bluuebunny/crossref_metadata_2025 huggingface dataset:
Body size evolution of a shell‐brooding cichlid fish from Lake Tanganyika
Authors: Takahashi T. , Ota K.
Published: August 2016

The substrate‐brooding cichlid fishTelmatochromis temporalisin Lake Tanganyika demonstrates a simple example of ecological speciation between normal and dwarf morphs through divergent natural selection on body size. The dwarf morph most likely evolved from the ancestral normal morph; therefore, elucidating the evolution of its small body size is a key to understanding this ecological speciation event. Previous studies suggest that the small body size of the dwarf morph is an adaptation to the use of empty snail shells as shelters (males) and spawning sites (females), but this idea has not been fully evaluated. Combining original and previously published information, this study compared likelihood values to determine the primary factor that would be responsible for regulating the body size of the dwarf morph. Male body size is most likely regulated by the ability to turn within shells, which may influence the predation avoidance of adult fish. Females are smaller than males, and their body size is most likely regulated by the ability to lay eggs in the small spaces within shells close to the shell apices where predation risk on eggs is lower. This study provides new evidence supporting the hypothesis that different natural selection factors affected body size of the different sexes of the dwarf morph, which has not been reported in other animal species.
Fecal calprotectin as a non‐invasive biomarker for intestinal involvement of Behçet's disease
Authors: Kim Duk Hwan , Park Yehyun , Kim Bun , Kim Seung Won , Park Soo Jung , Hong Sung Pil , Kim Tae Il , Kim Won Ho , Cheon Jae Hee
Published: August 2016

Background and Aim

The diagnostic and prognostic values of fecal calprotectin (FC) levels in patients with inflammatory bowel diseases have been proven. However, little is known about the usefulness of FC measurement in predicting intestinal involvement of Behçet's disease (BD).

Methods

Forty‐four consecutive patients with systemic BD who underwent colonoscopy for the evaluation of gastrointestinal symptoms were prospectively enrolled between November 2012 and March 2014 in a single tertiary medical center. Fecal specimens from the patients were obtained the day before bowel cleansing and 3 months after colonoscopy.

Results

Twenty‐five patients showed intestinal ulcerations on colonoscopy (12 [48.0%] typical and 13 [52.0%] atypical ulcerations). The median FC level in the intestinal BD group was significantly higher than that in the non‐diagnostic group (112.53 [6.86–1604.39] vs 31.64 [5.46–347.60] µg/g, respectively, P = 0.003). Moreover, the typical ulceration group showed a significantly higher median FC level than the atypical ulceration group in patients with intestinal BD (435.995 [75.65–1604.39] vs 71.42 [6.86–476.94] µg/g, respectively, P = 0.033). Multivariate analysis revealed higher FC as an independent predictor of intestinal BD (OR = 38.776; 95% CI = 2.306–652.021; P = 0.011). The cut‐off level of FC for predicting intestinal BD was 68.89 µg/g (76% sensitivity and 79% specificity). The absolute changes between fecal calprotectin levels and the disease activity index of intestinal BD from initial diagnosis of intestinal BD to 3 months after diagnosis were significantly correlated (Pearson's correlation coefficient = 0.470, P = 0.027).

Conclusion

The FC level might serve as a non‐invasive surrogate marker of intestinal involvement of BD.
Assessment of treatment failure in endodontic therapy
Authors: Bergenholtz G.
Published: August 2016

There is a paucity of guidelines for the dental profession to assess failure of endodontic therapy. While a successful treatment can be well defined by the absence of apical periodontitis and clinical symptoms after a period of observation, failed treatment has escaped a distinct standing over the years. This article highlights aspects of significance and concludes that research ought to better explore the general health properties of persistent apical periodontitis on root‐filled teeth and finally confirm the extent there is an association between apical periodontitis and adverse systemic health effects. Clearing this condition will determine whether clinicians should take a serious or relaxed attitude to persistent apical periodontitis subsequent to endodontic treatment.
CREDIT CRUNCHAND INSURANCE CONSUMPTION: THE AFTERMATHOF THE SUBPRIME MORTGAGE CRISIS
Authors: Kamiya Shinichi
Published: August 2016

Using cross‐state panel data of the U.S. personal auto insurance premiums from 2007 to 2012, this study provides evidence that consumer purchases of insurance were reduced by more than expected from losses of risk exposure during and after the subprime mortgage crisis. Analyses show that the credit crunch of auto loans and a deterioration of net worth in housing resulting from the bursting housing bubble contributed to the reduced consumption of auto insurance. This result is robust even after controlling for associated factors, such as the insurance price, personal spending on vehicles, and general consumption. These findings provide evidence for a real effect of the financial crisis.
Neurological mechanism of Xiaochaihutang's antidepressant-like effects to socially isolated adult rats
Authors: Ma Jie , Wu Chun Fu , Wang Fang , Yang Jing Yu , Dong Ying Xu , Su Guang Yue , Zhang Kuo , Wang Zhi Qian , Xu Long Wen , Pan Xing , Zhou Ting Shuo , Ma Ping , Song Shao Jiang
Published: August 2016

Objectives

Xiaochaihutang (XCHT) has antidepressant effects in multiple animal models of depression in our previous studies. But the antidepressant effects and exact mechanisms of XCHT in a rat model of chronic social isolation stress (CSIS) have never been studied. We therefore aimed to investigate the effects of XCHT on depressive/anxiety-related behaviours of CSIS-exposed rats and understand the neurological mechanism involving neurogenesis.

Methods

We established the CSIS model and then investigated the effects of XCHT on behavioural change. HPLC-MS/MS was adopted to quantify neurotransmitter levels in the cerebrospinal fluid (CSF). Immunofluorescence technology was used to study the effects of XCHT on neurogenesis; while expressions of 5-HT1A receptor signalling pathway in the hippocampus were measured using Western blotting.

Key Findings

Xiaochaihutang significantly alleviated depressive/anxiety-like behaviours of CSIS-exposed rats. XCHT significantly regulated levels of monoamine neurotransmitters in the CSF without affecting Glu, GABA and ACh. XCHT also significantly increased neurogenesis in CSIS-exposed rats. Additionally, XCHT reversed CSIS-induced decrease of 5-HT1A receptor expression and promoted the expression of BDNF in the hippocampus.

Conclusion

Our results suggest that XCHT could significantly regulate the depressive/anxiety-like behaviours induced by CSIS, which are likely attributed to the promotion of hippocampal neurogenesis and neurotrophin expressions through the activation of serotonergic system.
Virulence of Pectobacterium carotovorum subsp. brasiliense on potato compared with that of other Pectobacterium and Dickeya species under climatic conditions prevailing in the Netherlands
Authors: van der Wolf J. M. , de Haan E. G. , Kastelein P. , Krijger M. , de Haas B. H. , Velvis H. , Mendes O. , Kooman‐Gersmann M. , van der Zouwen P. S.
Published: August 2016

In western Europe, Pectobacterium carotovorum subsp. brasiliense is emerging as a causal agent of blackleg disease. In field experiments in the Netherlands, the virulence of this pathogen was compared with strains of other Dickeya and Pectobacterium species. In 2013 and 2014, seed potato tubers were vacuum infiltrated with high densities of bacteria (106 CFU mL−1) and planted in clay soil. Inoculation with P. carotovorum subsp. brasiliense and P. atrosepticum resulted in high disease incidences (75–95%), inoculation with D. solani and P. wasabiae led to incidences between 5% and 25%, but no significant disease development was observed in treatments with P. carotovorum subsp. carotovorum, D. dianthicola or the water control. Co‐inoculations of seed potatoes with P. carotovorum subsp. brasiliense and D. solani gave a similar disease incidence to inoculation with only P. carotovorum subsp. brasiliense. However, co‐inoculation of P. carotovorum subsp. brasiliense with P. wasabiae resulted in a decrease in disease incidence compared to inoculation with only P. carotovorum subsp. brasiliense. In 2015, seed potatoes were inoculated with increasing densities of P. carotovorum subsp. brasiliense, D. solani or P. atrosepticum (103–106 CFU mL−1). After vacuum infiltration, even a low inoculum density resulted in high disease incidence. However, immersion without vacuum caused disease only at high bacterial densities. Specific TaqMan assays were evaluated and developed for detection of P. carotovorum subsp. brasiliense, P. wasabiae and P. atrosepticum and confirmed the presence of these pathogens in progeny tubers of plants derived from vacuum‐infiltrated seed tubers.
Evaluating nest supplementation as a recovery strategy for the endangered rodents of the Florida Keys
Authors: Cove Michael V. , Simons Theodore R. , Gardner Beth , Maurer Andrew S. , O'Connell Allan F.
Published: August 2016

The Key Largo woodrat (Neotoma floridana smalli) and Key Largo cotton mouse (Peromyscus gossypinus allapaticola) are federally endangered subspecies endemic to the tropical hardwood hammocks of Key Largo, Florida. Woodrats are considered generalists in habitat and diet, yet a steady decline in natural stick nests and capture rates over the past several decades suggests that they are limited by the availability of nesting habitat due to habitat loss and fragmentation. The more specialized Key Largo cotton mouse appears to rely on old growth hammock, a habitat type that is rare following past land clearing. In 2004, the U.S. Fish and Wildlife Service started building supplemental nest structures to restore habitat quality and connectivity for these endangered rodents, but nest use requires evaluation. We used camera traps and occupancy models to evaluate the factors influencing woodrat and cotton mouse use of the supplemental nests. We detected woodrats at 65 and cotton mice at 175 of 284 sampled nest structures, with co‐occurrence at 38 nests. Woodrat nest use followed a gradient from low nest use in the north to high nest use in the south, which might relate to the proximity of free‐ranging domestic cat (Felis catus) colonies in residential developments. Cotton mouse nest use, however, was related positively to mature hammock and related negatively to disturbed areas (e.g. scarified lands). The two species occurred independently of each other. Stick‐stacking behavior was observed at supplemental nests and, although it was correlated with detection of woodrats, it was not a strong predictor of their occurrence. We suggest that nest supplementation can be an important tool for species recovery as habitat quality continues to improve with succession.
Does wing morphology affect recolonization of restored farmland by ground‐dwelling beetles?
Authors: Gibb Heloise , Retter Bryony , Cunningham Saul A. , Barton Philip S.
Published: August 2016

Revegetation of previously cleared land is widely used to increase habitat area and connectivity of remnant vegetation for biodiversity conservation. Whether new habitat attracts or supports fauna depends on the dispersal traits of those fauna as well as the structure and composition of the surrounding landscape. Here, we examined wing morphology as a key dispersal trait for beetles in a revegetated landscape and asked, first, how it was related to phylogeny (family), trophic position, and body size. Second, we asked if wing morphology of recolonizing (or persisting) beetles varied with habitat characteristics at multiple scales, from microhabitat to landscape context. Third, we examined how common winged and wingless species responded to habitat at multiple scales. We measured the wing morphology of ground‐dwelling beetles from a restoration chronosequence, including paddocks, “young” revegetation (8–11 years old), “old” revegetation (14–19 years old), and fenced remnant vegetation. We found that body size and family membership were significant predictors of winglessness, with wingless species of carabids and curculionids being larger than their winged counterparts. We found no difference in the number of sites occupied by winged and wingless species, and no relationship between the wing morphology traits represented in different locations and habitat characteristics or landscape context. Furthermore, the most abundant species of both winged and wingless ground‐dwelling beetles had relatively little affinity to any habitat successional stage. Thus, despite intrinsic differences in wing morphology among species of ground‐dwelling beetle, we found no evidence that flight‐related dispersal limitations influenced recolonization (or persistence) in this landscape.
Strategic R&D Commitment and the Gains from Trade
Authors: Dewit Gerda , Leahy Dermot
Published: August 2016

This paper examines how trade liberalization affects innovation, profits and welfare in a model of reciprocal markets when firms pre‐commit to research and development (R&D). We establish that the equilibrium is not always unique and show that, with trade, R&D commitment leads to higher levels of innovation, lower profits, higher consumer surplus and higher welfare than when R&D is chosen simultaneously to output levels. Furthermore, if the effectiveness of R&D is sufficiently high, trade always yields higher welfare than autarky, implying that R&D commitment may significantly enhance the welfare gains from trade liberalization.
Are Population and Land Use Changes Perceived as Threats to Sense of Place in the New West? A Multilevel Modeling Approach
Authors: Keske Catherine M. H. , Bixler R. Patrick , Bastian Christopher T. , Cross Jennifer E.
Published: August 2016

The Intermountain West's rapid changes in population growth and land use may be welcome to some, but others perceive such changes as threats to sense of place. The objective of this study is to assess whether New West and Old West contextual variables predict how agricultural landowners view threats to agricultural lifestyles and sense of place. We analyze survey data collected from 2,270 agricultural landowners in Colorado and Wyoming utilizing a multilevel regression model (MLM). We posit that this analytical approach is effective for evaluating hierarchal New West or Old West economic configurations that may otherwise be difficult to observe. Our study specifically examines whether population pressures threaten agricultural lifestyles in the amenity‐based New West or in Old West economic regimes with proclivity toward large‐scale agricultural production. Our results show that landowners in farming‐dependent counties and in high‐amenity areas express greater concern than other landowners surveyed about increases in population growth that could threaten an agricultural way of life. Furthermore, we demonstrate that these perceptions relate to whether individuals reside in New West or Old West counties. In summary, some of the contextual variables of New West and Old West economic structures predict whether individuals perceive population growth and land use changes as threats to sense of place.
A naturally occurring promoter polymorphism of the Arabidopsis FUM2 gene causes expression variation, and is associated with metabolic and growth traits
Authors: Riewe David , Jeon Hea‐Jung , Lisec Jan , Heuermann Marc C. , Schmeichel Judith , Seyfarth Monique , Meyer Rhonda C. , Willmitzer Lothar , Altmann Thomas
Published: August 2016

Fumarate and malate are known intermediates of the TCA cycle, a mitochondrial metabolic pathway generating NADH for respiration. Arabidopsis thaliana and other Brassicaceae contain an additional cytosolic fumarase (FUM2) that functions in carbon assimilation and nitrogen use. Here, we report the identification of a hitherto unknown FUM2 promoter insertion/deletion (InDel) polymorphism found between the Col‐0 and C24 accessions, which also divides a large number of Arabidopsis accessions carrying either the Col‐0 or the C24 allele. The polymorphism consists of two stretches of 2.1 and 3.8 kb, which are both absent from the promotor region of Col‐0 FUM2. By analysing mutants as well as mapping and natural populations with contrasting FUM2 alleles, the promotor insertion was linked to reduced FUM2 mRNA expression, reduced fumarase activity and reduced fumarate/malate ratio in leaves. In a large population of 174 natural accessions, the polymorphism was also found to be associated with the fumarate/malate ratio, malate and fumarate levels, and with dry weight at 15 days after sowing (DAS). The association with biomass production was confirmed in an even larger (251) accession population for dry weight at 22 DAS. The dominant Col‐0 allele that results in increased fumarate/malate ratios and enhanced biomass production is predominantly found in central/eastern European accessions, whereas the C24 type allele is prevalent on the Iberian Peninsula, west of the Rhine and in the British Isles. Our findings support the role of FUM2 in diurnal carbon storage, and point to a growth advantage of accessions carrying the FUM2 Col‐0 allele.
Histiocytic chorioretinitis in a dog
Authors: Sherman Amanda B. , Cullen John M. , Westermeyer Hans D. , Grindem Carol , Gilger Brian C.
Published: August 2016

A 3‐year‐old castrated male mixed‐breed dog presented with an acute bullous retinal detachment and thickened choroid of the right eye. Subretinal cytology revealed an atypical cell proliferation suggestive of neoplasia. The eye was enucleated, and the original diagnosis was a histologically benign choroidal melanocytic tumor. Further diagnostics revealed no other systemic abnormalities other than a nonhealing shoulder wound. Six months later, the left eye developed a bullous retinal detachment. This eye responded well to systemic steroids and the dog regained vision within a few weeks of initiating therapy. Results of immunohistochemistry with Melan‐A and CD204 of the previously enucleated right eye caused a revision of the histologic diagnosis from melanocytic tumor to histiocytic chorioretinitis. This case highlights the subtle and sometimes confusing distinction between neoplastic and inflammatory processes on both cytology and histopathology.
Intra‐ and interobserver reliability of lens equatorial length measurement using 35‐MHz ultrasound biomicroscopy in dogs with cataract
Authors: Barbé Charlotte , Harran Nathaniel , Goulle Frédéric
Published: August 2016

Purpose

To determine intra‐ and interobserver reliability of lens equatorial length measurement using 35‐MHz ultrasound biomicroscopy in dogs with cataract.

Methods

Ocular ultrasonography was performed on 28 dogs (50 eyes) before phacoemulsification. Lens equatorial length was measured on still images obtained at 35 MHz in all dogs. Each observer (A and B) obtained the measurements independently. Coefficients of variation (CVs) were used to assess intraobserver repeatability and interobserver reproducibility. Intraobserver repeatability was assessed by comparing measurements obtained on the same image on four different occasions by observer A. Interobserver reproducibility was assessed by comparing measurements obtained independently by both observers on the same image.

Results

CV used to assess intraobserver repeatability was 2.4% with good agreement and no significant difference between repetitions (P> 0.05).CVused to assess interobserver reproducibility was 5.8% without significant difference between measurements obtained by the two observers (P> 0.05).

Conclusions

Intraobserver repeatability and interobserver reproducibility were considered good for lens equatorial length measurement at 35 MHz in dogs with cataract. Ultrasound biomicroscopy could be an acceptable method to assess lens equatorial dimension before phacoemulsification and intraocular lens implantation in dogs with cataract.
Human hypertension, sympathetic activity and the selfish brain
Authors: Hart Emma C.
Published: August 2016

New Findings

What is the topic of this review?

This review article revisits an historical hypothesis that cerebral hypoperfusion, caused by elevated cerebral vascular resistances, causes the onset of high sympathetic nerve activity and hypertension in humans.

What advances does it highlight?

The review article highlights new evidence indicating that congenital cerebrovascular abnormalities, namely vertebral artery hypoplasia and an incomplete posterior circle of Willis, may play a role in the onset of hypertension.

Despite the harmful consequences of high blood pressure (hypertension; e.g. stroke, renal failure, dementia and even death), the underlying physiological mechanisms that cause the onset of hypertension are poorly understood. The most established finding is that hypertension occurs alongside activation of the sympathetic nervous system, yet exactly what triggers this in humans is ambiguous. This review discusses evidence for elevated sympathetic nerve activity, particularly in human hypertension, and revisits an historical theory regarding the aetiology underlying human hypertension that was proposed by Seymour Kety and John Dickinson in the 1940s–1950s. My research group hypothesizes that elevated sympathetic nerve activity and hypertension develop as a fundamental mechanism to maintain adequate cerebral blood flow, which is now termed Cushing's mechanism or the selfish brain hypothesis. Moreover, it goes against the traditional belief that high cerebrovascular resistance is a consequence of hypertension; we propose that this elevated resistance drives hypertension. This review discusses historical and new evidence in animals and humans supporting this hypothesis. In particular, unique human data indicating a higher prevalence of congenital cerebral vascular abnormalities in hypertension are considered.
Self-rolling and light-trapping in flexible quantum well–embedded nanomembranes for wide-angle infrared photodetectors
Authors: Wang Han , Zhen Honglou , Li Shilong , Jing Youliang , Huang Gaoshan , Mei Yongfeng , Lu Wei
Published: August 2016

Flexible semiconductor nanomembranes bend into microscale scroll architectures for wide-angle infrared photodetection.
Thiacalix[4]arene: New protection for metal nanoclusters
Authors: Guan Zong-Jie , Zeng Jiu-Lian , Nan Zi-Ang , Wan Xian-Kai , Lin Yu-Mei , Wang Quan-Ming
Published: August 2016

An organic macrocycle ligand is promising in precisely controlling the structures and optical properties of silver nanoclusters.
A fault-tolerant addressable spin qubit in a natural silicon quantum dot
Authors: Takeda Kenta , Kamioka Jun , Otsuka Tomohiro , Yoneda Jun , Nakajima Takashi , Delbecq Matthieu R. , Amaha Shinichi , Allison Giles , Kodera Tetsuo , Oda Shunri , Tarucha Seigo
Published: August 2016

This is the first experimental demonstration of a fault-tolerant spin qubit in industry-compatible isotopically natural silicon.
Doping-dependent charge order correlations in electron-doped cuprates
Authors: da Silva Neto Eduardo H. , Yu Biqiong , Minola Matteo , Sutarto Ronny , Schierle Enrico , Boschini Fabio , Zonno Marta , Bluschke Martin , Higgins Joshua , Li Yangmu , Yu Guichuan , Weschke Eugen , He Feizhou , Le Tacon Mathieu , Greene Richard L. , Greven Martin , Sawatzky George A. , Keimer Bernhard , Damascelli Andrea
Published: August 2016

Resonant x-ray scattering clarifies the link between charge order and magnetism/superconductivity in n-doped cuprates.
Three-dimensional all-dielectric metamaterial solid immersion lens for subwavelength imaging at visible frequencies
Authors: Fan Wen , Yan Bing , Wang Zengbo , Wu Limin
Published: August 2016

TiO
2
nanoparticles are demonstrated to assemble low-loss three-dimensional all-dielectric metamaterials working at visible frequencies.
Antimicrobial and Virulence-Modulating Effects of Clove Essential Oil on the Foodborne Pathogen Campylobacter jejuni
Authors: Kovács Judit K. , Felső Péter , Makszin Lilla , Pápai Zoltán , Horváth Györgyi , Ábrahám Hajnalka , Palkovics Tamás , Böszörményi Andrea , Emődy Levente , Schneider György
Published: August 2016

Our study investigated the antimicrobial action of clove (
Syzygium aromaticum
) essential oil (EO) on the zoonotic pathogen
Campylobacter jejuni
. After confirming the clove essential oil's general antibacterial effect, we analyzed the reference strain
Campylobacter jejuni
NCTC 11168. Phenotypic, proteomic, and transcriptomic methods were used to reveal changes in cell morphology and functions when exposed to sublethal concentrations of clove EO. The normally curved cells showed markedly straightened and shrunken morphology on the scanning electron micrographs as a result of stress. Although, oxidative stress, as a generally accepted response to essential oils, was also present, the dominance of a general stress response was demonstrated by reverse transcription-PCR (RT-PCR). The results of RT-PCR and two-dimensional (2D) PAGE revealed that clove oil perturbs the expression of virulence-associated genes taking part in the synthesis of flagella, PEB1, PEB4, lipopolysaccharide (LPS), and serine protease. Loss of motility was also detected by a phenotypic test. Bioautographic analysis revealed that besides its major component, eugenol, at least four other spots of clove EO possessed bactericidal activity against
C. jejuni
. Our findings show that clove EO has a marked antibacterial and potential virulence-modulating effect on
C. jejuni
.

IMPORTANCE
This study demonstrates that the components of clove essential oil influence not only the expression of general stress genes but also the expression of virulence-associated genes. Based on this finding, alternative strategies can be worked on to control this important foodborne pathogen.
Lysine and Threonine Biosynthesis from Aspartate Contributes to Staphylococcus aureus Growth in Calf Serum
Authors: Oogai Yuichi , Yamaguchi Masaya , Kawada-Matsuo Miki , Sumitomo Tomoko , Kawabata Shigetada , Komatsuzawa Hitoshi
Published: August 2016

Staphylococcus aureus
is a human pathogen, and
S. aureus
bacteremia can cause serious problems in humans. To identify the genes required for bacterial growth in calf serum (CS), a library of
S. aureus
mutants with randomly inserted transposons were analyzed for growth in CS, and the aspartate semialdehyde dehydrogenase (
asd
)-inactivated mutant exhibited significantly reduced growth in CS compared with the wild type (WT). The mutant also exhibited significantly reduced growth in medium, mimicking the concentrations of amino acids and glucose in CS. Asd is an essential enzyme for the biosynthesis of lysine, methionine, and threonine from aspartate. We constructed inactivated mutants of the genes for lysine (
lysA
), methionine (
metE
), and threonine (
thrC
) biosynthesis and found that the inactivated mutants of
lysA
and
thrC
exhibited significantly lower growth in CS than the WT, but the growth of the
metE
mutant was similar to that of the WT. The reduced growth of the
asd
mutant was recovered by addition of 100 μg/ml lysine and threonine in CS. These results suggest that
S. aureus
requires lysine and threonine biosynthesis to grow in CS. On the other hand, the
asd
-,
lysA
-,
metE
-, and
thrC
-inactivated mutants exhibited significantly reduced growth in mouse serum compared with the WT. In mouse bacteremia experiments, the
asd
-,
lysA
-,
metE
-, and
thrC
-inactivated mutants exhibited attenuated virulence compared with WT infection. In conclusion, our results suggest that the biosynthesis of
de novo
aspartate family amino acids, especially lysine and threonine, is important for staphylococcal bloodstream infection.

IMPORTANCE
Studying the growth of bacteria in blood is important for understanding its pathogenicity in the host.
Staphylococcus aureus
sometimes causes bacteremia or sepsis. However, the factors responsible for
S. aureus
growth in the blood are not well understood. In this study, using a library of 2,914 transposon-insertional mutants in the
S. aureus
MW2 strain, we identified the factors responsible for bacterial growth in CS. We found that inactivation of the lysine and threonine biosynthesis genes led to deficient growth in CS. However, the inactivation of these genes did not affect
S. aureus
growth in general medium. Because the concentration of amino acids in CS is low compared to that in general bacterial medium, our results suggest that lysine and threonine biosynthesis is important for the growth of
S. aureus
in CS. Our findings provide new insights for
S. aureus
adaptation in the host and for understanding the pathogenesis of bacteremia.
Light-Controlled Cell Factories: Employing Photocaged Isopropyl-β-
d
-Thiogalactopyranoside for Light-Mediated Optimization of
lac
Promoter-Based Gene Expression and (+)-Valencene Biosynthesis in Corynebacterium glutamicum
Authors: Binder Dennis , Frohwitter Jonas , Mahr Regina , Bier Claus , Grünberger Alexander , Loeschcke Anita , Peters-Wendisch Petra , Kohlheyer Dietrich , Pietruszka Jörg , Frunzke Julia , Jaeger Karl-Erich , Wendisch Volker F. , Drepper Thomas
Published: August 2016

Precise control of microbial gene expression resulting in a defined, fast, and homogeneous response is of utmost importance for synthetic bio(techno)logical applications. However, even broadly applied biotechnological workhorses, such as
Corynebacterium glutamicum
, for which induction of recombinant gene expression commonly relies on the addition of appropriate inducer molecules, perform moderately in this respect. Light offers an alternative to accurately control gene expression, as it allows for simple triggering in a noninvasive fashion with unprecedented spatiotemporal resolution. Thus, optogenetic switches are promising tools to improve the controllability of existing gene expression systems. In this regard, photocaged inducers, whose activities are initially inhibited by light-removable protection groups, represent one of the most valuable photoswitches for microbial gene expression. Here, we report on the evaluation of photocaged isopropyl-β-
d
-thiogalactopyranoside (IPTG) as a light-responsive control element for the frequently applied
tac
-based expression module in
C. glutamicum
. In contrast to conventional IPTG, the photocaged inducer mediates a tightly controlled, strong, and homogeneous expression response upon short exposure to UV-A light. To further demonstrate the unique potential of photocaged IPTG for the optimization of production processes in
C. glutamicum
, the optogenetic switch was finally used to improve biosynthesis of the growth-inhibiting sesquiterpene (+)-valencene, a flavoring agent and aroma compound precursor in food industry. The variation in light intensity as well as the time point of light induction proved crucial for efficient production of this toxic compound.

IMPORTANCE
Optogenetic tools are light-responsive modules that allow for a simple triggering of cellular functions with unprecedented spatiotemporal resolution and in a noninvasive fashion. Specifically, light-controlled gene expression exhibits an enormous potential for various synthetic bio(techno)logical purposes. Before our study, poor inducibility, together with phenotypic heterogeneity, was reported for the IPTG-mediated induction of
lac
-based gene expression in
Corynebacterium glutamicum
. By applying photocaged IPTG as a synthetic inducer, however, these drawbacks could be almost completely abolished. Especially for increasing numbers of parallelized expression cultures, noninvasive and spatiotemporal light induction qualifies for a precise, homogeneous, and thus higher-order control to fully automatize or optimize future biotechnological applications.
Whole-Genome Sequencing Analysis of Salmonella enterica Serovar Enteritidis Isolates in Chile Provides Insights into Possible Transmission between Gulls, Poultry, and Humans
Authors: Toro Magaly , Retamal Patricio , Ayers Sherry , Barreto Marlen , Allard Marc , Brown Eric W. , Gonzalez-Escalona Narjol
Published: August 2016

Salmonella enterica
subsp.
enterica
serotype Enteritidis is a major cause of human salmonellosis worldwide; however, little is known about the genetic relationships between
S
. Enteritidis clinical strains and
S
. Enteritidis strains from other sources in Chile. We compared the whole genomes of 30
S
. Enteritidis strains isolated from gulls, domestic chicken eggs, and humans in Chile, to investigate their phylogenetic relationships and to establish their relatedness to international strains. Core genome multilocus sequence typing (cgMLST) analysis showed that only 246/4,065 shared loci differed among these Chilean strains, separating them into two clusters (I and II), with cluster II being further divided into five subclusters. One subcluster (subcluster 2) contained strains from all surveyed sources that differed at 1 to 18 loci (of 4,065 loci) with 1 to 18 single-nucleotide polymorphisms (SNPs), suggesting interspecies transmission of
S
. Enteritidis in Chile. Moreover, clusters were formed by strains that were distant geographically, which could imply that gulls might be spreading the pathogen throughout the country. Our cgMLST analysis, using other
S
. Enteritidis genomes available in the National Center for Biotechnology Information (NCBI) database, showed that
S
. Enteritidis strains from Chile and the United States belonged to different lineages, which suggests that
S
. Enteritidis regional markers might exist and could be used for trace-back investigations.

IMPORTANCE
This study highlights the importance of gulls in the spread of
Salmonella
Enteritidis in Chile. We revealed a close genetic relationship between some human and gull
S
. Enteritidis strains (with as few as 2 of 4,065 genes being different), and we also found that gull strains were present in clusters formed by strains isolated from other sources or distant locations. Together with previously published evidence, this suggests that gulls might be spreading this pathogen between different regions in Chile and that some of those strains have been transmitted to humans. Moreover, we discovered that Chilean
S
. Enteritidis strains clustered separately from most of
S
. Enteritidis strains isolated throughout the world (in the GenBank database) and thus it might be possible to distinguish the geographical origins of strains based on specific genomic features. This could be useful for trace-back investigations of foodborne illnesses throughout the world.
High serum selenium levels are associated with increased risk for diabetes mellitus independent of central obesity and insulin resistance
Authors: Lu Chia-Wen , Chang Hao-Hsiang , Yang Kuen-Cheh , Kuo Chia-Sheng , Lee Long-Teng , Huang Kuo-Chin
Published: August 2016

Objective

Selenium is an essential micronutrient for human health. Although many observational and interventional studies have examined the associations between selenium and diabetes mellitus, the findings were inconclusive. This study aimed to investigate the relationship between serum selenium levels and prevalence of diabetes, and correlated the relationship to insulin resistance and central obesity.

Research design and methods

This was a hospital-based case–control study of 847 adults aged more than 40 years (diabetes: non-diabetes =1:2) in Northern Taiwan. Serum selenium was measured by an inductively coupled plasma-mass spectrometer. The association between serum selenium and diabetes was examined using multivariate logistic regression analyses.

Results

After adjusting for age, gender, current smoking, current drinking, and physical activity, the ORs (95% CI, p value) of having diabetes in the second (Q2), third (Q3), and fourth (Q4) selenium quartile groups were 1.24 (95% CI 0.78 to 1.98, p>0.05), 1.90 (95% CI 1.22 to 2.97, p<0.05), and 5.11 (95% CI 3.27 to 8.00, p<0.001), respectively, compared with the first (Q1) quartile group. Further adjustments for waist circumference and homeostatic model assessment-insulin resistance (HOMA-IR) largely removed the association of serum selenium levels with diabetes but not in the highest quartile (compared with Q1, Q3: 1.57, 95% CI 0.91 to 2.70, Q4: 3.79, 95% CI 2.17 to 6.32).

Conclusions

We found that serum selenium levels were positively associated with prevalence of diabetes. This is the first human study to link insulin resistance and central obesity to the association between selenium and diabetes. Furthermore, the association between selenium and diabetes was independent of insulin resistance and central obesity at high serum selenium levels. The mechanism behind warrants further confirmation.
Socioeconomic disparities in coverage of full immunisation among children of adolescent mothers in India, 1990–2006: a repeated cross-sectional analysis
Authors: Kumar Chandan , Singh Prashant Kumar , Singh Lucky , Rai Rajesh Kumar
Published: August 2016

Objective

Studies have highlighted that children of adolescent (aged 15–19 years) mothers are likely to receive relatively poor healthcare. With an unacceptably high adolescent birth rate, India houses the highest number of adolescent mothers globally, putting children at risk of inadequate vaccination. This paper assesses trends and extent of socioeconomic disparities in the coverage of full immunisation among children of adolescent mothers in India.

Design

Repeated cross-sectional analytical study.

Data sources

3 consecutive rounds of the National Family Health Survey (NFHS) conducted during 1992–1993, 1998–1999 and 2005–2006 were used. Besides, the required information is also extracted from the 2011 Indian Census.

Participants

Children (aged 12–23 months) of adolescent (aged 15–19 years) mothers. Sample inclusion criteria involved the last child of the adolescent eligible to avail full immunisation.

Setting

Nationally representative sample.

Data analysis

The Cochran-Armitage test, χ2test and binary logistic regression methods were applied to attain the study objective.

Results

Between 1990 and 2006, a non-significant increase of 4 percentage points in full immunisation of children of adolescent mothers was estimated. During the same period, a large difference between the probability of children of adolescent mothers receiving full immunisation belonging to the least (predicted probability (PP): 0.196 in 1990–1993, and PP: 0.213 in 2003–2006) and the most (PP: 0.589 in 1990–1993, and PP: 0.645 in 2003–2006) socioeconomically privileged group was estimated, and this disparity persisted over the survey period.

Conclusions

During 1990–2006, an insufficient improvement in provision of full immunisation to children born to adolescent mothers was recorded. The study underscored the suboptimum immunisation of rural, illiterate and poor children of adolescent women. The programme and policymakers could focus on district-wise concentration of adolescent women, especially those belonging to the underprivileged groups, to design a targeted intervention to elevate the level of immunisation of children of adolescent mothers.
Vitamin B12status in women of childbearing age in the UK and its relationship with national nutrient intake guidelines: results from two National Diet and Nutrition Surveys
Authors: Sukumar Nithya , Adaikalakoteswari Antonysunil , Venkataraman Hema , Maheswaran Hendramoorthy , Saravanan Ponnusamy
Published: August 2016

Objective

To assess serum B12, folate and the associated homocysteine (Hcy) levels among women of childbearing age in the UK and examine their association with dietary intake in relation to the UK Recommended Nutrient Intakes (RNIs) for B12and folate.

Design

Cross-sectional study.

Setting

Data from two publicly available National Diet and Nutrition Surveys (NDNS 2000/2001 and 2008/2012) were used. These were population-based surveys of randomly selected samples of adults which were carried out in their households.

Participants

Women of childbearing age (aged 19–39 years), representative of the UK population. Those who were pregnant or breastfeeding were excluded.

Outcome measures

The associations between micronutrient intakes and blood levels of B12, folate and Hcy were assessed by correlation and stepwise linear regression. B12intake was divided into quintiles and plotted against blood B12and Hcy concentrations to determine the threshold of any associations.

Results

299 women from the first NDNS cohort had complete intake and biomarker data. The prevalence of serum vitamin B12(≤150 pmol/L) and serum folate (≤10 nmol/L) deficiency and hyperhomocysteinemia (≥12 µmol/L) was 12.4%, 6.4% and 21.2%, respectively, despite seemingly adequate B12intakes (median 3.8 μg/day, 96% consumed more than the UK RNI of 1.5 μg/day). B12concentrations increased across all quintiles of intake with serum levels in quintiles 4 and 5 (median intake 4.9 and 7.1 μg/day, respectively) significantly higher than quintile 1. However, Hcy concentrations levelled off between quintiles 4 and 5. Comparison of micronutrient intake between the two surveys found that folate intake has reduced in the more recent cohort.

Conclusions

The UK RNI for B12intake should be increased for women of childbearing age with intakes of around 5–7 μg/day likely to be associated with stable biomarker levels. B12levels should also be measured in women preconceptionally or in early pregnancy given the high rates of deficiency.
HALON—hysterectomy by transabdominal laparoscopy or natural orifice transluminal endoscopic surgery: a randomised controlled trial (study protocol)
Authors: Baekelandt Jan , De Mulder Peter A , Le Roy Ilse , Mathieu Chantal , Laenen Annouschka , Enzlin Paul , Weyers Steven , Mol Ben WJ , Bosteels Jan JA
Published: August 2016

Introduction

Natural orifice transluminal endoscopic surgery (NOTES) uses natural body orifices to access the cavities of the human body to perform surgery. NOTES limits the magnitude of surgical trauma and has the potential to reduce postoperative pain. This is the first randomised study in women bound to undergo hysterectomy for benign gynaecological disease comparing NOTES with classical laparoscopy.

Methods and analysis

All women aged 18–70 years, regardless of parity, consulting at our practice with an indication for hysterectomy due to benign gynaecological disease will be eligible. After stratification according to uterine size on clinical examination, participants will be randomised to be treated by laparoscopy or by transvaginal NOTES. Participants will be evaluated on day 0, days 1–7 and at 3 and 6 months. The following data will be collected: the proportion of women successfully treated by removing the uterus by the intended approach as randomised; the proportion of women admitted to the inpatient hospital; postoperative pain scores measured twice daily by the women from day 1 to 7; the total amount of analgesics used from day 1 to 7; readmission during the first 6 weeks; presence and intensity of dyspareunia and sexual well-being at baseline, 3 and 6 months (Short Sexual Functioning Scale (SSFS) scale); duration of surgery; postoperative infection or other surgical complications; direct and indirect costs incurred up to 6 weeks following surgery. The primary outcome will be the proportion of women successfully treated by the intended technique; all other outcomes are secondary.

Ethics and dissemination

The study was approved on 1 December 2015 by the Ethics Committee of the Imelda Hospital, Bonheiden, Belgium. The first patient was randomised on 17 December 2015. The last participant randomised should be treated before 30 November 2017. The results will be presented in peer-reviewed journals and at scientific meetings within 4 years after starting recruitment.

Trial registration number

NCT02631837; Pre-results.
False-positive findings in Cochrane meta-analyses with and without application of trial sequential analysis: an empirical review
Authors: Imberger Georgina , Thorlund Kristian , Gluud Christian , Wetterslev Jørn
Published: August 2016

Objective

Many published meta-analyses are underpowered. We explored the role of trial sequential analysis (TSA) in assessing the reliability of conclusions in underpowered meta-analyses.

Methods

We screened The Cochrane Database of Systematic Reviews and selected 100 meta-analyses with a binary outcome, a negative result and sufficient power. We defined a negative result as one where the 95% CI for the effect included 1.00, a positive result as one where the 95% CI did not include 1.00, and sufficient power as the required information size for 80% power, 5% type 1 error, relative risk reduction of 10% or number needed to treat of 100, and control event proportion and heterogeneity taken from the included studies. We re-conducted the meta-analyses, using conventional cumulative techniques, to measure how many false positives would have occurred if these meta-analyses had been updated after each new trial. For each false positive, we performed TSA, using three different approaches.

Results

We screened 4736 systematic reviews to find 100 meta-analyses that fulfilled our inclusion criteria. Using conventional cumulative meta-analysis, false positives were present in seven of the meta-analyses (7%, 95% CI 3% to 14%), occurring more than once in three. The total number of false positives was 14 and TSA prevented 13 of these (93%, 95% CI 68% to 98%). In a post hoc analysis, we found that Cochrane meta-analyses that are negative are 1.67 times more likely to be updated (95% CI 0.92 to 2.68) than those that are positive.

Conclusions

We found false positives in 7% (95% CI 3% to 14%) of the included meta-analyses. Owing to limitations of external validity and to the decreased likelihood of updating positive meta-analyses, the true proportion of false positives in meta-analysis is probably higher. TSA prevented 93% of the false positives (95% CI 68% to 98%).
General practitioners’ experiences with out-of-hours cardiorespiratory consultations: a qualitative study
Authors: Schols Angel M R , van Boekholt Tessa A , Oversier Lex M R , Dinant Geert-Jan , Cals Jochen W L
Published: August 2016

Objectives

To explore general practitioners’ (GPs’) experiences with and views on the diagnosis and management of patients with cardiorespiratory symptoms during GP out-of-hours care. We also aimed to identify ways of (diagnostic) support during these consultations.

Design

Qualitative study; face-to-face semistructured interviews.

Setting

GP out-of-hours care in the Netherlands.

Participants

15 GPs in the province of Limburg, the Netherlands.

Results

Overall, GPs find cardiorespiratory consultations challenging and difficult. Tension and uncertainty as well as defensive behaviour were the key themes that characterised GPs’ experiences. We identified several subthemes underlying the key themes: setting, potentially severe consequences, absence of a pre-existing relationship and little knowledge of the patient's background, difficulties differentiating between possible causes of symptoms, changed public opinion and patient population, and previous experiences. GPs approach cardiorespiratory consultations differently and their threshold for referring patients and performing diagnostic tests is lower. We identified differing views on the use of additional diagnostic tests at GP out-of-hours services.

Conclusions

This study sheds further light on how GPs experience cardiorespiratory consultations during out-of-hours care and how this leads to a high number of cardiorespiratory referrals. GPs relate cardiorespiratory consultation during out-of-hours care with tension and uncertainty leading to defensive behaviour, which can be translated into a different approach towards cardiorespiratory consultations and a lower threshold for referring patients and performing diagnostic tests. Opinions on the possible added value of additional diagnostics in reducing the number of referrals should be further investigated, as we identified differing views on the use of additional diagnostic tests at GP out-of-hours services.