bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial Succession in the Broiler Gastrointestinal Tract
Authors: Ranjitkar Samir , Lawley Blair , Tannock Gerald , Engberg Ricarda M.
Published: February 2016

A feeding trial was performed with broilers receiving a diet of wheat-based feed (WBF), maize-based feed (MBF), or maize-based concentrates supplemented with 15% or 30% crimped kernel maize silage (CKMS-15 or CKMS-30, respectively). The aim of the study was to investigate the bacterial community compositions of the crop, gizzard, ileum, and cecum contents in relation to the feeding strategy and age (8, 15, 22, 25, 29, or 36 days). Among the four dietary treatments, bacterial diversity was analyzed for MBF and CKMS-30 by 454 pyrosequencing of the 16S rRNA gene. Since the diets had no significant influence on bacterial diversity, data were pooled for downstream analysis. With increasing age, a clear succession of bacterial communities and increased bacterial diversity were observed.
Lactobacillaceae
(belonging mainly to the genus
Lactobacillus
) represented most of the
Firmicutes
at all ages and in all segments of the gut except the cecum. The development of a “mature” microbiota in broilers occurred during the period from days 15 to 22. Striking increases in the relative abundances of
Lactobacillus salivarius
(17 to 36%) and clostridia (11 to 18%), and a concomitant decrease in the relative abundance of
Lactobacillus reuteri
, were found in the ileum after day 15. The concentration of deconjugated bile salts increased in association with the increased populations of
L. salivarius
and clostridia. Both
L. salivarius
and clostridia deconjugate bile acids, and increases in the abundances of these bacteria might be associated with growth reduction and gastrointestinal (GI) disorders occurring in the critical period of broiler life between days 20 and 30.
Alpha- and Gammaproteobacterial Methanotrophs Codominate the Active Methane-Oxidizing Communities in an Acidic Boreal Peat Bog
Authors: Esson Kaitlin C. , Lin Xueju , Kumaresan Deepak , Chanton Jeffrey P. , Murrell J. Colin , Kostka Joel E.
Published: February 2016

The objective of this study was to characterize metabolically active, aerobic methanotrophs in an ombrotrophic peatland in the Marcell Experimental Forest, in Minnesota. Methanotrophs were investigated in the field and in laboratory incubations using DNA-stable isotope probing (SIP), expression studies on particulate methane monooxygenase (
pmoA
) genes, and amplicon sequencing of 16S rRNA genes. Potential rates of oxidation ranged from 14 to 17 μmol of CH
4
g dry weight soil
−1
day
−1
. Within DNA-SIP incubations, the relative abundance of methanotrophs increased from 4%
in situ
to 25 to 36% after 8 to 14 days. Phylogenetic analysis of the
13
C-enriched DNA fractions revealed that the active methanotrophs were dominated by the genera
Methylocystis
(type II;
Alphaproteobacteria
),
Methylomonas
, and
Methylovulum
(both, type I;
Gammaproteobacteria
). In field samples, a transcript-to-gene ratio of 1 to 2 was observed for
pmoA
in surface peat layers, which attenuated rapidly with depth, indicating that the highest methane consumption was associated with a depth of 0 to 10 cm. Metagenomes and sequencing of cDNA
pmoA
amplicons from field samples confirmed that the dominant active methanotrophs were
Methylocystis
and
Methylomonas
. Although type II methanotrophs have long been shown to mediate methane consumption in peatlands, our results indicate that members of the genera
Methylomonas
and
Methylovulum
(type I) can significantly contribute to aerobic methane oxidation in these ecosystems.
Rapid Detection of Viable Bacillus anthracis Spores in Environmental Samples by Using Engineered Reporter Phages
Authors: Sharp Natasha J. , Molineux Ian J. , Page Martin A. , Schofield David A.
Published: February 2016

Bacillus anthracis
, the causative agent of anthrax, was utilized as a bioterrorism agent in 2001 when spores were distributed via the U.S. postal system. In responding to this event, the Federal Bureau of Investigation used traditional bacterial culture viability assays to ascertain the extent of contamination of the postal facilities within 24 to 48 h of environmental sample acquisition. Here, we describe a low-complexity, second-generation reporter phage assay for the rapid detection of viable
B. anthracis
spores in environmental samples. The assay uses an engineered
B. anthracis
reporter phage (Wβ::
luxAB
-2) which transduces bioluminescence to infected cells. To facilitate low-level environmental detection and maximize the signal response, expression of
luxAB
in an earlier version of the reporter phage (Wβ::
luxAB
-1) was optimized. These alterations prolonged signal kinetics, increased light output, and improved assay sensitivity. Using Wβ::
luxAB
-2, detection of
B. anthracis
spores was 1 CFU in 8 h from pure cultures and as low as 10 CFU/g in sterile soil but increased to 10
5
CFU/g in unprocessed soil due to an unstable signal and the presence of competing bacteria. Inclusion of semiselective medium, mediated by a phage-expressed antibiotic resistance gene, maintained signal stability and enabled the detection of 10
4
CFU/g in 6 h. The assay does not require spore extraction and relies on the phage infecting germinating cells directly in the soil sample. This reporter phage displays promise for the rapid detection of low levels of spores on clean surfaces and also in grossly contaminated environmental samples from complex matrices such as soils.
Killing of Staphylococcus aureus via Magnetic Hyperthermia Mediated by Magnetotactic Bacteria
Authors: Chen Changyou , Chen Linjie , Yi Yong , Chen Chuanfang , Wu Long-Fei , Song Tao
Published: February 2016

Staphylococcus aureus
is a common hospital and household pathogen. Given the emergence of antibiotic-resistant derivatives of this pathogen resulting from the use of antibiotics as general treatment, development of alternative therapeutic strategies is urgently needed. Here, we assess the feasibility of killing
S. aureus
cells
in vitro
and
in vivo
through magnetic hyperthermia mediated by magnetotactic bacteria that possess magnetic nanocrystals and demonstrate magnetically steered swimming. The
S. aureus
suspension was added to magnetotactic MO-1 bacteria either directly or after coating with anti-MO-1 polyclonal antibodies. The suspensions were then subjected to an alternating magnetic field (AMF) for 1 h.
S. aureus
viability was subsequently assessed through conventional plate counting and flow cytometry. We found that approximately 30% of the
S. aureus
cells mixed with uncoated MO-1 cells were killed after AMF treatment. Moreover, attachment between the magnetotactic bacteria and
S. aureus
increased the killing efficiency of hyperthermia to more than 50%. Using mouse models, we demonstrated that magnetic hyperthermia mediated by antibody-coated magnetotactic MO-1 bacteria significantly improved wound healing. These results collectively demonstrated the effective eradication of
S. aureus
both
in vitro
and
in vivo
, indicating the potential of magnetotactic bacterium-mediated magnetic hyperthermia as a treatment for
S. aureus
-induced skin or wound infections.
Endovascular repair or open repair for ruptured abdominal aortic aneurysm: a Cochrane systematic review
Authors: Badger S A , Harkin D W , Blair P H , Ellis P K , Kee F , Forster R
Published: February 2016

Objectives

Emergency endovascular aneurysm repair (eEVAR) may improve outcomes for patients with ruptured abdominal aortic aneurysm (RAAA). The study aim was to compare the outcomes for eEVAR with conventional open surgical repair for the treatment of RAAA.

Setting

A systematic review of relevant publications was performed. Randomised controlled trials (RCTs) comparing eEVAR with open surgical repair for RAAA were included.

Participants

3 RCTs were included, with a total of 761 patients with RAAA.

Interventions

Meta-analysis was performed with fixed-effects models with ORs and 95% CIs for dichotomous data and mean differences with 95% CIs for continuous data.

Primary and secondary outcome measures

Primary outcome was short-term mortality. Secondary outcome measures included aneurysm-specific and general complication rates, quality of life and economic analysis.

Results

Overall risk of bias was low. There was no difference between the 2 interventions on 30-day (or in-hospital) mortality, OR 0.91 (95% CI 0.67 to 1.22; p=0.52). 30-day complications included myocardial infarction, stroke, composite cardiac complications, renal complications, severe bowel ischaemia, spinal cord ischaemia, reoperation, amputation and respiratory failure. Reporting was incomplete, and no robust conclusion was drawn. For complication outcomes that did include at least 2 studies in the meta-analysis, there was no clear evidence to support a difference between eEVAR and open repair. Longer term outcomes and cost per patient were evaluated in only a single study, thus precluding definite conclusions.

Conclusions

Outcomes between eEVAR and open repair, specifically 30-day mortality, are similar. However, further high-quality trials are required, as the paucity of data currently limits the conclusions.
Which are the most useful scales for predicting repeat self-harm? A systematic review evaluating risk scales using measures of diagnostic accuracy
Authors: Quinlivan L , Cooper J , Davies L , Hawton K , Gunnell D , Kapur N
Published: February 2016

Objectives

The aims of this review were to calculate the diagnostic accuracy statistics of risk scales following self-harm and consider which might be the most useful scales in clinical practice.

Design

Systematic review.

Methods

We based our search terms on those used in the systematic reviews carried out for the National Institute for Health and Care Excellence self-harm guidelines (2012) and evidence update (2013), and updated the searches through to February 2015 (CINAHL, EMBASE, MEDLINE, and PsychINFO). Methodological quality was assessed and three reviewers extracted data independently. We limited our analysis to cohort studies in adults using the outcome of repeat self-harm or attempted suicide. We calculated diagnostic accuracy statistics including measures of global accuracy. Statistical pooling was not possible due to heterogeneity.

Results

The eight papers included in the final analysis varied widely according to methodological quality and the content of scales employed. Overall, sensitivity of scales ranged from 6% (95% CI 5% to 6%) to 97% (CI 95% 94% to 98%). The positive predictive value (PPV) ranged from 5% (95% CI 3% to 9%) to 84% (95% CI 80% to 87%). The diagnostic OR ranged from 1.01 (95% CI 0.434 to 2.5) to 16.3 (95%CI 12.5 to 21.4). Scales with high sensitivity tended to have low PPVs.

Conclusions

It is difficult to be certain which, if any, are the most useful scales for self-harm risk assessment. No scales perform sufficiently well so as to be recommended for routine clinical use. Further robust prospective studies are warranted to evaluate risk scales following an episode of self-harm. Diagnostic accuracy statistics should be considered in relation to the specific service needs, and scales should only be used as an adjunct to assessment.
Factors associated with exit block and impact on the emergency department
Authors: Knowles Emma , Mason Suzanne M , Smith Craig
Published: February 2016

We used routinely available data to identify the likelihood of exit block within type 1 EDs across acute trusts in England. While the findings are based on exploratory work and should be treated with caution, some patterns appeared to emerge from the data and require further exploration. NHS Trusts at risk of exit block were more likely to be large trusts, located in larger catchment areas, having higher admission rates and inpatient bed occupancy and higher levels of patients leaving the ED without being seen or reattending. Some of the factors identified may well be symptomatic of exit block rather than causal, while other factors may be acting as proxies for differences in casemix, social deprivation or ability to access alternative urgent care services.
Comparison of a lateral flow milk progesterone test with enzyme immunoassay as an aid for reproductive status determination in cows
Authors: Waldmann A. , Raud A.
Published: February 2016

The lateral flow test (LFT) is an immunochromatographic method that utilises an immunostrip for non‐laboratory diagnostic purposes. The present study evaluated a milk progesterone LFT against the enzyme immunoassay (EIA) to confirm oestrus and a non‐pregnancy diagnosis. In total, 277 milk samples from 70 cows were analysed, collected on the day of artificial insemination and at 19 days, 21 days and 24 days post insemination. The level of accuracy of the LFT compared with the EIA was 95.0 per cent for milk samples containing <2 ng/ml progesterone and 97.0 per cent for milk samples containing >10 ng/ml progesterone. The validation of oestrus by the LFT was 98.6 per cent accurate using 2 ng/ml progesterone as the EIA estimate for oestrus. The test performance for a non‐pregnancy diagnosis was subject to the day of milk sampling, showing the highest accuracy on day 24 post insemination for both tests. When optimised for maximum specificity, and compared with rectal palpation, the LFT had a sensitivity and specificity for non‐pregnancy diagnosis on day 24 post insemination of 75.0 per cent and 100.0 per cent, respectively, with an overall accuracy of 84.4 per cent. The corresponding characteristics for the quantitative EIA were 85.0 per cent, 100.0 per cent and 90.6 per cent, respectively. The LFT results compared favourably with the quantitative milk progesterone EIA.
No seed zone effects on the survival, growth, and stem form of Pacific silver fir (Abies amabilis) in Britain
Authors: Kerr Gary , Stokes Victoria , Peace Andrew , Fletcher Alan , Samuel Sam , Mackintosh Hamish , Mason W.L.
Published: February 2016

Pacific silver fir (Abies amabilis Douglas ex J. Forbes) was first introduced to Britain in 1830 but has not been widely planted and occupies a minute part of the forest estate. The results of six experiments established in the uplands of Britain examining material from 30 collection sites in 14 seed zones clearly demonstrate that its potential has not been recognised. The trials were assessed after 28 years and show that Pacific silver fir has the potential to be as productive as other common species options. There was little variation in performance between the 14 seed zones, and future seed collections could be carried out within a wide geographical range, including mainland British Columbia and Vancouver Island and the Olympic Mountains and western Cascades of Washington. The silvicultural characteristics of the species mean that it could be used more widely to diversify forests in Britain both as a plantation species and in the wider use of continuous cover management. More work is justified to determine its susceptibility to Annosum root rot (Heterobasidion annosum (Fr.) Bref), confirm its productivity on sites with rainfall below 800 mm·a–1 and (or) with a high peat content, and provide more detail on its wood properties.
Post-rift subsidence of the French Guiana hyper-oblique margin: from rift-inherited subsidence to Amazon deposition effect
Authors: Sapin Francois , Davaux Mélanie , Dall'asta Massimo , Lahmi Marjolaine , Baudot Gautier , Ringenbach Jean-Claude
Published: February 2016

The recent surge of exploration activities over distal margins, with the acquisition of more and more high-quality and deep seismic data, has led to enhance concepts of the deformation and subsidence history of passive margins in general and sheared margins in particular. The French Guiana sheared margin is very narrow. The thinning of the upper crust is accommodated by few major faults relayed by well-expressed transfer zones, giving a general oblique trend to the margin. Another possible effect of the shear component during the rifting is the presence in the distal domain of a Moho high. Its exhumation is coeval with the emplacement of a deltaic system coming from the Demerara Plateau, evidencing a probably important early subsidence of the margin. This early subsidence in the late-rifting stage is increased during the early drifting, when the thinned crust reached its isostatic/thermal equilibrium in the Cenomano-Turonian before suffering an important Late Cretaceous sedimentation load. In the Palaeogene, starving of the margin and significant uplifts in the Guiana Craton are observed, possibly resulting from the rise of the Purus Arch (Andes fore-bulge?). Finally, the Amazon deposition by the Late Miocene–Pliocene provoked a large subsidence in the distal domain.
Central respiratory chemosensitivity and cerebrovascular CO2reactivity: a rebreathing demonstration illustrating integrative human physiology
Authors: MacKay Christina M. , Skow Rachel J. , Tymko Michael M. , Boulet Lindsey M. , Davenport Margie H. , Steinback Craig D. , Ainslie Philip N. , Lemieux Chantelle E. M. , Day Trevor A.
Published: February 2016

One of the most effective ways of engaging students of physiology and medicine is through laboratory demonstrations and case studies that combine 1) the use of equipment, 2) problem solving, 3) visual representations, and 4) manipulation and interpretation of data. Depending on the measurements made and the type of test, laboratory demonstrations have the added benefit of being able to show multiple organ system integration. Many research techniques can also serve as effective demonstrations of integrative human physiology. The “Duffin” hyperoxic rebreathing test is often used in research settings as a test of central respiratory chemosensitivity and cerebrovascular reactivity to CO2. We aimed to demonstrate the utility of the hyperoxic rebreathing test for both respiratory and cerebrovascular responses to increases in CO2and illustrate the integration of the respiratory and cerebrovascular systems. In the present article, methods such as spirometry, respiratory gas analysis, and transcranial Doppler ultrasound are described, and raw data traces can be adopted for discussion in a tutorial setting. If educators have these instruments available, instructions on how to carry out the test are provided so students can collect their own data. In either case, data analysis and quantification are discussed, including principles of linear regression, calculation of slope, the coefficient of determination ( R2), and differences between plotting absolute versus normalized data. Using the hyperoxic rebreathing test as a demonstration of the complex interaction and integration between the respiratory and cerebrovascular systems provides senior undergraduate, graduate, and medical students with an advanced understanding of the integrative nature of human physiology.
Value of artisanal simulators to train veterinary students in performing invasive ultrasound-guided procedures
Authors: Hage Maria Cristina F. N. S. , Massaferro Ana Beatriz , Lopes Érika Rondon , Beraldo Carolina Mariano , Daniel Jéssika
Published: February 2016

Pericardial effusion can lead to cardiac tamponade, which endangers an animal's life. Ultrasound-guided pericardiocentesis is used to remove abnormal liquid; however, it requires technical expertise. In veterinary medical education, the opportunity to teach this procedure to save lives during emergencies is rare; therefore, simulators are recommended for this practice. The present study aimed to create a model that can be made “at home” at low cost for ultrasound-guided pericardiocentesis training and to gather feedback about this model through questionnaires given to the participants. Eighteen professionals and thirty-six students were introduced to the simulator in pairs. After the simulation training session, participants filled out the questionnaire. Participants considered the model strong in the following areas: visualization of the pericardium, the heart, fluid in the pericardium, and fluid decrease during fictitious pericardiocentesis and its realism. They considered the model weak or moderate in the following areas: visualization of the surrounding tissues, difficulty of pericardial puncture, and visualization of the catheter. The professionals classified the realism of the experimental heart as moderate, whereas the undergraduate students classified it as strong. All participants believed that the experimental model could be useful in preparing for a future real situation. This model fulfills the need for a practical, realistic, and cost-effective model for ultrasound-guided pericardiocentesis training.
“Sickle cell anemia: tracking down a mutation”: an interactive learning laboratory that communicates basic principles of genetics and cellular biology
Authors: Jarrett Kevin , Williams Mary , Horn Spencer , Radford David , Wyss J. Michael
Published: February 2016

“Sickle cell anemia: tracking down a mutation” is a full-day, inquiry-based, biology experience for high school students enrolled in genetics or advanced biology courses. In the experience, students use restriction endonuclease digestion, cellulose acetate gel electrophoresis, and microscopy to discover which of three putative patients have the sickle cell genotype/phenotype using DNA and blood samples from wild-type and transgenic mice that carry a sickle cell mutation. The inquiry-based, problem-solving approach facilitates the students' understanding of the basic concepts of genetics and cellular and molecular biology and provides experience with contemporary tools of biotechnology. It also leads to students' appreciation of the causes and consequences of this genetic disease, which is relatively common in individuals of African descent, and increases their understanding of the first principles of genetics. This protocol provides optimal learning when led by well-trained facilitators (including the classroom teacher) and carried out in small groups (6:1 student-to-teacher ratio). This high-quality experience can be offered to a large number of students at a relatively low cost, and it is especially effective in collaboration with a local science museum and/or university. Over the past 15 yr, >12,000 students have completed this inquiry-based learning experience and demonstrated a consistent, substantial increase in their understanding of the disease and genetics in general.
Development of a servo pump system for in vivo loading of pathological pulmonary artery impedance on the right ventricle of normal rats
Authors: Fukumitsu Masafumi , Kawada Toru , Shimizu Shuji , Turner Michael J. , Uemura Kazunori , Sugimachi Masaru
Published: February 2016

Pulmonary artery (PA) impedance provides detailed information on right ventricular (RV) afterload in pulmonary hypertension (PH). This study aimed to examine PA impedance in a rat model of monocrotaline-induced PH (MCT-PH) and to develop an experimental system for in vivo loading of pathological PA impedance on the RV of normal rats. PA impedance was quantified in normal ( n = 10) and MCT-PH rats ( n = 10) using a three-element Windkessel (3-WK) model. Compared with normal rats, MCT-PH rats had higher characteristic impedance ( ZC) and peripheral pulmonary resistance ( RP) ( ZC: 0.121 ± 0.039 vs. 0.053 ± 0.017 mmHg·min·ml−1, P < 0.001; RP: 0.581 ± 0.334 vs. 0.252 ± 0.105 mmHg·min·ml−1, P = 0.013) and lower pulmonary artery compliance ( CP) (0.242 ± 0.131 vs. 0.700 ± 0.186 ml/mmHg, P < 0.001). In another group of 10 normal rats, a computer-controlled servo pump was connected to the left PA for loading PA impedance with parameters in pathological ranges designed by the 3-WK model. Activation of the servo pump decreased the error of measured vs. target PA impedance (modulus: from 0.047 ± 0.020 without pump activation to 0.019 ± 0.007 with pump activation, P < 0.001; phase: 0.085 ± 0.028 to 0.043 ± 0.012 radians, P < 0.001). In conclusion, MCT-PH increases ZCand RPand decreases CP. Our servo pump system, which is capable of imposing arbitrary PA impedance with pathological parameters, may offer a unique opportunity to delineate the pathological significance of PA impedance in PH.
Sirt3 protects mitochondrial DNA damage and blocks the development of doxorubicin-induced cardiomyopathy in mice
Authors: Pillai Vinodkumar B. , Bindu Samik , Sharp Will , Fang Yong Hu , Kim Gene , Gupta Madhu , Samant Sadhana , Gupta Mahesh P.
Published: February 2016

Doxorubicin (Doxo) is a chemotherapeutic drug widely used to treat variety of cancers. One of the most serious side effects of Doxo is its dose-dependent and delayed toxicity to the heart. Doxo is known to induce cardiac mitochondrial damage. Recently, the mitochondrial sirtuin SIRT3 has been shown to protect mitochondria from oxidative stress. Here we show that overexpression of SIRT3 protects the heart from toxicity of Doxo by preventing the drug-induced mitochondrial DNA (mtDNA) damage. Doxo treatment caused depletion of Sirt3 levels both in primary cultures of cardiomyocytes and in mouse hearts, which led to massive acetylation of mitochondrial proteins. Doxo-induced toxicity to cardiomyocytes was associated with increased reactive oxygen species (ROS) production, mitochondrial fragmentation, and cell death. Overexpression of SIRT3 helped to attenuate Doxo-induced ROS levels and cardiomyocyte death. Sirt3 knockout (Sirt3.KO) mice could not endure the full dose of Doxo treatment, developed exacerbated cardiac hypertrophy, and died during the course of treatment, whereas Sirt3 transgenic (Sirt3.tg) mice were protected against Doxo-induced cardiotoxicity. Along with Sirt3, we also observed a concomitant decrease in levels of oxoguanine-DNA glycosylase-1 (OGG1), a major DNA glycosylase that hydrolyzes oxidized-guanine (8-oxo-dG) to guanine. Depletion of OGG1 levels was associated with increased mtDNA damage. Sirt3.KO mice and Doxo-treated mice showed increased 8-oxo-dG adducts in DNA and corresponding increase in mtDNA damage, whereas, 8-oxo-dG adducts and mtDNA damage were markedly reduced in Sirt3 overexpressing transgenic mice hearts. These results thus demonstrated that Sirt3 activation protects the heart from Doxo-induced cardiotoxicity by maintaining OGG1 levels and protecting mitochondria from DNA damage.
Cardiac angiotensin-(1–12) expression and systemic hypertension in rats expressing the human angiotensinogen gene
Authors: Ferrario Carlos M. , VonCannon Jessica , Jiao Yan , Ahmad Sarfaraz , Bader Michael , Dell'Italia Louis J. , Groban Leanne , Varagic Jasmina
Published: February 2016

Angiotensin-(1–12) [ANG-(1–12)] is processed into ANG II by chymase in rodent and human heart tissue. Differences in the amino acid sequence of rat and human ANG-(1–12) render the human angiotensinogen (hAGT) protein refractory to cleavage by renin. We used transgenic rats harboring the hAGT gene [TGR(hAGT)L1623] to assess the non-renin-dependent effects of increased hAGT expression on heart function and arterial pressure. Compared with Sprague-Dawley (SD) control rats ( n = 11), male homozygous TGR(hAGT)L1623 ( n = 9) demonstrated sustained daytime and nighttime hypertension associated with no changes in heart rate but increased heart rate lability. Increased heart weight/tibial length ratio and echocardiographic indexes of cardiac hypertrophy were associated with modest reduction of systolic function in hAGT rats. Robust human ANG-(1–12) immunofluorescence within myocytes of TGR(hAGT)L1623 rats was associated with a fourfold increase in cardiac ANG II content. Chymase enzymatic activity, using the rat or human ANG-(1–12) as a substrate, was not different in the cardiac tissue of SD and hAGT rats. Since both cardiac angiotensin-converting enzyme (ACE) and ACE2 activities were not different among the two strains, the changes in cardiac structure and function, blood pressure, and left ventricular ANG II content might be a product of an increased cardiac expression of ANG II generated through a non-renin-dependent mechanism. The data also underscore the existence in the rat of alternate enzymes capable of acting on hAGT protein. Homozygous transgenic rats expressing the hAGT gene represent a novel tool to investigate the contribution of human relevant renin-independent cardiac ANG II formation and function.
Exposure to stimulatory CpG oligonucleotides during gestation induces maternal hypertension and excess vasoconstriction in pregnant rats
Authors: Goulopoulou Styliani , Wenceslau Camilla F. , McCarthy Cameron G. , Matsumoto Takayuki , Webb R. Clinton
Published: February 2016

Bacterial infections increase risk for pregnancy complications, such as preeclampsia and preterm birth. Unmethylated CpG DNA sequences are present in bacterial DNA and have immunostimulatory effects. Maternal exposure to CpG DNA induces fetal demise and craniofacial malformations; however, the effects of CpG DNA on maternal cardiovascular health have not been examined. We tested the hypothesis that exposure to synthetic CpG oligonucleotides (ODNs) during gestation would increase blood pressure and cause vascular dysfunction in pregnant rats. Pregnant and nonpregnant female rats were treated with CpG ODN (ODN 2395) or saline (Veh) starting on gestational day 14 or corresponding day for the nonpregnant groups. Exposure to CpG ODN increased systolic blood pressure in pregnant (Veh: 121 ± 2 mmHg vs. ODN 2395: 134 ± 2 mmHg, P < 0.05) but not in nonpregnant rats (Veh: 111 ± 2 mmHg vs. ODN 2395: 108 ± 5 mmHg, P > 0.05). Mesenteric resistance arteries from pregnant CpG ODN-treated rats had increased contractile responses to U46619 [thromboxane A2 (TxA2) mimetic] compared with arteries from vehicle-treated rats [Emax (%KCl), Veh: 87 ± 4 vs. ODN 2395: 104 ± 4, P < 0.05]. Nitric oxide synthase (NOS) inhibition increased contractile responses to U46619, and CpG ODN treatment abolished this effect in arteries from pregnant ODN 2395-treated rats. CpG ODN potentiated the involvement of cyclooxygenase (COX) to U46619-induced contractions. In conclusion, exposure to CpG ODN during gestation induces maternal hypertension, augments resistance artery contraction, increases the involvement of COX-dependent mechanisms and reduces the contribution of NOS-dependent mechanisms to TxA2-induced contractions in mesenteric resistance arteries.
Rotenone-stimulated superoxide release from mitochondrial complex I acutely augments L-type Ca2+ current in A7r5 aortic smooth muscle cells
Authors: Ochi Rikuo , Dhagia Vidhi , Lakhkar Anand , Patel Dhara , Wolin Michael S. , Gupte Sachin A.
Published: February 2016

Voltage-gated L-type Ca2+ current ( ICa,L) induces contraction of arterial smooth muscle cells (ASMCs), and ICa,L is increased by H2O2 in ASMCs. Superoxide released from the mitochondrial respiratory chain (MRC) is dismutated to H2O2. We studied whether superoxide per se acutely modulates ICa,L in ASMCs using cultured A7r5 cells derived from rat aorta. Rotenone is a toxin that inhibits complex I of the MRC and increases mitochondrial superoxide release. The superoxide content of mitochondria was estimated using mitochondrial-specific MitoSOX and HPLC methods, and was shown to be increased by a brief exposure to 10 μM rotenone. ICa,L was recorded with 5 mM BAPTA in the pipette solution. Rotenone administration (10 nM to 10 μM) resulted in a greater ICa,L increase in a dose-dependent manner to a maximum of 22.1% at 10 μM for 1 min, which gradually decreased to 9% after 5 min. The rotenone-induced ICa,L increase was associated with a shift in the current-voltage relationship ( I-V) to a hyperpolarizing direction. DTT administration resulted in a 17.9% increase in ICa,L without a negative shift in I–V, and rotenone produced an additional increase with a shift. H2O2 (0.3 mM) inhibited ICa,L by 13%, and additional rotenone induced an increase with a negative shift. Sustained treatment with Tempol (4-hydroxy tempo) led to a significant ICa,L increase but it inhibited the rotenone-induced increase. Staurosporine, a broad-spectrum protein kinase inhibitor, partially inhibited ICa,L and completely suppressed the rotenone-induced increase. Superoxide released from mitochondria affected protein kinases and resulted in stronger ICa,L preceding its dismutation to H2O2. The removal of nitric oxide is a likely mechanism for the increase in ICa,L.
A Defected Structure Shaped CPW-Fed Wideband Microstrip Antenna for Wireless Applications
Authors: Khanna Puneet , Sharma Amar , Shinghal Kshitij , Kumar Arun
Published: February 2016

A coplanar waveguide- (CPW-) fed compact wideband defected structure shaped microstrip antenna is proposed for wireless applications. Defected structure is produced by cutting theUshape antenna in the form of two-sided T shape. The proposed antenna consists of two-sidedTshape strip as compared to usual monopole patch antenna for minimizing the height of the antenna. The large space around the radiator is fully utilized as the ground is on the same plane as of radiator. Microstrip line feed is used to excite the proposed antenna placed on an FR4 substrate (dielectric constantεr=4.4). The antenna is practically fabricated and simulated. Simulated results of the proposed antenna have been obtained by using Ansoft High-Frequency Structure Simulator (HFSS) software. These results are compared with measured results by using network analyzer. Measured result shows good agreement with the simulated results. It is observed that the proposed antenna shows a wideband from 2.96 GHz to 7.95 GHz with three bands atf1=3.23 GHz,f2=4.93 GHz, andf3=7.04 GHz.
A Genome-Wide Association Study of Cutaneous Squamous Cell Carcinoma among European Descendants
Authors: Siiskonen Satu J. , Zhang Mingfeng , Li Wen-Qing , Liang Liming , Kraft Peter , Nijsten Tamar , Han Jiali , Qureshi Abrar A.
Published: February 2016

Background: No GWAS on the risk of cutaneous squamous cell carcinoma (SCC) has been published. We conducted a multistage genome-wide association study (GWAS) to identify novel genetic loci for SCC.

Methods: The study included 745 SCC cases and 12,805 controls of European descent in the discovery stage and 531 SCC cases and 551 controls of European ancestry in the replication stage. We selected 64 independent loci that showed the most significant associations with SCC in the discovery stage (linkage disequilibrium r2 < 0.4) for replication.

Results: Rs8063761 in the DEF8 gene on chromosome 16 showed the strongest association with SCC (P = 1.7 × 10−9 in the combined set; P = 1.0 × 10−6 in the discovery set and P = 4.1 × 10−4 in the replication set). The variant allele of rs8063761 (T allele) was associated with a decreased expression of DEF8 (P = 1.2 × 10−6). Besides, we validated four other SNPs associated with SCC in the replication set, including rs9689649 in PARK2 gene (P = 2.7 × 10−6 in combined set; P = 3.2 × 10−5 in the discovery; and P = 0.02 in the replication), rs754626 in the SRC gene (P = 1.1 × 10−6 in combined set; P = 1.4 × 10−5 in the discovery and P = 0.02 in the replication), rs9643297 in ST3GAL1 gene (P = 8.2 × 10−6 in combined set; P = 3.3 × 10−5 in the discovery; and P = 0.04 in the replication), and rs17247181 in ERBB2IP gene (P = 4.2 × 10−6 in combined set; P = 3.1 × 10−5 in the discovery; and P = 0.048 in the replication).

Conclusion: Several genetic variants were associated with risk of SCC in a multistage GWAS of subjects of European ancestry.

Impact: Further studies are warranted to validate our finding and elucidate the genetic function of these variants. Cancer Epidemiol Biomarkers Prev; 25(4); 714–20. ©2016 AACR.
Identification of Niclosamide as a Novel Anticancer Agent for Adrenocortical Carcinoma
Authors: Satoh Kei , Zhang Lisa , Zhang Yaqin , Chelluri Raju , Boufraqech Myriem , Nilubol Naris , Patel Dhaval , Shen Min , Kebebew Electron
Published: February 2016

Purpose: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer, and no current effective therapy is available for locally advanced and metastatic ACC. Drug repurposing is an emerging approach for identifying new indications for existing drugs, especially for rare cancers such as ACC. The objective of this study was to use quantitative high-throughput screening to identify agents with antineoplastic activity against ACC.

Experimental Design: A screening of 4,292 compounds was performed on three ACC cell lines: BD140A, SW-13, and NCI-H295R.

Results: Twenty-one active compounds were identified, with an efficacy of >80% in all three cell lines. Of these, niclosamide showed higher efficacy and lower IC50 than established anti-ACC drugs. We then validated niclosamide-inhibited cellular proliferation in all three ACC cell lines. Next, we investigated the mechanism by which niclosamide inhibited ACC cell proliferation, and found that it induced caspase-dependent apoptosis and G1 cell-cycle arrest. Niclosamide also decreased cellular migration and reduced the level of mediators of epithelial-to-mesenchymal transition, such as N-cadherin and vimentin. Furthermore, niclosamide treatment resulted in decreased expression of β-catenin. We also evaluated the effect of niclosamide on energy metabolism in ACC cell lines and found it resulted in mitochondrial uncoupling. Niclosamide treatment inhibited ACC tumor growth with no observed toxicity in mice in vivo.

Conclusions: Our findings suggest that niclosamide has anti-ACC activity through its inhibition of multiple altered cellular pathways and cellular metabolism in ACC. Our results provide a preclinical rationale for evaluating niclosamide therapy in a clinical trial for ACC. Clin Cancer Res; 22(14); 3458–66. ©2016 AACR.
Applying Small Molecule Signal Transducer and Activator of Transcription-3 (STAT3) Protein Inhibitors as Pancreatic Cancer Therapeutics
Authors: Arpin Carolyn C. , Mac Stephen , Jiang Yanlin , Cheng Huiwen , Grimard Michelle , Page Brent D.G. , Kamocka Malgorzata M. , Haftchenary Sina , Su Han , Ball Daniel P. , Rosa David A. , Lai Ping-Shan , Gómez-Biagi Rodolfo F. , Ali Ahmed M. , Rana Rahul , Hanenberg Helmut , Kerman Kagan , McElyea Kyle C. , Sandusky George E. , Gunning Patrick T. , Fishel Melissa L.
Published: February 2016

Constitutively activated STAT3 protein has been found to be a key regulator of pancreatic cancer and a target for molecular therapeutic intervention. In this study, PG-S3-001, a small molecule derived from the SH-4-54 class of STAT3 inhibitors, was found to inhibit patient-derived pancreatic cancer cell proliferation in vitro and in vivo in the low micromolar range. PG-S3-001 binds the STAT3 protein potently, Kd = 324 nmol/L by surface plasmon resonance, and showed no effect in a kinome screen (>100 cancer-relevant kinases). In vitro studies demonstrated potent cell killing as well as inhibition of STAT3 activation in pancreatic cancer cells. To better model the tumor and its microenvironment, we utilized three-dimensional (3D) cultures of patient-derived pancreatic cancer cells in the absence and presence of cancer-associated fibroblasts (CAF). In this coculture model, inhibition of tumor growth is maintained following STAT3 inhibition in the presence of CAFs. Confocal microscopy was used to verify tumor cell death following treatment of 3D cocultures with PG-S3-001. The 3D model was predictive of in vivo efficacy as significant tumor growth inhibition was observed upon administration of PG-S3-001. These studies showed that the inhibition of STAT3 was able to impact the survival of tumor cells in a relevant 3D model, as well as in a xenograft model using patient-derived cells. Mol Cancer Ther; 15(5); 794–805. ©2016 AACR.
Precision Oncology: The UC San Diego Moores Cancer Center PREDICT Experience
Authors: Schwaederle Maria , Parker Barbara A. , Schwab Richard B. , Daniels Gregory A. , Piccioni David E. , Kesari Santosh , Helsten Teresa L. , Bazhenova Lyudmila A. , Romero Julio , Fanta Paul T. , Lippman Scott M. , Kurzrock Razelle
Published: February 2016

By profiling their patients' tumors, oncologists now have the option to use molecular results to match patients with drug(s) based on specific biomarkers. In this observational study, 347 patients with solid advanced cancers and next-generation sequencing (NGS) results were evaluated. Outcomes for patients who received a “matched” versus “unmatched” therapy following their NGS results were compared. Eighty-seven patients (25%) were treated with a “matched” therapy, 93 (26.8%) with an “unmatched” therapy. More patients in the matched group achieved stable disease (SD) ≥ 6 months/partial response (PR)/complete response (CR), 34.5% vs. 16.1%, (P ≤ 0.020 multivariable or propensity score methods). Matched patients had a longer median progression-free survival (PFS; 4.0 vs. 3.0 months, P = 0.039 in the Cox regression model). In analysis using PFS1 (PFS on the prior line of therapy) as a comparator to PFS after NGS, as expected, the unmatched group demonstrated a PFS2 significantly shorter than PFS1 (P = 0.009); however, this shortening was not observed in the matched patients (P = 0.595). Furthermore, 45.3% of the matched patients (24/53) had a PFS2/PFS1 ratio ≥1.3 compared with 19.3% of patients (11/57) in the unmatched group (P = 0.004 univariable and P ≥ 0.057 in multivariable/propensity score analysis). Patients with a “matching-score” (the number of matched drugs divided by the number of aberrations; unmatched patients had a score of zero) > 0.2 had a median overall survival (OS) of 15.7 months compared with 10.6 months when their matching-score was ≤ 0.2, (P = 0.040 in the Cox regression model). Matched versus unmatched patients had higher rates of SD ≥ 6 months/PR/CR and longer PFS, and improvement in OS correlated with a higher matching score in multivariable analysis. Mol Cancer Ther; 15(4); 743–52. ©2016 AACR.
High Expression of miR-532-5p, a Tumor Suppressor, Leads to Better Prognosis in Ovarian Cancer Both In Vivo and In Vitro
Authors: Wang Fan , Chang Jeremy T.-H. , Kao Chester Jingshiu , Huang R. Stephanie
Published: February 2016

Ovarian cancer is the leading cause of death for gynecologic cancers, ranking fifth overall for cancer-related death among women. The identification of biomarkers and the elucidation of molecular mechanisms for improving treatment options have received extensive efforts in ovarian cancer research. miRNAs have high potential to act as both ovarian cancer biomarkers and as critical regulators of ovarian tumor behavior. We comprehensively analyzed global mRNA, miRNA expression, and survival data for ovarian cancer from The Cancer Genome Atlas (TCGA) to pinpoint miRNAs that play critical roles in ovarian cancer survival through their effect on mRNA expression. We performed miRNA overexpression and gene knockdown experiments to confirm mechanisms predicted in our bioinformatics approach. We established that overexpression of miR-532-5p in OVCAR-3 cells resulted in a significant decrease in cell viability over a 96-hour time period. In the TCGA ovarian cancer dataset, we found 67 genes whose expression levels were negatively correlated with miR-532-5p expression and correlated with patient survival, such as WNT9A, CSNK2A2, CHD4, and SH3PXD2A. The potential miR-532-5p–regulated gene targets were found to be enriched in the Wnt pathway. Overexpression of miR-532-5p through miRNA mimic caused downregulation of CSNK2A2, CHD4, and SH3PXD2A in the OVCAR-3 cell line. We have discovered and validated the tumor-suppressing capabilities of miR-532-5p both in vivo through TCGA analysis and in vitro through ovarian cancer cell lines. Our work highlights the potential clinical importance of miR-532-5p expression in ovarian cancer patients. Mol Cancer Ther; 15(5); 1123–31. ©2016 AACR.
Apoptotic Cells Release IL1 Receptor Antagonist in Response to Genotoxic Stress
Authors: Chwee Jyh Yun , Khatoo Muznah , Tan Nikki Yi Jie , Gasser Stephan
Published: February 2016

Apoptosis is a controlled means of eliminating damaged cells without causing an inflammatory response or tissue damage. The mechanisms that contribute to the suppression of an inflammatory response upon apoptosis of cells are poorly understood. Here, we report that apoptotic cells release the interleukin-1 receptor antagonist (IL1RA). The release of IL1RA depended on the DNA damage response, caspase 9, and caspase 3. De novo translation, classical secretion pathways, or N-glycosylation was not required for the release of IL1RA. The amounts of IL1RA released by apoptotic cells impaired IL1-induced expression of IL6. In summary, we demonstrate that the release of IL1RA in response to genotoxic stress contributes to the immunosuppressive effects of apoptotic cells. Cancer Immunol Res; 4(4); 294–302. ©2016 AACR.
Nitzschia papillosa (Bacillariaceae, Bacillariophyta): a new species from a Brazilian salt marsh
Authors: Bertolli Lucielle Merlym , Talgatti Dávia Marciana , Torgan Lezilda Carvalho
Published: February 2016

A new species of the genus Nitzschia was found in epiphyton and microphytobenthos at the Patos Lagoon salt marsh (Rio Grande do Sul State, southern Brazil). Nitzschia papillosa sp. nov. was described under light and scanning electron microscopy and compared with other species from the section Lanceolatae. The species presents features shared by several species of the genus such as a linear-lanceolate outline, cuneate ends and irregularly distributed fibulae. The distinguishable feature is a row of dots on the margin opposite to the fibulae. In scanning electron microscopy, these structures appear as silica excrescences, little rounded or squared, which we refer as papillae, situated at the transapical costae in the internal valve face. This is the first record of this kind of ornamentation in Nitzschia species.
Wary Partners
Authors: Fernandes Jorge M. , Meinfelder Florian , Moury Catherine
Published: February 2016

Are political parties willing to partially forgo their office and policy goals to maximize their coalition governance capacities? Multiparty governments are plagued with preference heterogeneity and uncertainty about policy outcomes. In this article, we argue that parties choose to make a strategic allocation of portfolios to curb delegation perils. They use portfolios with jurisdiction overlaps to shadow each other at the ministerial level. We define a wary partners’ situation when different parties control the portfolios that form a jurisdiction combination. We test this hypothesis for 12 West European parliamentary democracies since 1945. Our contribution conjugates a Monte Carlo simulation, which estimates whether real-world distribution differs significantly from expected allocation under nonstrategic behavior, with in-depth interviews with more than 40 former ministers. Results show that wary partners are used extensively as coalition governance mechanisms, particularly because of their capacity to curb information asymmetries and to avoid interministerial gridlock.
Looked after young people: Reducing health inequalities through an evidence- and theory-informed intervention
Authors: Dale Hannah , Watson Lorna , Adair Pauline , Humphris Gerry
Published: February 2016

Objective:

The study aimed to design and evaluate a health behaviour change intervention for looked after young people, targeting sexual health, smoking, exercise, healthy eating and non-dependent alcohol and drug use.

Design:

A pre–post intervention evaluation was undertaken exploring health behaviours and wellbeing.

Methodology:

The one-to-one intervention was individually tailored to each person. Young people eligible for the intervention were aged 11 years and over and were ‘looked after’, meaning they were under a supervision order with a local authority in Scotland, or were a care leaver. A total of 144 young people referred to the intervention service between March 2009 and January 2014 were eligible for the evaluation. Evaluation data were analysed using standard statistical tests on SPSS.

Results:

Behaviour change techniques, including goal setting, action planning, barrier identification/problem solving and motivational interviewing contributed to improvements in all areas. Difficulties with consent and follow-up were highlighted as barriers to effective evaluation.

Conclusion:

Improving the current health of looked after young people with a view to prevent future ill health using a tailored intervention with behaviour change techniques enables this group to improve health behaviours, despite numerous challenges in working with these vulnerable clients.