bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between immune function recovery and infectious complications in patients following living donor liver transplantation
Authors: Kobayashi Shinichiro , Soyama Akihiko , Takatsuki Mitsuhisa , Hidaka Masaaki , Adachi Tomohiko , Kitasato Amane , Kinoshita Ayaka , Hara Takanobu , Kanetaka Kengo , Fujita Fumihiko , Kuroki Tamotsu , Eguchi Susumu
Published: December 2015

Aim

The ImmuKnow (IK) assay enables the evaluation of peripheral blood CD4+ adenosine triphosphate activity to facilitate an objective assessment of the cellular immune function in immunosuppressed patients. However, it is unclear whether the IK assay is utilized during the acute postoperative periods following living donor liver transplantation (LDLT).

Methods

The IK values of 43 LDLT recipients were measured during the month following LDLT to evaluate the relationship between the measured IK values and infectious events.

Results

The IK values after LDLT were significantly increased compared with the IK values before LDLT ( P < 0.01). During the month following transplantation, the rate of bacterial infection in the recipients with IK values of more than 225 ng/mL was significantly lower than that in the recipients with IK values of 225 ng/mL or less ( 42.1% vs 91.7%, respectively; P < 0.01). The rate of severe infections among the recipients who maintained IK values of more than 150 ng/mL was significantly lower than that among the recipients with IK values of 150 ng/mL or less during the month following transplantation ( 3.7% vs 56.3%, respectively; P < 0.01).

Conclusion

The immune system of LDLT recipients dramatically improved following transplantation. The IK values of LDLT recipients were associated with the incidence of infectious events during the perioperative period after LDLT. Monitoring IK values was useful during both the acute and long‐term postoperative periods.
Calcium sulphate‐induced soya bean protein tofu‐type gels: influence of denaturation and particle size
Authors: Zhao Haibo , Li Weiwei , Qin Fang , Chen Jie
Published: December 2015

Soya bean protein isolate (SPI) dispersions (7.25%, w/v) were heated at 65, 75, 85 or 90 °C for different time periods to produce SPI aggregates with diverse degrees of denaturation and particle size to investigate the effects on calcium sulphate (CaSO4)‐induced tofu‐type gel. The results revealed that gel hardness and water‐holding capacity correlated positively with the degree of denaturation of glycinin (11S) and the particle size of the SPI aggregates. The formed gels showed more uniform and denser network structures with increasing degrees of denaturation and particle size of SPI. Hydrophobic interaction was speculated to be the crucial factor for the retention of gels prepared by SPI whose degree of denaturation by 11S was lower than 4.35%. However, disulphide bonds probably played a more important role in the retention of gels generated by SPI with the 11S denaturation degree of >84.47%. Moreover, the bulk density of the protein aggregates might determine the gel structures to a certain extent.
Effect of puffing conditions on physical properties and rehydration characteristic of instant rice product
Authors: Wongsa Jittimon , Uttapap Dudsadee , Lamsal Buddhi P. , Rungsardthong Vilai
Published: December 2015

The aim of this work was to study the effects of puffing conditions on the properties of instant rice and to obtain optimal processing condition for product with rehydration time within 5 min. Thai jasmine rice was soaked, cooked and dried at 80 °C in a tray dryer before being puffed at different moisture contents (15–20% wb), temperatures (200–220 °C) and time intervals (20–30 s). The rice puffed at higher moisture contents and puffing temperatures for longer time exhibited higher volume expansion ratios and shorter rehydration times. Presumably, case hardening of the grain surface occurred. Instant rice that can be rehydrated in 5 min with more acceptable hardness than the commercial instant rice was obtained. Regression models to predict the quality of instant rice were developed using response surface methodology.
Utilization and impact of surgical technique on the performance of pelvic lymph node dissection at radical prostatectomy: Results from the Shared Equal Access Regional Cancer Hospital database
Authors: McGinley Kathleen F , Sun Xizi , Howard Lauren E , Aronson William J , Terris Martha K , Kane Christopher J , Amling Christopher L , Cooperberg Matthew R , Freedland Stephen J
Published: December 2015

Objective

To evaluate performance of pelvic lymph node dissection during radical prostatectomy within an equal access care setting over a period of time, and stratified by prostate cancer risk group and surgical technique.

Methods

We identified men in the Shared Equal Access Regional Cancer Hospital database who had open or robotic‐assisted radical prostatectomy from 2006 to 2013. Univariable logistic regression was used to test the association between age, race, body mass index, total biopsy cores, number of positive biopsy cores, risk group, year, center, surgical volume and surgical technique on pelvic lymph node dissection use. Multivariable logistic analysis was used to examine surgical technique and pelvic lymph node dissection performance. Spearman's correlation examined temporal changes in pelvic lymph node dissection utilization stratified by risk group and surgical technique.

Results

A total of 1425 men met inclusion criteria; 67% of them underwent pelvic lymph node dissection. On multivariable analysis, robotic‐assisted radical prostatectomy was associated with an 92% decreased use of pelvic lymph node dissection in low‐risk, 84% decreased in intermediate‐risk and 91% decreased in high‐risk men (all P < 0.001). In robotic‐assisted radical prostatectomy, there was a trend for increased pelvic lymph node dissection utilization over time in high‐risk men (Spearman; P = 0.077) reaching ~85% in 2012–2013, which was accompanied by increased use in low‐risk men (P = 0.016). For open radical prostatectomy, fewer pelvic lymph node dissections were carried out in low‐risk men over time, decreasing to ~35% (P = 0.047) in 2012–2013, whereas rates remained high for high‐risk men throughout (~95%; P = 0.621).

Conclusion

Regardless of risk group, pelvic lymph node dissection is carried out significantly less during robotic‐assisted radical prostatectomy. For robotic‐assisted radical prostatectomy, pelvic lymph node dissection utilization increased over time for high‐risk men, but rates also increased for low‐risk men. Further attention to the discrepancy between provided and guideline recommended pelvic lymph node dissection performance is required to improve prostate cancer care.
The Influence of Attitudes toward Immigrants on International Migration
Authors: Gorinas Cédric , Pytliková Mariola
Published: December 2015

We investigate whether anti-immigrant attitudes affect migrant inflows in Organisation for Economic Co-operation and Development (OECD) countries. Using longitudinal exhaustive data, we find that natives’ hostility, particularly natives’ propensity to discriminate on the labor market, reduces immigration. This effect is comparable to more conventional migration factors. We obtain robust results when we, for example, capture hostility with far-right parties’ popularity instead and control for tighter immigration policies or multilateral resistance to migration. We find a stronger effect for EU-to-EU migrants, migrants from developed countries and linguistically close countries. Our results raise a challenge for policy makers when the demand for foreign workers and anti-immigrant sentiment are present.
Serum homocysteine level and gestational diabetes mellitus: A meta‐analysis
Authors: Gong Tian , Wang Jing , Yang Mei , Shao Yan , Liu Juning , Wu Qianlan , Xu Qinhua , Wang Huiying , He Xiuyu , Chen Yunzhen , Xu Rong , Wang Yun
Published: December 2015

Aims/Introduction

Homocysteine levels during pregnancy in women with gestational diabetes mellitus (GDM) have been studied; however, it remains unclear whether hyperhomocysteinemia is a useful predictor of insulin resistance. The present study aimed to evaluate the relationship between homocysteine level and GDM.

Materials and Methods

PubMed, Elsevier, Web of Science and CNKI were searched for relevant studies published up to January 2015. Manual searches of references of the relevant original studies were carried out. Meta‐analysis was used to assessed the relationship between homocysteine level and GDM using the stata 12.0 software.

Results

Homocysteine levels were significantly elevated in women with GDM compared with those without GDM (weighted mean difference 0.77, 95% confidence interval 0.44–1.10). This evidence was more consistent during the second trimester measurement of homocysteine (weighted mean difference 0.95, 95% confidence interval 0.67–1.23) and for women aged older than 30 years (weighted mean difference 0.90, 95% confidence interval 0.63–1.17).

Conclusions

The present meta‐analysis shows that homocysteine level is significantly elevated among women with GDM compared with women with normal glucose tolerance, and this finding persists more during the second trimester.
Intraventricular apolipoprotein ApoJ infusion acts protectively in Traumatic Brain Injury
Authors: Huang Zhijian , Cheng Chongjie , Jiang Li , Yu Zhanyang , Cao Fang , Zhong Jianjun , Guo Zongduo , Sun Xiaochuan
Published: December 2015

Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in youth, but to date, effective therapies are still lacking. Previous studies revealed a marked response of apolipoprotein J (ApoJ) expression to the brain injury. The aim of this study was to determine the potential roles of ApoJ in functional recovery following TBI. After controlled cortex impact (CCI), a TBI model, in adult wild‐type mice, ApoJ expression was up‐regulated since 6 h post‐injury and sustained for 5 days. Animals infused with recombinant human ApoJ intraventricularly at 30 min prior to CCI showed significantly reduced oxidative stress (3‐nitrotyrosine, 4‐hydroxynonenal) and complement activation (C5b‐9). In addition, ApoJ treatment was shown to suppress the inflammatory response (glial activation, cytokine expression), blood–brain barrier disruption (Evans blue extravasation), and cerebral edema (water content) induced by CCI. Concomitantly, improved neuronal maintenance and neurological behavioral performance were observed in ApoJ‐treated mice compared with the vehicle group. These findings support a neuroprotective role of ApoJ via multifunctional pathways, providing a novel and encouraging treatment strategy for TBI.

image

Apolipoprotein J (ApoJ) was up‐regulated after controlled cortical impact (CCI). Mice infused with human recombinant ApoJ prior to CCI showed reduced expression of complement and oxidative marker proteins as well as reduced inflammatory response and attenuated blood–brain barrier (BBB) disruption and cerebral edema. Neuronal maintenance and behavioral performance were improved by ApoJ infusion. These findings demonstrated the protective function of ApoJ for traumatic brain injury (TBI) therapy.
Identification and Characterization of Paraphoma chrysanthemicola Causing Leaf Spot Disease on Atractylodes japonica in China
Authors: Ge Xinxin , Zhou Rujun , Yuan Yue , Xu Haijiao , Fu Junfan , Li Hongbo
Published: December 2015

Atractylodes japonica is a perennial herb in Compositae family, which is used for stomach disorders as a traditional Chinese medicine (Guo et al. ). In 2013, a leaf spot disease was first observed on plants of A. japonica in a production field of Fushun County, Liaoning Province, China. The disease had a speckled appearance initially. Lesions with grey–white centre and brown margin gradually developed and enlarged. Eventually, infections usually caused yellowing of the leaves and premature defoliation. The causal agent of infection on plants was identified as Paraphoma chrysanthemicola based on morphological and cultural characteristics, pathogenicity tests and phylogenetic analysis. To our knowledge, this is the first report of a leaf spot disease on A. japonica caused by P. chrysanthemicola in China.
Antidiarrhoeal, antimicrobial and antioxidant effects of myrtle berries (Myrtus communis L.) seeds extract
Authors: Jabri Mohamed-Amine , Rtibi Kais , Ben-Said Amira , Aouadhi Chedia , Hosni Karim , Sakly Mohsen , Sebai Hichem
Published: December 2015

Objectives

The present study was carried out to determine the antidiarrheal effects of myrtle (Myrtus communis L.) berries seeds aqueous extract (MBSAE) from Tunisia as well as the involvement of its antimicrobial and antioxidant properties in such protection.

Methods

Adult male wistar rats were used and divided into six groups of ten each: control, Castor oil, Castor oil + Loperamide and Castor oil + various doses of MBSAE. Animals were per orally (p.o.) pre-treated with MBSAE for one hour and intoxicated by castor oil acute oral administration.

Key findings

Our results demonstrated that the MBSAE is rich in total and condensed tannins and exhibited a broad spectrum of antibacterial activity. In vivo, we found that MBSAE administration induced a significant dose-dependent protection against diarrhoea and intestinal fluid accumulation. Castor oil-induced intestinal hypersecretion was accompanied by an oxidative stress status in the intestine. More importantly, we showed that acute diarrhoea was accompanied by an increase in intestinal mucosa hydrogen peroxide (H2O2), calcium and free iron levels while MBSAE pre-treatment reversed all castor oil-induced intracellular mediators disturbances.

Conclusions

We suggest that MBSAE had a potent protective effects against castor oil-induced acute diarrhoea due in part to its antioxidant and antimicrobial properties.
Mutual Deformity: Ignaz Moscheles's Seventh and William Sterndale Bennett's Fourth Piano Concertos
Authors: Taylor Benedict
Published: December 2015

While neither the music of Ignaz Moscheles nor that of William Sterndale Bennett feature in the modern repertoire, the piano concertos of both composers form part of a significant body of works from the early nineteenth century that offer models at variance with conventional accounts of the concerto genre. The opening movements of Moscheles's Concerto No. 7 in C minor (Concerto pathétique, 1835–6) and Bennett's Concerto No. 4 in F minor (1838) are cast in single‐exposition concerto form, but each has features that complicate its relationship with the five types of Sonata Form set out in Hepokoski and Darcy's Elements of Sonata Theory. Both are similarly unusual in that they return to the tonic minor for the second ritornello statement, which by convention signifies the closure of the ‘larger exposition’; and, probably as a consequence of the pre‐emptive reappearance of primary material in the tonic here, their recapitulations are drastically abridged, complicating the post‐expositional stages of the form. These two works thus provide a rich theoretical and hermeneutical challenge to the historiography of nineteenth‐century instrumental form.
Protoporphyrin IX‐Functionalized AgSiO2 Core–Shell Nanoparticles: Plasmonic Enhancement of Fluorescence and Singlet Oxygen Production
Authors: Lismont Marjorie , Dreesen Laurent , Heinrichs Benoît , Páez Carlos A.
Published: December 2015

Metal‐enhanced processes arising from the coupling of a dye with metallic nanoparticles (NPs) have been widely reported. However, few studies have simultaneously investigated these mechanisms from the viewpoint of dye fluorescence and photoactivity. Herein, protoporphyrin IX (PpIX) is grafted onto the surface of silver core silica shell NPs in order to investigate the effect of silver (Ag) localized surface plasmon resonance (LSPR) on PpIX fluorescence and PpIX singlet oxygen (1O2) production. Using two Ag core sizes, we report a systematic study of these photophysical processes as a function of silica (SiO2) spacer thickness, LSPR band position and excitation wavelength. The excitation of Ag NP LSPR, which overlaps the PpIX absorption band, leads to the concomitant enhancement of PpIX fluorescence and 1O2 production independently of the Ag core size, but in a more pronounced way for larger Ag cores. These enhancements result from the increase in the PpIX excitation rate through the LSPR excitation and decrease when the distance between PpIX and Ag NPs increases. A maximum fluorescence enhancement of up to 14‐fold, together with an increase in photogenerated 1O2 production of up to five times are obtained using 100 nm Ag cores coated with a 5 nm thick silica coating.
Immunopathology in Taenia solium neurocysticercosis
Authors: Fleury A. , Cardenas G. , Adalid‐Peralta L. , Fragoso G. , Sciutto E.
Published: December 2015

Neurocysticercosis is a clinically and radiologically heterogeneous disease, ranging from asymptomatic infection to a severe, potentially fatal clinical picture. The intensity and extension of the parasite‐elicited inflammatory reaction is a key factor for such variability. The main features of the inflammatory process found in the brain and in the peripheral blood of neurocysticercosis patients will be discussed in this review, and the factors involved in its modulation will be herein presented.
Elevated CO2 enhances photosynthetic efficiency, ion uptake and antioxidant activity of Gynura bicolor DC. grown in a porous‐tube nutrient delivery system under simulated microgravity
Authors: Wang M. , Liu H. , Dong C. , Fu Y. , Liu H.
Published: December 2015

It is well known that plants can grow under space conditions, however, perturbations of many biological phenomena have been highlighted due to the effect of altered gravity and its possible interaction with other factors (e.g., CO2, ion radiation, etc. Our aim was to test whether elevated CO2 could provide ‘protection’ to Gynura bicolor against the damaging effects of simulated microgravity (SM) on photosynthesis, ion uptake and antioxidant activity. As compared to G. bicolor grown in ambient CO2 with no SM (ACO2), growth and yield of the plants increased under elevated ambient CO2 with no SM (ECO2) and decreased under ACO2+SM, whereas there was no significant effect on ECO2+SM. Reductions in the content of Chl a, carotenoids and Chl a+b were 17.9%, 20.7% and 17.9% under ACO2+SM, respectively, but under ECO2 there was a significant effect on all photosynthetic pigments except Chl b, compared to ACO2. Photosynthesis was improved under ECO2 with SM and such an improvement was associated with improved water use efficiency and instantaneous carboxylation efficiency. Furthermore, SM caused a reduction in ion absorption rate, except for Ca2+, while ECO2 increased the uptake rate. Finally, the activity of SOD, POD and the content of MDA and H2O2 were enhanced under SM treatments and were highest in ACO2+SM. In contrast, T‐AOC activity and GSH content significantly declined in ACO2+SM compared to other treatments. These results suggest that ACO2 is not sufficient to counteract SM impact, but the increase is usually caused by improvement in CO2 nutrition in ECO2+SM in comparison with ACO2+SM.
Loss of FTO in adipose tissue decreases
Angptl4
translation and alters triglyceride metabolism
Authors: Wang Chao-Yung , Shie Shian-Sen , Wen Ming-Shien , Hung Kuo-Chun , Hsieh I-Chang , Yeh Ta-Sen , Wu Delon
Published: December 2015

Body weight is regulated by posttranslational regulation of an mRNA encoding an adipokine that promotes lipolysis in adipocytes.
Depletion of H
2
S during obesity enhances store-operated Ca
2+
entry in adipose tissue macrophages to increase cytokine production
Authors: Velmurugan Gopal V. , Huang Huiya , Sun Hongbin , Candela Joseph , Jaiswal Mukesh K. , Beaman Kenneth D. , Yamashita Megumi , Prakriya Murali , White Carl
Published: December 2015

The gaseous signaling molecule H
2
S limits inflammation in adipose tissue by suppressing calcium signaling in resident macrophages.
Correlation of β-Lactamase Production and Colistin Resistance among Enterobacteriaceae Isolates from a Global Surveillance Program
Authors: Bradford Patricia A. , Kazmierczak Krystyna M. , Biedenbach Douglas J. , Wise Mark G. , Hackel Meredith , Sahm Daniel F.
Published: December 2015

The increasing use of carbapenems for treating multidrug-resistant (MDR) Gram-negative bacterial infections has contributed to the global dissemination of carbapenem-resistant
Enterobacteriaceae
(CRE). Serine and metallo-β-lactamases (MBLs) that hydrolyze carbapenems have become prevalent and endemic in some countries, necessitating the use of older classes of agents, such as colistin. A total of 19,719 isolates of
Enterobacteriaceae
(excluding
Proteeae
and
Serratia
spp., which have innate resistance to colistin) were collected from infected patients during 2012 and 2013 in a global surveillance program and tested for antimicrobial susceptibility using CLSI methods. Isolates of CRE were characterized for carbapenemases and extended-spectrum β-lactamases (ESBLs) by PCR and sequencing. Using EUCAST breakpoints, the rate of colistin susceptibility was 98.4% overall, but it was reduced to 88.0% among 482 carbapenemase-positive isolates. Colistin susceptibility was higher among MBL-positive isolates (92.6%) than those positive for a KPC (87.9%) or OXA-48 (84.2%). Of the agents tested, only tigecycline (MIC
90
, 2 to 4 μg/ml) and aztreonam-avibactam (MIC
90
, 0.5 to 1 μg/ml) consistently tested with low MIC values against colistin-resistant, ESBL-positive, and carbapenemase-positive isolates. Among the 309 (1.6%) colistin-resistant isolates from 10 species collected in 38 countries, 58 carried a carbapenemase that included KPCs (38 isolates), MBLs (6 isolates), and OXA-48 (12 isolates). These isolates were distributed globally (16 countries), and 95% were
Klebsiella pneumoniae
. Thirty-nine (67.2%) isolates carried additional ESBL variants of CTX-M, SHV, and VEB. This sample of
Enterobacteriaceae
demonstrated a low prevalence of colistin resistance overall. However, the wide geographic dispersion of colistin resistance within diverse genus and species groups and the higher incidence observed among carbapenemase-producing MDR pathogens are concerning.
Colistin-Resistant Acinetobacter baumannii Clinical Strains with Deficient Biofilm Formation
Authors: Dafopoulou Konstantina , Xavier Basil Britto , Hotterbeekx An , Janssens Lore , Lammens Christine , Dé Emmanuelle , Goossens Herman , Tsakris Athanasios , Malhotra-Kumar Surbhi , Pournaras Spyros
Published: December 2015

In two pairs of clinical colistin-susceptible/colistin-resistant (Cst
s
/Cst
r
)
Acinetobacter baumannii
strains, the Cst
r
strains showed significantly decreased biofilm formation in static and dynamic assays (
P
< 0.001) and lower relative fitness (
P
< 0.05) compared with those of the Cst
s
counterparts. The whole-genome sequencing comparison of strain pairs identified a mutation converting a stop codon to lysine (*241K) in LpsB (involved in lipopolysaccharide [LPS] synthesis) in one Cst
r
strain and a frameshift mutation in CarO and the loss of a 47,969-bp element containing multiple genes associated with biofilm production in the other.
Effects of Stress, Reactive Oxygen Species, and the SOS Response on
De Novo
Acquisition of Antibiotic Resistance in Escherichia coli
Authors: Händel Nadine , Hoeksema Marloes , Freijo Mata Marina , Brul Stanley , ter Kuile Benno H.
Published: December 2015

Strategies to prevent the development of antibiotic resistance in bacteria are needed to reduce the threat of infectious diseases to human health. The
de novo
acquisition of resistance due to mutations and/or phenotypic adaptation occurs rapidly as a result of interactions of gene expression and mutations (N. Handel, J. M. Schuurmans, Y. Feng, S. Brul, and B. H. Ter Kuile, Antimicrob Agents Chemother 58:4371–4379, 2014,
http://dx.doi.org/10.1128/AAC.02892-14
). In this study, the contribution of several individual genes to the
de novo
acquisition of antibiotic resistance in
Escherichia coli
was investigated using mutants with deletions of genes known to be involved in antibiotic resistance. The results indicate that
recA
, vital for the SOS response, plays a crucial role in the development of antibiotic resistance. Likewise, deletion of global transcriptional regulators, such as
gadE
or
soxS
, involved in pH homeostasis and superoxide removal, respectively, can slow the acquisition of resistance to a degree depending on the antibiotic. Deletion of the transcriptional regulator
soxS
, involved in superoxide removal, slowed the acquisition of resistance to enrofloxacin. Acquisition of resistance occurred at a lower rate in the presence of a second stress factor, such as a lowered pH or increased salt concentration, than in the presence of optimal growth conditions. The overall outcome suggests that a central cellular mechanism is crucial for the development of resistance and that genes involved in the regulation of transcription play an essential role. The actual cellular response, however, depends on the class of antibiotic in combination with environmental conditions.
Tailoring a Combination Preerythrocytic Malaria Vaccine
Authors: Bauza Karolis , Atcheson Erwan , Malinauskas Tomas , Blagborough Andrew M. , Reyes-Sandoval Arturo
Published: December 2015

The leading malaria vaccine candidate, RTS,S, based on thePlasmodium falciparumcircumsporozoite protein (CSP), will likely be the first publicly adopted malaria vaccine. However, this and other subunit vaccines, such as virus-vectored thrombospondin-related adhesive protein (TRAP), provide only intermediate to low levels of protection. In this study, thePlasmodium bergheihomologues of antigens CSP and TRAP are combined. TRAP is delivered using adenovirus- and vaccinia virus-based vectors in a prime-boost regime. Initially, CSP is also delivered using these viral vectors; however, a reduction of anti-CSP antibodies is seen when combined with virus-vectored TRAP, and the combination is no more protective than either subunit vaccine alone. Using an adenovirus-CSP prime, protein-CSP boost regime, however, increases anti-CSP antibody titers by an order of magnitude, which is maintained when combined with virus-vectored TRAP. This combination regime using protein CSP provided 100% protection in C57BL/6 mice compared to no protection using virus-vectored TRAP alone and 40% protection using adenovirus-CSP prime and protein-CSP boost alone. This suggests that a combination of CSP and TRAP subunit vaccines could enhance protection against malaria.
The C-Type Lectin Receptor MCL Mediates Vaccine-Induced Immunity against Infection with Blastomyces dermatitidis
Authors: Wang Huafeng , Li Mengyi , Lerksuthirat Tassanee , Klein Bruce , Wüthrich Marcel
Published: December 2015

C-type lectin receptors (CLRs) are essential in shaping the immune response to fungal pathogens. Vaccine-induced resistance requires Dectin-2 to promote differentiation of antifungal Th1 and Th17 cells. Since Dectin-2 and MCL heterodimerize and both CLRs use FcRγ as the signaling adaptor, we investigated the role of MCL in vaccine immunity to the fungal pathogen
Blastomyces dermatitidis
. MCL
−/−
mice showed impaired vaccine resistance against
B. dermatitidis
infection compared to that of wild-type animals. The lack of resistance correlated with the reduced recruitment of Th17 cells to the lung upon recall following experimental challenge and impaired interleukin-17 (IL-17) production by vaccine antigen-stimulated splenocytes
in vitro
. Soluble MCL fusion protein recognized and bound a water-soluble ligand from the cell wall of vaccine yeast, but the addition of soluble Dectin-2 fusion protein did not augment ligand recognition by MCL. Taken together, our data indicate that MCL regulates the development of vaccine-induced Th17 cells and protective immunity against lethal experimental infection with
B. dermatitidis
.
Stability of the GraA Antitoxin Depends on Growth Phase, ATP Level, and Global Regulator MexT
Authors: Tamman Hedvig , Ainelo Andres , Tagel Mari , Hõrak Rita
Published: December 2015

Bacterial type II toxin-antitoxin systems consist of a potentially poisonous toxin and an antitoxin that inactivates the toxic protein by binding to it. Most of the toxins regulate stress survival, but their activation depends on the stability of the antitoxin that has to be degraded in order for the toxin to be able to attack its cellular targets. The degradation of antitoxins is usually rapid and carried out by ATP-dependent protease Lon or Clp, which is activated under stress conditions. ThegraTAsystem ofPseudomonas putidaencodes the toxin GraT, which can affect the growth rate and stress tolerance of bacteria but is under most conditions inactivated by the unusually stable antitoxin GraA. Here, we aimed to describe the stability features of the antitoxin GraA by analyzing its degradation rate in total cell lysates ofP. putida. We show that the degradation rate of GraA depends on the growth phase of bacteria being fastest in the transition from exponential to stationary phase. In accordance with this, higher ATP levels were shown to stabilize GraA. Differently from other antitoxins, the main cellular proteases Lon and Clp are not involved in GraA stability. Instead, GraA seems to be degraded through a unique pathway involving an endoprotease that cleaves the antitoxin into two unequal parts. We also identified the global transcriptional regulator MexT as a factor for destabilization of GraA, which indicates that the degradation of GraA may be induced by conditions similar to those that activate MexT.

IMPORTANCEToxin-antitoxin (TA) modules are widespread in bacterial chromosomes and have important roles in stress tolerance. As activation of a type II toxin is triggered by proteolytic degradation of the antitoxin, knowledge about the regulation of the antitoxin stability is critical for understanding the activation of a particular TA module. Here, we report on the unusual degradation pathway of the antitoxin GraA of the recently characterized GraTA system. While GraA is uncommonly stable in the exponential and late-stationary phases, its degradation increases in the transition phase. The degradation pathway of GraA involves neither Lon nor Clp, which usually targets antitoxins, but rather an unknown endoprotease and the global regulator MexT, suggesting a new type of regulation of antitoxin stability.
Altering the Structure of Carbohydrate Storage Granules in the Cyanobacterium Synechocystis sp. Strain PCC 6803 through Branching-Enzyme Truncations
Authors: Welkie David G. , Lee Byung-Hoo , Sherman Louis A.
Published: December 2015

Carbohydrate storage is an important element of metabolism in cyanobacteria and in the chloroplasts of plants. Understanding how to manipulate the metabolism and storage of carbohydrate is also an important factor toward harnessing cyanobacteria for energy production. While most cyanobacteria produce glycogen, some have been found to accumulate polysaccharides in the form of water-insoluble α-glucan similar to amylopectin. Notably, this alternative form, termed “semi-amylopectin,” forms in cyanobacterial species harboring three branching-enzyme (BE) homologs, designated BE1, BE2, and BE3. In this study, mutagenesis of the branching genes found in
Synechocystis
sp. strain PCC 6803 was performed in order to characterize their possible impact on polysaccharide storage granule morphology. N-terminal truncations were made to the native BE gene of
Synechocystis
sp. PCC 6803. In addition, one of the two native debranching enzyme genes was replaced with a heterologous debranching enzyme gene from a semi-amylopectin-forming strain. Growth and glycogen content of mutant strains did not significantly differ from those of the wild type, and ultrastructure analysis revealed only slight changes to granule morphology. However, analysis of chain length distribution by anion-exchange chromatography revealed modest changes to the branched-chain length profile. The resulting glycogen shared structure characteristics similar to that of granules isolated from semi-amylopectin-producing strains.

IMPORTANCE
This study is the first to investigate the impact of branching-enzyme truncations on the structure of storage carbohydrates in cyanobacteria. The results of this study are an important contribution toward understanding the relationship between the enzymatic repertoire of a cyanobacterial species and the morphology of its storage carbohydrates.
The Use of Online Pre-Lab Assessments Compared with Written Pre-Lab Assignments Requiring Experimental Result Prediction Shows No Difference in Student Performance
Authors: Suchman Erica
Published: December 2015

Exam performance was compared for students who hand wrote questions designed to prepare them for daily lab activities in a senior level virology laboratory course versus those who answered questions created to mirror the written questions on-line. No significant difference was noted in exam scores on any of the three midterms, written final exam, nor the practical exam. Neither was there a significant difference in the quality of the laboratory reports turned in as evidenced by similar average scores over four years. These results indicate that using online pre-labs to prepare students for the laboratory sessions leads to equivalent learning as answering handwritten pre-lab assignments. Online pre-labs significantly reduced the amount of grading without reducing student learning, allowing a reduction in the number of teaching assistants required per section.
Self-Driven Service Learning: Community-Student-Faculty Collaboratives Outside of the Classroom
Authors: Segarra Verónica A. , DeLucia Alexandra A. , DeLucia Alyssa A. , Fonseca Renee , Penfold Michael P. , Sawyer Katlyn M. , Harold Cecelia M. , Reddig Courtney , Singh Ashima , Musri Ibrahim , Wright Jacqueline C. , Leissing J. J. , Dennis Samantha , Pflug Mary Catherine , Fogle Niki , Moore Monique , Sims Sade , Matteson Kelsey , Hein Meredith
Published: December 2015

Service learning is a community engagement pedagogy often used in the context of the undergraduate classroom to synergize course-learning objectives with community needs. We find that an effective way to catalyze student engagement in service learning is for student participation to occur outside the context of a graded course, driven by students’ own interests and initiative. In this paper, we describe the creation and implementation of a self-driven service learning program and discuss its benefits from the community, student, and faculty points of view. This experience allows students to explore careers in the sciences as well as identify skill strengths and weaknesses in an environment where mentoring is available but where student initiative and self-motivation are the driving forces behind the project’s success. Self-driven service learning introduces young scientists to the idea that their careers serve a larger community that benefits not only from their discoveries but also from effective communication about how these discoveries are relevant to everyday life.
Lifeguard Final Exam—Encouraging the Use of Active Learning
Authors: Griswold Elise N. , Klionsky Daniel J.
Published: December 2015

To anyone familiar with the extensive literature on teaching and learning, there is little question that active learning is more effective than passive learning. Thus, we are not directing this letter to that particular audience. Instead, we are attempting to address the question of the best way to convince instructors who have not tried to incorporate elements of active learning into their courses to make such an attempt. There are numerous examples where it becomes immediately clear that active learning is preferable to a lecture/note-taking approach. Here, we provide a question for group discussion that can be used as one such illustration.
A Comprehensive Review of Shiga Toxin-Producing
Escherichia coli
(STEC)Review of:
Enterohemorrhagic
Escherichia coli
and Other Shiga Toxin-Producing
E. coli; Vanessa Sperandio and Carolyn H. Hovde (ed.); (2015). ASM Press, Washington, DC. 553 pages.
Authors: Oliver Julie A.
Published: December 2015

Review of: Enterohemorrhagic Escherichia coli and Other Shiga Toxin-Producing E. coli; Vanessa Sperandio and Carolyn H. Hovde (ed.); (2015). ASM Press, Washington, DC. 553 pages.
PULSE Pilot Certification Results
Authors: Pape-Lindstrom Pamela , Jack Tom , Miller Kathy , Aguirre Karen , Awong-Taylor Judy , Balser Teri , Brancaccio-Taras Loretta , Marley Kate , Osgood Marcy , Peteroy-Kelly Marcy , Romano Sandra
Published: December 2015

The pilot certification process is an ambitious, nationwide endeavor designed to motivate important changes in life sciences education that are in line with the recommendations of the 2011 Vision and Change Report: A Call to Action (American Association for the Advancement of Science [AAAS], 2011). It is the goal of the certification process to acknowledge departments that have progressed towards full implementation of the tenets of Vision and Change and to motivate departments that have not begun to adopt the recommendations to consider doing so. More than 70 life science departments applied to be part of the pilot certification process, funded by a National Science Foundation grant, and eight were selected based on initial evidence of transformed and innovative educational practices. The programs chosen represent a wide variety of schools, including two-year colleges, liberal-arts institutions, regional comprehensive colleges, research universities and minority serving institutions. Outcomes from this pilot were released June 1, 2015 (www.pulsecommunity.org), with all eight programs being recognized as having progressed along a continuum of change. Five levels of achievement were defined as PULSE Pilot Progression Levels. Of the eight departments in the pilot, one achieved “PULSE Progression Level III: Accomplished”. Six departments achieved “PULSE Progression Level II: Developing” and one pilot department achieved “PULSE Progression Level I: Beginning”. All of the schools have made significant movement towards the recommendations of Vision and Change relative to a traditional life sciences curriculum. Overall, the response from the eight pilot schools has been positive.
Clarification to Points in “Correlating Student Knowledge and Confidence Using a Graded Knowledge Survey to Assess Student Learning in a General Microbiology Classroom”
Authors: Nuhfer Edward B.
Published: December 2015

This letter to the editor provides supplemental information to and clarifies the attribution of our work in Favazzo, L., J. D. Willford, and R. M. Watson. 2014. Correlating student knowledge and confidence using a graded knowledge survey to assess student learning in a general microbiology classroom. J. Microbiol. Biol. Educ. 15(2):251-258. [Online.] http://jmbe.asm.org/index.php/jmbe/article/view/693/html_178. Accessed 9 July 2015.
Variation in paediatric hospital antibiotic guidelines in Europe
Authors: Spyridis N , Syridou G , Goossens H , Versporten A , Kopsidas J , Kourlaba G , Bielicki J , Drapier N , Zaoutis T , Tsolia M , Sharland M
Published: December 2015

Objective

To assess the availability and source of guidelines for common infections in European paediatric hospitals and determine their content and characteristics.

Design

Participating hospitals completed an online questionnaire on the availability and characteristics of antibiotic prescribing guidelines and on empirical antibiotic treatment including duration of therapy for 5 common infection syndromes: respiratory tract, urinary tract, skin and soft tissue, osteoarticular and sepsis in neonates and children.

Results

84 hospitals from 19 European countries participated in the survey of which 74 confirmed the existence of guidelines. Complete guidelines (existing guidelines for all requested infection syndromes) were reported by 20% of hospitals and the majority (71%) used a range of different sources. Guidelines most commonly available were those for urinary tract infection (UTI) (74%), neonatal sepsis (71%) and sepsis in children (65%). Penicillin and amoxicillin were the antibiotics most commonly recommended for respiratory tract infections (RTIs) (up to 76%), cephalosporin for UTI (up to 50%) and for skin and soft tissue infection (SSTI) and bone infection (20% and 30%, respectively). Antistaphylococcal penicillins were recommended for SSTIs and bone infections in 43% and 36%, respectively. Recommendations for neonatal sepsis included 20 different antibiotic combinations. Duration of therapy guidelines was mostly available for RTI and UTI (82%). A third of hospitals with guidelines for sepsis provided recommendations for length of therapy.

Conclusions

Comprehensive antibiotic guideline recommendations are generally lacking from European paediatric hospitals. We documented multiple antibiotics and combinations for most infections. Considerable improvement in the quality of guidelines and their evidence base is required, linking empirical therapy to resistance rates.
THE ONTOGENY OF P-GLYCOPROTEIN IN THE DEVELOPING HUMAN BLOOD BRAIN BARRIER: IMPLICATION FOR OPIOID TOXICITY IN NEONATES
Authors: Koren Gideon , Lam Jessica , Kelly Lauren , Baella Stephanie , Chitayat David , Shannon Patrick , Matthews Stephen
Published: December 2015

Neonates have been shown to have a heightened sensitivity to the central depressive effects of opioids compared to older infants and adults. The limited development of P-glycoprotein (P-gp), located on the luminal membrane of the brain endothelial cells, may limit the ability of the neonate to efflux morphine from the brain back to the systemic circulation. Presently, little is known about blood brain barrier P-gp expression during human development. The objective of the study was to determine the ontogeny of P-gp in the human BBB. Postmortem cortex samples from gestational age (GA) 20–26 weeks, GA 36–40 weeks, postnatal age (PNA) 0–3 months, PNA 3–6 months, and adults were immunostained for P-gp. Analysis was carried out by spinning disc confocal microscopy. The intensity of P-gp staining in adults was significantly higher compared to at GA 20–26 weeks (p=0.0002), GA 36–40 weeks (p=0.0002), and PNA 0–3 months (p=0.0044). P-gp intensity at GA 20–26 weeks (p=0.0011), GA 36–40 weeks (p=0.0013), and PNA 0–3 months (p=0.0173) was significantly lower compared to at PNA 3–6 months. P-gp expression in the BBB is limited at birth, increases with postnatal maturation, and reaches adult levels at approximately 3–6 months of age. Given the immaturity of BBB P-gp after birth, morphine may concentrate in the brain. This provides mechanistic support to life threatening opioid toxicity seen with maternal codeine use during breastfeeding.
PERSONALIZATION OF 6-MERCAPTOPURINE THERAPY FOR CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Milošević Goran , Dokmanović Lidija , Krstovski Nada , Lazić Jelena , Rodić Predrag , Pavlović Sonja , Zukić Branka , Kotur Nikola , Janić Dragana
Published: December 2015

Introduction

Treatment of acute lymphoblastic leukemia (ALL) in children has been significantly improved over past few decades. Optimal use of known antileukemic drugs has lead to four-fold increase of overall survival. Nevertheless, therapy failure occurs in 15–20% of patients. Individualized use of cytostatic drugs can help us reducing toxicity-related deaths and improve therapy outcome.

Materials and methods

We studied multidrug resistance protein 4 gene (ABCC4) and inosin triphosphate pyrophosphatase (ITPA) gene polymorphisms to assess their influence on occurrence and intensity of 6-MP toxicity during maintenance phase of ALL treatment in children as well as on treatment outcome.

Results

Thiopurine S-methyltransferase (TPMT) genotype was known for all patients before start of therapy and doses were adjusted accordingly. Five patients (7%) were carriers of ITPAc.94C>A genotype. Heterozygote and homozygote carriers of variant alleles for ABCC4 rs9516519 T>G, genotype were represented in 35% and 4% of our patients, respectively. We did not show correlation of variant alleles with increased number of off-therapy weeks neither with number of episodes of leukopenia. Cross-validated AUC for each of genetic markers individually showed low predictive power (cross-validated AUC around 0.5) for predicting toxicity. However, combination of two genetic markers and known TPMT gentotype improved the predictability (cross-validated AUC was 0.65).

Conclusions

Our results did not show correlation with toxicity using individual genetic markers. However, in the settings of known TPMT genotype, we showed the potential of using all three genetic markers (including TPMT) in predicting who might be in danger of having increased toxicity.
EUROPEAN PAEDIATRIC ONCOLOGY OFF-PATENT MEDICINES CONSORTIUM (EPOC): A PHARMACOKINETIC STUDY OF DOXORUBICIN IN CHILDREN WITH CANCER
Authors: Krischke Miriam , Boddy Alan V , Hempel Georg , Völler Swantje , André Nicolas , D'Incalci Mauricio
Published: December 2015

Background

Doxorubicin is a key component of a number of treatment regimens used in paediatric oncology. The pharmacology data on which current dosing regimens are based are very limited.

Methods

We conducted a multicentre, multinational pharmacokinetic study investigating age-dependency in the clearance of doxorubicin in children with solid tumours and leukaemia. Blood samples for measurement of doxorubicin and its metabolite doxorubicinol were collected after 2 administrations, with 5 samples collected in children 3 yrs. A population pharmacokinetic approach was used for analysis, including pharmacogenetic covariates. NT-proBNP and cardiac troponin T were measured to evaluate their role as early indicators of cardiotoxicity.

Results

101 children could be recruited including 27 patients less than 3 years and among those 5 infants younger than 1 year. Overall, the patient acceptance of the trial was very good.

Age dependence of doxorubicin clearance was demonstrated, with children less than 3 years having a lower clearance (21.1±5.8 l/h/m2) than older children (26.6±6.7 l/h/m2) (p=0.0004), after correcting for body weight. Pharmacogenetic variants, including those in transporters and drug metabolizing enzymes, had little influence on pharmacokinetic parameters.

Natriuretic peptides plasma levels increased significantly shortly after doxorubicin administration, whereas cardiac troponin levels increased only with the administered cumulative anthracycline dose. Only limited correlation could be observed between their blood levels and doxorubicin pharmacokinetics.

Conclusion

The paediatric need concerning missing PK-data could be addressed with limited burden for the patients. Empirically used dose adaptations for infants were found to be justified based on our PK analyses.