bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive evolution of theMHCclassIII‐encoded receptorRAGEin primates and murine rodents
Authors: Wu X. , Wu J. , Thompson C. W. , Li Y.
Published: September 2015

The receptor for advanced glycation end products is associated with a series of physiological and pathological processes. Here, we studied the evolution of this multiligand receptor in primates and murine rodents. The evolutionary analyses reveal that adaptive selection had contributed to the variation at a number of amino acid sites in both taxa. Further, the major adaptively selected sites of both taxa are located on the extracellular ligand‐ and intracellular adaptor‐binding regions and receptor oligomerization‐related surfaces. The co‐occurrence of adaptive evolution on the homologue domains suggests that they could play similar roles in these taxa. In terms of advantage fitness, the adaptive changes at these sites could contribute to host defence against the potential challenges towards these interactions and relevant signalling pathways, or the specificity of these essential points.
CTLA4+49G allele associates with early onset of type 1 diabetes in North Indians
Authors: Kumar N. , Kaur G. , Kanga U. , Mehra N. K. , Neolia S. C. , Tandon N. , Zucman S. C.
Published: September 2015

Type 1 diabetes (T1D) is a complex autoimmune disease with strong genetic influence. In this study, we investigated +49A/G SNP (rs 231775) in exon 1 of cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA4) by PCR‐RFLP and its influence as a risk factor for the disease in the North Indian population. This polymorphism at codon 17 results in an amino acid substitution (Thr/Ala) in the leader peptide of the molecule. The study included 232 patients with T1D (age at onset of disease (AOD): 0.5–37 years) and 305 ethnically matched healthy controls. The DNA obtained from these 537 individuals was amplified using a set of specific primers followed by restriction enzyme digestion with Fnu4HI. The +49G allele as well as its homozygous genotype G/G was observed to be significantly higher in patients as compared to the healthy controls {(37.3% vs. 25.6%, P = 4.96E−05, OR = 1.73; 95%CI = 1.33–2.25) (15.52% vs. 6.6%, P = 0.001, OR = 2.62; 95% CI = 1.48–4.63) respectively}. The frequency of G/G genotype was significantly higher in patients with early age at onset of disease (AOD:<12 years) as compared to that in the late‐onset patients with AOD: ≥12 years (21.1% vs. 10.6%, P = 0.042, OR = 2.26; 95% CI = 1.09–4.67) as well as to that in the healthy controls (21.1% vs. 6.6%, P = 0.00004, OR = 3.8; 95% CI = 2.01–7.2). Further analysis revealed that the median AOD significantly reduced (P = 0.049) from 14 years in patients with A/A genotype to 11 and 10 years in those with A/G and G/G genotypes, respectively. These results suggest that CTLA4+49G allele, particularly in homozygous G/G condition, associates with early onset of T1D.
Is acute reperfusion therapy safe in acute ischemic stroke patients who harbor unruptured intracranial aneurysm?
Authors: Mowla Ashkan , Singh Karanbir , Mehla Sandhya , Ahmed Mohammad K. , Shirani Peyman , Kamal Haris , Krishna Chandan , Sawyer Robert N. , Ching Marilou , Siddiqui Adnan H. , Levy Elad I. , Snyder Kenneth V. , Crumlish Annemarie , Hopkins L. N.
Published: September 2015

Background

Intracranial aneurysms are currently considered as contraindication for intravenous thrombolysis in acute ischemic stroke, very likely due to a possible increase in the risk of bleeding from aneurysm rupture; however, there is limited data available on whether intravenous thrombolysis is safe for acute ischemic stroke patients with pre-existing intracranial aneurysms.

Aims and/or hypothesis

To find out the safety of intravenous thrombolysis in acute ischemic stroke patients who harbor unruptured intracranial aneurysms.

Methods

We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with intravenous thrombolysis for acute ischemic stroke in our center from the beginning of 2006 till the end of April 2014. Those with unruptured intracranial aneurysm present on cerebrovascular images prior to acute reperfusion therapy were identified. Post-thrombolysis brain imaging was reviewed to evaluate for any intraparenchymal or subarachnoid hemorrhage related or unrelated to the aneurysm.

Results

A total of 637 patients received intravenous thrombolysis for acute ischemic stroke in our center during an 8.3-year period. Thirty-three (5.2%) were found to have at least one intracranial aneurysms. Twenty-three (70%) of those received only intravenous thrombolysis, and 10 patients received combination of intravenous and intra-arterial throm-bolysis. The size of the largest aneurysm was 10 mm in maximum diameter (range: 2-10 mm). The mean size of aneurysms was 4.8 mm. No symptomatic intracranial hemorrhage occurred among the 23 patients receiving only intravenous thrombolysis. Out of those who received a combination of intravenous and intra-arterial thrombolysis, one developed symptomatic intracranial hemorrhage in the location of acute infarct, distant to the aneurysm location.

Conclusion

Our findings suggest that neither intravenous thrombolysis nor combination of intravenous and intra-arterial thrombolysis increases the risk of aneurysmal hemorrhage in acute ischemic stroke patients who harbor unruptured intracranial aneurysms less than 10 mm in diameter. Their listing in exclusion criteria for intravenous throm-bolysis should be reconsidered to assure appropriate use of acute reperfusion therapy in this group of patients.
A 7‐day team‐based model of care in general medicine: implementation and outcomes at 12 months
Authors: Gilfillan C. , Newnham E. , Nagappan R. , Evans J. , Compton J.
Published: September 2015

Background

Demand for inpatient beds is increasing whilst supply is diminishing. General medical services are feeling this demand as the ageing population presents more patients with undifferentiated illness traditionally cared for by this service. Redesign efforts need to focus on improving the quality and speed of decision‐making to utilise resources efficiently.

Aims

The aim of this study was to improve patient flow through general medical services by undertaking a comprehensive redesign process targeting each stage of the patient journey.

Methods

We utilised a rapid improvement event to identify waste and design a new model of care (MOC) that eliminated as much waste as possible. The model had three main elements: (i) ward‐based teams; (ii) 7‐day per week standard work; and (iii) pull systems to operate for all transfers and referrals. Here, we analyse the first 12 months of the new MOC with regard to key outcomes: length of stay, occupancy, weekend discharges, clinical incidents and Medical Emergency Team (MET) calls, emergency department length of stay and National Emergency Access Target (NEAT) performance and elective surgical throughput.

Results

The new MOC resulted in a 0.88‐day reduction in length of stay. This resulted in reduced general medical bed occupancy of 19 beds. Weekend discharges improved by 54.6%. There were no significant increases in serious clinical incidents or MET calls. Emergency department admitted NEAT performance improved also.

Conclusion

Redesign of the general medicine model of care eliminating waste has resulted in a significant improvement in patient flow and reduced length of stay without compromising quality of care.
Beyond informality: effectiveness of a new actor for representing call centre workers in Turkey
Authors: Tartanoğlu Şafak
Published: September 2015

This article explores the organisational dynamics of the ‘Association of Call Centre Workers’ and aims to discover the effectiveness and sustainability of it as a new actor for representing the interests of call centre workers in Turkey. While traditional trade unions have fundamental problems such as efficacy and representation of various worker groups in changing workplaces, in the Turkish context, they have additional difficulties based on structural and legal constraints. Call centre workers seldom utilise the formal representation channels because of these and some other individual reasons such as a lack of information about their rights and labour movements. Moving from the importance of analysing the informal worker organisational dynamics in the case of a new trade union for call centre workers, the emphasis of the research is on the ability of the Association to develop a form of resistance and representation for the previously unrepresented.
Pensions as a Form of Executive Compensation
Authors: Goh Lisa , Li Yong
Published: September 2015

This paper investigates the role of pensions as an element of total executive compensation, and the relationship between pensions and performance‐based compensation in executive pay. Using hand‐collected data on FTSE 100 CEOs and senior executives from 2004−2011, we document that pensions function as a substitute for performance‐based compensation (primarily bonuses) in both cross‐sectional and time‐series settings. We also examine the effect of corporate governance characteristics on executive pensions. We find that corporate governance characteristics associated with stronger board monitoring play a constraining role on the magnitude of pensions. Our evidence of substitution effects between pensions and performance‐based compensation is consistent with a managerial power view of executive compensation‐setting, and the use of pensions as a ‘stealth’ element of compensation. Our findings are robust to considering different types of pensions, product market competition, and cross‐listing. Sub‐period analysis shows that pensions decrease and substitution effects weaken following the 2008 financial crisis. Moreover, we find no evidence that the use of compensation consultants with potential conflicts of interest is associated with higher pensions. Overall, our study contributes to a greater understanding of the role of pensions in executive compensation, and shows the importance of including pensions in analysis of executive compensation.
Specific binding of [18F]fluoroethyl‐harmol to monoamine oxidase A in rat brain cryostat sections, and compartmental analysis of binding in living brain
Authors: Maschauer Simone , Haller Adelina , Riss Patrick J. , Kuwert Torsten , Prante Olaf , Cumming Paul
Published: September 2015

We investigated [18F]fluoroethyl‐harmol ([18F]FEH) as a reversible and selective ligand for positron emission tomography (PET) studies of monoamine oxidase A (MAO‐A). Binding of [18F]FEH in rat brain cryostat sections indicated high affinity (KD = 3 nM), and density (Bmax; 600 pmol/g). The plasma free fraction was 45%, and untransformed parent constituted only 13% of plasma radioactivity at 10 min after injection. Compartmental analysis of PET recordings in pargyline‐treated rats showed high permeability to brain (K1; 0.32 mL/g/min) and slow washout (k2; 0.024/min), resulting in a uniformly high equilibrium distribution volume (VD; 20 mL/g). Using this VD to estimate unbound ligand in brain of untreated rats, the binding potential ranged from 4.2 in cerebellum to 7.2 in thalamus. We also calculated maps of rats receiving [18F]FEH at a range of specific activities, and then estimated saturation binding parameters in the living brain. In thalamus, striatum and frontal cortex KD was globally close to 300 nM and Bmax was close to 1600 pmol/g; the 100‐fold discrepancy in affinity suggests a very low free fraction for [18F]FEH in the living brain. Based on a synthesis of findings, we calculate the endogenous dopamine concentration to be 0.4 μM in the striatal compartment containing MAO‐A, thus unlikely to exert competition against [18F]FEH binding in vivo. In summary, [18F]FEH has good properties for the detection of MAO‐A in the rat brain by PET, and may present logistic advantages for clinical research at centers lacking a medical cyclotron.

image

We made a compartmental analysis of [18F]fluoroethylharmol ([18F]FEH) binding to monoamine oxidase A (MAO‐A) in living rat brain and estimated the saturation binding parameters from the binding potential (BPND). The Bmax was of comparable magnitude to that in vitro, but with apparent affinity (300 nM), it was 100‐fold lower in vivo. PET imaging with [18F]FEH is well suited for quantitation of MAO‐A in living brain.
Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model
Authors: Son Seung‐Wan , Lee Jin‐Seok , Kim Hyeong‐Geug , Kim Dong‐Woon , Ahn Yo‐Chan , Son Chang‐Gue
Published: September 2015

Among sex hormones, estrogen is particularly well known to act as neuroprotective agent. Unlike estrogen, testosterone has not been well investigated in regard to its effects on the brain, especially under psychological stress. To investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. BALB/c mice were subjected to either an orchiectomy or sham operation. After allowing 15 days for recovery, mice were re‐divided into four groups according to exposure of restraint stress: sham, sham plus stress, orchiectomy, and orchiectomy plus stress. Serum testosterone was undetectable in orchiectomized groups and restraint‐induced stress significantly reduced testosterone levels in sham plus stress group. The serum levels of corticosterone and adrenaline were notably elevated by restraint stress, and these elevated hormones were markedly augmented by orchiectomy. Two oxidative stressors and biomarkers for lipid and protein peroxidation were significantly increased in the cerebral cortex and hippocampus by restraint stress, while the reverse pattern was observed in antioxidant enzymes. These results were supported by histopathological findings, with 4‐hydroxynonenal staining for oxidative injury and Fluoro‐Jade B staining showing the degenerating neurons. The aforementioned patterns of oxidative injury were accelerated by orchiectomy. These findings strongly suggest the conclusion that testosterone exerts a protective effect against oxidative brain damage, especially under stressed conditions.

image

Unlike estrogen, the effects of testosterone on the brain have not been thoroughly investigated. In order to investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. Orchiectomy markedly augmented the restraint stress‐induced elevation of serum corticosterone and adrenaline levels as well as oxidative alterations in brain tissues, especially in the hippocampus. These findings are the first evidence that testosterone depletion makes the brain prone to oxidative injury.
Workgroup Climates and Employees’ Counterproductive Work Behaviours: A Social‐Cognitive Perspective
Authors: Bollmann Grégoire , Krings Franciska
Published: September 2015

This research examines employees' anticipation of social and self‐sanctions as a self‐regulatory mechanism linking workgroup climates and counterproductive work behaviours (CWBs) and personality as a limit to these effects. A cross‐level study with 158 employees from 26 workgroups demonstrated that in groups with a high compliance climate – a climate emphasizing the importance of complying with organizational rules – employees anticipate more social and self‐sanctions, leading those low in conscientiousness and low in agreeableness to engage less frequently in CWBs. In contrast, a high relational climate – a climate emphasizing the importance of positive social relations over self‐interest – indirectly unbridles the CWBs of these employees by alleviating the social and self‐sanctions they anticipate for CWBs. Climates did not have indirect effects for employees high in agreeableness and high in conscientiousness. These findings elucidate why workgroup climates do not affect the CWBs of all members in the same way.
Obsessive Passion: A Compensatory Response to Unsatisfied Needs
Authors: Lalande Daniel , Vallerand Robert J. , Lafrenière Marc‐André K. , Verner‐Filion Jérémie , Laurent François‐Albert , Forest Jacques , Paquet Yvan
Published: September 2015

The present research investigated the role of two sources of psychological need satisfaction (inside and outside a passionate activity) as determinants of harmonious (HP) and obsessive (OP) passion. Four studies were carried out with different samples of young and middle‐aged adults (e.g., athletes, musicians; totalN = 648). Different research designs (cross‐sectional, mixed, longitudinal) were also used. Results showed that only a rigid engagement in a passionate activity (OP) was predicted by low levels of need satisfaction outside the passionate activity (in an important life context or in life in general), whereas both OP and a more favorable and balanced type of passion, HP were positively predicted by need satisfaction inside the passionate activity. Further, OP led to negative outcomes, and HP predicted positive outcomes. These results suggest that OP may represent a form of compensatory striving for psychological need satisfaction. It appears important to consider two distinct sources of need satisfaction, inside and outside the passionate activity, when investigating determinants of optimal and less optimal forms of activity engagement.
A novel large deletion combined with a nonsense mutation in a Chinese child with Papillon–Lefèvre syndrome
Authors: Wu W. , Chen B. , Chen X. , Chen L. , Yi L. , Wang Y. , Yan F. , Sun W.
Published: September 2015

Background and objective

Papillon‐Lefèvre Syndrome (PLS) is a rare autosomal recessive hereditary disease (MIM245000). The syndrome is characterized by palmoplantar keratoderma and early onset periodontitis, caused by CTSC gene mutation. The mutation in CTSC previously reported is mainly point mutations. Large deletion in the CTSC gene has not yet been reported.

Material and methods

We collected 5 mL peripheral blood from a patient with PLS and her family members and used the direct sequencing method to perform CTSC bidirectional sequencing. We also used FISH to analyze the approximate locations of the ends of the missing fragment and then determined the fragment sequence through direct sequencing.

Results

The result demonstrated that the patient have a 110 kb deletion (Chr11: 88032292: 88142997(NC_000011)) combined with a nonsense mutation (Gln182Ter) in this gene.

Conclusion

Our study reveals a compound mutation consisting of a large deletion and a nonsense mutation, which provides a new insight in the mutation type of CTSC gene.
Early diagnosis of liver cancer: an appraisal of international recommendations and future perspectives
Authors: Della Corte Cristina , Triolo Michela , Iavarone Massimo , Sangiovanni Angelo
Published: September 2015

All Societies, AASLD, EASL, APASL and JSH, identify patients with cirrhosis as a target population for surveillance, with minor differences for additional categories of patients, such as chronic hepatitis B and hepatitis C patients with advanced fibrosis. According to AASLD, liver disease related to metabolic diseases including diabetes and obesity is a recognized target of screening, since those conditions have been causally related to HCC. All societies endorse radiological non‐invasive techniques as the mainstay for early diagnosis of HCC, but discrepancies exist between Societies on the utilization of contrast‐enhanced ultrasound and utilization of serum markers for surveillance and diagnosis of HCC. The diagnostic algorithm of the international societies differ substantially in the anatomic paradigm of EASL and APASL which identify 1 cm size as the starting point for radiological diagnosis of HCC compared to APASL algorithm based on the dynamic pattern of contrast imaging, independently on tumour size. While strengthening prediction in individual patients is expected to improve cost‐effectiveness ratios of screening, the benefits of pre‐treatment patient stratification by clinical, histological and genetic scores remain uncertain and exclusion of patients with severe co‐morbidities and advanced age is still debated.
An R2R3‐MYB transcription factor regulates carotenoid pigmentation in Mimulus lewisii flowers
Authors: Sagawa Janelle M. , Stanley Lauren E. , LaFountain Amy M. , Frank Harry A. , Liu Chang , Yuan Yao‐Wu
Published: September 2015

Carotenoids are yellow, orange, and red pigments that contribute to the beautiful colors and nutritive value of many flowers and fruits. The structural genes in the highly conserved carotenoid biosynthetic pathway have been well characterized in multiple plant systems, but little is known about the transcription factors that control the expression of these structural genes.

By analyzing a chemically induced mutant of Mimulus lewisii through bulk segregant analysis and transgenic experiments, we have identified an R2R3‐MYB, Reduced Carotenoid Pigmentation 1 (RCP1), as the first transcription factor that positively regulates carotenoid biosynthesis during flower development.

Loss‐of‐function mutations in RCP1 lead to down‐regulation of all carotenoid biosynthetic genes and reduced carotenoid content in M. lewisii flowers, a phenotype recapitulated by RNA interference in the wild‐type background. Overexpression of this gene in the rcp1 mutant background restores carotenoid production and, unexpectedly, results in simultaneous decrease of anthocyanin production in some transgenic lines by down‐regulating the expression of an activator of anthocyanin biosynthesis.

Identification of transcriptional regulators of carotenoid biosynthesis provides the ‘toolbox’ genes for understanding the molecular basis of flower color diversification in nature and for potential enhancement of carotenoid production in crop plants via genetic engineering.
Genetics of melanoma progression: the rise and fall of cell senescence
Authors: Bennett Dorothy C.
Published: September 2015

There are many links between cell senescence and the genetics of melanoma, meaning both familial susceptibility and somatic–genetic changes in sporadic melanoma. For example, CDKN2A, the best‐known melanoma susceptibility gene, encodes two effectors of cell senescence, while other familial melanoma genes are related to telomeres and their maintenance. This article aimed to analyze our current knowledge of the genetic or epigenetic driver changes necessary to generate a cutaneous metastatic melanoma, the commonest order in which these occur, and the relation of these changes to the biology and pathology of melanoma progression. Emphasis is laid on the role of cell senescence and the escape from senescence leading to cellular immortality, the ability to divide indefinitely.
Photosynthetic Performance of the Red Alga Pyropia haitanensis During Emersion, With Special Reference to Effects of Solar UV Radiation, Dehydration and Elevated CO2 Concentration
Authors: Xu Juntian , Gao Kunshan
Published: September 2015

Macroalgae distributed in intertidal zones experience a series of environmental changes, such as periodical desiccation associated with tidal cycles, increasing CO2 concentration and solar UVB (280–315 nm) irradiance in the context of climate change. We investigated how the economic red macroalga, Pyropia haitanensis, perform its photosynthesis under elevated atmospheric CO2 concentration and in the presence of solar UV radiation (280–400 nm) during emersion. Our results showed that the elevated CO2 (800 ppmv) significantly increased the photosynthetic carbon fixation rate of P. haitanensis by about 100% when the alga was dehydrated. Solar UV radiation had insignificant effects on the net photosynthesis without desiccation stress and under low levels of sunlight, but significantly inhibited it with increased levels of desiccation and sunlight intensity, to the highest extent at the highest levels of water loss and solar radiation. Presence of UV radiation and the elevated CO2 acted synergistically to cause higher inhibition of the photosynthetic carbon fixation, which exacerbated at higher levels of desiccation and sunlight. While P. haitanensis can benefit from increasing atmospheric CO2 concentration during emersion under low and moderate levels of solar radiation, combined effects of elevated CO2 and UV radiation acted synergistically to reduce its photosynthesis under high solar radiation levels during noon periods.
First‐mover strategy, resource capacity alignment, and new product performance: a framework for mediation and moderation effects
Authors: Hsiao Yung‐Chang , Chen Chung‐Jen , Guo Ruey‐Shan , Hu Kae‐Kuen
Published: September 2015

Based on the competence‐based perspective and contingency perspective, this study attempts to examine the relationships among first‐mover strategy, a firm's core capacity, resource allocation, and new product performance. Our findings indicate that (1) firms achieve a better new product performance when adopting first‐mover strategy and having an excellent core capacity, and (2) firms achieve a better new product performance if their core capacity (technical and managerial) fits the resource allocation they implement. Managerial implications and future research directions are discussed.
Empowered Women, Failed Patriarchs: Neoliberalism and Global Gender Anxieties
Authors: Radhakrishnan Smitha , Solari Cinzia
Published: September 2015

Notions of “empowered women,” promoted by NGOs, economists, and feminists beginning in the 1970s, do not necessitate a countervailing notion of “failed patriarchs.” However, our review of the feminist literatures on globalization, development, and migration in the United States, the former Soviet Union, and South Asia suggests that discourses of empowered women and failed patriarchs are fused in the specter of the “reverse gender order.” A presumption of this new order is that global capitalism has liberated women to such an extent that they have surpassed men who are now the truly “disadvantaged.” Drawing on these literatures as evidence, we argue that the large‐scale incorporation of poor and working‐class women into global capitalism relies upon an ideology of the family that keeps women's labor “cheap” and draws support from the feminist idea that work is empowering for women. Diverse nationalisms uphold the ideology of the family as central to capitalist expansion, providing culturally resonant justifications for women's unpaid reproductive work, while men are breadwinners. Thus, poor and working‐class men experience a painful dissonance between breadwinning expectations and economic opportunities. We show that these tensions between ideologies and material conditions make women's responsibility for reproductive work a structural feature of neoliberalism.
Scientists, the Media, and the Public Communication of Science
Authors: Dudo Anthony
Published: September 2015

The relationship between scientists and journalists has evolved in recent years with the advent of numerous sociocultural changes and drastic shifts within the media ecosystem. Media professionals have traditionally been the gatekeepers of scientific information, but new media technologies grant scientists more power than ever before to be proactive about their public communication. In this article, I provide an overview of the science–media relationship and scientists as public communicators. Specifically, I recount the relationship that has traditionally existed between scientists and media professionals, explain how this relationship has evolved over recent years, and highlight what I believe are some of the most salient and exciting areas for future research examining scientists' efforts to engage with the public.
A Course Connecting Astronomy to Art, History, and Literature
Authors: Olson Don
Published: September 2015

For the past 20 years the author has taught an Honors College course combining astronomy and the humanities. The purpose of this note is to give examples of methods that can be adapted to classroom use for topics including night sky paintings by Vincent van Gogh, Edvard Munch, and Claude Monet, historical events influenced by astronomical factors, and literary references to the sky by authors including Chaucer, Shakespeare, and Walt Whitman.
Unraveling metamaterial properties in zigzag-base folded sheets
Authors: Eidini Maryam , Paulino Glaucio H.
Published: September 2015

Zigzag-base mechanical metamaterials have the outstanding properties of Miura-ori and expand on its design space.
Phylogenetic and Kinetic Characterization of a Suite of Dehydrogenases from a Newly Isolated Bacterium, Strain SG61-1L, That Catalyze the Turnover of Guaiacylglycerol-β-Guaiacyl Ether Stereoisomers
Authors: Palamuru Shannu , Dellas Nikki , Pearce Stephen L. , Warden Andrew C. , Oakeshott John G. , Pandey Gunjan
Published: September 2015

Lignin is a complex aromatic polymer found in plant cell walls that makes up 15 to 40% of plant biomass. The degradation of lignin substructures by bacteria is of emerging interest because it could provide renewable alternative feedstocks and intermediates for chemical manufacturing industries. We have isolated a bacterium, strain SG61-1L, that rapidly degrades all of the stereoisomers of one lignin substructure, guaiacylglycerol-β-guaiacyl ether (GGE), which contains a key β-
O
-4 linkage found in most intermonomer linkages in lignin. In an effort to understand the rapid degradation of GGE by this bacterium, we heterologously expressed and kinetically characterized a suite of dehydrogenase candidates for the first known step of GGE degradation. We identified a clade of active GGE dehydrogenases and also several other dehydrogenases outside this clade that were all able to oxidize GGE. Several candidates exhibited stereoselectivity toward the GGE stereoisomers, while others had higher levels of catalytic performance than previously described GGE dehydrogenases for all four stereoisomers, indicating a variety of potential applications for these enzymes in the manufacture of lignin-derived commodities.
Single Cells within the Puerto Rico Trench Suggest Hadal Adaptation of Microbial Lineages
Authors: León-Zayas Rosa , Novotny Mark , Podell Sheila , Shepard Charles M. , Berkenpas Eric , Nikolenko Sergey , Pevzner Pavel , Lasken Roger S. , Bartlett Douglas H.
Published: September 2015

Hadal ecosystems are found at a depth of 6,000 m below sea level and below, occupying less than 1% of the total area of the ocean. The microbial communities and metabolic potential in these ecosystems are largely uncharacterized. Here, we present four single amplified genomes (SAGs) obtained from 8,219 m below the sea surface within the hadal ecosystem of the Puerto Rico Trench (PRT). These SAGs are derived from members of deep-sea clades, including the
Thaumarchaeota
and SAR11 clade, and two are related to previously isolated piezophilic (high-pressure-adapted) microorganisms. In order to identify genes that might play a role in adaptation to deep-sea environments, comparative analyses were performed with genomes from closely related shallow-water microbes. The archaeal SAG possesses genes associated with mixotrophy, including lipoylation and the glycine cleavage pathway. The SAR11 SAG encodes glycolytic enzymes previously reported to be missing from this abundant and cosmopolitan group. The other SAGs, which are related to piezophilic isolates, possess genes that may supplement energy demands through the oxidation of hydrogen or the reduction of nitrous oxide. We found evidence for potential trench-specific gene distributions, as several SAG genes were observed only in a PRT metagenome and not in shallower deep-sea metagenomes. These results illustrate new ecotype features that might perform important roles in the adaptation of microorganisms to life in hadal environments.
Infection of Tribolium castaneum with Bacillus thuringiensis: Quantification of Bacterial Replication within Cadavers, Transmission via Cannibalism, and Inhibition of Spore Germination
Authors: Milutinović Barbara , Höfling Christina , Futo Momir , Scharsack Jörn P. , Kurtz Joachim
Published: September 2015

Reproduction within a host and transmission to the next host are crucial for the virulence and fitness of pathogens. Nevertheless, basic knowledge about such parameters is often missing from the literature, even for well-studied bacteria, such as
Bacillus thuringiensis
, an endospore-forming insect pathogen, which infects its hosts via the oral route. To characterize bacterial replication success, we made use of an experimental oral infection system for the red flour beetle
Tribolium castaneum
and developed a flow cytometric assay for the quantification of both spore ingestion by the individual beetle larvae and the resulting spore load after bacterial replication and resporulation within cadavers. On average, spore numbers increased 460-fold, showing that
Bacillus thuringiensis
grows and replicates successfully in insect cadavers. By inoculating cadaver-derived spores and spores from bacterial stock cultures into nutrient medium, we next investigated outgrowth characteristics of vegetative cells and found that cadaver-derived bacteria showed reduced growth compared to bacteria from the stock cultures. Interestingly, this reduced growth was a consequence of inhibited spore germination, probably originating from the host and resulting in reduced host mortality in subsequent infections by cadaver-derived spores. Nevertheless, we further showed that
Bacillus thuringiensis
transmission was possible via larval cannibalism when no other food was offered. These results contribute to our understanding of the ecology of
Bacillus thuringiensis
as an insect pathogen.
PbaR, an IclR Family Transcriptional Activator for the Regulation of the 3-Phenoxybenzoate 1′,2′-Dioxygenase Gene Cluster in Sphingobium wenxiniae JZ-1
T
Authors: Cheng Minggen , Chen Kai , Guo Suhui , Huang Xing , He Jian , Li Shunpeng , Jiang Jiandong
Published: September 2015

The 3-phenoxybenzoate (3-PBA) 1′,2′-dioxygenase gene cluster (
pbaA1A2B
cluster), which is responsible for catalyzing 3-phenoxybenzoate to 3-hydroxybenzoate and catechol, is inducibly expressed in
Sphingobium wenxiniae
strain JZ-1
T
by its substrate 3-PBA. In this study, we identified a transcriptional activator of the
pbaA1A2B
cluster, PbaR, using a DNA affinity approach. PbaR is a 253-amino-acid protein with a molecular mass of 28,000 Da. PbaR belongs to the IclR family of transcriptional regulators and shows 99% identity to a putative transcriptional regulator that is located on the carbazole-degrading plasmid pCAR3 in
Sphingomonas
sp. strain KA1. Gene disruption and complementation showed that PbaR was essential for transcription of the
pbaA1A2B
cluster in response to 3-PBA in strain JZ-1
T
. However, PbaR does not regulate the reductase component gene
pbaC
. An electrophoretic mobility shift assay and DNase I footprinting showed that PbaR binds specifically to the 29-bp motif AATAGAAAGTCTGCCGTACGGCTATTTTT in the
pbaA1A2B
promoter area and that the palindromic sequence (GCCGTACGGC) within the motif is essential for PbaR binding. The binding site was located between the −10 box and the ribosome-binding site (downstream of the transcriptional start site), which is distinct from the location of the binding site in previously reported IclR family transcriptional regulators. This study reveals the regulatory mechanism for 3-PBA degradation in strain JZ-1
T
, and the identification of PbaR increases the variety of regulatory models in the IclR family of transcriptional regulators.
Genomic Evidence Reveals Numerous Salmonella enterica Serovar Newport Reintroduction Events in Suwannee Watershed Irrigation Ponds
Authors: Li Baoguang , Jackson Scott A. , Gangiredla Jayanthi , Wang Weimin , Liu Huanli , Tall Ben D. , Beaubrun Junia Jean-Gilles , Jay-Russell Michele , Vellidis George , Elkins Christopher A.
Published: September 2015

Our previous work indicated a predominance (56.8%) of
Salmonella enterica
serovar Newport among isolates recovered from irrigation ponds used in produce farms over a 2-year period (B. Li et al., Appl Environ Microbiol 80:6355–6365,
http://dx.doi.org/10.1128/AEM.02063-14
). This observation provided a valuable set of metrics to explore an underaddressed issue of environmental survival of
Salmonella
by DNA microarray. Microarray analysis correctly identified all the isolates (
n
= 53) and differentiated the
S
. Newport isolates into two phylogenetic lineages (
S
. Newport II and
S
. Newport III). Serovar distribution analysis showed no instances where the same serovar was recovered from a pond for more than a month. Furthermore, during the study, numerous isolates with an indistinguishable genotype were recovered from different ponds as far as 180 km apart for time intervals as long as 2 years. Although isolates within either lineage were phylogenetically related as determined by microarray analysis, subtle genotypic differences were detected within the lineages, suggesting that isolates in either lineage could have come from several unique hosts. For example, strains in four different subgroups (A, B, C, and D) possessed an indistinguishable genotype within their subgroups as measured by gene differences, suggesting that strains in each subgroup shared a common host. Based on this comparative genomic evidence and the spatial and temporal factors, we speculated that the presence of
Salmonella
in the ponds was likely due to numerous punctuated reintroduction events associated with several different but common hosts in the environment. These findings may have implications for the development of strategies for efficient and safe irrigation to minimize the risk of
Salmonella
outbreaks associated with fresh produce.
The High Prevalence and Diversity of Chlamydiales DNA within Ixodes ricinus Ticks Suggest a Role for Ticks as Reservoirs and Vectors of Chlamydia-Related Bacteria
Authors: Pilloux Ludovic , Aeby Sébastien , Gaümann Rahel , Burri Caroline , Beuret Christian , Greub Gilbert
Published: September 2015

The
Chlamydiales
order is composed of nine families of strictly intracellular bacteria. Among them,
Chlamydia trachomatis
,
C. pneumoniae
, and
C. psittaci
are established human pathogens, whereas
Waddlia chondrophila
and
Parachlamydia acanthamoebae
have emerged as new pathogens in humans. However, despite their medical importance, their biodiversity and ecology remain to be studied. Even if arthropods and, particularly, ticks are well known to be vectors of numerous infectious agents such as viruses and bacteria, virtually nothing is known about ticks and chlamydia. This study investigated the prevalence of
Chlamydiae
in ticks. Specifically, 62,889
Ixodes ricinus
ticks, consolidated into 8,534 pools, were sampled in 172 collection sites throughout Switzerland and were investigated using pan-
Chlamydiales
quantitative PCR (qPCR) for the presence of
Chlamydiales
DNA. Among the pools, 543 (6.4%) gave positive results and the estimated prevalence in individual ticks was 0.89%. Among those pools with positive results, we obtained 16S rRNA sequences for 359 samples, allowing classification of
Chlamydiales
DNA at the family level. A high level of biodiversity was observed, since six of the nine families belonging to the
Chlamydiales
order were detected. Those most common were
Parachlamydiaceae
(33.1%) and
Rhabdochlamydiaceae
(29.2%). “Unclassified
Chlamydiales
” (31.8%) were also often detected. Thanks to the huge amount of
Chlamydiales
DNA recovered from ticks, this report opens up new perspectives on further work focusing on whole-genome sequencing to increase our knowledge about
Chlamydiales
biodiversity. This report of an epidemiological study also demonstrates the presence of
Chlamydia
-related bacteria within
Ixodes ricinus
ticks and suggests a role for ticks in the transmission of and as a reservoir for these emerging pathogenic
Chlamydia
-related bacteria.
Effect of Whole-Grain Barley on the Human Fecal Microbiota and Metabolome
Authors: De Angelis Maria , Montemurno Eustacchio , Vannini Lucia , Cosola Carmela , Cavallo Noemi , Gozzi Giorgia , Maranzano Valentina , Di Cagno Raffaella , Gobbetti Marco , Gesualdo Loreto
Published: September 2015

In this study, we compared the fecal microbiota and metabolomes of 26 healthy subjects before (HS) and after (HSB) 2 months of diet intervention based on the administration of durum wheat flour and whole-grain barley pasta containing the minimum recommended daily intake (3 g) of barley β-glucans. Metabolically active bacteria were analyzed through pyrosequencing of the 16S rRNA gene and community-level catabolic profiles. Pyrosequencing data showed that levels of
Clostridiaceae
(
Clostridium orbiscindens
and
Clostridium
sp.),
Roseburia hominis
, and
Ruminococcus
sp. increased, while levels of other
Firmicutes
and
Fusobacteria
decreased, from the HSB samples to the HS fecal samples. Community-level catabolic profiles were lower in HSB samples. Compared to the results for HS samples, cultivable lactobacilli increased in HSB fecal samples, while the numbers of
Enterobacteriaceae
, total coliforms, and
Bacteroides
,
Porphyromonas
,
Prevotella
,
Pseudomonas
,
Alcaligenes
, and
Aeromonas
bacteria decreased. Metabolome analyses were performed using an amino acid analyzer and gas chromatography-mass spectrometry solid-phase microextraction. A marked increase in short-chain fatty acids (SCFA), such as 2-methyl-propanoic, acetic, butyric, and propionic acids, was found in HSB samples with respect to the HS fecal samples. Durum wheat flour and whole-grain barley pasta containing 3% barley β-glucans appeared to be effective in modulating the composition and metabolic pathways of the intestinal microbiota, leading to an increased level of SCFA in the HSB samples.
Role of Substitutions in the Hemagglutinin in the Emergence of the 1968 Pandemic Influenza Virus
Authors: Van Poucke Sjouke , Doedt Jennifer , Baumann Jan , Qiu Yu , Matrosovich Tatyana , Klenk Hans-Dieter , Van Reeth Kristien , Matrosovich Mikhail
Published: September 2015

Hemagglutinin (HA) of H3N2/1968 pandemic influenza viruses differs from the putative avian precursor by seven amino acid substitutions. Substitutions Q226L and G228S are known to be essential for adaptation of avian HA to mammals. We found that introduction of avian-virus-like amino acids at five other HA positions (positions 62, 81, 92, 144, and 193) of A/Hong Kong/1/1968 virus decreased viral replication in human cells and transmission in pigs. Thus, substitutions at some of these positions facilitated emergence of the pandemic virus.
Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239
Authors: Hassounah Said A. , Liu Yannan , Quashie Peter K. , Oliveira Maureen , Moisi Daniela , Brenner Bluma G. , Sandstrom Paul A. , Mesplède Thibault , Wainberg Mark A.
Published: September 2015

We previously showed that the simian immunodeficiency virus SIVmac239 is susceptible to human immunodeficiency virus (HIV) integrase (IN) strand transfer inhibitors (INSTIs) and that the same IN drug resistance mutations result in similar phenotypes in both viruses. Now we wished to determine whether tissue culture drug selection studies with SIV would yield the same resistance mutations as in HIV. Tissue culture selection experiments were performed using rhesus macaque peripheral blood mononuclear cells (PBMCs) infected with SIVmac239 viruses in the presence of increasing concentrations of dolutegravir (DTG), elvitegravir (EVG), and raltegravir (RAL). We now show that 22 weeks of selection pressure with DTG yielded a mutation at position R263K in SIV, similar to what has been observed in HIV, and that selections with EVG led to emergence of the E92Q substitution, which is a primary INSTI resistance mutation in HIV associated with EVG treatment failure. To study this at a biochemical level, purified recombinant SIVmac239 wild-type (WT) and E92Q, T97A, G118R, Y143R, Q148R, N155H, R263K, E92Q T97A, E92Q Y143R, R263K H51Y, and G140S Q148R recombinant substitution-containing IN enzymes were produced, and each of the characteristics strand transfer, 3′-processing activity, and INSTI inhibitory constants was assessed in cell-free assays. The results show that the G118R and G140S Q148R substitutions decreasedKm′ andVmax′/Km′ for strand transfer compared to those of the WT. RAL and EVG showed reduced activity against both viruses and against enzymes containing Q148R, E92Q Y143R, and G140S Q148R. Both viruses and enzymes containing Q148R and G140S Q148R showed moderate levels of resistance against DTG. This study further confirms that the same mutations associated with drug resistance in HIV display similar profiles in SIV.

IMPORTANCEOur goal was to definitively establish whether HIV and simian immunodeficiency virus (SIV) share similar resistance pathways under tissue culture drug selection pressure with integrase strand transfer inhibitors and to test the effect of HIV-1 integrase resistance-associated mutations on SIV integrase catalytic activity and resistance to integrase strand transfer inhibitors. Clinically relevant HIV integrase resistance-associated mutations were selected in SIV in our tissue culture experiments. Not only do we report on the characterization of SIV recombinant integrase enzyme catalytic activities, we also provide the first research anywhere on the effect of mutations within recombinant integrase SIV enzymes on drug resistance.
Arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and harms
Authors: Thorlund J B , Juhl C B , Roos E M , Lohmander LS
Published: September 2015

Objective

To determine benefits and harms of arthroscopic knee surgery involving partial meniscectomy, debridement, or both for middle aged or older patients with knee pain and degenerative knee disease.

Design

Systematic review and meta-analysis.

Main outcome measures

Pain and physical function.

Data sources

Systematic searches for benefits and harms were carried out in Medline, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to August 2014. Only studies published in 2000 or later were included for harms.

Eligibility criteria for selecting studies

Randomised controlled trials assessing benefit of arthroscopic surgery involving partial meniscectomy, debridement, or both for patients with or without radiographic signs of osteoarthritis were included. For harms, cohort studies, register based studies, and case series were also allowed.

Results

The search identified nine trials assessing the benefits of knee arthroscopic surgery in middle aged and older patients with knee pain and degenerative knee disease. The main analysis, combining the primary endpoints of the individual trials from three to 24 months postoperatively, showed a small difference in favour of interventions including arthroscopic surgery compared with control treatments for pain (effect size 0.14, 95% confidence interval 0.03 to 0.26). This difference corresponds to a benefit of 2.4 (95% confidence interval 0.4 to 4.3) mm on a 0–100 mm visual analogue scale. When analysed over time of follow-up, interventions including arthroscopy showed a small benefit of 3–5 mm for pain at three and six months but not later up to 24 months. No significant benefit on physical function was found (effect size 0.09, −0.05 to 0.24). Nine studies reporting on harms were identified. Harms included symptomatic deep venous thrombosis (4.13 (95% confidence interval 1.78 to 9.60) events per 1000 procedures), pulmonary embolism, infection, and death.

Conclusions

The small inconsequential benefit seen from interventions that include arthroscopy for the degenerative knee is limited in time and absent at one to two years after surgery. Knee arthroscopy is associated with harms. Taken together, these findings do not support the practise of arthroscopic surgery for middle aged or older patients with knee pain with or without signs of osteoarthritis.

Systematic review registration

PROSPERO CRD42014009145.