bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solution structures of the trihelix DNA‐binding domains of the wild‐type and a phosphomimetic mutant of Arabidopsis GT‐1: Mechanism for an increase in DNA‐binding affinity through phosphorylation
Authors: Nagata Takashi , Niyada Emi , Fujimoto Natsuki , Nagasaki Yuuya , Noto Kazuaki , Miyanoiri Youhei , Murata Jun , Hiratsuka Kazuyuki , Katahira Masato 
Published: July 2010

AbstractGT‐1 is a plant transcription factor that binds to one of the cis‐acting elements, BoxII, which resides within the upstream promoter region of light‐responsive genes. GT‐1 was assumed to act as a molecular switch modulated through Ca2+‐dependent phosphorylation/dephosphorylation in response to light signals. It was shown previously that the phosphorylation of threonine 133 in the DNA‐binding domain (DBD) of GT‐1 results in enhancement of the BoxII‐binding activity. Interestingly, point mutation of Thr133 to Asp also enhances the BoxII‐binding activity. Here, we report the solution structures of hypothetical trihelix DBDs of the wild‐type (WT) and a phosphomimetic mutant (T133D) of GT‐1. First, we demonstrated that the isolated DBD of GT‐1 alone has the ability to bind to DNA, and that the T133D mutation of the isolated DBD can enhance the DNA‐binding affinity. The structures of these DBDs turned out to be almost identical. The structural topology resembles that of Myb DBDs, but all α‐helices are longer in GT‐1. Our NMR titration experiments suggested that these longer α‐helices yield an enlarged DNA‐binding surface. The phosphorylation site is located at the N‐terminus of the third α‐helix. We built a structural model of the T133D DBD:BoxII complex with the program HADDOCK. The model resembles the structure of the TRF1 DBD:telomeric DNA complex. Interestingly, the model implies that the phosphorylated side chain may directly interact with the bases of DNA. On the basis of our findings, we propose a mechanism by which the DNA‐binding activity toward BoxII of the phosphorylated GT‐1 could be enhanced. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Protein homomers in point‐group assembly: Symmetry making and breaking are specific and distinctive in their codes of chemical alphabet in side chains
Authors: Pednekar Deepa , Durani Susheel 
Published: July 2010

AbstractOligomerizing to point‐group symmetry, protein oligomers need to have the symmetry broken for biologically crucial functions, such as, allosteric regulation, enzyme catalysis, and so forth. In the making of symmetry, based on self assembly, and the breaking of symmetry, based on intermolecular interactions, proteins may manifest, like their other functions, specific scripts over the coding alphabet in side chains. To address the possibility, we analyzed 82 protein homodimers in their C2‐symmetry‐related side chains across noncrystallographic interfaces, to know if they may be identical or distinct in conformation, and thus conserved or broken in symmetry. We find the propensity to conformational mismatch across interfaces correlated with side‐chain chemical structure, low to very low in aromatic Trp, Tyr, His, Phe, and Arg, and high to very high in aliphatic Val, Pro, Met, Glu, Ser, Lys, Gln, Asn, and Asp, related not to polarity but, interestingly, to aromaticity of the structure. The organizational plan having aromatics embedded in a hub of aliphatic‐nonpolar groups and a surrounding rim of aliphatic‐polar groups, called “hotspot,” has been known to direct protein–protein interaction. Finding conformational‐mismatch propensities of side chains congruous with their specific chemical roles in protein‐protein interaction, we propose that aromatic side chains will drive protein homomers to high symmetry, while polar‐ and nonpolar aliphatic side chains will drive them to the functionally‐necessitated breaks of symmetry. Side chains are in their roles as protein‐coding alphabet illuminated in the physics, which is discussed. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Protein–protein docking with binding site patch prediction and network‐based terms enhanced combinatorial scoring
Authors: Gong Xinqi , Wang Panwen , Yang Feng , Chang Shan , Liu Bin , He Hongqiu , Cao Libin , Xu Xianjin , Li Chunhua , Chen Weizu , Wang Cunxin 
Published: July 2010

AbstractProtein–protein docking has made much progress in recent years, but challenges still exist. Here we present the application of our docking approach HoDock in CAPRI. In this approach, a binding site prediction is implemented to reduce docking sampling space and filter out unreasonable docked structures, and a network‐based enhanced combinatorial scoring function HPNCscore is used to evaluate the decoys. The experimental information was combined with the predicted binding site to pick out the most likely key binding site residues. We applied the HoDock method in the recent rounds of the CAPRI experiments, and got good results as predictors on targets 39, 40, and 41. We also got good results as scorers on targets 35, 37, 40, and 41. This indicates that our docking approach can contribute to the progress of protein–protein docking methods and to the understanding of the mechanism of protein–protein interactions. Proteins 2010. © 2010 Wiley‐Liss, Inc.
On the mechanism of protein fold‐switching by a molecular sensor
Authors: Stratton Margaret M. , Loh Stewart N. 
Published: July 2010

AbstractAlternate frame folding (AFF) is a mechanism by which conformational change can be engineered into a protein. The protein structure switches from the wild‐type fold (N) to a circularly‐permuted fold (N′), or vice versa, in response to a signaling event such as ligand binding. Despite the fact that the two native states have similar structures, their interconversion involves folding and unfolding of large parts of the molecule. This rearrangement is reported by fluorescent groups whose relative proximities change as a result of the order–disorder transition. The nature of the conformational change is expected to be similar from protein to protein; thus, it may be possible to employ AFF as a general method to create optical biosensors. Toward that goal, we test basic aspects of the AFF mechanism using the AFF variant of calbindin D9k. A simple three‐state model for fold switching holds that N and N′ interconvert through the unfolded state. This model predicts that the fundamental properties of the switch—calcium binding affinity, signal response (i.e., fluorescence change upon binding), and switching rate—can be controlled by altering the relative stabilities of N and N′. We find that selectively destabilizing N or N′ changes the equilibrium properties of the switch (binding affinity and signal response) in accordance with the model. However, kinetic data indicate that the switching pathway does not require whole‐molecule unfolding. The rate is instead limited by unfolding of a portion of the protein, possibly in concert with folding of a corresponding region. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Decomposition of the Brier score for weighted forecast‐verification pairs
Authors: Young R. M. B. 
Published: July 2010

AbstractThe Brier score is widely used in meteorology for quantifying probability forecast quality. The score can be decomposed into terms representing different aspects of forecast quality, but this implicitly requires each forecast‐verification pair to be allocated equal weight. In this note an expression is derived for the decomposed Brier score that accounts for weighted forecast‐verification pairs. A comparison of the unweighted and weighted cases using seasonal forecasts from the ENSEMBLES project shows that when weights are assigned proportional to the area represented by each grid point (weighting by cosine of latitude), the weighted forecasts give improved Brier and reliability scores compared with the unweighted case. This result is consistent with what is expected, given that tropical predictability is generally better than extratropical predictability. Copyright © 2010 Royal Meteorological Society
Effect of VEGF and its receptor antagonist SU‐5416, an inhibitor of angiogenesis, on processing of the β‐amyloid precursor protein in primary neuronal cells derived from brain tissue of Tg2576 mice
Authors: Bürger Susanne , Yafai Yousef , Bigl Marina , Wiedemann Peter , Schliebs Reinhard 
Published: July 2010

AbstractA large number of Alzheimer patients demonstrate cerebrovascular pathology, which has been assumed to be related to β‐amyloid (Aβ) deposition. Aβ peptides have been described to inhibit angiogenesis both in vitro and in vivo, and deregulation of angiogenic factors may contribute to various neurological disorders including neurodegeneration. One of the key angiogenic factor is the vascular endothelial growth factor (VEGF). Increased levels of VEGF have been observed in brains of Alzheimer patients, while the functional significance of VEGF up‐regulation in the pathogenesis and progression of AD is still a matter of debate.To test whether VEGF may affect neuronal APP processing, primary neuronal cells derived from brain tissue of E16 embryos of Tg2576 mice were exposed with 1 ng/ml VEGF for 6, 12, and 24 h, followed by monitoring formation and secretion of soluble Aβ peptides, release of the human APP cleavage products, sAPPβswe and sAPPα, into the culture medium as well as the activities of α‐ and β‐secretases in neuronal cell extracts.Exposure of primary neuronal cells by VEGF for 24 h led to slightly reduced sAPPβ release, accompanied by decreased β‐secretase activity 12 h after VEGF exposure. Incubation of neurons by the VEGF receptor antagonist and angiogenesis inhibitor SU‐5416 for 24 h resulted in increased release of sAPPβswe, and strikingly enhanced secretion of Aβ peptides into the culture medium, which was accompanied by a significant increase in β‐secretase activity, as compared to control incubations. The SU‐5416‐induced effects on APP processing could not be suppressed by the additional presence of VEGF, suggesting that SU‐5416 affects pathways that are apparently independent of VEGF receptor signaling. The data obtained indicate that VEGF‐driven mechanisms may affect APP processing, suggesting a link of angiogenesis and pathogenesis of Alzheimer's disease.
Distribution of gold in igneous granitoid complexes in the central and southwestern areas of eastern Transbaikalia
Authors: Spiridonov A.M. , Kozlov V.D. , Zorina L.D. , Men’shikov V.I. , Bychinskii V.A. 
Published: July 2010

Abstract
The distribution of gold in rocks from some igneous complexes of the central and southwestern areas of eastern Transbaikalia (Daurian, Aga, and Argun structure-formational zones) was studied by quantitative extraction–atomic-absorption analysis and mass spectrometry with inductively coupled plasma (Element-2 mass spectrometer). High gold concentrations (on average, 0.0043 ppm) are typical of the most widespread hornblende-biotite granodiorites and granites of the main phases of batholith intrusions in the Upper Paleozoic Unda complex in the east of the study area and in the Triassic–Middle Jurassic Kyra complex in the west. The rocks of the Early–Middle Jurassic (Sokhondo) and Middle–Upper Jurassic (Shakhtama, Kharalga, and Kukul’bei) complexes have much lower Au concentrations (mainly 0.0014–0.0030 ppm), with the minimum ones established in the Shakhtama complex. During the magmatic differentiation of granitoid intrusions, the concentrations of gold in the late leucogranite differentiates decreased.
The Au concentrations in the studied complexes do not depend on the composition of the host terrigenous rocks of different ages, which evidences the endogenous nature of the revealed differences in Au concentrations in the regional granitoids. Abnormally high concentrations of gold in some studied samples are observed mainly in the regional hydrothermal mineralization occurrences.
The classification R-type cluster analysis showed that all variables of the studied igneous rocks are subdivided into three groups by the degree of correlation. Gold shows a distinct tendency to the correlation with siderophile oxy- and sulfurophile groups of metals. The Q-type analysis generally confirmed the correctness of the known formational classification of the regional granitoids.
Upper mantle roots of Siberian craton basement structures along the Rift DSS profile
Authors: Suvorov V.D. , Mishen’kina Z.R. , Melnik E.A. 
Published: July 2010

Abstract
We investigate the upper mantle velocity structure through processing first arrival data from peaceful nuclear explosions. The reported 2D model has been obtained by ray tracing for a spherical Earth, unlike the classical plane-approximation approach with subsequent spherical symmetry corrections, which is not always applicable to a laterally heterogeneous subsurface. The upper mantle velocity highs and lows imaged to 200–220 km depths show obvious correlation with major structures of the craton basement. Namely, low-velocity zones are observed beneath basins, the largest (to 8.0–8.1 km/s) under the Vendian–Early Cambrian Sayan–Yenisei syneclise. A discontinuous high-velocity layer (8.6–8.7 km/s) at depths between 150 and 240 km is underlain by a zone of lower velocity (8.50–8.55 km/s) down to the 410 km discontinuity, where the velocity at the top of the transition zone is 9.4–9.5 km/s.
Latest erosional incision in river valleys of southern East Siberia
Authors: Ufimtsev G.F. , Shchetnikov A.A. , Filinov I.A. 
Published: July 2010

Abstract
Examples of the geological and geomorphic framework of river valleys in the Tunka rift basin (Baikal rift system) and in the Irkutsk amphitheater (Siberian craton) have been used to show that horizontal and vertical motions of tectonic units in southern East Siberia are superposed with periodic movements. In the latter, the waves of slow uplift are attendant with erosional incision events, whereas during the subsidence cycles the incised valleys become filled with mainly alluvial sediments. The latest incision events in the area occurred in the past 70 kyr.
Apatite-bearing greenstone belts in Russia
Authors: Belyaev E.V. 
Published: July 2010

Abstract
The paper discusses the important and urgent problem of enlarging the mineral resources of Russia. Volcanosedimentary complexes of greenstone belts are suggested as a new alternative source of apatite ores. The distinguishing features and minerageny of greenstone complexes in the Karelian, Aldan, and Anabar Shields have been considered. Apatite occurrences have been described in brief. The paper suggests the main lines of study and geological exploration of apatite-bearing metavolcanic sedimentary complexes.
The effects of gabapentin in human experimental pain models
Authors: Enggaard Thomas P. , Mikkelsen Søren S. , Zwisler Stine T. , Klitgaard Niels A. , Sindrup Søren H. 
Published: July 2010

Abstract

Background
The antidepressant drugs imipramine and venlafaxine relieve clinical neuropathic pain and have been shown to increase pain thresholds in healthy volunteers during repetitive electrical sural nerve stimulation causing temporal pain summation, whereas pain during the cold pressor test is unaltered by these drugs. If this pattern of effect in experimental pain models reflects potential efficacy in clinical neuropathic pain, the pain summation model may potentially be used to identify new drugs for such pain conditions. Gabapentinoids are evidence-based treatments of clinical neuropathic pain and could contribute with additional knowledge of the usefulness of the pain summation model.

The aim of this study
To test the analgesic effect of the gabapentinoid gabapentin in a sural nerve stimulation pain model including temporal pain summation and the cold pressor test.

Method
18 healthy volunteers completed a randomized, double-blind, cross-over trial with medication of 600 mg gabapentin orally dosed 3 times over 24 h against placebo. Pain tests were performed before and 24 h after medication including pain detection and tolerance to single sural nerve stimulation and pain summation threshold to repetitive stimulation (3 Hz). Peak pain intensity and discomfort were rated during a cold pressor test.

Results
Compared to placebo, gabapentin had a highly significant effect on the threshold of pain summation to repetitive electrical sural nerve stimulation (P = 0.009). Gabapentin significantly increased the pain tolerance threshold to single electrical sural nerve stimulation (P = 0.04), whereas the pain detection threshold to single electrical sural nerve stimulation tended to be increased (P = 0.06). No significant differences were found on pain ratings during the cold pressor test.

Conclusion
Gabapentin had a selective hypoalgesic effect in a human experimental pain model of temporal pain summation and the results lend further support to the usefulness of the pain summation model to identify drugs for neuropathic pain.
Offset analgesia evoked by non-contact thermal stimulator
Authors: Frahm K.S. , Andersen O.K. , Arendt-Nielsen L. , Mørch C.D. 
Published: July 2010

Abstract

Objective
The objective of this study was to test if offset analgesia could be evoked using a noncontact thermal stimulator. Offset analgesia [J. Neurophysiol. 87:2205–2208, 2002] is defined as an unproportionally large decrease in pain intensity following a slight decrease in stimulation intensity. The importance of differences in thermal properties between human hairy and glabrous skin was investigated.

Methods
A 20W diode laser (970 nm) was used for the thermal stimulation. A fast (50 images/s) infrared camera measured the skin temperature and a temperature controlled feedback control loop adjusted the laser power. 8 subjects participated in this study. Stimulations were applied on the dorsum side and in the palm of the hand. Subjects were instructed to continuously rate the pain intensity. First the subject was stimulated using both a rising 35–45 °C staircase and a decreasing 45–35 °C staircase in both skin types; each staircase step was 1 °C and lasted for 15 s. Offset analgesia was tested by stimulating the hairy skin on the dorsum of the hand using two sequential temperature plateaus (48–48 °C, 48–49 °C, 49–48 °C and 49–49 °C). Each plateau was held for 5 s.

Results
For the staircase stimulations identical surface temperatures were perceived significantly higher in glabrous than in hairy skin (p < 0.001). The offset analgesia test showed that a decrease in temperature from 49 to 48 °C evoked a drop in the pain rating which was significantly lower than observed during a 48–48 °C stimulation (p < 0.001) indicating offset analgesia.

Conclusion
A non-contact thermal stimulator is able to evoke offset analgesia. Furthermore, it was noted that a high penetration laser causes higher pain ratings in glabrous skin than in hairy skin—a relationship which is opposite to low penetration lasers (CO2 laser) and contact heat stimulation.
Girl presenting with oesophageal spasm pain after fundoplication
Authors: Gawecka Ewa , Viken Oddbjørn 
Published: July 2010

Abstract

Introduction
A previously healthy 19-year-old woman, who had symptoms of gastric-oesophagela reflux disease for over one year, was transferred to our specialist hospital three weeks post fundoplication operation at a local hospital. She had several episodes with severe retrosternal pain lasting minutes to hours which was stabbing in character. She persistently experienced what was thought to be episodes of oesophageal spasm associated with food intake or movement. She required gradually escalating doses of opioids, both transdermal, intramuscular and intravenous. She was started on a regime of transdermal opioids in addition to iv opioids for the acute pain episodes. This was later supplemented with a PCA pump. Despite the increase in pain and in CRP, the patient was continued on an opioid reduction regime initiated by the surgeons six weeks post surgery. Two months post fundoplication she developed respiratory failure.

Discussion
The patient had a prolonged and painful postoperative period after an elective fundoplication. Her retrosternal pain had lasted over a year prior to surgery, but postoperatively a spasmic pain escalated substantially leaving her hospitalised. The symptoms where initially thought to be due to oesophageal spasm, but gastroscopy was normal and manometry showed normal contraction pressures in the oesophagus. It was discovered that she had right sided pleuritis that had developed into an empyema. She was intubated, sedated and initially treated with two chest drains before undergoing a right sided thoracotomy that removed the remaining pleural fluid areas and the postinfectious tissue. The exact mechanism of this complication is not known.

Conclusion
Oesophageal spasms after fundoplication is a known complication in about 1 in 1000 patients and is associated with intense spasmic retrosternal pain. However, empyema also needs to be considered where postoperative pain persists. It is an extremely rare and painful complication.
Epidemiology of persistent postoperative pain: Association of persistent pain and sensory abnormalities
Authors: Johansen A. , Romundstad L. , Nielsen C.S. , Schirmer H. , Eggen A.E. , Stubhaug A. 
Published: July 2010

Abstract

Background
The prevalence of persistent postoperative pain in the general population is poorly documented, but clinical studies indicate that the problem is common.

Aim
The aim of this study was (1) to assess the prevalence of persistent postoperative pain among individuals operated during the last 3 years in a general population and (2) to describe factors associated with chronic postoperative pain.

Materials and methods
As part of a cross-sectional health survey in the municipality of Tromsø, North Norway, all participants answered questions on surgery, persisting pain and sensory abnormalities in the area of surgery. N = 12,984. Age 30–87 years, median 59. 53.4% women.
Pain intensity was reported using a 0–10 Numeric Rating Scale (0–10 NRS). Logistic regression was used to reveal any associations between pain and self-reported hyposensitivity, hypersensitivity and allodynia.

Results
2316 individuals (17.8%) had surgery between 3 months and 3 years prior to the survey.
826 (40.4%)of the 2044 who answered a questionnaire on postsurgical pain, reported having some degree of pain in the area of surgery. Of these 826 individuals, 45.2% had pain, when at worst, of moderate or severe intensity, i.e. 0–10 NRS of 4 or higher.
The areas of surgery carrying the strongest association with persistent pain were (in descending order of frequency): (1) Shoulder/ upper arm [74.5% (108/145)], (2) back [73.9% (65/88)], (3) lungs [66.7% (8/12)], (4) knee/lower leg [63.7% (179/281)], (5) hand [58.8% (90/153)]. (6) hip/thigh [58.3% (74/127)] and (7) ankle/foot [58.7% (84/143)].
18.3% (413) had reduced sensitivity in the area near the surgical scar, while 10.6% (240) reported hypersensitivity and 5.6% (127) allodynia.
For those reporting hypoesthesia, the odds ratio (OR) for having pain was 2.71 (95% confidence interval 2.08–3.53), for those reporting hyperesthesia, OR was 4.82 (3.24–7.18) and for those with allodynia 5.83 (3.12–10.90).

Conclusions
3 months or more after surgery, nearly half of the respondents report having pain in the area of surgery. In this survey, there is a strong association between persistent pain and the presence of both hyposensitivity, hypersensitivity and allodynia.