bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natively unstructured regions in proteins identified from contact predictions
Authors: Schlessinger Avner , Punta Marco , Rost Burkhard 
Published: August 2007

AbstractMotivation: Natively unstructured (also dubbed intrinsically disordered) regions in proteins lack a defined 3D structure under physiological conditions and often adopt regular structures under particular conditions. Proteins with such regions are overly abundant in eukaryotes, they may increase functional complexity of organisms and they usually evade structure determination in the unbound form. Low propensity for the formation of internal residue contacts has been previously used to predict natively unstructured regions.Results: We combined PROFcon predictions for protein-specific contacts with a generic pairwise potential to predict unstructured regions. This novel method, Ucon, outperformed the best available methods in predicting proteins with long unstructured regions. Furthermore, Ucon correctly identified cases missed by other methods. By computing the difference between predictions based on specific contacts (approach introduced here) and those based on generic potentials (realized in other methods), we might identify unstructured regions that are involved in protein–protein binding. We discussed one example to illustrate this ambitious aim. Overall, Ucon added quality and an orthogonal aspect that may help in the experimental study of unstructured regions in network hubs.Availability: http://www.predictprotein.org/submit_ucon.htmlContact: as2067@columbia.eduSupplementary information: Supplementary data are available at Bioinformatics online.
Con-Struct Map: a comparative contact map analysis tool
Authors: Chung Jo-Lan , Beaver John E. , Scheeff Eric D. , Bourne Philip E. 
Published: August 2007

AbstractSummary: Con-Struct Map is a graphical tool for the comparative study of protein structures. The tool detects potential conserved residue contacts shared by multiple protein structures by superimposing their contact maps according to a multiple structure alignment. In general, Con-Struct Map allows the study of structural changes resulting from, e.g. sequence substitutions, or alternatively, the study of conserved components of a structure framework across structurally aligned proteins. Specific applications include the study of sequence-structure relationship in distantly related proteins and the comparisons of wild type and mutant proteins.Availability: http://pdbrs3.sdsc.edu/ConStructMap/viewer_argument_generator/singleArgumentsContact: bourne@sdsc.eduSupplementary information: Supplementary data are available at Bioinformatics online.
A Laboratory Information Management System (LIMS) for a high throughput genetic platform aimed at candidate gene mutation screening
Authors: Voegele C. , Tavtigian S.V. , de Silva D. , Cuber S. , Thomas A. , Le Calvez-Kelm F. 
Published: August 2007

AbstractSummary: High throughput mutation screening in an automated environment generates large data sets that have to be organized and stored reliably. Complex multistep workflows require strict process management and careful data tracking. We have developed a Laboratory Information Management Systems (LIMS) tailored to high throughput candidate gene mutation scanning and resequencing that respects these requirements. Designed with a client/server architecture, our system is platform independent and based on open-source tools from the database to the web application development strategy. Flexible, expandable and secure, the LIMS, by communicating with most of the laboratory instruments and robots, tracks samples and laboratory information, capturing data at every step of our automated mutation screening workflow. An important feature of our LIMS is that it enables tracking of information through a laboratory workflow where the process at one step is contingent on results from a previous step.Availability: Script for MySQL database table creation and source code of the whole JSP application are freely available on our website: http://www-gcs.iarc.fr/lims/.Contact: voegele@iarc.frSupplementary information: System server configuration, database structure and additional details on the LIMS and the mutation screening workflow are available on our website: http://www-gcs.iarc.fr/lims/
Differential Contribution of Sodium Channel Subtypes to Action Potential Generation in Unmyelinated Human C-type Nerve Fibers
Authors: Lang Philip M. , Hilmer Verena B. , Grafe Peter 
Published: August 2007

Background
Multiple voltage-dependent sodium channels (Na(v)) contribute to action potentials and excitability of primary nociceptive neurons. The aim of the current study was to characterize subtypes of Na(v) that contribute to action potential generation in peripheral unmyelinated human C-type nerve fibers.

Methods
Registration of C-fiber compound action potentials and determination of membrane threshold was performed by a computerized threshold tracking program. Nerve fibers were stimulated with a 1-ms current pulse either alone or after a small ramp current lasting 300 ms.

Results
Compound C-fiber action potentials elicited by supramaximal 1-ms current pulses were rather resistant to application of tetrodotoxin (30-90 nM). However, the same concentrations of tetrodotoxin strongly reduced the peak height and elevated membrane threshold of action potentials evoked at the end of a 300-ms current ramp. A similar effect was observed during application of lidocaine and mexiletine (50 microM each).

Conclusions
These data indicate that more than one type of Na(v) contributes to the generation of action potentials in unmyelinated human C-type nerve fibers. The peak height of an action potential produced by a short electrical impulse is dependent on the activation of tetrodotoxin-resistant ion channels. In contrast, membrane threshold and action potential peak height at the end of a slow membrane depolarization are regulated by a subtype of Na(v) with high sensitivity to low concentrations of tetrodotoxin, lidocaine, and mexiletine. The electrophysiologic and pharmacologic characteristics may indicate the functional activity of the Na(v) 1.7 subtype of voltage-dependent sodium channels.
Neonatal Exposure to a Combination of N -Methyl-d-aspartate and γ-Aminobutyric Acid Type A Receptor Anesthetic Agents Potentiates Apoptotic Neurodegeneration and Persistent Behavioral Deficits
Authors: Fredriksson Anders , Pontén Emma , Gordh Torsten , Eriksson Per 
Published: August 2007

Background
During the brain growth spurt, the brain develops and modifies rapidly. In rodents this period is neonatal, spanning the first weeks of life, whereas in humans it begins during the third trimester and continues 2 yr. This study examined whether different anesthetic agents, alone and in combination, administered to neonate mice, can trigger apoptosis and whether behavioral deficits occur later in adulthood.

Methods
Ten-day-old mice were injected subcutaneously with ketamine (25 mg/kg), thiopental (5 mg/kg or 25 mg/kg), propofol (10 mg/kg or 60 mg/kg), a combination of ketamine (25 mg/kg) and thiopental (5 mg/kg), a combination of ketamine (25 mg/kg) and propofol (10 mg/kg), or control (saline). Fluoro-Jade staining revealed neurodegeneration 24 h after treatment. The behavioral tests--spontaneous behavior, radial arm maze, and elevated plus maze (before and after anxiolytic)--were conducted on mice aged 55-70 days.

Results
Coadministration of ketamine plus propofol or ketamine plus thiopental or a high dose of propofol alone significantly triggered apoptosis. Mice exposed to a combination of anesthetic agents or ketamine alone displayed disrupted spontaneous activity and learning. The anxiolytic action of diazepam was less effective when given to adult mice that were neonatally exposed to propofol.

Conclusion
This study shows that both a gamma-aminobutyric acid type A agonist (thiopental or propofol) and an N-methyl-D-aspartate antagonist (ketamine) during a critical stage of brain development potentiated neonatal brain cell death and resulted in functional deficits in adulthood. The use of thiopental, propofol, and ketamine individually elicited no or only minor changes.
Median Frequency Revisited
Authors: Jordan Denis , Stockmanns Gudrun , Kochs Eberhard F. , Schneider Gerhard 
Published: August 2007

Background
In the past, several electroencephalographic parameters have been presented and discussed with regard to their reliability in discerning consciousness from unconsciousness. Some of them, such as the median frequency and spectral edge frequency, are based on classic spectral analysis, and it has been demonstrated that they are of limited capacity in differing consciousness and unconsciousness.

Methods
A generalized approach based on the Fourier transform is presented to improve the performance of electroencephalographic parameters with respect to the separation of consciousness from unconsciousness. Electroencephalographic data from two similar clinical studies (for parameter development and evaluation) in adult patients undergoing general anesthesia with sevoflurane or propofol are used. The study period was from induction of anesthesia until patients followed command after surgery and includes a reduction of the hypnotic agent after tracheal intubation until patients followed command. Prediction probability was calculated to assess the ability of the parameters to separate consciousness from unconsciousness.

Results
On the basis of the training set of 40 patients, a new spectral parameter called weighted spectral median frequency was designed, achieving a prediction probability of 0.82 on the basis of the "classic" electroencephalographic frequency range up to 30 Hz. Next, in the evaluation data set, the prediction probability was 0.79, which is higher than the prediction probability of median frequency (0.58) or spectral edge frequency (0.59) and the Bispectral Index (0.68) as calculated from the same data set.

Conclusions
A more general approach of the design of spectral parameters leads to a new electroencephalographic spectral parameter that separates consciousness from unconsciousness significantly better than the Bispectral Index.
Apolipoprotein E e4 Allele Increases the Risk of Early Postoperative Delirium in Older Patients Undergoing Noncardiac Surgery
Authors: Leung Jacqueline M. , Sands Laura P. , Wang Yun , Poon Annie , Kwok Pui-yan , Kane John P. , Pullinger Clive R. 
Published: August 2007

Background
Whether patients who subsequently develop early postoperative delirium have a genetic predisposition that renders them at risk for postoperative delirium has not been determined.

Methods
The authors conducted a nested cohort study to include patients aged > or = 65 yr who were scheduled to undergo major noncardiac surgery requiring anesthesia. A structured interview was conducted preoperatively and for the first 2 days postoperatively to determine the presence of delirium, defined using the Confusion Assessment Method. Blood was drawn for measurement of the apolipoprotein genotypes. Bivariate tests of association were conducted between delirium and apolipoprotein genotypes and other potentially important risk factors. Variables that had significant bivariate association with postoperative delirium were entered in a forward multivariable logistic regression model.

Results
Of the 190 patients studied, 15.3% developed delirium on both days 1 and 2 after surgery. Forty-six patients (24.2%) had at least one copy of the apolipoprotein e4 allele. The presence of one copy of the e4 allele was associated with an increased risk of early postoperative delirium (28.3% vs. 11.1%; P = 0.005). Even after adjusting for covariates, patients with one copy of the e4 allele were still more likely to have an increased risk of early postoperative delirium (odds ratio, 3.64; 95% confidence interval, 1.51-8.77) compared with those without the e4 allele.

Conclusions
Apolipoprotein e4 carrier status was associated with an increased risk for early postoperative delirium after controlling for known demographic and clinical risk factors. These results suggest that genetic predisposition plays a role and may interact with anesthetic/surgical factors contributing to the development of early postoperative delirium.
Mechanical Ventilation in Healthy Mice Induces Reversible Pulmonary and Systemic Cytokine Elevation with Preserved Alveolar Integrity
Authors: Vaneker Michiel , Halbertsma Feico J. , van Egmond Jan , Netea Mihai G. , Dijkman Henry B. , Snijdelaar Dirk G. , Joosten Leo A. , van der Hoeven Johannes G. , Scheffer Gert Jan 
Published: August 2007

Background
Mechanical ventilation (MV) may activate the innate immune system, causing the release of cytokines. The resulting proinflammatory state is a risk factor for ventilator-induced lung injury. Cytokine increase results from direct cellular injury but may also result from cyclic stretch alone as demonstrated in vitro: mechanotransduction. To study mechanotransduction in vivo, the authors used an animal MV model with clinically relevant ventilator settings, avoiding alveolar damage.

Methods
Healthy C57BL6 mice (n = 82) were ventilated (tidal volume, 8 ml/kg; positive end-expiratory pressure, 4 cm H2O; fraction of inspired oxygen, 0.4) for 30, 60, 120, and 240 min. Assigned animals were allowed to recover for 2 days after MV. Both pulmonary tissue and plasma interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor alpha, IL-6, IL-10, and keratinocyte-derived chemokine levels were measured. Histopathologic appearance of lung tissue was analyzed by light microscopy and electron microscopy.

Results
In lung tissue, all measured cytokines and keratinocyte-derived chemokine levels increased progressively with MV duration. Light microscopy showed increased leukocyte influx but no signs of alveolar leakage or albumin deposition. Electron microscopy revealed intact epithelial cell and basement membranes with sporadically minimal signs of partial endothelial detachment. In plasma, increased levels of IL-1alpha, tumor necrosis factor alpha, IL-6, and keratinocyte-derived chemokine were measured after MV. In the recovery animals, cytokine levels had normalized and no histologic alterations could be found.

Conclusions
Mechanical ventilation induces reversible cytokine increase and leukocyte influx with preserved tissue integrity. This model offers opportunities to study the pathophysiologic mechanisms behind ventilator-induced lung injury and the contribution of MV to the "multiple-hit" concept.
Altered Contractile Response due to Increased β3-Adrenoceptor Stimulation in Diabetic Cardiomyopathy
Authors: Amour Julien , Loyer Xavier , Le Guen Morgan , Mabrouk Nejma , David Jean-Stéphane , Camors Emmanuel , Carusio Nunzia , Vivien Benoît , Andriantsitohaina Ramaroson , Heymes Christophe , Riou Bruno 
Published: August 2007

Background
In the diabetic heart, the positive inotropic response to beta-adrenoceptor stimulation is altered and beta1 and beta2 adrenoceptors are down-regulated, whereas beta3 adrenoceptor is up-regulated. In heart failure, beta3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of beta3-adrenoceptor in diabetic cardiomyopathy.

Methods
beta-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of beta3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline +/- SD.

Results
The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 +/- 15% vs. 160 +/- 16%; P < 0.05) and in vitro (112 +/- 5% vs. 179 +/- 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of beta3-adrenoceptor antagonist (174 +/- 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 +/- 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino-3-butenyl)-l-ornithine [l-VNIO]; 172 +/- 13%). In diabetes, in parallel with the increase in beta3-adrenoceptor protein expression, the positive inotropic effect was partially restored by beta3-adrenoceptor antagonist (137 +/- 8%; P < 0.05), l-NAME (133 +/- 11%; P < 0.05), or l-VNIO (130 +/- 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable.

Conclusions
beta3-Adrenoceptor is involved in altered positive inotropic response to beta-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic cardiomyocyte.
Diet and food preference of the waterbuck (Kobus ellipsiprymnus defassa) in the Pendjari National Park, Benin
Authors: Kassa Barthélémy , Libois Roland , Sinsin Brice 
Published: August 2007

AbstractThis study investigated composition and selectivity in diet for waterbuck in the Pendjari National Park in north‐western Benin, through the use of micrographic analysis of faecal samples. Three plant species (Panicum anabaptistum, Echinochloa stagnina and Andropogon gayanus) were regularly consumed all year round. Meanwhile, three other species (i.e., Hyparrhenia involucrata, Acroceras amplectens and Oryza barthii) are mostly found in its diet during the beginning of the rainy season. During the dry season, long life grasses (>40%) and tree forage (about 35%) were the most dominant life form in the diet. On the contrary at the beginning of the rainy season, annual species (> 50%) were dominant. In conclusion, the waterbuck has a grazer regime when plant species are abundant and a mixed diet during the dry season. Waterbuck’s food niche breath, defined by Hespenheide [Ecology and Evolution of communities. Harvard Univ. Press, 1975], was lower than 1, implying this antelope does not eat all food categories in a proportional way. Shannon diversity index showed that the diet was more diversified during the rainy season and less diversified at the end of the dry season. Based on [Ecology, 64 (1983), 1297] diet selectivity index, waterbuck exerted a positive selection on the major graminaceous species.
How much do junior staff know about common legal situations in paediatrics?
Authors: Ashtekar C. S. , Hande A. , Stallard E. , Tuthill D. 
Published: August 2007

AbstractBackground  Recent high‐profile medico‐legal cases such as the death of Victoria Climbie and the subsequent Laming report have highlighted widespread deficiencies in child protection practice. Junior doctors are the frontline staff regularly facing issues with potentially major legal implications, including child protection, Gillick competence, consent, and professional responsibility/accountability. It is therefore important for them to be aware and understand the Children Act, common medico‐legal principles and practices, particularly in the current, increasingly litigious climate.Aims  (1) To determine junior medical staff's knowledge of legal issues involved in child protection and common basic legal situations, and (2) to assess whether experience and training improved this knowledge.Methods  A standardized structured interview was developed exploring common issues with important legal implications for paediatric practice. It focused on: legal issues in child protection, the Children Act, awareness of the General Medical Council (GMC), principles of professional responsibility/accountability, the Bolam principle for good medical practice and Gillick competence. Basic demographic data were recorded. We attempted to contact all 180 paediatric junior medical staff in Wales by telephone.Results  Interviews were conducted with 119/180 (66%) doctors: 46/56 specialist registrars (SpRs; 82%) and 73/124 senior house officers (SHOs; 59%). SpRs scored a median of 6.5 correct responses from a possible of 12 (range 3–11), compared with a median of 5 (range 1–11) by the SHOs (P < 0.0001; Mann–Whitney test). A third of SHOs and a fifth of SpRs were unaware that the GMC was the organization responsible for good medical practice in the UK. Similarly, a fifth of all juniors were ignorant of the legal age for consent. Approximately two‐thirds of the SHOs and half of the SpRs were ignorant that the police and social services have the legal power to protect the child in child protection cases. Alarmingly, none of the SHOs and only 11% of the SpRs were aware of the Bolam principle. SpRs scored significantly higher on topics of Gillick competence, legal right to see medical notes, consent, Children Act, burden of proof in civil and criminal court, and on Bolam principle. They also had received training more frequently than SHOs, which, when combined with their greater experience, probably explains these statistically significant differences.Conclusion  Few junior staff have adequate knowledge of the basic legal principles and practice as they relate to children. Widespread deficiencies concerning the understanding of the Children Act and child protection powers exist.
Mental health of young people: a global public‐health challenge
Authors: Reading Richard 
Published: August 2007

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Patel V.,
Flisher A. J.,
Hetrick S. &
McGorry P.
(
2007
)

,
369
,
1302
–
13
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DOI: 10.1016/S0140‐6736(07)60368–7.