bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of β-adrenergic receptor agonists on drinking and arterial blood pressure in young and old rats
Authors: Thunhorst Robert L. , Grobe Connie L. , Beltz Terry G. , Johnson Alan Kim
Published: February 2011

These experiments examined water-drinking and arterial blood pressure responses to β-adrenergic receptor activation in young (4 mo), “middle-aged” adult (12 mo), and old (29 mo) male rats of the Brown-Norway strain. We used isoproterenol to simultaneously activate β1- and β2-adrenergic receptors, salbutamol to selectively activate β2-adrenergic receptors, and the combination of isoproterenol and the β2-adrenergic receptor antagonist ICI 118,551 to stimulate only β1-adrenergic receptors. Animals received one of the drug treatments, and water drinking was measured for 90 min. About 1 wk later, animals received the same drug treatment for measurement of arterial blood pressure responses for 90 min. In some rats, levels of renin and aldosterone secretion in response to isoproterenol or salbutamol were measured in additional tests. Old and middle-aged rats drank significantly less after isoproterenol than did young rats and also had greater reductions in arterial blood pressure. Old and middle-aged rats drank significantly less after salbutamol than did young rats, although reductions in arterial blood pressure were equivalent across the ages. The β2-adrenergic antagonist ICI 118,551 abolished drinking after isoproterenol and prevented most of the observed hypotension. Renin secretion after isoproterenol and salbutamol was greater in young rats than in middle-aged rats, and wholly absent in old rats. Aldosterone secretion was reduced in old rats compared with young and middle-aged rats after treatment with isoproterenol, but not after treatment with salbutamol. In conclusion, there are age-related differences in β-adrenergic receptor-mediated drinking that can be explained only in part by age-related differences in renin secretion after β-adrenergic receptor stimulation.
End-tidal carbon dioxide tension reflects arterial carbon dioxide tension in the heat-stressed human with and without simulated hemorrhage
Authors: Brothers R. Matthew , Ganio Matthew S. , Hubing Kimberly A. , Hastings Jeffrey L. , Crandall Craig G.
Published: February 2011

End-tidal carbon dioxide tension (PetCO2) is reduced during an orthostatic challenge, during heat stress, and during a combination of these two conditions. The importance of these changes is dependent on PetCO2 being an accurate surrogate for arterial carbon dioxide tension (PaCO2), the latter being the physiologically relevant variable. This study tested the hypothesis that PetCO2 provides an accurate assessment of PaCO2 during the aforementioned conditions. Comparisons between these measures were made: 1) after two levels of heat stress ( N = 11); 2) during combined heat stress and simulated hemorrhage [via lower-body negative pressure (LBNP), N = 8]; and 3) during an end-tidal clamping protocol to attenuate heat stress-induced reductions in PetCO2 ( N = 7). PetCO2 and PaCO2 decreased during heat stress ( P < 0.001); however, there was no group difference between PaCO2 and PetCO2 ( P = 0.36) nor was there a significant interaction between thermal condition and measurement technique ( P = 0.06). To verify that this nonsignificant trend for the interaction was not due to a type II error, PetCO2 and PaCO2 at three distinct thermal conditions were also compared using paired t-tests, revealing no difference between PaCO2 and PetCO2 while normothermic ( P = 0.14) and following a 1.0 ± 0.2°C ( P = 0.21) and 1.4 ± 0.2°C ( P = 0.28) increase in internal temperature. During LBNP while heat stressed, measures of PetCO2 and PaCO2 were similar ( P = 0.61). Likewise, during the end-tidal carbon dioxide clamping protocol, the increases in PetCO2 (7.5 ± 2.8 mmHg) and PaCO2 (6.6 ± 3.4 mmHg) were similar ( P = 0.31). These data indicate that mean PetCO2 reflects mean PaCO2 during the evaluated conditions.
Effects of hypohydration on thermoregulation during exercise before and after 5-day aerobic training in a warm environment in young men
Authors: Ikegawa Shigeki , Kamijo Yoshi-ichiro , Okazaki Kazunobu , Masuki Shizue , Okada Yoshiyuki , Nose Hiroshi
Published: February 2011

We examined whether enhanced cardiovascular and thermoregulatory responses during exercise after short-term aerobic training in a warm environment were reversed when plasma volume (PV) expansion was reversed by acute isotonic hypohydration. Seven young men performed aerobic training at the 70% peak oxygen consumption rate (V̇o2peak) at 30°C atmospheric temperature and 50% relative humidity, 30 min/day for 5 days. Before and after training, we performed the thermoregulatory response test while measuring esophageal temperature (Tes), forearm skin vascular conductance, sweat rate (SR), and PV during 30 min exercise at the metabolic rate equivalent to pretraining 65% V̇o2peak in euhydration under the same environment as during training in four trials (euhydration and hypohydration, respectively). Hypohydration targeting 3% body mass was attained by combined treatment with low-salt meals to subjects from ∼48 h before the test and administration of a diuretic ∼4 h before the test. After training, the Tes thresholds for cutaneous vasodilation and sweating decreased by 0.3 and 0.2°C ( P = 0.008 and 0.012, respectively) when PV increased by ∼10%. When PV before and after training was reduced to a similar level, ∼10% reduction from that in euhydration before training, the training-induced reduction in the threshold for cutaneous vasodilation increased to a level similar to hypohydration before training ( P = 0.093) while that for sweating remained significantly lower than that before training ( P = 0.004). Thus the enhanced cutaneous vasodilation response after aerobic training in a warm environment was reversed when PV expansion was reversed while the enhanced SR response remained partially.
Network hyperexcitability in hippocampal slices fromMecp2mutant mice revealed by voltage-sensitive dye imaging
Authors: Calfa Gaston , Hablitz John J. , Pozzo-Miller Lucas
Published: February 2011

Dysfunctions of neuronal and network excitability have emerged as common features in disorders associated with intellectual disabilities, autism, and seizure activity, all common clinical manifestations of Rett syndrome (RTT), a neurodevelopmental disorder caused by loss-of-function mutations in the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2). Here, we evaluated the consequences of Mecp2 mutation on hippocampal network excitability, as well as synapse structure and function using a combination of imaging and electrophysiological approaches in acute slices. Imaging the amplitude and spatiotemporal spread of neuronal depolarizations with voltage-sensitive dyes (VSD) revealed that the CA1 and CA3 regions of hippocampal slices from symptomatic male Mecp2 mutant mice are highly hyperexcitable. However, only the density of docked synaptic vesicles and the rate of release from the readily releasable pool are impaired in Mecp2 mutant mice, while synapse density and morphology are unaffected. The differences in network excitability were not observed in surgically isolated CA1 minislices, and blockade of GABAergic inhibition enhanced VSD signals to the same extent in Mecp2 mutant and wild-type mice, suggesting that network excitability originates in area CA3. Indeed, extracellular multiunit recordings revealed a higher level of spontaneous firing of CA3 pyramidal neurons in slices from symptomatic Mecp2 mutant mice. The neuromodulator adenosine reduced the amplitude and spatiotemporal spread of VSD signals evoked in CA1 of Mecp2 mutant slices to wild-type levels, suggesting its potential use as an anticonvulsant in RTT individuals. The present results suggest that hyperactive CA3 pyramidal neurons contribute to hippocampal dysfunction and possibly to limbic seizures observed in Mecp2 mutant mice and RTT individuals.
Effects of visual stimulation on LFPs, spikes, and LFP-spike relations in PRR
Authors: Hwang Eun Jung , Andersen Richard A.
Published: February 2011

Local field potentials (LFPs) have shown diverse relations to the spikes across different brain areas and stimulus features, suggesting that LFP-spike relationships are highly specific to the underlying connectivity of a local network. If so, the LFP-spike relationship may vary even within one brain area under the same task condition if neurons have heterogeneous connectivity with the active input sources during the task. Here, we tested this hypothesis in the parietal reach region (PRR), which includes two distinct classes of motor goal planning neurons with different connectivity to the visual input, i.e., visuomotor neurons receive stronger visual input than motor neurons. We predicted that the visual stimulation would render both the spike response and the LFP-spike relationship different between the two neuronal subpopulations. Thus we examined how visual stimulations affect spikes, LFPs, and LFP-spike relationships in PRR by comparing their planning (delay) period activity between two conditions: with or without a visual stimulus at the reach target. Neurons were classified as visuomotor if the visual stimulation increased their firing rate, or as motor otherwise. We found that the visual stimulation increased LFP power in gamma bands >40 Hz for both classes. Moreover, confirming our prediction, the correlation between the LFP gamma power and the firing rate became higher for the visuomotor than motor neurons in the presence of visual stimulation. We conclude that LFPs vary with the stimulation condition and that the LFP-spike relationship depends on a given neuron's connectivity to the dominant input sources in a particular stimulation condition.
Advance cueing produces enhanced action-boundary patterns of spike activity in the sensorimotor striatum
Authors: Barnes Terra D. , Mao Jian-Bin , Hu Dan , Kubota Yasuo , Dreyer Anna A. , Stamoulis Catherine , Brown Emery N. , Graybiel Ann M.
Published: February 2011

One of the most characteristic features of habitual behaviors is that they can be evoked by a single cue. In the experiments reported here, we tested for the effects of such advance cueing on the firing patterns of striatal neurons in the sensorimotor striatum. Rats ran in a T-maze with instruction cues about the location of reward given at the start of the runs. This advance cueing about reward produced a highly augmented task-bracketing pattern of activity at the beginning and end of procedural task performance relative to the patterns found previously with midtask cueing. Remarkably, the largest increase in activity early during the T-maze runs was not associated with the instruction cues themselves, the earliest predictors of reward; instead, the highest peak of early activity was associated with the beginning of the motor period of the task. We suggest that the advance cueing, reducing midrun demands for decision making but adding a working-memory load, facilitated chunking of the maze runs as executable scripts anchored to sensorimotor aspects of the task and unencumbered by midtask decision-making demands. Our findings suggest that the acquisition of stronger task-bracketing patterns of striatal activity in the sensorimotor striatum could reflect this enhancement of behavioral chunking. Deficits in such representations of learned sequential behaviors could contribute to motor and cognitive problems in a range of neurological disorders affecting the basal ganglia, including Parkinson's disease.
State-dependent sensorimotor processing: gaze and posture stability during simulated flight in birds
Authors: McArthur Kimberly L. , Dickman J. David
Published: February 2011

Vestibular responses play an important role in maintaining gaze and posture stability during rotational motion. Previous studies suggest that these responses are state dependent, their expression varying with the environmental and locomotor conditions of the animal. In this study, we simulated an ethologically relevant state in the laboratory to study state-dependent vestibular responses in birds. We used frontal airflow to simulate gliding flight and measured pigeons′ eye, head, and tail responses to rotational motion in darkness, under both head-fixed and head-free conditions. We show that both eye and head response gains are significantly higher during flight, thus enhancing gaze and head-in-space stability. We also characterize state-specific tail responses to pitch and roll rotation that would help to maintain body-in-space orientation during flight. These results demonstrate that vestibular sensorimotor processing is not fixed but depends instead on the animal's behavioral state.
Rationale for Targeting CD6 as a Treatment for Autoimmune Diseases
Authors: Alonso-Ramirez Ruby , Loisel Séverine , Buors Caroline , Pers Jacques-Olivier , Montero Enrique , Youinou Pierre , Renaudineau Yves
Published: February 2011

CD6 is a 105–130 kDa surface glycoprotein expressed on the majority of T cells and a subset of B cells. The humancd6gene maps to chromosome 11, and the expression of its protein product is tightly regulated. CD6 mediates cellular adhesion migration across the endothelial and epithelial cells. In addition, it participates in the antigen presentation by B cells and the subsequent proliferation of T cells. CD6 may bind intransto surface glycoproteins (such as ALCAM and 3A11), or to microbial lipopolysaccharides, and may bind incisto endogenous ligands (such as CD3 and CD5), and thereby deliver a costimulatory signal. Transinteractions are reinforced during autoimmune diseases (e.g., rheumatoid arthritis (RA), Sjögren's syndrome, and multiple sclerosis) and some cancers. Based on experimental data and on clinical results in RA and psoriasis, we believe that the recent humanized anti-CD6-specific mAb T1h may act as a regulator of the immunological response in addition to its function as an anti-T- and -B cell agent.
A Geometrical Setting for Constructing Nonlinear Lorentz Transformations of the Albano-Dresden Type
Authors: Lyra Alexandre , Carvalho Marcelo
Published: February 2011

We investigate a nonlinear realization of the Lorentz transformation defined in 4-dimensional
spacetime, and the corresponding invariant interval. This new interval is not a quadratic form in
the standard Minkowski spacetime, then we search for a description where it becomes a quadratic
form in an infinite dimensional vector space. In this extended space, we show how to generate two
classes of nonlinear transformations, which form a group and interpret the non-linear transformation
as compatible relations between atlas of a Lyra manifold.
Clinical Applications of Heart Rate Variability in the Triage and Assessment of Traumatically Injured Patients
Authors: Ryan Mark L. , Thorson Chad M. , Otero Christian A. , Vu Thai , Proctor Kenneth G.
Published: February 2011

Heart rate variability (HRV) is a method of physiologic assessment which uses fluctuations in the RR intervals to evaluate modulation of the heart rate by the autonomic nervous system (ANS). Decreased variability has been studied as a marker of increased pathology and a predictor of morbidity and mortality in multiple medical disciplines. HRV is potentially useful in trauma as a tool for prehospital triage, initial patient assessment, and continuous monitoring of critically injured patients. However, several technical limitations and a lack of standardized values have inhibited its clinical implementation in trauma. The purpose of this paper is to describe the three analytical methods (time domain, frequency domain, and entropy) and specific clinical populations that have been evaluated in trauma patients and to identify key issues regarding HRV that must be explored if it is to be widely adopted for the assessment of trauma patients.
Floorplacement for Partial Reconfigurable FPGA-Based Systems
Authors: Montone A. , Santambrogio M. D. , Redaelli F. , Sciuto D.
Published: February 2011

We presented a resource- and configuration-aware floorplacement framework, tailored for Xilinx Virtex 4 and 5 FPGAs, using an objective function based onexternal wirelength. Our work aims at identifying groups ofReconfigurable Functional Unitsthat are likely to be configured in the same chip area, identifying these areas based on resource requirements, device capabilities, and wirelength. Task graphs with few externally connected RRs lead to the biggest decrease, while external wirelength in task graphs with many externally connected RRs show lower improvement. The proposed approach results, as also demonstrated in the experimental results section, in a shorter external wirelength (an average reduction of 50%) with respect to purely area-driven approaches and a highly increased probability of reuse of existing links (90% reduction can be obtained in the best case).
Occult Tumor Burden Predicts Disease Recurrence in Lymph Node–Negative Colorectal Cancer
Authors: Hyslop Terry , Weinberg David S. , Schulz Stephanie , Barkun Alan , Waldman Scott A.
Published: February 2011

Purpose: Lymph node involvement by histopathology informs colorectal cancer prognosis, whereas recurrence in 25% of node-negative patients suggests the presence of occult metastasis. GUCY2C (guanylyl cyclase C) is a marker of colorectal cancer cells that identifies occult nodal metastases associated with recurrence risk. Here, we defined the association of occult tumor burden, quantified by GUCY2C reverse transcriptase-PCR (RT-PCR), with outcomes in colorectal cancer.

Experimental Design: Lymph nodes (range: 2–159) from 291 prospectively enrolled node-negative colorectal cancer patients were analyzed by histopathology and GUCY2C quantitative RT-PCR. Participants were followed for a median of 24 months (range: 2–63). Time to recurrence and disease-free survival served as primary and secondary outcomes, respectively. Association of outcomes with prognostic markers, including molecular tumor burden, was estimated by recursive partitioning and Cox models.

Results: In this cohort, 176 (60%) patients exhibited low tumor burden (MolLow), and all but four remained free of disease [recurrence rate 2.3% (95% CI, 0.1–4.5%)]. Also, 90 (31%) patients exhibited intermediate tumor burden (MolInt) and 30 [33.3% (23.7–44.1)] developed recurrent disease. Furthermore, 25 (9%) patients exhibited high tumor burden (MolHigh) and 17 [68.0% (46.5–85.1)] developed recurrent disease (P < 0.001). Occult tumor burden was an independent marker of prognosis. MolInt and MolHigh patients exhibited a graded risk of earlier time to recurrence [MolInt, adjusted HR 25.52 (11.08–143.18); P < 0.001; MolHigh, 65.38 (39.01–676.94); P < 0.001] and reduced disease-free survival [MolInt, 9.77 (6.26–87.26); P < 0.001; MolHigh, 22.97 (21.59–316.16); P < 0.001].

Conclusion: Molecular tumor burden in lymph nodes is independently associated with time to recurrence and disease-free survival in patients with node-negative colorectal cancer. Clin Cancer Res; 17(10); 3293–303. ©2011 AACR.
Eosinophilic Pleural Effusion Complicating Allergic Bronchopulmonary Aspergillosis
Authors: Kirschner Austin N. , Kuhlmann Erica , Kuzniar Tomasz J.
Published: February 2011

Allergic bronchopulmonary aspergillosis (ABPA) is primarily a disease of patients with cystic fibrosis or asthma, who typically present with bronchial obstruction, fever, malaise, and expectoration of mucus plugs. We report a case of a young man with a history of asthma who presented with cough, left-sided pleuritic chest pain and was found to have lobar atelectasis and an eosinophilic, empyematous pleural effusion. Bronchoscopy and sputum cultures grew Aspergillus fumigatus, and testing confirmed strong allergic response to this mold, all consistent with a diagnosis of ABPA. This novel and unique presentation of ABPA expands on the differential diagnosis of eosinophilic pleural effusions.
Safety of Stenting and Endarterectomy by Symptomatic Status in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)
Authors: Silver Frank L. , Mackey Ariane , Clark Wayne M. , Brooks William , Timaran Carlos H. , Chiu David , Goldstein Larry B. , Meschia James F. , Ferguson Robert D. , Moore Wesley S. , Howard George , Brott Thomas G.
Published: February 2011

Background and Purpose—

The safety of carotid artery stenting (CAS) and carotid endarterectomy (CEA) has varied by symptomatic status in previous trials. The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) data were analyzed to determine safety in symptomatic and asymptomatic patients.

Methods—

CREST is a randomized trial comparing safety and efficacy of CAS versus CEA in patients with high-grade carotid stenoses. Patients were defined as symptomatic if they had relevant symptoms within 180 days of randomization. The primary end point was stroke, myocardial infarction, or death within the periprocedural period or ipsilateral stroke up to 4 years.

Results—

For 1321 symptomatic and 1181 asymptomatic patients, the periprocedural aggregate of stroke, myocardial infarction, and death did not differ between CAS and CEA (5.2% versus 4.5%; hazard ratio, 1.18; 95% CI, 0.82 to 1.68;
P
=0.38). The stroke and death rate was higher for CAS versus CEA (4.4% versus 2.3%; hazard ratio, 1.90; 95% CI, 1.21 to 2.98;
P
=0.005). For symptomatic patients, the periprocedural stroke and death rates were 6.0%±0.9% for CAS and 3.2%±0.7% for CEA (hazard ratio, 1.89; 95% CI, 1.11 to 3.21;
P
=0.02). For asymptomatic patients, the stroke and death rates were 2.5%±0.6% for CAS and 1.4%±0.5% for CEA (hazard ratio, 1.88; 95% CI, 0.79 to 4.42;
P
=0.15). Rates were lower for those aged <80 years.

Conclusions—

There were no significant differences between CAS versus CEA by symptomatic status for the primary CREST end point. Periprocedural stroke and death rates were significantly lower for CEA in symptomatic patients. However, for both CAS and CEA, stroke and death rates were below or comparable to those of previous randomized trials and were within the complication thresholds suggested in current guidelines for both symptomatic and asymptomatic patients.
The Effects of Higher Levels of Immersion on Procedure Memorization Performance and Implications for Educational Virtual Environments
Authors: Ragan Eric D.
Published: February 2011

Researchers have proposed that immersion could have advantages for tasks involving abstract mental activities, such as conceptual learning; however, there are few empirical results that support this idea. We hypothesized that higher levels of immersion would benefit such tasks if the mental activity could be mapped to objects or locations in a 3D environment. To investigate this hypothesis, we performed an experiment in which participants memorized procedures in a virtual environment and then attempted to recall those procedures. We aimed to understand the effects of three components of immersion on performance. The results demonstrate that a matched software field of view (SFOV), a higher physical field of view (FOV), and a higher field of regard (FOR) all contributed to more effective memorization. The best performance was achieved with a matched SFOV and either a high FOV or a high FOR, or both. In addition, our experiment demonstrated that memorization in a virtual environment could be transferred to the real world. The results suggest that, for procedure memorization tasks, increasing the level of immersion even to moderate levels, such as those found in head mounted displays (HMDs) and display walls, can improve performance significantly compared to lower levels of immersion. Hypothesizing that the performance improvements provided by higher levels of immersion can be attributed to enhanced spatial cues, we discuss the values and limitations of supplementing conceptual information with spatial information in educational VR.
Transoral Incisionless Fundoplication Offers High Patient Satisfaction and Relief of Therapy-Resistant Typical and Atypical Symptoms of GERD in Community Practice
Authors: Barnes William E. , Hoddinott Kevin M. , Mundy Stephanie , Williams Madeline
Published: February 2011

This retrospective study evaluated clinical outcomes in 124 consecutive gastroesophageal reflux disease (GERD) patients who underwent transoral incisionless fundoplication (TIF) at 2 community hospitals. Out of 123 patients treated successfully, 110 gave consent (74% female, median age 60 [range 21-87] years, body mass index 27.5 [19.0-47.9]). At a median 7-month follow-up (range 5-17), typical and atypical symptom scores were normalized in 75% to 80% of patients, proton pump inhibitors (PPIs) were completely discontinued by 93%, and 83% were satisfied with their current health condition. Endoscopy in 53 patients revealed Hill grade I tight valves in 89% of the cases, reduced hiatal hernia in 33/34 (97%), and healed reflux esophagitis in 25/30 (83%). Based on global analysis, 72% of the patients were in remission, 20% improved symptomatically, and only 8% had ongoing GERD. These results supported the safety and efficacy of TIF as well as encouraged its application as an alternative treatment of GERD refractory to PPIs.
Genomic organization and splicing evolution of the doublesex gene, a Drosophila regulator of sexual differentiation, in the dengue and yellow fever mosquito Aedes aegypti
Authors: Salvemini Marco , Mauro Umberto , Lombardo Fabrizio , Milano Andreina , Zazzaro Vincenzo , Arcà Bruno , Polito Lino C , Saccone Giuseppe
Published: February 2011

Background

In the model system Drosophila melanogaster, doublesex (dsx) is the double-switch gene at the bottom of the somatic sex determination cascade that determines the differentiation of sexually dimorphic traits. Homologues of dsx are functionally conserved in various dipteran species, including the malaria vector Anopheles gambiae. They show a striking conservation of sex-specific regulation, based on alternative splicing, and of the encoded sex-specific proteins, which are transcriptional regulators of downstream terminal genes that influence sexual differentiation of cells, tissues and organs.

Results

In this work, we report on the molecular characterization of the dsx homologue in the dengue and yellow fever vector Aedes aegypti (Aeadsx). Aeadsx produces sex-specific transcripts by alternative splicing, which encode isoforms with a high degree of identity to Anopheles gambiae and Drosophila melanogaster homologues. Interestingly, Aeadsx produces an additional novel female-specific splicing variant. Genomic comparative analyses between the Aedes and Anopheles dsx genes revealed a partial conservation of the exon organization and extensive divergence in the intron lengths. An expression analysis showed that Aeadsx transcripts were present from early stages of development and that sex-specific regulation starts at least from late larval stages. The analysis of the female-specific untranslated region (UTR) led to the identification of putative regulatory cis-elements potentially involved in the sex-specific splicing regulation. The Aedes dsx sex-specific splicing regulation seems to be more complex with the respect of other dipteran species, suggesting slightly novel evolutionary trajectories for its regulation and hence for the recruitment of upstream splicing regulators.

Conclusions

This study led to uncover the molecular evolution of Aedes aegypti dsx splicing regulation with the respect of the more closely related Culicidae Anopheles gambiae orthologue. In Aedes aegypti, the dsx gene is sex-specifically regulated and encodes two female-specific and one male-specific isoforms, all sharing a doublesex/mab-3 (DM) domain-containing N-terminus and different C-termini. The sex-specific regulation is based on a combination of exon skipping, 5' alternative splice site choice and, most likely, alternative polyadenylation. Interestingly, when the Aeadsx gene is compared to the Anopheles dsx ortholog, there are differences in the in silico predicted default and regulated sex-specific splicing events, which suggests that the upstream regulators either are different or act in a slightly different manner. Furthermore, this study is a premise for the future development of transgenic sexing strains in mosquitoes useful for sterile insect technique (SIT) programs.
What's in a name; Genetic structure in Solanum section Petota studied using population-genetic tools
Authors: Jacobs Mirjam MJ , Smulders Marinus JM , van den Berg Ronald G , Vosman Ben
Published: February 2011

Background

The taxonomy and systematic relationships among species of Solanum section Petota are complicated and the section seems overclassified. Many of the presumed (sub)species from South America are very similar and they are able to exchange genetic material. We applied a population genetic approach to evaluate support for subgroups within this material, using AFLP data. Our approach is based on the following assumptions: (i) accessions that may exchange genetic material can be analyzed as if they are part of one gene pool, and (ii) genetic differentiation among species is expected to be higher than within species.

Results

A dataset of 566 South-American accessions (encompassing 89 species and subspecies) was analyzed in two steps. First, with the program STRUCTURE 2.2 in an 'unsupervised' procedure, individual accessions were assigned to inferred clusters based on genetic similarity. The results showed that the South American members of section Petota could be arranged in 16 clusters of various size and composition. Next, the accessions within the clusters were grouped by maximizing the partitioning of genetic diversity among subgroups (i.e., maximizing Fst values) for all available individuals of the accessions (2767 genotypes). This two-step approach produced an optimal partitioning into 44 groups.

Some of the species clustered as genetically distinct groups, either on their own, or combined with one or more other species. However, accessions of other species were distributed over more than one cluster, and did not form genetically distinct units.

Conclusions

We could not find any support for 43 species (almost half of our dataset). For 28 species some level of support could be found varying from good to weak. For 18 species no conclusions could be drawn as the number of accessions included in our dataset was too low. These molecular data should be combined with data from morphological surveys, with geographical distribution data, and with information from crossing experiments to identify natural units at the species level. However, the data do indicate which taxa or combinations of taxa are clearly supported by a distinct set of molecular marker data, leaving other taxa unsupported. Therefore, the approach taken provides a general method to evaluate the taxonomic system in any species complex for which molecular data are available.
Differential utilization of NF-kappaB RELA and RELB in response to extracellular versus intracellular polyIC stimulation in HT1080 cells
Authors: Yun James J , Tsao Ming-Sound , Der Sandy D
Published: February 2011

Background

Pattern recognition receptors (PRRs) for double-stranded RNA (dsRNA) are components of innate immunity that recognize the presence of viral infection and initiate efficient defense mechanisms. In addition to previously well-characterized signaling pathways that are mediated by PKR and TLR3, new intracellular dsRNA sensors, that are members of CARD and DExD/H box helicase family, have been identified. However, the molecular mechanisms involved in the signaling pathways mediated by these new dsRNA sensors have not been extensively characterized.

Results

Here, we studied an intracellular dsRNA pathway in the human fibrosarcoma cell line HT1080, which is distinct from the TLR3-mediated extracellular dsRNA pathway. Particularly, the NF-kB subunits RELA and RELB were differentially utilized by these two dsRNA signaling pathways. In TLR3-mediated dsRNA signaling, siRNA knock-down studies suggested a limited role for RELA on regulation of interferon beta and other cytokines whereas RELB appeared to have a negative regulatory role. By contrast, intracellular dsRNA signaling was dependent on RELA, but not RELB.

Conclusions

Our study suggests that extracellular and intracellular dsRNA signaling pathways may utilize different NF-kB members, and particularly the differential utilization of RELB may be a key mechanism for powerful inductions of NF-kB regulated genes in the intracellular dsRNA signaling pathway.
Reduction of claustrophobia during magnetic resonance imaging: methods and design of the "CLAUSTRO" randomized controlled trial
Authors: Enders Judith , Zimmermann Elke , Rief Matthias , Martus Peter , Klingebiel Randolf , Asbach Patrick , Klessen Christian , Diederichs Gerd , Bengner Thomas , Teichgräber Ulf , Hamm Bernd , Dewey Marc
Published: February 2011

Background

Magnetic resonance (MR) imaging has been described as the most important medical innovation in the last 25 years. Over 80 million MR procedures are now performed each year and on average 2.3% (95% confidence interval: 2.0 to 2.5%) of all patients scheduled for MR imaging suffer from claustrophobia. Thus, prevention of MR imaging by claustrophobia is a common problem and approximately 2,000,000 MR procedures worldwide cannot be completed due to this situation. Patients with claustrophobic anxiety are more likely to be frightened and experience a feeling of confinement or being closed in during MR imaging. In these patients, conscious sedation and additional sequences (after sedation) may be necessary to complete the examinations. Further improvements in MR design appear to be essential to alleviate this situation and broaden the applicability of MR imaging. A more open scanner configuration might help reduce claustrophobic reactions while maintaining image quality and diagnostic accuracy.

Methods/Design

We propose to analyze the rate of claustrophobic reactions, clinical utility, image quality, patient acceptance, and cost-effectiveness of an open MR scanner in a randomized comparison with a recently designed short-bore but closed scanner with 97% noise reduction. The primary aim of this study is thus to determine whether an open MR scanner can reduce claustrophobic reactions, thereby enabling more examinations of claustrophobic patients without incurring the safety issues associated with conscious sedation. In this manuscript we detail the methods and design of the prospective "CLAUSTRO" trial.

Discussion

This randomized controlled trial will be the first direct comparison of open vertical and closed short-bore MR systems in regards to claustrophobia and image quality as well as diagnostic utility.

Trial Registration

ClinicalTrials.gov:NCT00715806
An automated growth enclosure for metabolic labeling of Arabidopsis thaliana with 13C-carbon dioxide - an in vivo labeling system for proteomics and metabolomics research
Authors: Chen Wen-Ping , Yang Xiao-Yuan , Harms Geoffrey L , Gray William M , Hegeman Adrian D , Cohen Jerry D
Published: February 2011

Background

Labeling whole Arabidopsis (Arabidopsis thaliana) plants to high enrichment with 13C for proteomics and metabolomics applications would facilitate experimental approaches not possible by conventional methods. Such a system would use the plant's native capacity for carbon fixation to ubiquitously incorporate 13C from 13CO2 gas. Because of the high cost of 13CO2 it is critical that the design conserve the labeled gas.

Results

A fully enclosed automated plant growth enclosure has been designed and assembled where the system simultaneously monitors humidity, temperature, pressure and 13CO2 concentration with continuous adjustment of humidity, pressure and 13CO2 levels controlled by a computer running LabView software. The enclosure is mounted on a movable cart for mobility among growth environments. Arabidopsis was grown in the enclosure for up to 8 weeks and obtained on average >95 atom% enrichment for small metabolites, such as amino acids and >91 atom% for large metabolites, including proteins and peptides.

Conclusion

The capability of this labeling system for isotope dilution experiments was demonstrated by evaluation of amino acid turnover using GC-MS as well as protein turnover using LC-MS/MS. Because this 'open source' Arabidopsis
13C-labeling growth environment was built using readily available materials and software, it can be adapted easily to accommodate many different experimental designs.
Superlattices: problems and new opportunities, nanosolids
Authors: Tsu Raphael
Published: February 2011

Superlattices were introduced 40 years ago as man-made solids to enrich the class of materials for electronic and optoelectronic applications. The field metamorphosed to quantum wells and quantum dots, with ever decreasing dimensions dictated by the technological advancements in nanometer regime. In recent years, the field has gone beyond semiconductors to metals and organic solids. Superlattice is simply a way of forming a uniform continuum for whatever purpose at hand. There are problems with doping, defect-induced random switching, and I/O involving quantum dots. However, new opportunities in component-based nanostructures may lead the field of endeavor to new heights. The all important translational symmetry of solids is relaxed and local symmetry is needed in nanosolids.
Rapid thermal annealing and crystallization mechanisms study of silicon nanocrystal in silicon carbide matrix
Authors: Wan Zhenyu , Huang Shujuan , Green Martin A , Conibeer Gavin
Published: February 2011

In this paper, a positive effect of rapid thermal annealing (RTA) technique has been researched and compared with conventional furnace annealing for Si nanocrystalline in silicon carbide (SiC) matrix system. Amorphous Si-rich SiC layer has been deposited by co-sputtering in different Si concentrations (50 to approximately 80 v%). Si nanocrystals (Si-NC) containing different grain sizes have been fabricated within the SiC matrix under two different annealing conditions: furnace annealing and RTA both at 1,100°C. HRTEM image clearly reveals both Si and SiC-NC formed in the films. Much better "degree of crystallization" of Si-NC can be achieved in RTA than furnace annealing from the research of GIXRD and Raman analysis, especially in high-Si-concentration situation. Differences from the two annealing procedures and the crystallization mechanism have been discussed based on the experimental results.
A human cancer-predisposing polymorphism in Cdc25A is embryonic lethal in the mouse and promotes ASK-1 mediated apoptosis
Authors: Bahassi El Mustapha , Yin Moying , Robbins Susan B , Li Ya-Qin , Conrady Deborah G , Yuan Zhenyu , Kovall Rhett A , Herr Andrew B , Stambrook Peter J
Published: February 2011

Background

Failure to regulate the levels of Cdc25A phosphatase during the cell cycle or during a checkpoint response causes bypass of DNA damage and replication checkpoints resulting in genomic instability and cancer. During G1 and S and in cellular response to DNA damage, Cdc25A is targeted for degradation through the Skp1-cullin-β-TrCP (SCFβ-TrCP) complex. This complex binds to the Cdc25A DSG motif which contains serine residues at positions 82 and 88. Phosphorylation of one or both residues is necessary for the binding and degradation to occur.

Results

We now show that mutation of serine 88 to phenylalanine, which is a cancer-predisposing polymorphic variant in humans, leads to early embryonic lethality in mice. The mutant protein retains its phosphatase activity both in vitro and in cultured cells. It fails to interact with the apoptosis signal-regulating kinase 1 (ASK1), however, and therefore does not suppress ASK1-mediated apoptosis.

Conclusions

These data suggest that the DSG motif, in addition to its function in Cdc25A-mediated degradation, plays a role in cell survival during early embyogenesis through suppression of ASK1-mediated apoptosis.
Reciprocal relationship between APP positioning relative to the membrane and PS1 conformation
Authors: Uemura Kengo , Farner Katherine C , Nasser-Ghodsi Navine , Jones Phill , Berezovska Oksana
Published: February 2011

Background

Several familial Alzheimer disease (FAD) mutations within the transmembrane region of the amyloid precursor protein (APP) increase the Aβ42/40 ratio without increasing total Aβ production. In the present study, we analyzed the impact of FAD mutations and γ-secretase modulators (GSMs) that alter the Aβ42/40 ratio on APP C-terminus (CT) positioning relative to the membrane, reasoning that changes in the alignment of the APP intramembranous domain and presenilin 1 (PS1) may impact the PS1/γ-secretase cleavage site on APP.

Results

By using a Förster resonance energy transfer (FRET)-based technique, fluorescent lifetime imaging microscopy (FLIM), we show that Aβ42/40 ratio-modulating factors which target either APP substrate or PS1/γ-secretase affect proximity of the APP-CT to the membrane and change PS1 conformation.

Conclusions

Thus, we propose that there is a reciprocal relationship between APP-CT positioning relative to the membrane and PS1 conformation, suggesting that factors that modulate either APP positioning in the membrane or PS1 conformation could be exploited therapeutically.
Implications of ICU triage decisions on patient mortality: a cost-effectiveness analysis
Authors: Edbrooke David L , Minelli Cosetta , Mills Gary H , Iapichino Gaetano , Pezzi Angelo , Corbella Davide , Jacobs Philip , Lippert Anne , Wiis Joergen , Pesenti Antonio , Patroniti Nicolo , Pirracchio Romain , Payen Didier , Gurman Gabriel , Bakker Jan , Kesecioglu Jozef , Hargreaves Chris , Cohen Simon L , Baras Mario , Artigas Antonio , Sprung Charles L
Published: February 2011

Introduction

Intensive care is generally regarded as expensive, and as a result beds are limited. This has raised serious questions about rationing when there are insufficient beds for all those referred. However, the evidence for the cost effectiveness of intensive care is weak and the work that does exist usually assumes that those who are not admitted do not survive, which is not always the case. Randomised studies of the effectiveness of intensive care are difficult to justify on ethical grounds; therefore, this observational study examined the cost effectiveness of ICU admission by comparing patients who were accepted into ICU after ICU triage to those who were not accepted, while attempting to adjust such comparison for confounding factors.

Methods

This multi-centre observational cohort study involved 11 hospitals in 7 EU countries and was designed to assess the cost effectiveness of admission to intensive care after ICU triage. A total of 7,659 consecutive patients referred to the intensive care unit (ICU) were divided into those accepted for admission and those not accepted. The two groups were compared in terms of cost and mortality using multilevel regression models to account for differences across centres, and after adjusting for age, Karnofsky score and indication for ICU admission. The analyses were also stratified by categories of Simplified Acute Physiology Score (SAPS) II predicted mortality (< 5%, 5% to 40% and >40%). Cost effectiveness was evaluated as cost per life saved and cost per life-year saved.

Results

Admission to ICU produced a relative reduction in mortality risk, expressed as odds ratio, of 0.70 (0.52 to 0.94) at 28 days. When stratified by predicted mortality, the odds ratio was 1.49 (0.79 to 2.81), 0.7 (0.51 to 0.97) and 0.55 (0.37 to 0.83) for <5%, 5% to 40% and >40% predicted mortality, respectively. Average cost per life saved for all patients was $103,771 (€82,358) and cost per life-year saved was $7,065 (€5,607). These figures decreased substantially for patients with predicted mortality higher than 40%, $60,046 (€47,656) and $4,088 (€3,244), respectively. Results were very similar when considering three-month mortality. Sensitivity analyses performed to assess the robustness of the results provided findings similar to the main analyses.

Conclusions

Not only does ICU appear to produce an improvement in survival, but the cost per life saved falls for patients with greater severity of illness. This suggests that intensive care is similarly cost effective to other therapies that are generally regarded as essential.
Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia: a prospective, observational, genetic study
Authors: García-Laorden MIsabel , Rodríguez de Castro Felipe , Solé-Violán Jordi , Rajas Olga , Blanquer José , Borderías Luis , Aspa Javier , Briones M Luisa , Saavedra Pedro , Marcos-Ramos J Alberto , González-Quevedo Nereida , Sologuren Ithaisa , Herrera-Ramos Estefanía , Ferrer José M , Rello Jordi , Rodríguez-Gallego Carlos
Published: February 2011

Introduction

Genetic variability of the pulmonary surfactant proteins A and D may affect clearance of microorganisms and the extent of the inflammatory response. The genes of these collectins (SFTPA1, SFTPA2 and SFTPD) are located in a cluster at 10q21-24. The objective of this study was to evaluate the existence of linkage disequilibrium (LD) among these genes, and the association of variability at these genes with susceptibility and outcome of community-acquired pneumonia (CAP). We also studied the effect of genetic variability on SP-D serum levels.

Methods

Seven non-synonymous polymorphisms of SFTPA1, SFTPA2 and SFTPD were analyzed. For susceptibility, 682 CAP patients and 769 controls were studied in a case-control study. Severity and outcome were evaluated in a prospective study. Haplotypes were inferred and LD was characterized. SP-D serum levels were measured in healthy controls.

Results

The SFTPD aa11-C allele was significantly associated with lower SP-D serum levels, in a dose-dependent manner. We observed the existence of LD among the studied genes. Haplotypes SFTPA1 6A
2
(P = 0.0009, odds ration (OR) = 0.78), SFTPA2 1A
0
(P = 0.002, OR = 0.79), SFTPA1-SFTPA2 6A
2
-1A
0
(P = 0.0005, OR = 0.77), and SFTPD-SFTPA1-SFTPA2 C-6A
2
-1A
0
(P = 0.00001, OR = 0.62) were underrepresented in patients, whereas haplotypes SFTPA2 1A
10
(P = 0.00007, OR = 6.58) and SFTPA1-SFTPA2 6A
3
-1A (P = 0.0007, OR = 3.92) were overrepresented. Similar results were observed in CAP due to pneumococcus, though no significant differences were now observed after Bonferroni corrections. 1A
10
and 6A-1A were associated with higher 28-day and 90-day mortality, and with multi-organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) respectively. SFTPD aa11-C allele was associated with development of MODS and ARDS.

Conclusions

Our study indicates that missense single nucleotide polymorphisms and haplotypes of SFTPA1, SFTPA2 and SFTPD are associated with susceptibility to CAP, and that several haplotypes also influence severity and outcome of CAP.