase in resistance. Expression analysis found that
CgSTB5
shares many transcriptional targets with
CgPDR1
but, unlike the latter, is a negative regulator of pleiotropic drug resistance, including the ABC transporter genes
CDR1
,
PDH1
, and
YOR1
.
Effect of Single Nucleotide Polymorphisms in Cytochrome P450 Isoenzyme and
N
-Acetyltransferase 2 Genes on the Metabolism of Artemisinin-Based Combination Therapies in Malaria Patients from Cambodia and Tanzania
Authors: Staehli Hodel Eva Maria , Csajka Chantal , Ariey Frédéric , Guidi Monia , Kabanywanyi Abdunoor Mulokozi , Duong Socheat , Decosterd Laurent Arthur , Olliaro Piero , Beck Hans-Peter , Genton Blaise
Published: December 2012

The pharmacogenetics of antimalarial agents are poorly known, although the application of pharmacogenetics might be critical in optimizing treatment. This population pharmacokinetic-pharmacogenetic study aimed at assessing the effects of single nucleotide polymorphisms (SNPs) in cytochrome P450 isoenzyme genes (
CYP
, namely,
CYP2A6
,
CYP2B6
,
CYP2C8
,
CYP2C9
,
CYP2C19
,
CYP2D6
,
CYP3A4
, and
CYP3A5
) and the
N
-acetyltransferase 2 gene (
NAT2
) on the pharmacokinetics of artemisinin-based combination therapies in 150 Tanzanian patients treated with artemether-lumefantrine, 64 Cambodian patients treated with artesunate-mefloquine, and 61 Cambodian patients treated with dihydroartemisinin-piperaquine. The frequency of SNPs varied with the enzyme and the population. Higher frequencies of mutant alleles were found in Cambodians than Tanzanians for
CYP2C9
*
3
,
CYP2D6
*
10
(100C→T),
CYP3A5
*
3
,
NAT2
*
6
, and
NAT2
*
7
. In contrast, higher frequencies of mutant alleles were found in Tanzanians for
CYP2D6
*
17
(1023C→T and 2850C→T),
CYP3A4
*
1B
,
NAT2
*
5
, and
NAT2
*
14
. For 8 SNPs, no significant differences in frequencies were observed. In the genetic-based population pharmacokinetic analyses, none of the SNPs improved model fit. This suggests that pharmacogenetic data need not be included in appropriate first-line treatments with the current artemisinin derivatives and quinolines for uncomplicated malaria in specific populations. However, it cannot be ruled out that our results represent isolated findings, and therefore more studies in different populations, ideally with the same artemisinin-based combination therapies, are needed to evaluate the influence of pharmacogenetic factors on the clearance of antimalarials.
Gentamicin in Hemodialyzed Critical Care Patients: Early Dialysis after Administration of a High Dose Should Be Considered
Authors: Veinstein Anne , Venisse Nicolas , Badin Julie , Pinsard Michel , Robert René , Dupuis Antoine
Published: December 2012

Gentamicin is a widely used antibiotic in the intensive care unit (ICU). Its dosage is difficult to adapt to hemodialyzed ICU patients. The FDA-approved regimen consists of the administration of 1 to 1.7 mg/kg of gentamicin at the end of each dialysis session. Better pharmacokinetic management could be obtained if gentamicin were administered just before the dialysis session. We performed Monte Carlo simulations (MCS) to determine the best gentamicin pharmacokinetic profile (high peak and low trough concentrations). Then, 6 mg/kg of gentamicin was infused into 10 ICU patients over a period of 30 min. A 4-h-long hemodialysis session was started 30 min after the end of the infusion. Pharmacokinetic samples were regularly collected over 24 h. A one-compartment model with zero-order input and first-order elimination was developed in Nonmem version VI to analyze patients' measured gentamicin concentration-versus-time profiles. Finally, additional MCS were performed to compare the regimen chosen with the FDA-approved gentamicin regimen. High peak concentrations (
C
max
, 31.8 ± 16.8 mg/liter) were achieved. The estimated
C
24
and
C
48
values (concentrations 24 and 48 h, respectively, after the beginning of the infusion) were 4.1 ± 2.3 and 1.8 ± 1.2 mg/liter, respectively. The volume of distribution was 0.21 ± 0.06 liter/kg. MCS confirmed that the dosing regimen chosen achieved the target
C
max
whereas the FDA-approved regimen did not (31.0 ± 10.9 versus 8.8 ± 3.1 mg · liter
−1
). Moreover, the
C
24
values were similar while the AUC
0-24
values were moderately increased (190.8 ± 65.0 versus 135 ± 42.2 mg · h · liter
−1
). Therefore, administration of 6 mg/kg of gentamicin before hemodialysis to critically ill patients achieves a high
C
max
and an acceptable AUC, maximizing pharmacokinetic/pharmacodynamic endpoints.
Plasmid Content of a Clinically Relevant Klebsiella pneumoniae Clone from the Czech Republic Producing CTX-M-15 and QnrB1
Authors: Dolejska Monika , Villa Laura , Dobiasova Hana , Fortini Daniela , Feudi Claudia , Carattoli Alessandra
Published: December 2012

The entire plasmid content of a multidrug-resistant, CTX-M-15-producing
Klebsiella pneumoniae
ST416 clone was investigated. Two FII
K
plasmids, pKDO1 (127 kb) and pKPN-CZ (207 kb), were identified and found to carry a formidable set of genes conferring resistance to toxic compounds, metals, and antimicrobial drugs and exhibiting novel features putatively associated with adaptation and fitness of the bacterium in the human host.
Bruton's Tyrosine Kinase Regulates Shigella flexneri Dissemination in HT-29 Intestinal Cells
Authors: Dragoi Ana-Maria , Talman Arthur M. , Agaisse Hervé
Published: December 2012

Shigella flexneri
is a Gram-negative intracellular pathogen that infects the intestinal epithelium and utilizes actin-based motility to spread from cell to cell.
S. flexneri
actin-based motility has been characterized in various cell lines, but studies in intestinal cells are limited. Here we characterized
S. flexneri
actin-based motility in HT-29 intestinal cells. In agreement with studies conducted in various cell lines, we showed that
S. flexneri
relies on neural Wiskott-Aldrich Syndrome protein (N-WASP) in HT-29 cells. We tested the potential role of various tyrosine kinases involved in N-WASP activation and uncovered a previously unappreciated role for Bruton's tyrosine kinase (Btk) in actin tail formation in intestinal cells. We showed that Btk depletion led to a decrease in N-WASP phosphorylation which affected N-WASP recruitment to the bacterial surface, decreased the number of bacteria displaying actin-based motility, and ultimately affected the efficiency of spread from cell to cell. Finally, we showed that the levels of N-WASP phosphorylation and Btk expression were increased in response to infection, which suggests that
S. flexneri
infection not only triggers the production of proinflammatory factors as previously described but also manipulates cellular processes required for dissemination in intestinal cells.
Intracellularly Induced Cyclophilins Play an Important Role in Stress Adaptation and Virulence of Brucella abortus
Authors: Roset Mara S. , García Fernández Lucía , DelVecchio Vito G. , Briones Gabriel
Published: December 2012

Brucella
is an intracellular bacterial pathogen that causes the worldwide zoonotic disease brucellosis.
Brucella
virulence relies on its ability to transition to an intracellular lifestyle within host cells. Thus, this pathogen must sense its intracellular localization and then reprogram gene expression for survival within the host cell. A comparative proteomic investigation was performed to identify differentially expressed proteins potentially relevant for
Brucella
intracellular adaptation. Two proteins identified as cyclophilins (CypA and CypB) were overexpressed in the intracellular environment of the host cell in comparison to laboratory-grown
Brucella
. To define the potential role of cyclophilins in
Brucella
virulence, a double-deletion mutant was constructed and its resulting phenotype was characterized. The
Brucella abortus
Δ
cypAB
mutant displayed increased sensitivity to environmental stressors, such as oxidative stress, pH, and detergents. In addition, the
B. abortus
Δ
cypAB
mutant strain had a reduced growth rate at lower temperature, a phenotype associated with defective expression of cyclophilins in other microorganisms. The
B. abortus
Δ
cypAB
mutant also displays reduced virulence in BALB/c mice and defective intracellular survival in HeLa cells. These findings suggest that cyclophilins are important for
Brucella
virulence and survival in the host cells.
Microbial Modulation of Host Immunity with the Small Molecule Phosphorylcholine
Authors: Clark Sarah E. , Weiser Jeffrey N.
Published: December 2012

All microorganisms dependent on persistence in a host for survival rely on either hiding from or modulating host responses to infection. The small molecule phosphorylcholine, or choline phosphate (ChoP), is used for both of these purposes by a wide array of bacterial and parasitic microbes. While the mechanisms underlying ChoP acquisition and expression are diverse, a unifying theme is the use of ChoP to reduce the immune response to infection, creating an advantage for ChoP-expressing microorganisms. In this minireview, we discuss several benefits of ChoP expression during infection as well as how the immune system fights back against ChoP-expressing pathogens.
Characterization of two alternative splice variants associated with the Arabidopsis rhomboid protein gene At1g25290
Authors: Sedivy-Haley Katharine , Powles Joshua , Ko Kenton
Published: December 2012

Rhomboid proteases are involved in various cellular activities, from development to cancer, and cellular processes and substrates associated with rhomboid proteases or rhomboid-like proteins have been identified for a range of organisms. Plant rhomboid proteases or rhomboid-like proteins are the least understood of the group. Moreover, the general phenomenon of alternative splicing and rhomboid protein genes has yet to be studied robustly. This study thus focused on the alternative splicing events associated with the Arabidopsis rhomboid protein gene At1g25290. The patterns obtained through RT-PCR and DNA sequencing provided evidence of alternative splicing in the At1g25290 transcript population, especially in the region spanning exons 5 and 6. The levels of the two splice variants involving exons 5 and 6 appear to be sufficiently abundant to possess functional significance and appear to adjust relative to each other in different contexts. Adjustments were observed in tissues of different developmental stages, in an Arabidopsis plant bearing a mutation in another rhomboid protein, and in response to transgenic manipulations affecting the levels of Tic40, a plastid translocon component. The resulting change to the protein sequence may, in turn, affect how At1g25290 proteins interact with their substrates. Collectively, the evidence suggests that alternative splicing of At1g25290 bears functional significance in Arabidopsis.
Construction and analysis of a SSH cDNA library of Eucalyptus grandis × Eucalyptus urophylla 9224 induced by Cylindrocladium quinqueseptatum
Authors: Feng Li-Zhen , Guo Wen-Shuo , Xie Wan-Feng , Chen Quan-Zhu , Ye Xiao-Zhen
Published: December 2012

Leaf blight caused by Cylindrocladium quinqueseptatum Boedijn & Reitsma is a major disease occurring in Eucalyptus plantlets and saplings worldwide. Current studies on the resistance to this disease in eucalypti have focused primarily on analyzing the relationship between the disease and the metabolic products from the anatomic structure of Eucalyptus leaves and their physiological responses to pathogen invasion. There have been no reports on the mechanisms of molecular responses. Previous research suggests that Eucalyptus grandis × Eucalyptus urophylla 9224 is the highest resistant cultivar among the 11 ones planted in Fujian Province. Therefore, in this study, the molecular responses of E. grandis × E. urophylla 9224 to C. quinqueseptatum were investigated by means of suppression subtractive hybridization (SSH). In total, 928 clones were obtained from the forward SSH cDNA library of E. grandis × E. urophylla 9224, and 25 up-regulated genes were identified by screening the library using the method of reverse northern hybridization. The results show that among these, 23 up-regulated genes with known functions were involved in signal transduction, plant resistance response, photosynthesis, energy transfer, protein metabolism, and plant growth.
Taxonomic identification errors generate misleading ecological niche model predictions of an invasive hawkweed
Authors: Ensing David J. , Moffat Chandra E. , Pither Jason
Published: December 2012

Ecological niche models (ENMs) have been proposed and applied as tools for predicting the extent of exotic species invasion risk and for identifying areas at risk of invasion. Despite the acknowledged concern of relying on occurrence records of variable and (or) unknown quality, the effect of taxonomically uncertain occurrence records on ENMs has not been investigated. We first present a schematic model describing how taxonomic uncertainty could yield varying predictions of invasion potential depending on the spatial characteristics of all versus “reliable” occurrence records. We then explore the issue in more detail by way of a case study on the morphologically and taxonomically difficult yellowdevil hawkweed (Pilosella glomerata (Froel.) Fr.), which is invasive in North America. We compared the climate niche properties and ENM predictions of invasion risk by P. glomerata in North America among models based on (i) all available occurrence records and (ii) records that are taxonomically “reliable”. “Total” records yielded niche properties that were significantly more heterogeneous than reliable records, and consequently, the potential invasion range of P. glomerata based on total records was predicted to be substantially larger. Our results provide rare empirical evidence that vetting occurrence records for taxonomic reliability is of critical importance for niche modeling.
Unexpected lyotropic liquid crystals from ion-induced columnar assembly of Schiff-base macrocycles
Authors: Hui Joseph K.-H. , Jiang Jian , MacLachlan Mark J.
Published: December 2012

Schiff-base macrocycles 1, which have a crown ether-like interior, form ionic nematic lyotropic liquid crystals in various organic solvents when functionalized with long alkoxy substituents and complexed to diverse ammonium and alkali metal salts. From X-ray diffraction and transmission electron microscopy studies, and by comparison with the organization of macrocycles functionalized with shorter chains, these macrocycles assemble into lyotropic liquid crystals where the macrocycles are stacked and the cation is included in their interiors.
Trends in Scientific Publications of Chinese Medicine
Authors: Wang Chong-Zhi , He Hui , Wang Xiaoyu , Yuan Chun-Su
Published: December 2012

Traditional Chinese medicine (TCM) is an important component of complementary and alternative medicine (CAM). The fast economic growth of mainland China in the past two decades has promoted the use of TCM beyond Chinese-speaking countries. Chinese researchers have published more TCM research studies in CAM-related professional journals, including the American Journal of Chinese Medicine (AJCM), the highest impact journal in Chinese medicine. The consistent increase of the impact factor of the AJCM suggests a growth in TCM popularity. This study analyzed articles published in the AJCM between 2004 and 2011. Our data show that while enthusiasm towards cardiovascular, nervous system and inflammation related research remained high, more herbal investigations and cancer studies were published. Furthermore, a reduction in TCM formulation studies was replaced by increasing botanical single constituent research. Examples of frequently cited studies, including those before 2004, are presented. These data are not only important to the scientific community for recognition of trends in TCM research, but also for providing information to TCM researchers who are targeting potentially highly cited studies.
The Effect of Qigong Exercise on Immunity and Infections: A Systematic Review of Controlled Trials
Authors: Wang Chong-Wen , Ng Siu-Man , Ho Rainbow T.H. , Ziea Eric T.C. , Wong Vivian C.W. , Chan Cecilia L.W.
Published: December 2012

The objective of this review was to summarize and critically evaluate the clinical evidence of the effect of qigong exercise on immunity and its efficacy in the prevention or treatment of infectious diseases. Thirteen databases were searched from their respective inceptions through January 2011, and all controlled clinical trials of qigong exercise on immunity and infections were included. Quality and validity of the included studies were evaluated using standard scales. Seven studies including two randomized controlled trials (RCTs), two controlled clinical trials (CCTs) and three retrospective observational studies (ROSs) met the inclusion criteria. One study focused on functional measures of immunity (antigen-induced immunity) and six studies on enumerative parameters of immunity. No study on clinical symptoms relevant to infectious diseases could be identified. Overall, the included studies suggested favorable effects of qigong exercise on immunity, but the quality of research for most of the studies examined in this review was poor. Further rigorously designed studies are required, which should adhere to accepted standards of methodology for clinical trials.
Efficacy of Electro-Acupuncture in Chronic Plantar Fasciitis: A Randomized Controlled Trial
Authors: Kumnerddee Wipoo , Pattapong Nitsara
Published: December 2012

The aim of the study was to investigate the efficacy of electro-acupuncture coupled with conventional treatments and compare it with the efficacy of conventional treatments alone in patients with chronic plantar fasciitis. Thirty patients with chronic refractory plantar fasciitis were randomly assigned to two groups. Subjects in the control group received five weeks of conventional treatments, including stretching exercise, shoe modification and rescue analgesics. Subjects in the acupuncture group received the same treatments plus ten sessions of electro-acupuncture twice weekly. Endpoints included a success rate determined by a minimum of a 50% decrease in Visual Analog Scale (VAS) and Foot Function Index (FFI). At the end of treatment, VAS decreased significantly from 6.00 ± 1.69 to 1.89 ± 1.59 and from 6.27 ± 2.34 to 5.40 ± 2.26 in the acupuncture and control groups, respectively. FFI decreased significantly only in the acupuncture group (p < 0.05). Subjects in the acupuncture group obtained higher success rates than those in control group (80% and 13.3%, respectively). FFI in the acupuncture group was better than those in the control group (p < 0.001). At the sixth week follow-up, subjects in the acupuncture group showed a better FFI and success rate for pain during the day than those in the control group (p < 0.05). Electro-acupuncture coupled with conventional treatments provided a success rate of 80% in chronic planar fasciitis which was more effective than conventional treatments alone. The effects lasted for at least six weeks.