bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term shifts in the patterns and underlying processes of plant associations in Wisconsin forests
Authors: Li Daijiang , Waller Donald 
Published: January 2016

AbstractAimPlant species co‐occur within communities in response to variation in environmental conditions, limited species dispersal and biotic interactions. We used surveys and resurveys of the same sites of three temperate forest plant communities to study patterns of association between co‐occurring species pairs and to infer how these mechanisms contribute to community assembly. Our goal was to compare these forces among communities occupying more and less disturbed landscapes and examine how these have changed over the last 50 years.LocationWisconsin, USA.MethodsWe resurveyed 266 sites first surveyed in the 1950s to assess the patterns and dynamics of co‐occurrence among understorey plant species in three community types. We then used checkerboard scores, null models and a newly developed framework to infer the mechanisms likely to have driven community assembly. Finally, we compared these across the three communities and two time periods.ResultsSpecies co‐occur less often than expected in all three vegetation types and both periods. We detected high fractions of aggregated and segregated species pairs (up to 14% and 17%, respectively). In the fragmented southern upland forests and central sand plains, both biotic interactions and dispersal limitation may play important roles in community assembly with inferred dispersal limitation becoming more important since the 1950s. In the more continuous and intact northern upland forests, environmental filtering and biotic interactions appear to dominate community dynamics with little change over time. Aggregated and segregated species pairs made a similar contribution to our ability to infer these mechanisms.Main conclusionsEnvironmental filtering, biotic interactions and dispersal limitation all appear to affect plant community structure in both time periods. However, the influence of dispersal limitation seems to be increasing in more fragmented forest landscapes, portending shifts in community composition and dynamics. Because aggregated and segregated species pairs may be shaped by similar processes both can be used to infer processes of community assembly.
Timing Matters ‐ Influenza Vaccination to HIV‐Infected Patients
Authors: Glinka ER , Smith DM , Johns ST 
Published: January 2016

ObjectivesPatients with HIV infection vaccinated early in the flu season are more likely to contract influenza or influenza‐like illness (ILI) compared with those receiving late vaccination. It is known that antibody titres wane over time, particularly among individuals with HIV infection. It is unclear if the timing of influenza vaccination within the flu season affects the probability of an influenza infection later during the flu season. The aim of this study is to evaluate if there is a relationship between the timing of influenza vaccination and incidence of influenza or ILI in patients with HIV infection.MethodsA retrospective cohort study of HIV‐infected patients in care at the Department of Veterans Affairs San Diego Healthcare System was conducted from 1 September 2005 to 31 May 2013. Among these patients, we evaluated whether there was a relationship between the timing of influenza vaccination and the incidence of laboratory‐confirmed influenza, influenza diagnosed by a physician, or ILI.ResultsPatients who received influenza vaccine early in the season were more likely to contract influenza or ILI than patients who were vaccinated late (P < 0.01). Vaccinated patients who developed influenza or ILI were more likely to do so later in the season (P < 0.01).ConclusionsHIV‐infected patients vaccinated early in the flu season were more likely to contract influenza or ILI than those vaccinated later in the season.
Development and Validation of a Modified Multiple Errands Test for Adults with Intellectual Disabilities
Authors: Steverson Tom , Adlam Anna‐Lynne R. , Langdon Peter E. 
Published: January 2016

BackgroundThe aims of the current study were to adapt a version of the MET for people with intellectual disabilities and assess its ecological and construct validity.Material and MethodsUsing a correlational design, 40 participants with intellectual disabilities were invited to complete a battery of neuropsychological assessments and the modified Multiple Errands Test for Intellectual Disabilities (mMET‐IDs).ResultsThe ability to successfully complete tasks on the mMET‐IDs correlated significantly with measures of the Supervisory Attentional System, namely, the Tower of London Test and the Six Parts Test. However, performance on the mMET‐IDs and the Six Parts Test could be accounted for by Verbal IQ and receptive vocabulary. The mMET‐IDs failed to correlate with the DEX‐IR.ConclusionsThe mMET‐IDs can be successfully used to assess some aspects of the Supervisory Attentional System in people with intellectual disabilities. Further development is needed, however, to improve the ecological validity of the mMET‐IDs.
Oxaloacetate enhances neuronal cell bioenergetic fluxes and infrastructure
Authors: Wilkins Heather M. , Koppel Scott , Carl Steven M. , Ramanujan Suruchi , Weidling Ian , Michaelis Mary L. , Michaelis Elias K. , Swerdlow Russell H. 
Published: January 2016

AbstractWe tested how the addition of oxaloacetate (OAA) to SH‐SY5Y cells affected bioenergetic fluxes and infrastructure, and compared the effects of OAA to malate, pyruvate, and glucose deprivation. OAA displayed pro‐glycolysis and pro‐respiration effects. OAA pro‐glycolysis effects were not a consequence of decarboxylation to pyruvate because unlike OAA, pyruvate lowered the glycolysis flux. Malate did not alter glycolysis flux and reduced mitochondrial respiration. Glucose deprivation essentially eliminated glycolysis and increased mitochondrial respiration. OAA increased, while malate decreased, the cell NAD+/NADH ratio. Cytosolic malate dehydrogenase 1 protein increased with OAA treatment, but not with malate or glucose deprivation. Glucose deprivation increased protein levels of ATP citrate lyase, an enzyme which produces cytosolic OAA, whereas OAA altered neither ATP citrate lyase mRNA nor protein levels. OAA, but not glucose deprivation, increased cytochrome oxidase subunit 2, PGC1α, PGC1β, and PGC1 related co‐activator protein levels. OAA increased total and phosphorylated SIRT1 protein. We conclude that adding OAA to SH‐SY5Y cells can support or enhance both glycolysis and respiration fluxes. These effects appear to depend, at least partly, on OAA causing a shift in the cell redox balance to a more oxidized state, that it is not a glycolysis pathway intermediate, and possibly its ability to act in an anaplerotic fashion.
image
We examined how oxaloacetate (OAA) affects bioenergetic fluxes. To advance the understanding of how OAA mediates these changes, we compared the effects of OAA to malate, pyruvate, and glucose deprivation. We further examined how OAA affects levels of enzymes that facilitate its cytosolic metabolism, and found OAA increased the expression of malate dehydrogenase 1 (MDH1‐cytosolic). We propose the following: OAA supports both glycolysis and respiration fluxes, shifts the cell redox balance toward a more oxidized state, and acts in an anaplerotic fashion. Abbreviations not defined in the text: MDH2, malate dehydrogenase 2 (mitochondrial).
Assessment of brain metabolite correlates of adeno‐associated virus‐mediated over‐expression of human alpha‐synuclein in cortical neurons by in vivo1H‐MR spectroscopy at 9.4 T
Authors: Cuellar‐Baena Sandra , Landeck Natalie , Sonnay Sarah , Buck Kerstin , Mlynarik Vladimir , in ‘t Zandt René , Kirik Deniz 
Published: January 2016

AbstractIn this study, we used proton‐localized spectroscopy (1H‐MRS) for the acquisition of the neurochemical profile longitudinally in a novel rat model of human wild‐type alpha‐synuclein (α‐syn) over‐expression. Our goal was to find out if the increased α‐syn load in this model could be linked to changes in metabolites in the frontal cortex. Animals injected with AAV vectors encoding for human α‐syn formed the experimental group, whereas green fluorescent protein expressing animals were used as the vector‐treated control group and a third group of uninjected animals were used as naïve controls. Data were acquired at 2, 4, and 8 month time points. Nineteen metabolites were quantified in the MR spectra using LCModel software. On the basis of 92 spectra, we evaluated any potential gender effect and found that lactate (Lac) levels were lower in males compared to females, while the opposite was observed for ascorbate (Asc). Next, we assessed the effect of age and found increased levels of GABA, Tau, and GPC+PCho. Finally, we analyzed the effect of treatment and found that Lac levels (p = 0.005) were specifically lower in the α‐syn group compared to the green fluorescent protein and control groups. In addition, Asc levels (p = 0.05) were increased in the vector‐injected groups, whereas glucose levels remained unchanged. This study indicates that the metabolic switch between glucose‐lactate could be detectable in vivo and might be modulated by Asc. No concomitant changes were found in markers of neuronal integrity (e.g., N‐acetylaspartate) consistent with the fact that α‐syn over‐expression in cortical neurons did not result in neurodegeneration in this model.
image
We acquired the neurochemical profile longitudinally in a rat model of human wild‐type alpha‐synuclein (α‐syn) over‐expression in cortical neurons. We found that Lactate levels were reduced in the α‐syn group compared to the control groups and Ascorbate levels were increased in the vector‐injected groups. No changes were found in markers of neuronal integrity consistent with the fact that α‐syn over‐expression did not result in frank neurodegeneration.
Neuronal filopodium formation induced by the membrane glycoprotein M6a (Gpm6a) is facilitated by coronin‐1a, Rac1, and p21‐activated kinase 1 (Pak1)
Authors: Alvarez Juliá Anabel , Frasch Alberto C. , Fuchsova Beata 
Published: January 2016

AbstractStress‐responsive neuronal membrane glycoprotein M6a (Gpm6a) functions in neurite extension, filopodium and spine formation and synaptogenesis. The mechanisms of Gpm6a action in these processes are incompletely understood. Previously, we identified the actin regulator coronin‐1a (Coro1a) as a putative Gpm6a interacting partner. Here, we used co‐immunoprecipitation assays with the anti‐Coro1a antibody to show that Coro1a associates with Gpm6a in rat hippocampal neurons. By immunofluorescence microscopy, we demonstrated that in hippocampal neurons Coro1a localizes in F‐actin‐enriched regions and some of Coro1a spots co‐localize with Gpm6a labeling. Notably, the over‐expression of a dominant‐negative form of Coro1a as well as its down‐regulation by siRNA interfered with Gpm6a‐induced filopodium formation. Coro1a is known to regulate the plasma membrane translocation and activation of small GTPase Rac1. We show that Coro1a co‐immunoprecipitates with Rac1 together with Gpm6a. Pharmacological inhibition of Rac1 resulted in a significant decrease in filopodium formation by Gpm6a. The same was observed upon the co‐expression of Gpm6a with the inactive GDP‐bound form of Rac1. In this case, the elevated membrane recruitment of GDP‐bound Rac1 was detected as well. Moreover, the kinase activity of the p21‐activated kinase 1 (Pak1), a main downstream effector of Rac1 that acts downstream of Coro1a, was required for Gpm6a‐induced filopodium formation. Taken together, our results provide evidence that a signaling pathway including Coro1a, Rac1, and Pak1 facilitates Gpm6a‐induced filopodium formation.
image
Formation of filopodia by membrane glycoprotein M6a (Gpm6a) requires actin regulator coronin‐1a (Coro1a), known to regulate plasma membrane localization and activation of Rac1 and its downstream effector Pak1. Coro1a associates with Gpm6a. Blockage of Coro1a, Rac1, or Pak1 interferes with Gpm6a‐induced filopodium formation. Moreover, Gpm6a facilitates Rac1 membrane recruitment. Altogether, a mechanistic insight into the process of Gpm6a‐induced neuronal filopodium formation is provided.
BMPR2 gene therapy for PAH acts via Smad and non‐Smad signalling
Authors: Harper Rebecca L. , Reynolds Ann M. , Bonder Claudine S. , Reynolds Paul N. 
Published: January 2016

AbstractBackground and objectivePulmonary arterial hypertension (PAH) continues to be a fatal disease and is associated with downregulation of bone morphogenetic protein receptor type‐2 (BMPR2). Our approach is to upregulate BMPR2 in the pulmonary vasculature allowing us to examine the changes in endothelial cell signalling and better understand what pathways are altered when disease is attenuated using this treatment approach.MethodsWe used gene delivery of BMPR2 to human pulmonary endothelial cells to investigate downstream signalling, then assessed the impact of this approach on downstream signalling in vivo in rats with PAH using the monocrotaline (MCT) model.ResultsGene delivery of BMPR2 leads to an increase in BMPR2 protein expression, and this is associated with increased Smad1/5/8 and reduced Smad2/3 signalling. Additionally, we have found that BMPR2 modulation has effects on non‐Smad signalling with increases found in phosphoinositide‐3 kinase (PI3K) and a decrease in phosphorylated‐p38‐mitogen activated protein kinase (p38‐MAPK) in vivo. These findings are associated with amelioration of PAH (reduced right ventricular, mean pulmonary artery pressures and Fulton Index).ConclusionThese results indicate that the therapeutic effect of BMPR2 gene delivery on PAH is associated with a switch between TGF‐β‐Smad2/3 signalling to BMPR2‐Smad1/5/8 signalling. This supports the further development of this treatment approach.
Retracted: Development and Validation of the Mathematics Teachers' Beliefs About English Language Learners Survey (MTBELL)
Authors: Gann Linda , Bonner Emily P. , Moseley Christine 
Published: January 2016

Given the increasing number of English Language Learners (ELLs) in secondary mathematics classrooms, it is imperative that mathematics teacher educators develop measures for determining how and why secondary mathematics teachers (SMTs) understand and respond instructionally to these students. This paper reports on the initial development and validation of the Mathematics Teachers' Beliefs about English Language Learners survey, an instrument that measures SMTs beliefs, attitudes, knowledge base, and instructional practices in relation to meeting the academic and language needs of ELLs. Through piloting processes, the instrument was refined for a research study through which reliability and validity were established. The five constructs identified from exploratory factor analysis illustrate perceived opportunities and barriers in meeting ELLs' academic and language needs among SMTs.This article features a Research to Practice Companion Article. Please click on the supporting information link below to access.
Fumarate-Mediated Persistence of Escherichia coli against Antibiotics
Authors: Kim Jun-Seob , Cho Da-Hyeong , Heo Paul , Jung Suk-Chae , Park Myungseo , Oh Eun-Joong , Sung Jaeyun , Kim Pan-Jun , Lee Suk-Chan , Lee Dae-Hee , Lee Sarah , Lee Choong Hwan , Shin Dongwoo , Jin Yong-Su , Kweon Dae-Hyuk 
Published: January 2016

ABSTRACT

Bacterial persisters are a small fraction of quiescent cells that survive in the presence of lethal concentrations of antibiotics. They can regrow to give rise to a new population that has the same vulnerability to the antibiotics as did the parental population. Although formation of bacterial persisters in the presence of various antibiotics has been documented, the molecular mechanisms by which these persisters tolerate the antibiotics are still controversial. We found that amplification of the fumarate reductase operon (
FRD
) in
Escherichia coli
led to a higher frequency of persister formation. The persister frequency of
E. coli
was increased when the cells contained elevated levels of intracellular fumarate. Genetic perturbations of the electron transport chain (ETC), a metabolite supplementation assay, and even the toxin-antitoxin-related
hipA7
mutation indicated that surplus fumarate markedly elevated the
E. coli
persister frequency. An
E. coli
strain lacking succinate dehydrogenase (
SDH
), thereby showing a lower intracellular fumarate concentration, was killed ∼1,000-fold more effectively than the wild-type strain in the stationary phase. It appears that
SDH
and
FRD
represent a paired system that gives rise to and maintains
E. coli
persisters by producing and utilizing fumarate, respectively.
Population Pharmacokinetic Assessment and Pharmacodynamic Implications of Pediatric Cefepime Dosing for Susceptible-Dose-Dependent Organisms
Authors: Shoji Kensuke , Bradley John S. , Reed Michael D. , van den Anker John N. , Domonoske Christine , Capparelli Edmund V. 
Published: January 2016

ABSTRACT

The Clinical and Laboratory Standards Institute (CLSI) revised cefepime (CFP) breakpoints for
Enterobacteriaceae
in 2014, and MICs of 4 and 8 μg/ml were reclassified as susceptible-dose dependent (SDD). Pediatric dosing to provide therapeutic concentrations against SDD organisms has not been defined. CFP pharmacokinetics (PK) data from published pediatric studies were analyzed. Population PK parameters were determined using NONMEM, and Monte Carlo simulation was performed to determine an appropriate CFP dosage regimen for SDD organisms in children. A total of 664 CFP plasma concentrations from 91 neonates, infants, and children were included in this analysis. The median patient age was 1.0 month (interquartile range [IQR], 0.2 to 11.2 months). Serum creatinine (SCR) and postmenstrual age (PMA) were covariates in the final PK model. Simulations indicated that CFP dosing at 50 mg/kg every 8 h (q8h) (as 0.5-h intravenous [i.v.] infusions) will maintain free-CFP concentrations in serum of >4 and 8 μg/ml for >60% of the dose interval in 87.1% and 68.6% of pediatric patients (age, ≥30 days), respectively, and extending the i.v. infusion duration to 3 h results in 92.3% of patients with free-CFP levels above 8 μg/ml for >60% of the dose interval. CFP clearance (CL) is significantly correlated with PMA and SCR. A dose of 50 mg/kg of CFP every 8 to 12 h does not achieve adequate serum exposure for older children with serious infections caused by Gram-negative bacilli with a MIC of 8 μg/ml. Prolonged i.v. infusions may be useful for this population.
Pharmacokinetics of Rifampin, Isoniazid, Pyrazinamide, and Ethambutol in Infants Dosed According to Revised WHO-Recommended Treatment Guidelines
Authors: Bekker A. , Schaaf H. S. , Draper H. R. , van der Laan L. , Murray S. , Wiesner L. , Donald P. R. , McIlleron H. M. , Hesseling A. C. 
Published: January 2016

ABSTRACT

There are limited pharmacokinetic data for use of the first-line antituberculosis drugs during infancy (<12 months of age), when drug disposition may differ. Intensive pharmacokinetic sampling was performed in infants routinely receiving antituberculosis treatment, including rifampin, isoniazid, pyrazinamide, and ethambutol, using World Health Organization-recommended doses. Regulatory-approved single-drug formulations, including two rifampin suspensions, were used on the sampling day. Assays were conducted using liquid chromatography-mass spectrometry; pharmacokinetic parameters were generated using noncompartmental analysis. Thirty-nine infants were studied; 14 (36%) had culture-confirmed tuberculosis. Fifteen (38%) were premature (<37 weeks gestation); 5 (13%) were HIV infected. The mean corrected age and weight were 6.6 months and 6.45 kg, respectively. The mean maximum plasma concentrations (
C
max
) for rifampin, isoniazid, pyrazinamide, and ethambutol were 2.9, 7.9, 41.9, and 1.3 μg/ml, respectively (current recommended adult target concentrations: 8 to 24, 3 to 6, 20 to 50, and 2 to 6 μg/ml, respectively), and the mean areas under the concentration-time curves from 0 to 8 h (AUC
0–8
) were 12.1, 24.7, 239.4, and 5.1 μg · h/ml, respectively. After adjusting for age and weight, rifampin exposures for the two formulations used differed in
C
max
(geometric mean ratio [GMR]
,
2.55; 95% confidence interval [CI], 1.47 to 4.41;
P
= 0.001) and AUC
0–8
(GMR, 2.52; 95% CI, 1.34 to 4.73;
P
= 0.005). HIV status was associated with lower pyrazinamide
C
max
(GMR, 0.85; 95% CI, 0.75 to 0.96;
P
= 0.013) and AUC
0–8
(GMR, 0.79; 95% CI, 0.69 to 0.90;
P
< 0.001) values. No other important differences were observed due to age, weight, prematurity, ethnicity, or gender. In summary, isoniazid and pyrazinamide concentrations in infants compared well with proposed adult target concentrations; ethambutol concentrations were lower but similar to previously reported pediatric studies. The low rifampin exposures require further investigation. (This study has been registered at ClinicalTrials.gov under registration no. NCT01637558.)
Effect of Media Modified To Mimic Cystic Fibrosis Sputum on the Susceptibility of Aspergillus fumigatus, and the Frequency of Resistance at One Center
Authors: Stevens David A. , Moss Richard B. , Hernandez Cathy , Clemons Karl V. , Martinez Marife 
Published: January 2016

ABSTRACT

Studies of cystic fibrosis (CF) patient exacerbations attributed to
Pseudomonas aeruginosa
infection have indicated a lack of correlation of outcome with
in vitro
susceptibility results. One explanation is that the media used for testing do not mimic the airway milieu, resulting in incorrect conclusions. Therefore, media have been devised to mimic CF sputum.
Aspergillus fumigatus
is the leading fungal pathogen in CF, and susceptibility testing is also used to decide therapeutic choices. We assessed whether media designed to mimic CF sputa would give different fungal susceptibility results than those of classical methods, assaying voriconazole, the most utilized anti-
Aspergillus
drug in this setting, and 30 CF
Aspergillus
isolates. The frequency of marked resistance (defined as an MIC of >4 μg/ml) in our CF unit by classical methods is 7%. Studies performed with classical methods and with digested sputum medium, synthetic sputum medium, and artificial sputum medium revealed prominent differences in
Aspergillus
susceptibility results, as well as growth rate, with each medium. Clinical correlative studies are required to determine which results are most useful in predicting outcome. Comparison of MICs with non-CF isolates also indicated the CF isolates were generally more resistant.