bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of a multinutrient intervention after ischemic stroke in female C57Bl/6 mice
Authors: Wiesmann Maximilian , Timmer Nienke M. , Zinnhardt Bastian , Reinhard Dirk , Eligehausen Sarah , Königs Anja , Ben Jeddi Hasnae , Dederen Pieter J. , Jacobs Andreas H. , Kiliaan Amanda J.
Published: September 2017

Stroke can affect females very differently from males, and therefore preclinical research on underlying mechanisms and the effects of interventions should not be restricted to male subjects, and treatment strategies for stroke should be tailored to benefit both sexes. Previously, we demonstrated that a multinutrient intervention (Fortasyn) improved impairments after ischemic stroke induction in male C57Bl/6 mice, but the therapeutic potential of this dietary treatment remained to be investigated in females. We now induced a transient middle cerebral artery occlusion (tMCAo) in C57Bl/6 female mice and immediately after surgery switched to either Fortasyn or an isocaloric Control diet. The stroke females performed several behavioral and motor tasks before and after tMCAo and were scanned in an 11.7 Tesla magnetic resonance imaging (MRI) scanner to assess brain perfusion, integrity, and functional connectivity. To assess brain plasticity, inflammation, and vascular integrity, immunohistochemistry was performed after killing of the mice. We found that the multinutrient intervention had diverse effects on the stroke‐induced impairments in females. Similar to previous observations in male stroke mice, brain integrity, sensorimotor integration and neurogenesis benefitted from Fortasyn, but impairments in activity and motor skills were not improved in female stroke mice. Overall, Fortasyn effects in the female stroke mice seem more modest in comparison to previously investigated male stroke mice. We suggest that with further optimization of treatment protocols more information on the efficacy of specific interventions in stroked females can be gathered. This in turn will help with the development of (gender‐specific) treatment regimens for cerebrovascular diseases such as stroke.

image

This article is part of the Special Issue “Vascular Dementia”.
Interindividual differences in the intraindividual association of competence and well‐being: Combining experimental and intensive longitudinal designs
Authors: Neubauer Andreas B. , Lerche Veronika , Voss Andreas
Published: September 2017

Objective

The aim of the present study is to assess whether people differ in the degree to which their well‐being is affected by fulfillment of the need for competence. Specifically, we want to examine (a) whether interindividual differences in the within‐person coupling of competence satisfaction and well‐being (competence satisfaction effect) and of competence dissatisfaction and well‐being (competence dissatisfaction effect) exist, and (b) whether these differences moderate the effects of an experimentally induced frustration of the need for competence.

Method

A daily diary study (N = 89) and a laboratory based experiment (N = 150) were conducted to investigate interindividual differences in need effects. In a third study, participants of an additional daily diary study (N = 129) were subsequently subjected to an experimental frustration of the need for competence.

Results

Including interindividual differences in the within‐person coupling of need fulfillment and well‐being improved model fit significantly, indicating that there were statistically meaningful interindividual differences in need effects. The interaction of competence satisfaction effect and competence dissatisfaction effect moderated the effect of an experimental competence frustration on negative affect.

Conclusion

Results show that interindividual differences in the association of competence fulfillment and well‐being are a matter of degree, but not quality. They also support the claim that need satisfaction and dissatisfaction are more than psychometric opposites.
A numerical classification system for cleft lip and palate in the dog
Authors: Moura E. , Pimpão C. T.
Published: September 2017

An easy‐to‐use classification that enables an accurate record of canine cleft lip and palate is fundamental for effective communication between professionals and researchers and optimal use of published information. Here we present how a classification system for human cleft lip and palate can be used to register spontaneous cases in dogs, highlighting its advantages. This system is based on four topographic areas with a numerical representation of the severity of the cleft in each area. The use of spontaneous cases has the advantage of providing clefts that are naturally similar to their human counterparts for surgical, genetic and genomic studies and, furthermore, will reduce the need for experimental models of this condition.
Opportunistic Invasive Cutaneous Fungal Infections Associated with Administration of Cyclosporine to Dogs with Immune‐mediated Disease
Authors: McAtee B.B. , Cummings K.J. , Cook A.K. , Lidbury J.A. , Heseltine J.C. , Willard M.D.
Published: September 2017

Background

Opportunistic invasive fungal infections (OIFIs) occur in dogs administered immunosuppressive medications. However, the epidemiology ofOIFIs among dogs undergoing immunosuppressive treatment is poorly understood. The aims of this study were to (1) estimate the incidence ofOIFIs among dogs diagnosed with certain immune‐mediated diseases and treated with immunosuppressive drugs, and (2) determine if administration of particular drug(s) was a risk factor forOIFIs.

Hypothesis

Dogs receiving cyclosporine treatment (alone or as part of a multidrug protocol) are at higher risk of developingOIFIs.

Animals

One hundred and thirteen client‐owned dogs diagnosed with select immune‐mediated diseases: 42 withIMHA, 29 withITP, 34 withIMPA, and 8 with Evans syndrome.

Methods

Retrospective cohort study. Medical records of dogs presenting to the Texas A&M University, Veterinary Medical Teaching Hospital between January 2008 and December 2015, and treated for 1 or more ofIMHA,IMPA,ITP, or Evans syndrome were retrospectively reviewed. Dogs that did not develop anOIFIwere excluded if they died, were euthanized, or were lost to follow‐up within 120 days of initiation of immunosuppressive treatment.

Results

Fifteen dogs of 113 (13%) were diagnosed with anOIFIbased on 1 or more of cytology, culture, or histopathology. The odds of developing anOIFIwere greater among dogs that were treated with cyclosporine (OR= 7.1,P= 0.017; 95%CI, 1.5–34.4) and among male dogs (OR= 5.1,P= 0.018; 95%CI, 1.4–17.9).

Conclusions and Clinical Importance

OIFIs were significantly more likely in male dogs and those receiving cyclosporine. It is important to considerOIFIs as a potential complication of immunosuppressive treatment, particularly cyclosporine.
SERPINA1 and MAN1B1 polymorphisms are not linked to severe liver disease in a French cohort of alpha‐1 antitrypsin deficiency children
Authors: Joly Philippe , Lachaux Alain , Ruiz Mathias , Restier Lioara , Belmalih Abdelhouaed , Chapuis‐Cellier Colette , Francina Alain , Renoux Céline , Bouchecareilh Marion
Published: September 2017

Background & Aims

Fifteen to twenty percent of alpha‐1 antitrypsin deficiency patients (A1ATD) have a severe liver outcome (portal hypertension ‐ PHT) during childhood. Since they all share the same ZZSERPINA1 genotype and that environmental factors such as alcohol cannot be advanced, the presence of modifier genes is now well recognized. SNPs located on the SERPINA1 and MAN1B1 genes have already been tested in very few studies with contradictory or not replicated results.

Methods

Our genotype–phenotype correlation study, performed on 92 ZZ children, aimed at determining once and for all if SERPINA1 and MAN1B1 polymorphisms may be implied in the onset of PHT. To do so, we also performed for the first time a complete haplotype reconstruction for data analysis.

Results

The two genetic associations with severe liver disease that had been suspected previously (one SNP for SERPINA1 and another for MAN1B1) were not confirmed in our cohort. Moreover, the haplotype analysis identified only one major genetic background for the SERPINA1 Z‐allele, allowing us to exclude the presence of a frequent modifier SNP within. For MAN1B1, four major haplotypes were identified but the prevalence of PHT did not significantly differ between them.

Conclusion

We conclude that genetic polymorphisms in these two genes probably do not influence the onset of severe liver disease in A1ATD.
Absolute Time: The Limit of Kant's Idealism
Authors: Stan Marius
Published: September 2017

I examine here if Kant can explain our knowledge of duration by showing that time has metric structure. To do so, I spell out two possible solutions: time's metric could be intrinsic or extrinsic. I argue that Kant's resources are too weak to secure any intrinsic, transcendentally‐based temporal metrics; but he can supply an extrinsic metric, based in ametaphysicalfact about matter. I conclude that Transcendental Idealism is incomplete: it cannot account for the durative aspects of experience—or it can do so only with help from a non‐trivial metaphysics of material substance.
Extracellular vesicles from oral squamous carcinoma cells display pro‐ and anti‐angiogenic properties
Authors: de Andrade ALDL , de Oliveira CE , Dourado MR , Macedo CCS , Winck FV , Paes Leme AF , Salo T , Coletta RD , de Almeida Freitas R , Galvão HC
Published: September 2017

Background

A new intercellular communication mode established by neoplastic cells and tumor microenvironment components is based on extracellular vesicles (EVs). However, the biological effects of the EVs released by tumor cells on angiogenesis are not completely understood. Here, we aimed to understand the biological effects of EVs isolated from two cell lines of oral squamous cell carcinoma (OSCC) (SCC15 and HSC3) on endothelial cell tubulogenesis.

Methods

OSCC‐derived EVs were isolated with a polymer‐based precipitation method, quantified using nanoparticle tracking analysis and verified for EV markers by dot blot. Functional assays were performed to assess the angiogenic potential of the OSCC‐derived EVs.

Results

The results showed that EVs derived from both cell lines displayed typical spherical‐shaped morphology and expressed the EV markers CD63 and Annexin II. Although the average particle concentration and size were quite similar, SCC15‐derived EVs promoted a pronounced tubular formation associated with significant migration and apoptosis rates of the endothelial cells, whereas EVs derived from HSC3 cells inhibited significantly endothelial cell tubulogenesis and proliferation.

Conclusion

The findings of this study reveal that EVs derived from different OSCC cell lines by a polymer‐based precipitation method promote pro‐ or anti‐angiogenic effects.
Polls and Elections: Terror, War, and the Economy in George W. Bush's Approval Ratings: The Importance of Salience in Presidential Approval
Authors: Ostrom Charles W. , Kraitzman Alon P. , Newman Brian , Abramson Paul R.
Published: September 2017

George W. Bush's presidency provides a fertile ground to further develop the standard model of presidential approval. In contrast to the vast presidential approval literature, early studies of Bush conclude economic conditions had no effect once the war in Iraq began. Rather than require a fundamental rethinking of presidential approval theories, we argue that approval models must take into account issue salience. When a factor is salient, it has a stronger effect. During the Bush presidency, with considerable over‐time variation in the salience of the economy, terrorism, and the war in Iraq, each, in turn, powerfully affected Bush's approval.
TLR‐Induced SMPD3 Defects Enhance Inflammatory Response of B Cell and Macrophage in the Pathogenesis of SLE
Authors: Liu F. , Li X. , Yue H. , Ji J. , You M. , Ding L. , Fan H. , Hou Y.
Published: September 2017

B lymphocyte and macrophages may contribute to SLE pathogenesis through cytokine production after TLR stimulation. Emerging evidences suggested that defects of sphingolipid metabolism were responsible for SLE pathogenesis. However, it is not clear whether these defects exist in B cells and macrophages under SLE condition and whether TLR signalling pathway was related to the dysfunction of sphingolipid metabolism in SLE. Here, we demonstrated that the enzymes involved in the sphingolipid metabolism expressed abnormally in B cells from SLE patients and lupus‐prone mice. Moreover, we found that TLR signalling induced the abnormal expression of sphingomyelin phosphodiesterase 3 (SMPD3), sphingosine‐1‐phosphate phosphatase 2 (SGPP2), ceramide kinase (CERK) and UDP glycosyltransferase 8 (UGT8), which were involved in sphingolipid metabolism. TLR signalling also induced the transportation of SMPD3 from Golgi apparatus. Furthermore, the dysfunction of SMPD3 enhanced TLR‐induced inflammatory response of B cells and macrophages in turn. Thus, these findings provide an innovative direction and a new target for research and treatment of SLE.
Increased Expression of Programmed Cell Death‐1 in Regulatory T Cells of Patients with Severe Sepsis and Septic Shock: An Observational Clinical Study
Authors: Liu Q. , An L. , Qi Z. , Zhao Y. , Li C.
Published: September 2017

While regulatory T cells (Tregs) constitutively express programmed cell death‐1 (PD‐1), the role of PD‐1 expression in Tregs of patients with sepsis remains unclear. Thus, we determined PD‐1 expression in Tregs from the peripheral blood of patients with severe sepsis and septic shock. Seventy‐eight patients with severe sepsis and 40 with septic shock, as well as 21 healthy subjects, were enrolled in this study. The percentage of peripheral blood PD‐1+ Tregs, as well as absolute Treg counts, were compared between these three groups. PD‐1 expression in Tregs and absolute Treg counts were also compared between survivors and non‐survivors in patients with sepsis. PD‐1 expression in Tregs increased in patients with sepsis compared to healthy controls. Conversely, absolute Treg counts were significantly decreased in patients with sepsis compared to healthy controls; patients with septic shock had the lowest absolute Treg counts. Among patients with sepsis, survivors had lower levels of PD‐1 expression in Tregs, as well as higher absolute Treg counts, than non‐survivors. Additionally, the percentage of PD‐1+ Tregs correlated positively with lactate levels as well as the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores in patients with sepsis. PD‐1 was upregulated in Tregs of patients with sepsis and may indicate a state of immune dysfunction. Overexpression of PD‐1 in Tregs was associated with more severe sepsis as well as poor outcomes.
Mesenchymal Stem Cells Overexpressing Interleukin‐35 Propagate Immunosuppressive Effects in Mice
Authors: Guo H. , Zhao N. , Gao H. , He X.
Published: September 2017

To explore generation of interleukin (IL)‐35‐expressing mouse adipocyte‐derived mesenchymal stem cells (Ad‐MSCs) using lentiviral vector and their potential immunosuppressive effects in mice. Ad‐MSCs were isolated and cultured in vitro and transfected with a lentivirus vector for overexpression of the therapeutic murine IL‐35 gene. IL‐35 expression in transfected MSCs (IL‐35‐MSCs) was quantified by enzyme‐linked immunosorbent assay (ELISA). The lymphocytes subsets after one‐way mixed lymphocyte culture and in vivo intravenous transplantation were analysed by flow cytometry to evaluate the immunosuppressive effects of IL‐35‐MSCs. ELISA was performed to examine IL‐10, IL‐17A and IL‐35 expression in lymphocyte culture. Mouse Ad‐MSCs were isolated and cultured. IL‐35 was expressed in the MSC supernatant and serum after IL‐35 transduction into Ad‐MSCs by lentiviral vector transfection in vitro and in vivo. The percentage of CD4+ CD25+ T regulatory (Treg) cells in mice treated with IL‐35‐MSCs significantly increased. IL‐35‐MSCs upregulated the CD4+ CD25+ Treg cells in the allogeneic mixed lymphocyte reaction system, and lowered the percentage of CD4+ T cells compared with the other two control groups (P < 0.01). IL‐17A expression significantly decreased and IL‐10 expression significantly increased in IL‐35‐MSCs and MSCs when compared by ELISA to the control groups (P < 0.01). IL‐35‐transduced Ad‐MSCs in vivo can enhance proliferation of CD4+ CD25+ Treg cells and suppress the function of effector T cells such as T helper (Th) 1, Th2 and Th17 cells and may reduce the development of allograft rejection. Our data suggest that transduced Ad‐MSCs overexpressing IL‐35 may provide a useful approach for basic research on cell‐based immunotolerance therapy for inducing transplantation tolerance.
Pre‐clinical evaluation of N‐acetylcysteine reveals side effects in the mdx mouse model of Duchenne muscular dystrophy
Authors: Pinniger Gavin J. , Terrill Jessica R. , Assan Evanna B. , Grounds Miranda D. , Arthur Peter G.
Published: September 2017

Key points

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation and oxidative stress.

The antioxidant N‐acetylcysteine (NAC) has been proposed as a therapeutic intervention for DMD boys, but potential adverse effects of NAC have not been widely investigated.

We used young (6 weeks old) growing mdx mice to investigate the capacity of NAC supplementation (2% in drinking water for 6 weeks) to improve dystrophic muscle function and to explore broader systemic effects of NAC treatment.

NAC treatment improved normalised measures of muscle function, and decreased inflammation and oxidative stress, but significantly reduced body weight gain, muscle weight and liver weight.

Unexpected significant adverse effects of NAC on body and muscle weights indicate that interpretation of muscle function based on normalised force measures should be made with caution and careful consideration is needed when proposing the use of NAC as a therapeutic treatment for young DMD boys.

Duchenne muscular dystrophy (DMD) is a fatal X‐linked muscle wasting disease characterised by severe muscle weakness, necrosis, inflammation and oxidative stress. The antioxidant N‐acetylcysteine (NAC) has been proposed as a potential therapeutic intervention for DMD boys. We investigated the capacity of NAC to improve dystrophic muscle function in the mdx mouse model of DMD. Young (6 weeks old) mdx and non‐dystrophic C57 mice receiving 2% NAC in drinking water for 6 weeks were compared with untreated mice. Grip strength and body weight were measured weekly, before the 12 week old mice were anaesthetised and extensor digitorum longus (EDL) muscles were excised for functional analysis and tissues were sampled for biochemical analyses. Compared to untreated mice, the mean (SD) normalised grip strength was significantly greater in NAC‐treated mdx [3.13 (0.58) vs 4.87 (0.78) g body weight (bw)−1; P < 0.001] and C57 mice [3.90 (0.32) vs 5.32 (0.60) g bw−1; P < 0.001]. Maximum specific force was significantly greater in NAC‐treated mdx muscles [9.80 (2.27) vs 13.07 (3.37) N cm−2; P = 0.038]. Increased force in mdx mice was associated with reduced thiol oxidation and inflammation in fast muscles, and increased citrate synthase activity in slow muscle. Importantly, NAC significantly impaired body weight gain in both strains of young growing mice, and reduced liver weight in C57 mice and muscle weight in mdx mice. These potentially adverse effects of NAC emphasise the need for caution when interpreting improvements in muscle function based on normalised force measures, and that careful consideration be given to these effects when proposing NAC as a potential treatment for young DMD boys.
Artificial solid electrolyte interphase for aqueous lithium energy storage systems
Authors: Zhi Jian , Yazdi Alireza Zehtab , Valappil Gayathri , Haime Jessica , Chen P.
Published: September 2017

An ultrathin graphene artificial interphase stabilizes active material and conductive carbon in aqueous energy storage systems.
Ultrahigh–current density anodes with interconnected Li metal reservoir through overlithiation of mesoporous AlF
3
framework
Authors: Wang Hansen , Lin Dingchang , Liu Yayuan , Li Yuzhang , Cui Yi
Published: September 2017

Overlithiation of mesoporous AlF
3
framework enables ultrahigh–current density Li metal anodes.
Self-determined shapes and velocities of giant near-zero drag gas cavities
Authors: Vakarelski Ivan U. , Klaseboer Evert , Jetly Aditya , Mansoor Mohammad M. , Aguirre-Pablo Andres A. , Chan Derek Y. C. , Thoroddsen Sigurdur T.
Published: September 2017

A gas cavity can reduce the hydrodynamic drag on a falling sphere in liquid to near zero by providing perfect slip conditions.
Chitinase Expression in Listeria monocytogenes Is Influenced by
lmo0327
, Which Encodes an Internalin-Like Protein
Authors: Paspaliari Dafni Katerina , Kastbjerg Vicky Gaedt , Ingmer Hanne , Popowska Magdalena , Larsen Marianne Halberg
Published: September 2017

The chitinolytic system of
Listeria monocytogenes
thus far comprises two chitinases, ChiA and ChiB, and a lytic polysaccharide monooxygenase, Lmo2467. The role of the system in the bacterium appears to be pleiotropic, as besides mediating the hydrolysis of chitin, the second most ubiquitous carbohydrate in nature, the chitinases have been deemed important for the colonization of unicellular molds, as well as mammalian hosts. To identify additional components of the chitinolytic system, we screened a transposon mutant library for mutants exhibiting impaired chitin hydrolysis. The screening yielded a mutant with a transposon insertion in a locus corresponding to
lmo0327
of the EGD-e strain.
lmo0327
encodes a large (1,349 amino acids [aa]) cell wall-associated protein that has been proposed to possess murein hydrolase activity. The single inactivation of
lmo0327
, as well as of
lmo0325
that codes for a putative transcriptional regulator functionally related to
lmo0327
, led to an almost complete abolishment of chitinolytic activity. The effect could be traced at the transcriptional level, as both
chiA
and
chiB
transcripts were dramatically decreased in the
lmo0327
mutant. In accordance with that, we could barely detect ChiA and ChiB in the culture supernatants of the mutant strain. Our results provide new information regarding the function of the
lmo0325-lmo0327
locus in
L. monocytogenes
and link it to the expression of chitinolytic activity.

IMPORTANCE
Many bacteria from terrestrial and marine environments express chitinase activities enabling them to utilize chitin as the sole source of carbon and nitrogen. Interestingly, several bacterial chitinases may also be involved in host pathogenesis. For example, in the important foodborne pathogen
Listeria monocytogenes
, the chitinases ChiA and ChiB and the lytic polysaccharide monooxygenase Lmo2467 are implicated in chitin assimilation but also act as virulence factors during the infection of mammalian hosts. Therefore, it is important to identify their regulators and induction cues to understand how the different roles of the chitinolytic system are controlled and mediated. Here, we provide evidence for the importance of
lmo0327
and
lmo0325
, encoding a putative internalin/autolysin and a putative transcriptional activator, respectively, in the efficient expression of chitinase activity in
L. monocytogenes
and thereby provide new information regarding the function of the
lmo0325-lmo0327
locus.
Oxidative Stressors Modify the Response of Streptococcus mutans to Its Competence Signal Peptides
Authors: De Furio Matthew , Ahn Sang Joon , Burne Robert A. , Hagen Stephen J.
Published: September 2017

The dental caries pathogen
Streptococcus mutans
is continually exposed to several types of stress in the oral biofilm environment. Oxidative stress generated by reactive oxygen species has a major impact on the establishment, persistence, and virulence of
S. mutans
. Here, we combined fluorescent reporter-promoter fusions with single-cell imaging to study the effects of reactive oxygen species on activation of genetic competence in
S. mutans
. Exposure to paraquat, which generates superoxide anion, produced a qualitatively different effect on activation of expression of the gene for the master competence regulator, ComX, than did treatment with hydrogen peroxide (H
2
O
2
), which can yield hydroxyl radical. Paraquat suppressed peptide-mediated induction of
comX
in a progressive and cumulative fashion, whereas the response to H
2
O
2
displayed a strong threshold behavior. Low concentrations of H
2
O
2
had little effect on induction of
comX
or the bacteriocin gene
cipB
, but expression of these genes declined sharply if extracellular H
2
O
2
exceeded a threshold concentration. These effects were not due to decreased reporter gene fluorescence. Two different threshold concentrations were observed in the response to H
2
O
2
, depending on the gene promoter that was analyzed and the pathway by which the competence regulon was stimulated. The results show that paraquat and H
2
O
2
affect the
S. mutans
competence signaling pathway differently, and that some portions of the competence signaling pathway are more sensitive to oxidative stress than others.

IMPORTANCE
Streptococcus mutans
inhabits the oral biofilm, where it plays an important role in the development of dental caries. Environmental stresses such as oxidative stress influence the growth of
S. mutans
and its important virulence-associated behaviors, such as genetic competence.
S. mutans
competence development is a complex behavior that involves two different signaling peptides and can exhibit cell-to-cell heterogeneity. Although oxidative stress is known to influence
S. mutans
competence, it is not understood how oxidative stress interacts with the peptide signaling or affects heterogeneity. In this study, we used fluorescent reporters to probe the effect of reactive oxygen species on competence signaling at the single-cell level. Our data show that different reactive oxygen species have different effects on
S. mutans
competence, and that some portions of the signaling pathway are more acutely sensitive to oxidative stress than others.
Acyl-Homoserine Lactone Production in Nitrifying Bacteria of the Genera Nitrosospira, Nitrobacter, and Nitrospira Identified via a Survey of Putative Quorum-Sensing Genes
Authors: Mellbye Brett L. , Spieck Eva , Bottomley Peter J. , Sayavedra-Soto Luis A.
Published: September 2017

The genomes of many bacteria that participate in nitrogen cycling through the process of nitrification contain putative genes associated with acyl-homoserine lactone (AHL) quorum sensing (QS). AHL QS or bacterial cell-cell signaling is a method of bacterial communication and gene regulation and may be involved in nitrogen oxide fluxes or other important phenotypes in nitrifying bacteria. Here, we carried out a broad survey of AHL production in nitrifying bacteria in three steps. First, we analyzed the evolutionary history of AHL synthase and AHL receptor homologs in sequenced genomes and metagenomes of nitrifying bacteria to identify AHL synthase homologs in ammonia-oxidizing bacteria (AOB) of the genus
Nitrosospira
and nitrite-oxidizing bacteria (NOB) of the genera
Nitrococcus
,
Nitrobacter
, and
Nitrospira
. Next, we screened cultures of both AOB and NOB with uncharacterized AHL synthase genes and AHL synthase-negative nitrifiers by a bioassay. Our results suggest that an AHL synthase gene is required for, but does not guarantee, cell density-dependent AHL production under the conditions tested. Finally, we utilized mass spectrometry to identify the AHLs produced by the AOB
Nitrosospira multiformis
and
Nitrosospira briensis
and the NOB
Nitrobacter vulgaris
and
Nitrospira moscoviensis
as
N
-decanoyl-
l
-homoserine lactone (C
10
-HSL),
N
-3-hydroxy-tetradecanoyl-
l
-homoserine lactone (3-OH-C
14
-HSL), a monounsaturated AHL (C
10:1
-HSL), and
N
-octanoyl-
l
-homoserine lactone (C
8
-HSL), respectively. Our survey expands the list of AHL-producing nitrifiers to include a representative of
Nitrospira
lineage II and suggests that AHL production is widespread in nitrifying bacteria.

IMPORTANCE
Nitrification, the aerobic oxidation of ammonia to nitrate via nitrite by nitrifying microorganisms, plays an important role in environmental nitrogen cycling from agricultural fertilization to wastewater treatment. The genomes of many nitrifying bacteria contain genes associated with bacterial cell-cell signaling or quorum sensing (QS). QS is a method of bacterial communication and gene regulation that is well studied in bacterial pathogens, but less is known about QS in environmental systems. Our previous work suggested that QS might be involved in the regulation of nitrogen oxide gas production during nitrite metabolism. This study characterized putative QS signals produced by different genera and species of nitrifiers. Our work lays the foundation for future experiments investigating communication between nitrifying bacteria, the purpose of QS in these microorganisms, and the manipulation of QS during nitrification.
High Substrate Uptake Rates Empower Vibrio natriegens as Production Host for Industrial Biotechnology
Authors: Hoffart Eugenia , Grenz Sebastian , Lange Julian , Nitschel Robert , Müller Felix , Schwentner Andreas , Feith André , Lenfers-Lücker Mira , Takors Ralf , Blombach Bastian
Published: September 2017

The productivity of industrial fermentation processes is essentially limited by the biomass-specific substrate consumption rate (

q
S

) of the applied microbial production system. Since

q
S

depends on the growth rate (μ), we highlight the potential of the fastest-growing nonpathogenic bacterium,
Vibrio natriegens
, as a novel candidate for future biotechnological processes.
V. natriegens
grows rapidly in BHIN complex medium with a μ of up to 4.43 h
−1
(doubling time of 9.4 min) as well as in minimal medium supplemented with various industrially relevant substrates. Bioreactor cultivations in minimal medium with glucose showed that
V. natriegens
possesses an exceptionally high

q
S

under aerobic (3.90 ± 0.08 g g
−1
h
−1
) and anaerobic (7.81 ± 0.71 g g
−1
h
−1
) conditions. Fermentations with resting cells of genetically engineered
V. natriegens
under anaerobic conditions yielded an overall volumetric productivity of 0.56 ± 0.10 g alanine liter
−1
min
−1
(i.e., 34 g liter
−1
h
−1
). These inherent properties render
V. natriegens
a promising new microbial platform for future industrial fermentation processes operating with high productivity.

IMPORTANCE
Low conversion rates are one major challenge to realizing microbial fermentation processes for the production of commodities operating competitively with existing petrochemical approaches. For this reason, we screened for a novel platform organism possessing characteristics superior to those of traditionally employed microbial systems. We identified the fast-growing
V. natriegens
, which exhibits a versatile metabolism and shows striking growth and conversion rates, as a solid candidate to reach outstanding productivities. Due to these inherent characteristics,
V. natriegens
can speed up common laboratory routines, is suitable for already existing production procedures, and forms an excellent foundation for engineering next-generation bioprocesses.
Impact of “Raised without Antibiotics” Beef Cattle Production Practices on Occurrences of Antimicrobial Resistance
Authors: Vikram Amit , Rovira Pablo , Agga Getahun E. , Arthur Terrance M. , Bosilevac Joseph M. , Wheeler Tommy L. , Morley Paul S. , Belk Keith E. , Schmidt John W.
Published: September 2017

The specific antimicrobial resistance (AMR) decreases that can be expected from reducing antimicrobial (AM) use in U.S. beef production have not been defined. To address this data gap, feces were recovered from 36 lots of “raised without antibiotics” (RWA) and 36 lots of “conventional” (CONV) beef cattle. Samples (
n
= 719) were collected during harvest and distributed over a year. AMR was assessed by (i) the culture of six AM-resistant bacteria (ARB), (ii) quantitative PCR (qPCR) for 10 AMR genes (ARGs), (iii) a qPCR array of 84 ARGs, and (iv) metagenomic sequencing. Generally, AMR levels were similar, but some were higher in CONV beef cattle. The prevalence of third-generation cephalosporin-resistant (3GC
r
)
Escherichia coli
was marginally different between production systems (CONV, 47.5%; RWA, 34.8%;
P
= 0.04), but the seasonal effect (summer, 92.8%; winter, 48.3%;
P
< 0.01) was greater. Erythromycin-resistant (ERY
r
)
Enterococcus
sp. concentrations significantly differed between production systems (CONV, 1.91 log
10
CFU/g; RWA, 0.73 log
10
CFU/g;
P
< 0.01). Levels of
aadA1
,
ant
(
6
)-
I
,
bla
ACI
,
erm
(A),
erm
(B),
erm
(C),
erm
(F),
erm
(Q),
tet
(A),
tet
(B),
tet
(M), and
tet
(X) ARGs were higher (
P
< 0.05) in the CONV system. Aggregate abundances of all 43 ARGs detected by metagenomic sequencing and the aggregate abundances of ARGs in the aminoglycoside, β-lactam, macrolide-lincosamide-streptogramin B (MLS), and tetracycline AM classes did not differ (log
2
fold change < 1.0) between CONV and RWA systems. These results suggest that further reductions of AM use in U.S. beef cattle production may not yield significant AMR reductions beyond MLS and tetracycline resistance.

IMPORTANCE
The majority of antimicrobial (AM) use in the United States is for food-animal production, leading to concerns that typical AM use patterns during “conventional” (CONV) beef cattle production in the United States contribute broadly to antimicrobial resistance (AMR) occurrence. In the present study, levels of AMR were generally similar between CONV and “raised without antibiotics” (RWA) cattle. Only a limited number of modest AMR increases was observed in CONV cattle, primarily involving macrolide-lincosamide-streptogramin B (MLS) and tetracycline resistance. Macrolides (tylosin) and tetracyclines (chlortetracycline) are administered in-feed for relatively long durations to reduce liver abscesses. To ensure judicious AM use, the animal health, economic, and AMR impacts of shorter duration in-feed administration of these AMs should be examined. However, given the modest AMR reductions observed, further reductions of AM use in U.S. beef cattle production may not yield significant AMR reductions beyond MLS and tetracycline resistance.
Identifying the Active Microbiome Associated with Roots and Rhizosphere Soil of Oilseed Rape
Authors: Gkarmiri Konstantia , Mahmood Shahid , Ekblad Alf , Alström Sadhna , Högberg Nils , Finlay Roger
Published: September 2017

RNA stable isotope probing and high-throughput sequencing were used to characterize the active microbiomes of bacteria and fungi colonizing the roots and rhizosphere soil of oilseed rape to identify taxa assimilating plant-derived carbon following
13
CO
2
labeling. Root- and rhizosphere soil-associated communities of both bacteria and fungi differed from each other, and there were highly significant differences between their DNA- and RNA-based community profiles.
Verrucomicrobia
,
Proteobacteria
,
Planctomycetes
,
Acidobacteria
,
Gemmatimonadetes
,
Actinobacteria
, and
Chloroflexi
were the most active bacterial phyla in the rhizosphere soil.
Bacteroidetes
were more active in roots. The most abundant bacterial genera were well represented in both the
13
C- and
12
C-RNA fractions, while the fungal taxa were more differentiated.
Streptomyces
,
Rhizobium
, and
Flavobacterium
were dominant in roots, whereas
Rhodoplanes
and
Sphingomonas
(
Kaistobacter
) were dominant in rhizosphere soil. “
Candidatus
Nitrososphaera” was enriched in
13
C in rhizosphere soil.
Olpidium
and
Dendryphion
were abundant in the
12
C-RNA fraction of roots;
Clonostachys
was abundant in both roots and rhizosphere soil and heavily
13
C enriched.
Cryptococcus
was dominant in rhizosphere soil and less abundant, but was
13
C enriched in roots. The patterns of colonization and C acquisition revealed in this study assist in identifying microbial taxa that may be superior competitors for plant-derived carbon in the rhizosphere of
Brassica napus
.

IMPORTANCE
This microbiome study characterizes the active bacteria and fungi colonizing the roots and rhizosphere soil of
Brassica napus
using high-throughput sequencing and RNA-stable isotope probing. It identifies taxa assimilating plant-derived carbon following
13
CO
2
labeling and compares these with other less active groups not incorporating a plant assimilate.
Brassica napus
is an economically and globally important oilseed crop, cultivated for edible oil, biofuel production, and phytoextraction of heavy metals; however, it is susceptible to several diseases. The identification of the fungal and bacterial species successfully competing for plant-derived carbon, enabling them to colonize the roots and rhizosphere soil of this plant, should enable the identification of microorganisms that can be evaluated in more detailed functional studies and ultimately be used to improve plant health and productivity in sustainable agriculture.
Striatal molecular alterations in HD gene carriers: a systematic review and meta-analysis of PET studies
Authors: Niccolini Flavia , Pagano Gennaro , Fusar-Poli Paolo , Wood Andrew , Mrzljak Ladislav , Sampaio Cristina , Politis Marios
Published: September 2017

Background

Over the past years, positron emission tomography (PET) imaging studies have investigated striatal molecular changes in premanifest and manifest Huntington’s disease (HD) gene expansion carriers (HDGECs), but they have yielded inconsistent results.

Objective

To systematically examine the evidence of striatal molecular alterations in manifest and premanifest HDGECs as measured by PET imaging studies.

Methods

MEDLINE, ISI Web of Science, Cochrane Library and Scopus databases were searched for articles published until 7 June 2017 that included PET studies in manifest and premanifest HDGECs. Meta-analyses were conducted with random effect models, and heterogeneity was addressed with I2 index, controlling for publication bias and quality of study. The primary outcome was the standardised mean difference (SMD) of PET uptakes in the whole striatum, caudate and putamen in manifest and premanifest HDGECs compared with healthy controls (HCs).

Results

Twenty-four out of 63 PET studies in premanifest (n=158) and manifest (n=191) HDGECs and HCs (n=333) were included in the meta-analysis. Premanifest and manifest HDGECs showed significant decreases in dopamine D2 receptors in caudate (SMD=−1.233, 95% CI −1.753 to −0.713, p<0.0001; SMD=−5.792, 95% CI −7.695 to −3.890, p<0.0001) and putamen (SMD=−1.479, 95% CI −1.965 to −0.992, p<0.0001; SMD=−5.053, 95% CI −6.558 to −3.549, p<0.0001), in glucose metabolism in caudate (SMD=−0.758, 95% CI −1.139 to −0.376, p<0.0001; SMD=−3.738, 95% CI −4.880 to −2.597, p<0.0001) and putamen (SMD=−2.462, 95% CI −4.208 to −0.717, p=0.006; SMD=−1.650, 95% CI −2.842 to −0.458, p<0.001) and in striatal PDE10A binding (SMD=−1.663, 95% CI −2.603 to −0.723, p=0.001; SMD=−2.445, 95% CI −3.371 to −1.519, p<0.001).

Conclusions

PET imaging has the potential to detect striatal molecular changes even at the early premanifest stage of HD, which are relevant to the neuropathological mechanisms underlying the development of the disease.
Analysis of known amyotrophic lateral sclerosis and frontotemporal dementia genes reveals a substantial genetic burden in patients manifesting both diseases not carrying the C9orf72 expansion mutation
Authors: Dols-Icardo Oriol , García-Redondo Alberto , Rojas-García Ricardo , Borrego-Hernández Daniel , Illán-Gala Ignacio , Muñoz-Blanco José Luís , Rábano Alberto , Cervera-Carles Laura , Juárez-Rufián Alexandra , Spataro Nino , De Luna Noemí , Galán Lucía , Cortes-Vicente Elena , Fortea Juan , Blesa Rafael , Grau-Rivera Oriol , Lleó Alberto , Esteban-Pérez Jesús , Gelpi Ellen , Clarimón Jordi
Published: September 2017

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of a clinical, pathological and genetic continuum.

Objectives

The purpose of the present study was to assess the mutation burden that is present in patients with concurrent ALS and FTD (ALS/FTD) not carrying the chromosome 9 open reading frame 72 (C9orf72) hexanucleotide repeat expansion, the most important genetic cause in both diseases.

Methods

From an initial group of 973 patients with ALS, we retrospectively selected those patients fulfilling diagnostic criteria of concomitant ALS and FTD lacking the repeat expansion mutation in C9orf72. Our final study group consisted of 54 patients clinically diagnosed with ALS/FTD (16 with available postmortem neuropathological diagnosis). Data from whole exome sequencing were used to screen for mutations in known ALS and/or FTD genes.

Results

We identified 11 patients carrying a probable pathogenic mutation, representing an overall mutation frequency of 20.4%. TBK1 was the most important genetic cause of ALS/FTD (n=5; 9.3%). The second most common mutated gene was SQSTM1, with three mutation carriers (one of them also harboured a TBK1 mutation). We also detected probable pathogenic genetic alterations in TAF15, VCP and TARDBP and possible pathogenic mutations in FIG4 and ERBB4.

Conclusion

Our results indicate a high genetic burden underlying the co-occurrence of ALS and FTD and expand the phenotype associated with TAF15, FIG4 and ERBB4 to FTD. A systematic screening of ALS and FTD genes could be indicated in patients manifesting both diseases without the C9orf72 expansion mutation, regardless of family history of disease.
The Abdication of King Edward VIII: a study of estrangement between an adult son and elderly mother
Authors: Abrams Robert C
Published: September 2017

In this article the Abdication of King Edward VIII of Great Britain and his estrangement from the dowager Queen Mary are reconsidered as prototypes of intergenerational conflict arising from a collision of values between an adult child and an elderly mother. Historical materials on the Abdication and other respected secondary sources, including biographies of key individuals, were consulted, and the limited sociological and clinical literature on estrangement between elderly parents and adult children was referenced. Although estrangement was perpetuated by the rigid and incompatible positions taken up by both the former king and his widowed mother, the elderly Queen Mary, it was the latter who suffered the greater emotional consequences of the permanent separation that followed the Abdication. Most accounts of the Abdication have put forward views of the conflict of values at its centre that emphasise the vulnerability of the elderly mother. The clinical narrative supports a characterisation of estrangement as a subtype of bereavement with particular relevance to the geriatric population.
Impact of plain packaging of cigarettes on the risk perception of Uruguayan smokers: an experimental study
Authors: Harris Jeffrey E , Ares Gastón , Gerstenblüth Mariana , Machin Leandro , Triunfo Patricia
Published: September 2017

Background

Uruguay, a South American country of 3.4 million inhabitants that has already banned tobacco advertising, prohibited such terms as light, mild and low-tar and required graphic warnings covering 80% of cigarette packs, is considering the imposition of plain, standardised packaging.

Methods

We conducted an experimental choice-based conjoint analysis of the impact of alternative cigarette package designs on the risk perceptions of 180 adult current Uruguayan smokers. We compared plain packaging, with a standardised brand description and the dark brown background colour required on Australian cigarette packages, to two controls: the current package design with distinctive brand elements and colours; and a modified package design, with distinctive brand elements and the dark brown background colour. Graphic warnings were also varied.

Results

Plain packaging significantly reduced the probability of perceiving the stimulus cigarettes as less harmful in comparison to the current package design (OR 0.398, 95% CI 0.333 to 0.476, p<0.001) and the modified package design (OR 0.729, 95% CI 0.626 to 0.849, p<0.001).

Conclusions

Plain packaging enhanced the perceived risk of cigarette products even in a highly regulated setting such as Uruguay. Both the elimination of distinctive brand elements and the use of Australia’s dark brown background colour contributed to the observed effect.
To what extent and why adolescents do or do not support future tobacco control measures: a multimethod study in the Netherlands
Authors: Schreuders Michael , Lagerweij Naomi A , van den Putte Bas , Kunst Anton E
Published: September 2017

Background

In the Netherlands, the adoption of new tobacco control measures is needed to further reduce rates of adolescent smoking. Adolescents’ support for future measures could increase the likelihood of adoption as this provides political leverage for tobacco control advocates. There is, however, scant evidence about to what extent and why adolescents support future measures. We therefore assessed adolescents’ support for a range of future measures and explored the criteria that adolescents use to underpin their support.

Methods

A mixed-method design involved surveys and group interviews with fourth-year students (predominantly 15–16 years). The survey, completed by 345 adolescents, included statements about future tobacco control measures and a smoke-free future where nobody starts or continues smoking. Thereafter, 15 adolescents participated in five group interviews to discuss their support for future measures.

Results

The survey showed that adolescents generally support a smoke-free future. They expressed most support for product measures, mixed support for smoke-free areas, ambivalent support for price increases and least support for sales restrictions. The group interviews revealed that differences in support were explained by adolescents’ criteria that future measures should: have the potential to be effective, not violate individuals’ right to smoke, protect children from pro-smoking social influences and protect non-smokers from secondhand smoke.

Conclusion

Adolescents’ high support for a smoke-free future does not lead to categorical support for any measure. Addressing the underlying criteria may increase adolescents’ support and therewith provide political leverage for the adoption of future measures.
Mass formula for light nonstrange mesons and Regge trajectories in quark model
Authors: Jia Duojie , Pang Cheng-Qun , Hosaka Atsushi
Published: September 2017

We study the Regge-like spectra of light mesons in a relativized quark model. An analytical mass formula is presented for the light unflavored mesons with the help of auxiliary field method, by which a quasi-linear Regge–Chew–Frautschi plot is predicted for the orbitally excited states. We show that the trajectory slope is proportional to the inverse of the confining parameter [Formula: see text] when the orbital angular momentum [Formula: see text] is large. The result is tested against the experimental data of the spectra of the meson families [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] in the [Formula: see text] planes, with the fitted parameters consistent with that in the literatures.
Bogdanov–Takens and Triple Zero Bifurcations of Coupled van der Pol–Duffing Oscillators with Multiple Delays
Authors: Liu Xia , Zhang Tonghua
Published: September 2017

In this paper, the Bogdanov–Takens (B–T) and triple zero bifurcations are investigated for coupled van der Pol–Duffing oscillators with [Formula: see text] symmetry, in the presence of time delays due to the intrinsic response and coupling. Different from previous works, third order unfolding normal forms associated with B–T and triple zero bifurcations are needed, which are obtained by using the normal form theory of delay differential equations. Numerical simulations are also presented to illustrate the theoretical results.