bluuebunny/crossref_metadata_2025 huggingface dataset:
Photogrammetric Record Template
Authors: Author Arthur , Author Maria J. , Author S.
Published: December 2015

This is an example of an original article in the layout expected by The Photogrammetric Record. The abstract is a concise summary of the essential elements of the paper, and should not contain detailed results. It should be no longer than 170 words. This template indicates how a paper submitted to the journal should be structured and formatted, including figures, tables, mathematics and references.
Phylogenetic relationships of Acronictinae with discussion of the abdominal courtship brush in Noctuidae (Lepidoptera)
Authors: ROTA JADRANKA , ZACHARCZENKO BRIGETTE V. , WAHLBERG NIKLAS , ZAHIRI REZA , SCHMIDT B. C. , WAGNER DAVID L.
Published: December 2015

We present results of an eight‐gene molecular study of the subfamily Acronictinae and related Noctuidae. Amphipyrinae are recovered as sister to Acronictinae, but with weak support – not surprisingly, the content of the two subfamilies has often been mixed in classifications. Balsinae, previously placed near Acronictinae or within Noctuinae, is recovered within an unresolved polytomy of Cuculliinae, Eustrotiinae, Raphiinae and Dilobinae. Gerbathodes Warren, Moma Hübner and Nacna Fletcher are excluded from Acronictinae. Three genera recently transferred into the subfamily – Cerma Hübner, Chloronycta Schmidt & Anweiler and Comachara Franclemont – are confirmed as acronictines. Lophonycta Sugi (the type genus of Lophonyctinae) is returned to the Acronictinae. Sinocharis Püngeler, formerly considered to be Acontiinae or as the basis of its own subfamily Sinocharinae, is nested within early diverging Acronictinae genera. Both subfamilies are formally synonymized: i.e. Lophonyctinae syn.n. and Sinocharinae syn.n. Nine acronictine genus‐level taxa were found to nest within the nominate genus Acronicta Ochsenheimer: Eogena Guenée, Hyboma Hübner, Hylonycta Sugi, Jocheaera Hübner, Oxicesta Hübner, Simyra Ochsenheimer, Subacronicta Kozhanchikov, Triaena Hübner, and Viminia Chapman. Eogena, Oxicesta, and Simyra, currently treated as valid genera, nest within terminal clades of the genus Acronicta and are here subsumed within the genus: Eogena syn.n., Oxicesta syn.n. and Simyra syn.n. Four well‐supported species groups within Acronicta are identified: the alni clade, the leporina clade, the nervosa clade and the psi clade. While many previous treatments have stated explicitly that Acronictinae lack abdominal scent brushes, or excluded genera with brushes from the subfamily, we show that well‐developed brushes are present in three early diverging acronictine genera: Cerma, Lophonycta, and Sinocharis. We illustrate and describe the brushes of all three genera, and briefly review the taxonomic distribution of the anterior abdominal courtship brushes in Noctuidae, emphasizing the labile evolutionary distribution of these structures.
Serial testing for latent tuberculosis infection in transplant candidates: a retrospective review
Authors: Roth P.J. , Grim S.A. , Gallitano S. , Adams W. , Clark N.M. , Layden J.E.
Published: December 2015

Background

Accurately identifying latent tuberculosis (TB) infection (LTBI) in liver and renal transplant candidates is important because of the risks associated with both treatment of LTBI and reactivation of disease in this population. Many programs advocate yearly screening of patients awaiting organ transplantation. The reproducibility of serial interferon‐gamma release assay (IGRA) testing in transplant candidates has not been studied.

Methods

We conducted a retrospective longitudinal study of patients listed for liver or kidney transplantation between January 1, 2005 and February 1, 2012 at the University of Illinois Medical Center at Chicago. Data collected included demographics, transplant type, IGRA results, treatment received, and mortality.

Results

The study population was comprised of 795 adults; 79 (10%) had at least 1 indeterminate result; indeterminate results were less common in men (P = 0.01) and more common in liver transplant candidates (P < 0.001). The reversion frequency was 27% with a rate of 158.1 reversions in 1000 person‐years. A higher magnitude of initial TB response values was predictive of consistently positive results (P < 0.001). The conversion frequency was 15% with a rate of 82.6 conversions in 1000 person‐years. Among those who converted, the values of the IGRA varied, with 48% having a TB response of <1 IU/mL, 41% 1–5 IU/mL, and only 10% >5 IU/mL.

Conclusions

A significant number of conversions and reversions occur during serial IGRA testing of transplant candidates. Delineating true‐positive converters from false‐positives is an issue that warrants further study.
The c.64_80del SMIM1 allele is segregating in the Hutterite population
Authors: Coghlan Gail , Zelinski Teresa
Published: December 2015

BACKGROUND

The high‐incidence red blood cell (RBC) antigen Vel is coded by SMIM1 (small‐membrane molecule 1 gene), where a homozygous 17 base pair deletion underlies the majority of Vel− phenotypes. Because anti‐Vel has been reported to cause severe hemolytic transfusion reactions and periodically hemolytic disease of the newborn and fetus, identification of individuals negative for Vel is clinically important.

STUDY DESIGN AND METHODS

RBCs from the members of a large three‐generation Hutterite family were serologically determined to be Vel+w. Genomic DNA from these family members was polymerase chain reaction amplified and analyzed for SMIM1 polymorphisms by either Sanger sequencing or restriction fragment length polymorphisms. SMIM1 genotyping was also conducted on DNA from an additional 104 Hutterites.

RESULTS

All family members whose RBCs weakly expressed the Vel antigen were found to be heterozygous for the c.64_80del mutation in SMIM1. Of the 104 additional Hutterite samples, four were found to be heterozygous for the same SMIM1 mutation.

CONCLUSION

After emigrating to the United States and Canada, the Hutterite population has expanded dramatically. Alleles that initially entered the population have been maintained within the population. The c.64_80del null allele of SMIM1 is one such allele, thus having implications for transfusion medicine and child or maternal health.
IL‐31‐induced pruritus in dogs: a novel experimental model to evaluate anti‐pruritic effects of canine therapeutics
Authors: Gonzales Andrea J. , Fleck Timothy J. , Humphrey William R. , Galvan Betsy A. , Aleo Michelle M. , Mahabir Sean P. , Tena Jezaniah‐Kira , Greenwood Karen G. , McCall Robert B.
Published: December 2015

Background

Pruritus is a characteristic clinical sign of allergic skin conditions including atopic dermatitis (AD) in the dog. IL‐31 is a cytokine found in the serum of some dogs with AD and can induce pruritic behaviours in laboratory beagle dogs.

Hypothesis/Objectives

The objectives were to characterize an IL‐31‐induced pruritus model by evaluating the efficacy of prednisolone, dexamethasone and oclacitinib, and to compare the speed of anti‐pruritic effects of oclacitinib against those of prednisolone and dexamethasone.

Animals

Purpose‐bred beagle dogs were used in all studies.

Methods

Randomized, blinded, placebo‐controlled studies were designed to evaluate and compare the anti‐pruritic properties of prednisolone, dexamethasone and oclacitinib following a single intravenous injection of recombinant canine IL‐31. Video surveillance was used to monitor and score pruritic behaviours in study animals.

Results

Prednisolone [0.5 mg/kg, per os (p.o.)] reduced IL‐31‐induced pruritus when given 10 h prior to observation. When the time interval between drug treatment and observation was shortened to 1 h, dexamethasone (0.2 mg/kg, intramuscular) but not prednisolone (0.25 or 0.5 mg/kg, p.o.) reduced IL‐31‐induced pruritus. Oclacitinib (0.4 mg/kg, p.o.) reduced pruritus when given 1, 6, 11 and 16 h prior to the observation period, and the anti‐pruritic activity of oclacitinib was greater when compared to prednisolone and dexamethasone at all time points assessed.

Conclusion and clinical importance

The efficacy of prednisolone, dexamethasone and oclacitinib in the IL‐31‐induced pruritus model gives confidence that this may be a relevant model for acute pruritus associated with allergic dermatitis including AD and can be used to evaluate novel compounds or formulations.
ToF-SIMS multivariate analysis of surface-grafted small bioactive molecules
Authors: Jasieniak Marek , Coad Bryan R. , Griesser Hans J.
Published: December 2015

In the development of bioactive coatings on biomaterials, it is essential to characterize the successful fabrication and the uniformity of intended coatings by sensitive surface analytical techniques, so as to ensure reliable interpretation of observed biointerfacial responses. This can, however, be challenging when small bioactive molecules are grafted onto biomaterials surfaces at sub- and near-monolayer densities. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) provides the required sensitivity, but ion signals from small grafted molecules may still be dominated by fragment ions from the underlying polymer. In such cases, multivariate analysis provides valuable enhancement of spectral data, as illustrated here by examples comprising the surface grafting of bioactive serrulatane molecules, the peptide GRGDSP, the oligonucleotide 15-thymidine, and the antifungal compound Amphotericin B. The authors also show how ToF-SIMS plus principal component analysis can distinguish between covalent grafting and physisorption of the antibiotics caspofungin and micafungin.
Low-temperature SiON films deposited by plasma-enhanced atomic layer deposition method using activated silicon precursor
Authors: Suh Sungin , Ryu Seung Wook , Cho Seongjae , Kim Jun-Rae , Kim Seongkyung , Hwang Cheol Seong , Kim Hyeong Joon
Published: December 2015

It has not been an easy task to deposit SiN at low temperature by conventional plasma-enhanced atomic layer deposition (PE-ALD) since Si organic precursors generally have high activation energy for adsorption of the Si atoms on the Si-N networks. In this work, in order to achieve successful deposition of SiN film at low temperature, the plasma processing steps in the PE-ALD have been modified for easier activation of Si precursors. In this modification, the efficiency of chemisorption of Si precursor has been improved by additional plasma steps after purging of the Si precursor. As the result, the SiN films prepared by the modified PE-ALD processes demonstrated higher purity of Si and N atoms with unwanted impurities such as C and O having below 10 at. % and Si-rich films could be formed consequently. Also, a very high step coverage ratio of 97% was obtained. Furthermore, the process-optimized SiN film showed a permissible charge-trapping capability with a wide memory window of 3.1 V when a capacitor structure was fabricated and measured with an insertion of the SiN film as the charge-trap layer. The modified PE-ALD process using the activated Si precursor would be one of the most practical and promising solutions for SiN deposition with lower thermal budget and higher cost-effectiveness.
Algal toxin impairs sea lion memory and hippocampal connectivity, with implications for strandings
Authors: Cook Peter F. , Reichmuth Colleen , Rouse Andrew A. , Libby Laura A. , Dennison Sophie E. , Carmichael Owen T. , Kruse-Elliott Kris T. , Bloom Josh , Singh Baljeet , Fravel Vanessa A. , Barbosa Lorraine , Stuppino Jim J. , Van Bonn William G. , Gulland Frances M. D. , Ranganath Charan
Published: December 2015

Red tides make dinner hard to find

Domoic acid (DA) is a neurotoxin produced by marine algae. When present in large amounts, it is harmful to marine organisms and to humans. Cook
et al.
tested California sea lions being treated at a marine mammal rescue facility. Animals that had evidence of exposure to DA had lesions in their hippocampus and displayed reduced performance on spatial memory tasks. Because such tasks are essential to foraging in a marine environment, increasing exposure to DA may be contributing to increasing sea lion strandings.

Science
, this issue p.
1545
Aging: All in the head—and the gut
Authors: Ray L. Bryan
Published: December 2015

Two life-span–extending pathways in the worm converge to increase production of an enzyme in the intestine.
Evolution of Resistance to Continuously Increasing Streptomycin Concentrations in Populations of Escherichia coli
Authors: Spagnolo Fabrizio , Rinaldi Conrad , Sajorda Dannah Rae , Dykhuizen Daniel E.
Published: December 2015

The evolution of antibiotic resistance in bacteria has become one of the defining problems in modern biology. Bacterial resistance to antimicrobial therapy threatens to eliminate one of the pillars of the practice of modern medicine. Yet, in spite of the importance of this problem, only recently have the dynamics of the shift from antibiotic sensitivity to resistance in a bacterial population been studied. In this study, a novel chemostat method was used to observe the evolution of resistance to streptomycin in a sensitive population of
Escherichia coli
, which grew while the concentration of antibiotic was constantly increasing. The results indicate that resistant mutants remain at a low frequency for longer than expected and do not begin to rise to a high frequency until the antibiotic concentrations are above the measured MIC, creating a “lull period” in which there were few bacterial cells growing in the chemostats. Overall, mutants resistant to streptomycin were found in >60% of the experimental trial replicates. All of the mutants detected were found to have MICs far above the maximum levels of streptomycin to which they were exposed and reached a high frequency within 96 h.
Complete Sequence of a Novel IncR-F33:A–:B– Plasmid, pKP1034, Harboring
fosA3
,
bla
KPC-2
,
bla
CTX-M-65
,
bla
SHV-12
, and
rmtB
from an Epidemic Klebsiella pneumoniae Sequence Type 11 Strain in China
Authors: Xiang Dai-Rong , Li Jun-Jie , Sheng Zi-Ke , Yu Hai-Ying , Deng Mei , Bi Sheng , Hu Fei-Shu , Chen Wei , Xue Xiao-Wei , Zhou Zhi-Bo , Doi Yohei , Sheng Ji-Fang , Li Lan-Juan
Published: December 2015

A high fosfomycin resistance rate was observed in
Klebsiella pneumoniae
carbapenemase (KPC)-producing
K. pneumoniae
(KPC-KP) in our previous study, but little is known about its mechanisms. In this study, we explored the prevalence of plasmid-mediated fosfomycin resistance determinants among fosfomycin-resistant KPC-KP strains from a Chinese university hospital and determined the complete sequence of a novel
fosA3
-carrying plasmid isolated from an epidemic
K. pneumoniae
sequence type (ST) 11 strain. A total of 97 KPC-KP strains were studied, of which 57 (58.8%) were resistant to fosfomycin, including 44 (45.4%) harboring
fosA3
and 1 harboring
fosA
. All
fosA3
-positive strains belonged to the dominant ST11-pulse type (PT) A clone according to multilocus sequence typing and pulsed-field gel electrophoresis, suggesting clonal dissemination. The
fosA
-positive isolate belonged to ST11-PTE. The
fosA3
-carrying plasmid pKP1034 is 136,848 bp in length and is not self-transmissible. It is a multireplicon plasmid belonging to IncR-F33:A−: B−. Besides
fosA3
, a variety of other resistance determinants, including
bla
KPC-2
,
rmtB
,
bla
CTX-M-65
, and
bla
SHV-12
, are identified in pKP1034, which would allow for coselection of
fosA3
by most β-lactams and/or aminoglycosides and facilitate its dissemination despite limited use of fosfomycin in China. Detailed comparisons with related plasmids revealed that pKP1034 is highly mosaic and might have evolved from alarming recombination of the
bla
KPC-2
-carrying plasmid pKPC-LK30 from Taiwan and the epidemic
fosA3
-carrying plasmid pHN7A8 from mainland China.
In Vitro
Activity of Retapamulin and Antimicrobial Susceptibility Patterns in a Longitudinal Collection of Methicillin-Resistant Staphylococcus aureus Isolates from a Veterans Affairs Medical Center
Authors: Harrington Amanda T. , Black Jennifer A. , Clarridge Jill E.
Published: December 2015

Mupirocin is a topical antimicrobial used to decolonize patients who carry methicillin-resistant
Staphylococcus aureus
(MRSA), and the topical agent retapamulin may be a potential alternative therapy. The goal of this study was to determine the
in vitro
activity of retapamulin as well as a panel of 15 antimicrobial agents, including mupirocin, for 403 MRSA isolates collected longitudinally from a naive population at the Veterans Affairs Puget Sound Health Care System. The MICs for retapamulin had a unimodal distribution, ranging from 0.008 to 0.5 μg/ml. One isolate had an MIC of >16 μg/ml, was also resistant to clindamycin and erythromycin, and was recovered from the nares of a patient undergoing hemodialysis. Twenty-four isolates (6%) and 11 isolates (3%) demonstrated low-level resistance (MICs of 8 to 64 μg/ml) and high-level resistance (MICs of ≥512 μg/ml), respectively, to mupirocin. Isolates were recovered from 10 patients both before and after mupirocin therapy. Of those, isolates from 2 patients demonstrated MIC changes postmupirocin therapy; in both cases, however, strain typing demonstrated that the pre- and postmupirocin strains were different. A total of 386 isolates (96%) had vancomycin MICs of ≤1.0 μg/ml; 340 isolates (84%) were resistant to levofloxacin, 18 isolates (4.5%) were resistant to trimethoprim-sulfamethoxazole, and 135 isolates (33%) had elevated MICs of 4 μg/ml for linezolid. The baseline levels of resistance were low for mupirocin (9%) and even lower for retapamulin (0.25%) Although the use of mupirocin is currently the standard therapy for decolonization practices, the activity of retapamulin warrants its consideration as an alternative therapy in MRSA decolonization regimens.
Novel Bone-Targeting Agent for Enhanced Delivery of Vancomycin to Bone
Authors: Albayati Zaineb A. F. , Sunkara Manjula , Schmidt-Malan Suzannah M. , Karau Melissa J. , Morris Andrew J. , Steckelberg James M. , Patel Robin , Breen Philip J. , Smeltzer Mark S. , Taylor K. Grant , Merten Kevyn E. , Pierce William M. , Crooks Peter A.
Published: December 2015

We examined the pharmacokinetic properties of vancomycin conjugated to a bone-targeting agent (BT) with high affinity for hydroxyapatite after systemic intravenous administration. The results confirm enhanced persistence of BT-vancomycin in plasma and enhanced accumulation in bone relative to vancomycin. This suggests that BT-vancomycin may be a potential carrier for the systemic targeted delivery of vancomycin in the treatment of bone infections, potentially reducing the reliance on surgical debridement to achieve the desired therapeutic outcome.
Defining Clinical Exposures of Cefepime for Gram-Negative Bloodstream Infections That Are Associated with Improved Survival
Authors: Rhodes Nathaniel J. , Kuti Joseph L. , Nicolau David P. , Van Wart Scott , Nicasio Anthony M. , Liu Jiajun , Lee Benjamin J. , Neely Michael N. , Scheetz Marc H.
Published: December 2015

The percentage of time that free drug concentrations remain above the MIC (
f
T
>MIC
) that is necessary to prevent mortality among cefepime-treated patients with Gram-negative bloodstream infections (GNBSI) is poorly defined. We conducted a retrospective study of adult patients with GNBSI. Eligible cases were frequency matched to ensure categorical representation from all MICs. Organism, MIC, infection source, gender, age, serum creatinine, weight, antibiotic history, and modified APACHE II score were collected from hospital records. Two population pharmacokinetic models (models 1 and 2) were used to impute exposures over the first 24 h in each patient from mean model parameters, covariates, and dosing history. From the imputed exposures, survival thresholds for
f
T
>MIC
were identified using classification and regression tree (CART) analysis and analyzed as nominal variables for univariate and multivariate regressions. A total of 180 patients were included in the analysis, of whom 13.9% died and 86.1% survived. Many patients (46.7% [
n
= 84/180]) received combination therapy with cefepime. Survivors had higher mean (standard deviation [SD])
f
T
>MIC
than those who died (model 1, 74.2% [29.6%] versus 52.1% [33.8%],
P
< 0.001; model 2, 85.9% [24.0%] versus 64.4% [31.4%],
P
< 0.001). CART identified
f
T
>MIC
threshold values for greater survival according to models 1 and 2 at >68% and >74%, respectively. Survival was improved for those with
f
T
>MIC
of >68% (model 1 adjusted odds ratio [aOR], 7.12; 95% confidence interval [CI], 1.90 to 26.7;
P
= 0.004) and >74% (model 2 aOR, 6.48; 95% CI, 1.90 to 22.1) after controlling for clinical covariates. Similarly, each 1% increase in cefepime
f
T
>MIC
resulted in a 2% improvement in multivariate survival probability (
P
= 0.015). Achieving a cefepime
f
T
>MIC
of 68 to 74% was associated with a higher odds of survival for patients with GNBSI. Regimens targeting this exposure should be aggressively pursued.
Clinical and Molecular Features of Decreased Chlorhexidine Susceptibility among Nosocomial Staphylococcus aureus Isolates at Texas Children's Hospital
Authors: McNeil J. Chase , Kok Eric Y. , Vallejo Jesus G. , Campbell Judith R. , Hulten Kristina G. , Mason Edward O. , Kaplan Sheldon L.
Published: December 2015

One of the strategies utilized to decrease infections in the hospital setting relies on topical antimicrobials and antiseptics. While their use is beneficial, concerns arise over the potential to develop resistance or tolerance to these agents. We examined nosocomial
Staphylococcus aureus
isolates from 2007 to 2013 for the presence of genes associated with tolerance to chlorhexidine. Isolates and patients were identified from an
S. aureus
surveillance study at Texas Children's Hospital. Nosocomial
S. aureus
isolates (those causing infection at ≥72 h of hospitalization) were identified and underwent PCR for the
qacA
or
qacB
(
qacA/B
) and
smr
genes associated with elevated minimum bactericidal concentrations of chlorhexidine. Molecular typing with pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and
agr
typing and a review of the medical record were performed. Two hundred forty-seven nosocomial
S. aureus
infections were identified. Overall, 111 isolates carried one or both genes (44.9%); 33.1% were positive for
smr
, 22.7% were positive for
qacA/B
, and 10.9% of the isolates possessed both genes. The
smr
-positive isolates were more often resistant to methicillin, ciprofloxacin, and/or clindamycin. The isolates positive for
qacA/B
were more often associated with indwelling central venous catheters and a vancomycin MIC of ≥2 μg/ml. Isolates carrying either
smr
or
qacA/B
were associated with a diagnosis of bacteremia. The
smr
-positive isolates more often belonged to sequence type 8 (ST8) than the isolates that were positive for
qacA/B
. Mupirocin resistance was detected in 2.8% of the isolates. Antiseptic-tolerant
S. aureus
strains are common in our children's hospital and are associated with decreased susceptibility to other systemic antimicrobials and with bloodstream infections. Further work is needed to understand the implications that these organisms have on the hospital environment and antiseptic use in the future.
In Vivo
Pharmacodynamics of Cefquinome in a Neutropenic Mouse Thigh Model of Streptococcus suis Serotype 2 at Varied Initial Inoculum Sizes
Authors: Guo Chunna , Liao Xiaoping , Wang Mingru , Wang Feng , Yan Chaoqun , Xiao Xia , Sun Jiang , Liu Yahong
Published: December 2015

Streptococcus suis
serotype 2 is an emerging zoonotic pathogen and causes severe disease in both pigs and human beings. Cefquinome (CEQ), a fourth-generation cephalosporin, exhibits broad-spectrum activity against Gram-positive bacteria such as
S. suis
. This study evaluated the
in vitro
and
in vivo
antimicrobial activities of CEQ against four strains of
S. suis
serotype 2 in a murine neutropenic thigh infection model. We investigated the effect of varied inoculum sizes (10
6
to 10
8
CFU/thigh) on the pharmacokinetic (PK)/pharmacodynamic (PD) indices and magnitudes of a particular PK/PD index or dose required for efficacy. Dose fractionation studies included total CEQ doses ranging from 0.625 to 640 mg/kg/24 h. Data were analyzed via a maximum effect (
E
max
) model using nonlinear regression. The PK/PD studies demonstrated that the percentage of time that serum drug levels were above the MIC of free drug (%ƒ
T
>MIC
) in a 24-h dosing interval was the primary index driving the efficacy of both inoculum sizes (
R
2
= 91% and
R
2
= 63%). CEQ doses of 2.5 and 40 mg/kg body weight produced prolonged postantibiotic effects (PAEs) of 2.45 to 8.55 h. Inoculum sizes had a significant influence on CEQ efficacy. Compared to the CEQ exposure and dosages in tests using standard inocula, a 4-fold dose (
P
= 0.006) and a 2-fold exposure time (
P
= 0.01) were required for a 1-log kill using large inocula of 10
8
CFU/thigh.
Activity of Eravacycline against Escherichia coli Clinical Isolates Collected from U.S. Veterans in 2011 in Relation to Coresistance Phenotype and Sequence Type 131 Genotype
Authors: Johnson James R. , Porter Stephen B. , Johnston Brian D. , Thuras Paul
Published: December 2015

Eravacycline is a novel broad-spectrum fluorocycline with potent Gram-negative activity, including for multidrug-resistant strains. Among 472
Escherichia coli
clinical isolates from 24 Veterans Affairs medical centers (in 2011), divided equally as susceptible versus resistant to fluoroquinolones, broth microdilution eravacycline MICs were distributed unimodally, ranging from 0.03 to 1.0 μg/ml (MIC
50
of 0.125 μg/ml, MIC
90
of 0.25 μg/ml). Eravacycline MICs were ∼2-fold higher among fluoroquinolone-resistant, gentamicin-resistant, multidrug-resistant, and sequence type 131 (ST131) isolates (
P
< 0.01 for each comparison).
The
IL17F
and
IL17RA
Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations
Authors: Marquet Sandrine , Conte Ianina , Poudiougou Belco , Argiro Laurent , Cabantous Sandrine , Dessein Hélia , Burté Florence , Oumar Aboubacar A. , Brown Biobele J. , Traore Abdoualye , Afolabi Nathaniel K. , Barry Abdoulaye , Omokhodion Samuel , Ndoumbe Ursule Ewanda , Shokunbi Wuraola A. , Sodeinde Olugbemiro , Doumbo Ogobara , Fernandez-Reyes Delmiro , Dessein Alain J.
Published: December 2015

Cerebral malaria (CM) is a neurological complication of infection with
Plasmodium falciparum
that is partly caused by cytokine-mediated inflammation. It is not known whether interleukin-17 (IL-17) cytokines, which regulate inflammation, control the development of CM. To evaluate the involvement of IL-17 cytokines in CM, we analyzed 46 common polymorphisms in
IL17A
,
IL17F
, and
IL17RA
(which encodes the common receptor chain of the members of the IL-17 family) in two independent African populations. A case-control study involving 115 Nigerian children with CM and 160 controls from the community (CC) showed that
IL17F
reference single nucleotide polymorphism (SNP) 6913472 (rs6913472) (
P
= 0.004; odds ratio [OR] = 3.12),
IL17F
rs4715291 (
P
= 0.004; OR = 2.82),
IL17RA
rs12159217 (
P
= 0.01; OR = 2.27), and
IL17RA
rs41396547 (
P
= 0.026; OR = 3.15) were independently associated with CM. A replication study was performed in 240 nuclear Malian family trios (two parents with one CM child). We replicated the association for 3 SNPs,
IL17F
rs6913472 (
P
= 0.03; OR = 1.39),
IL17RA
rs12159217 (
P
= 0.01; OR = 1.52), and
IL17RA
rs41396547 (
P
= 0.04; OR = 3.50). We also found that one additional SNP,
IL17RA
rs41433045, in linkage disequilibrium (LD) with rs41396547, was associated with CM in both Nigeria and Mali (
P
= 0.002; OR = 4.12 in the combined sample). We excluded the possibility that SNPs outside
IL17F
and
IL17RA
, in strong LD with the associated SNPs, could account for the observed associations. Furthermore, the results of a functional study indicated that the aggravating GA genotype of
IL17F
rs6913472 was associated with lower IL-17F concentrations. Our findings show for the first time that
IL17F
and
IL17RA
polymorphisms modulate susceptibility to CM and provide evidence that IL-17F protects against CM.
Network of Surface-Displayed Glycolytic Enzymes in Mycoplasma pneumoniae and Their Interactions with Human Plasminogen
Authors: Gründel Anne , Pfeiffer Melanie , Jacobs Enno , Dumke Roger
Published: December 2015

In different bacteria, primarily cytosolic and metabolic proteins are characterized as surface localized and interacting with different host factors. These moonlighting proteins include glycolytic enzymes, and it has been hypothesized that they influence the virulence of pathogenic species. The presence of surface-displayed glycolytic enzymes and their interaction with human plasminogen as an important host factor were investigated in the genome-reduced and cell wall-less microorganism
Mycoplasma pneumoniae
, a common agent of respiratory tract infections of humans. After successful expression of 19 glycolytic enzymes and production of polyclonal antisera, the localization of proteins in the mycoplasma cell was characterized using fractionation of total proteins, colony blot, mild proteolysis and immunofluorescence of
M. pneumoniae
cells. Eight glycolytic enzymes, pyruvate dehydrogenases A to C (PdhA-C), glyceraldehyde-3-phosphate dehydrogenase (GapA), lactate dehydrogenase (Ldh), phosphoglycerate mutase (Pgm), pyruvate kinase (Pyk), and transketolase (Tkt), were confirmed as surface expressed and all are able to interact with plasminogen. Plasminogen bound to recombinant proteins PdhB, GapA, and Pyk was converted to plasmin in the presence of urokinase plasminogen activator and plasmin-specific substrate
d
-valyl-leucyl-lysine-
p
-nitroanilide dihydrochloride. Furthermore, human fibrinogen was degraded by the complex of plasminogen and recombinant protein PdhB or Pgm. In addition, surface-displayed proteins (except PdhC) bind to human lung epithelial cells, and the interaction was reduced significantly by preincubation of cells with antiplasminogen. Our results suggest that plasminogen binding and activation by different surface-localized glycolytic enzymes of
M. pneumoniae
may play a role in successful and long-term colonization of the human respiratory tract.
The Effector Protein BPE005 from Brucella abortus Induces Collagen Deposition and Matrix Metalloproteinase 9 Downmodulation via Transforming Growth Factor β1 in Hepatic Stellate Cells
Authors: Arriola Benitez Paula Constanza , Rey Serantes Diego , Herrmann Claudia Karina , Pesce Viglietti Ayelén Ivana , Vanzulli Silvia , Giambartolomei Guillermo Hernán , Comerci Diego José , Delpino María Victoria
Published: December 2015

The liver is frequently affected in patients with active brucellosis. In the present study, we identified a virulence factor involved in the modulation of hepatic stellate cell function and consequent fibrosis duringBrucella abortusinfection. This study assessed the role of BPE005 protein fromB. abortusin the fibrotic phenotype induced on hepatic stellate cells duringB. abortusinfectionin vitroandin vivo. We demonstrated that the fibrotic phenotype induced byB. abortuson hepatic stellate (LX-2) cells was dependent on BPE005, a protein associated with the type IV secretion system (T4SS) VirB fromB. abortus. Our results indicated thatB. abortusinhibits matrix metalloproteinase 9 (MMP-9) secretion through the activity of the BPE005-secreted protein and induces concomitant collagen deposition by LX-2 cells. BPE005 is a small protein containing a cyclic nucleotide monophosphate binding domain (cNMP) that modulates the LX-2 cell phenotype through a mechanism that is dependent on the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway. Altogether, these results indicate thatB. abortustilts LX-2 cells to a profibrogenic phenotype employing a functional T4SS and the secreted BPE005 protein through a mechanism that involves the cAMP and PKA signaling pathway.
From the Editor-in-Chief: The Next Phase of Discipline-Based Education Research Is Here!
Authors: Elliott Samantha L.
Published: December 2015

A look at the current state of discipline-based education research (DBER) and how JMBE is adapting to new breakthroughs in the field of biology education.
A Cross-Course Investigation of Integrative Cases for Evolution Education
Authors: White Peter John Thomas , Heidemann Merle K. , Smith James J.
Published: December 2015

Evolution is a cornerstone theory in biology, yet many undergraduate students have difficulty understanding it. One reason for this is that evolution is often taught in a macro-scale context without explicit links to micro-scale processes. To address this, we developed a series of integrative evolution cases that present the evolution of various traits from their origin in genetic mutation, to the synthesis of modified proteins, to how these proteins produce novel phenotypes, to the related macro-scale impacts that the novel phenotypes have on populations in ecological communities. We postulated that students would develop a fuller understanding of evolution when learning biology in a context where these integrative evolution cases are used. We used a previously developed assessment tool, the ATEEK (Assessment Tool for Evaluating Evolution Knowledge), within a pre-course/post-course assessment framework. Students who learned biology in courses using the integrative cases performed significantly better on the evolution assessment than did students in courses that did not use the cases. We also found that student understanding of evolution increased with increased exposure to the integrative evolution cases. These findings support the general hypothesis that students acquire a more complete understanding of evolution when they learn about its genetic and molecular mechanisms along with macro-scale explanations.
A Publicly Available PCR Methods Laboratory Manual and Supporting Material
Authors: DeCaire Jason , Ker Cappi , Johnston William , Muslow Mary , Shultz Jeffry
Published: December 2015

We report the creation of a PCR methods laboratory manual and supporting material. The manual contains 24 different procedures designed to illustrate basic PCR concepts and promote independent problem-solving skills. Each lab poses a question about PCR and provides a list of materials the student may use to investigate the question. Supplemental materials available to instructors include answers to post-lab questions, lab set-up information, 82 assessment questions and answers, 22 PowerPoint slides, a sample syllabus, experiment set-up illustrations and example results for most labs. The student lab book is available as a supplemental file and at http://ans.latech.edu/BasicPCRMethods.html, while Instructor-specific materials are available from the corresponding author at no charge.
The Emerging Microbe Project: Developing Clinical Care Plans Based on Pathogen Identification and Clinical Case Studies
Authors: O’Donnell Lauren A. , Perry Michael W. , Doup Dane’t R.
Published: December 2015

For many students in the health sciences, including doctor of pharmacy (PharmD) students, basic and clinical sciences often appear detached from each other. In the infectious disease field, PharmD students additionally struggle with mastering the diversity of microorganisms and the corresponding therapies. The objective of this study was to design an interdisciplinary project that integrates fundamental microbiology with clinical research and decision-making skills. The Emerging Microbe Project guided students through the identification of a microorganism via genetic sequence analysis. The unknown microbe provided the basis for a patient case that asked the student to design a therapeutic treatment strategy for an infected patient. Outside of lecture, students had two weeks to identify the pathogen using nucleotide sequences, compose a microbiology report on the pathogen, and recommend an appropriate therapeutic treatment plan for the corresponding clinical case. We hypothesized that the students would develop a better understanding of the interplay between basic microbiology and infectious disease clinical practice, and that they would gain confidence and skill in independently selecting appropriate antimicrobial therapies for a new disease state. The exercise was conducted with PharmD students in their second professional year of pharmacy school in a required infectious disease course. Here, we demonstrate that the Emerging Microbe Project significantly improved student learning through two assessment strategies (assignment grades and exam questions), and increased student confidence in clinical infectious disease practice. This exercise could be modified for other health sciences students or undergraduates depending upon the level of clinical focus required of the course.
Brewing for Students: An Inquiry-Based Microbiology Lab
Authors: Sato Brian K. , Alam Usman , Dacanay Samantha J. , Lee Amanda K. , Shaffer Justin F.
Published: December 2015

In an effort to improve and assess student learning, there has been a push to increase the incorporation of discovery-driven modules and those that contain real-world relevance into laboratory curricula. To further this effort, we have developed, implemented, and assessed an undergraduate microbiology laboratory experiment that requires students to use the scientific method while brewing beer. The experiment allows students to brew their own beer and characterize it based on taste, alcohol content, calorie content, pH, and standard reference method. In addition, we assessed whether students were capable of achieving the module learning objectives through a pre-/posttest, student self-evaluation, exam-embedded questions, and an associated worksheet. These objectives included describing the role of the brewing ingredients and predicting how altering the ingredients would affect the characteristics of the beer, amongst others. By completing this experimental module, students accomplished the module objectives, had greater interest in brewing, and were more likely to view beer in scientific terms. Journal of Microbiology & Biology Education
Action Research to Improve the Learning Space for Diagnostic Techniques
Authors: Ariel Ellen , Owens Leigh
Published: December 2015

The module described and evaluated here was created in response to perceived learning difficulties in diagnostic test design and interpretation for students in third-year Clinical Microbiology. Previously, the activities in lectures and laboratory classes in the module fell into the lower cognitive operations of “knowledge” and “understanding.” The new approach was to exchange part of the traditional activities with elements of interactive learning, where students had the opportunity to engage in deep learning using a variety of learning styles. The effectiveness of the new curriculum was assessed by means of on-course student assessment throughout the module, a final exam, an anonymous questionnaire on student evaluation of the different activities and a focus group of volunteers. Although the new curriculum enabled a major part of the student cohort to achieve higher pass grades (p < 0.001), it did not meet the requirements of the weaker students, and the proportion of the students failing the module remained at 34%. The action research applied here provided a number of valuable suggestions from students on how to improve future curricula from their perspective. Most importantly, an interactive online program that facilitated flexibility in the learning space for the different reagents and their interaction in diagnostic tests was proposed. The methods applied to improve and assess a curriculum refresh by involving students as partners in the process, as well as the outcomes, are discussed. Journal of Microbiology & Biology Education
Laboratory Activity to Teach about the Proliferation of
Salmonella
in Vegetables
Authors: Marvasi Massimiliano , Choudhury Manika , Teplitski Max
Published: December 2015

We designed a three-week laboratory experience that can complement any microbiology teaching laboratory to expand students’ knowledge of the ecology of human enteric pathogens outside of their animal hosts. Through their participation in this laboratory activity, students learned that vegetative and reproductive plant parts could be a natural habitat for enteric bacteria such as non-typhoidal strains of
Salmonella enterica
. This field was recently brought to the forefront of the scientific community and public interest by outbreaks of human illness linked to the consumption of fresh fruits and vegetables. Students were encouraged to develop their own testable hypotheses to compare proliferation of
Salmonella enterica
sv Typhimurium LT2 in different vegetables: cherry and regular-size tomatoes, onions, lettuce, and yellow and red bell peppers (
Escherichia coli
can be substituted for BSL1 laboratories). Upon completion of the laboratory experience, students were able to: 1) Develop testable hypotheses addressing the ability of a human pathogen,
Salmonella enterica
, to colonize and proliferate in vegetables; 2) Determine that different vegetables support the growth of
Salmonella
to different extents; 3) Conduct statistical analysis and identify any significant differences. The teaching-learning process was assessed with a pre-/posttest, with an average increase in content understanding from ~15% to 85%. We also measured students’ proficiency while conducting specific technical tasks, revealing no major difficulties while conducting the experiments. Students indicated satisfaction with the organization and content of the practices. All of the students (100%) agreed that the exercises improved their knowledge of this subject.
Presenting Clicker Questions with an Open- Versus Closed-Response Format
Authors: Fisher Ginger R. , DeChenne Sue Ellen
Published: December 2015

Active learning can improve student learning but can be more difficult to use in large classrooms. Course response systems (clickers) can be used to increase active learning and student discussion. In this study, students in a large introductory biology course were given clicker questions in different formats. Students were first presented with an open response question on a PowerPoint slide where no potential answers were visible. After peer discussion, the same question was presented with potential answers in a multiple choice format and students used their clickers to answer. For comparison, the same questions were asked in a different section of the same course but all questions were in the standard multiple choice format. The results show that C students perform better when required to create their own answer for the question. The instructor also noted that student discussions were longer, most likely because students had to discuss the biology rather than just confirming a specific answer choice.
Deciphering Primary and Popular Literature: An Interactive Approach for Promoting Students’ Development of Scientific, Digital, and Information Literacy in Post-Secondary Contexts
Authors: Cleveland Lacy M. , Olimpo Jeffrey T.
Published: December 2015

In an era of unprecedented scientific and technological advancement, it is imperative that individuals possess the ability to interpret and make meaning of current scientific phenomena, including those of both national and global importance. Despite this necessity, research suggests that less than 30% of Americans are able to understand the science section of the New York Times or other popular media resources. In this paper, we present an interactive approach utilizing primary and popular literature that is designed to: a) enhance students’ understanding of science content; b) promote students’ ability to make use of evidence to support or reject claims regarding controversial science topics; and c) improve students’ oral and written communication skills. Applications for use in post-secondary classrooms are discussed.
The therapeutic value of atropine for critical care intubation
Authors: Jones Peter
Published: December 2015

Recent studies of atropine during critical care intubation (CCI) have revealed that neonates frequently experience bradycardia, are infrequently affected by ventricular arrhythmias and conduction disturbances and deaths have not been reported in a series of studies. The indiscriminate use of atropine is unlikely to alter the outcome during neonatal CCI other than reducing the frequency of sinus tachycardia. In contrast, older children experience a similar frequency of bradycardia to neonates and are more frequently affected by ventricular arrhythmias and conduction disturbances. Mortality during CCI is in the order of 0.5%. Atropine has a beneficial effect on arrhythmias and conduction disturbances and may reduce paediatric intensive care unit mortality. The use of atropine for children >1 month of age may positively influence outcomes beyond a reduction in the frequency of sinus bradycardia. There is indirect evidence that atropine should be used for intubation during sepsis. Atropine should be considered when using suxamethonium. The reliance on heart rate as the sole measure of haemodynamic function during CCI is no longer justifiable. Randomised trials of atropine for mortality during CCI in general intensive care unit populations are unlikely to happen. As such, future research should be focused on establishing of a gold standard for haemodynamic decompensation for CCI. Cardiac output or blood pressure are the most likely candidates. The ‘lost beat score’ requires development but has the potential to be developed to provide an estimation of risk of haemodynamic decompensation from ECG data in real time during CCI.
Enter B and W: two new meningococcal vaccine programmes launched
Authors: Ladhani Shamez N , Ramsay Mary , Borrow Ray , Riordan Andrew , Watson John M , Pollard Andrew J
Published: December 2015

In 2015, the UK became the first country in the world to have a comprehensive routine meningococcal vaccine programme targeting all of the main capsular groups ofN. meningitidis. 1 An infant vaccine programme against meningococcal capsular group BNeisseria meningitidis(MenB) was launched from 1st September with an aim to reduce endemic MenB disease in early childhood. On 1st August 2015, an adolescent programme against groups A, C, W and Y meningococci (MenACWY) was rolled out to halt a growing outbreak of capsular group W disease (MenW) caused by a hypervirulent clone ofN. meningitidis, in addition to maintaining control against MenC disease provided by the current adolescent programme. 2