bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure‐based design of robust glucose biosensors using a Thermotoga maritima periplasmic glucose‐binding protein
Authors: Tian Yaji , Cuneo Matthew J. , Changela Anita , Höcker Birte , Beese Lorena S. , Hellinga Homme W. 
Published: September 2007

AbstractWe report the design and engineering of a robust, reagentless fluorescent glucose biosensor based on the periplasmic glucose‐binding protein obtained from Thermotoga maritima (tmGBP). The gene for this protein was cloned from genomic DNA and overexpressed in Escherichia coli, the identity of its cognate sugar was confirmed, ligand binding was studied, and the structure of its glucose complex was solved to 1.7 Å resolution by X‐ray crystallography. TmGBP is specific for glucose and exhibits high thermostability (midpoint of thermal denaturation is 119 ± 1°C and 144 ± 2°C in the absence and presence of 1 mM glucose, respectively). A series of fluorescent conjugates was constructed by coupling single, environmentally sensitive fluorophores to unique cysteines introduced by site‐specific mutagenesis at positions predicted to be responsive to ligand‐induced conformational changes based on the structure. These conjugates were screened to identify engineered tmGBPs that function as reagentless fluorescent glucose biosensors. The Y13C•Cy5 conjugate is bright, gives a large response to glucose over concentration ranges appropriate for in vivo monitoring of blood glucose levels (1–30 mM), and can be immobilized in an orientation‐specific manner in microtiter plates to give a reversible response to glucose. The immobilized protein retains its response after long‐term storage at room temperature.
Models of S/π interactions in protein structures: Comparison of the H2S–benzene complex with PDB data
Authors: Ringer Ashley L. , Senenko Anastasia , Sherrill C. David 
Published: September 2007

AbstractS/π interactions are prevalent in biochemistry and play an important role in protein folding and stabilization. Geometries of cysteine/aromatic interactions found in crystal structures from the Brookhaven Protein Data Bank (PDB) are analyzed and compared with the equilibrium configurations predicted by high‐level quantum mechanical results for the H2S–benzene complex. A correlation is observed between the energetically favorable configurations on the quantum mechanical potential energy surface of the H2S–benzene model and the cysteine/aromatic configurations most frequently found in crystal structures of the PDB. In contrast to some previous PDB analyses, configurations with the sulfur over the aromatic ring are found to be the most important. Our results suggest that accurate quantum computations on models of noncovalent interactions may be helpful in understanding the structures of proteins and other complex systems.
Conformational changes induced by a single amino acid substitution in the trans‐membrane domain of Vpu: Implications for HIV‐1 susceptibility to channel blocking drugs
Authors: Park Sang Ho , Opella Stanley J. 
Published: September 2007

AbstractThe channel‐forming trans‐membrane domain of Vpu (Vpu TM) from HIV‐1 is known to enhance virion release from the infected cells and is a potential target for ion‐channel blockers. The substitution of alanine at position 18 by a histidine (A18H) has been shown to render HIV‐1 infections susceptible to rimantadine, a channel blocker of M2 protein from the influenza virus. In order to describe the influence of the mutation on the structure and rimantadine susceptibility of Vpu, we determined the structure of A18H Vpu TM, and compared it to those of wild‐type Vpu TM and M2 TM. Both isotropic and orientationally dependent NMR frequencies of the backbone amide resonance of His18 were perturbed by rimantadine, and those of Ile15 and Trp22 were also affected, suggesting that His18 is the key residue for rimantadine binding and that residues located on the same face of the TM helix are also involved. A18H Vpu TM has an ideal, straight α‐helix spanning residues 6–27 with an average tilt angle of 41° in C14 phospholipid bicelles, indicating that the tilt angle is increased by 11° compared to that of wild‐type Vpu TM. The longer helix formed by the A18H mutation has a larger tilt angle to compensate for the hydrophobic mismatch with the length of the phospholipids in the bilayer. These results demonstrate that the local change of the primary structure plays an important role in secondary and tertiary structures of Vpu TM in lipid bilayers and affects its ability to interact with channel blockers.
Soy‐derived isoflavones inhibit the growth of adult T‐cell leukemia cells in vitro and in vivo
Authors: Yamasaki Masao , Fujita Satoshi , Ishiyama Erina , Mukai Ayako , Madhyastha Harishkumar , Sakakibara Yoichi , Suiko Masahito , Hatakeyama Kinta , Nemoto Takayuki , Morishita Kazuhiro , Kataoka Hiroaki , Tsubouchi Hirohito , Nishiyama Kazuo 
Published: September 2007

Adult T‐cell leukemia occurs in human T‐lymphotropic virus type I‐infected individuals and is endemic to the south‐western area of Kyushu in Japan. In this communication, we examined the effect of soy isoflavones on the growth of adult T‐cell leukemia cells in vitro and in vivo. In the in vitro study, daidzein and genistein but not glycitein significantly inhibited the proliferation of ED‐40515 and Hut102 cells in a dose‐dependent manner. Among the isoflavones studied, genistein had the highest growth‐inhibitory effect; however, genistein did not exert an apparent growth‐inhibitory effect on Jurkat and Molt‐4 cells, which were non‐adult T‐cell leukemia cells. Genistein prevented the G1/S or G2/M transition at 3 and 10 or 30 µM, respectively. Genistein upregulated p21 protein expression together with p53 accumulation. In addition, treatment with 30 µM genistein strongly induced phosphorylation of checkpoint kinase (CHK) 2 and p53 at serines 15, 20 and 37. Caffeine, an inhibitor of ataxia‐telangiectasia mutated protein kinase, alleviated the genistein‐induced p53 and CHK2 phosphorylation, suggesting the involvement of DNA damage at 30 µM. However, marked phosphorylation of CHK2 and p53 could not be detected at 3 and 10 µM genistein. These data indicate that genistein has biphasic growth‐inhibitory properties. The in vivo studies demonstrated that soy‐derived isoflavones significantly inhibit ED‐40515 cell growth and infiltration into various organs in non‐obese diabetic severe combined‐immunodeficiency common γ‐chain knockout mice. Taken together, it is evident that soy isoflavones might serve as a promising compound for the treatment of adult T‐cell leukemia. (Cancer Sci 2007; 98: 1740–1746)
CCAAT/enhancer binding protein‐β promotes the survival of intravascular rat pancreatic tumor cells via antiapoptotic effects
Authors: Shimizu Yasuhito , Kishimoto Takashi , Ohtsuka Masayuki , Kimura Fumio , Shimizu Hiroaki , Yoshidome Hiroyuki , Miyazaki Masaru 
Published: September 2007

A transcriptional factor, CCAAT/enhancer binding protein‐β (C/EBP‐β), regulates a variety of cell functions in normal and neoplastic cells. Although the involvement of C/EBP‐β in metastasis has been demonstrated clinicopathologically in several types of human cancer, the mechanism by which it functions during the multistep process of metastasis remains largely unknown. We investigated the role of C/EBP‐β in the intravascular step of hematogenous metastasis in a rat pancreatic tumor cell line, AR42J‐B13, as this step profoundly affects metastatic efficiency. C/EBP‐β‐transfected AR42J‐B13 (βB13) cells acquired considerable resistance against serum toxicity, which was primarily mediated by apoptosis in vitro. Upregulated expression of Bcl‐2 and Bcl‐xL was seen in βB13 cells. Enhanced early survival of intraportally injected βB13 cells in the BALB/c nu/nu male mice liver, detected by the mRNA of a vector‐specific gene, was observed. Nick‐end labeling analysis of the tumor‐injected liver revealed significantly lower rates of apoptosis among intravascular βB13 tumor cells than among empty vector‐transfected AR42J‐B13 (mB13) cells. Finally, intrasplenically injected βB13 cells established a larger number of colonies in the liver than did the mB13 cells. These findings suggest that C/EBP‐β may enhance hematogenous metastasis and its antiapoptotic effects may promote the survival of intravascular tumor cells. (Cancer Sci 2007; 98: 1706–1713)
Nuclear translocation of ADAM‐10 contributes to the pathogenesis and progression of human prostate cancer
Authors: Arima Takashi , Enokida Hideki , Kubo Hiroyuki , Kagara Ichiro , Matsuda Ryouichirou , Toki Kazuki , Nishimura Hiroaki , Chiyomaru Takeshi , Tatarano Shuichi , Idesako Toshihiko , Nishiyama Kenryu , Nakagawa Masayuki 
Published: September 2007

A disintegrin and metalloproteases (ADAM) are cell membrane‐anchored proteins with potential implications for the metastasis of human cancer cells via cell adhesion and protease activities. In prostate cancer (PC), the ADAM‐10 protein showed a nuclear localization whereas in benign prostate hypertrophy (BPH) it was predominantly bound to the cell membrane. We hypothesized that the pathogenesis and progression of PC are attributable to the nuclear translocation of ADAM‐10. Immunoblotting revealed that after 5α‐dihydrotestosterone treatment, a 60‐kDa active form of ADAM‐10 was increased in the nuclear fraction but decreased in the cell membrane and cytoplasmic fractions of human androgen‐dependent PC cells. Immunocytochemistry revealed that after 5α‐dihydrotestosterone treatment, the ADAM‐10 protein was translocated from the cell membrane to the nucleus. Coimmunoprecipitation of androgen receptor and ADAM‐10 was detected in the nuclear fraction but not in the cell membrane and cytoplasmic fractions. Immunohistochemical study of 64 PC and 20 BPH samples showed that the intensity of ADAM‐10 staining was significantly higher in the nuclei of PC cells than in the nuclei of BPH cells (P < 0.0001). It was also significantly lower in the cell membrane of PC cells than in the cell membrane of BPH cells (P = 0.0017). Nuclear staining intensity was significantly correlated with the clinical T‐factor (P = 0.004), the Gleason score (P < 0.0001) and preoperative prostate‐specific antigen levels (P = 0.0061). ADAM‐10 small interfering RNA transfectants showed a significant decrease in cell growth compared to the controls. Our results suggest that in human PC, the nuclear translocation of ADAM‐10 coupled with the androgen receptor is involved in tumor growth and progression. (Cancer Sci 2007; 98: 1720–1726)
Testing long‐term patterns of basin sedimentation by detrital zircon geochronology, Centralian Superbasin, Australia
Authors: Maidment D. W. , Williams I. S. , Hand M. 
Published: September 2007

ABSTRACTDetrital zircon geochronology of Neoproterozoic to Devonian sedimentary rocks from the Georgina and Amadeus basins has been used to track changes in provenance that reflect the development and inversion of the former Australian Superbasin. Through much of the Neoproterozoic, sediments appear to have been predominantly derived from local sources in the Arunta and Musgrave inliers. Close similarities between the detrital age signatures of late Neoproterozoic sedimentary rocks in the two basins suggests that they were contiguous at this time. A dominant population of 1.2–1.0 Ga zircon in Early Cambrian sediments of the Amadeus Basin reflects the uplift of the Musgrave Inlier during the Petermann Orogeny between 560 and 520 Ma, which shed a large volume of detritus northwards into the Amadeus Basin. Early Cambrian sedimentary rocks in the Georgina Basin have a much smaller proportion of 1.2–1.0 Ga detritus, possibly due to the formation of sub‐basins along the northern margin of the Amadeus Basin which might have acted as a barrier to sediment transfer. An influx of 0.6–0.5 Ga zircon towards the end of the Cambrian coincides with the transgression of the Larapintine Sea across central Australia, possibly as a result of intracratonic rifting. Detrital zircon age spectra of sedimentary rocks deposited within this epicontinental sea are very similar to those of coeval sedimentary rocks from the Pacific Gondwana margin, implying that sediment was transported into central Australia from the eastern continental margin. The remarkably consistent ‘Pacific Gondwana’ signature of Cambro‐Ordovician sediments in central and eastern Australia reflects a distal source, possibly from east Antarctica or the East African Orogen. The peak of the marine incursion into central Australia in the early to mid Ordovician coincides with granulite‐facies metamorphism at mid‐crustal depths between the Amadeus and Georgina basins (the Larapinta Event). The presence of the epicontinental sea, the relative lack of a local basement zircon component in Cambro‐Ordovician sedimentary rocks and their maturity suggest that metamorphism was not accompanied by mountain building, consistent with an extensional or transtensional setting for this tectonism. Sediments deposited at ∼435–405 and ∼365 Ma during the Alice Springs Orogeny have detrital age signatures similar to those of Cambro‐Ordovician sedimentary rocks, reflecting uplift and reworking of the older succession into narrow foreland basins adjacent to the orogen.
Orthogonal to oblique rifting: effect of rift basin orientation in the evolution of the North basin, Malawi Rift, East Africa
Authors: Mortimer E. , Paton D. A. , Scholz C. A. , Strecker M. R. , Blisniuk P. 
Published: September 2007

ABSTRACTThe East African Rift system has long been considered the best modern example of the initial stages of continental rifting. The Malawi Rift is characteristic of the western branch of the East African Rift system, composed of half‐grabens of opposing asymmetry along its length. There are striking similarities between basins within the Malawi Rift, and others along the western branch. Each exhibits similar bathymetry, border‐fault length, rift zone width and fault segment length. The North Basin of the Malawi Rift differs from others in the rift only in its orientation: trending NW–SE as opposed to N–S. Although there is general agreement as to the geometry of the Malawi Rift; debate as to the amount of strike–slip vs. dip–slip deformation and the influence of underlying Pan‐African foliation remains. This study presents new data from a closely spaced shallow [2 s two‐way travel time (TWT)] seismic reflection data set integrated with basin‐scale deeper (6 s TWT) seismic reflection data that document the structural evolution of the border and intra‐basin faults. These data reveal that the different trend of the North Basin, most likely to have been influenced by the underlying Pan‐African foliation, has played an extremely important role in the structural style of basin evolution. The border‐fault and intra‐basin structures nucleated during extension that was initially orthogonal (ENE). During this time (>8.6 to ∼0.5–0.4 Ma) intra‐basin faults synthetic to the west‐dipping border‐fault nucleated, whereas strain was localised on the segmented border‐fault early on. A later rotation of extension orientation (to NW) led to these established faults orienting oblique to rifting. This generated an overall dextral strike–slip setting that led to the development of transfer faults adjacent to the border‐fault, and the generation of flower structures and folds over the greater displacement intra‐basin faults.
Late‐ to post‐orogenic exhumation of the Central Pyrenees revealed through combined thermochronological data and modelling
Authors: Gibson M. , Sinclair H. D. , Lynn G. J. , Stuart F. M. 
Published: September 2007

ABSTRACTApatite (U–Th)/He and fission track thermochronometry have been combined with 3D thermal modelling to constrain the late‐ to post‐orogenic exhumation history of the Central Pyrenees, Spain. Data from four massifs immediately north and south of the present drainage divide of the mountain belt reveal a diachroneity in the transition from syn‐ to post‐orogenic forcing of exhumation. Immediately south of the drainage divide, rapid exhumation of ∼1.5 mm year−1 decelerated after ∼30 Ma to ∼0.03 mm year−1. A similar transition occurred immediately north of the drainage divide at the same time. Further south, in the core of the Axial Zone antiformal stack of the Pyrenees, rapid (∼1 mm year−1), syn‐orogenic exhumation continued to ∼20 Ma, but slowed to ∼0.1–0.2 mm year−1 soon after that time. This order of magnitude decrease in exhumation rates across the orogen records the diachronous transition into a post‐orogenic state for the mountain belt. These data do not record rejuvenation of exhumation in Late Miocene or Pliocene times driven either by large‐scale base‐level change or an evolution to more erosive climatic conditions.
Prevalence of allergy and anaphylactic symptoms in 210 adult and pediatric patients with mastocytosis in Spain: a study of the Spanish network on mastocytosis (REMA)
Authors: González de Olano D. , De La Hoz Caballer B. , Núñez López R. , Sánchez Muñoz L. , Cuevas Agustín M. , Diéguez M. C. , Álvarez Twose I. , Castells M. C. , Escribano Mora L. 
Published: September 2007

SummaryBackground
Mast cells (MCs) play a key role in allergic diseases through the release of inflammatory mediators, which are responsible of allergic symptoms. Mastocytosis is characterized by an abnormal proliferation and accumulation of mast cells, in which mediators are released intermittingly or continuously. Despite these clinical similarities, few studies have addressed the presence of allergic symptoms in mastocytosis patients, including anaphylaxis.Objective
A prospective evaluation was carried out to study the prevalence of allergic diseases in patients with mastocytosis and their impact on the natural history of mastocytosis.Methods
A questionnaire was given to 210 patients with mastocytosis to evaluate the history of asthma, rhinitis, conjunctivitis, atopic dermatitis, urticaria and anaphylaxis. Patients underwent total IgE, Phadiatop® infant (aeroallergens and food allergens), specific IgE to latex and to Anisakis simplex determinations. Skin tests were done to 72 patients.Results
The prevalence of allergy, as defined by clinical symptoms associated to specific IgE, was 23.9%. Total IgE level was significantly higher in patients with allergy as compared with patients without allergy (median 58 vs. 16.5 kU/L, P<0.0001). Anaphylactic symptoms were present in 36 patients (22%), in nine the allergen was identified. Males had more allergy and anaphylactic symptoms than females (61.5% vs. 38.5% and 72% vs. 28%, respectively).Conclusions
Allergic diseases coexist in patients with mastocytosis with similar frequency as compared with the general population. Anaphylactic symptoms are more prevalent in males with mastocytosis and in patients with elevated IgE.Capsule summary
The prevalence of allergy in mastocytosis is similar to the general population. Anaphylactic symptoms are more prevalent in males and in patients with elevated IgE. The coexistence of atopy does not influence mastocytosis‐associated symptoms.
Allergic skin disease: investigation of both immediate‐ and delayed‐type hypersensitivity is essential
Authors: Usmani N. , Wilkinson S. M. 
Published: September 2007

SummaryBackground
In our clinic we routinely patch test patients referred from occupational health for the investigation of latex contact urticaria. We also undertake both patch and prick testing (where indicated) in patients referred with persistent dermatitis/eczema. If investigation of allergic skin disease is undertaken by a non‐dermatologist, it is unlikely that patch testing will be performed.Objective
To carry out a retrospective analysis of patients who had been prick tested to establish whether an incomplete diagnosis would have been reached if patch testing had been omitted.Methods
Details of patients who had attended for patch testing between July 2004 and December 2005 were analysed. Patients who had had prick tests and patch testing were identified. The outcomes of prick tests and patch testing were documented together with the clinical relevance.Results
Three hundred and thirty out of 1060 patients referred to the clinic were prick tested. 54.2% patients were referred from dermatologists. 26.6% were referred from occupational health, 68 patients had positive reactions on prick testing of whom 36 had positive patch tests (52.9%), which were of current relevance in 27 patients (39.7%). Nine out of 106 health workers referred to exclude latex contact urticaria had positive prick tests to latex. Fifty of these patients demonstrated delayed‐type hypersensitivity with nickel, cobalt, rubber and its additives being the most common allergens found. Of the 262 patients who had negative prick tests, 121 had positive patch tests (46.1%) of current relevance to patient history in 92 subjects (35.1%). While none of the six patients referred for investigation of reaction to local anaesthetics had a positive prick test, one was allergic to local anaesthetic on patch testing.Conclusion
Omission of patch testing from the investigation of allergic skin disease, even when contact urticaria may be the sole suspected diagnosis, would result in the frequent missed diagnosis of contact allergy. We recommend that patients with suspected allergic skin disease are investigated in an environment where investigation of both immediate‐ and delayed‐type hypersensitivity can be undertaken. In particular, patients with atopic eczema, suspected latex rubber allergy, hand dermatitis (particularly occupational) and drug reactions should be targeted to receive both investigations.
Quality of life in allergic rhinitis: relationship with clinical, immunological, and functional aspects
Authors: Ciprandi G. , Klersy C. , Cirillo I. , Marseglia G. L. 
Published: September 2007

SummaryBackground
The relationship among nasal obstruction, T‐helper type 2‐dependent inflammation, nasal airflow limitation, and reversibility to the nasal decongestion test has been evidenced in allergic rhinitis (AR). Moreover, quality of life (QoL) has been widely evaluated in AR and its evaluation is considered in numerous trials.Objective
The aim of this cross‐sectional study was to identify the QoL as measured by the Quality of Life Questionnaire in a population of patients with AR and to compare it with clinical, immunological, and functional parameters.Methods
One hundred and twenty‐three patients with persistent AR were prospectively and consecutively evaluated. Clinical evaluation, skin prick test, nasal scraping for cytology, rhinomanometry, decongestion test, and QoL questionnaire were performed in all subjects.Results
There was a significant relationship among QoL and functional and immunological parameters. Particularly, the multivariate analysis showed that having more than two sensitivities was a determinant of the QoL. The eosinophil count was significantly associated with QoL as well as the baseline nasal flow (mL/s) with the eye symptoms scale only.Conclusions
This study provides the first evidence that QoL in AR is strictly associated with allergic inflammation and eye symptoms significantly contribute to impairment of QoL. QoL, moreover, represents an important aspect to consider in managing patients with AR as it has a relationship with clinical, immunological, and functional parameters.