bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seeing the trees for the wood – beech (Fagus sylvatica) decay fungal volatiles influence the structure of saproxylic beetle communities
Authors: Leather Simon R. , Baumgart Eligiusz A. , Evans Hugh F. , Quicke Donald L. J. 
Published: October 2013

Abstract

Two experiments were conducted to investigate the role of basidiomycetes and volatiles in the ecology of saproxylic Coleoptera. Volatile organic compounds (VOCs) were sampled from beech (Fagus sylvatica) logs experimentally inoculated with the basidiomycetes Stereum hirsutum, Coriolus versicolor, Phanerochaete velutina, Hypholoma fasiculare, Bjerkandera adusta both singly and in various combinations. Volatile emissions were found to be in accordance with amounts detectable to insects suggesting that in a natural decay situation, saproxylic volatiles are readily available as insect semiochemicals.

Furthermore, fungal community structure was found to significantly affect the volatile profile of decaying wood, with specific VOCs associated with particular fungal treatments. Thus, volatiles of fungal origin are a strong potential source of semiochemicals for those insects utilising the saproxylic habitat and their natural enemies.

Beetles were reared from logs inoculated with the same basidiomycete treatments as described earlier and a total of 604 individuals comprising 84 species were obtained. Eleven species (Cis boleti, C. micans, Dacne bipustulata, Latridius consimilis, Mycetophagus atomarius, M. quadripustulatus, Octotemnus glabriculus, Platystomus albinos, Ptilinus pectinicornis, Stictoleptura scutellata, Tomoxia bucephala) exhibited significant associations with one or more fungal treatments.

Explanations are provided for the various beetle–fungus associations observed. The data set is notable for the presence of various wood boring species that tend to be absent in experiments where volatiles from fungi are presented in isolation.

Coarse woody debris (CWD) and its interaction with fungi CWD, are shown to give off VOCs of varying degrees of specificity. These VOCs are potential semiochemicals for saproxylic insects and may mediate fungus/CWD‐specific interactions. We conclude that future work in this direction would be profitable.
Mini Nutritional Assessment as a Useful Method of Predicting the Development of Pressure Ulcers in Elderly Inpatients
Authors: Yatabe Midori S. , Taguchi Fumie , Ishida Izumi , Sato Atsuko , Kameda Toshio , Ueno Shuichi , Takano Kozue , Watanabe Tsuyoshi , Sanada Hironobu , Yatabe Junichi 
Published: October 2013

ObjectivesTo determine the usefulness of the Mini Nutritional Assessment (MNA) and plasma amino acid analysis in predicting the formation of pressure ulcers (PUs) in inpatients.DesignProspective, observational cohort study with a mean observation period of 62.2 ± 86.4 days.SettingIntermediate and acute care wards of a hospital in rural Japan.ParticipantsInpatients with an average age of 85.0 ± 7.6 (N = 422).MeasurementsMini Nutritional Assessment, Subjective Global Assessment (SGA), Braden Scale (PU prognostic score), PU formation, and biochemical analysis including plasma amino acid concentrations.ResultsPUs developed in 7.1% of participants. A MNA score of less than 8 was more sensitive than a rating of moderate or severe malnourishment on the SGA combined with a Braden Scale score of less than 15 in predicting future PUs. The area under the receiver operating characteristic curve (AUC) of the MNA was superior to that of the Braden Scale. The Braden Scale nutrition subscore had the lowest AUC of the six Braden Scale subscores. Individuals who developed PUs had significantly lower plasma arginine concentrations than those who did not.ConclusionMini Nutritional Assessment was able to predict the development of PUs. A MNA score of less than 8 performed better than the SGA, Braden Scale, and plasma arginine levels in predicting PU development. Although lower plasma arginine concentration at time of admission was associated with PU development, the AUC for arginine was not significantly different from 0.50. The findings from this prospective study support the use of nutritional assessment in inpatients to predict PU risk and target appropriate interventions.
Corticospinal modulation induced by sounds depends on action preparedness
Authors: Marinovic Welber , Tresilian James R. , de Rugy Aymar , Sidhu Simranjit , Riek Stephan 
Published: October 2013

Key pointsUnexpected loud auditory stimuli can trigger the involuntary release of motor actions during preparation to move.Because acoustic stimulation can suppress motor cortex excitability during action, this early release could be independent of the motor cortex, and interpreted as pre‐planned action stored and triggered from subcortical areas.In contrast, we show that corticospinal excitability in response to the loud auditory stimuli was increased when people were highly prepared to move, and reduced otherwise.Our results also indicate that auditory stimuli can affect intracortical excitability by increasing intracortical facilitation and reducing short‐interval intracortical inhibition.Together, our findings demonstrate that the early release of motor responses by auditory stimuli involves the motor cortex.Abstract A loud acoustic stimulus (LAS) presented during movement preparation can induce an early release of the prepared action. Because loud sound has been found to have an inhibitory effect on motor cortex excitability, it is possible that the motor cortex plays little role in the early release of prepared responses. We sought to shed new light on this suggestion by probing changes in corticospinal excitability after LAS presentation during preparation for an anticipatory action. Unexpectedly, we show that the changes in corticospinal excitability after LAS presentation are not fixed. Based on the magnitude of motor‐evoked potentials elicited by transcranial magnetic and electric stimulation of the motor cortex, we demonstrate that the effects of auditory stimuli on corticospinal excitability depend on the level of readiness for action: inhibition in early preparation and facilitation close to movement onset. We also show that auditory stimuli can regulate intracortical excitability by increasing intracortical facilitation and reducing short‐interval intracortical inhibition. Together, these findings indicate that, at least in part, the early release of motor responses by auditory stimuli involves the motor cortex.
Calcineurin inhibitor induces pain hypersensitivity by potentiating pre‐ and postsynaptic NMDA receptor activity in spinal cords
Authors: Chen Shao‐Rui , Hu Yi‐Min , Chen Hong , Pan Hui‐Lin 
Published: October 2013

Key points
We developed an animal model to study the mechanisms underlying the pain syndrome commonly seen in organ transplant patients receiving calcineurin inhibitors.
Systemic treatment with the calcineurin inhibitor induces long‐lasting pain hypersensitivity and increases glutamate receptor activity in the spinal cord.
Blocking glutamate receptor activity at the spinal cord level effectively reduces pain hypersensitivity induced by the calcineurin inhibitor.
This information advances our understanding of the molecular basis of pain caused by calcineurin inhibitors and identifies new strategies for treating such pain syndrome in transplant patients.
Abstract  Calcineurin inhibitors, such as cyclosporin A and tacrolimus (FK506), have played a pivotal role in the preservation of allograft function. However, these drugs can cause unexplained severe pain in patients, often referred to as calcineurin inhibitor‐induced pain syndrome (CIPS). Although calcineurin can regulate NMDA receptor (NMDAR) activity, the causal relationship between spinal synaptic plasticity and CIPS remains unknown. In this study, we showed that systemic administration of FK506 (1.5 mg kg−1 day−1) for 7 days in rats led to long‐lasting nociceptive and mechanical hypersensitivity. Whole‐cell patch‐clamp recordings in spinal cord slices revealed that FK506 treatment caused a large increase in the amplitude of NMDAR‐mediated excitatory postsynaptic currents (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation. The amplitude of NMDAR currents elicited by puff NMDA application to dorsal horn neurons was also significantly greater in FK506‐treated than in vehicle‐treated rats. The frequency of spontaneous and miniature EPSCs in most dorsal horn neurons was profoundly increased in FK506‐treated rats and was reduced by blocking NMDARs. Furthermore, blocking GluN2A or GluN2B subunits similarly reduced the amplitude of evoked EPSCs and the frequency of miniature EPSCs in dorsal horn neurons of FK506‐treated rats. In addition, intrathecal injection of an NMDAR antagonist or systemic administration of memantine effectively reversed nociceptive and mechanical hypersensitivity in FK506‐treated rats. Our findings indicate that calcineurin inhibition increases glutamate‐mediated nociceptive input by potentiating presynaptic and postsynaptic NMDAR activity in spinal cords. NMDAR antagonists may represent a new therapeutic option for the treatment of CIPS.
Safety, Tolerability, and Pharmacokinetics of Ribavirin in Hepatitis C Virus-Infected Patients with Various Degrees of Renal Impairment
Authors: Brennan B. J. , Wang K. , Blotner S. , Magnusson M. O. , Wilkins J. J. , Martin P. , Solsky J. , Nieforth K. , Wat C. , Grippo J. F. 
Published: October 2013

ABSTRACT

Ribavirin (RBV) is an integral part of standard-of-care hepatitis C virus (HCV) treatments and many future regimens under investigation. The pharmacokinetics (PK), safety, and tolerability of RBV in chronically HCV-infected patients with renal impairment are not well defined and were the focus of an open-label PK study in HCV-infected patients receiving RBV plus pegylated interferon. Serial RBV plasma samples were collected over 12 h on day 1 of weeks 1 and 12 from patients with moderate renal impairment (creatinine clearance [CL
CR
], 30 to 50 ml/min; RBV, 600 mg daily), severe renal impairment (CL
CR
, <30 ml/min; RBV, 400 mg daily), end-stage renal disease (ESRD) (RBV, 200 mg daily), or normal renal function (CL
CR
, >80 ml/min; RBV, 800 to 1,200 mg daily). Of the 44 patients, 9 had moderately impaired renal function, 10 had severely impaired renal function, 13 had ESRD, and 12 had normal renal function. The RBV dose was reduced because of adverse events (AEs) in 71% and 53% of severe and moderate renal impairment groups, respectively. Despite this modification, patients with moderate and severe impairment had 12-hour (area under the concentration-time curve from 0 to 12 h [AUC
0–12
]) values 36% (38,452 ng · h/ml) and 25% (35,101 ng · h/ml) higher, respectively, than those with normal renal function (28,192 ng · h/ml). Patients with ESRD tolerated a 200-mg daily dose, and AUC
0–12
was 20% lower (22,629 ng · h/ml) than in patients with normal renal function. PK modeling and simulation (M&S) indicated that doses of 200 mg or 400 mg alternating daily for patients with moderate renal impairment and 200 mg daily for patients with severe renal impairment were the most appropriate dose regimens in these patients.
Antibiotic Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae: Systematic Evaluation of the Available Evidence
Authors: Falagas Matthew E. , Lourida Panagiota , Poulikakos Panagiotis , Rafailidis Petros I. , Tansarli Giannoula S. 
Published: October 2013

ABSTRACT

We sought to evaluate the effectiveness of the antibiotic treatment administered for infections caused by carbapenemase-producing
Enterobacteriaceae
. The PubMed and Scopus databases were systematically searched. Articles reporting the clinical outcomes of patients infected with carbapenemase-producing
Enterobacteriaceae
according to the antibiotic treatment administered were eligible. Twenty nonrandomized studies comprising 692 patients who received definitive treatment were included. Almost all studies reported on
Klebsiella
spp. In 8 studies, the majority of infections were bacteremia, while pneumonia and urinary tract infections were the most common infections in 12 studies. In 10 studies, the majority of patients were critically ill. There are methodological issues, including clinical heterogeneity, that preclude the synthesis of the available evidence using statistical analyses, including meta-analysis. From the descriptive point of view, among patients who received combination treatment, mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the monotherapy-treated patients, mortality was up to 57% for colistin and up to 80% for tigecycline. Certain regimens were administered to a small number of patients in certain studies. Three studies reporting on 194 critically ill patients with bacteremia showed individually significantly lower mortality in the combination arm than in the monotherapy arm. In the other studies, no significant difference in mortality was recorded between the compared groups. Combination antibiotic treatment may be considered the optimal option for severely ill patients with severe infections. However, well-designed randomized studies of specific patient populations are needed to further clarify this issue.
A Novel Investigational Fc-Modified Humanized Monoclonal Antibody, Motavizumab-YTE, Has an Extended Half-Life in Healthy Adults
Authors: Robbie Gabriel J. , Criste Ryan , Dall'Acqua William F. , Jensen Kathryn , Patel Nita K. , Losonsky Genevieve A. , Griffin M. Pamela 
Published: October 2013

ABSTRACT

The study objective was to evaluate the pharmacokinetics (PK), antidrug antibody (ADA), and safety of motavizumab-YTE (motavizumab with amino acid substitutions M252Y/S254T/T256E [YTE]), an Fc-modified anti-respiratory syncytial virus (RSV) monoclonal antibody. Healthy adults (
n
= 31) were randomized to receive a single intravenous (i.v.) dose of motavizumab-YTE or motavizumab (0.3, 3, 15, or 30 mg/kg) and followed for 240 days. Clearance of motavizumab-YTE was significantly lower (71% to 86%) and the half-life (
t
1/2
) was 2- to 4-fold longer than with motavizumab. However, similar peak concentrations and volume-of-distribution values, indicative of similar distribution properties, were seen at all dose levels. The sustained serum concentrations of motavizumab-YTE were fully functional, as shown by RSV neutralizing activity that persisted for 240 days with motavizumab-YTE versus 90 days postdose for motavizumab. Safety and incidence of ADA were comparable between groups. In this first study of an Fc-modified monoclonal antibody in humans, motavizumab-YTE was well tolerated and exhibited an extended half-life of up to 100 days. (This study has been registered at ClinicalTrials.gov under registration no. NCT00578682.)
Cell Culture-Selected Substitutions in Influenza A(H3N2) Neuraminidase Affect Drug Susceptibility Assessment
Authors: Tamura Daisuke , Nguyen Ha T. , Sleeman Katrina , Levine Marnie , Mishin Vasiliy P. , Yang Hua , Guo Zhu , Okomo-Adhiambo Margaret , Xu Xiyan , Stevens James , Gubareva Larisa V. 
Published: October 2013

ABSTRACT

Assessment of drug susceptibility has become an integral part of influenza virus surveillance. In this study, we describe the drug resistance profile of influenza A(H3N2) virus, A/Mississippi/05/2011, collected from a patient treated with oseltamivir and detected via surveillance. An MDCK cell-grown isolate of this virus exhibited highly reduced inhibition by the neuraminidase (NA) inhibitors (NAIs) oseltamivir (8,005-fold), zanamivir (813-fold), peramivir (116-fold), and laninamivir (257-fold) in the NA inhibition assay. Sequence analysis of its NA gene revealed a known oseltamivir-resistance marker, the glutamic acid-to-valine substitution at position 119 (E119V), and an additional change, threonine to isoleucine at position 148 (T148I). Unlike E119V, T148I was not detected in the clinical sample but acquired during viral propagation in MDCK cells. Using recombinant proteins, T148I by itself was shown to cause only a 6-fold increase in the zanamivir 50% inhibitory concentration (IC
50
) and had no effect on inhibition by other drugs. The T148I substitution reduced NA activity by 50%, most likely by affecting the positioning of the 150 loop at the NA catalytic site. Using pyrosequencing, changes at T148 were detected in 35 (23%) of 150 MDCK cell-grown A(H3N2) viruses tested, which was lower than the frequency of changes at D151 (85%), an NA residue previously implicated in cell selection. We demonstrate that culturing of the A(H3N2) viruses (
n
= 11) at a low multiplicity of infection delayed the emergence of the NA variants with changes at position 148 and/or 151, especially when conducted in MDCK-SIAT1 cells. Our findings highlight the current challenges in monitoring susceptibility of influenza A(H3N2) viruses to the NAI class of antiviral drugs.
Repeat Polymorphisms in the Low-Complexity Regions of Plasmodium falciparum ABC Transporters and Associations with
In Vitro
Antimalarial Responses
Authors: Okombo John , Abdi Abdirahman I. , Kiara Steven M. , Mwai Leah , Pole Lewa , Sutherland Colin J. , Nzila Alexis , Ochola-Oyier Lynette Isabella 
Published: October 2013

ABSTRACT

The
Plasmodium falciparum
genome is rich in regions of low amino acid complexity which evolve with few constraints on size. To explore the extent of diversity in these loci, we sequenced repeat regions in
pfmdr1
,
pfmdr5
,
pfmdr6
,
pfmrp2
, and the antigenic locus
pfmsp8
in laboratory and cultured-adapted clinical isolates. We further assessed associations between the repeats and parasite
in vitro
responses to 7 antimalarials to determine possible adaptive roles of these repeats in drug tolerance. Our results show extensive repeat variations in the reference and clinical isolates in all loci. We also observed a modest increase in dihydroartemisinin activity in parasites harboring the
pfmdr1
sequence profile 7-2-10 (reflecting the number of asparagine repeats, number of aspartate repeats, and number of asparagine repeats in the final series of the gene product) (
P
= 0.0321) and reduced sensitivity to chloroquine, mefloquine, quinine, and dihydroartemisinin in those with the 7-2-11 profile (
P
= 0.0051, 0.0068, 0.0011, and 0.0052, respectively). Interestingly, we noted an inverse association between two drugs whereby isolates with 6 asparagine repeats encoded by
pfmdr6
were significantly more susceptible to piperaquine than those with 8 (
P
= 0.0057). Against lumefantrine, those with 8 repeats were, however, more sensitive (
P
= 0.0144). In
pfmrp2
, the 7-
D
NNNTS/
N
NNNTS (number of DNNNTS or NNNNTS motifs; underlining indicates dimorphism) repeat group was significantly associated with a higher lumefantrine 50% inhibitory concentration (IC
50
) (
P
= 0.008) than in those without. No associations were observed with
pfmsp8
. These results hint at the probable utility of some repeat conformations as markers of
in vitro
antimalarial response; hence, biochemical functional studies to ascertain their role in
P. falciparum
are required.
Within-Host Selection Is Limited by an Effective Population of Streptococcus pneumoniae during Nasopharyngeal Colonization
Authors: Li Yuan , Thompson Claudette M. , Trzciński Krzysztof , Lipsitch Marc 
Published: October 2013

ABSTRACT

Streptococcus pneumoniae
(pneumococcus) is a significant pathogen that frequently colonizes the human nasopharynx. Environmental factors, including antimicrobial use and host immunity, exert selection on members of the nasopharyngeal population, and the dynamics of selection are influenced by the effective population size of the selected population, about which little is known. We measured here the variance effective population size (N
e
) of pneumococcus in a mouse colonization model by monitoring the frequency change of two cocolonizing, competitively neutral pneumococcal strains over time. The point estimate of N
e
during nasal carriage in 16 BALB/c mice was 133 (95% confidence interval [CI] = 11 to 203). In contrast, the lower-bound census population exhibited a mean of 5768 (95% CI = 2,515 to 9,021). Therefore, pneumococcal N
e
during nasal carriage is substantially smaller than the census population. The N
e
during day 1 to day 4 of colonization was comparable to the N
e
during day 4 to day 8. Similarly, a low N
e
was also evident for the colonization of pneumococcus in BALB/c mice exposed to cholera toxin 4 weeks prior to challenge and in another mouse strain (DO11.10 RAG
−/−
). We developed a mathematical model of pneumococcal colonization composed of two subpopulations with differential contribution to future generations. By stochastic simulation, this model can reproduce the pattern of observed pneumococcal N
e
and predicts that the selection coefficients may be difficult to measure
in vivo
. We hypothesized that such a small N
e
may reduce the effectiveness of within host selection for pneumococcus.
Differential Roles of ASK1 and TAK1 in Helicobacter pylori-Induced Cellular Responses
Authors: Hayakawa Yoku , Hirata Yoshihiro , Kinoshita Hiroto , Sakitani Kosuke , Nakagawa Hayato , Nakata Wachiko , Takahashi Ryota , Sakamoto Kei , Maeda Shin , Koike Kazuhiko 
Published: October 2013

ABSTRACT

The mitogen-activated protein kinase (MAPK) signaling pathway regulates various cellular functions, including those induced by
Helicobacter pylori
. TAK1 is an upstream MAPK kinase kinase (MAP3K) required for
H. pylori
-induced MAPK and NF-κB activation, but it remains unclear whether other MAP3Ks are involved in
H. pylori
-induced cellular responses. In this study, we focused on the MAP3K ASK1, which plays a critical role in gastric tumorigenesis. In gastric epithelial cells,
H. pylori
activates ASK1 in a reactive oxygen species (ROS)- and
cag
pathogenicity island-dependent manner, and ASK1 regulates sustained JNK activation and apoptosis induced by
H. pylori
. In contrast, TAK1 regulates
H. pylori
-mediated early JNK activation and cytokine production. We also found reciprocal regulation between ASK1 and TAK1 in
H. pylori
-related responses, whereby inhibition of TAK1 or downstream p38 MAPK activates ASK1 through ROS production, and ASK1 suppresses TAK1 and downstream NF-κB activation. We identified ROS/ASK1/JNK as a new signaling pathway induced by
H. pylori
, which regulates apoptotic cell death. The balance of ASK1-induced apoptosis and TAK1-induced antiapoptotic or inflammatory responses may determine the fate of epithelial cells infected with
H. pylori
and thus be involved in the pathogenesis of gastritis and gastric cancer.
B Cell Activating Factor Inhibition Impairs Bacterial Immunity by Reducing T Cell-Independent IgM Secretion
Authors: Jones Derek D. , Jones Maura , DeIulio Gregory A. , Racine Rachael , MacNamara Katherine C. , Winslow Gary M. 
Published: October 2013

ABSTRACT

B cell activating factor of the tumor necrosis factor family (BAFF) is an essential survival factor for B cells and has been shown to regulate T cell-independent (TI) IgM production. During
Ehrlichia muris
infection, TI IgM secretion in the spleen was BAFF dependent, and antibody-mediated BAFF neutralization led to an impairment of IgM-mediated host defense. The failure of TI plasmablasts to secrete IgM was not a consequence of alterations in their generation, survival, or early differentiation, since all occurred normally in infected mice following BAFF neutralization. Gene expression characteristic of plasma cell differentiation was also unaffected by BAFF neutralization
in vivo
, and except for CD138, plasmablast cell surface marker expression was unaffected. IgM was produced, since it was detected intracellularly, and impaired secretion was not due to a failure to express the IgM secretory exon. Addition of BAFF to plasmablasts
in vitro
rescued IgM secretion, suggesting that BAFF signaling can directly regulate secretory processes. Our findings indicate that BAFF signaling can modulate TI host defense by acting at a late stage in B cell differentiation, via its regulation of terminal plasmablast differentiation and/or IgM secretion.