bluuebunny/crossref_metadata_2025 huggingface dataset:
Nearly 50 years in the making: defining the catalytic mechanism of the multifunctional enzyme, pyruvate carboxylase
Authors: Menefee Ann L. , Zeczycki Tonya N.
Published: January 2014

Numerous steady‐state kinetic studies have examined the complex catalytic reaction mechanism of the multifunctional enzyme, pyruvate carboxylase (PC). Through initial velocity, product inhibition, isotopic exchange and alternate substrate experiments, early investigators established that PC catalyzes the MgATP‐dependent carboxylation of pyruvate by HCO3– through a nonclassical sequential Bi Bi Uni Uni reaction mechanism. This review surveys previous steady‐state kinetic investigations of PC and evaluates the proposed hypotheses concerning the overall catalytic mechanism, nonlinear kinetics and active site coupling in the context of recent structural and mutagenic analyses of this multifunctional enzyme. The determination several PC holoenzyme structures have aided in corroborating the proposed molecular mechanisms by which catalysis occurs and established the inextricable link between the dynamic protein motions and complex kinetic mechanisms associated with PC activity. Unexpectedly, the conclusions drawn from these early steady‐state kinetic investigations have consistently proven to be in fundamental agreement with our current understanding of PC catalysis, which is a testament to the overarching sophistication of the methods pioneered by Michaelis and Menten and further developed by Northrop, Cleland and others.
Monitoring DNA triplex formation using multicolor fluorescence and application to insulin‐like growth factor I promoter downregulation
Authors: Hégarat Nadia , Novopashina Darya , Fokina Alesya A. , Boutorine Alexandre S. , Venyaminova Alya G. , Praseuth Danièle , François Jean‐Christophe
Published: January 2014

Inhibition of insulin‐like growth factor I (IGF–I) signaling is a promising antitumor strategy and nucleic acid‐based approaches have been investigated to target genes in the pathway. Here, we sought to modulate IGF‐I transcriptional activity using triple helix formation. The IGF‐I P1 promoter contains a purine/pyrimidine (R/Y) sequence that is pivotal for transcription as determined by deletion analysis and can be targeted with a triplex‐forming oligonucleotide (TFO). We designed modified purine‐ and pyrimidine‐rich TFOs to bind to the R/Y sequence. To monitor TFO binding, we developed a fluorescence‐based gel‐retardation assay that allowed independent detection of each strand in three‐stranded complexes using end‐labeling with Alexa 488, cyanine (Cy)3 and Cy5 fluorochromes. We characterized TFOs for their ability to inhibit restriction enzyme activity, compete with DNA‐binding proteins and inhibit IGF‐I transcription in reporter assays. TFOs containing modified nucleobases, 5‐methyl‐2′‐deoxycytidine and 5‐propynyl‐2′‐deoxyuridine, specifically inhibited restriction enzyme cleavage and formed triplexes on the P1 promoter fragment. In cells, deletion of the R/Y‐rich sequence led to 48% transcriptional inhibition of a reporter gene. Transfection with TFOs inhibited reporter gene activity to a similar extent, whereas transcription from a mutant construct with an interrupted R/Y region was unaffected, strongly suggesting the involvement of triplex formation in the inhibitory mechanisms. Our results indicate that nuclease‐resistant TFOs will likely inhibit endogenous IGF‐I gene function in cells.
Climate change effects on animal and plant phylogenetic diversity in southern Africa
Authors: Pio Dorothea V. , Engler Robin , Linder H. Peter , Monadjem Ara , Cotterill Fenton P.D. , Taylor Peter J. , Schoeman M. Corrie , Price Benjamin W. , Villet Martin H. , Eick Geeta , Salamin Nicolas , Guisan Antoine
Published: January 2014

Much attention has been paid to the effects of climate change on species' range reductions and extinctions. There is however surprisingly little information on how climate change driven threat may impact the tree of life and result in loss of phylogenetic diversity (PD). Some plant families and mammalian orders reveal nonrandom extinction patterns, but many other plant families do not. Do these discrepancies reflect different speciation histories and does climate induced extinction result in the same discrepancies among different groups? Answers to these questions require representative taxon sampling. Here, we combine phylogenetic analyses, species distribution modeling, and climate change projections on two of the largest plant families in the Cape Floristic Region (Proteaceae and Restionaceae), as well as the second most diverse mammalian order in Southern Africa (Chiroptera), and an herbivorous insect genus (Platypleura) in the family Cicadidae to answer this question. We model current and future species distributions to assess species threat levels over the next 70 years, and then compare projected with random PD survival. Results for these animal and plant clades reveal congruence. PD losses are not significantly higher under predicted extinction than under random extinction simulations. So far the evidence suggests that focusing resources on climate threatened species alone may not result in disproportionate benefits for the preservation of evolutionary history.
The subtle role of climate change on population genetic structure in Canada lynx
Authors: Row Jeffrey R. , Wilson Paul J. , Gomez Celine , Koen Erin L. , Bowman Jeff , Thornton Daniel , Murray Dennis L.
Published: January 2014

Anthropogenically driven climatic change is expected to reshape global patterns of species distribution and abundance. Given recent links between genetic variation and environmental patterns, climate change may similarly impact genetic population structure, but we lack information on the spatial and mechanistic underpinnings of genetic–climate associations. Here, we show that current genetic variability of Canada lynx (Lynx canadensis) is strongly correlated with a winter climate gradient (i.e. increasing snow depth and winter precipitation from west‐to‐east) across the Pacific‐North American (PNO) to North Atlantic Oscillation (NAO) climatic systems. This relationship was stronger than isolation by distance and not explained by landscape variables or changes in abundance. Thus, these patterns suggest that individuals restricted dispersal across the climate boundary, likely in the absence of changes in habitat quality. We propose habitat imprinting on snow conditions as one possible explanation for this unusual phenomenon. Coupling historical climate data with future projections, we also found increasingly diverging snow conditions between the two climate systems. Based on genetic simulations using projected climate data (2041–2070), we predicted that this divergence could lead to a threefold increase in genetic differentiation, potentially leading to isolated east–west populations of lynx in North America. Our results imply that subtle genetic structure can be governed by current climate and that substantive genetic differentiation and related ecological divergence may arise from changing climate patterns.
Characterisation of spray‐dried microparticles containing iron coated by pectin/resistant starch
Authors: Moslemi Masoumeh , Hosseini Hedayat , Erfan Mohammad , Mortazavian Amir Mohammad , Fard Ramin Mazaheri Nezhad , Neyestani Tirang Reza , Komeyli Rozita
Published: January 2014

Iron is one of three major minerals in human body. However, the iron deficiency is a medical problem in developed and underdeveloped countries due to its poor oral absorption or insufficient iron intake. Encapsulation could solve problems associated with oral iron consumption. Various advantages including low cost, biodegradability, biocompatibility and large‐scale production have been included in the current study. In a modified encapsulation method, iron microparticles were prepared using low methoxy pectin and resistant starch during spray drying. Covalent and hydrogen bonds were formed between iron and pectin and between polymers, respectively. Particles sized 3.5 ± 1.14 μm and showed spherical shapes. The yield of particles was 72.07%, and solubility and loading efficiency were 33.64% ± 0.88 and 34.79%, respectively. In conclusion, using iron as a cross‐linker of pectin molecules resulted in microparticles with appropriate properties of lowering organoleptic changes and a better bioavailability especially in dairy‐based products for food fortification.
Raman Responses in Mechanically Activated BaTiO3
Authors: Pavlovic Vera P. , Nikolic Maria V. , Pavlovic Vladimir B. , Blanusa Jovan , Stevanovic Suzana , Mitic Vojislav V. , Scepanovic Maja , Vlahovic Branislav
Published: January 2014

The structure and lattice dynamics of mechanically activated BaTiO3 was investigated in this study. Phonon behavior and crystal structure stability of the obtained nanocrystalline BaTiO3 were discussed from the view point of crystallite size effects and microstrains induced by mechanical activation. A systematic study of Raman responses indicates that mechanical activation has a distinct influence on BaTiO3 lattice spectra affecting the intensity, width, and position of Raman modes. The measured Raman spectra were deconvoluted and phonon parameters were estimated. It has been established that applied mechanical activation leads to a significant decrease in the mean crystallites size, but nevertheless enables formation of tetragonal nanocrystalline BaTiO3.
Role of Interface(s) for the Growth of Ultra‐Thin Amorphous Oxides on Al–Si Alloys: A Thermodynamic Analysis
Authors: Panda Emila , Manwani Krishna
Published: January 2014

This study presents a thermodynamic analysis to predict the type of initial, amorphous oxide overgrowth (i.e., am‐Al2O3 or am‐SiO2) on bare Al–Si alloy substrates. This analysis have taken into account the energies associated with both its interfaces (interface between the Al–Si alloy substrate and the thin oxide film and interface between the thin oxide film and vacuum) along with the bulk Gibbs free energy of oxide formation. This developed analysis is then applied for various parameters, such as, Si alloying element content at the substrate/oxide interface, the growth temperature, the oxide film thickness (up to 1 nm), and various low‐index crystallographic surfaces of the substrate. It is found that am‐SiO2 overgrowth is thermodynamically preferred for a combination of lower oxide film thickness, lower growth temperature, and lower Si alloying content at the alloy/oxide interface. This is because of the overcompensation of the lower energies of both the interfaces over the bulk Gibbs free energy. Furthermore, it is found that for all cases, am‐Al2O3 forms a more stable interface with Al–Si alloy than am‐SiO2.
Longitudinal trajectories of peer relations in children with specific language impairment
Authors: Mok Pearl L. H. , Pickles Andrew , Durkin Kevin , Conti‐Ramsden Gina
Published: January 2014

Background

Peer relations is a vulnerable area of functioning in children with specific language impairment (SLI), but little is known about the developmental trajectories of individuals.

Methods

Peer problems were investigated over a 9‐year period (from 7 to 16 years of age) in 171 children with a history of SLI. Discrete factor growth modelling was used to chart developmental trajectories. Multinomial logistic regression analysis was conducted to investigate factors associated with group membership.

Results

Four distinct developmental trajectories were identified: low‐level/no problems in peer relations (22.2% of participants), childhood‐limited problems (12.3%), childhood‐onset persistent problems (39.2%) and adolescent‐onset problems (26.3%). Risk of poor trajectories of peer relations was greater for those children with pragmatic language difficulties. Prosocial behaviour was the factor most strongly associated with trajectory group membership. Overall, the more prosocial children with better pragmatic language skills and lower levels of emotional problems had less difficulty in developing peer relations.

Conclusions

Analysis of developmental trajectories enriches our understanding of social development. A sizeable minority in the present sample sustained positive relations through childhood and adolescence, and others overcame early difficulties to achieve low levels of problems by their early teens; the majority, however, showed childhood‐onset persistent or adolescent‐onset problems.
Early Development and Tissue Distribution of Pseudoloma neurophilia in the Zebrafish, Danio rerio
Authors: Sanders Justin L. , Peterson Tracy S. , Kent Michael L.
Published: January 2014

The early proliferative stages of the microsporidian parasite, Pseudoloma neurophilia were visualized in larval zebrafish, Danio rerio, using histological sections with a combination of an in situ hybridization probe specific to the P. neurophilia small‐subunit ribosomal RNA gene, standard hematoxylin‐eosin stain, and the Luna stain to visualize spores. Beginning at 5 d post fertilization, fish were exposed to P. neurophilia and examined at 12, 24, 36, 48, 72, 96, and 120 h post exposure (hpe). At 12 hpe, intact spores in the intestinal lumen and proliferative stages developing in the epithelial cells of the anterior intestine and the pharynx and within hepatocytes were observed. Proliferative stages were visualized in the pancreas and kidney at 36–48 hpe and in the spinal cord, eye, and skeletal muscle beginning at 72 hpe. The first spore stages of P. neurophilia were observed at 96 hpe in the pharyngeal epithelium, liver, spinal cord, and skeletal muscle. The parasite was only observed in the brain of larval fish at 120 hpe. The distribution of the early stages of P. neurophilia and the lack of mature spores until 96 hpe indicates that the parasite gains access to organs distant from the initial site of entry, likely by penetrating the intestinal wall with the polar tube.
A survey of practices of tunnel preparation among dentists who attended the 100th FDI Annual World Dental Congress
Authors: Chu Chun‐Hung , Mei May L. , Nalliah Romesh P.
Published: January 2014

Aim

To study the practice of tunnel restoration (TR) among dentists who attended the 100th World Dental Federation (FDI) Annual World Dental Congress (AWDC).

Methods

An anonymous questionnaire was administered to a sample of 150 dentists who attended the 100th FDI AWDC in 2012. The participants were asked about TR and their practice of TR. They were also asked to provide their years of dental practice and the countries in which they received their dental training.

Results

Fifteen respondents were not performing restoration, and they were excluded from analysis. Most respondents (123/135) practiced general dentistry. Their basic dental training was from 46 countries and regions. Most of them (n = 117, 87%) knew about TR, and 53% (n = 71) practiced it. There were 12 dentists (9%) who had performed more than 10 TRs in the previous 12 months. Practice of TR among dentists who graduated more than 10 years previously was more common (odds ratio 5.87–5.98) than those who graduated <3 years previously.

Conclusions

The current study found that about half of the surveyed dentists practiced TR, although most of them knew about it. Tunnel restoration was performed more frequently among dentists who had more than 10 years of clinical experience.
Effect of experimental silane‐based primers with various contents of 2‐hydroxyethyl methacrylate on the bond strength of orthodontic adhesives
Authors: Mustafa Ammar A. , Matinlinna Jukka P. , Razak Aziz A. , Hussin Akbar S.
Published: January 2014

Aim

To evaluate in vitro the effect of different concentrations of 2‐hydroxyethyl methacrylate (HEMA) in experimental silane‐based primers on shear bond strength of orthodontic adhesives.

Methods

Different volume percentages of HEMA were tested in four experimental silane‐based primer solutions (additions of HEMA: 0, 5.0 vol%, 25.0 vol% and 50.0 vol%). An experimental silane blend (primer) of 1.0 vol% 3‐isocyanatopropyltrimethoxysilane (ICMS) + 0.5% bis‐1,2‐(triethoxysilyl) ethane (BTSE) was prepared and used. The experimental primers together with the control group were applied onto acid‐etched premolars for attachment of orthodontic brackets. After artificial aging by thermocycling the shear‐bond strength was measured. The fractured surfaces of all specimens were examined under scanning electron microscopy (SEM) to evaluate the failure mode on the enamel surface.

Results

The experimental primers showed the highest shear‐bond strength of 21.15 MPa (SD ± 2.70 MPa) and with 25 vol% showed a highly significant increase (P < 0.05) in bond strength. The SEM images showed full penetration of adhesive agents when using silane‐based primers. In addition, the SEM images suggested that the predominant failure type was not necessarily the same as for the failure propagation.

Conclusions

This preliminary study suggested that nonacidic silane‐based primers with HEMA addition might be an alternative to for use as adhesion promoting primers.
Lawsonite metasomatism and trace element recycling in subduction zones
Authors: Vitale Brovarone A. , Alard O. , Beyssac O. , Martin L. , Picatto M.
Published: January 2014

Although lawsonite‐bearing rocks are rare in exhumed high‐pressure (HP) terranes, they are considered to exert a primary role in subduction dynamics. Recent observations in natural settings have shown that fluid–rock interaction at HP conditions, including metasomatism, may lead to unusually high lawsonite amounts even in rocks that originally contained little or no lawsonite. This process may therefore bear important implications for element recycling in subduction zones. A detailed characterization of the geochemical fingerprints associated with lawsonite metasomatism is presented in this contribution. The studied rocks belong to the HP terranes of Alpine Corsica (France), which is the largest documented exposure for lawsonite metasomatism. Metasomatic lawsonite displays complex compositional zoning, including high trace element, Cr and Ti content. The trace element content is much higher compared with the average of non‐metasomatic lawsonite, and is in line with the re‐incorporation of large amounts of trace elements (e.g. REE, Sr, Pb, Th) in the rock during metasomatism, as shown by mass transfer calculations. Our data suggest that serpentinites represented the main fluid source for the metasomatism, with concurrent contribution of other, possibly Ca‐rich lithologies, such as mafic or meta‐sedimentary rocks. We propose that the breakdown of metasomatic lawsonite may contribute to the genesis of magmas and their characteristic geochemical signatures.
Submitting a manuscript for peer review–integrity, integrity, integrity
Authors: Murphy Sean P. , Bulman Christopher , Shariati Behnam , Hausmann Laura ,   the ISN Publications Committee
Published: January 2014

Publication of a flawed manuscript has significant consequences for the progress of science. When this proves to be intentional, science is brought into disrepute and this puts even more pressure on the shrinking resources that society is prepared to invest in research. All scientific journals, including the Journal of Neurochemistry, have witnessed a marked increase in the number of corrections and retractions of published articles over the last 10 years, and uncovered a depressingly large number of fabrications among submitted manuscripts. The increase in number of ‘spoiled’ manuscripts reflects not only the improved methods that journals employ to detect plagiarism in its many forms but also suggests a measurable change in the behavior of authors. The increased policing of submissions by reviewers, editors, and publishers expends time and money. The sanctions imposed by journal editors on authors found guilty of malpractice are transparent and severe.
ser31 tyrosine hydroxylase phosphorylation parallels differences in dopamine recovery in nigrostriatal pathway following 6‐OHDA lesion
Authors: Salvatore Michael F.
Published: January 2014

Compensatory mechanisms in dopamine (DA) signaling have long been proposed to delay onset of locomotor symptoms during Parkinson's disease progression until ~ 80% loss of striatal DA occurs. Increased striatal dopamine turnover has been proposed to be a part of this compensatory response, but may occur after locomotor symptoms. Increased tyrosine hydroxylase (TH) activity has also been proposed as a mechanism, but the impact of TH protein loss upon site‐specific TH phosphorylation in conjunction with the impact on DA tissue content is not known. The tissue content of DA was determined against TH protein loss in the striatum and substantia nigra (SN) following 6‐hydroxydopamine lesion in the medial forebrain bundle in young Sprague–Dawley male rats. Although DA predictably decreased in both regions following 6‐hydroxydopamine, there was a significant difference in DA loss between the striatum (75%) and SN (40%), despite similar TH protein loss. Paradoxically, there was a significant decrease in DA against remaining TH protein in striatum, but a significant increase in DA against remaining TH in SN. In the SN, increased DA per remaining TH protein was matched by increased ser31, but not ser40, TH phosphorylation. In striatum, both ser31 and ser40 phosphorylation decreased, reflecting decreased DA per TH. However, in control nigral and striatal tissue, only ser31 phosphorylation correlated with DA per TH protein. Combined, these results suggest that the phosphorylation of ser31 in the SN may be a mechanism to increase DA biosynthesis against TH protein loss in an in vivo model of Parkinson's disease.

image

Properties of dopamine biosynthesis were evaluated in the 6‐OHDA model of Parkinson's disease by studying the impact of tyrosine hydroxylase (TH) protein loss on its own phosphorylation and dopamine (DA) tissue content in rat nigrostriatal pathway. A dichotomous response was observed between striatum and substantia nigra in that dopamine per remaining TH decreased in striatum, but increased in substantia nigra. Phosphorylation at ser31 reflected these differences, indicating that ser31 phosphorylation may be critical to maintain dopamine with progressive TH protein loss. Drawings are from slides purchased from Motifolio (http://motifolio.com/).
Wnt signaling regulates homeostasis of the periodontal ligament
Authors: Lim W. H. , Liu B. , Cheng D. , Williams B. O. , Mah S. J. , Helms J. A.
Published: January 2014

Background and Objective

In health, the periodontal ligament maintains a constant width throughout an organism's lifetime. The molecular signals responsible for maintaining homeostatic control over the periodontal ligament are unknown. The purpose of this study was to investigate the role of Wnt signaling in this process by removing an essential chaperone protein, Wntless (Wls), from odontoblasts and cementoblasts, and observing the effects of Wnt depletion on cells of the periodontal complex.

Material and Methods

The Wnt responsive status of the periodontal complex was assessed using two strains of Wnt reporter mice: Axin2LacZ/+ and Lgr5LacZ/+. The function of this endogenous Wnt signal was evaluated by conditionally eliminating the Wntless (Wls) gene using an osteocalcin Cre driver. The resulting OCN‐Cre;Wls fl/fl mice were examined using micro‐computed tomography and histology, immunohistochemical analyses for osteopontin, Runx2 and fibromodulin, in‐situ hybridization for osterix and alkaline phosphatase activity.

Results

The adult periodontal ligament is Wnt responsive. Elimination of Wnt signaling in the periodontal complex of OCN‐Cre;Wlsfl/fl mice resulted in a wider periodontal ligament space. This pathologically increased periodontal width is caused by a reduction in the expression of osteogenic genes and proteins, which results in thinner alveolar bone. A concomitant increase in fibrous tissue occupying the periodontal space was observed, along with a disruption in the orientation of the periodontal ligament.

Conclusion

The periodontal ligament is a Wnt‐dependent tissue. Cells in the periodontal complex are Wnt responsive, and eliminating an essential component of the Wnt signaling network leads to a pathological widening of the periodontal ligament space. Osteogenic stimuli are reduced, and a disorganized fibrillary matrix results from the depletion of Wnt signaling. Collectively, these data underscore the importance of Wnt signaling in homeostasis of the periodontal ligament.
Prostaglandin E2 inhibits in‐vitro mineral deposition by human periodontal ligament cells via modulating the expression of TWIST1 and RUNX2
Authors: Manokawinchoke J. , Pimkhaokhum A. , Everts V. , Pavasant P.
Published: January 2014

Background and Objective

Prostaglandin E2 (PGE2) has been shown to be able to influence both bone formation and resorption. The purpose of this study was to investigate the effect of PGE2 on the osteogenic differentiation of human periodontal ligament (HPDL) cells.

Material and Methods

HPDL cells were cultured with 0.001–1 μm PGE2 in osteogenic medium. In‐vitro mineral deposition was determined by Alizarin Red S staining, and gene expression was determined by real‐time PCR.

Results

PGE2 inhibited in‐vitro mineral deposition by HPDL cells in a dose‐dependent manner. PCR analyses showed that PGE2 upregulated the expression of Runt‐related transcription factor 2 (RUNX2), but had no effect on osteocalcin expression. Upregulation of TWIST‐related protein1 (TWIST1), a functional antagonist of RUNX2, was also observed. In addition, increased levels of RUNX2 and TWIST1 proteins, induced by PGE2, were detected by western blot analysis. Using a chemical activator of E prostanoid (EP) receptors as well as small interfering RNA against an EP receptor, it was shown that PGE2 regulated RUNX2 and TWIST1 via the EP2 receptor. The role of protein kinase A in the inductive effect of PGE2 was also demonstrated.

Conclusion

The results of this study revealed that PGE2 modulates the osteogenic differentiation of HPDL cells via regulating the expression of RUNX2 and TWIST1. The results suggest a possible role for PGE2 in regulating the homeostasis of periodontal ligament tissue.
Placenta Growth Factor and Vascular Endothelial Growth Factor A Have Differential, Cell‐Type Specific Patterns of Expression in Vascular Cells
Authors: Xiang Lingjin , Varshney Rohan , Rashdan Nabil A. , Shaw Jennifer H. , Lloyd Pamela G.
Published: January 2014

Objective

PLGF, a VEGF‐A related protein, mediates collateral enlargement via monocytes but plays little role in capillary proliferation. In contrast, VEGF‐A mediates both collateral enlargement and capillary proliferation. PLGF has been less thoroughly studied than VEGF‐A, and questions remain regarding its regulation and function. Therefore, our goal was to characterize the expression of PLGF by vascular cells. We hypothesized that vascular SMC would express more PLGF than EC, since VEGF‐A is primarily expressed by non‐EC.

Methods

We compared PLGF and VEGF‐A across eight EC and SMC lines, then knocked down PLGF and evaluated cell function. We also assessed the effect of hypoxia on PLGF expression and promoter activity.

Results

PLGF was most highly expressed in EC, whereas VEGF‐A was most highly expressed in SMC. PLGF knockdown did not affect EC number, migration, or tube formation, but reduced monocyte migration toward EC. Monocyte migration was rescued by exogenous PLGF. Hypoxia increased PLGF protein without activating PLGF gene transcription.

Conclusions

PLGF and VEGF‐A have distinct patterns of expression in vascular cells. EC derived PLGF may function primarily in communication between EC and circulating cells. Hypoxia increases EC PLGF expression posttranscriptionally.
Using encapsulated freeze‐dried lipids to trigger a gastrointestinal vagal reflex: validation in a pig model
Authors: Val‐Laillet D. , Guerin S. , Malbert C.‐H.
Published: January 2014

Background

Nutrient‐sensing studies in humans frequently use intragastric intubation. A non‐invasive alternative would be the use of freeze‐dried lipids (FDL) capsules. We proposed to validate this method in pigs by (i) demonstrating that low‐dose FDL can increase vagal activity, gastric compliance (GC), and delay gastric emptying time (GET); (ii) evaluating the release kinetics of encapsulated FDL.

Methods

Nine conscious pigs fitted with duodenal catheter and gastric cannula were administered FDL (3‐mL freeze‐dried Intralipid®). Vagal tone was estimated via heart rate variability (HRV) measurements, GC was measured via the barostatic method, and GET after a test meal was evaluated via scintigraphy. FDL vs placebo (methylcellulose [MC]) capsules release kinetics were also evaluated via scintigraphy.

Key Results

Duodenal FDL infusion increased GC in 2/8 trials only, but systematically delayed GET compared to saline (96 vs 70 min; p = 0.018). The presence of FDL in the duodenum decreased heart rate, increased vagal tone, and HRV. FDL capsules released their content in the duodenum before MC capsules (41 vs 67 min; p = 0.013), and MC induced ECG data quite similar to FDL except for HRV (p = 0.011).

Conclusions & Inferences

Low‐dose FDL was a potent signal to induce vagal reflex and increase GET. FDL capsules released their content in the duodenum and activated the vagal pathway after approximately 40 min, which is an important data for designing future paradigms in humans. MC was not a good placebo because of its stickiness and ability to activate the vagal pathway too.
Pain management during bone marrow aspiration and biopsy in pediatric cancer patients
Authors: Kato Yoko , Maeda Miho , Aoki Yuki , Ishii Eizaburo , Ishida Ysushi , Kiyotani Chikako , Goto Shoko , Sakaguchi Sachi , Sugita Kenichi , Tokuyama Mika , Nakadate Hisaya , Kikuchi Akira , Tsuchida Masahiro , Ohara Akira
Published: January 2014

Background

The pain associated with bone marrow aspiration and biopsy (BMAB) has an enormous impact on pediatric cancer patients and their families, but no specific reference standards for sedation and analgesia have been developed inJapan. To determine the problems associated with pain management duringBMAB, a cross‐sectional investigation was conducted.

Methods

A survey was sent inOctober 2011 to data managers in institutions belonging to theTokyoChildren'sCancerStudyGroup, addressing the non‐pharmacological and pharmacological pain management forBMABperformed on pediatric cancer inpatients betweenJanuary 2010 andDecember 2010.

Results

The eligible response rate was 41 of 57 institutions (71.9%). Non‐pharmacological pain intervention was provided in 68% of surveyed institutions. All institutions provided pharmacological pain management. In most institutions, sedation/analgesia was performed by pediatric oncologists in a treatment room in the ward. Standards for pain management were developed and utilized in only four institutions. Other means of pain management were provided in various settings. Twelve institutions reported insufficient sedation/analgesia. In total, 80% of institutions reported some adverse events. Two serious adverse events were reported in cases of underlying or complicated conditions. No serious long‐term consequences were reported.

Conclusions

Significant issues were identified regarding the efficacy and safety of pain management. Adverse events can occur in any institution. Children with underlying or complicated conditions are at high risk for serious adverse events. Therefore, adequate and systematic assessment, patient monitoring, preparation and treatment for adverse events, and cooperation with skilled specialists of pediatric oncology, anesthesiology, and intensive care are essential.
CCR7 facilitates the pro‐inflammatory function of dendritic cells in experimental leishmaniasis
Authors: Kling J. C. , Darby J. , Körner H.
Published: January 2014

Cutaneous leishmaniasis, caused by the parasite Leishmania major, results in lesions at the site of infection, which are self‐healing in resistant hosts. However, in the absence of the chemokine receptor CCR7, mice are unable to heal the lesion and develop chronic disease. These B6.CCR7−/− mice display an increased number of Th2 cells and immunosuppressive cytokine levels, as well as more regulatory T cells. As CCR7 is expressed on activated dendritic cells (DCs), and these cells require CCR7 to migrate to the draining lymph node, we expected decreased migration of DCs into the lymph node in the absence of CCR7 during cutaneous leishmaniasis. Consequently, in an attempt to initiate a self‐healing response, we adoptively transferred CCR7+ (B6.WT) DCs into the site of infection of B6.CCR7−/− mice. Surprisingly, instead of healing the lesion, B6.CCR7−/− mice inoculated with B6.WT DCs developed augmented lesions and showed increased immunosuppression compared to control B6.CCR7−/− mice transferred with B6.CCR7−/− DCs or B6.WT mice with B6.WT DCs. Finally, B6.WT mice injected with B6.CCR7−/− DCs also presented delayed healing of the lesion. These results indicate that CCR7 must be expressed on DCs, as well as peripheral cells, to allow an efficient immune response to L. major.
How Groups Affect Our Health and Well‐Being: The Path from Theory to Policy
Authors: Jetten Jolanda , Haslam Catherine , Haslam S. Alexander , Dingle Genevieve , Jones Janelle M.
Published: January 2014

Considerable evidence now exists that people can draw on social groups in order to maintain and enhance health and well‐being. We review this evidence and suggest that social identity theorizing, and its development in the social identity approach to health and well‐being, can help us to understand the way that groups, and the identities that underpin them, can promote a social cure. Specifically, we propose that social groups are important psychological resources that have the capacity to protect health and well‐being, but that they are only utilized effectively when individuals perceive they share identity with another individual or group. However, as powerful as shared identities may be, their consequences for health are largely ignored in policy and practice. In this review, we offer a novel direction for policy, identifying ways in which building and consolidating group identification can help to capitalize effectively on the potential of group membership for health. Using this as a basis to increase awareness, we go further to offer practical interventions aimed at assessing identity resources as substantial and concrete assets, which can be cultivated and harnessed in order to realize their health‐enhancing potential.
Characterization of a novel HLA‐DRB1 allele: DRB1*11:153
Authors: Santos S. , Balas A. , Azcarate M. , Vesga M. A. , Vicario J. L.
Published: January 2014

HLA‐DRB1*11:153 differs from DRB1*11:131 by one nucleotide at position 286 where C > A, (codon 67 CTC>ATC), resulting in an amino acid substitution, 67L>67I.
Cocaine: The Complementarity Between Legal and Illegal Trade
Authors: Russo Francesco Flaviano
Published: January 2014

I show that the decreased price of cocaine in its major destination markets is partly explained by a lower smuggling cost, which is itself the consequence of an increased international trade in legal goods. First, because more legal imports are associated with a bigger number of transporters and therefore with a bigger supply of potential drug smugglers. Second, because, as the number of legal shipments grows, the individual inspection probability decreases, lowering the risk born by the smugglers and thus their compensation. The cocaine market provides evidence of a complementarity between legal and illegal trade.
Angiotensin‐converting enzyme (ACE and ACE2) imbalance correlates with the severity of cerulein‐induced acute pancreatitis in mice
Authors: Liu Ruixia , Qi Haiyu , Wang Jing , Wang Yan , Cui Lijian , Wen Yan , Yin Chenghong
Published: January 2014

New Findings

What is the central question of this study?

Angiotensin‐converting enzyme 2 (ACE2) degrades angiotensin II to angiotensin‐(1–7) and has recently been described to have an antagonistic effect on angiotensin‐converting enzyme (ACE) signalling. However, the specific underlying role of ACE2 in the pathogenesis of severe acute pancreatitis (SAP) is unclear.

What is the main finding and its importance?

Using wild‐type, ACE2 knock‐out and ACE2 transgenic mice, we show that ACE2–ACE imbalance plays an important role in the pathogenesis of SAP and that pancreatic ACE2 is an important factor in determining the severity of SAP.

Angiotensin‐converting enzyme (ACE) and its effector peptide angiotensin II (Ang II) have been implicated in the pathogenesis of pancreatitis. Angiotensin‐converting enzyme 2 (ACE2) degrades Ang II to angiotensin‐(1–7) [Ang‐(1–7)] and has recently been described to have an antagonistic effect on ACE signalling. However, the specific underlying role of ACE2 in the pathogenesis of severe acute pancreatitis (SAP) is unclear. In the present study, the local imbalance of ACE and ACE2, as well as Ang II and Ang‐(1–7) expression, was compared in wild‐type (WT) and ACE2 knock‐out (KO) or ACE2 transgenic (TG) mice subjected to cerulein‐induced SAP. Serum amylase, tumour necrosis factor‐α, interleukin (IL)‐1β, IL‐6 and IL‐10 levels and histological morphometry were used to determine the severity of pancreatitis. In WT mice, pancreatic ACE and Ang II and serum Ang II expression increased (P < 0.05), while pancreatic ACE2 and Ang‐(1–7) and serum Ang‐(1–7) levels were also significantly elevated (P < 0.05) from 2 to 72 h after the onset of SAP. However, the ratio of pancreatic ACE2 to ACE expression was significantly reduced (from 1.46 ± 0.09 to 0.27 ± 0.05, P < 0.001) and paralleled the severity of pancreatitis. The Ace2 KO mice exhibited increased levels of tumour necrosis factor‐α, IL‐1β, IL‐6, multifocal coagulative necrosis and inflammatory infiltrate, and lower levels of serum IL‐10 and pancreatic Ang‐(1–7) (4.70 ± 2.13 versus 10.87 ± 2.51, P < 0.001) compared with cerulein‐treated WT mice at the same time point. Conversely, Ace2 TG mice with normal ACE expression were more resistant to SAP challenge as evidenced by a decreased inflammatory response, attenuated pathological changes and increased survival rates. These data suggest that the ACE2–ACE imbalance plays an important role in the pathogenesis of SAP and that pancreatic ACE2 is an important factor in determining the severity of SAP.
Model Organisms Retain an “Ecological Memory” of Complex Ecologically Relevant Environmental Variation
Authors: Beer Karlyn D. , Wurtmann Elisabeth J. , Pinel Nicolás , Baliga Nitin S.
Published: January 2014

Although tractable model organisms are essential to characterize the molecular mechanisms of evolution and adaptation, the ecological relevance of their behavior is not always clear because certain traits are easily lost during long-term laboratory culturing. Here, we demonstrate that despite their long tenure in the laboratory, model organisms retain “ecological memory” of complex environmental changes. We have discovered that
Halobacterium salinarum
NRC-1, a halophilic archaeon that dominates microbial communities in a dynamically changing hypersaline environment, simultaneously optimizes fitness to total salinity, NaCl concentration, and the [K]/[Mg] ratio. Despite being maintained under controlled conditions over the last 50 years, peaks in the three-dimensional fitness landscape occur in salinity and ionic compositions that are not replicated in laboratory culturing but are routinely observed in the natural hypersaline environment of this organism. Intriguingly, adaptation to variations in ion composition was associated with differential regulation of anaerobic metabolism genes, suggesting an intertwined relationship between responses to oxygen and salinity. Our results suggest that the ecological memory of complex environmental variations is imprinted in the networks for coordinating multiple cellular processes. These coordination networks are also essential for dealing with changes in other physicochemically linked factors present during routine laboratory culturing and, hence, retained in model organisms.
Oxidation of Metabolites Highlights the Microbial Interactions and Role of
Acetobacter pasteurianus
during Cocoa Bean Fermentation
Authors: Moens Frédéric , Lefeber Timothy , De Vuyst Luc
Published: January 2014

Four cocoa-specific acetic acid bacterium (AAB) strains, namely,
Acetobacter pasteurianus
386B,
Acetobacter ghanensis
LMG 23848
T
,
Acetobacter fabarum
LMG 24244
T
, and
Acetobacter senegalensis
108B, were analyzed kinetically and metabolically during monoculture laboratory fermentations. A cocoa pulp simulation medium (CPSM) for AAB, containing ethanol, lactic acid, and mannitol, was used. All AAB strains differed in their ethanol and lactic acid oxidation kinetics, whereby only
A. pasteurianus
386B performed a fast oxidation of ethanol and lactic acid into acetic acid and acetoin, respectively. Only
A. pasteurianus
386B and
A. ghanensis
LMG 23848
T
oxidized mannitol into fructose. Coculture fermentations with
A. pasteurianus
386B or
A. ghanensis
LMG 23848
T
and
Lactobacillus fermentum
222 in CPSM for lactic acid bacteria (LAB) containing glucose, fructose, and citric acid revealed oxidation of lactic acid produced by the LAB strain into acetic acid and acetoin that was faster in the case of
A. pasteurianus
386B. A triculture fermentation with
Saccharomyces cerevisiae
H5S5K23,
L. fermentum
222, and
A. pasteurianus
386B, using CPSM for LAB, showed oxidation of ethanol and lactic acid produced by the yeast and LAB strain, respectively, into acetic acid and acetoin. Hence, acetic acid and acetoin are the major end metabolites of cocoa bean fermentation. All data highlight that
A. pasteurianus
386B displayed beneficial functional roles to be used as a starter culture, namely, a fast oxidation of ethanol and lactic acid, and that these metabolites play a key role as substrates for
A. pasteurianus
in its indispensable cross-feeding interactions with yeast and LAB during cocoa bean fermentation.
Biogeography of the Sediment Bacterial Community Responds to a Nitrogen Pollution Gradient in the East China Sea
Authors: Xiong Jinbo , Ye Xiansen , Wang Kai , Chen Heping , Hu Changju , Zhu Jianlin , Zhang Demin
Published: January 2014

Patterns of microbial distribution represent the integrated effects of historical and biological processes and are thus a central issue in ecology. However, there is still active debate on whether dispersal limitation contributes to microbial diversification in strongly connected systems. In this study, sediment samples were collected along a transect representing a variety of seawater pollution levels in the East China Sea. We investigated whether changes in sediment bacterial community structures would indicate the effects of the pollution gradient and of dispersal limitation. Our results showed consistent shifts in bacterial communities in response to pollution. More geographically distant sites had more dissimilar communities (
r
= −0.886,
P
< 0.001) in this strongly connected sediment ecosystem. A variance analysis based on partitioning by principal coordinates of neighbor matrices (PCNM) showed that spatial distance (dispersal limitation) contributed more to bacterial community variation (8.2%) than any other factor, although the environmental factors explained more variance when combined (11.2%). In addition, potential indicator taxa (primarily affiliated with
Deltaproteobacteria
and
Gammaproteobacteria
) were identified; these taxa characterized the pollution gradient. This study provides direct evidence that dispersal limitation exists in a strongly connected marine sediment ecosystem and that candidate indicator taxa can be applied to evaluate coastal pollution levels.
Prevalence in Bulk Tank Milk and Epidemiology of
Campylobacter jejuni
in Dairy Herds in Northern Italy
Authors: Bianchini Valentina , Borella Laura , Benedetti Valentina , Parisi Antonio , Miccolupo Angela , Santoro Eliana , Recordati Camilla , Luini Mario
Published: January 2014

Thermotolerant
Campylobacter
spp. are frequently the cause of human gastroenteritis and have assumed more importance in Italy following the increased consumption of raw milk. Our objectives were to determine the prevalence and genotypes of
Campylobacter
spp. in dairy herds and to investigate the possible sources of bulk milk contamination. Bulk milk from dairy herds (
n
= 282) was cultured for
Campylobacter
spp. and
Enterobacteriaceae
. At three
Campylobacter jejuni
-positive farms, bovine feces, pigeon intestines, milk, and water points were also investigated. Isolates were identified by PCR and genotyped using multilocus sequence typing (MLST).
C. jejuni
was detected in 34 (12%) bulk milk samples. The strains belonged to 14 sequence types, and the most common clonal complexes were CC-21, CC-48, and CC-403. No association was demonstrated between the presence of
C. jejuni
and high levels of
Enterobacteriaceae
in bulk milk. At the three farms examined,
C. jejuni
was isolated from bovine feces (25/82 [30.5%]), pigeon intestines (13/60 [21.7%]), bulk milk (10/24 [41.7%]), and water points (4/16 [25%]). MLST revealed lineages that were common between milk and bovine feces but distinct between cattle and pigeons. In one herd,
C. jejuni
with the same genotype was isolated repeatedly from bulk milk and a cow with an udder infection. Our results showed a high prevalence of
C. jejuni
in bulk milk and suggested that udder excretion, in addition to fecal matter, may be a route of bulk milk contamination. MLST analysis indicated that pigeons are probably not relevant for the transmission of
C. jejuni
to cattle and for milk contamination.
Synergistic Bactericidal Effect of Simultaneous Near-Infrared Radiant Heating and UV Radiation against
Cronobacter sakazakii
in Powdered Infant Formula
Authors: Ha Jae-Won , Kang Dong-Hyun
Published: January 2014

The aim of this study was to investigate the synergistic bactericidal effects of the simultaneous application of near-infrared (NIR) heating and UV irradiation against
Cronobacter sakazakii
in powdered infant formula and to determine the effect on quality by measuring color changes and performing sensory evaluation. A cocktail of
C. sakazakii
strains was inoculated into powdered infant formula, followed by NIR, UV, and combined NIR-UV treatments. The sum of NIR and UV inactivation was lower than that obtained by the simultaneous application of both technologies due to their synergism. Simultaneous NIR-UV combined treatment for 7 min achieved a 2.79-log-unit CFU reduction of
C. sakazakii
. The underlying inactivation mechanisms of the combined NIR-UV treatment were evaluated by the propidium iodide (PI) uptake test, and we confirmed that disruption of the bacterial cell membrane was the main factor contributing to the synergistic lethal effect. The color values and sensory characteristics of simultaneously NIR-UV-treated infant formula powder were not significantly (
P
> 0.05) different from those of the control. The results of this study suggest that a NIR-UV decontaminating system can be applied as an alternative to other interventions in powdered weaning foods.