bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure-Guided Transformation of Channelrhodopsin into a Light-Activated Chloride Channel
Authors: Berndt Andre , Lee Soo Yeun , Ramakrishnan Charu , Deisseroth Karl
Published: April 2014

Optogenetic Insights

Mapping functional neural circuits for many behaviors has been almost impossible, so

Vogelstein
et al.

(p.
386
, published online 27 March; see the Perspective by

O'Leary and Marder

) developed a broadly applicable optogenetic method for neuron-behavior mapping and used it to phenotype larval
Drosophila
and thus developed a reference atlas. As optogenetic experiments become routine in certain fields of neuroscience research, creating even more specialized tools is imperative (see the Perspective by

Hayashi

). By engineering channelrhodopsin,

Wietek
et al.

(p.
409
, published online 27 March) and

Berndt
et al.

(p.
420
) created two different light-gated anion channels to block action potential generation during synaptic stimulation or depolarizing current injections. These new tools not only improve understanding of channelrhodopsins but also provide a way to silence cells.
Reproductions Through Technology
Biological Relatives
IVF, Stem Cells, and the Future of Kinship

by Sarah Franklin

Duke University Press, Durham, NC, 2013. 374 pp. $94.95, £62. ISBN 9780822354857. Paper, $26.95, £17.99. ISBN 9780822354994. Experimental Futures: Technological Lives, Scientific Arts, Anthropological Voices.
Authors: Thompson Charis
Published: April 2014

Franklin explores how the development of in vitro fertilization into a routine procedure has changed our understanding of technology and biology.
A Two-Catalyst Photochemistry Route to Homochiral Rings
Authors: Neier Reinhard
Published: April 2014

A synthetic route photoactivates one reactant and then controls stereochemistry of subsequent steps to form a single isomer of a four-membered ring.

[Also see Report by

Du
et al.

]
Being Selective in the
Prochlorococcus
Collective
Authors: Bowler Chris , Scanlan David J.
Published: April 2014

Single-cell sequencing reveals the microdiversity of the most abundant photosynthetic organism on Earth.

[Also see Report by

Kashtan
et al.

]
Addressing Vaccine Hesitancy
Authors: Bloom Barry R. , Marcuse Edgar , Mnookin Seth
Published: April 2014

Last month, the World Health Organization certified India and Southeast Asia as being polio-free, an extraordinary achievement given that the polio vaccine was declared safe and effective only 59 years ago. Vaccines are one of the safest and most cost-effective medical interventions in history. By immunizing infants, children, and teenagers, vaccines protect the entire community. Nevertheless, there is a surge of outbreaks in vaccine-preventable diseases in the United States. What research is needed to reverse this trend?
Suppression of p21Rac Signaling and Increased Innate Immunity Mediate Remission in Crohn’s Disease
Authors: Parikh Kaushal , Zhou Lu , Somasundaram Rajesh , Fuhler Gwenny M. , Deuring J. Jasper , Blokzijl Tjasso , Regeling Anouk , Kuipers Ernst J. , Weersma Rinse K. , Nuij Veerle J. , Alves Maria , Vogelaar Lauran , Visser Lydia , de Haar Colin , Krishnadath Kausilia K. , van der Woude C. Janneke , Dijkstra Gerard , Faber Klaas Nico , Peppelenbosch Maikel P.
Published: April 2014

Overactivation of p21Rac1 is a rate-limiting step for innate immune function in Crohn’s disease and prevents remission.
Close-Field Electroporation Gene Delivery Using the Cochlear Implant Electrode Array Enhances the Bionic Ear
Authors: Pinyon Jeremy L. , Tadros Sherif F. , Froud Kristina E. , Y. Wong Ann C. , Tompson Isabella T. , Crawford Edward N. , Ko Myungseo , Morris Renée , Klugmann Matthias , Housley Gary D.
Published: April 2014

Neurotrophin gene delivery, achieved by “close-field” electroporation of mesenchymal cells adjacent to the cochlear implant, improved hearing in deafened guinea pigs.
Gene Therapy Boosts the Bionic Ear
Authors: Shepherd Robert K. , Wise Andrew K.
Published: April 2014

Close-field electroporation gene delivery using the cochlear implant electrode array enhances the bionic ear (Pinyon
et al
., this issue).
A Chink in Glioblastoma’s Armor
Authors: Lathia Justin D.
Published: April 2014

Inducing vacuole formation with a quinolone alcohol–based drug stimulates cell death in glioblastoma cells.
Avidity of Antibodies against Infecting Pneumococcal Serotypes Increases with Age and Severity of Disease
Authors: Cremers Amelieke J. H. , Lut Jonneke , Hermans Peter W. M. , Meis Jacques F. , de Jonge Marien I. , Ferwerda Gerben
Published: April 2014

The incidence of invasive pneumococcal disease (IPD) rises with age. Among adult IPD patients, the avidity of antipneumococcal polysaccharide antibodies against the infecting serotype increased with age and severity of disease, indicating that susceptibility to IPD in the elderly may rather be due to flaws in other aspects of opsonophagocytosis.
Prevalence and Duration of Asymptomatic Clostridium difficile Carriage among Healthy Subjects in Pittsburgh, Pennsylvania
Authors: Galdys Alison L. , Nelson Jemma S. , Shutt Kathleen A. , Schlackman Jessica L. , Pakstis Diana L. , Pasculle A. William , Marsh Jane W. , Harrison Lee H. , Curry Scott R.
Published: April 2014

Previous studies suggested that 7 to 15% of healthy adults are colonized with toxigenic
Clostridium difficile
. To investigate the epidemiology, genetic diversity, and duration of
C. difficile
colonization in asymptomatic persons, we recruited healthy adults from the general population in Allegheny County, Pennsylvania. Participants provided epidemiological and dietary intake data and submitted stool specimens. The presence of
C. difficile
in stool specimens was determined by anaerobic culture. Stool specimens yielding
C. difficile
underwent nucleic acid testing of the
tcdA
gene segment with a commercial assay;
tcdC
genotyping was performed on
C. difficile
isolates. Subjects positive for
C. difficile
by toxigenic anaerobic culture were asked to submit additional specimens. One hundred six (81%) of 130 subjects submitted specimens, and 7 (6.6%) of those subjects were colonized with
C. difficile
. Seven distinct
tcdC
genotypes were observed among the 7
C. difficile
-colonized individuals, including
tcdC
genotype 20, which has been found in uncooked ground pork in this region. Two (33%) out of 6
C. difficile
-colonized subjects who submitted additional specimens tested positive for identical
C. difficile
strains on successive occasions, 1 month apart. The prevalence of
C. difficile
carriage in this healthy cohort is concordant with prior estimates.
C. difficile
-colonized individuals may be important reservoirs for
C. difficile
and may falsely test positive for infections due to
C. difficile
when evaluated for community-acquired diarrhea caused by other enteric pathogens.
Bacterial Whole-Genome Sequencing Revisited: Portable, Scalable, and Standardized Analysis for Typing and Detection of Virulence and Antibiotic Resistance Genes
Authors: Leopold Shana R. , Goering Richard V. , Witten Anika , Harmsen Dag , Mellmann Alexander
Published: April 2014

Multidrug-resistant nosocomial pathogens present a major burden for hospitals. Rapid cluster identification and pathogen profiling, i.e., of antibiotic resistance and virulence genes, are crucial for effective infection control. Methicillin-resistant
Staphylococcus aureus
(MRSA), in particular, is now one of the leading causes of nosocomial infections. In this study, whole-genome sequencing (WGS) was applied retrospectively to an unusual spike in MRSA cases in two intensive care units (ICUs) over the course of 4 weeks. While the epidemiological investigation concluded that there were two separate clusters, each associated with one ICU,
S. aureus
protein A gene (
spa
) typing data suggested that they belonged to single clonal cluster (all cases shared
spa
type t001). Standardized gene sets were used to extract an allele-based profile for typing and an antibiotic resistance and toxin gene profile. The WGS results produced high-resolution allelic profiles, which were used to discriminate the MRSA clusters, corroborating the epidemiological investigation and identifying previously unsuspected transmission events. The antibiotic resistance profile was in agreement with the original clinical laboratory susceptibility profile, and the toxin profile provided additional, previously unknown information. WGS coupled with allelic profiling provided a high-resolution method that can be implemented as regular screening for effective infection control.
Isolation and Identification of an Enterobacter cloacae Strain Producing a Novel Subtype of Shiga Toxin Type 1
Authors: Probert William S. , McQuaid Cassandra , Schrader Kimmi
Published: April 2014

We describe here the isolation and identification of a Shiga toxin 1 (Stx1)-producing
Enterobacter cloacae
strain, M12X01451, from a human clinical specimen. The bacterial isolate was identified as
E. cloacae
using a polyphasic approach that included phenotypic, genetic, and proteomic analyses. The M12X01451
stx
1
was sequenced, and the holotoxin was found to share only 87% amino acid sequence identity with the nearest Stx1 subtype reference sequence. Sequence analysis of the regions immediately flanking
stx
1
displayed similarities with bacteriophage-related sequences, suggesting a prophage origin. The
stx
1
gene was a stable element within the M12X01451 genome, as demonstrated by real-time PCR detection following successive subculturing of the bacterial isolate. Culture supernatant from M12X01451 was cytotoxic to Vero cells but was not neutralized by an anti-Stx1 monoclonal antibody. In addition, Stx1 from M12X01451 demonstrated limited antigenicity with two commercially available lateral flow immunoassays. The M12X01451 Stx represents a new Stx1 subtype based on the degree of sequence dissimilarity with Stx1 subtype reference sequences and its limited reactivity with anti-Stx1 antibodies.
Usefulness of Pneumotest-Latex for Direct Serotyping of Streptococcus pneumoniae Isolates in Clinical Samples
Authors: Kuch Alicja , Gołȩbiewska Agnieszka , Waśko Izabela , Ronkiewicz Patrycja , Markowska Marlena , Hryniewicz Waleria , Skoczyńska Anna
Published: April 2014

This study evaluated the usefulness of the Pneumotest-Latex assay for serotyping
Streptococcus pneumoniae
isolates directly in clinical samples. With an agreement of 88.1% with a PCR-based reference method, this test can be a useful tool for this study purpose, especially in clinical laboratories that do not have access to nucleic acid amplification technologies.
Cross-Infection of Solid Organ Transplant Recipients by a Multidrug-Resistant Klebsiella pneumoniae Isolate Producing the OXA-48 Carbapenemase, Likely Derived from a Multiorgan Donor
Authors: Giani Tommaso , Conte Viola , Mandalà Salvatore , D'Andrea Marco Maria , Luzzaro Francesco , Conaldi Pier Giulio , Grossi Paolo , Rossolini Gian Maria
Published: April 2014

We describe two cases of bacteremic infections caused by a multidrug-resistant
Klebsiella pneumoniae
isolate producing the OXA-48 carbapenemase that occurred in two solid organ transplant (liver and kidney) recipients, which was apparently transmitted with the allografts. This finding underscores the risk of donor-derived infections by multidrug-resistant Gram-negative pathogens in solid organ transplant recipients and emphasizes the need for rapid screening of organ donors for carriage of similar pathogens.
Molecular Epidemiology and Identification of a Staphylococcus aureus Clone Causing Food Poisoning Outbreaks in Japan
Authors: Sato'o Yusuke , Omoe Katsuhiko , Naito Ikunori , Ono Hisaya K. , Nakane Akio , Sugai Motoyuki , Yamagishi Norio , Hu Dong-Liang
Published: April 2014

Molecular characterization of isolates from staphylococcal food poisoning (SFP) outbreaks in Japan showed that the dominant lineage causing SFP outbreaks is clonal complex 81 (CC81), a single-locus variant of sequence type 1, coagulase type VII, positive for
sea
and/or
seb
, and positive for
seh
. Among various CC lineages producing staphylococcal enterotoxin A, CC81 showed the highest toxin productivity.
Novel Selective Medium for Isolation of Staphylococcus lugdunensis from Wound Specimens
Authors: Ho Pak-Leung , Leung Sammy Man-Him , Tse Herman , Chow Kin-Hung , Cheng Vincent Chi-Chung , Que Tak-Lun
Published: April 2014

We compared a novel selective
Staphylococcus lugdunensis
(SSL) medium with routine media (blood and chocolate agars) for the detection of
S. lugdunensis
in 990 clinical specimens (from tissue, pus, or wound swabs). Significantly more
S. lugdunensis
isolates were detected on SSL medium (34/990) than on routine medium (7/990) (
P
= 0.001, McNemar's test).
Pediatric Multicenter Evaluation of the Verigene Gram-Negative Blood Culture Test for Rapid Detection of Inpatient Bacteremia Involving Gram-Negative Organisms, Extended-Spectrum Beta-Lactamases, and Carbapenemases
Authors: Sullivan K. V. , Deburger B. , Roundtree S. S. , Ventrola C. A. , Blecker-Shelly D. L. , Mortensen J. E.
Published: April 2014

We evaluated the investigational use only (IUO) version of the rapid Verigene Gram-negative blood culture test (BC-GN), a microarray that detects 9 genus/species targets (
Acinetobacter
spp.,
Citrobacter
spp.,
Enterobacter
spp.,
Escherichia coli
/
Shigella
spp.,
Klebsiella oxytoca
,
Klebsiella pneumoniae
,
Proteus
spp.,
Pseudomonas aeruginosa
, and
Serratia marcescens
) and 6 antimicrobial resistance determinants (
bla
CTX-M
,
bla
KPC
,
bla
NDM
,
bla
VIM
,
bla
IMP
, and
bla
OXA
) directly from positive blood cultures. BC-GN was performed on positive BacT/Alert Pediatric FAN and Bactec Peds Plus blood cultures with Gram-negative organisms at two tertiary pediatric centers. Vitek MS (bioMérieux, Durham, NC) was used to assign gold standard organism identification. The Check MDR CT-102 microarray (Check Points B.V., Wageningen, Netherlands) was used as an alternative method for detecting resistance determinants. In total, 104 organisms were isolated from 97 clinical blood cultures. BC-GN correctly detected 26/26 cultures with
Acinetobacter
spp.,
P. aeruginosa
, and
S. marcescens
, 5/6 with
Citrobacter
spp., 13/14 with
Enterobacter
spp., 23/24 with
E. coli
, 2/3 with
K. oxytoca
, 16/17 with
K. pneumoniae
, and 0/1 with
Proteus
spp. BC-GN appropriately reported negative BC-GN results in 8/13 blood cultures that grew organisms that were not represented on the microarray but failed to detect targets in 3/5 cultures that grew multiple Gram-negative organisms. BC-GN detected 5/5 and 1/1 clinical blood cultures with
bla
CTX-M
and
bla
VIM
. All 6 results were corroborated by Check MDR CT-102 microarray testing. The Verigene BC-GN test has the potential to expedite therapeutic decision making in pediatric patients with Gram-negative bacteremia. Sensitivity was satisfactory but may be suboptimal in mixed Gram-negative blood cultures.
Residue 41 of the Eurasian Avian-Like Swine Influenza A Virus Matrix Protein Modulates Virion Filament Length and Efficiency of Contact Transmission
Authors: Campbell Patricia J. , Kyriakis Constantinos S. , Marshall Nicolle , Suppiah Suganthi , Seladi-Schulman Jill , Danzy Shamika , Lowen Anice C. , Steel John
Published: April 2014

Position 41 of the influenza A virus matrix protein encodes a highly conserved alanine in human and avian lineages. Nonetheless, strains of the Eurasian avian-like swine (Easw) lineage contain a change at this position: position 41 of A/swine/Spain/53207/04 (H1N1) (SPN04) encodes a proline. To assess the impact of this naturally occurring polymorphism on viral fitness, we utilized reverse genetics to produce recombinant viruses encoding wild-type M1 41P (rSPN04-P) and consensus 41A (rSPN04-A) residues. Relative to rSPN04-A, rSPN04-P virus displayed reduced growth
in vitro
. In the guinea pig model, rSPN04-P was transmitted to fewer contact animals than rSPN04-A and failed to infect guinea pigs that received a low-dose inoculum. Moreover, the P41A change altered virion morphology, reducing the number and length of filamentous virions, as well as reducing the neuraminidase activity of virions. The lab-adapted human isolate, A/PR/8/34 (H1N1) (PR8), is nontransmissible in the guinea pig model, making it a useful background in which to identify certain viral factors that enhance transmissibility. We assessed transmission in the context of single-, double-, and triple-reassortant viruses between PR8 and SPN04; PR8/SPN04 M, PR8/SPN04 M+NA, and PR8/SPN04 M+NA+HA, encoding either matrix 41 A or P, were generated. In each case, the virus possessing 41P transmitted less well than the corresponding 41A-encoding virus. In summary, we have identified a naturally occurring mutation in the influenza A virus matrix protein that impacts transmission efficiency and can alter virion morphology and neuraminidase activity.

IMPORTANCE
We have developed a practical model for examining the genetics underlying transmissibility of the Eurasian avian-like swine lineage viruses, which contributed M and NA segments to the 2009 pandemic strain. Here, we use our system to investigate the impact on viral fitness of a naturally occurring polymorphism at matrix (M1) position 41 in an Easw isolate. Position 41 has been implicated previously in adaptation to laboratory substrates and to mice. Here we show that the polymorphism at M1 41 has a limited effect on growth
in vitro
but changes the morphology of the virus and impacts growth and transmission in the guinea pig model.
Protective Properties of Vaccinia Virus-Based Vaccines: Skin Scarification Promotes a Nonspecific Immune Response That Protects against Orthopoxvirus Disease
Authors: Rice Amanda D. , Adams Mathew M. , Lindsey Scott F. , Swetnam Daniele M. , Manning Brandi R. , Smith Andrew J. , Burrage Andrew M. , Wallace Greg , MacNeill Amy L. , Moyer Richard W.
Published: April 2014

The process of vaccination introduced by Jenner generated immunity against smallpox and ultimately led to the eradication of the disease. Procedurally, in modern times, the virus is introduced into patients via a process called scarification, performed with a bifurcated needle containing a small amount of virus. What was unappreciated was the role that scarification itself plays in generating protective immunity. In rabbits, protection from lethal disease is induced by intradermal injection of vaccinia virus, whereas a protective response occurs within the first 2 min after scarification with or without virus, suggesting that the scarification process itself is a major contributor to immunoprotection.

IMPORTANCE
These results show the importance of local nonspecific immunity in controlling poxvirus infections and indicate that the process of scarification should be critically considered during the development of vaccination protocols for other infectious agents.
Tumor Suppressor Cylindromatosis (CYLD) Controls HIV Transcription in an NF-κB-Dependent Manner
Authors: Manganaro Lara , Pache Lars , Herrmann Tobias , Marlett John , Hwang Young , Murry Jeffrey , Miorin Lisa , Ting Adrian T. , König Renate , García-Sastre Adolfo , Bushman Frederic D. , Chanda Sumit K. , Young John A. T. , Fernandez-Sesma Ana , Simon Viviana
Published: April 2014

Characterizing the cellular factors that play a role in the HIV replication cycle is fundamental to fully understanding mechanisms of viral replication and pathogenesis. Whole-genome small interfering RNA (siRNA) screens have identified positive and negative regulators of HIV replication, providing starting points for investigating new cellular factors. We report here that silencing of the deubiquitinase cylindromatosis protein (CYLD), increases HIV infection by enhancing HIV long terminal repeat (LTR)-driven transcription via the NF-κB pathway. CYLD is highly expressed in CD4
+
T lymphocytes, monocyte-derived macrophages, and dendritic cells. We found that CYLD silencing increases HIV replication in T cell lines. We confirmed the positive role of CYLD silencing in HIV infection in primary human CD4
+
T cells, in which CYLD protein was partially processed upon activation. Lastly, Jurkat T cells latently infected with HIV (JLat cells) were more responsive to phorbol 12-myristate 13-acetate (PMA) reactivation in the absence of CYLD, indicating that CYLD activity could play a role in HIV reactivation from latency. In summary, we show that CYLD acts as a potent negative regulator of HIV mRNA expression by specifically inhibiting NF-κB-driven transcription. These findings suggest a function for this protein in modulating productive viral replication as well as in viral reactivation.

IMPORTANCE
HIV transcription is regulated by a number of host cell factors. Here we report that silencing of the lysine 63 deubiquitinase CYLD increases HIV transcription in an NF-κB-dependent manner. We show that CYLD is expressed in HIV target cells and that its silencing increases HIV infection in transformed T cell lines as well as primary CD4
+
T cells. Similarly, reactivation of latent provirus was facilitated in the absence of CYLD. These data suggest that CYLD, which is highly expressed in CD4
+
T cells, can control HIV transcription in productive infection as well as during reactivation from latency.
Mutations in HIV-1 Reverse Transcriptase Affect the Errors Made in a Single Cycle of Viral Replication
Authors: Abram Michael E. , Ferris Andrea L. , Das Kalyan , Quinoñes Octavio , Shao Wei , Tuske Steven , Alvord W. Gregory , Arnold Eddy , Hughes Stephen H.
Published: April 2014

The genetic variation in HIV-1 in patients is due to the high rate of viral replication, the high viral load, and the errors made during viral replication. Some of the mutations in reverse transcriptase (RT) that alter the deoxynucleoside triphosphate (dNTP)-binding pocket, including those that confer resistance to nucleoside/nucleotide analogs, affect dNTP selection during replication. The effects of mutations in RT on the spectrum (nature, position, and frequency) of errors made
in vivo
are poorly understood. We previously determined the mutation rate and the frequency of different types of mutations and identified hot spots for mutations in a
lacZ
α (the α complementing region of
lacZ
) reporter gene carried by an HIV-1 vector that replicates using wild-type RT. We show here that four mutations (Y115F, M184V, M184I, and Q151M) in the dNTP-binding pocket of RT that had relatively small effects on the overall HIV-1 mutation rate (less than 3-fold compared to the wild type) significantly increased mutations at some specific positions in the
lacZ
α reporter gene. We also show that changes in a sequence that flanks the reporter gene can affect the mutations that arise in the reporter. These data show that changes either in HIV-1 RT or in the sequence of the nucleic acid template can affect the spectrum of mutations made during viral replication. This could, by implication, affect the generation of drug-resistant mutants and immunological-escape mutants in patients.

IMPORTANCE
RT is the viral enzyme that converts the RNA genome of HIV into DNA. Errors made during replication allow the virus to escape from the host's immune system and to develop resistance to the available anti-HIV drugs. We show that four different mutations in RT which are known to be associated with resistance to anti-RT drugs modestly increased the overall frequency of errors made during viral replication. However, the increased errors were not uniformly distributed; the additional errors occurred at a small number of positions (hot spots). Moreover, some of the RT mutations preferentially affected the nature of the errors that were made (some RT mutations caused an increase in insertion and deletion errors; others caused an increase in substitution errors). We also show that sequence changes in a region adjacent to a target gene can affect the errors made within the target gene.
Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling
Authors: Kuuranne Tiia , Saugy Martial , Baume Norbert
Published: April 2014

In the fight against doping, steroid profiling is a powerful tool to detect drug misuse with endogenous anabolic androgenic steroids. To establish sensitive and reliable models, the factors influencing profiling should be recognised. We performed an extensive literature review of the multiple factors that could influence the quantitative levels and ratios of endogenous steroids in urine matrix. For a comprehensive and scientific evaluation of the urinary steroid profile, it is necessary to define the target analytes as well as testosterone metabolism. The two main confounding factors, that is, endogenous and exogenous factors, are detailed to show the complex process of quantifying the steroid profile within WADA-accredited laboratories. Technical aspects are also discussed as they could have a significant impact on the steroid profile, and thus the steroid module of the athlete biological passport (ABP). The different factors impacting the major components of the steroid profile must be understood to ensure scientifically sound interpretation through the Bayesian model of the ABP. Not only should the statistical data be considered but also the experts in the field must be consulted for successful implementation of the steroidal module.
Blood doping: potential of blood and urine sampling to detect autologous transfusion
Authors: Segura J , Lundby C
Published: April 2014

The collection of blood, its storage as red blood cell (RBC) concentrates and its reinjection is prohibited; until now, the practice cannot be reliably detected. A recent innovation—the haematological module of the athlete's biological passport—can provide authorities with indications towards autologous blood transfusion. In situations where a given athlete has been exposed to altitude, heat stress, sickness, etc, additional evidence may be needed to establish beyond any reasonable doubt that a blood transfusion may actually have occurred. Additional evidence may be obtained from at least three different approaches using parameters related to blood and urine matrices.Genomics applied to mRNA or miRNA is one of the most promising analytical tools. Proteomics of changes associated with RBC membranes may reveal the presence of cells stored for some time, as can an abnormal pattern of size distribution of aged cells. In urine, high concentrations of metabolites of plasticisers originating from the blood storing bags strongly suggest a recent blood transfusion. We emphasise the usefulness of simultaneously obtaining and then analysing blood and urine for complementary evidence of autologous blood transfusion (‘blood doping’).
Bee venom acupuncture for rheumatoid arthritis: a systematic review protocol
Authors: Lee Ju Ah , Son Mi Ju , Choi Jiae , Yun Kyung-Jin , Jun Ji Hee , Lee Myeong Soo
Published: April 2014

Introduction

This systematic review aims to analyse the trial data on the effects of bee venom acupuncture (BVA) for rheumatoid arthritis (RA).

Methods and analysis

The following 14 databases will be searched from their inception to March 2014: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), AMED, CINAHL, six Korean medical databases (OASIS, Korean Traditional Knowledge Portal, Korean Studies Information Service System, KoreaMed, Korean Medical Database and DBPIA) and three Chinese databases including CNKI (China National Knowledge Infrastructure), Wanfang and VIP. The methodological quality will be assessed using the Cochrane risk of bias tool.

Dissemination

The systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically and in print.

Trial registration number

PROSPERO 2013: CRD42013005853
Factors associated with anxiety and depression among type 2 diabetes outpatients in Malaysia: a descriptive cross-sectional single-centre study
Authors: Ganasegeran Kurubaran , Renganathan Pukunan , Manaf Rizal Abdul , Al-Dubai Sami Abdo Radman
Published: April 2014

Objective

To determine the prevalence and factors associated with anxiety and depression among type 2 diabetes outpatients in Malaysia.

Design

Descriptive, cross-sectional single-centre study with universal sampling of all patients with type 2 diabetes.

Setting

Endocrinology clinic of medical outpatient department in a Malaysian public hospital.

Participants

All 169 patients with type 2 diabetes (men, n=99; women, n=70) aged between 18 and 90 years who acquired follow-up treatment from the endocrinology clinic in the month of September 2013.

Main outcome measures

The validated Hospital Anxiety and Depression Scale (HADS), sociodemographic characteristics and clinical health information from patient records.

Results

Of the total 169 patients surveyed, anxiety and depression were found in 53 (31.4%) and 68 (40.3%), respectively. In multivariate analysis, age, ethnicity and ischaemic heart disease were significantly associated with anxiety, while age, ethnicity and monthly household income were significantly associated with depression.

Conclusions

Sociodemographics and clinical health factors were important correlates of anxiety and depression among patients with diabetes. Integrated psychological and medical care to boost self-determination and confidence in the management of diabetes would catalyse optimal health outcomes among patients with diabetes.
Association between dietary intakes of PCBs and the risk of obesity: the SUN project
Authors: Donat-Vargas C , Gea A , Sayon-Orea C , Carlos S , Martinez-Gonzalez M A , Bes-Rastrollo M
Published: April 2014

Background

Polychlorinated biphenyls (PCB) are persistent organic pollutants (POP) that are consumed because of their bioaccumulation through the food chain. Recent studies have suggested the implication of POPs in the development of metabolic diseases such as type 2 diabetes and obesity. However, this relationship is not entirely consistent, and has not been investigated in longitudinal studies. The purpose of this study was to prospectively examine the association between dietary intake of PCBs and the incidence of obesity in the Seguimiento Universidad de Navarra (SUN) Project.

Methods

Our study included 12 313 participants without obesity at baseline, who were followed-up for a median of 8.1 years. Dietary intakes of PCBs, expressed as WHO toxic equivalents, were assessed at baseline through a 136-item semiquantitative food-frequency questionnaire. The published concentration levels of PCBs measured in samples of food consumed in Spain were used to estimate intakes. Multivariable Cox regression models were fitted to estimate HRs and 95% CI for incident obesity.

Results

During follow-up, we observed 621 incident cases of obesity. After adjustment for total energy intake and additional adjustment for potential confounders, participants in the fifth quintile of PCBs intake were at higher risk of becoming obese (adjusted HR: 1.58; (95% CI 1.21 to 2.06)) compared to those in the first quintile. The linear trend test was statistically significant (p<0.001).

Conclusions

Dietary intake of PCBs as estimated using a food frequency questionnaire was associated with a higher incidence of obesity. Nevertheless, further longitudinal studies are needed to confirm our results.
A proposed model for community-assisted alcohol withdrawal in primary care in the UK Armed Forces
Authors: Faerestrand Nicholas H , Coetzee R H
Published: April 2014

Alcohol misuse and related morbidity continues to represent a challenge to the both the National Health Service (NHS) and the Defence Medical Services (DMS). A significant part of the management of patients who misuse alcohol involves planned assisted withdrawal for dependent drinkers. Traditionally, assisted alcohol withdrawal has been conducted in an in-patient setting owing to the perceived risks of carrying out this treatment. Current evidence shows that community-based approaches offer a safe and effective alternative to the traditional in-patient model with significant cost savings. This article proposes a model for community-assisted alcohol withdrawal (CAAW) for use within the DMS. It considers current guidelines and models already in operation within the NHS, offering evaluation and adjustments to fit the requirements that are applicable to the UK Armed Forces medical environment.
Targeting angiogenic pathway for chemoprevention of experimental colon cancer using C-phycocyanin as cyclooxygenase-2 inhibitor
Authors: Saini Manpreet Kaur , Sanyal Sankar Nath
Published: April 2014

An angiogenic pathway was studied that involved stromal tissue degradation with matrix metalloproteinases (MMPs), vesicular endothelial growth factor-A (VEGF-A), and hypoxia inducible factor-1α (HIF-1α) mediated growth regulation in a complex interaction with chemokines, such as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β). Gene and protein expression was studied with real-time PCR, Western immunoblot, and immunofluorescence. Morphological and histopathological analysis of tumor was done, as also the activity of MMPs and HIF-1α by gelatin zymography and ELISA. Binding interactions of proteins were studied by molecular docking. Piroxicam, a traditional NSAID and C-phycocyanin, a biliprotein from Spirulina platensis, were utilized in the chemoprevention of DMH-induced rat colon cancer. A significant number of tumors was evident in DMH treated animals, while with piroxicam and C-phycocyanin, the number and size of tumors/lesions were reduced. Colonic tissues showed severe dysplasia, tubular adenoma, and adenocarcinoma from DMH, with invasive features along with signet ring cell carcinoma. No occurrence of carcinoma was detected in either of the drug treatments or in a combination regimen. An elevated VEGF-A, MMP-2, and MMP-9 level was observed, which is required for metastasis and invasion into surrounding tissues. Drugs induced chemoprevention by down-regulating these proteins. Piroxicam docked in VEGF-A binding site of VEGF-A receptors i.e., VEGFR1 and VEGFR2, while phycocyanobilin (a chromophore of C-phycocyanin) docked with VEGFR1 alone. HIF-1α is up-regulated which is associated with increased oxygen demand and angiogenesis. MCP-1 and MIP-1β expression was also found altered in DMH and regulated by the drugs. Anti-angiogenic role of piroxicam and C-phycocyanin is well demonstrated.
Can behavioral fish-guidance devices protect juvenile Chinook salmon (Oncorhynchus tshawytscha) from entrainment into unscreened water-diversion pipes?
Authors: Mussen Timothy D. , Patton Oliver , Cocherell Dennis , Ercan Ali , Bandeh Hossein , Kavvas M. Levent , Cech Joseph J. , Fangue Nann A.
Published: April 2014

Entrainment through water-diversion structures is a major passage challenge for fishes in watersheds worldwide. Behavioral guidance devices may be effective in passing fish by diversion inlets, thereby decreasing entrainment without reducing water-diversion rates, but data on their effectiveness is limited. In California’s central valley, out-migrating Chinook salmon (Oncorhynchus tshawytscha) are a species at risk for entrainment through unscreened, small-scale water-diversion pipes. Therefore, we tested entrainment susceptibility and behavior of juvenile Chinook salmon in a large-river-simulation flume at a “river” velocity of 0.15 m·s–1 with a 0.46 m diameter pipe diverting water at 0.57 m3·s–1, during the day and night. Compared with control conditions (no fish deterrent devices present), mean fish entrainment increased by 61% (day) and 43% (night) when underwater strobe lights were active, decreased by 30% when using a metal vibrating (12 Hz) ring during the night, and was unaffected by velocity cap attachments. Fish entrainments started at water velocities of 0.8 m·s–1 and decreased by 54% from spring to summer, possibly resulting from decreased pipe-passage frequency and smaller fish-school sizes. Our findings suggest that substantial entrainment can occur if fish repeatedly pass within 1.5 m of active unscreened diversions, with an estimated 50% of fish lost after encountering 18 pipes in spring and 50 pipes in summer.
How do difference bodies in complex vector spaces look like? A geometrical approach
Authors: Abardia Judit , Saorín Gómez Eugenia
Published: April 2014

We investigate geometrical properties and inequalities satisfied by the complex difference body, in the sense of studying which of the classical ones for the difference body have an analog in the complex framework. Among others we give an equivalent expression for the support function of the complex difference body and prove that, unlike the classical case, the dimension of the complex difference body depends on the position of the body with respect to the complex structure of the vector space. We use spherical harmonics to characterize the bodies for which the complex difference body is a ball, we prove that it is a polytope if and only if the two bodies involved in the construction are polytopes and provide several inequalities for classical magnitudes of the complex difference body, as volume, quermassintegrals and diameter, in terms of the corresponding ones for the involved bodies.
Quantum limits to estimation of photon deformation
Authors: De Cillis Giovanni , Paris Matteo G. A.
Published: April 2014

We address potential deviations of radiation field from the bosonic behavior and employ local quantum estimation theory to evaluate the ultimate bounds to precision in the estimation of these deviations using quantum-limited measurements on optical signals. We consider different classes of boson deformations and found that intensity measurement on coherent or thermal states would be suitable for their detection making, at least in principle, tests of boson deformation feasible with current quantum optical technology. On the other hand, we found that the quantum signal-to-noise ratio (QSNR) is vanishing with the deformation itself for all the considered classes of deformations and probe signals, thus making any estimation procedure of photon deformation inherently inefficient. A partial way out is provided by the polynomial dependence of the QSNR on the average number of photons, which suggests that, in principle, it would be possible to detect deformation by intensity measurements on high-energy thermal states.
A STUDY ON MECHANICAL BEHAVIOR OF FUNCTIONALLY-GRADED CARBON NANOTUBE-REINFORCED NANOCOMPOSITES
Authors: BAFEKRPOUR EHSAN , YANG CHUNHUI , SIMON GEORGE P. , ABVABI AKBAR , KHOSHMANESH KHASHAYAR , FOX BRONWYN L.
Published: April 2014

In this study, we are focusing on the investigation of the effects of gradient patterns on mechanical behavior of functionally-graded carbon nanotube-reinforced nanocomposites and considering typical beams made of such nanocomposites. Both analytic and finite element-based numerical models were developed. Analytic model was developed based on the first-order shear deformation and Timoshenko beam theories meanwhile finite element models were developed using Abaqus in conjunction with user-defined subroutines for defining the continuously gradient material properties for different gradient patterns. Position-dependent elastic modulus equations for four continuously graded patterns were studied. A nongraded pattern was used for benchmarking with the same geometry and total carbon nanotube (CNT) contents. For validation and verification, the results on both deflection and stress of these nanocomposite beams were analyzed, which clearly showed high influence from gradient patterns on these mechanical behaviors of such beams.
NUMERICAL INVESTIGATION OF MECHANICAL AND THERMAL DYNAMIC PROPERTIES OF THE INDUSTRIAL TRANSFORMER
Authors: LIU HUA-SHU , MA LIN , GU YUAN-TONG , NIELSEN SHAWN
Published: April 2014

Industrial transformer is one of the most critical assets in the power and heavy industry. Failures of transformers can cause enormous losses. The poor joints of the electrical circuit on transformers can cause overheating and results in stress concentration on the structure which is the major cause of catastrophic failure. Few researches have been focused on the mechanical properties of industrial transformers under overheating thermal conditions. In this paper, both mechanical and thermal properties of industrial transformers are jointly investigated using finite element analysis (FEA). Dynamic response analysis is conducted on a modified transformer FEA model, and the computational results are compared with experimental results from literature to validate this simulation model. Based on the FEA model, thermal stress is calculated under different temperature conditions. These analysis results can provide insights to the understanding of the failure of transformers due to overheating, therefore are significant to assess winding fault, especially to the manufacturing and maintenance of large transformers.
EXPRESSION OF VP2 PROTEIN OF RAT MINUTE VIRUS TYPE 1 (RMV-1) IN RECOMBINANT BACULOVIRUS AND ITS APPLICATION TO DIAGNOSIS OF RMV-1 INFECTION
Authors: Wan Cho-Hua , Pintel David J. , Riley Lela K.
Published: April 2014

Rat minute virus type 1 (RMV-1) was identified in laboratory rats. In this study, an ELISA using a recombinant capsid protein (rVP2) of RMV-1 was developed to diagnose RMV infections. The developed RMV-1 rVP2 ELISA exhibited a sensitivity of 97.5% and a specificity of 100%, and was more sensitive and specific in detecting RMV-1 infection than the ELISA using a recombinant minute virus of mice non-structural protein as antigen.
ADAPTIVE INCREMENTAL FINITE ELEMENT PROCEDURE FOR SOLVING ELASTOPLASTIC FRICTIONAL CONTACT PROBLEMS SUBJECTED TO NORMAL AND TANGENTIAL LOADS
Authors: ABDALLA W. S. , ALI-ELDIN S. S. , GHAZY M. R.
Published: April 2014

This paper presents a numerical model for analyzing the stresses and displacements of deformable bodies in contact with the presence of friction and material nonlinearity. Based on the finite element method (FEM), the elastoplastic frictional contact problem is formulated as an incremental convex programming model (ICPM) under inequality contact constraints and friction conditions. The classical Coulomb's friction law and the Prandtl–Reuss flow rule with the von Mises yield criterion are used to simulate the interface friction conditions and the elastoplastic behavior of the contacting bodies, respectively. The Lagrange multiplier approach is adopted for imposing the contact constraints. Furthermore, an effective adaptive incremental procedure is developed for solving the elastoplastic frictional contact problems. Examples for the frictional contact having advancing and receding nature are analyzed. The obtained results prove the ability of the developed procedure to investigate the sequence of different events during monotonic application of external loads. In addition, the results elucidate the effect of external side force on the friction behavior in the presence of plastic deformation. Good agreement has been found with published results.
Global stability of an epidemic model for HIV–TB co-infection with infection-age
Authors: Wang Xiao-Yan , Bai Yan-Ping , Yang Jun-Yuan , Zhang Feng-Qin
Published: April 2014

A nonlinear mathematical HIV–TB model with infection-age is proposed in this paper. The basic reproduction numbers according to HIV and TB are respectively determined whether one of the diseases dies out or persists. The local and global stability of the disease-free and dominated equilibria are discussed by employing integral semigroup theory and Lyapunov functionals. The persistence of the system is also obtained by the persistence theories of the systems. The simulation illustrates the theoretical results.
Lysophosphatidic acid stimulation of NHE3 exocytosis in polarized epithelial cells occurs with release from NHERF2 via ERK-PLC-PKCδ signaling
Authors: Cha Boyoung , Chen Tiane , Sarker Rafiquel , Yang Jianbo , Raben Daniel , Tse C. Ming , Kovbasnjuk Olga , Donowitz Mark
Published: April 2014

The Na+/H+ exchanger 3 (NHE3) is a brush border (BB) Na+/H+ antiporter that accounts for the majority of physiologic small intestinal and renal Na+ absorption. It is regulated physiologically and in disease via changes in endocytosis/exocytosis. Paradoxically, NHE3 is fixed to the microvillar (MV) actin cytoskeleton and has little basal mobility. This fixation requires NHE3 binding to the multi-PDZ domain scaffold proteins Na+/H+ exchanger regulatory factor (NHERF)1 and NHERF2 and to ezrin. Coordinated release of NHE3 from the MV cytoskeleton has been demonstrated during both stimulation and inhibition of NHE3. However, the signaling molecules involved in coordinating NHE3 trafficking and cytoskeletal association have not been identified. This question was addressed by studying lysophosphatidic acid (LPA) stimulation of NHE3 in polarized renal proximal tubule opossum kidney (OK) cells that occurs via apical LPA5 receptors and is NHERF2 dependent and mediated by epidermal growth factor receptor (EGFR), Rho/Rho-associated kinase (ROCK), and ERK. NHE3 activity was determined by BCECF/fluorometry and NHE3 microvillar mobility by FRAP/confocal microscopy using NHE3-EGFP. Apical LPA (3 μM)/LPA5R stimulated NHE3 activity, increased NHE3 mobility, and decreased the NHE3/NHERF2 association. The LPA stimulation of NHE3 was also PKCδ dependent. PKCδ was necessary for LPA stimulation of NHE3 mobility and NHE3/NHERF2 association. Moreover, the LPA-induced translocation to the membrane of PKCδ was both ERK and phospholipase C dependent with ERK acting upstream of PLC. We conclude that LPA stimulation of NHE3 exocytosis includes a signaling pathway that regulates fixation of NHE3 to the MV cytoskeleton. This involves a signaling module consisting of ERK-PLC-PKCδ, which dynamically and reversibly releases NHE3 from NHERF2 to contribute to the changes in NHE3 MV mobility.
Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements
Authors: Lakeland Thomas V. , Borg Melissa L. , Matzaris Maria , Abdelkader Amany , Evans Roger G. , Watt Matthew J.
Published: April 2014

Impaired coupling of adipose tissue expansion and vascularization is proposed to lead to adipocyte hypoxia and inflammation, which in turn contributes to systemic metabolic derangements. Pigment epithelium-derived factor (PEDF) is a powerful antiangiogenic factor that is secreted by adipocytes, elevated in obesity, and implicated in the development of insulin resistance. We explored the angiogenic and metabolic role of adipose-derived PEDF through in vivo studies of mice with overexpression of PEDF in adipocytes (PEDF-aP2). PEDF expression in white adipocytes and PEDF secretion from adipose tissue was increased in transgenic mice, but circulating levels of PEDF were not increased. Overexpression of PEDF did not alter vascularization, the partial pressure of O2, cellular hypoxia, or gene expression of inflammatory markers in adipose tissue. Energy expenditure and metabolic substrate utilization, body mass, and adiposity were not altered in PEDF-aP2 mice. Whole body glycemic control was normal as assessed by glucose and insulin tolerance tests, and adipocyte-specific glucose uptake was unaffected by PEDF overexpression. Adipocyte lipolysis was increased in PEDF-aP2 mice and associated with increased adipose triglyceride lipase and decreased perilipin 1 expression. Experiments conducted in mice rendered obese by high-fat feeding showed no differences between PEDF-aP2 and wild-type mice for body mass, adiposity, whole body energy expenditure, glucose tolerance, or adipose tissue oxygenation. Together, these data indicate that adipocyte-generated PEDF enhances lipolysis but question the role of PEDF as a major antiangiogenic or proinflammatory mediator in adipose tissue in vivo.