bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro comparison of 3 techniques of prosthesis attachment to the muscular process of the equine arytenoid cartilage
Authors: Ahern Benjamin J. , Van Eps Andrew W. , Boston Raymond C. , Franklin Samantha H. 
Published: May 2017

AbstractObjectiveTo determine the degree and ease of arytenoid abduction achieved with abaxial placement of a FASTak II suture anchor compared to 2 suture patterns with different directions of insertion—caudomedial to craniolateral and medial to lateral.Study designEx vivo experimental.Study populationCadaveric larynges from 10 Standardbred racehorses.MethodsEach larynx was sequentially instrumented with all 3 arytenoid suture attachment in random order: (1) abaxial placement of a FASTak II suture, (2) caudomedial to craniolateral suture, and (3) medial to lateral suture placement. Each construct was abducted at 5N increments from 0 to 25N and the left to right quotient angle ratio (LRQ) measured from digital pictures acquired at each sequential increment.ResultsArytenoid abduction (higher LRQ) was greater with FASTak II construct than either of the suture patterns. The largest difference occurred at 5N. Approximately 50% less force was required to achieve an LRQ of 1.0 with the FASTak II anchor compared to the suture patterns. No difference was detected between the 2 suture constructs throughout the study.ConclusionUse of the FASTak II suture anchor improved arytenoid abduction compared to 2 suture patterns and minimized the suture loads required to achieve maximum arytenoid abduction.Clinical relevanceUse of the FASTak II anchor may decrease the suture load required to achieve arytenoid abduction in clinical cases. This may reduce the load placed on the laryngoplasty, thereby, minimizing postoperative loss of abduction.
THE CHRISTIAN'S DILEMMA: ORGANICISM OR MECHANISM?
Authors: Ruse Michael 
Published: May 2017

AbstractIs organicism inherently Christian‐friendly, and for that matter, is mechanism inherently religion nonfriendly? They have tended to be, but the story is much more complicated. The long history of the intertwined metaphors of nature taken as an organism, versus that of nature as a machine, reveals that both metaphors have flourished in the endeavors of philosophers, scientists, and persons of faith alike. Different kinds of Christians have been receptive to both organicist and mechanistic models, just as various kinds of nonreligious scientists have been receptive to both holistic and machine metaphors. Although, it is true, organicism has been generally more attractive to persons of faith than mechanism (and vice versa), an overview of the rich and varied history of allegiances to these metaphors—religious and nonreligious alike—shows that debate is much more interesting and complex. A brief inspection of conversation surrounding recent scientific discoveries shows that this debate between metaphors is still very much alive today.
DEVELOPMENTAL BIOLOGY, NATURAL SELECTION, AND THE CONCEPTUAL BOUNDARIES OF THE MODERN EVOLUTIONARY SYNTHESIS
Authors: Depew David J. , Weber Bruce H. 
Published: May 2017

AbstractUsing the evolution of the stickleback family of subarctic fish as a touchstone, we explore the effect of new discoveries about regulatory genetics, developmental plasticity, and epigenetic inheritance on the conceptual foundations of the Modern Evolutionary Synthesis. Identifying the creativity of natural selection as the hallmark of the Modern Synthesis, we show that since its inception its adherents have pursued a variety of research projects that at first seemed to conflict with its principles, but were accommodated. We situate challenges coming from developmental biology in a dialectic between innovation and tradition, suggesting on the basis of past episodes that even if developmental plasticity and epigenetic inheritance are aligned with its principles the Modern Synthesis (and its image in the public reception of evolution) will be significantly affected.
THE PROBLEM OF “GOD” IN PSYCHOLOGY OF RELIGION: LONERGAN'S “COMMON SENSE” (RELIGION) VERSUS “THEORY” (THEOLOGY)
Authors: Helminiak Daniel A. 
Published: May 2017

AbstractThe emphasis on God in American psychology of religion generates the problem of explaining divine‐versus‐natural causality in “spiritual experiences.” Especially “theistic psychology” champions divine involvement. However, its argument exposes a methodological error: to pit popular religious opinions against technical scientific conclusions. Countering such homogenizing “postmodern agnosticism,” Bernard Lonergan explained these two as different modes of thinking: “common sense” and “theory”—which resolves the problem: When theoretical science is matched with theoretical theology, “the God‐hypothesis” explains the existence of things whereas science explains their natures; and, barring miracles, God is irrelevant to natural science. A review of the field shows that the problem is pervasive; attention to “miracles”—popularly so‐named versus technically—focuses the claims of divine‐versus‐natural causality; and specifications of the meaning ofspiritual,spirituality,science,worldview, andmeaningitself (suffering that same ambiguity: personal import versus cognitive content) offer further clarity. The problem is not naturalism versus theism, but commonsensical versus theoretical thinking. This solution demands “hard” social science.
In Vitro
Evaluation of Antileishmanial Activity of Computationally Screened Compounds against Ascorbate Peroxidase To Combat Amphotericin B Drug Resistance
Authors: Mansuri Rani , Kumar Ashish , Rana Sindhuprava , Panthi Bhavana , Ansari M. Yousuf , Das Sushmita , Dikhit Manas Ranjan , Sahoo Ganesh Chandra , Das Pradeep 
Published: May 2017

ABSTRACT

In visceral leishmaniasis (VL), the host macrophages generate oxidative stress to destroy the pathogen, while
Leishmania
combats the harmful effect of radicals by redox homeostasis through its unique trypanothione cascade.
Leishmania donovani
ascorbate peroxidase (LdAPx) is a redox enzyme that regulates the trypanothione cascade and detoxifies the effect of H
2
O
2
. The absence of an LdAPx homologue in humans makes it an excellent drug target. In this study, the homology model of LdAPx was built, including heme, and diverse compounds were prefiltered (PAINS, ADMET, and Lipinski's rule of five) and thereafter screened against the LdAPx model. Compounds having good affinity in terms of the Glide XP (extra precision) score were clustered to select diverse compounds for experimental validation. A total of 26 cluster representatives were procured and tested on promastigote culture, yielding 12 compounds with good antileishmanial activity. Out of them, six compounds were safer on the BALB/c peritoneal macrophages and were also effective against disease-causing intracellular amastigotes. Three out of six compounds inhibited recombinant LdAPx in a noncompetitive manner and also demonstrated partial reversion of the resistance property in an amphotericin B (AmB)-resistant strain, which may be due to an increased level of reactive oxygen species (ROS) and decrease of glutathione (GSH) content. However, inhibition of LdAPx in resistant parasites enhanced annexin V staining and activation of metacaspase-like protease activity, which may help in DNA fragmentation and apoptosis-like cell death. Thus, the present study will help in the search for specific hits and templates of potential therapeutic interest and therefore may facilitate the development of new drugs for combination therapy against VL.
Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent
Authors: Schuch Raymond , Khan Babar K. , Raz Assaf , Rotolo Jimmy A. , Wittekind Michael 
Published: May 2017

ABSTRACTBiofilms pose a unique therapeutic challenge because of the antibiotic tolerance of constituent bacteria. Treatments for biofilm-based infections represent a major unmet medical need, requiring novel agents to eradicate mature biofilms. Our objective was to evaluate bacteriophage lysin CF-301 as a new agent to targetStaphylococcus aureusbiofilms. We used minimum biofilm-eradicating concentration (MBEC) assays on 95S. aureusstrains to obtain a 90% MBEC (MBEC90) value of ≤0.25 μg/ml for CF-301. Mature biofilms of coagulase-negative staphylococci,Streptococcus pyogenes, andStreptococcus agalactiaewere also sensitive to disruption, with MBEC90values ranging from 0.25 to 8 μg/ml. The potency of CF-301 was demonstrated againstS. aureusbiofilms formed on polystyrene, glass, surgical mesh, and catheters. In catheters, CF-301 removed all biofilm within 1 h and killed all released bacteria by 6 h. Mixed-species biofilms, formed byS. aureusandStaphylococcus epidermidison several surfaces, were removed by CF-301, as wereS. aureusbiofilms either enriched for small-colony variants (SCVs) or grown in human synovial fluid. The antibacterial activity of CF-301 was further demonstrated againstS. aureuspersister cells in exponential-phase and stationary-phase populations. Finally, the antibiofilm activity of CF-301 was greatly improved in combinations with the cell wall hydrolase lysostaphin when tested against a range ofS. aureusstrains. In all, the data show that CF-301 is highly effective at disrupting biofilms and killing biofilm bacteria, and, as such, it may be an efficient new agent for treating staphylococcal infections with a biofilm component.
A Novel Two-Component System, GluR-GluK, Involved in Glutamate Sensing and Uptake in Streptomyces coelicolor
Authors: Li Lei , Jiang Weihong , Lu Yinhua 
Published: May 2017

ABSTRACT

Two-component systems (TCSs), the predominant signal transduction pathways employed by bacteria, play important roles in physiological metabolism in
Streptomyces
. Here, a novel TCS, GluR-GluK (encoded by
SCO5778-SCO5779
), which is located divergently from the
gluABCD
operon encoding a glutamate uptake system, was identified as being involved in glutamate sensing and uptake as well as antibiotic biosynthesis in
Streptomyces coelicolor
. Under the condition of minimal medium (MM) supplemented with different concentrations of glutamate, deletion of the
gluR-gluK
operon (
gluR-K
) resulted in enhanced actinorhodin (ACT) but reduced undecylprodigiosin (RED) and yellow type I polyketide (yCPK) production, suggesting that GluR-GluK plays a differential role in antibiotic biosynthesis. Furthermore, we found that the response regulator GluR directly promotes the expression of
gluABCD
under the culture condition of MM with a high concentration of glutamate (75 mM). Using the biolayer interferometry assay, we demonstrated that glutamate acts as the direct signal of the histidine kinase GluK. It was therefore suggested that upon sensing high concentrations of glutamate, GluR-GluK would be activated and thereby facilitate glutamate uptake by increasing
gluABCD
expression. Finally, we demonstrated that the role of GluR-GluK in antibiotic biosynthesis is independent of its function in glutamate uptake. Considering the wide distribution of the glutamate-sensing (GluR-GluK) and uptake (GluABCD) module in actinobacteria, it could be concluded that the GluR-GluK signal transduction pathway involved in secondary metabolism and glutamate uptake should be highly conserved in this bacterial phylum.

IMPORTANCE
In this study, a novel two-component system (TCS), GluR-GluK, was identified to be involved in glutamate sensing and uptake as well as antibiotic biosynthesis in
Streptomyces coelicolor
. A possible GluR-GluK working model was proposed. Upon sensing high glutamate concentrations (such as 75 mM), activated GluR-GluK could regulate both glutamate uptake and antibiotic biosynthesis. However, under a culture condition of MM supplemented with low concentrations of glutamate (such as 10 mM), although GluR-GluK is activated, its activity is sufficient only for the regulation of antibiotic biosynthesis. To the best of our knowledge, this is the first report describing a TCS signal transduction pathway for glutamate sensing and uptake in actinobacteria.
Linearmycins Activate a Two-Component Signaling System Involved in Bacterial Competition and Biofilm Morphology
Authors: Stubbendieck Reed M. , Straight Paul D. 
Published: May 2017

ABSTRACT

Bacteria use two-component signaling systems to adapt and respond to their competitors and changing environments. For instance, competitor bacteria may produce antibiotics and other bioactive metabolites and sequester nutrients. To survive, some species of bacteria escape competition through antibiotic production, biofilm formation, or motility. Specialized metabolite production and biofilm formation are relatively well understood for bacterial species in isolation. How bacteria control these functions when competitors are present is not well studied. To address fundamental questions relating to the competitive mechanisms of different species, we have developed a model system using two species of soil bacteria,
Bacillus subtilis
and
Streptomyces
sp. strain Mg1. Using this model, we previously found that linearmycins produced by
Streptomyces
sp. strain Mg1 cause lysis of
B. subtilis
cells and degradation of colony matrix. We identified strains of
B. subtilis
with mutations in the two-component signaling system
yfiJK
operon that confer dual phenotypes of specific linearmycin resistance and biofilm morphology. We determined that expression of the ATP-binding cassette (ABC) transporter
yfiLMN
operon, particularly
yfiM
and
yfiN
, is necessary for biofilm morphology. Using transposon mutagenesis, we identified genes that are required for YfiLMN-mediated biofilm morphology, including several chaperones. Using transcriptional fusions, we found that YfiJ signaling is activated by linearmycins and other polyene metabolites. Finally, using a truncated YfiJ, we show that YfiJ requires its transmembrane domain to activate downstream signaling. Taken together, these results suggest coordinated dual antibiotic resistance and biofilm morphology by a single multifunctional ABC transporter promotes competitive fitness of
B. subtilis
.

IMPORTANCE
DNA sequencing approaches have revealed hitherto unexplored diversity of bacterial species in a wide variety of environments that includes the gastrointestinal tract of animals and the rhizosphere of plants. Interactions between different species in bacterial communities have impacts on our health and industry. However, many approaches currently used to study whole bacterial communities do not resolve mechanistic details of interspecies interactions, including how bacteria sense and respond to their competitors. Using a competition model, we have uncovered dual functions for a previously uncharacterized two-component signaling system involved in specific antibiotic resistance and biofilm morphology. Insights gleaned from signaling within interspecies interaction models build a more complete understanding of gene functions important for bacterial communities and will enhance community-level analytical approaches.
RETRACTED: Role of Rac1 Pathway in Epithelial-to-Mesenchymal Transition and Cancer Stem-like Cell Phenotypes in Gastric Adenocarcinoma
Authors: Yoon Changhwan , Cho Soo-Jeong , Chang Kevin K. , Park Do Joong , Ryeom Sandra W. , Yoon Sam S. 
Published: May 2017

Abstract
Rac1, a Rho GTPase family member, is dysregulated in a variety of tumor types including gastric adenocarcinoma, but little is known about its role in cancer stem-like cells (CSCs). Therefore, Rac1 activity and inhibition were examined in gastric adenocarcinoma cells and mouse xenograft models for epithelial-to-mesenchymal transition (EMT) and CSC phenotypes. Rac1 activity was significantly higher in spheroid-forming or CD44+ gastric adenocarcinoma CSCs compared with unselected cells. Rac1 inhibition using Rac1 shRNA or a Rac1 inhibitor (NSC23766) decreased expression of the self-renewal transcription factor, Sox-2, decreased spheroid formation by 78%–81%, and prevented tumor initiation in immunodeficient mice. Gastric adenocarcinoma CSCs had increased expression of the EMT transcription factor Slug, 4.4- to 8.3-fold greater migration, and 4.2- to 12.6-fold greater invasion than unselected cells, and these increases could be blocked completely with Rac1 inhibition. Gastric adenocarcinoma spheroid cells were resistant to 5-fluorouracil and cisplatin chemotherapy, and this chemotherapy resistance could be reversed with Rac1 shRNA or NSC23766. The PI3K/Akt pathway may be upstream of Rac1, and JNK may be downstream of Rac1. In the MKN-45 xenograft model, cisplatin inhibited tumor growth by 50%, Rac1 inhibition by 35%, and the combination by 77%. Higher Rac1 activity, in clinical specimens from gastric adenocarcinoma patients who underwent potentially curative surgery, correlated with significantly worse survival (P = 0.017). In conclusion, Rac1 promotes the EMT program in gastric adenocarcinoma and the acquisition of a CSC state. Rac1 inhibition in gastric adenocarcinoma cells blocks EMT and CSC phenotypes, and thus may prevent metastasis and augment chemotherapy.
Implications: In gastric adenocarcinoma, therapeutic targeting of the Rac1 pathway may prevent or reverse EMT and CSC phenotypes that drive tumor progression, metastasis, and chemotherapy resistance. Mol Cancer Res; 15(8); 1106–16. ©2017 AACR.
Human Tumor Antigens Yesterday, Today, and Tomorrow
Authors: Finn Olivera J. 
Published: May 2017

AbstractThe question of whether human tumors express antigens that can be recognized by the immune system has been answered with a resounding YES. Most were identified through spontaneous antitumor humoral and cellular immune responses found in cancer patients and include peptides, glycopeptides, phosphopeptides, viral peptides, and peptides resulting from common mutations in oncogenes and tumor-suppressor genes, or common gene fusion events. Many have been extensively tested as candidates for anticancer vaccines. More recently, attention has been focused on the potentially large number of unique tumor antigens, mutated neoantigens, that are the predicted products of the numerous mutations revealed by exome sequencing of primary tumors. Only a few have been confirmed as targets of spontaneous immunity and immunosurveillance, and even fewer have been tested in preclinical and clinical settings. The field has been divided for a long time on the relative importance of shared versus mutated antigens in tumor surveillance and as candidates for vaccines. This question will eventually need to be answered in a head to head comparison in well-designed clinical trials. One advantage that shared antigens have over mutated antigens is their potential to be used in vaccines for primary cancer prevention. Cancer Immunol Res; 5(5); 347–54. ©2017 AACR.
Loss of Cardioprotective Effects at the
ADAMTS7
Locus as a Result of Gene-Smoking Interactions
Authors: Saleheen Danish , Zhao Wei , Young Robin , Nelson Christopher P. , Ho WeangKee , Ferguson Jane F. , Rasheed Asif , Ou Kristy , Nurnberg Sylvia T. , Bauer Robert C. , Goel Anuj , Do Ron , Stewart Alexandre F.R. , Hartiala Jaana , Zhang Weihua , Thorleifsson Gudmar , Strawbridge Rona J. , Sinisalo Juha , Kanoni Stavroula , Sedaghat Sanaz , Marouli Eirini , Kristiansson Kati , Hua Zhao Jing , Scott Robert , Gauguier Dominique , Shah Svati H. , Smith Albert Vernon , van Zuydam Natalie , Cox Amanda J. , Willenborg Christina , Kessler Thorsten , Zeng Lingyao , Province Michael A. , Ganna Andrea , Lind Lars , Pedersen Nancy L. , White Charles C. , Joensuu Anni , Edi Kleber Marcus , Hall Alistair S. , März Winfried , Salomaa Veikko , O’Donnell Christopher , Ingelsson Erik , Feitosa Mary F. , Erdmann Jeanette , Bowden Donald W. , Palmer Colin N.A. , Gudnason Vilmundur , Faire Ulf De , Zalloua Pierre , Wareham Nicholas , Thompson John R. , Kuulasmaa Kari , Dedoussis George , Perola Markus , Dehghan Abbas , Chambers John C. , Kooner Jaspal , Allayee Hooman , Deloukas Panos , McPherson Ruth , Stefansson Kari , Schunkert Heribert , Kathiresan Sekar , Farrall Martin , Marcel Frossard Philippe , Rader Daniel J. , Samani Nilesh J. , Reilly Muredach P. 
Published: May 2017

Background:
Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with genotypes that have been shown to associate with CHD risk.

Methods:

We analyzed data on 60 919 CHD cases and 80 243 controls from 29 studies for gene-smoking interactions for genetic variants at 45 loci previously reported to be associated with CHD risk. We also studied 5 loci associated with smoking behavior. Study-specific gene-smoking interaction effects were calculated and pooled using fixed-effects meta-analyses. Interaction analyses were declared to be significant at a
P
value of <1.0×10
–3
(Bonferroni correction for 50 tests).

Results:

We identified novel gene-smoking interaction for a variant upstream of the
ADAMTS7
gene. Every T allele of rs7178051 was associated with lower CHD risk by 12% in never-smokers (
P
=1.3×10
–16
) in comparison with 5% in ever-smokers (
P
=2.5×10
–4
), translating to a 60% loss of CHD protection conferred by this allelic variation in people who smoked tobacco (interaction
P
value=8.7×10
–5
). The protective T allele at rs7178051 was also associated with reduced
ADAMTS7
expression in human aortic endothelial cells and lymphoblastoid cell lines. Exposure of human coronary artery smooth muscle cells to cigarette smoke extract led to induction of
ADAMTS7.

Conclusions:

Allelic variation at rs7178051 that associates with reduced
ADAMTS7
expression confers stronger CHD protection in never-smokers than in ever-smokers. Increased vascular
ADAMTS7
expression may contribute to the loss of CHD protection in smokers.
Letters of Recommendation: Association with Interviewers’ Perceptions and Preferences
Authors: Young VyVy N. 
Published: May 2017

ObjectiveLetters of recommendation (LORs) are an inescapable aspect of the application process. Standardized LORs (SLORs) have been developed and compared with traditional narrative LORs (NLORs). This study investigated whether there was a difference in degree of association between LOR types and face‐to‐face interviews. Interviewer preference for LOR was anonymously surveyed.Study DesignSurvey.SettingSingle‐institution otolaryngology residency program, 1 year before and 4 years after introduction of SLORs.Subjects and MethodsResidency interviewers indicated on a visual analog scale how well their impression of an applicant compared between the LOR and the face‐to‐face interview. Interviewers assessed each applicant, each year, based on LOR type.ResultsOf 2573 assessments, 964 were collected (37.5% response rate), including 927 responses related to NLORs, 561 to SLORs, and 316 to medical student performance evaluations (ie, dean’s letters). The average association of VAS scores between LORs and interviews ranged from 72 to 81 across years and LOR types. Sixty‐one percent of interviewers preferred NLORs, and 13% preferred SLORs. Reasons for these preferences included more information provided in NLORs versus faster read time with SLORs.ConclusionsInterviewers’ perceptions of applicants based on LORs and face‐to‐face interviews were comparable across LOR types over the last 5 years. For many reasons, the general utility of the LOR remains questionable, and the continued need for it should be critically assessed.