bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytochrome P450 Genetic Variation Associated with Tamoxifen Biotransformation in American Indian and Alaska Native People
Authors: Khan Burhan A. , Robinson Renee , Fohner Alison E. , Muzquiz LeeAnna I. , Schilling Brian D. , Beans Julie A. , Olnes Matthew J. , Trawicki Laura , Frydenlund Holly , Laukes Cindi , Beatty Patrick , Phillips Brian , Nickerson Deborah , Howlett Kevin , Dillard Denise A. , Thornton Timothy A. , Thummel Kenneth E. , Woodahl Erica L. 
Published: February 2018

AbstractDespite evidence that pharmacogenetics can improve tamoxifen pharmacotherapy, there are few studies with American Indian and Alaska Native (AIAN) people. We examined variation in cytochrome P450 (CYP) genes (CYP2D6, CYP3A4, CYP3A5, and CYP2C9) and tamoxifen biotransformation in AIAN patients with breast cancer (n = 42) from the Southcentral Foundation in Alaska and the Confederated Salish and Kootenai Tribes in Montana. We tested for associations between CYP diplotypes and plasma concentrations of tamoxifen and metabolites. Only the CYP2D6 variation was significantly associated with concentrations of endoxifen (P = 0.0008) and 4‐hydroxytamoxifen (P = 0.0074), tamoxifen's principal active metabolites, as well as key metabolic ratios. The CYP2D6 was also the most significant predictor of active metabolites and metabolic ratios in a multivariate regression model, including all four genes as predictors, with minor roles for other CYP genes. In AIAN populations, CYP2D6 is the largest contributor to tamoxifen bioactivation, illustrating the importance of validating pharmacogenetic testing for therapy optimization in an understudied population.
Optimisation of antithrombin resistance assay as a practical clinical laboratory test: Development of prothrombin activator using factors Xa/Va and automation of assay
Authors: Tamura S. , Suga Y. , Tanamura M. , Murata‐Kawakami M. , Takagi Y. , Hottori Y. , Kakihara M. , Suzuki S. , Takagi A. , Kojima T. 
Published: February 2018

AbstractIntroductionAntithrombin resistance (ATR) is a novel thrombotic risk in abnormal prothrombins. A manual ATR assay using Oxyuranus scutellatus (Ox) venom as a prothrombin activator was established for detecting antithrombin‐resistant prothrombin. However, this assay was limited because of Ox snake venom availability and its throughput capacity. Here, we have improved the ATR assay using bovine factors Xa and Va (FXa/Va) as prothrombin activators and have optimised assay conditions for an automated instrument (ACL TOP 500).MethodsDiluted plasma was incubated with a prothrombin activator mix (phospholipids, CaCl2, and bovine FXa/Va), followed by inactivation with antithrombin for 10, 20 and 30 minutes. We added a chromogenic substrate S‐2238, and assessed changes in absorbance/min at 405 nm. We also adapted assay conditions for ACL TOP 500.ResultsOptimum conditions for FXa/Va treatment were 6.25% phospholipids, 5 mM CaCL2, 0.01 μg/mL FXa and 0.1 μg/mL FVa. ATR assay kinetics with the FXa/Va activator was comparable with that with the Ox activator in heterozygous reconstituted plasma with the recombinant wild‐type or antithrombin‐resistant prothrombin. Using ACL TOP 500, optimum conditions for the FXa/Va treatment were 10.0% phospholipids, 5 mM CaCl2, 0.02 μg/mL FXa and 0.2 μg/mL FVa. The automated ATR assay with the FXa/Va activator demonstrated good detectability for antithrombin‐resistant prothrombin in plasma from a heterozygous carrier with prothrombin Yukuhashi or Belgrade.ConclusionWe optimised the ATR assay with the FXa/Va activator and adapted the assay for ACL TOP 500; the assay showed the ability to clearly detect antithrombin‐resistant prothrombin in manual and automated procedures.
Much ado about flu: A mixed methods study of parental perceptions, trust and information seeking in a pandemic
Authors: King Catherine L. , Chow Maria Y. K. , Wiley Kerrie E. , Leask Julie 
Published: February 2018

BackgroundEffective public health messaging is essential in both the planning phase and duration of a pandemic.ObjectivesThis study aimed to gain an understanding of parental information seeking, trusted sources and needs in relation to pandemic influenza A 2009 (pH1N1) to inform future policy planning and resource development.Patients/MethodsWe conducted a mixed methods study; parents from 16 childcare centres in Sydney, Australia, were surveyed between 16 November and 9 December 2009, and interviews were conducted with participants from six childcare centres between June 2009 and May 2011.ResultsFrom 972 surveys distributed, 431 were completed; a response rate of 44%. Most parents (90%) reported that doctors were “trusted a lot” as a source of influenza information, followed by nurses (59%), government (56%) and childcare centres (52%). Less trusted sources included media (7% selected “trusted a lot”), antivaccination groups (6%) and celebrities (1%). Parents identified a range of key search terms for influenza infection and vaccine. From 42 in‐depth interviews, key themes were as follows: “Action trigger,” “In an emergency, think Emergency,” “Fright to hype” and “Dr Google and beyond.” Parents relied heavily on media messages, but cynicism emerged when the pandemic was milder than expected. Parents viewed a range of information sources as trustworthy, including doctors, authoritative hospital or government websites, and childcare centres and schools.ConclusionsA user‐centred orientation is vital for pandemic communications including tailored information provision, via trusted sources based on what parents want to know and how they can find it.
CONTINUOUS PREFERENCE ORDERINGS REPRESENTABLE BY UTILITY FUNCTIONS
Authors: Hervés‐Beloso Carlos , del Valle‐Inclán Cruces Hugo 
Published: February 2018

AbstractThis paper surveys the conditions under which it is possible to represent a continuous preference ordering using utility functions. We start with a historical perspective on the notions of utility and preferences, continue by defining the mathematical concepts employed in this literature, and then list several key contributions to the topic of representability. These contributions concern both the preference orderings and the spaces where they are defined. For any continuous preference ordering, we show the need for separability and the sufficiency of connectedness and separability, or second countability, of the space where it is defined. We emphasize the need for separability by showing that in any nonseparable metric space, there are continuous preference orderings without utility representation. However, by reinforcing connectedness, we show that countably boundedness of the preference ordering is a necessary and sufficient condition for the existence of a (continuous) utility representation. Finally, we discuss the special case of strictly monotonic preferences.
Laparoscopic diagnosis and treatment of an isolated epithelioid trophoblastic tumor in recto‐uterine pouch
Authors: Jiang Fang , Xiang Yang , Guo Li‐na 
Published: February 2018

AbstractA 30‐year‐old Chinese woman with irregular vaginal bleeding was admitted to our department. Serum β‐human chorionic gonadotropin (β‐hCG) was moderately elevated, and ultrasound and magnetic resonance imaging revealed an irregular, retro‐uterine lesion without intrauterine pregnancy. Ectopic pregnancy was the primary consideration, with trophoblastic tumor being another possibility. Laparoscopy revealed a 2 × 3 × 3 cm3 irregular, infiltrating, yellow‐white lesion in the left recto‐uterine pouch, which was completely resected without rectal damage. Final pathological/immunohistochemical analyses revealed an epithelial trophoblastic tumor (ETT) (Ki‐67 reactive index~45%). Postoperative recovery was smooth, and the patient received three chemotherapy courses (etoposide, methotrexate and actinomycin, alternating weekly with cyclophosphamide and vincristine) beginning 6 days postsurgery (β‐hCG = 46.4 mIU/mL). β‐hCG returned to an undetectable level after one chemotherapy course. Herein, we describe a rare case of isolated ETT that was difficult to differentiate from other pregnancy‐related diseases. Laparoscopy could be an effective, safe diagnostic method in select patients.
Infertility treatment strategy involving combined freeze‐all embryos and single vitrified‐warmed embryo transfer during hormonal replacement cycle for in vitro fertilization of women with hypogonadotropic hypogonadism
Authors: Kuroda Keiji , Ezoe Kenji , Kato Keiichi , Yabuuchi Akiko , Segawa Tomoya , Kobayashi Tamotsu , Ochiai Asako , Katoh Noriko , Takeda Satoru 
Published: February 2018

AbstractAimHypogonadotropic hypogonadism (HH) is a condition caused by the deficient secretion of pituitary gonadotropins, leading to diminished ovarian function. Several studies of in vitro fertilization (IVF) in women with HH revealed acceptable clinical pregnancy outcomes but high multiple pregnancy rates after multiple fresh embryo transfer (ET). The purpose of this study was to analyze the outcomes of combined freeze‐all embryos and single vitrified‐warmed ET in women with HH.MethodsOf 91 infertile women with HH (basal luteinizing hormone and follicle‐stimulating hormone levels <2.0 mIU/mL), we excluded patients aged ≥40 years (n = 2) and women who preferred fresh ET (n = 10). Seventy‐nine women underwent 117 oocyte retrieval cycles and 135 vitrified‐warmed ET during hormone replacement (HR) cycles from 2008 to 2014 at the Kato Ladies Clinic and Juntendo University Hospital.ResultsIn 26 single cleavage ET cycles, the rates of clinical pregnancy and live birth were 34.6% (9/26 ET) and 26.9% (7/26 ET), respectively. Regarding the outcomes after single vitrified‐warmed blastocyst transfer, clinical pregnancy and live birth rates were 65.1% (71/109 ET) and 50.5% (55/109 ET), respectively. Multiple conceptions and ovarian hyperstimulation syndrome did not occur in any of the women with HH.ConclusionOur results demonstrated that IVF followed by single vitrified‐warmed ET in adjusted endocrine milieu during the HR cycle is an effective fertility treatment for women with HH and decreases the incidence of complications, including multiple conceptions.
Credit portfolio selection with decaying contagion intensities
Authors: Bo Lijun , Capponi Agostino , Chen Peng‐Chu 
Published: February 2018

AbstractWe develop a fixed‐income portfolio framework capturing the exponential decay of contagious intensities between successive default events. We show that the value function of the control problem is the classical solution to a recursive system of second‐order uniformly parabolic Hamilton–Jacobi–Bellman partial differential equations. We analyze the interplay between risk premia, decay of default intensities, and their volatilities. Our comparative statics analysis finds that the investor chooses to go long only if he is capturing enough risk premia. If the default intensities deteriorate faster, the investor increases the size of his position if he goes short, or reduces the size of his position if he goes long.
Prediction Model for Antimalarial Activities of Hemozoin Inhibitors by Using Physicochemical Properties
Authors: Mosaddeque Farhana , Mizukami Shusaku , Kamel Mohamed Gomaa , Teklemichael Awet Alem , Dat Truong Van , Mizuta Satoshi , Toan Dinh Van , Ahmed Ali Mahmoud , Vuong Nguyen Lam , Elhady Mohamed Tamer , Giang Hoang Thi Nam , Dang Tran Ngoc , Fukuda Michiko , Huynh Lam K. , Tanaka Yoshimasa , Egan Timothy J. , Kaneko Osamu , Huy Nguyen Tien , Hirayama Kenji 
Published: February 2018

ABSTRACT

The rapid spread of strains of malaria parasites that are resistant to several drugs has threatened global malaria control. Hence, the aim of this study was to predict the antimalarial activity of chemical compounds that possess anti-hemozoin-formation activity as a new means of antimalarial drug discovery. After the initial
in vitro
anti-hemozoin-formation high-throughput screening (HTS) of 9,600 compounds, a total of 224 hit compounds were identified as hemozoin inhibitors. These 224 compounds were tested for
in vitro
erythrocytic antimalarial activity at 10 μM by using chloroquine-mefloquine-sensitive
Plasmodium falciparum
strain 3D7A. Two independent experiments were conducted. The physicochemical properties of the active compounds were extracted from the ChemSpider and SciFinder databases. We analyzed the extracted data by using Bayesian model averaging (BMA). Our findings revealed that lower numbers of S atoms; lower distribution coefficient (log D) values at pH 3, 4, and 5; and higher predicted distribution coefficient (ACD log D) values at pH 7.4 had significant associations with antimalarial activity among compounds that possess anti-hemozoin-formation activity. The BMA model revealed an accuracy of 91.23%. We report new prediction models containing physicochemical properties that shed light on effective chemical groups for synthetic antimalarial compounds and help with
in silico
screening for novel antimalarial drugs.
Ecology and Biotechnological Potential of Bacteria Belonging to the Genus Pseudovibrio
Authors: Romano Stefano 
Published: February 2018

ABSTRACT

Members of the genus
Pseudovibrio
have been isolated worldwide from a great variety of marine sources as both free-living and host-associated bacteria. So far, the available data depict a group of alphaproteobacteria characterized by a versatile metabolism, which allows them to use a variety of substrates to meet their carbon, nitrogen, sulfur, and phosphorous requirements. Additionally,
Pseudovibrio
-related bacteria have been shown to proliferate under extreme oligotrophic conditions, tolerate high heavy-metal concentrations, and metabolize potentially toxic compounds. Considering this versatility, it is not surprising that they have been detected from temperate to tropical regions and are often the most abundant isolates obtained from marine invertebrates. Such an association is particularly recurrent with marine sponges and corals, animals that play a key role in benthic marine systems. The data so far available indicate that these bacteria are mainly beneficial to the host, and besides being involved in major nutrient cycles, they could provide the host with both vitamins/cofactors and protection from potential pathogens via the synthesis of antimicrobial secondary metabolites. In fact, the biosynthetic abilities of
Pseudovibrio
spp. have been emerging in recent years, and both genomic and analytic studies have underlined how these organisms promise novel natural products of biotechnological value.
Structural Characterization and Directed Evolution of a Novel Acetyl Xylan Esterase Reveals Thermostability Determinants of the Carbohydrate Esterase 7 Family
Authors: Adesioye Fiyinfoluwa A. , Makhalanyane Thulani P. , Vikram Surendra , Sewell Bryan T. , Schubert Wolf-Dieter , Cowan Don A. 
Published: February 2018

ABSTRACT

A hot desert hypolith metagenomic DNA sequence data set was screened
in silico
for genes annotated as acetyl xylan esterases (AcXEs). One of the genes identified encoded an ∼36-kDa protein (Axe1
NaM1
). The synthesized gene was cloned and expressed, and the resulting protein was purified. NaM1 was optimally active at pH 8.5 and 30°C and functionally stable at salt concentrations of up to 5 M. The specific activity and catalytic efficiency were 488.9 U mg
−1
and 3.26 × 10
6
M
−1
s
−1
, respectively. The crystal structure of wild-type NaM1 was solved at a resolution of 2.03 Å, and a comparison with the structures and models of more thermostable carbohydrate esterase 7 (CE7) family enzymes and variants of NaM1 from a directed evolution experiment suggests that reduced side-chain volume of protein core residues is relevant to the thermal stability of NaM1. Surprisingly, a single point mutation (N96S) not only resulted in a simultaneous improvement in thermal stability and catalytic efficiency but also increased the acyl moiety substrate range of NaM1.

IMPORTANCE
AcXEs belong to nine carbohydrate esterase families (CE1 to CE7, CE12, and CE16), of which CE7 enzymes possess a unique and narrow specificity for acetylated substrates. All structurally characterized members of this family are moderately to highly thermostable. The crystal structure of a novel, mesophilic CE7 AcXE (Axe1
NaM1
), from a soil metagenome, provides a basis for comparisons with thermostable CE7 enzymes. Using error-prone PCR and site-directed mutagenesis, we enhanced both the stability and activity of the mesophilic AcXE. With comparative structural analyses, we have also identified possible thermal stability determinants. These are valuable for understanding the thermal stability of enzymes within this family and as a guide for future protein engineering of CE7 and other α/β hydrolase enzymes.
Facile Arsenazo III-Based Assay for Monitoring Rare Earth Element Depletion from Cultivation Media for Methanotrophic and Methylotrophic Bacteria
Authors: Hogendoorn Carmen , Roszczenko-Jasińska Paula , Martinez-Gomez N. Cecilia , de Graaff Johann , Grassl Patrick , Pol Arjan , Op den Camp Huub J. M. , Daumann Lena J. 
Published: February 2018

ABSTRACT

Recently, methanotrophic and methylotrophic bacteria were found to utilize rare earth elements (REEs). To monitor the REE content in culture media of these bacteria, we have developed a rapid screening method using the Arsenazo III (AS III) dye for spectrophotometric REE detection in the low μM (0.1 to 10 μM) range. We designed this assay to follow La
III
and Eu
III
depletion from the culture medium by the acidophilic verrucomicrobial methanotroph
Methylacidiphilum fumariolicum
strain SolV. The assay can also be modified to screen the uptake of other REEs, such as Pr
III
, or to monitor the depletion of La
III
from growth media in neutrophilic methylotrophs such as
Methylobacterium extorquens
strain AM1. The AS III assay presents a convenient and fast detection method for REE levels in culture media and is a sensitive alternative to inductively coupled plasma mass spectrometry (ICP-MS) or atomic absorption spectroscopy (AAS).

IMPORTANCE
REE-dependent bacterial metabolism is a quickly emerging field, and while the importance of REEs for both methanotrophic and methylotrophic bacteria is now firmly established, many important questions, such as how these insoluble elements are taken up into cells, are still unanswered. Here, an Arsenazo III dye-based assay has been developed for fast, specific, and sensitive determination of REE content in different culture media. This assay presents a useful tool for optimizing cultivation protocols, as well as for routine REE monitoring during bacterial growth without the need for specialized analytical instrumentation. Furthermore, this assay has the potential to promote the discovery of other REE-dependent microorganisms and can help to elucidate the mechanisms for acquisition of REEs by methanotrophic and methylotrophic bacteria.
A Natural Mouse Model for Neisseria Colonization
Authors: Ma Mancheong , Powell Daniel A. , Weyand Nathan J. , Rhodes Katherine A. , Rendón María A. , Frelinger Jeffrey A. , So Magdalene 
Published: February 2018

ABSTRACT

Commensals are important for the proper functioning of multicellular organisms. How a commensal establishes persistent colonization of its host is little understood. Studies of this aspect of microbe-host interactions are impeded by the absence of an animal model. We have developed a natural small animal model for identifying host and commensal determinants of colonization and of the elusive process of persistence. Our system couples a commensal bacterium of wild mice,
Neisseria musculi
, with the laboratory mouse. The pairing of a mouse commensal with its natural host circumvents issues of host restriction. Studies are performed in the absence of antibiotics, hormones, invasive procedures, or genetic manipulation of the host. A single dose of
N. musculi
, administered orally, leads to long-term colonization of the oral cavity and gut. All mice are healthy. Susceptibility to colonization is determined by host genetics and innate immunity. For
N. musculi
, colonization requires the type IV pilus. Reagents and powerful tools are readily available for manipulating the laboratory mouse, allowing easy dissection of host determinants controlling colonization resistance.
N. musculi
is genetically related to human-dwelling commensal and pathogenic
Neisseria
and encodes host interaction factors and vaccine antigens of pathogenic
Neisseria
. Our system provides a natural approach for studying
Neisseria
-host interactions and is potentially useful for vaccine efficacy studies.
Increased Activity of Cystathionine β-Lyase Suppresses 2-Aminoacrylate Stress in Salmonella enterica
Authors: Ernst Dustin C. , Christopherson Melissa R. , Downs Diana M. 
Published: February 2018

ABSTRACT

Reactive enamine stress caused by intracellular 2-aminoacrylate accumulation leads to pleiotropic growth defects in a variety of organisms. Members of the well-conserved RidA/YER057c/UK114 protein family prevent enamine stress by enhancing the breakdown of 2-aminoacrylate to pyruvate. In
Salmonella enterica
, disruption of RidA allows 2-aminoacrylate to accumulate and to inactivate a variety of pyridoxal 5′-phosphate-dependent enzymes by generating covalent bonds with the enzyme and/or cofactor. This study was initiated to identify mechanisms that can overcome 2-aminoacrylate stress in the absence of RidA. Multicopy suppressor analysis revealed that overproduction of the methionine biosynthesis enzyme cystathionine β-lyase (MetC) (EC 4.4.1.8) alleviated the pleiotropic consequences of 2-aminoacrylate stress in a
ridA
mutant strain. Degradation of cystathionine by MetC was not required for suppression of
ridA
phenotypes. The data support a model in which MetC acts on a noncystathionine substrate to generate a metabolite that reduces 2-aminoacrylate levels, representing a nonenzymatic mechanism of 2-aminoacrylate depletion.

IMPORTANCE
RidA proteins are broadly conserved and have been demonstrated to deaminate 2-aminoacrylate and other enamines. 2-Aminoacrylate is generated as an obligatory intermediate in several pyridoxal 5′-phosphate-dependent reactions; if it accumulates, it damages cellular enzymes. This study identified a novel mechanism to eliminate 2-aminoacrylate stress that required the overproduction, but not the canonical activity, of cystathionine β-lyase. The data suggest that a metabolite-metabolite interaction is responsible for quenching 2-aminoacrylate, and they emphasize the need for emerging technologies to probe metabolism
in vivo
.