bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the causes and consequences of animal movement: a cautionary note on fitting and interpreting regression models with time‐dependent covariates
Authors: Fieberg J. , Ditmer M.
Published: September 2012

New technologies have made it possible to simultaneously, and remotely, collect time series of animal location data along with indicators of individuals' physiological condition. These data, along with animal movement models that incorporate individual physiological and behavioural states, promise to offer new insights into determinants of animal behaviour. Care must be taken, however, when attempting to infer causal relationships from biotelemetry data. The possibility of unmeasured confounders, responsible for driving both physiological measurements and animal movement, must be considered. Further, response valuesmay be predictive of future covariate values. When this occurs, the covariate process is said to be endogenous with respect to the response variable, which has implications for both choosing statistical estimation targets and also estimators of these quantities.

We explore models that attempt to relate =  log(daily movement rate) to =  log(average daily heart rate) using data collected from a black bear (Ursus americanus) population in Minnesota. The regression parameter forwas 0·19 and statistically different from 0 (P < 0·001) when daily measurements were assumed to be independent, but residuals were highly autocorrelated. Assuming an autoregressive model (ar(1)) for the residuals, however, resulted in a negative slope estimate (‐0·001) that was not statistically different from 0.

The sensitivity of regression parameters to the assumed error structure can be explained by exploring relationships between lagged and current values ofxandyand between parameters in the independence and ar(1) models. We hypothesize that an unmeasured confounder may be responsible for the behaviour of the regression parameters. In addition, measurement error associated with daily movement rates may also play a role.

Similar issues often arise in epidemiological, biostatistical and econometrics applications; directed acyclical graphs, representing causal pathways, are central to understanding potential problems (and their solutions) associated with modelling time‐dependent covariates. In addition, we suggest that incorporating lagged responses and lagged predictors as covariates may prove useful for diagnosing when and explaining why some conclusions are sensitive to model assumptions.
Effect of butorphanol on thermal nociceptive threshold in healthy pony foals
Authors: McGowan K. T. , Elfenbein J. R. , Robertson S. A. , Sanchez L. C.
Published: September 2012

Reasons for performing study

Pain management is an important component of foal nursing care, and no objective data currently exist regarding the analgesic efficacy of opioids in foals.

Objectives

To evaluate the somatic antinociceptive effects of 2 commonly used doses of intravenous (i.v.) butorphanol in healthy foals. Our hypothesis was that thermal nociceptive threshold would increase following i.v. butorphanol in a dose‐dependent manner in both neonatal and older pony foals.

Methods

Seven healthy neonatal pony foals (age 1–2 weeks), and 11 healthy older pony foals (age 4–8 weeks). Five foals were used during both age periods. Treatments, which included saline (0.5 ml), butorphanol (0.05 mg/kg bwt) and butorphanol (0.1 mg/kg bwt), were administered i.v. in a randomised crossover design with at least 2 days between treatments. Response variables included thermal nociceptive threshold, skin temperature and behaviour score. Data within each age period were analysed using a 2‐way repeated measures ANOVA, followed by a Holm–Sidak multiple comparison procedure if warranted.

Results

There was a significant (P<0.05) increase in thermal threshold, relative to Time 0, following butorphanol (0.1 mg/kg bwt) administration in both age groups. No significant time or treatment effects were apparent for skin temperature. Significant time, but not treatment, effects were evident for behaviour score in both age groups.

Conclusions

Butorphanol (0.1 mg/kg bwt, but not 0.05 mg/kg bwt) significantly increased thermal nociceptive threshold in neonatal and older foals without apparent adverse behavioural effects.

Potential relevance

Butorphanol shows analgesic potential in foals for management of somatic painful conditions.
Human–Animal Interaction: A Concept Analysis
Authors: Vitztum Coley
Published: September 2012

PURPOSE:  A concept analysis was performed on human–animal interaction (HAI).

DATA SOURCE:  Nursing, psychology, and behavioral sciences literature.

DATA SYNTHESIS:  Uses and definitions associated with HAI were used to articulate the attributes, antecedents, consequences, and empirical referents. Model, borderline, and contrary cases were developed.

CONCLUSIONS:  HAI is operationally defined.

IMPLICATIONS FOR NURSING PRACTICE:  Including HAI as a health promotion behavior, within a theoretical framework, appears to be a promising intervention and may be linked to physical activity.
Psychometric Evaluation of the Functional Health Pattern Assessment Screening Tool (FHPAST)
Authors: Jones Dorothy , Duffy Mary E. , Flanagan Jane , Foster Frances
Published: September 2012

PURPOSE:  To report findings of psychometric testing of the Functional Health Pattern Screening Tool (FHPAST).

METHODS:  Psychometric evaluation including internal consistency and principal components analysis.

FINDINGS:  The findings indicate that the FHPAST is a reliable, three‐component, 57‐item valid instrument.

CONCLUSIONS:  Psychometric testing supports the use of the FHPAST in research. The instrument captures each of the 11 functional health patterns as described by Gordon (1994) and has been translated into, and is available in, several languages.

PRACTICE IMPLICATIONS:  Continued testing and refinement is needed across populations to support the findings from this investigation and to evaluate the outcomes of patient‐centered interventions over time.
Smoking initiation and personal characteristics of secondary students in Hong Kong
Authors: Tang Sze Man , Loke Alice Yuen
Published: September 2012

Aim

To explore the relationship between personal characteristics and smoking initiation among adolescents in Hong Kong.

Background

Adolescents have been initiating cigarette smoking at an increasing rate in recent years. Preventing tobacco use among young children has become one of the most effective strategies to reduce the harmful effects of tobacco use.

Design

A cross‐sectional study.

Methods

Secondary students were recruited by convenience sampling from schools in the New Territories of Hong Kong in 2010. Questionnaires were used to collect information relating to their demographic and personal characteristics, including behavioural control, coping styles, sociability, locus of control, rebelliousness, self‐esteem, emotional distress, and intention to smoke.

Results

A total of 644 secondary students were recruited. The prevalence of having ever tried smoking was 19·4% and that of regular smoking was 3·9% among these students. The results of this study show that secondary students who were living in public housing and had lower behavioural control and higher smoking intention were more likely to have tried smoking or to be regular smokers, indicating that these factors contribute to smoking initiation among secondary students.

Conclusions

The personal characteristics of secondary students do play a role in smoking initiation. Parents and school personnel should work together to help young people to improve their self‐esteem and behavioural control and to overcome their rebelliousness. The causes of smoking intention should also be explored to stop young people from picking up their first cigarette.
Characterization of Freshwater Diatom Communities: Comparing Taxonomic and Genetic‐Fingerprinting Approaches
Authors: Morin Soizic , Roubeix Vincent , Batisson Isabelle , Winterton Peter , Pesce Stéphane
Published: September 2012

Benthic diatom assemblages from five sampling sites located on two rivers were characterized simultaneously by means of traditional microscopic observations and PCR‐DGGE fingerprinting with primers specifically designed for Bacillariophyceae. Community structure, richness, and diversity assessed by both methods were compared. Diatom lists obtained from morphological identification were separated into subsets, depending on (i) the taxonomic level considered (genus, species, variety) and, for each of them, (ii) the relative abundance (RA) of each component (the whole data set, RA > 1%, RA > 2%). These data were then compared to genetic fingerprinting data. Clusters based on taxonomic composition and DGGE banding patterns were very similar, showing good correspondence of community structure between the two methods. Data were compared by linear regressions between indices (richness, diversity) and by Mantel tests on dissimilarity matrices generated for each community composition data set. Statistical analysis indicated that the most reliable correlations with fingerprinting were obtained for genera representing more than 1% RA or species representing more than 2% RA. The results reveal that the PCR‐DGGE protocol described here offers a satisfactory alternative for performing preliminary screening of coarse differences in diatom global community structure between samples. It can be regarded as a good complement to taxonomic analyses, which still remain necessary to detect precise changes in richness and diversity, especially when considering species with low abundance in natural assemblages.
Exercise Training‐Enhanced, Endothelium‐Dependent Dilation Mediated by Altered Regulation of BKCa Channels in Collateral‐Dependent Porcine Coronary Arterioles
Authors: Xie Wei , Parker Janet L. , Heaps Cristine L.
Published: September 2012

Objective

Test the hypothesis that exercise training increases the contribution of BKCa channels to endothelium‐mediated dilation in coronary arterioles from collateral‐dependent myocardial regions of chronically occluded pig hearts and may function downstream of H2O2.

Methods

An ameroid constrictor was placed around the proximal left circumflex coronary artery to induce gradual occlusion in Yucatan miniature swine. Eight weeks postoperatively, pigs were randomly assigned to sedentary or exercise training (treadmill; 14 week) regimens.

Results

Exercise training significantly enhanced bradykinin‐mediated dilation in collateral‐dependent arterioles (~125 μm diameter) compared with sedentary pigs. The BKCa‐channel blocker, iberiotoxin alone or in combination with the H2O2 scavenger, polyethylene glycol catalase, reversed exercise training‐enhanced dilation in collateral‐dependent arterioles. Iberiotoxin‐sensitive whole‐cell K+ currents (i.e., BKCa‐channel currents) were not different between smooth muscle cells of nonoccluded and collateral‐dependent arterioles of sedentary and exercise trained groups.

Conclusions

These data provide evidence that BKCa‐channel activity contributes to exercise training‐enhanced endothelium‐dependent dilation in collateral‐dependent coronary arterioles despite no change in smooth muscle BKCa‐channel current. Taken together, our findings suggest that a component of the bradykinin signaling pathway, which stimulates BKCa channels, is enhanced by exercise training in collateral‐dependent arterioles and suggest a potential role for H2O2 as the mediator.
Heterologous assembly of type IV pili by a type II secretion system reveals the role of minor pilins in assembly initiation
Authors: Cisneros David A. , Pehau‐Arnaudet Gerard , Francetic Olivera
Published: September 2012

In Gram‐negative bacteria, type IV pilus assembly (T4PS) and type II secretion (T2SS) systems polymerize inner membrane proteins called major pilins or pseudopilins respectively, into thin filaments. Four minor pilins are required in both systems for efficient fibre assembly. Escherichia coli K‐12 has a set of T4PS assembly genes that are silent under standard growth conditions. We studied the heterologous assembly of the E. coli type IV pilin PpdD by the Klebsiella oxytoca T2SS called the Pul system. PpdD pilus assembly in this context depended on the expression of the K. oxytoca minor pseudopilin genes pulHIJK or of the E. coli minor pilin genes ppdAB‐ygdB‐ppdC. The E. coli minor pilins restored assembly of the major pseudopilin PulG in a pulHIJK mutant, but not the secretion of the T2SS substrate pullulanase. Thus, minor pilins and minor pseudopilins are functionally interchangeable in initiating major pilin assembly, further extending the fundamental similarities between the two systems. The data suggest that, in both systems, minor pilins activate the assembly machinery through a common self‐assembly mechanism. When produced together, PulG and PpdD assembled into distinct homopolymers, establishing major pilins as key determinants of pilus elongation and structure.
Association of pertussis and measles infections and immunizations with asthma and allergic sensitization in ISAAC Phase Two
Authors: Nagel Gabriele , Weinmayr Gudrun , Flohr Carsten , Kleiner Andrea , Strachan David P. ,   ISAAC Phase Two Study Group
Published: September 2012

Background

Pertussis and measles infection as well as vaccination have been suspected as possible mediating factors of allergic disease in childhood.

Methods

Between 1995 and 2005 cross‐sectional studies were performed in 29 centers in 21 countries. Parental questionnaires were used to collect information on allergic diseases and exposures. We analyzed data from 54,943 randomly selected schoolchildren aged 8–12 yr. A subgroup of 31,759 children was also skin prick tested (SPT) to common environmental allergens. Combined odds ratios were calculated by random effect models for meta‐analysis.

Results

Pertussis and measles vaccination were not significantly associated with any of the allergy outcomes or SPT positivity. However, pertussis infection was associated with wheeze (ORad 1.68; 95% CI 1.44–1.97) and rhinoconjunctivitis (ORad 1.63; 95% 1.33–2.00). Pertussis infection was also significantly associated with a higher prevalence of reported eczema during the past year in non‐affluent countries. Measles infection was associated with a higher prevalence of wheeze (ORad 1.26; 95% 1.10–1.43) and reported eczema (ORad 1.22; 95% 1.08–1.39). No association with SPT positivity was found, suggesting that these associations are unlikely to be mediated by an allergic component.

Conclusions

Associations of pertussis and measles infection with symptoms of asthma, rhinoconjunctivitis and eczema were found in both affluent and non‐affluent countries and are unlikely to be mediated by IgE.
Clinical experience with intraoperative jugular venous oximetry during pediatric intracranial neurosurgery
Authors: Sharma Deepak , Siriussawakul Arunotai , Dooney Neil , Hecker James G. , Vavilala Monica S.
Published: September 2012

Aim

To report our institutional experience with intraoperative jugular venous oximetry during pediatric intracranial surgery to guide anesthetic care.

Background

The utility of intraoperative jugular venous oximetry in adults undergoing intracranial surgery is well known. However, there is a little information on its' application in children during intracranial surgery.

Methods

After IRB approval, we examined patient, equipment, placement, and sampling characteristics for jugular bulb catheters in children aged <18 years who were monitored with jugular oximetry during elective intracranial surgery between 2006 and 2010. We also determined the prevalence of intraoperative cerebral desaturation (SjvO2 < 55%), its causes, and the interventions based on jugular oximetry values.

Results

Data from 19 children (10 males and nine females), aged 12 ± 1 years (range 7–17) who underwent craniotomy for arteriovenous malformation (AVM) resection (68%), tumor removal (21%), or aneurysm clipping (11%), were reviewed. We analyzed 88 coincident SjvO2, PaCO2, and mean arterial pressure data points. Eleven (58%) patients experienced at least one episode of cerebral desaturation. There were 25 (28%) episodes of cerebral desaturation, six of which we attributed to relative hypotension, four to hypocarbia, and 15 to a combination of both. There were no intraoperative or immediate postoperative (first 24 h) complications because of jugular oximetry.

Conclusion

Findings from this series indicate that (i) intraoperative jugular venous oximetry in children is feasible in experienced hands, (ii) cerebral desaturation detected by jugular oximetry is common during pediatric intracranial procedures, and (iii) monitoring jugular venous saturation can impact anesthetic interventions to optimize cerebral physiology.
Information and Support Needs among Parents of Young Children in a Region of Canada: A Cross‐Sectional Survey
Authors: Devolin Maureen , Phelps Dawn , Duhaney Tara , Benzies Karen , Hildebrandt Clare , Rikhy Shivani , Churchill Jocelyn
Published: September 2012

Objective

To determine the information and support needs among parents of young children in a region of Canada.

Design and Sample

A cross‐sectional survey was mailed to a stratified random sample of 1,064 parents of children aged 6 years and under. Of the 359 respondents, the majority were Caucasian, female, married, and well educated.

Measures

An investigator designed questionnaire measured preferred sources of parenting information and support, sources and modes of program delivery, and perceived barriers to accessing information and programs.

Results

Breastfeeding, car seat safety, caring for a new baby, supporting their child's development, and sleep issues were considered “somewhat” or “very” important by 95.8% of respondents. Informal sources of support were rated as more important and more valuable than formal supports. The internet, drop‐in programs for parents and children, books, organized play groups, classes and information sessions were identified as the most preferred modes to access parenting information. Respondents reported a lack of knowledge and awareness of programs, lack of time, lack of child care, and inconvenient scheduling as the top barriers to accessing information and programs.

Conclusions

Parents want information to support their parenting. These results have implications for planning and implementation of future parenting information and support programs and services.
Photophysical Properties of 7‐(diethylamino)Coumarin‐3‐carboxylic Acid in the Nanocage of Cyclodextrins and in Different Solvents and Solvent Mixtures
Authors: Chatterjee Aninda , Seth Debabrata
Published: September 2012

The photophysical properties of 7‐(diethylamino) coumarin‐3‐carboxylic acid (7‐DCCA) were studied in cyclodextrins (α, β, γ,‐CDs), different neat solvents and solvent mixtures by using steady state absorption, emission and time‐resolved fluorescence spectroscopy. We have observed that with gradual increase in concentration of β‐CD the fluorescence quantum yield and lifetime decreased in a regular pattern whereas with gradual increase in concentration of γ‐CD the fluorescence quantum yield and lifetime gradually increased. With addition of urea, the fluorescence quantum yield and lifetime of 7‐DCCA in CDs increased. Binding constant calculation shows that 7‐DDCA forms 1:1 complex with β‐CD and with γ‐CD it forms 1:1 and 1:2 (guest:host) inclusion complex. We proposed that the dye molecule formed capping complex with β‐CD by means of hydrogen bonding and after addition of urea the hydrogen bonding network broke down and part of dye molecule entered inside the cavity of β‐CD. The photophysics of 7‐DCCA was studied in dioxane‐water mixture and ethylene glycol‐acetonitrile mixture to know the effect of polarity and viscosity of the media. The photophysics of 7‐DCCA was also studied in different neat solvents. It was found that the photophysics of 7‐DCCA depended on the structural feature of the solvents and solvent mixtures.
Tolerance to Solar Ultraviolet‐B Radiation in the Citrus Red Mite, An Upper Surface User of Host Plant Leaves
Authors: Fukaya Midori , Uesugi Ryuji , Ohashi Hirokazu , Sakai Yuta , Sudo Masaaki , Kasai Atsushi , Kishimoto Hidenari , Osakabe Masahiro
Published: September 2012

Plant‐dwelling mites are potentially exposed to solar ultraviolet‐B (UVB) radiation that causes deleterious and often lethal effects, leading most mites to inhabit the lower (underside) leaf surfaces. However, in species of spider mite belonging to the Genus Panonychus, a substantial portion of individuals occur on upper leaf surfaces. We investigated whether the upper leaf surfaces of citrus trees are favorable for P. citri, and to what extent they are tolerant to UVB radiation. If eggs are not adequately protected from UVB damage, females may avoid ovipositing on the upper surfaces of sunny leaves. To test this, we conducted laboratory experiments using a UVB lamp, and semioutdoor manipulative experiments. As a result, P. citri eggs are tolerant to UVB. Field studies revealed that the ratio of eggs and adult females on upper leaf surfaces were larger for shaded than for sunny leaves. However, 64–89% of eggs hatched successfully even on sunny upper leaf surfaces. Nutritional evaluation revealed that whether on sunny or shaded leaves, in fecundity and juvenile development P. citri reaped the fitness benefits of upper leaf surfaces. Consequently, P. citri is tolerant to UVB damage, and inhabiting the upper surfaces of shaded leaves is advantageous to this mite.
Intermolecular π‐Electron Perturbations Generate Extrinsic Visible Contributions to Eumelanin Black Chromophore in Model Polymers with Interrupted Interring Conjugation
Authors: Ascione Laura , Pezzella Alessandro , Ambrogi Veronica , Carfagna Cosimo , d'Ischia Marco
Published: September 2012

The key structural factors underlying the unique black chromophore of eumelanin biopolymers have so far defied elucidation. Capitalizing on the ability of 1% polyvinylalcohol (PVA) to prevent pigment precipitation during melanogenesis in vitro, we have investigated the visible chromophore properties of soluble eumelanin‐like polymers produced by biomimetic oxidation of 5,6‐dihydroxyindole (DHI) and 5,6‐dihydroxyindole‐2‐carboxylic (DHICA) in 1% PVA‐containing buffer at pH 7. Upon dilution DHI‐eumelanin solutions exhibited almost linear visible absorbance changes, whereas DHICA‐eumelanin displayed a remarkable deviation from linearity in simple buffer, but not in PVA‐containing buffer. It is suggested that in DHICA polymers, exhibiting repeated interruptions of interring conjugation due to lack of planar conformations, the black chromophore is not due to an overlap of static entities defined intrinsically by the conjugation length across the carbon frame, but results largely from aggregation‐related intermolecular perturbations of the π‐electron systems which are extrinsic in character.
Late Aptian long‐lived glacio‐eustatic lowstand recorded on the Arabian Plate
Authors: Maurer Florian , van Buchem Frans S.P. , Eberli Gregor P. , Pierson Bernard J. , Raven Madeleine J. , Larsen Poul‐Henrik , Al‐Husseini Moujahed I. , Vincent Benoit
Published: September 2012

Terra Nova, 25, 87–94, 2013

Compelling physical evidence for a Late Aptian lowstand with an amplitude of at least 50 m is presented in subsurface seismic and core data from the Arabian Plate. Biostratigraphic dating indicates that the fall and rise bracketing this lowstand were rapid, and that the lowstand lasted for around 5 ma with distinctly cyclic sedimentation at the 0.4–0.5 ma scale (eccentricity band). A glacio‐eustatic mechanism is invoked as the most likely cause, which is supported by cooling indicated in oxygen isotope shifts and by evidence for a global expression of this lowstand from a number of locations at the mid and high latitudes. Hence, the Late Aptian data presented here document the longest Cretaceous sea‐level lowstand, interpreted as the longest cooling phase during the Cretaceous greenhouse.
Were ancient granitoid compositions influenced by contemporaneous atmospheric and hydrosphere oxidation states?
Authors: Jagoutz Oliver
Published: September 2012

Terra Nova, 00, 1–7, 2012

A feedback loop between subducted oceanic plate composition, subduction zone processes, arc magma chemistry, and the newly formed continental crust composition links to atmospheric and hydrosphere oxidation conditions through the low temperature weathering mechanisms of seafloor basalts. Sea‐floor weathering and the Na/K of the altered oceanic crust strongly depends on f(O2) conditions during alteration, that changed with earth history. The rise of oxygen at ∼2600–2400 Ma triggered associated changes in f(O2) seafloor alteration conditions providing a possible explanation for the observed change from the Na‐rich tonalite‐trondhjemite‐granodiorite (TTG) rocks in the Archean to the K‐rich granodiorite‐granite (GG) granitoids in post‐Archean times.
Design of chimeric expression elements that confer high‐level gene activity in chromoplasts
Authors: Caroca Rodrigo , Howell Katharine A. , Hasse Claudia , Ruf Stephanie , Bock Ralph
Published: September 2012

Non‐green plastids, such as chromoplasts, generally have much lower activity of gene expression than chloroplasts in photosynthetically active tissues. Suppression of plastid genes in non‐green tissues occurs through a complex interplay of transcriptional and translational control, with the contribution of regulation of transcript abundance versus translational activity being highly variable between genes. Here, we have investigated whether the low expression of the plastid genome in chromoplasts results from inherent limitations in gene expression capacity, or can be overcome by designing appropriate combinations of promoters and translation initiation signals in the 5′ untranslated region (5′–UTR). We constructed chimeric expression elements that combine promoters and 5′–UTRs from plastid genes, which are suppressed during chloroplast‐to‐chromoplast conversion in Solanum lycopersicum (tomato) fruit ripening, either just at the translational level or just at the level of mRNA accumulation. These chimeric expression elements were introduced into the tomato plastid genome by stable chloroplast transformation. We report the identification of promoter‐UTR combinations that confer high‐level gene expression in chromoplasts of ripe tomato fruits, resulting in the accumulation of reporter protein GFP to up to 1% of total cellular protein. Our work demonstrates that non‐green plastids are capable of expressing genes to high levels. Moreover, the chimeric cis‐elements for chromoplasts developed here are widely applicable in basic and applied research using transplastomic methods.
Genetic and pharmacological modulation of giant depolarizing potentials in the neonatal hippocampus associates with increased seizure susceptibility
Authors: Vargas Ernesto , Petrou Steven , Reid Christopher A.
Published: September 2012

Key points

Our earlier work established that seizure susceptibility in the GABAAγ2R43Q epilepsy mouse may be in part due to the developmental consequences of impaired GABA­A receptor function.

Giant depolarizing potentials (GDP) are brain network activity that involve GABA transmission, and they are thought to be important for the wiring of the developing brain.

The GABAAγ2R43Q epilepsy mutation may have an impact on this function.

To test this, we measured GPD events in a mouse model with the human mutation and showed a significantly lower frequency of these events.

We also reduced GDPs using a drug called bumetanide and showed an increased seizure susceptibility.

Our data suggest that both genetic and pharmacological reductions in GDP expression can increase the likelihood of having a seizure when exposed to heat.

Abstract  The expression of Na+–K+–2Cl− cotransporter (NKCC1) is responsible for high intracellular Cl− resulting in the excitatory action of GABAA receptor activation in the developing brain. Giant depolarizing potentials (GDPs) are spontaneous network oscillations that involve GABAA receptors and are thought to be important in establishing neuronal circuit wiring. Earlier work established that seizure susceptibility in the GABAAγ2R43Q epilepsy mouse is impacted by developmental consequences of impaired GABAA receptor function. We investigated the potential mechanism of the developmental influence by recording GDPs in the CA3 pyramidal neurons from brain slices of the neonatal GABAAγ2R43Q mouse. Interestingly, the number of GPDs was significantly lower in slices from mutant mouse compared with wild‐type control, suggesting an involvement in setting seizure susceptibility. To test this idea we blocked NKCC1 with bumetanide in neonatal mice and reduced the number of GDPs to a level similar to that seen in the mutant mice. We found that neonatal treatment with bumetanide resulted in a similar level of susceptibility to thermally induced seizures as described for the GABAAγ2R43Q mouse. These results provide evidence that a human GABAA receptor epilepsy mutation exerts a developmental influence by modulating the number of GDPs. It also draws attention to the potential risk of early treatment with bumetanide.
Features of proximal and distal excitatory synaptic inputs to layer V neurons of the rat medial entorhinal cortex
Authors: Medinilla Virginia , Johnson Oralee , Gasparini Sonia
Published: September 2012

Key points

Layer V principal neurons of the entorhinal cortex receive the hippocampal output on their proximal and basal dendrites and send their axons to cortical areas, playing a fundamental role in memory processing.

The apical dendrites of these neurons are rich in spines and extend to the entorhinal superficial layers, in the proximity of axons from cortical neurons, which could make synapses onto these spines.

We stimulated afferent fibres in the superficial layers and recorded depolarizing responses in entorhinal layer V neurons, indicating that they receive excitatory inputs onto their distal dendrites.

The responses were completely blocked by glutamatergic receptor antagonists; stimulation of distal afferents could initiate dendritic spikes, which propagated to the soma to generate an action potential.

These results show that the distal dendrites of entorhinal layer V neurons have access to information that could affect the integration of the input from the hippocampus.

Abstract  The entorhinal cortex (EC) has a fundamental function in transferring information between the hippocampus and the neocortex. EC layer V principal neurons are the main recipients of the hippocampal output and send processed information to the neocortex, likely playing an important role in memory processing and consolidation. Most of these neurons have apical dendrites that extend to the superficial layers and are rich in spines, which could be the targets of excitatory inputs from fibres innervating that region. We have used electrical stimulation of afferent fibres coupled with whole‐cell patch‐clamp somatic recordings to study the features of distal excitatory inputs and compare them with those of proximal ones. The amplitude of putative unitary excitatory responses was ∼1.5 times larger for distal compared with proximal inputs. The responses were purely glutamatergic, as they were abolished by a combination of AMPA and NMDA glutamatergic receptor antagonists. Blockade of Ih by 4‐ethylphenylamino‐1,2‐dimethyl‐6‐methylaminopyrimidinium chloride (ZD7288) increased temporal summation; the increase was comparable for proximal and distal inputs. Proximal inputs initiated a somatic spike more reliably than distal ones; in some instances, somatic action potentials triggered by distal stimulation were preceded by dendritic spikes that fully propagated to the soma. Altogether, our results show that medial layer V entorhinal neurons receive excitatory synapses at distal dendritic locations, which gives them access to information encoded by inputs to the superficial layers as well as the deep layers. These findings are fundamentally relevant to understanding the role of the EC in the formation and consolidation of episodic memory.
A key circulatory defence against asphyxia in infancy – the heart of the matter!
Authors: Cohen Gary , Katz‐Salamon Miriam , Malcolm Girvan
Published: September 2012

Key points

A rise in heart rate boosts cardiac output and blood pressure, improves perfusion and oxygen delivery, and speeds recovery during an emergency.

Breathing efforts and lung inflation reflexively elevate heart rate during experimental asphyxia, and may rescue (‘auto resuscitate’) an animal from imminent death.

We analysed whether this mechanism elevates heart rate when a healthy, sleeping infant is confronted by mild, progressive asphyxia.

Term‐born infants aged 1–8 days rebreathed the expired gas for short periods to stimulate breathing and heart rate but not arousal from sleep.

We show that a rising CO2 level during asphyxia is much more strongly cardio‐acceleratory than either vigorous breathing efforts or lung inflation.

This excitatory action of CO2 on the heart develops soon after birth.

We suggest that (i) the hypercapnia during asphyxia helps raise heart rate; (ii) excitation by respiratory manoeuvres alone is relatively weak and short lived and may not produce the sustained heart rate rise needed to counteract circulatory depression.

Abstract  A resumption of, and escalation in, breathing efforts (hyperpnoea) reflexively accelerates heart rate (HR) and may facilitate cardiac and circulatory recovery from apnoea. We analysed whether this mechanism can produce a sustained rise in HR (tachycardia) when a sleeping infant is confronted by mild, rapidly worsening asphyxia, simulating apnoea. Twenty‐seven healthy term‐born infants aged 1–8 days rebreathed the expired gas for 90 s during quiet sleep to stimulate breathing and heart rate. To discriminate cardio‐excitatory effects of central respiratory drive, lung inflation, hypoxia, hypercapnia and asphyxia, we varied the inspired O2 level and compared temporal changes in response profiles as respiratory sensitivity to hypoxia and asphyxia ‘reset’ after birth. We demonstrate that asphyxia‐induced hyperpnoea and tachycardia strengthen dramatically over the first week with different time courses and via separate mechanisms. Cardiac excitation by hypercapnia improves first, followed by a slower improvement in respiratory hypoxic drive. A rise in CO2 consequently elicits stronger, longer lasting tachycardia than moderate increases in respiratory drive or lung expansion. We suggest that without a strong facilitating action of CO2 on the immature heart, respiratory manoeuvres may be unable to reflexively counteract strong vagal bradycardia. This may increase the vulnerability of some infants to apnoea – asphyxia.
Regulatory roles of the NMDA receptor GluN3A subunit in locomotion, pain perception and cognitive functions in adult mice
Authors: Mohamad Osama , Song Mingke , Wei Ling , Yu Shan Ping
Published: September 2012

Key points

Adult glutamate NMDA receptor subunit 3A (GluN3A) knockout (KO) mice showed slow locomotor activity, motor deficits and increased pain sensation.

Hippocampal slices from juvenile and adult GluN3A KO mice showed greater long‐term potentiation compared with wild‐type slices.

Adult GluN3A KO mice showed enhanced abilities in learning and memory tasks.

GluN3A deletion resulted in increased expression and/or phosphorylation of Ca2+/calmodulin‐ dependent kinase II in the brain.

This is the first investigation showing that deletion of GluN3A in the embryonic stage has imperative impacts on multiple behaviours in adults.

Abstract  Since the discovery of the glutamate NMDA receptor subunit 3A (GluN3A), the functional role of this unique inhibitory subunit has been largely obscure. GluN3A expression is high in the neonatal brain but declines to a low level in the adult brain; it is thus commonly believed that GluN3A does not have a major functional impact in adulthood. Using wild‐type (WT) and GluN3A knockout (KO) mice, we show here that deletion of GluN3A affected multiple behavioural functions in adult animals. GluN3A KO mice showed impaired locomotor activity on a variety of motor function tests, and increased sensitivity to acute and sub‐acute inflammatory pain. GluN3A KO mice also showed enhanced recognition and spatial learning and memory functions. Hippocampal slices from juvenile and adult GluN3A KO mice showed greater long‐term potentiation (LTP) compared with WT slices. GluN3A deletion resulted in increased expression of Ca2+/calmodulin‐dependent kinase II (CaMKII) in the forebrain, and the phosphorylated CaMKII level upon LTP induction was significantly higher in the GluN3A KO hippocampus compared with WT controls. CaMKII inhibition abrogated the enhanced LTP in GluN3A KO slices. These data reveal for the first time that the presence of GluN3A may have profound impacts on several functional/behavioural activities in adult animals, and could be a therapeutic target for neurological disorders associated with NMDA receptor functions.
Virulent Bacteriophages Can Target O104:H4 Enteroaggregative Escherichia coli in the Mouse Intestine
Authors: Maura Damien , Galtier Matthieu , Le Bouguénec Chantal , Debarbieux Laurent
Published: September 2012

In vivo
bacteriophage targeting of enteroaggregative
Escherichia coli
(EAEC) was assessed using a mouse intestinal model of colonization with the O104:H4 55989Str strain and a cocktail of three virulent bacteriophages. The colonization model was shown to mimic asymptomatic intestinal carriage found in humans. The addition of the cocktail to drinking water for 24 h strongly decreased ileal and weakly decreased fecal 55989Str concentrations in a dose-dependent manner. These decreases in ileal and fecal bacterial concentrations were only transient, since 55989Str concentrations returned to their original levels 3 days later. These transient decreases were independent of the mouse microbiota, as similar results were obtained with axenic mice. We studied the infectivity of each bacteriophage in the ileal and fecal environments and found that 55989Str bacteria in the mouse ileum were permissive to all three bacteriophages, whereas those in the feces were permissive to only one bacteriophage. Our results provide the first demonstration that bacterial permissivity to infection with virulent bacteriophages is not uniform throughout the gut; this highlights the need for a detailed characterization of the interactions between bacteria and bacteriophages
in vivo
for the further development of phage therapy targeting intestinal pathogens found in the gut of asymptomatic human carriers.
Frequency, Spectrum, and Nonzero Fitness Costs of Resistance to Myxopyronin in Staphylococcus aureus
Authors: Srivastava Aashish , Degen David , Ebright Yon W. , Ebright Richard H.
Published: September 2012

The antibiotic myxopyronin (Myx) functions by inhibiting bacterial RNA polymerase (RNAP). The binding site on RNAP for Myx—the RNAP “switch region SW1/SW2 subregion”—is different from the binding site on RNAP for the RNAP inhibitor currently used in broad-spectrum antibacterial therapy, rifampin (Rif). Here, we report the frequency, spectrum, and fitness costs of Myx resistance in
Staphylococcus aureus
. The resistance rate for Myx is 4 × 10
−8
to 7 × 10
−8
per generation, which is equal within error to the resistance rate for Rif (3 × 10
−8
to 10 × 10
−8
per generation). Substitutions conferring Myx resistance were obtained in the RNAP β subunit [six substitutions: V1080(1275)I, V1080(1275)L, E1084(1279)K, D1101(1296)E, S1127(1322)L, and S1127(1322)P] and the RNAP β′ subunit [five substitutions: K334(345)N, T925(917)K, T925(917)R, G1172(1354)C, and G1172(1354)D] (residues numbered as in
Staphylococcus aureus
RNAP and, in parentheses, as in
Escherichia coli
RNAP). Sites of substitutions conferring Myx resistance map to the RNAP switch region SW1/SW2 subregion and do not overlap the binding site on RNAP for Rif, and, correspondingly, Myx-resistant mutants exhibit no cross-resistance to Rif. All substitutions conferring Myx resistance exhibit significant fitness costs (4 to 15% per generation). In contrast, at least three substitutions conferring Rif resistance exhibit no fitness costs (≤0% per generation). The observation that all Myx-resistant mutants have significant fitness costs whereas at least three Rif-resistant mutants have no fitness costs, together with the previously established inverse correlation between fitness cost and clinical prevalence, suggests that Myx resistance is likely to have lower clinical prevalence than Rif resistance.
The Sequence-Activity Relationship between Metallo-β-Lactamases IMP-1, IMP-6, and IMP-25 Suggests an Evolutionary Adaptation to Meropenem Exposure
Authors: Liu Eleanor M. , Pegg Kevin M. , Oelschlaeger Peter
Published: September 2012

Metallo-β-lactamases are important determinants of antibacterial resistance. In this study, we investigate the sequence-activity relationship between the closely related enzymes IMP-1, IMP-6, and IMP-25. While IMP-1 is the more efficient enzyme across the overall spectrum of tested β-lactam antibacterial agents, IMP-6 and IMP-25 seem to have evolved to specifically inactivate the newer carbapenem meropenem. Molecular modeling indicates that the G235S mutation distinguishing IMP-25 from IMP-1 and IMP-6 may affect enzyme activity via Asn233.
The Two-Component System CprRS Senses Cationic Peptides and Triggers Adaptive Resistance in Pseudomonas aeruginosa Independently of ParRS
Authors: Fernández Lucía , Jenssen Håvard , Bains Manjeet , Wiegand Irith , Gooderham W. James , Hancock Robert E. W.
Published: September 2012

Cationic antimicrobial peptides pass across the outer membrane by interacting with negatively charged lipopolysaccharide (LPS), leading to outer membrane permeabilization in a process termed self-promoted uptake. Resistance can be mediated by the addition of positively charged arabinosamine through the action of the
arnBCADTEF
operon. We recently described a series of two-component regulators that lead to the activation of the
arn
operon after recognizing environmental signals, including low-Mg
2+
(PhoPQ, PmrAB) or cationic (ParRS) peptides. However, some peptides did not activate the
arn
operon through ParRS. Here, we report the identification of a new two-component system, CprRS, which, upon exposure to a wide range of antimicrobial peptides, triggered the expression of the LPS modification operon. Thus, mutations in the
cprRS
operon blocked the induction of the
arn
operon in response to several antimicrobial peptides independently of ParRS but did not affect the response to low Mg
2+
. Distinct patterns of
arn
induction were identified. Thus, the responses to polymyxins were abrogated by either
parR
or
cprR
mutations, while responses to other peptides, including indolicidin, showed differential dependency on the CprRS and ParRS systems in a concentration-dependent manner. It was further demonstrated that, following exposure to inducing antimicrobial peptides,
cprRS
mutants did not become adaptively resistant to polymyxins as was observed for wild-type cells. Our microarray studies demonstrated that the CprRS system controlled a quite modest regulon, indicating that it was quite specific to adaptive peptide resistance. These findings provide greater insight into the complex regulation of LPS modification in
Pseudomonas aeruginosa
, which involves the participation of at least 4 two-component systems.
The Inactivation of Intrinsic Antibiotic Resistance Determinants Widens the Mutant Selection Window for Quinolones in Stenotrophomonas maltophilia
Authors: García-León Guillermo , Sánchez María B. , Martínez José L.
Published: September 2012

We have determined that the mutational inactivation of the SmeDEF efflux pump and the SmQnr quinolone resistance protein widens the mutant selection windows for ofloxacin and ciprofloxacin of
Stenotrophomonas maltophilia
by reducing their MICs. Resistant mutants arising from a strain lacking SmeDEF and SmQnr presented levels of susceptibility similar to those of the wild-type strain. This indicates that inactivation of intrinsic resistance determinants might increase the chances for selecting resistant mutants at low antibiotic concentrations.
Expression of
STM4467
-Encoded Arginine Deiminase Controlled by the
STM4463
Regulator Contributes to Salmonella enterica Serovar Typhimurium Virulence
Authors: Choi Younho , Choi Jeongjoon , Groisman Eduardo A. , Kang Dong-Hyun , Shin Dongwoo , Ryu Sangryeol
Published: September 2012

Arginine deiminase (ADI), carbamate kinase (CK), and ornithine transcarbamoylase (OTC) constitute the ADI system. In addition to metabolic functions, the ADI system has been implicated in the virulence of certain pathogens. The pathogenic intracellular bacterium
Salmonella enterica
serovar Typhimurium possesses the
STM4467
,
STM4466
, and
STM4465
genes, which are predicted to encode ADI, CK, and OTC, respectively. Here we report that the
STM4467
gene encodes an ADI and that ADI activity plays a role in the successful infection of a mammalian host by
S
. Typhimurium. An
STM4467
deletion mutant was defective for replication inside murine macrophages and was attenuated for virulence in mice. We determined that a regulatory protein encoded by the
STM4463
gene functions as an activator for
STM4467
expression. The expression of the ADI pathway genes was enhanced inside macrophages in a process that required STM4463. Lack of STM4463 impaired the ability of
S
. Typhimurium to replicate within macrophages. A mutant defective in
STM4467
-encoded ADI displayed normal production of nitric oxide by macrophages.
Postchemotherapy expulsion of oesophageal endoluminal stent with vomiting: a rare occurrence
Authors: Gupta Sameer , Kacker Luv K
Published: September 2012

Self-expandable metallic stents (SEMS) are currently the most widely used modality for palliation of dysphagia from oesophageal malignancy. However, placement of SEMS is associated with a number of complications. We report a rare late complication of SEMS placed for relief of malignant dysphagia (Locally advanced Carcinoma mid-esophagus) in a 65-year-old man. SEMS was expelled out intact with vomiting following complete response to disease after three cycles of chemotherapy. Check on endoscopy done the day after, patient's growth had shown partial response to chemotherapy with scope easily negotiable upto Gastroesophageal junction with area of scarring and healed ulceration and stent imprint on the oesophageal wall. Partial response of the disease to chemotherapy and lack of expected fibrosis between stent and oesophageal wall resulted in loss of scaffolding for the stent and its subsequent expulsion in vomiting and relief in patient's dysphagia.
Acute tuberculous abscess of the thyroid gland: Figure 1
Authors: Bahgat Mohammed , Bahgat Yassin , Bahgat Ahmed , Aly Samia
Published: September 2012

The authors are presenting our experience of managing an interesting case of a 28-year-old woman who presented to our clinic with a midline neck swelling of 1-month duration. There was a rapid increase in the degree of swelling associated with erythema, pain and fever 7 days before seeking medical help. Plain and contrast-enhanced CT scans of the neck were done. Diagnosis of acute suppurative abscess was made and the patient underwent emergency incision and drainage. Histopathological examination of the abscess wall showed epitheloid and Langhans’ giant cells. The findings were suggestive of tuberculosis. Subsequently, a positive culture forMycobacterium tuberculosiswas obtained on Lowenstein-Jenson medium. The patient was started on antituberculous chemotherapy for 6 months. On a 6-month clinical follow-up, the patient was asymptomatic and euthyroid. We discuss the clinical presentation, diagnosis and treatment of this case as well as a review of the literature.