bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel glucuronosyltransferase has an unprecedented ability to catalyse continuous two‐step glucuronosylation of glycyrrhetinic acid to yield glycyrrhizin
Authors: Xu Guojie , Cai Wei , Gao Wei , Liu Chunsheng
Published: June 2016

Glycyrrhizin is an important bioactive compound that is used clinically to treat chronic hepatitis and is also used as a sweetener world‐wide. However, the key UDP‐dependent glucuronosyltransferases (UGATs) involved in the biosynthesis of glycyrrhizin remain unknown.

To discover unknown UGATs, we fully annotated potential UGATs from Glycyrrhiza uralensis using deep transcriptome sequencing. The catalytic functions of candidate UGATs were determined by an in vitro enzyme assay.

Systematically screening 434 potential UGATs, we unexpectedly found one unique GuUGAT that was able to catalyse the glucuronosylation of glycyrrhetinic acid to directly yield glycyrrhizin via continuous two‐step glucuronosylation. Expression analysis further confirmed the key role of GuUGAT in the biosynthesis of glycyrrhizin. Site‐directed mutagenesis revealed that Gln‐352 may be important for the initial step of glucuronosylation, and His‐22, Trp‐370, Glu‐375 and Gln‐392 may be important residues for the second step of glucuronosylation. Notably, the ability of GuUGAT to catalyse a continuous two‐step glucuronosylation reaction was determined to be unprecedented among known glycosyltransferases of bioactive plant natural products.

Our findings increase the understanding of traditional glycosyltransferases and pave the way for the complete biosynthesis of glycyrrhizin.
The moral animal: virtue, vice, and human nature
Authors: Paulson Steve , Berlin Heather A. , Miller Christian B. , Shermer Michael
Published: June 2016

In Leo Tolstoy's famous novella, The Death of Ivan Ilyich, a rich and meaningful inner life is sacrificed in pursuit of material rewards and social status. How can we cultivate something intrinsic that transcends our worldly accomplishments? Assuming that a basic model or map of human nature is needed to navigate the road to the good life, what desires, tendencies, and aversions constitute our core nature? How has our evolutionary history shaped our moral impulses? Are we inherently good or fundamentally flawed? Steve Paulson, executive producer and host of To the Best of Our Knowledge, moderated a discussion with philosopher Christian Miller, neuroscientist Heather Berlin, and historian of science Michael Shermer to examine our moral ecology and its influence on our underlying assumptions about human nature.
Nutrition and bone health
Authors: Weaver CM
Published: June 2016

Low bone mass leads to fracture risk. Osteoporosis affects over 10% of the population and one of every two women over the age of 50 years. Genetics predicts more than half of bone mass. Diet and weight bearing exercise are two lifestyle choices that can influence the risk of fracture. Nutrients are the structural constituents of bone. As bone is a living tissue and turns over, albeit more slowly than other tissues, there is an obligatory loss of minerals daily that must be replaced through diet. Three servings of dairy products daily are recommended to replace those losses. Alternative sources of nutrients can come from calcium fortified orange juice, plant‐based beverages, or tofu to provide many nutrients needed for bone health. Supplements can provide nutrients at risk for being inadequate such as calcium or vitamin D.
Local Government Risk Assessment: The Effect of Government Type on Credit Rating Decisions in Texas
Authors: Greer Robert A.
Published: June 2016

In consideration of increased levels of debt issued by special purpose local governments, this study explores the relationship between local government type and credit rating decisions. Investors use credit ratings as a signal for default risk, and risk level is a function of local economic base including service responsibilities and revenue sources. Governmental functions and economic bases vary across local government types which affect credit rating decisions. Specifically, special purpose governments have more limited responsibilities and revenue sources compared to general purpose governments. To model the decision of agency selection a multivariate probit model is estimated using bond deals from six different types of local governments in Texas. Findings suggest differences among general purpose and special purpose local governments. This supports the hypothesis that economic base affects credit rating decisions. Results indicate that credit rating agencies evaluate and weight information differently, and that local governments chose rating agencies in response.
The Political Economy of Land Finance in China
Authors: Wang Wen , Ye Fangzhi
Published: June 2016

The heavy reliance of Chinese local governments on land‐leasing revenues in recent decades has attracted widespread criticism due to its potential risks and problems. This research, using a panel dataset of 280 prefecture‐level cities in China from 1999 to 2009, explores what factors affect Chinese city governments’ dependence on land finance. The findings provide strong support for hypotheses concerning the effects of both fiscal incentives and political incentives on local fiscal behavior. Both fiscal factors—such as local reliance on fiscal transfers and fiscal decentralization—and political factors—including local top leaders’ tenure and their distance to mandatory retirement—have exerted significant impacts on city governments’ reliance on land finance. These findings point to the significance of intergovernmental fiscal arrangements and political institutions in affecting local government fiscal behavior in developing countries.
Lights, Camera, Action: The Adoption of State Film Tax Credits
Authors: Sewordor Emefa , Sjoquist David L.
Published: June 2016

Over the last 20 years, states have adopted tax incentives focused on film production. Louisiana adopted the first state tax incentive program for film production in 1992, and by 2009 such tax incentive programs had expanded to 44 states plus the District of Columbia. The purpose of this paper is to identify the factors that explain the pattern of adoption of state film tax incentive programs. We develop a theoretical framework for analyzing states’ decision to adopt these programs that considers both internal characteristics and diffusion. We empirically investigate the timing of states’ adoption of film tax incentives using the Cox proportional hazards model with time‐varying predictors. The estimates of many of the hazard ratios are consistent with our expectation, although several are statistically insignificant. As expected, the pattern of adoption across states supports the hypothesis that it is a “mimicking” phenomenon. However, we find that fiscal stress results in faster adoption of film tax credits, contrary to expectations, but consistent with the notion that states look at them as a “luxury.”
Mapping of Lr56 translocation recombinants in wheat
Authors: Somo Mohamed , Pirseyedi Seyed Mostafa , Cai Xiwen , Sharma Poudel Roshan , Chao Shiaoman , Marais Francois
Published: June 2016

In an attempt to transfer the Lr56/Yr38 resistance loci from Aegilops sharonensis to wheat, a 6A‐6Ssh chromosome translocation was produced. It involves essentially the entire chromosome 6Ssh with a small terminal segment of 6AL. Induced homoeologous recombination of the translocated chromosome with 6A produced numerous recombinants including three recombined chromosomes carrying Lr56 that could not be precisely mapped for lack of suitable markers. This study aimed to determine the chromosomal locations of the translocation breakpoints in these three recombinants using various DNA markers as well as physical and genetic mapping. The three recombinants Lr56‐39, ‐157 and ‐175 carry small segments of Ae. sharonensis chromatin distally to the Xgpw4329 and IWA5416 loci near the 6AS telomere. The Ae. sharonensis chromatin that remains in each line includes a homoeolocus of the wheat marker locus Xdupw217 (on 6BS) and its characteristic amplification product can be used as a dominant marker for the presence of Lr56. Of the three recombined chromosomes, Lr56‐157 retained the least alien chromatin and appears to be the best candidate for use in wheat breeding.
Detection of serous precursor lesions in resected fallopian tubes from patients with benign diseases and a relatively low risk for ovarian cancer
Authors: Nishida Naoyo , Murakami Fumihiro , Higaki Koichi
Published: June 2016

The frequency of ovarian cancers in Japan has increased; however, doubts have been raised concerning the mechanism by which high‐grade serous adenocarcinomas (HGSCs) arise. Conventionally, HGSC is thought to originate from the ovarian surface epithelium or epithelial inclusion cyst. However, recent data indicate that HGSCs may in fact develop from precursor lesions in the fallopian tube, including epithelia with a p53 signature, serous tubal intraepithelial carcinomas (STICs), secretory cell outgrowths (SCOUTs), and tubal intraepithelial lesions in transition (TILT). Here, we determined the frequency of these fallopian tube precursors in surgically excised samples from 123 patients with benign pelvic diseases. We identified 12 cases with a p53 signature (9.7%), 26 with observable SCOUTs (21.1%), and 4 with TILT (3.2%), but no STIC cases. Although the lifetime risk for developing ovarian cancer is only around 1.4% for women without germ‐line mutations, it is important to evaluate the presence of precursor lesions to understand HGSC pathogenesis better. Taken together, salpingectomy appears to be an option for women who are past their childbearing age and plan to undergo elective pelvic surgery. To our knowledge, this is the first study to investigate the presence of these specific precursors post‐salpingectomy in low‐risk patients.
Unique infection structures produced by Pseudocercosporella capsellae on oilseed crops Brassica carinata, B. juncea and B. napus in Western Australia
Authors: Gunasinghe N. , You M. P. , Clode P. , Cawthray G. R. , Barbetti M. J.
Published: June 2016

White leaf spot disease (Pseudocercosporella capsellae) is widespread across oilseed, vegetable and forage brassicas. Light (LM) and scanning electron (SEM) microscope studies were undertaken to investigate host–pathogen interactions on cotyledons of resistant and susceptible Brassica carinata, B. juncea and B. napus. Under LM, unique brown structures were present, particularly on susceptible genotypes, in two morphologically distinct forms: first, as thread‐like structures within cortical tissue by 24 h post‐inoculation (hpi) and secondly, as brown ropy strand structures either within cortical tissues (internal ropy strands), or extruded out through stomatal pores (ropy strand extrusions). Under LM, these brown structures were most prevalent in highly susceptible B. juncea ‘Vardan’ that had both a high incidence within cortical tissue (70%) and of ropy strand extrusions (73%), as did susceptible B. napus ‘Trilogy’ within cortical tissue (60%). Under SEM, both these genotypes showed thread‐like structures smaller than hyphae forming highly branched networks and ropy strand‐like structures. While there were fewer brown structures in susceptible B. carinata UWA #012 (35%), fine, thread‐like structures forming networks were again prominent (SEM). In contrast, for resistant genotypes, brown structures (LM) were of very low frequency or absent; only 5% in resistant B. juncea ‘Dune’ and none in resistant B. napus ‘Hyola 42’ or highly resistant B. carinata ATC94129P. Under SEM, fine, thread‐like structures were present in the resistant B. juncea ‘Dune’ and B. napus ‘Hyola 42’. Liquid chromatographic analyses of brown structures revealed that both internal ropy strands within cortical tissues and ropy strand extrusions contained the mycotoxin cercosporin.
Diagnostic utility of additional conventional techniques after endobronchial ultrasonography guidance during transbronchial biopsy
Authors: Kunimasa Kei , Tachihara Motoko , Tamura Daisuke , Tokunaga Shuntaro , Nakata Kyosuke , Hazeki Nobuko , Kamiryo Hiroshi , Kobayashi Kazuyuki , Sakai Yasuhiro , Nishimura Yoshihiro
Published: June 2016

Background and objective

Endobronchial ultrasonography with a guide sheath transbronchial biopsy (EBUS‐GS TBB) has been used to diagnose peripheral pulmonary lesions (PPLs). In this study, we evaluated the diagnostic utility of conventional TBB after EBUS‐GS TBB.

Methods

A retrospective analysis of patients who underwent conventional TBB after EBUS‐GS TBB for PPL between August 1, 2012 and December 31, 2014. We performed multivariate analysis to examine the association of various clinical factors, including EBUS probe distance and sample size area, with diagnostic yield.

Results

Of 88 eligible patients, 57 (65%) were successfully diagnosed by EBUS‐GS TBB. In 31 patients not diagnosed by EBUS‐GS TBB, 15 (48%) were successfully diagnosed by additional conventional TBB. Ground glass opacity (GGO) was a significant factor associated with the diagnostic yield of additional conventional TBB following EBUS‐GS TBB. Multivariate analysis and receiver operator curves revealed that distance between the PPL and the EBUS probe of less than 2.55 mm favored the utility of conventional TBB.

Conclusion

Additional conventional TBB after EBUS‐GS TBB could be a useful procedure for the diagnosis of ground glass opacity PPLs and in cases of a distance of less than 2.55 mm between the EBUS probe and the lesion.
Effects of continuous positive airway pressure on diaphragmatic kinetics and breathing pattern in healthy individuals
Authors: Soilemezi Eleni , Koco Entela , Tsimpos Christos , Tsagourias Matthew , Savvidou Savvoula , Matamis Dimitris
Published: June 2016

Background and objective

In this study, we investigate the changes in diaphragmatic kinetics, breathing pattern and work of breathing induced by 10 cmH2O of continuous positive airway pressure (CPAP).

Methods

We used sonography to study diaphragmatic kinetics and measured energy expenditure using indirect calorimetry in 50 healthy volunteers at 0 cmH2O positive end expiratory pressure (ZEEP) and after application of 10 cmH2O CPAP. In a subgroup of 14 subjects, the changes in thoracic and abdominal volumes and thoraco‐abdominal asynchrony were recorded with inductive plethysmography, while accessory respiratory muscle activity was recorded with electromyography.

Results

Continuous positive airway pressure breathing induced acute lung hyperinflation of 600 mL above passive functional residual capacity. This hyperinflation induced changes in diaphragmatic kinetics and breathing pattern; diaphragmatic excursion, thickness and thickness ratio, tidal volume (Vt) and oxygen consumption (VO2) increased while respiratory rate decreased. The increase in Vt with CPAP was mainly due to rib cage contribution. Activation of the accessory inspiratory (scalene) and expiratory (transversus abdominis) muscles was recorded. The raised respiratory muscles workload induced an increase in VO2.

Conclusion

In healthy volunteers, CPAP therapy leads to lung overdistention and recruitment of respiratory muscles. These mechanisms operate at a high energy cost.
Beyond Individualised Approaches to Diabetes Type 2
Authors: Williams Claire R. , Buttfield Barbara
Published: June 2016

Explanations for type 2 diabetes are broadened beyond the individual body and ‘bad lifestyles’ to include major institutions, the social and material contexts of food and eating, and employment. Precarious employment, a social determinant of health, encourages changes to food practices, lowers working conditions, worsens health, can bring poverty and increases shift work, a causal risk factor for diabetes. Scientists have played a part in revolutionising foods and technologies which minimise labour and movement. There are excess additives in processed food. Genetic explanations for the higher rates of diabetes in First Nations peoples give way to social explanations: colonial history, British/Euro‐American cuisine, food insecurity, trauma and social conditions resulting in chronic stress. Self‐management education takes a ‘nutritionist’ approach towards food and eating and tends to minimise the social context and skills of those with the condition particularly women workers in poorer social groups who have higher rates of diabetes (T2DM).
Defining Women's Global Political Empowerment: Theories and Evidence
Authors: Alexander Amy C. , Bolzendahl Catherine , Jalalzai Farida
Published: June 2016

Although women's access to political power has increased tremendously, nowhere are women equal to men in their influence over and exercise of political authority. Scholarship on women's political empowerment is uneven and incomplete. This article interrogates ‘women's political empowerment’, considering its definition, measurement, and application. First, we establish that academics and practitioners have not articulated a clear definition of women's political empowerment. To fill this gap, we put forward a new definition that conceptualizes women's political empowerment as a transformative process. We then review existing social science literature on women's political empowerment. We argue that scholars must expand research to develop a broader vision of women's political empowerment and develop measures that capture this breadth.
Biology and phylogenetic placement of a new species of Lasiokapala Ashmead from Argentina (Hymenoptera: Eucharitidae)
Authors: TORRÉNS JAVIER , HERATY JOHN M. , MURRAY ELIZABETH , FIDALGO PATRICIO
Published: June 2016

Within the ant‐parasitic wasp family Eucharitidae (Hymenoptera), the Kapala clade is a monophyletic group attacking Ectatomminae and Ponerinae. Members often express extreme phenotypic features, especially in the morphology of the paired frenal spines. Although the means of attack and developmental history of the eucharitid wasps within the ant nest are very similar, the means by which they oviposit and optimize encounters of their active first‐instar larvae with ants is highly variable. The relationships and life‐history strategies of Lasiokapala Ashmead (Hymenoptera: Eucharitidae) and related taxa within the Kapala clade are discussed based on phylogenetic analyses of morphological and molecular data. Descriptions are provided for the adults (both sexes), eggs and planidia of Lasiokapala spiralicornis sp.n. from Santiago del Estero (Argentina). Females deposit their eggs on the underside of leaves of Sida cordifolia L. (Malvaceae) and the likely host is postulated to be the genus Ectatomma (Formicidae: Ectatomminae). Even within a closely related group of genera, there is extreme independent divergence in morphology of scutellar spines, antennae and other features, but the larvae and larval biology are highly conserved across a much larger group of Eucharitidae.

This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:pub:3536985B‐D193‐4771‐BFA3‐25A59EFF6AB5.
Out of the Neotropics: newly discovered relictual species sheds light on the biogeographical history of spider ants (Leptomyrmex, Dolichoderinae, Formicidae)
Authors: BOUDINOT BRENDON E. , PROBST RODOLFO S. , BRANDÃO CARLOS ROBERTO F. , FEITOSA RODRIGO M. , WARD PHILIP S.
Published: June 2016

Spider ants of the genus Leptomyrmex Mayr (Hymenoptera: Formicidae: Dolichoderinae) are conspicuous species of Australasian rainforests, with putative fossil relatives in the Neotropics and Europe. There is longstanding debate over the biogeographical history of the genus, with the Palaearctic and Neotropical regions proposed as alternate centres of origin. We propose a resolution of this debate with the recent discovery and analysis of an extant species from central Brazil, L. relictus sp.n., which we describe from workers, males and brood. We sequence ten nuclear genes in the new species and in several Australian Leptomyrmex species, and append these data to a 54‐taxon, 10‐gene data matrix previously generated for the subfamily Dolichoderinae. We conduct phylogenetic and divergence dating analyses, and re‐evaluate the fossil record of the group. We recover Leptomyrmex relictus sp.n. as a member of the Leptomyrmex clade with high support. It is sister to the Australasian species, and the genus Leptomyrmex is, in turn, sister to a pair of Neotropical genera, Forelius and Dorymyrmex. We infer a Neotropical origin for the genus and estimate a mid‐Eocene (46 Ma, 95% CI 56 to 36 Ma) origin for the crown genus and an Oligocene origin for the Australasian clade (29 Ma, 95% CI 40 to 19 Ma). We confirm placement of the Dominican amber species †L. neotropicus Baroni Urbani in the genus but reject a close relationship with the Palaearctic fossil taxa †Leptomyrmula Emery and †Usomyrma Dlussky, Radchenko & Dubovikoff, considering them incertae sedis in the subfamily (Dolichoderinae). In contrast to the mesophilic preferences of the Australasian species of Leptomyrmex, the new Brazilian species inhabits cerrado (dry savannah). Our results support a Neotropical origin for spider ants with dispersal to Australia. Rafting on west‐bound currents and/or a historical diversity imbalance between Australia and South America are proposed as alternate hypotheses to explain a pattern of biased E–W mid‐Tertiary dispersal for ants with austral distributions. This pattern is suggested by our results in conjunction with observations of other ant clades. Overall, our findings highlight the value of integrated taxonomy, critical interpretation of morphology, and a comparative phylogenetic framework when conducting palaeontological and biogeographical studies of insect species.

This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:pub:6E9E6617‐6E53‐40B8‐82C7‐67F89A83C553.
Hemostatic properties and protein expression profile of therapeutic apheresis plasma treated with amotosalen and ultraviolet A for pathogen inactivation
Authors: Ohlmann Philippe , Hechler Béatrice , Chafey Philippe , Ravanat Catherine , Isola Hervé , Wiesel Marie‐Louise , Cazenave Jean‐Pierre , Gachet Christian
Published: June 2016

BACKGROUND

The INTERCEPT Blood System (IBS) using amotosalen‐HCl and ultraviolet (UV)A inactivates a large spectrum of microbial pathogens and white blood cells in therapeutic plasma. Our aim was to evaluate to what extent IBS modifies the capacity of plasma to generate thrombin and induces qualitative or quantitative modifications of plasma proteins.

STUDY DESIGN AND METHODS

Plasma units from four donors were collected by apheresis. Samples were taken before (control [CTRL]) and after IBS treatment and stored at −80°C until use. The activities of plasma coagulation factors and inhibitors and the thrombin generation potential were determined using assays measuring clotting times and the calibrated automated thrombogram (CAT), respectively. The proteomic profile of plasma proteins was examined using a two‐dimensional differential in‐gel electrophoresis (2D‐DIGE) method.

RESULTS

Nearly all of the procoagulant and antithrombotic factors tested retained at least 78% of their initial pre‐IBS activity. Only FVII and FVIII displayed a lower level of conservation (67%), which nevertheless remained within the reference range for conventional plasma coagulation factors. The thrombin generation profile of plasma was conserved after IBS treatment. Among the 1331 protein spots revealed by 2D‐DIGE analysis, only four were differentially expressed in IBS plasma compared to CTRL plasma and two were identified by mass spectrometric analysis as transthyretin and apolipoprotein A1.

CONCLUSION

The IBS technique for plasma moderately decreases the activities of plasma coagulation factors and antithrombotic proteins, with no impact on the thrombin generation potential of plasma and very limited modifications of the proteomic profile.
Fast and low-cost method to fabricate large-area superhydrophobic surface on steel substrate with anticorrosion and anti-icing properties
Authors: Yan Wei , Liu Hongtao , Chen Tianchi , Sun Qinghe , Zhu Wei
Published: June 2016

A facile and quick fabrication method was proposed to prepare superhydrophobic surfaces on iron substrate by chemical immersion and subsequent stearic acid modification. The association between wettability and surface morphology was studied through altering the copper ion concentration and immersion time. Surface tension instrument, scanning electron microscopy, x-ray diffraction, x-ray photoelectron spectroscopy, and electrochemical workstation were used to characterize the wettability, physical morphology, chemical composition, and corrosion resistance ability of the prepared film. Results showed that both the rough micro/nanostructures and low surface energy material play critical roles in surface wettability. The superhydrophobic film achieved a better anticorrosion property compared to barrier iron by analysis of open circuit potential, potentiodynamic polarization curves, and Nyquist plots. In addition, the superhydrophobic surface showed excellent performance of acid and alkali resistance, anti-icing, and self-cleaning through a series of environmental tests. This study provides a valid method for quick-preparation of the stable superhydrophobic surfaces, which has a promising application in steel buildings and facilities.
Height-Adjustable Desks: Energy Expenditure, Liking, and Preference of Sitting and Standing
Authors: Roemmich James N.
Published: June 2016

Background:

Breaking periods of sitting with standing may prevent chronic diseases and increase energy expenditure (EE). Sit-to-stand height adjustable desks may promote workplace standing, but workers have to be willing to stand for portions of the workday.

Methods:

For studies 1 and 2, EE was measured during word processing while sitting in a chair and while standing. Subjects scored their liking of each posture and time they would be willing to work in each posture during an 8-hour workday. Study 2 included an intervention of replacing subjects’ sitting desks with a height adjustable desk. Liking of and willingness to work in each posture were measured before and after the 12-month intervention.

Results:

EE was 7.5 kcal/h greater when standing than when sitting. Subjects liked sitting more than standing in study 1. In study 2, liking of postures did not differ or change across 12 months use of height adjustable desks. Perceived willingness to stand decreased from 4.5 h/d at baseline to 3.4 h/d after 12 months.

Conclusions:

Standing rather than sitting increased EE by 7.5 kcal/h. Use of a height adjustable desk for 12 months did not alter the hedonic value of standing or sitting, which is promising for long-term increases in standing.
The Stress-Metabolic Syndrome Relationship in Adolescents: An Examination of the Moderating Potential of Physical Activity
Authors: Holmes Megan E. , Pivarnik Jim , Pfeiffer Karin , Maier Kimberly S. , Eisenmann Joey C. , Ewing Martha
Published: June 2016

Background:

The role of psychosocial stress in the development of obesity and metabolic syndrome is receiving increased attention and has led to examination of whether physical activity may moderate the stress-metabolic syndrome relationship. The current study examined relationships among physical activity, stress, and metabolic syndrome in adolescents.

Methods:

Participants (N = 126; 57 girls, 69 boys) were assessed for anthropometry, psychosocial stress, physical activity, and metabolic syndrome variables; t tests were used to examine sex differences, and regression analysis was used to assess relationships among variables controlling for sex and maturity status.

Results:

Mean body mass index approached the 75th percentile for both sexes. Typical sex differences were observed for systolic blood pressure, time spent in moderate and vigorous physical activity, and perceived stress. Although stress was not associated with MetS (β = –.001, P = .82), a modest, positive relationship was observed with BMI (β = .20, P = .04).

Conclusions:

Strong relationships between physical activity and stress with MetS or BMI were not found in this sample. Results may be partially explained by overall good physical health status of the participants. Additional research in groups exhibiting varying degrees of health is needed.
Drugging DNA repair
Authors: Jackson Stephen P. , Helleday Thomas
Published: June 2016

Inhibiting DNA repair can have a positive outcome on therapeutic interventions
Genomic and archaeological evidence suggest a dual origin of domestic dogs
Authors: Frantz Laurent A. F. , Mullin Victoria E. , Pionnier-Capitan Maud , Lebrasseur Ophélie , Ollivier Morgane , Perri Angela , Linderholm Anna , Mattiangeli Valeria , Teasdale Matthew D. , Dimopoulos Evangelos A. , Tresset Anne , Duffraisse Marilyne , McCormick Finbar , Bartosiewicz László , Gál Erika , Nyerges Éva A. , Sablin Mikhail V. , Bréhard Stéphanie , Mashkour Marjan , Bălăşescu Adrian , Gillet Benjamin , Hughes Sandrine , Chassaing Olivier , Hitte Christophe , Vigne Jean-Denis , Dobney Keith , Hänni Catherine , Bradley Daniel G. , Larson Greger
Published: June 2016

A dogged investigation of domestication

The history of how wolves became our pampered pooches of today has remained controversial. Frantz
et al.
describe high-coverage sequencing of the genome of an Irish dog from the Bronze Age as well as ancient dog mitochondrial DNA sequences. Comparing ancient dogs to a modern worldwide panel of dogs shows an old, deep split between East Asian and Western Eurasian dogs. Thus, dogs were domesticated from two separate wolf populations on either side of the Old World.

Science
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Confronting the challenges of precision oncology
Authors: Beltran Himisha
Published: June 2016

Mechanistic studies of samples from early-phase clinical trials can help clarify mechanisms of drug response.
Beta-lactamase inhibitors from laboratory to clinic
Authors: Bush K
Published: June 2016

beta-Lactamases constitute the major defense mechanism of pathogenic bacteria against beta-lactam antibiotics. When the beta-lactam ring of this antibiotic class is hydrolyzed, antimicrobial activity is destroyed. Although beta-lactamases have been identified with clinical failures for over 40 years, enzymes with various abilities to hydrolyze specific penicillins or cephalosporins are appearing more frequently in clinical isolates. One approach to counteracting this resistance mechanism has been through the development of beta-lactamase inactivators. beta-Lactamase inhibitors include clavulanic acid and sulbactam, molecules with minimal antibiotic activity. However, when combined with safe and efficacious penicillins or cephalosporins, these inhibitors can serve to protect the familiar beta-lactam antibiotics from hydrolysis by penicillinases or broad-spectrum beta-lactamases. Both of these molecules eventually inactivate the target enzymes permanently. Although clavulanic acid exhibits more potent inhibitory activity than sulbactam, especially against the TEM-type broad-spectrum beta-lactamases, the spectrum of inhibitory activities are very similar. Neither of these inhibitors acts as a good inhibitor of the cephalosporinases. Clavulanic acid has been most frequently combined with amoxicillin in the orally active Augmentin and with ticarcillin in the parenteral beta-lactam combination Timentin. Sulbactam has been used primarily to protect ampicillin from enzymatic hydrolysis. Sulbactam has been used either in the orally absorbed prodrug form as sultamicillin or as the injectable combination ampicillin-sulbactam. Synergy has been demonstrated for these combinations for most members of the Enterobacteriaceae, although those organisms that produce cephalosporinases are not well inhibited. Synergy has also been observed for Neisseria gonorrhoeae, Haemophilus influenzae, penicillinase-producing Staphylococcus aureus, and anaerobic organisms. These antibiotic combinations have been used clinically to treat urinary tract infections, bone and soft-tissue infections, gonorrhea, respiratory infections, and otitis media. Gastrointestinal side effects have been reported for Augmentin and sultamicillin; most side effects with these agents have been mild. Although combination therapy with beta-lactamase inactivators has been used successfully, the problem of resistance development to two agents must be considered. Induction of cephalosporinases can occur with clavulanic acid. Permeability mutants could arise, especially with added pressure from a second beta-lactam.(ABSTRACT TRUNCATED AT 250 WORDS)
Practical diagnostic testing for human immunodeficiency virus
Authors: Jackson J B , Balfour H H
Published: June 2016

Since the discovery of human immunodeficiency virus (HIV) as the causative agent of acquired immunodeficiency syndrome in 1983, there has been a proliferation of diagnostic tests. These assays can be used to detect the presence of HIV antibody, HIV antigen, HIV ribonucleic and deoxyribonucleic acids, and HIV reverse transcriptase. Enzyme-linked immunosorbent assays, Western blot, radioimmunoprecipitation assays, indirect immunofluorescence assays, reverse transcriptase assays, and several molecular hybridization techniques are currently available. Enzyme-linked immunosorbent, Western blot, and indirect immunofluorescence assays for HIV antibody are very sensitive, specific, and adaptable to most laboratories. An enzyme-linked immunosorbent assay for HIV antigen is also readily adaptable to most laboratories and will be commercially available soon. While the other assays are more tedious, they are valuable confirmatory tests and are suitable for reference laboratories. The biohazards of performing HIV testing can be minimized with proper biosafety measures.
Detection, pathogenesis, and therapy of respiratory syncytial virus infections
Authors: Welliver R C
Published: June 2016

Respiratory syncytial virus (RSV) infection is a major cause of serious lower respiratory disease in infancy and early childhood. The unique pathogenesis of lower respiratory illness due to RSV offers some intriguing clues to the role of the human immune system in both protection against and development of respiratory illness. More than any other virus, rapid diagnostic techniques have been especially successful in identifying RSV infection. Many of these techniques could be easily adaptable to diagnosis of influenza virus infection and other agents. Finally, ribavirin therapy of RSV infection represents one of the few instances in which antiviral therapy has been shown to be effective for respiratory illnesses. Fundamental observations in these areas in the case of RSV infection open up new and exciting pathways for investigation of respiratory infection due to other viral, chlamydial, and mycoplasmal agents.
Legionnaires disease: historical perspective
Authors: Winn W C
Published: June 2016

In the summer of 1976, a mysterious epidemic of fatal respiratory disease in Philadelphia launched an intensive investigation that resulted in the definition of a new family of pathogenic bacteria, the Legionellaceae. In retrospect, members of the family had been isolated from clinical specimens as early as 1943. Unsolved epidemics of acute respiratory disease dating to the 1950s were subsequently attributed to the newly described pathogens. In the intervening years, the Legionellaceae have been firmly established as important causes of sporadic and epidemic respiratory disease. The sources of the infecting bacteria are environmental, and geographic variation in the frequency of infection has been documented. Airborne dissemination of bacteria from cooling towers and evaporative condensers has been responsible for some epidemics, but potable water systems are perhaps more important sources. The mode of transmission from drinking water is unclear. The Legionellaceae are gram-negative, facultative, intracellular pathogens. The resident alveolar macrophage, usually an effective antibacterial defense, is the primary site of growth. Cell-mediated immunity appears to be the most important immunological defense; the role of humoral immunity is less clear. Erythromycin remains the antibiotic of choice for therapy of infected patients, but identification and eradication of environmental sources are also essential for the control of infection.
Role of the virology laboratory in diagnosis and management of patients with central nervous system disease
Authors: Chonmaitree T , Baldwin C D , Lucia H L
Published: June 2016

A number of viruses cause acute central nervous system disease. The two major clinical presentations are aseptic meningitis and the less common meningoencephalitis. Clinical virology laboratories are now more widely available than a decade ago; they can be operated on a modest scale and can be tailored to the needs of the patients they serve. Most laboratories can provide diagnostic information on diseases caused by enteroviruses, herpesviruses, and human immunodeficiency virus. Antiviral therapy for herpes simplex virus is now available. By providing a rapid diagnostic test or isolation of the virus or both, the virology laboratory plays a direct role in guiding antiviral therapy for patients with herpes simplex encephalitis. Although there is no specific drug available for enteroviruses, attention needs to be paid to these viruses since they are the most common cause of nonbacterial meningitis and the most common pathogens causing hospitalization for suspected sepsis in young infants in the United States during the warm months of the year. When the virology laboratory maximizes the speed of viral detection or isolation, it can make a significant impact on management of these patients. Early viral diagnosis benefits patients with enteroviral meningitis, most of whom are hospitalized and treated for bacterial sepsis or meningitis or both; these patients have the advantage of early withdrawal of antibiotics and intravenous therapy, early hospital discharge, and avoidance of the risks and costs of unnecessary tests and treatment. Enteroviral infection in young infants also is a risk factor for possible long-term sequelae. For compromised patients, the diagnostic information helps in selecting specific immunoglobulin therapy. Good communication between the physician and the laboratory will result in the most benefit to patients with central nervous system viral infection.
Chancroid and Haemophilus ducreyi
Authors: Morse S A
Published: June 2016

Haemophilus ducreyi is the causative agent of chancroid, one of the genital ulcerative diseases. H. ducreyi is the major cause of genital ulcer disease in Africa and Southeast Asia and is of increasing concern in the United States. Definitive diagnosis of chancroid requires the isolation and identification of H. ducreyi, but isolation of this organism is difficult and the available medium is not optimal for all strains. Fluorescent antibody and serologic tests are of limited value. In general, our knowledge of this organism is rather limited, and indeed, recent studies have questioned the placement of H. ducreyi in the genus Haemophilus. H. ducreyi has relatively few biochemical activities, and epidemiologic studies are limited because there are limited phenotypic markers available for strain typing. Specific virulence factors of H. ducreyi have yet to be identified. Antimicrobial resistance in H. ducreyi is of special concern, as this organism has acquired both gram-negative and gram-positive resistance determinants. In addition, some of these determinants can be mobilized and transferred to other Haemophilus species or to Neisseria gonorrhoeae.
The avian haemophili
Authors: Blackall P J
Published: June 2016

There are four currently recognized taxa to accommodate the avian haemophili: Haemophilus paragallinarum, Pasteurella avium, Pasteurella volantium, and Pasteurella species A (the last three being formerly united as Haemophilus avium). A range of other taxa has also been recognized, but they have been neither named nor assigned to a genus. All of these various taxa, legitimate and otherwise, have the common characteristic of requiring V factor, but not X factor, for in vitro growth. Several recent studies have established the phenotypic properties that allow the differentiation of the recognized taxa, both named and unnamed. The serological properties of H. paragallinarum, the causative agent of infectious coryza of chickens, has received considerable recent attention. In contrast, many questions on the pathogenicity and virulence mechanisms of H. paragallinarum remain unanswered. Another area requiring further work is the identification of those antigens responsible for inducing protective immunity in vaccinated or naturally infected chickens.
Mycobacterial disease, immunosuppression, and acquired immunodeficiency syndrome
Authors: Collins F M
Published: June 2016

The mycobacteria are an important group of acid-fast pathogens ranging from obligate intracellular parasites such as Mycobacterium leprae to environmental species such as M. gordonae and M. fortuitum. The latter may behave as opportunistic human pathogens if the host defenses have been depleted in some manner. The number and severity of such infections have increased markedly with the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic. These nontuberculous mycobacteria tend to be less virulent for humans than M. tuberculosis, usually giving rise to self-limiting infections involving the cervical and mesenteric lymph nodes of young children. However, the more virulent serovars of M. avium complex can colonize the bronchial and intestinal mucosal surfaces of healthy individuals, becoming virtual members of the commensal gut microflora and thus giving rise to low levels of skin hypersensitivity to tuberculins prepared from M. avium and M. intracellulare. Systemic disease develops when the normal T-cell-mediated defenses become depleted as a result of old age, cancer chemotherapy, or infection with human immunodeficiency virus. As many as 50% of human immunodeficiency virus antibody-positive individuals develop mycobacterial infections at some time during their disease. Most isolates of M. avium complex from AIDS patients fall into serotypes 4 and 8. The presence of these drug-resistant mycobacteria in the lungs of the AIDS patient makes their effective clinical treatment virtually impossible. More effective chemotherapeutic, prophylactic, and immunotherapeutic reagents are urgently needed to treat this rapidly increasing patient population.
Acquired immunodeficiency syndrome: more than a health-related dilemma
Authors: Severin M J
Published: June 2016

Many legal issues will affect the health care worker during the AIDS pandemic. These issues are now beginning to be contested in our courts. It is certain that their numbers will continue to grow in the foreseeable future. As local, state, and federal governments design and implement new laws concerning PWA, mechanisms for surveillance, and control of AIDS, new issues are sure to arise. These will undoubtedly involve persons concerned with providing service to those afflicted with this illness. The direction of health care research has already been altered by AIDS. Societal relationships have been affected, as evidenced by the increasing number of legal charges filed when the question of HIV infection involves a patient, student, employee, or other citizen. Inevitably, the health care worker who has contact with PWA will be asked to participate in the mechanisms of the resulting legal contests. If the case reports cited above are an indication of the legal struggles ahead, appearance as a witness to provide scientific information as well as information about the care and treatment afforded PWA will be required of health care workers with increasing frequency.
Gonococcal and meningococcal pathogenesis as defined by human cell, cell culture, and organ culture assays
Authors: Stephens D S
Published: June 2016

Human cells, cell cultures, and organ cultures have been extremely useful for studying the events that occur when gonococci and meningococci encounter human mucosal surfaces. The specificity and selectivity of these events for human cells are striking and correlate with the adaptation of these pathogens for survival on human mucous membranes. To colonize these sites, meningococci and gonococci have developed mechanisms to damage local host defenses such as the mucociliary blanket, to attach to epithelial cells, and to invade these cells. Attachment to epithelial cells mediated by pili, and to some types of cells mediated by PIIs, serves to anchor the organism close to sources of nutrition and allows multiplication. Intracellular invasion, possibly initiated by the major porin protein, may provide additional nutritional support and protection from host defenses. Mucosal invasion may also result in access of gonococci and meningococci to the bloodstream, leading to dissemination.
Campylobacter pylori and gastroduodenal disease
Authors: Buck G E
Published: June 2016

Campylobacter pylori is a newly described, spiral-shaped, gram-negative bacillus that is oxidase positive, catalase positive, and urease positive and grows slowly in culture. Although observed in human tissue at the beginning of the century, it was not cultured until 1982. Because there are significant morphological and genetic differences between this organism and other species of Campylobacter, it will probably be reclassified in a new genus. Current information indicates that the organism primarily resides in the stomach tissue of humans and nonhuman primates and may occasionally spread to the esophagus or other parts of the alimentary tract under appropriate conditions. Significant evidence has accumulated in the last several years to show that it causes gastritis, and there is mounting evidence that it may participate in the development of duodenal ulcers. It may also be associated with gastric ulcers and nonulcer dyspepsia. It can be detected in patients by culture of biopsy specimens or histological staining of biopsy tissue. Indirect evidence for the presence of the organism can be obtained by detection of urease in a tissue biopsy specimen, by urea breath tests, or by detection of specific antibody. It may not be necessary to implement these procedures for routine use, however, until the role of the organism can be defined better. Ultimately, the discovery of this organism may lead to radical changes in the diagnosis and treatment of gastric disease.
Laboratory diagnosis of invasive candidiasis
Authors: Jones J M
Published: June 2016

Severe infections due to Candida species have become more frequent during the past two decades because of the increasing numbers of immunosuppressed patients being treated in our hospitals. Distinguishing colonization from invasive disease requires knowledge of the pathogenetic mechanisms leading to invasion. To assist the clinician in therapeutic decisions, clinical microbiologists should identify to species Candida organisms isolated from immunosuppressed patients. Quantitative or semiquantitative cultures of urine, burn tissues, intravascular catheter tips, and bronchoalveolar lavage specimens may provide useful information. Immunofluorescent staining of certain specimens can enhance diagnostic yield. The lysis-centrifugation blood culture technique offers some advantages over traditional broth techniques in detecting Candida fungemia. Antibody testing is of limited diagnostic value in highly immunosuppressed patients. Developing simple and reliable tests for detecting antigens or metabolites of Candida spp. in the sera of infected patients has proven difficult. Methods for typing Candida albicans are evolving. Typing should prove useful for studying the epidemiology of candidiasis in hospitalized patients.