bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Proliferation of Vibrio parahaemolyticus, Vibrio vulnificus, and Vibrio cholerae during Freshwater Flash Floods in French Mediterranean Coastal Lagoons
Authors: Esteves Kevin , Hervio-Heath Dominique , Mosser Thomas , Rodier Claire , Tournoud Marie-George , Jumas-Bilak Estelle , Colwell Rita R. , Monfort Patrick
Published: August 2015

Vibrio parahaemolyticus
,
Vibrio vulnificus
, and
Vibrio cholerae
of the non-O1/non-O139 serotype are present in coastal lagoons of southern France. In these Mediterranean regions, the rivers have long low-flow periods followed by short-duration or flash floods during and after heavy intense rainstorms, particularly at the end of the summer and in autumn. These floods bring large volumes of freshwater into the lagoons, reducing their salinity. Water temperatures recorded during sampling (15 to 24°C) were favorable for the presence and multiplication of vibrios. In autumn 2011, before heavy rainfalls and flash floods, salinities ranged from 31.4 to 36.1‰ and concentrations of
V. parahaemolyticus
,
V. vulnificus
, and
V. cholerae
varied from 0 to 1.5 × 10
3
most probable number (MPN)/liter, 0.7 to 2.1 × 10
3
MPN/liter, and 0 to 93 MPN/liter, respectively. Following heavy rainstorms that generated severe flash flooding and heavy discharge of freshwater, salinity decreased, reaching 2.2 to 16.4‰ within 15 days, depending on the site, with a concomitant increase in
Vibrio
concentration to ca. 10
4
MPN/liter. The highest concentrations were reached with salinities between 10 and 20‰ for
V. parahaemolyticus
, 10 and 15‰ for
V. vulnificus
, and 5 and 12‰ for
V. cholerae
. Thus, an abrupt decrease in salinity caused by heavy rainfall and major flooding favored growth of human-pathogenic
Vibrio
spp. and their proliferation in the Languedocian lagoons. Based on these results, it is recommended that temperature and salinity monitoring be done to predict the presence of these
Vibrio
spp. in shellfish-harvesting areas of the lagoons.
Comparison of the Seasonal Variations of Synechococcus Assemblage Structures in Estuarine Waters and Coastal Waters of Hong Kong
Authors: Xia Xiaomin , Vidyarathna Nayani K. , Palenik Brian , Lee Puiyin , Liu Hongbin
Published: August 2015

Seasonal variation in the phylogenetic composition ofSynechococcusassemblages in estuarine and coastal waters of Hong Kong was examined through pyrosequencing of therpoC1gene. Sixteen samples were collected in 2009 from two stations representing estuarine and ocean-influenced coastal waters, respectively.Synechococcusabundance in coastal waters gradually increased from 3.6 × 103cells ml−1in March, reaching a peak value of 5.7 × 105cells ml−1in July, and then gradually decreased to 9.3 × 103cells ml−1in December. The changes inSynechococcusabundance in estuarine waters followed a pattern similar to that in coastal waters, whereas its composition shifted from being dominated by phycoerythrin-rich (PE-type) strains in winter to phycocyanin-only (PC-type) strains in summer owing to the increase in freshwater discharge from the Pearl River and higher water temperature. The high abundance of PC-typeSynechococcuswas composed of subcluster 5.2 marineSynechococcus, freshwaterSynechococcus(F-PC), andCyanobium. TheSynechococcusassemblage in the coastal waters, on the other hand, was dominated by marine PE-typeSynechococcus, with subcluster 5.1 clades II and VI as the major lineages from April to September, when the summer monsoon prevailed. Besides these two clades, clade III cooccurred with clade V at relatively high abundance in summer. During winter, theSynechococcusassemblage compositions at the two sites were similar and were dominated by subcluster 5.1 clades II and IX and an undescribed clade (represented bySynechococcussp. strain miyav). Clade IXSynechococcuswas a relatively ubiquitous PE-typeSynechococcusfound at both sites, and our study demonstrates that some strains of the clade have the ability to deal with large variation of salinity in subtropical estuarine environments. Our study suggests that changes in seawater temperature and salinity caused by the seasonal variation of monsoonal forcing are two major determinants of the community composition and abundance ofSynechococcusassemblages in Hong Kong waters.
Mutual Cross-Feeding Interactions between Bifidobacterium longum subsp. longum NCC2705 and Eubacterium rectale ATCC 33656 Explain the Bifidogenic and Butyrogenic Effects of Arabinoxylan Oligosaccharides
Authors: Rivière Audrey , Gagnon Mérilie , Weckx Stefan , Roy Denis , De Vuyst Luc
Published: August 2015

Arabinoxylan oligosaccharides (AXOS) are a promising class of prebiotics that have the potential to stimulate the growth of bifidobacteria and the production of butyrate in the human colon, known as the bifidogenic and butyrogenic effects, respectively. Although these dual effects of AXOS are considered beneficial for human health, their underlying mechanisms are still far from being understood. Therefore, this study investigated the metabolic interactions between
Bifidobacterium longum
subsp.
longum
NCC2705 (
B. longum
NCC2705), an acetate producer and arabinose substituent degrader of AXOS, and
Eubacterium rectale
ATCC 33656, an acetate-converting butyrate producer. Both strains belong to prevalent species of the human colon microbiota. The strains were grown on AXOS during mono- and coculture fermentations, and their growth, AXOS consumption, metabolite production, and expression of key genes were monitored. The results showed that the growth of both strains and gene expression in both strains were affected by cocultivation and that these effects could be linked to changes in carbohydrate consumption and concomitant metabolite production. The consumption of the arabinose substituents of AXOS by
B. longum
NCC2705 with the concomitant production of acetate allowed
E. rectale
ATCC 33656 to produce butyrate (by means of a butyryl coenzyme A [CoA]:acetate CoA-transferase), explaining the butyrogenic effect of AXOS.
Eubacterium rectale
ATCC 33656 released xylose from the AXOS substrate, which favored the
B. longum
NCC2705 production of acetate, explaining the bifidogenic effect of AXOS. Hence, those interactions represent mutual cross-feeding mechanisms that favor the coexistence of bifidobacterial strains and butyrate producers in the same ecological niche. In conclusion, this study provides new insights into the bifidogenic and butyrogenic effects of AXOS.
Rhodococcus erythropolis BG43 Genes Mediating Pseudomonas aeruginosa Quinolone Signal Degradation and Virulence Factor Attenuation
Authors: Müller Christine , Birmes Franziska S. , Rückert Christian , Kalinowski Jörn , Fetzner Susanne
Published: August 2015

Rhodococcus erythropolis
BG43 is able to degrade the
Pseudomonas aeruginosa
quorum sensing signal molecules PQS (
Pseudomonas
quinolone signal) [2-heptyl-3-hydroxy-4(1
H
)-quinolone] and HHQ [2-heptyl-4(1
H
)-quinolone] to anthranilic acid. Based on the hypothesis that degradation of HHQ might involve hydroxylation to PQS followed by dioxygenolytic cleavage of the heterocyclic ring and hydrolysis of the resulting
N
-octanoylanthranilate, the genome was searched for corresponding candidate genes. Two gene clusters,
aqdA1B1C1
and
aqdA2B2C2
, each predicted to code for a hydrolase, a flavin monooxygenase, and a dioxygenase related to 1
H
-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase, were identified on circular plasmid pRLCBG43 of strain BG43. Transcription of all genes was upregulated by PQS, suggesting that both gene clusters code for alkylquinolone-specific catabolic enzymes. An
aqdR
gene encoding a putative transcriptional regulator, which was also inducible by PQS, is located adjacent to the
aqdA2B2C2
cluster. Expression of
aqdA2B2C2
in
Escherichia coli
conferred the ability to degrade HHQ and PQS to anthranilic acid; however, for
E. coli
transformed with
aqdA1B1C1
, only PQS degradation was observed. Purification of the recombinant AqdC1 protein verified that it catalyzes the cleavage of PQS to form
N
-octanoylanthranilic acid and carbon monoxide and revealed apparent

K
m

and
k
cat
values for PQS of ∼27 μM and 21 s
−1
, respectively. Heterologous expression of the PQS dioxygenase gene
aqdC1
or
aqdC2
in
P. aeruginosa
PAO1 quenched the production of the virulence factors pyocyanin and rhamnolipid and reduced the synthesis of the siderophore pyoverdine. Thus, the toolbox of quorum-quenching enzymes is expanded by new PQS dioxygenases.
YjeH Is a Novel Exporter of
l
-Methionine and Branched-Chain Amino Acids in Escherichia coli
Authors: Liu Qian , Liang Yong , Zhang Yun , Shang Xiuling , Liu Shuwen , Wen Jifu , Wen Tingyi
Published: August 2015

Amino acid efflux transport systems have important physiological functions and play vital roles in the fermentative production of amino acids. However, no methionine exporter has yet been identified in
Escherichia coli
. In this study, we identified a novel amino acid exporter, YjeH, in
E. coli
. The
yjeH
overexpression strain exhibited high tolerance to the structural analogues of
l
-methionine and branched-chain amino acids, decreased intracellular amino acid levels, and enhanced export rates in the presence of a Met-Met, Leu-Leu, Ile-Ile, or Val-Val dipeptide, suggesting that YjeH functions as an exporter of
l
-methionine and the three branched-chain amino acids. The export of the four amino acids in the
yjeH
overexpression strain was competitively inhibited in relation to each other. The expression of
yjeH
was strongly induced by increasing cytoplasmic concentrations of substrate amino acids. Green fluorescent protein (GFP)-tagged YjeH was visualized by total internal reflection fluorescence microscopy to confirm the plasma membrane localization of YjeH. Phylogenetic analysis of transporters indicated that YjeH belongs to the amino acid efflux family of the amino acid/polyamine/organocation (APC) superfamily. Structural modeling revealed that YjeH has the typical “5 + 5” transmembrane α-helical segment (TMS) inverted-repeat fold of APC superfamily transporters, and its binding sites are strictly conserved. The enhanced capacity of
l
-methionine export by the overexpression of
yjeH
in an
l
-methionine-producing strain resulted in a 70% improvement in titer. This study supplements the transporter classification and provides a substantial basis for the application of the methionine exporter in metabolic engineering.
Cross-Immunity and Community Structure of a Multiple-Strain Pathogen in the Tick Vector
Authors: Durand Jonas , Jacquet Maxime , Paillard Lye , Rais Olivier , Gern Lise , Voordouw Maarten J.
Published: August 2015

Many vector-borne pathogens consist of multiple strains that circulate in both the vertebrate host and the arthropod vector. Characterization of the community of pathogen strains in the arthropod vector is therefore important for understanding the epidemiology of mixed vector-borne infections.
Borrelia afzelii
and
B. garinii
are two species of tick-borne bacteria that cause Lyme disease in humans. These two sympatric pathogens use the same tick,
Ixodes ricinus
, but are adapted to different classes of vertebrate hosts. Both
Borrelia
species consist of multiple strains that are classified using the highly polymorphic
ospC
gene. Vertebrate cross-immunity against the OspC antigen is predicted to structure the community of multiple-strain
Borrelia
pathogens.
Borrelia
isolates were cultured from field-collected
I. ricinus
ticks over a period spanning 11 years. The
Borrelia
species of each isolate was identified using a reverse line blot (RLB) assay. Deep sequencing was used to characterize the
ospC
communities of 190
B. afzelii
isolates and 193
B. garinii
isolates. Infections with multiple
ospC
strains were common in ticks, but vertebrate cross-immunity did not influence the strain structure in the tick vector. The pattern of genetic variation at the
ospC
locus suggested that vertebrate cross-immunity exerts strong selection against intermediately divergent
ospC
alleles. Deep sequencing found that more than 50% of our isolates contained exotic
ospC
alleles derived from other
Borrelia
species. Two alternative explanations for these exotic
ospC
alleles are cryptic coinfections that were not detected by the RLB assay or horizontal transfer of the
ospC
gene between
Borrelia
species.
Metabolism of Fructooligosaccharides in Lactobacillus plantarum ST-III via Differential Gene Transcription and Alteration of Cell Membrane Fluidity
Authors: Chen Chen , Zhao Guozhong , Chen Wei , Guo Benheng
Published: August 2015

Although fructooligosaccharides (FOS) can selectively stimulate the growth and activity of probiotics and beneficially modulate the balance of intestinal microbiota, knowledge of the molecular mechanism for FOS metabolism by probiotics is still limited. Here a combined transcriptomic and physiological approach was used to survey the global alterations that occurred during the logarithmic growth of
Lactobacillus plantarum
ST-III using FOS or glucose as the sole carbon source. A total of 363 genes were differentially transcribed; in particular, two gene clusters were induced by FOS. Gene inactivation revealed that both of the clusters participated in the metabolism of FOS, which were transported across the membrane by two phosphotransferase systems (PTSs) and were subsequently hydrolyzed by a β-fructofuranosidase (SacA) in the cytoplasm. Combining the measurements of the transcriptome- and membrane-related features, we discovered that the genes involved in the biosynthesis of fatty acids (FAs) were repressed in cells grown on FOS; as a result, the FA profiles were altered by shortening of the carbon chains, after which membrane fluidity increased in response to FOS transport and utilization. Furthermore, incremental production of acetate was observed in both the transcriptomic and the metabolic experiments. Our results provided new insights into gene transcription, the production of metabolites, and membrane alterations that could explain FOS metabolism in
L. plantarum
.
A MORN Repeat Protein Facilitates Protein Entry into the Flagellar Pocket of Trypanosoma brucei
Authors: Morriswood Brooke , Schmidt Katy
Published: August 2015

The parasite
Trypanosoma brucei
lives in the bloodstream of infected mammalian hosts, fully exposed to the adaptive immune system. It relies on a very high rate of endocytosis to clear bound antibodies from its cell surface. All endo- and exocytosis occurs at a single site on its plasma membrane, an intracellular invagination termed the flagellar pocket. Coiled around the neck of the flagellar pocket is a multiprotein complex containing the repeat motif protein
T. brucei
MORN1 (TbMORN1). In this study, the phenotypic effects of TbMORN1 depletion in the mammalian-infective form of
T. brucei
were analyzed. Depletion of TbMORN1 resulted in a rapid enlargement of the flagellar pocket. Dextran, a polysaccharide marker for fluid phase endocytosis, accumulated inside the enlarged flagellar pocket. Unexpectedly, however, the proteins concanavalin A and bovine serum albumin did not do so, and concanavalin A was instead found to concentrate outside it. This suggests that TbMORN1 may have a role in facilitating the entry of proteins into the flagellar pocket.
Unfolded Protein Response Pathways in Bloodstream-Form Trypanosoma brucei?
Authors: Tiengwe Calvin , Brown Abigail E. N. A. , Bangs James D.
Published: August 2015

The unfolded protein response (UPR) is a stress mechanism to cope with misfolded proteins in the early secretory pathway, the hallmark being transcriptional upregulation of endoplasmic reticulum (ER) molecular chaperones such as BiP and protein disulfide isomerase. Despite the lack of transcriptional regulation and the absence of the classical UPR machinery, African trypanosomes apparently respond to persistent ER stress by a UPR-like response, including upregulation of BiP, and a related spliced leader silencing (SLS) response whereby SL RNA transcription is shut down. Initially observed by knockdown of the secretory protein translocation machinery, both responses are also induced by chemical agents known to elicit UPR in mammalian cells (H. Goldshmidt, D. Matas, A. Kabi, A. Carmi, R. Hope, S. Michaeli, PLoS Pathog 6:e1000731, 2010,
http://dx.doi.org/10.1371/journal.ppat.1000731
). As these findings were generated primarily in procyclic-stage trypanosomes, we have investigated both responses in pathogenic bloodstream-stage parasites. RNA interference (RNAi) silencing of the core translocon subunit
Trypanosoma brucei
Sec61α (TbSec61α) failed to induce either response. Interestingly, cell growth halted within 16 h of silencing, but sufficient TbSec61α remained to allow full competence for translocation of nascent secretory proteins for up to 24 h, indicating that replication is finely coupled with the capacity to synthesize and transport secretory cargo. Tunicamycin and thapsigargin at concentrations compatible with short-term (4 h) and long-term (24 h) viability also failed to induce any of the indicators of UPR-like or SLS responses. Dithiothreitol (DTT) was lethal at all concentrations tested. These results indicate that UPR-like and SLS responses to persistent ER stress do not occur in bloodstream-stage trypanosomes.
Clinical profile of diabetes mellitus in tuberculosis
Authors: Ogbera Anthonia Okeoghene , Kapur Anil , Abdur-Razzaq Hussein , Harries Anthony D , Ramaiya Kaushik , Adeleye Olufunmilayo , Kuku Sonny
Published: August 2015

Objective

The objective is to document the clinical profile of diabetes mellitus (DM) in tuberculosis (TB).

Type of study

This was a descriptive observational study.

Methods

A total of 4000 persons aged above 12 years with a confirmed diagnosis of TB and on treatment were recruited. The study subjects were screened for DM and diagnoses were made on the basis of the WHO criteria. Clinical parameters were compared between persons with DM and those without DM.

Results

Mean age was higher in patients with TB and DM than in persons without DM, and this difference was statistically significant (40.9 vs 39.6 years, p=0.0002). DM/TB comorbidity was noted in 480 persons and these made up 12.3% of the study population. Some clinical features of patients with TB who had DM included a positive family history of DM, a history of hypertension, and central obesity.

Conclusions

Given the substantial burden of DM and TB comorbidity, we recommend that patients with TB be screened routinely for DM. However, further research is needed to clarify the risk factors for the occurrence of DM in TB.
Sitagliptin versus mitiglinide switched from mealtime dosing of a rapid-acting insulin analog in patients with type 2 diabetes: a randomized, parallel-group study
Authors: Takeshita Yumie , Takamura Toshinari , Kita Yuki , Takazakura Akiko , Kato Ken-ichiro , Isobe Yuki , Kaneko Shuichi
Published: August 2015

Purpose

We determined the feasibility of substituting sitagliptin or mitiglinide for bolus insulin injection therapy in patients with type 2 diabetes.

Methods

60 patients with type 2 diabetes were enrolled and randomized to switch from mealtime dosing of a rapid-acting insulin analog to either sitagliptin or mitiglinide for 16 weeks.

Results

Body weight, body mass index, and waist circumference decreased significantly in both groups at the end of the study. Mitiglinide significantly increased fasting plasma glucose (FPG) levels at the end of the study from 146.5±36.3 to 168.0±38.8 mg/dL, whereas sitagliptin did not affect FPG. Glycated hemoglobin (HbA1c) and 1,5-anhydroglucitol increased significantly in both groups. The C peptide immunoreactivity (CPR) responses after arginine were diminished in both groups. γ-GTP and triglycerides increased, and high-density lipoprotein cholesterol and adiponectin decreased, in the sitagliptin group, but not in the mitiglinide group. Mean Diabetes Treatment Satisfaction Questionnaire scores improved significantly in both groups. Patients whose mean total daily doses of rapid-acting insulin analog were 16.6 and 17.8 units were switched to sitagliptin and mitiglinide, respectively, without a change in the HbA1c level. Total insulin doses/body weight predicted changes in HbA1c only in the sitagliptin group, but not in the mitiglinide group. Use of >0.27 IU/kg of a rapid-acting insulin analog predicted an increase in HbA1c after switching to sitagliptin. The CPR index (CPI) was also a predictor for a change in HbA1c in the sitagliptin group, but not in the mitiglinide group; patients with a CPI<1.4 developed a worse HbA1c after switching to sitagliptin.

Conclusions

Sitagliptin may predominantly act on FPG, whereas mitiglinide may act on postprandial plasma glucose to achieve glycemic control after switching from a bolus insulin regimen. Additional therapy to sitagliptin or mitiglinide is clearly required to obtain equivalent glycemic control in patients using a higher dose of insulin.

Trial registration number

(UMIN 000007051)
Cohort profile: LifeLines DEEP, a prospective, general population cohort study in the northern Netherlands: study design and baseline characteristics
Authors: Tigchelaar Ettje F , Zhernakova Alexandra , Dekens Jackie A M , Hermes Gerben , Baranska Agnieszka , Mujagic Zlatan , Swertz Morris A , Muñoz Angélica M , Deelen Patrick , Cénit Maria C , Franke Lude , Scholtens Salome , Stolk Ronald P , Wijmenga Cisca , Feskens Edith J M
Published: August 2015

Purpose

There is a critical need for population-based prospective cohort studies because they follow individuals before the onset of disease, allowing for studies that can identify biomarkers and disease-modifying effects, and thereby contributing to systems epidemiology.

Participants

This paper describes the design and baseline characteristics of an intensively examined subpopulation of the LifeLines cohort in the Netherlands. In this unique subcohort, LifeLines DEEP, we included 1539 participants aged 18 years and older.

Findings to date

We collected additional blood (n=1387), exhaled air (n=1425) and faecal samples (n=1248), and elicited responses to gastrointestinal health questionnaires (n=1176) for analysis of the genome, epigenome, transcriptome, microbiome, metabolome and other biological levels. Here, we provide an overview of the different data layers in LifeLines DEEP and present baseline characteristics of the study population including food intake and quality of life. We also describe how the LifeLines DEEP cohort allows for the detailed investigation of genetic, genomic and metabolic variation for a wide range of phenotypic outcomes. Finally, we examine the determinants of gastrointestinal health, an area of particular interest to us that can be addressed by LifeLines DEEP.

Future plans

We have established a cohort of which multiple data levels allow for the integrative analysis of populations for translation of this information into biomarkers for disease, and which will offer new insights into disease mechanisms and prevention.
The effects of pleural fluid drainage on respiratory function in mechanically ventilated patients after cardiac surgery
Authors: Brims Fraser J H , Davies Michael G , Elia Andy , Griffiths Mark J D
Published: August 2015

Background

Pleural effusions occur commonly after cardiac surgery and the effects of drainage on gas exchange in this population are not well established. We examined pulmonary function indices following drainage of pleural effusions in cardiac surgery patients.

Methods

We performed a retrospective study examining the effects of pleural fluid drainage on the lung function indices of patients recovering from cardiac surgery requiring mechanical ventilation for more than 7 days. We specifically analysed patients who had pleural fluid removed via an intercostal tube (ICT: drain group) compared with those of a control group (no effusion, no ICT).

Results

In the drain group, 52 ICTs were sited in 45 patients. The mean (SD) volume of fluid drained was 1180 (634) mL. Indices of oxygenation were significantly worse in the drain group compared with controls prior to drainage. The arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) (P/F) ratio improved on day 1 after ICT placement (mean (SD), day 0: 31.01 (8.92) vs 37.18 (10.7); p<0.05) and both the P/F ratio and oxygenation index (OI: kPa/cm H2O=PaO2/mean airway pressure×FiO2) demonstrated sustained improvement to day 5 (P/F day 5: 39.85 (12.8); OI day 0: 2.88 (1.10) vs day 5: 4.06 (1.73); both p<0.01). The drain group patients were more likely to have an improved mode of ventilation on day 1 compared with controls (p=0.028).

Conclusions

Pleural effusion after cardiac surgery may impair oxygenation. Drainage of pleural fluid is associated with a rapid and sustained improvement in oxygenation.
Factors associated with protective eyewear use among cocoa farmers in Ghana
Authors: Boadi-Kusi Samuel B , Hansraj Rekha , Mashige Khathutshelo P , Ilechie Alex Azuka
Published: August 2015

To determine the factors that are associated with the use of protective eyewear (PEW) among cocoa farmers in Ghana, a multistage random sample of 556 cocoa farmers were recruited from four districts in the country. A questionnaire was used to elicit information on the use of PEW and barriers to its use among these farmers. Only 34 (6.1%) participants reported using PEW. Being female, old age and perception of good distance vision was associated with lower odds of PEW use. However, higher educational attainment, application of fertiliser and pesticides were associated with higher odds of PEW use. Participants cited non-availability, unaffordability and ignorance/lack of training as the main barriers to the use of PEW. The low use of PEW could be addressed through ocular health education and occupational health and safety policy initiatives.
Subtle increases in heart size persist into adulthood in growth restricted babies: the Cardiovascular Risk in Young Finns Study
Authors: Arnott Clare , Skilton Michael R , Ruohonen Saku , Juonala Markus , Viikari Jorma S A , Kähönen Mika , Lehtimäki Terho , Laitinen Tomi , Celermajer David S , Raitakari Olli T
Published: August 2015

Background and objectives

Impaired fetal growth is associated with increased cardiovascular morbidity and mortality in adulthood. We sought to determine whether adults born with intrauterine growth restriction have primary maladaptive changes in cardiac structure.

Methods

Study participants were adults (34–49 years) who attended the 31-year follow-up of theCardiovascular Risk in Young Finns Study(longitudinal cohort). Transthoracic echocardiograms and demographic and cardiovascular risk surveys were completed for 157 adults born small for gestational age (SGA, birth weight <10th population centile) and 627 born average for gestational age (average for gestational age (AGA), birth weight 50th–90th population centile).

Results

Those born growth restricted had subtly enlarged hearts with indexed left ventricular (LV) end-systolic and end-diastolic diameters slightly greater in the SGA individuals than the AGA group (LVESD 18.7 mm/m2SGA vs 18.1 mm/m2AGA, p<0.01; LVEDD 27.5 mm/m2SGA vs 26.6 mm/m2AGA, p<0.01); LV base-to-apex length (47.4 mm/m2SGA vs 46.0 mm/m2AGA, p<0.01); LV basal diameter (26.4 mm/m2SGA vs 25.7 mm/m2AGA, p<0.01); and right ventricular base-to-apex length (40.1 mm/m2SGA vs 39.2 mm/m2AGA, p=0.02). LV stroke volume was greater in those born AGA (74.5 mL SGA vs 78.8 mL AGA, p<0.01), with no significant difference in cardiac output (5 L/min SGA vs 5.2 L/min AGA, p=0.06), heart rate, diastolic indices or sphericity index.

Conclusions

Adults born SGA have some statistically significant but subtle changes in cardiac structure and function, which are less marked than have been described in childhood, and are unlikely to play a pathogenic role in their elevated cardiovascular risk.
A serosurvey for selected pathogens in Greek European wild boar
Authors: Touloudi A. , Valiakos G. , Athanasiou L. V. , Birtsas P. , Giannakopoulos A. , Papaspyropoulos K. , Kalaitzis C. , Sokos C. , Tsokana C. N. , Spyrou V. , Petrovska L. , Billinis C.
Published: August 2015

Objectives

Serum samples, collected from 94 European wild boar (Sus scrofa) during the hunting seasons 2006 ‐2010 from different regions of Greece, were examined in order to estimate the role of these wildlife species as reservoir of pathogens important for livestock and/or public health.

Materials and Methods

The assays used for this purpose were commercial indirect ELISA for the detection of antibodies against porcine circovirus type 2 (PCV‐2), porcine reproductive and respiratory syndrome (virus) (PRRSV), Aujeszky's disease virus (ADV), influenza A (IA) virus,Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Salmonella species, Trichinellaspecies and indirect immunofluorescence antibody test for the detection of antibodies againstToxoplasma gondiiandNeospora caninum.

Results

Antibodies against PCV‐2, PRRSV, ADV, IA virus,A. pleuropneumoniae, M. hyopneumoniae,Salmonellaspecies,Trichinellaspecies,T. gondiiandN. caninumwere detected in 19.1 per cent, 12.8 per cent, 35.1 per cent, 1.1 per cent, 57.4 per cent, 0 per cent, 4.3 per cent, 6.4 per cent, 5.2 per cent and 1.1 per cent of the samples, respectively. Cluster analysis revealed a hot spot of seropositivity near Bulgarian border; seropositivity to ADV was more common among female animals.

Conclusions

These results indicate exposure of wild boar to most of the above‐mentioned pathogens, raising concern about the possibility that these species may pose a significant health risk for livestock and/or humans.
Till geochemical signatures of volcanogenic massive sulphide deposits: an overview of Canadian examples
Authors: McClenaghan M. B. , Peter J. M.
Published: August 2015

Volcanogenic massive sulphide (VMS) deposits are an important source of Cu, Pb, Zn and Ag in Canada. These deposits formed on the paleo-seafloor in volcanic or volcano-sedimentary rocks. On the glaciated landscape of Canada, the bulk composition of till (so-called ‘till geochemistry’) is an important exploration method for VMS deposits. Herein we provide an overview of the 50-plus year history of the application of till geochemical methods to VMS exploration in Canada, and summarize best practices, including appropriate size fractions of till to analyse, analytical techniques and indicator and pathfinder elements. Till geochemical methods are now well-developed and used widely, most commonly employing the <0.063 mm till fraction and an extensive suite of VMS indicator elements Cu, Pb, Zn, Au, and Ag, as well as pathfinder elements Ag, Au As, Bi, Cd, Ga, Ge, Hg, In, Sb, Se, Sn, Tl. In order to detect the clastic glacial dispersal signal down-ice of a VMS deposit, unoxidized to weakly oxidized till should be collected and analysed, and not B-horizon soil. Case studies and examples of glacial dispersal patterns associated with known VMS mineralization in major mining camps and deposits across Canada are highlighted.
Geochemical assessment of mine waste cover performance post reclamation at Parc mine, North Wales
Authors: Davies Alice A. , Perkins William F. , Bowell Rob J.
Published: August 2015

Parc mine in north Wales was abandoned after closure in 1963 and spoil heaps were left to erode into the Nant Gwydyr and Conwy River. A storm event in 1964 caused the west slope of the tailings dam to collapse into the river, polluting 11 ha of farmland with lead and zinc. Reclamation work commenced in 1978 and involved reshaping the tailings pile and capping the north and central sections of the site with limestone quarry waste. The north section was also sown with metal-tolerant vegetation (
Festuca rubra, Argostis tenuis
and
Trifolium repens
). The aim of the study was to understand how different reclamation surfaces affected soil chemistry using GIS.

The uncapped south section, whilst having the most heavily polluted soil (74 mg/kg As, 24,000 mg/kg Pb, and 19,000 mg/kg Zn), supported the establishment of patchy but diverse metal-tolerant vegetation (
Alnus incana, Fagus sylvatica, Ulex, Sorbus aucuparia)
. The capped north section had the least polluted soil (19 mg/kg As, 478 mg/kg Pb, and 1400 mg/kg Zn), densely vegetated with a nitrogen-fixing legume (
Trifolium repens
), and was able to support grazing animals, but remained visually incongruous and failed to support the re-establishment of native vegetation. The central section, which combined capping with native vegetation (
Betula pubescens
and
Quercus petraea
), was considered moderately polluted (26 mg/kg As, 3908 mg/kg Pb, and 9000 mg/kg Zn). Zinc was found to be the limiting contaminant for vegetation growth with soil concentrations exceeding 12 000 mg/kg corresponding to areas of bare ground in the south and central sections. Barium was the only element to increase in the capped sections, indicating the limestone quarry waste used to cap the tailings was most likely barium-rich.
Theropod dinosaurs from the Middle Jurassic (Bajocian–Bathonian) of Skye, Scotland
Authors: Brusatte Stephen L. , Clark Neil D. L.
Published: August 2015

The Isle of Skye, Scotland, has yielded a diverse Middle Jurassic terrestrial vertebrate fauna, but little is known about the predatory dinosaurs (theropods) occupying the top and secondary carnivore roles in these ecosystems, as their fossils have been limited to rare footprints of small- to mid-sized taxa. We describe two isolated theropod body fossils, a tooth and a middle-posterior caudal vertebra, from the late Bajocian–Bathonian Valtos Sandstone Formation of northeastern Skye, and use a variety of quantitative techniques to determine their taxonomic affinities. We conservatively refer both specimens to Theropoda indet., but suggest that the tooth most likely belonged to a megalosaurid, basal tyrannosauroid, or dromaeosaurid, and that the vertebra belonged to a small-bodied basal coelurosaur of approximately the same size as
Coelurus
(
c
. 2 m long,
c
. 30 kg mass). Although fragmentary, these fossils and the footprints demonstrate that both small and mid to large theropods were present in the Middle Jurassic of Scotland, and that these may have included some of the oldest coelurosaurs, and potentially some of the earliest-diverging tyrannosauroids and dromaeosaurids.

Supplementary material

Skye Theropod Tooth: Data and Analyses are available at
www.geolsoc.org.uk/SUP18866
How hot are the Cairngorms?
Authors: Busby Jon , Gillespie Martin , Kender Sev
Published: August 2015

Heat flow measured over the East Grampians batholith in the 1980s was found to be unexpectedly low and at odds with high radiogenic heat production within the outcropping granites and a very large volume of granite predicted from an interpretation of gravity data. Past climate variations perturb temperature gradients in the shallow subsurface leading to erroneous estimates of heat flow. A reconstruction of the surface temperature history during the last glacial cycle has enabled a rigorous palaeoclimate correction to be applied to the heat flow that shows an increase of 25% over previously reported values; revised to 86 ± 7 mW m
−2
. An interpretation of recent mapping reveals that the surface exposures of the East Grampians granites are the roof zones of a highly evolved magma system. Rock composition, therefore, is likely to become more mafic with depth and the heat production will decrease with depth. This petrological model can be reconciled with the gravity data if the shape of the batholith is tabular with deep-seated feeder conduits. The increased heat flow value leads to revised predictions of subsurface temperatures of 129°C at 5 km depth and 176°C at 7 km depth, increases of 40% and 49%, respectively, compared to previous estimates. These temperatures are at the lower end of those currently required for power generation with Engineered Geothermal Systems, but could potentially be exploited as a direct heat use resource in the Cairngorm region by targeting permeable fractures with deep boreholes.
A collection of pelmatozoans (Echinodermata) from the Lady Burn Starfish Beds (Upper Ordovician, Katian), SW Scotland
Authors: Donovan Stephen K. , Clark Neil D. L.
Published: August 2015

A new collection of crinoids and rhombiferans from the Upper Ordovician (Katian) Lady Burn Starfish Beds of SW Scotland is small, yet contains several significant specimens. Two species hitherto known only from single specimens, the dendrocrinid cladid
Cupulocrinus drummuckensis
Kolata and the pisocrinid disparid
Eocicerocrinus sevastopuloi
Donovan, are represented by crowns retaining the proximal column. The latter species is the earliest member of an order that is otherwise known only from the Silurian and Devonian. Unusual preservation of the monobathrid camerate
Macrostylocrinus cirrifer
Ramsbottom, in which the radices (roots) of the proximal column are lost, but the delicate pinnules of the arms are preserved, is problematic. A long, contorted and gracile pluricolumnal is probably derived from a disparid, possibly
E. sevastopuloi
.
Exercise training in chronic heart failure: improving skeletal muscle O2transport and utilization
Authors: Hirai Daniel M. , Musch Timothy I. , Poole David C.
Published: August 2015

Chronic heart failure (CHF) impairs critical structural and functional components of the O2transport pathway resulting in exercise intolerance and, consequently, reduced quality of life. In contrast, exercise training is capable of combating many of the CHF-induced impairments and enhancing the matching between skeletal muscle O2delivery and utilization ( Q̇mO2and V̇mO2, respectively). The Q̇mO2/ V̇mO2ratio determines the microvascular O2partial pressure (PmvO2), which represents the ultimate force driving blood-myocyte O2flux (see Fig. 1). Improvements in perfusive and diffusive O2conductances are essential to support faster rates of oxidative phosphorylation (reflected as faster V̇mO2kinetics during transitions in metabolic demand) and reduce the reliance on anaerobic glycolysis and utilization of finite energy sources (thus lowering the magnitude of the O2deficit) in trained CHF muscle. These adaptations contribute to attenuated muscle metabolic perturbations (e.g., changes in [PCr], [Cr], [ADP], and pH) and improved physical capacity (i.e., elevated critical power and maximal V̇mO2). Preservation of such plasticity in response to exercise training is crucial considering the dominant role of skeletal muscle dysfunction in the pathophysiology and increased morbidity/mortality of the CHF patient. This brief review focuses on the mechanistic bases for improved Q̇mO2/ V̇mO2matching (and enhanced PmvO2) with exercise training in CHF with both preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Specifically, O2convection within the skeletal muscle microcirculation, O2diffusion from the red blood cell to the mitochondria, and muscle metabolic control are particularly susceptive to exercise training adaptations in CHF. Alternatives to traditional whole body endurance exercise training programs such as small muscle mass and inspiratory muscle training, pharmacological treatment (e.g., sildenafil and pentoxifylline), and dietary nitrate supplementation are also presented in light of their therapeutic potential. Adaptations within the skeletal muscle O2transport and utilization system underlie improvements in physical capacity and quality of life in CHF and thus take center stage in the therapeutic management of these patients.
Effect of the oral thrombin inhibitor dabigatran on allergic lung inflammation induced by repeated house dust mite administration in mice
Authors: de Boer Johannes D. , Berkhout Lea C. , de Stoppelaar Sacha F. , Yang Jack , Ottenhoff Roelof , Meijers Joost C. M. , Roelofs Joris J. T. H. , van't Veer Cornelis , van der Poll Tom
Published: August 2015

Asthma is a chronic disease of the airways; asthma patients are hampered by recurrent symptoms of dyspnoea and wheezing caused by bronchial obstruction. Most asthma patients suffer from chronic allergic lung inflammation triggered by allergens such as house dust mite (HDM). Coagulation activation in the pulmonary compartment is currently recognized as a feature of allergic lung inflammation, and data suggest that coagulation proteases further drive inflammatory mechanisms. Here, we tested whether treatment with the oral thrombin inhibitor dabigatran attenuates allergic lung inflammation in a recently developed HDM-based murine asthma model. Mice were fed dabigatran (10 mg/g) or placebo chow during a 3-wk HDM airway exposure model. Dabigatran treatment caused systemic thrombin inhibitory activity corresponding with dabigatran levels reported in human trials. Surprisingly, dabigatran did not lead to inhibition of HDM-evoked coagulation activation in the lung as measured by levels of thrombin-antithrombin complexes and D-dimer. Repeated HDM administration caused an influx of eosinophils and neutrophils into the lungs, mucus production in the airways, and a T helper 2 response, as reflected by a rise in bronchoalveolar IL-4 and IL-5 levels and a systemic rise in IgE and HDM-IgG1. Dabigatran modestly improved HDM-induced lung pathology ( P < 0.05) and decreased IL-4 levels ( P < 0.01), without influencing other HDM-induced responses. Considering the limited effects of dabigatran in spite of adequate plasma levels, these results argue against clinical evaluation of dabigatran in patients with asthma.
Resolvin E1 normalizes contractility, Ca2+ sensitivity and smooth muscle cell migration rate in TNF-α- and IL-6-pretreated human pulmonary arteries
Authors: Hiram Roddy , Rizcallah Edmond , Marouan Sofia , Sirois Chantal , Sirois Marco , Morin Caroline , Fortin Samuel , Rousseau Eric
Published: August 2015

Pulmonary hypertension (PH) is a rare disease in which pathophysiology is characterized by an increase in proinflammatory mediators, chronic endothelial dysfunctions, and a high migration rate of smooth muscle cells (SMC). Over the course of the last decade, various treatments have been proposed to relax the pulmonary arteries, none of which have been effective in resolving PH. Our hypothesis is that artery-relaxing drugs are not the long-term solution, but rather the inhibition of tissue inflammation, which underlies human pulmonary artery (HPA) dysfunctions that lead to abnormal vasoconstriction. The goal of the present study was to assess the anti-inflammatory effects of resolvin E1 (RvE1) with concomitant effects on SMC migration and on HPA reactivity. The role and mode of action of RvE1 and its precursor, monoacylglyceride eicosapentaenoic acid were assessed on HPA under proinflammatory conditions, involving a combined pretreatment with 10 ng/ml TNF-α and 10 ng/ml IL-6. Our results show that TNF-α and IL-6 treatment induced hyperreactivity and Ca2+ hypersensitivity in response to pharmaco-mechanical stimuli, including 80 mM KCl, 1 μM phorbol 12–13-dibutyrate, and 30 nM U-46619. Furthermore, the proinflammatory treatment increased the migration rate of SMC isolated from HPA. The phosphorylation level of regulatory contractile proteins (CPI-17, MYPT-1), and proinflammatory signaling pathways (c-Fos, c-Jun, NF-κB) were also significantly increased compared with control conditions. Conversely, 300 nM RvE1 was able to normalize all of the above abnormal events triggered by proinflammation. In conclusion, RvE1 can resolve human arterial hyperreactivity via the resolution of inflammatory markers.
Hippo and TGF-β interplay in the lung field
Authors: Saito Akira , Nagase Takahide
Published: August 2015

The Hippo pathway is comprised of a kinase cascade that involves mammalian Ste20-like serine/threonine kinases (MST1/2) and large tumor suppressor kinases (LATS1/2) and leads to inactivation of transcriptional coactivator with PDZ-binding motif (TAZ) and yes-associated protein (YAP). Protein stability and subcellular localization of TAZ/YAP determine its ability to regulate a diverse array of biological processes, including proliferation, apoptosis, differentiation, stem/progenitor cell properties, organ size control, and tumorigenesis. These actions are enabled by interactions with various transcription factors or through cross talk with other signaling pathways. Interestingly, mechanical stress has been shown to be an upstream regulator of TAZ/YAP activity, and this finding provides a novel clue for understanding how mechanical forces influence a broad spectrum of biological processes, which involve cytoskeletal structure, cell adhesion, and extracellular matrix (ECM) organization. Transforming growth factor-β (TGF-β) pathway is a critical component of lung development and the progression of lung diseases including emphysema, fibrosis, and cancer. In addition, TGF-β is a key regulator of ECM remodeling and cell differentiation processes such as epithelial-mesenchymal transition. In this review, we summarize the current knowledge of the Hippo pathway regarding lung development and diseases, with an emphasis on its interplay with TGF-β signaling.
Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia
Authors: Fredenburgh Laura E. , Kraft Bryan D. , Hess Dean R. , Harris R. Scott , Wolf Monroe A. , Suliman Hagir B. , Roggli Victor L. , Davies John D. , Winkler Tilo , Stenzler Alex , Baron Rebecca M. , Thompson B. Taylor , Choi Augustine M. , Welty-Wolf Karen E. , Piantadosi Claude A.
Published: August 2015

Inhaled carbon monoxide (CO) gas has therapeutic potential for patients with acute respiratory distress syndrome if a safe, evidence-based dosing strategy and a ventilator-compatible CO delivery system can be developed. In this study, we used a clinically relevant baboon model of Streptococcus pneumoniae pneumonia to 1) test a novel, ventilator-compatible CO delivery system; 2) establish a safe and effective CO dosing regimen; and 3) investigate the local and systemic effects of CO therapy on inflammation and acute lung injury (ALI). Animals were inoculated with S. pneumoniae (108-109CFU) ( n = 14) or saline vehicle ( n = 5); in a subset with pneumonia ( n = 5), we administered low-dose, inhaled CO gas (100–300 ppm × 60–90 min) at 0, 6, 24, and/or 48 h postinoculation and serially measured blood carboxyhemoglobin (COHb) levels. We found that CO inhalation at 200 ppm for 60 min is well tolerated and achieves a COHb of 6–8% with ambient CO levels ≤ 1 ppm. The COHb level measured at 20 min predicted the 60-min COHb level by the Coburn-Forster-Kane equation with high accuracy. Animals given inhaled CO + antibiotics displayed significantly less ALI at 8 days postinoculation compared with antibiotics alone. Inhaled CO was associated with activation of mitochondrial biogenesis in the lung and with augmentation of renal antioxidative programs. These data support the feasibility of safely delivering inhaled CO gas during mechanical ventilation and provide preliminary evidence that CO may accelerate the resolution of ALI in a clinically relevant nonhuman primate pneumonia model.
Platelets in the pathogenesis of acute respiratory distress syndrome
Authors: Yadav Hemang , Kor Daryl J.
Published: August 2015

Platelets have an emerging and incompletely understood role in a myriad of host immune responses, extending their role well beyond regulating thrombosis. Acute respiratory distress syndrome is a complex disease process characterized by a range of pathophysiologic processes including oxidative stress, lung deformation, inflammation, and intravascular coagulation. The objective of this review is to summarize existing knowledge on platelets and their putative role in the development and resolution of lung injury.