bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenosine A1 receptor activation mediates the developmental shift at layer 5 pyramidal cell synapses and is a determinant of mature synaptic strength
Authors: Kerr Michael I. , Wall Mark J. , Richardson Magnus J. E. 
Published: April 2013

Key points
Neocortical layer 5 pyramidal cell synapses exhibit a developmental reduction in neurotransmitter release probability. Mature synapses are weaker, less reliable and show greater facilitation than immature connections.
Using paired intracellular recordings our study identifies the mechanism that mediates this developmental change as being due to an increased activation of presynaptic adenosine A1 receptors.
Unlike immature connections, which showed little A1 receptor activation, mature connections demonstrated a broad range of activation that was inversely correlated to mature synaptic strength.
We show that the functional efficacy of A1 receptors does not change over development and so our evidence points to concentrations of extracellular adenosine at synapses increasing locally over development.
The increased adenosine levels significantly affect synaptic efficacy suggesting that the emplacement of adenosine sources and sinks might be a novel mechanism for long‐term plasticity at layer 5 pyramidal cell synapses.
Abstract  During the first postnatal month glutamatergic synapses between layer 5 pyramidal cells in the rodent neocortex switch from an immature state exhibiting a high probability of neurotransmitter release, large unitary amplitude and synaptic depression to a mature state with decreased probability of release, smaller unitary amplitude and synaptic facilitation. Using paired recordings, we demonstrate that the developmental shift in release probability at synapses between rat somatosensory layer 5 thick‐tufted pyramidal cells is mediated by a higher and more heterogeneous activation of presynaptic adenosine A1 receptors. Immature synapses under control conditions exhibited distributions of coefficient of variation, failure rate and release probability that were almost coincident with the A1 receptor blocked condition; however, mature synapses under control conditions exhibited much broader distributions that spanned those of both the A1 receptor agonized and antagonized conditions. Immature and mature synapses expressed A1 receptors with no observable difference in functional efficacy and therefore the heterogeneous A1 receptor activation seen in the mature neocortex appears due to increased adenosine concentrations that vary between synapses. Given the central role demonstrated for A1 receptor activation in determining synaptic amplitude and the statistics of transmission between mature layer 5 pyramidal cells, the emplacement of adenosine sources and sinks near the synaptic terminal could constitute a novel form of long‐term synaptic plasticity.
Excitability and the safety margin in human axons during hyperthermia
Authors: Howells James , Czesnik Dirk , Trevillion Louise , Burke David 
Published: April 2013

Key points
In six healthy subjects, the excitability of both motor and sensory axons was altered during hyperthermia, lowering their safety margin.
The results suggest that slow K+ channels play a significant role in these changes in axonal excitability during hyperthermia.
Inward rectification was reduced during hyperthermia, and the modelling suggests that the hyperpolarization‐activated cation current, Ih, was reduced, thus hampering its ability to counter activity‐dependent hyperpolarization.
Hyperthermia lowers the safety margin for action potential generation and propagation. Differences in their responses to hyperthermia suggest that motor axons undergo conduction block more readily than sensory axons during fever, particularly when the safety margin is already impaired.
Abstract  Hyperthermia challenges the nervous system's ability to transmit action potentials faithfully. Neuromuscular diseases, particularly those involving demyelination have an impaired safety margin for action potential generation and propagation, and symptoms are commonly accentuated by increases in temperature. The aim of this study was to examine the mechanisms responsible for reduced excitability during hyperthermia. Additionally, we sought to determine if motor and sensory axons differ in their propensity for conduction block during hyperthermia. Recordings of axonal excitability were performed at normal temperatures and during focal hyperthermia for motor and sensory axons in six healthy subjects. There were clear changes in excitability during hyperthermia, with reduced superexcitability following an action potential, faster accommodation to long‐lasting depolarization and reduced accommodation to hyperpolarization. A verified model of human motor and sensory axons was used to clarify the effects of hyperthermia. The hyperthermia‐induced changes in excitability could be accounted for by increasing the modelled temperature by 6°C (and adjusting the maximum conductances and activation kinetics according to their Q10 values; producing a 2 mV hyperpolarization of resting membrane potential), further hyperpolarizing the voltage dependence of Ih (motor, 11 mV; sensory, 7 mV) and adding a small depolarizing current at the internode (motor, 20 pA; sensory, 30 pA). The modelling suggested that slow K+ channels play a significant role in reducing axonal excitability during hyperthermia. The further hyperpolarization of the activation of Ih would limit its ability to counter the hyperpolarization produced by activity, thereby allowing conduction block to occur during hyperthermia.
Multiple Frequencies Elliptical Whirling Orbit Model and Transient RANS Solution Approach to Rotordynamic Coefficients of Annual Gas Seals Prediction
Authors: Li Zhigang , Li Jun , Yan Xin 
Published: April 2013

Abstract
A numerical method using the multiple frequencies elliptical whirling orbit model and transient Reynolds-averaged Navier–Stokes (RANS) solution was proposed for prediction of the frequency dependent rotordynamic coefficients of annular gas seals. The excitation signal was the multiple frequencies waveform that acts as the whirling motion of the rotor center. The transient RANS solution combined with mesh deformation method was utilized to solve the leakage flow field in the annular gas seal and obtain the transient response forces on the rotor surface. Frequency dependent rotordynamic coefficients were determined by transforming the dynamic monitoring data of response forces and rotor motions to the frequency domain using the fast fourier transform. The frequency dependent rotordynamic coefficients of three types of annular gas seals, including a labyrinth seal, a fully partitioned pocket damper seal and a hole-pattern seal, were computed using the presented numerical method at thirteen or fourteen frequencies of 20–300 Hz. The obtained rotordynamic coefficients of three types of annular gas seals were all well agreement with the experimental data. The accuracy and availability of the proposed numerical method was demonstrated. The static pressure distributions and leakage flow rate of three types of annular gas seals were also illustrated.
The braincase of
Prestosuchus chiniquensis
(Archosauria: Suchia)
Authors: Mastrantonio Bianca Martins , Schultz Cesar L. , Desojo Julia B. , Garcia Juliana Bittencourt 
Published: April 2013

Abstract

The osteology of an almost complete braincase of the rauisuchian archosaur
Prestosuchus chiniquensis
from the Middle Triassic of Brazil is described for first time, based on two specimens (UFRGS-PV-0629-T and UFRGS-PV-0156-T)
.
A comparative description with other taxa of rauisuchians is presented that forms the basis of a phylogenetic analysis. To perform the phylogenetic analysis, we describe and discuss each character codification for a modified version of the recent matrices of
Gower (2002)
,
Gower & Nesbitt (2006)
and

Brusatte
et al.
(2010)

. The analysis resulted in two most parsimonious trees that differ from the topologies recovered by
Gower (2002)
in a few aspects within Rauisuchia, and
Prestosuchus chiniquensis
was unequivocally depicted as deeply nested within Pseudosuchia, as the sister taxon of
Batrachotomus kuperferzellensis
in both topologies, supported by a single synapomorphy: the reduced to small fissure of the post-temporal fenestra between parietal, supraoccipital and exoccipital-opisthotic.
The Late Triassic dinosauromorph
Sacisaurus agudoensis
(Caturrita Formation; Rio Grande do Sul, Brazil): anatomy and affinities
Authors: Langer Max C. , Ferigolo Jorge 
Published: April 2013

Abstract

Silesauridae is an exclusively Triassic group of dinosauromorphs, knowledge on the diversity of which has increased dramatically in the last few years. Silesaurid relationships are still contentious, as a result in part of different homology statements, particularly regarding the typical edentulous mandible tip of these animals. One of the most complete silesaurids yet discovered is
Sacisaurus agudoensis
from the Caturrita Formation (Late Triassic: Norian) of Rio Grande do Sul, Brazil, represented by numerous isolated bones recovered from a single site. The anatomy of
S. agudoensis
is fully described for the first time here, and comparisons are provided to other basal dinosauromorphs.
S. agudoensis
is a small-bodied animal (less than 1 m in length) that possesses a dentition consisting of leaf-shaped crowns with large denticles in the carinae, a plesiomorphic propubic pelvis with an almost fully closed acetabulum, elongate distal hindlimbs suggesting well-developed cursorial ability, and a laterally projected outer malleolus in the tibia. All previous numerical phylogenies supported a non-dinosaur dinosauromorph affinity for Silesauridae, but the reanalysis of one of those studies suggests that a position within Dinosauria is not unlikely, with silesaurids forming the basal branch of the ornithischian lineage.
Microenvironmental Induced Essentiality of Autophagy
Authors: Singleton Dean C. , Harris Adrian L. 
Published: April 2013

Abstract
Angiogenesis inhibitors cause increased hypoxia in tumors and this results in the induction of cytoprotective autophagy. Targeting this adaptation using autophagy inhibitors can overcome resistance to antiangiogenic therapy and enhance the antitumor effects. Clin Cancer Res; 19(11); 2791–3. ©2013 AACR.
Uncertainty in Climate Change Projections of the Hadley Circulation: The Role of Internal Variability
Authors: Kang Sarah M. , Deser Clara , Polvani Lorenzo M. 
Published: April 2013

Abstract
The uncertainty arising from internal climate variability in climate change projections of the Hadley circulation (HC) is presently unknown. In this paper it is quantified by analyzing a 40-member ensemble of integrations of the Community Climate System Model, version 3 (CCSM3), under the Special Report on Emissions Scenarios (SRES) A1B scenario over the period 2000–60. An additional set of 100-yr-long time-slice integrations with the atmospheric component of the same model [Community Atmosphere Model, version 3.0 (CAM3)] is also analyzed.
Focusing on simple metrics of the HC—its strength, width, and height—three key results emerge from the analysis of the CCSM3 ensemble. First, the projected weakening of the HC is almost entirely confined to the Northern Hemisphere, and is stronger in winter than in summer. Second, the projected widening of the HC occurs only in the winter season but in both hemispheres. Third, the projected rise of the tropical tropopause occurs in both hemispheres and in all seasons and is, by far, the most robust of the three metrics.
This paper shows further that uncertainty in future trends of the HC width is largely controlled by extratropical variability, while those of HC strength and height are associated primarily with tropical dynamics. Comparison of the CCSM3 and CAM3 integrations reveals that ocean–atmosphere coupling is the dominant source of uncertainty in future trends of HC strength and height and of the tropical mean meridional circulation in general. Finally, uncertainty in future trends of the hydrological cycle is largely captured by the uncertainty in future trends of the mean meridional circulation.
The U.S. and the Convention on the Rights of the Child: What’s the hold-up?
Authors: Hagues Rachel 
Published: April 2013

Summary It took teaching a family policy course for me to realize just how behind the United States is on ratifying international treaties – especially those pertaining to human rights. Though the U.S. expresses a commitment to human rights, has helped draft treaties that proclaim such, and has even signed many of these documents, this means nothing within the continental U.S. if the Senate does not ratify them. Herein, I discuss some of the reasons the U.S. has held back ratifying the Convention on the Rights of the Child (CRC). Findings Of important human rights instruments the U.S. has ratified, it has taken an average of nearly 30 years after signing for the Senate to ratify each. Though the U.S. often sets a precedent and example for other countries to follow, it has yet to ratify the CRC. Every other country (minus Somalia) has ratified the Convention. Yet, these countries may not see the importance of enforcing it if the U.S. does not value ratifying it.
Rituximab causes a polarization of B cells that augments its therapeutic function in NK-cell–mediated antibody-dependent cellular cytotoxicity
Authors: Rudnicka Dominika , Oszmiana Anna , Finch Donna K. , Strickland Ian , Schofield Darren J. , Lowe David C. , Sleeman Matthew A. , Davis Daniel M. 
Published: April 2013

Key PointsRituximab causes a polarization of B cells, involving a reorganization of CD20, intercellular adhesion molecule 1, and moesin, and orientation of the microtubule organizing center. The polarization of B cells induced by rituximab augments its therapeutic role in triggering ADCC by effector NK cells.
Effect of physical training on airway inflammation in animal models of asthma: a systematic review
Authors: Luks Vanessa , Burkett Andrew , Turner Lucy , Pakhale Smita 
Published: April 2013

AbstractBackgroundThere is little data on the effect of exercise on markers of airway inflammation in human asthmatics. The main objective of this review is to determine the effects of physical training on markers of airway inflammation in animal models of asthma.MethodsA peer reviewed search was applied to Medline, Embase, Web of Science, Cochrane, and DARE databases. Data extraction was performed in a blinded fashion.ResultsFrom the initial 2336 studies, a total of 10 studies were selected for the final analysis. All were randomized controlled trials with low to moderate intensity training on ovalbumin-sensitized mice. In the exercised group of mice, there was a reduction in BAL eosinophils and Th-2 cytokines, no change in Th-1 cytokines, an increase in IL-10, and a reversal of airway remodeling. The data was not pooled owing to significant heterogeneity between studies, and a funnel plot test for publication bias was not performed because there were few studies reporting on any one outcome measure. The asthma models differed between studies in age and gender of mice, as well as in timing of physical training after sensitization. The risk of bias was unclear for some studies though this may not influence outcome measures. The accuracy of data extracted from graphics is unknown.ConclusionsPhysical training improves airway inflammation in animal asthma models.
Mining FDA drug labels for medical conditions
Authors: Li Qi , Deleger Louise , Lingren Todd , Zhai Haijun , Kaiser Megan , Stoutenborough Laura , Jegga Anil G , Cohen Kevin Bretonnel , Solti Imre 
Published: April 2013

Abstract

Background
Cincinnati Children’s Hospital Medical Center (CCHMC) has built the initial Natural Language Processing (NLP) component to extract medications with their corresponding medical conditions (Indications, Contraindications, Overdosage, and Adverse Reactions) as triples of medication-related information ([(1) drug name]-[(2) medical condition]-[(3) LOINC section header]) for an intelligent database system, in order to improve patient safety and the quality of health care. The Food and Drug Administration’s (FDA) drug labels are used to demonstrate the feasibility of building the triples as an intelligent database system task.

Methods
This paper discusses a hybrid NLP system, called AutoMCExtractor, to collect medical conditions (including disease/disorder and sign/symptom) from drug labels published by the FDA. Altogether, 6,611 medical conditions in a manually-annotated gold standard were used for the system evaluation. The pre-processing step extracted the plain text from XML file and detected eight related LOINC sections (e.g. Adverse Reactions, Warnings and Precautions) for medical condition extraction. Conditional Random Fields (CRF) classifiers, trained on token, linguistic, and semantic features, were then used for medical condition extraction. Lastly, dictionary-based post-processing corrected boundary-detection errors of the CRF step. We evaluated the AutoMCExtractor on manually-annotated FDA drug labels and report the results on both token and span levels.

Results
Precision, recall, and F-measure were 0.90, 0.81, and 0.85, respectively, for the span level exact match; for the token-level evaluation, precision, recall, and F-measure were 0.92, 0.73, and 0.82, respectively.

Conclusions
The results demonstrate that (1) medical conditions can be extracted from FDA drug labels with high performance; and (2) it is feasible to develop a framework for an intelligent database system.
Comparison of the differential expression miRNAs in Wistar rats before and 10 days after S.japonicum infection
Authors: Han Hongxiao , Peng Jinbiao , Hong Yang , Zhang Min , Han Yanhui , Fu Zhiqiang , Shi Yaojun , Xu Jinjun , Tao Jianping , Lin Jiaojiao 
Published: April 2013

Abstract

Background
When compared to the murine permissive host of Schistosoma japonicum, Wistar rats are less susceptible to Schistosoma japonicum infection, and are considered to provide a less suitable microenvironment for parasite growth and development. MicroRNAs (miRNAs), are a class of endogenous, non-coding small RNAs, that impose an additional, highly significant, level of gene regulation within eukaryotes.

Methods
To investigate the regulatory mechanisms provided by miRNA in the schistosome-infected rat model, we utilized a miRNA microarray to compare the progression of miRNA expression within different host tissues both before and 10 days after cercarial infection, in order to identify potential miRNAs with roles in responding to a schistosome infection.

Results
Among the analysed miRNAs, 16 within the liver, 61 within the spleen and 10 within the lung, were differentially expressed in infected Wistar rats. Further analysis of the differentially expressed miRNAs revealed that many important signal pathways are triggered after infection with S. japonicum in Wistar rats. These include the signal transduction mechanisms associated with the Wnt and MAPK signaling pathways, cellular differentiation, with a particular emphasis on adipocyte and erythroid differentiation.

Conclusions
The results presented here include the identification of specific differentially expressed miRNAs within the liver, lungs and spleen of Wistar rats. These results highlighted the function of host miRNA regulation during an active schistosome infection. Our study provides a better understanding of the regulatory role of miRNA in schistosome infection, and host–parasite interactions in a non-permissive host environment.
Teaching undergraduate students to draw phylogenetic trees: performance measures and partial successes
Authors: Young Aimee K , White Brian T , Skurtu Tara 
Published: April 2013

Abstract

Background
An in-depth understanding of the process and products of evolution is an essential part of a complete biology education. Phylogenetic trees are a very important tool for understanding evolution and presenting evolutionary data. Previous work by others has shown that undergraduate students have difficulty reading and interpreting phylogenetic trees. However, little is known about students’ ability to construct phylogenetic trees.

Methods
This study explores the ability of 160 introductory-level biology undergraduates to draw a correct phylogenetic tree of 20 familiar organisms before, during and after a General Biology course that included several lectures and laboratory activities addressing evolution, phylogeny and ‘tree thinking’. Students’ diagrams were assessed for the presence or absence of important structural features of a phylogenetic tree: connection of all organisms, extant taxa at branch termini, a single common ancestor, branching form, and hierarchical structure. Diagrams were also scored for how accurately they represented the evolutionary relationships of the organisms involved; this included separating major animal groups and particular classification misconceptions.

Results
Our analyses found significant improvement in the students’ ability to construct trees that were structured properly, however, there was essentially no improvement in their ability to accurately portray the evolutionary relationships between the 20 organisms. Students were also asked to describe their rationale for building the tree as they did; we observed only a small effect on this of the curriculum we describe.

Conclusions
Our results provide a measure, a benchmark, and a challenge for the development of effective curricula in this very important part of biology.
Evaluation of androgen-induced effects on the uptake of [18F]FDG, [11C]choline and [11C]acetate in an androgen-sensitive and androgen-independent prostate cancer xenograft model
Authors: Emonds Kimy M , Swinnen Johannes V , Lerut Evelyne , Koole Michel , Mortelmans Luc , Mottaghy Felix M 
Published: April 2013

Abstract

Background
Androgen deprivation (AD) is generally used as a first-line palliative treatment in prostate cancer (PCa) patients with rising prostate-specific antigen (PSA) after primary therapy. To acquire an accurate detection of tumour viability following AD with positron emission tomography (PET), an androgen-independent uptake of tracers would be advantageous. Several metabolic PET tracers are employed for detecting recurrent PCa. We evaluated the effect of AD on the uptake of 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG), [11C]choline and [11C]acetate in vivo.

Methods
An [18F]FDG, [11C]choline and [11C]acetate baseline micro(μ)PET/μ computed tomography (CT) scan was subsequently performed in xenografts of androgen-sensitive (LAPC-4) and androgen-independent (22Rv1) tumours in nude mice. An untreated control group was compared to a surgical castration group, i.e. androgen-deprived group. μPET/μCT imaging with the above-mentioned tracers was repeated 5 days after the start of treatment. The percentage change of SUVmax and SUVmeanTH in the tumours was calculated.

Results
AD did not significantly affect the uptake of [18F]FDG and [11C]choline in LAPC-4 tumours as compared with the uptake of both tracers in untreated tumours. In control 22Rv1 tumours, [11C]choline and [18F]FDG uptake increased over time. However, compared with the uptake in control tumours, AD significantly decreased the uptake of [11C]choline and tended to decrease [18F]FDG uptake. [11C]acetate uptake remained unaffected by AD in both PCa xenograft models.

Conclusions
[18F]FDG and especially [11C]choline PET, which is currently used for the detection of recurrent PCa, could miss or underestimate the presence of local recurrent PCa following AD therapy. [11C]acetate uptake occurs independently of androgens and thus may be more favourable for detecting tumour viability during or following AD.