bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complete Genome Sequence of
Yersinia pestis
Strains Antiqua and Nepal516: Evidence of Gene Reduction in an Emerging Pathogen
Authors: Chain Patrick S. G. , Hu Ping , Malfatti Stephanie A. , Radnedge Lyndsay , Larimer Frank , Vergez Lisa M. , Worsham Patricia , Chu May C. , Andersen Gary L. 
Published: June 2006

ABSTRACT

Yersinia pestis
, the causative agent of bubonic and pneumonic plagues, has undergone detailed study at the molecular level. To further investigate the genomic diversity among this group and to help characterize lineages of the plague organism that have no sequenced members, we present here the genomes of two isolates of the “classical” antiqua biovar, strains Antiqua and Nepal516. The genomes of Antiqua and Nepal516 are 4.7 Mb and 4.5 Mb and encode 4,138 and 3,956 open reading frames, respectively. Though both strains belong to one of the three classical biovars, they represent separate lineages defined by recent phylogenetic studies. We compare all five currently sequenced
Y. pestis
genomes and the corresponding features in
Yersinia pseudotuberculosis
. There are strain-specific rearrangements, insertions, deletions, single nucleotide polymorphisms, and a unique distribution of insertion sequences. We found 453 single nucleotide polymorphisms in protein-coding regions, which were used to assess the evolutionary relationships of these
Y. pestis
strains. Gene reduction analysis revealed that the gene deletion processes are under selective pressure, and many of the inactivations are probably related to the organism's interaction with its host environment. The results presented here clearly demonstrate the differences between the two biovar antiqua lineages and support the notion that grouping
Y. pestis
strains based strictly on the classical definition of biovars (predicated upon two biochemical assays) does not accurately reflect the phylogenetic relationships within this species. A comparison of four virulent
Y. pestis
strains with the human-avirulent strain 91001 provides further insight into the genetic basis of virulence to humans.
DNA Binding by the
Methanothermobacter thermautotrophicus
Cdc6 Protein Is Inhibited by the Minichromosome Maintenance Helicase
Authors: Kasiviswanathan Rajesh , Shin Jae-Ho , Kelman Zvi 
Published: June 2006

ABSTRACT

The Cdc6 proteins from the archaeon
Methanothermobacter thermautotrophicus
were previously shown to bind double-stranded DNA. It is shown here that the proteins also bind single-stranded DNA. Using minichromosome maintenance (MCM) helicase mutant proteins unable to bind DNA, it was found that the interaction of MCM with Cdc6 inhibits the DNA binding activity of Cdc6.
Cysteine-Scanning Analysis of the Chemoreceptor-Coupling Domain of the
Escherichia coli
Chemotaxis Signaling Kinase CheA
Authors: Zhao Jinshi , Parkinson John S. 
Published: June 2006

ABSTRACT

The C-terminal P5 domain of the histidine kinase CheA is essential for coupling CheA autophosphorylation activity to chemoreceptor control through a binding interaction with the CheW protein. To locate P5 determinants critical for CheW binding and chemoreceptor control, we surveyed cysteine replacements at 39 residues predicted to be at or near the P5 surface in
Escherichia coli
CheA. Two-thirds of the Cys replacement proteins exhibited in vitro defects in CheW binding, either before or after modification with a bulky fluorescein group. The binding-defective sites were widely distributed on the P5 surface and were often interspersed with sites that caused no functional defects, implying that relatively minor structural perturbations, often far from the actual binding site, can influence its conformation or accessibility. The most likely CheW docking area included loop 2 in P5 folding subdomain 1. All but four of the binding-defective P5-Cys proteins were defective in receptor-mediated activation, suggesting that CheW binding, as measured in vitro, is necessary for assembly of ternary signaling complexes and/or subsequent CheA activation. Other Cys sites specifically affected receptor-mediated activation or deactivation of CheA, demonstrating that CheW binding is not sufficient for assembly and/or operation of receptor signaling complexes. Because P5 is quite similar to CheW, whose structure is known to be dynamic, we suggest that conformational flexibility and dynamic motions govern the signaling activities of the P5 domain. In addition, relative movements of the CheA domains may be involved in CheW binding, in ternary complex assembly, and in subsequent stimulus-induced conformational changes in receptor signaling complexes.
Children’s acquisition and retention of safety skills: the Lifeskills program
Authors: Lamb R , Joshi M S , Carter W , Cowburn G , Matthews A 
Published: June 2006

Objectives:Assessment of safety skills performance and knowledge, to evaluate the education offered by the Lifeskills “Learning for Living” village, Bristol, UK which emphasizes interactive learning-by-doing.Design:Two quasi-experimental matched control group studies. Study 1: knowledge and performance three months post-intervention. Study 2: knowledge pre-intervention and post-intervention at three time points, to distinguish between immediate learning and longer term retention.Setting:The Lifeskills training village, Bristol, UK; primary schools in four education authorities in the area.Participants:Study 1: 145 children aged 10–11 years; 109 from the Lifeskills program, 36 control. Study 2: 671 children aged 10–11 years; 511 Lifeskills, 160 control.Outcome measures:Three areas (road, home, and fire safety). Five performance tests: observation of children’s safety skills. Five knowledge tests: pictorial quiz.Results:Study 1: Lifeskills/intervention children did better than control children on performance and knowledge tests. The knowledge-performance correlation wasr = 0.51. Study 2: intervention children did better than control children immediately after the intervention and three months later on all five knowledge tests. On three tests the intervention group showed retention of knowledge from immediately post-intervention to three months, but on two tests there was some loss. This loss was primarily among children from scholastically lower achieving schools. In all other respects the intervention was equally successful for boys and girls, and for children from higher and lower achieving schools.Conclusions:The Lifeskills package improved both knowledge and performance but had shortcomings. Complexity of material did not affect knowledge acquisition but did affect its retention.
The Structure of Dasatinib (BMS-354825) Bound to Activated ABL Kinase Domain Elucidates Its Inhibitory Activity against Imatinib-Resistant ABL Mutants
Authors: Tokarski John S. , Newitt John A. , Chang Chieh Ying J. , Cheng Janet D. , Wittekind Michael , Kiefer Susan E. , Kish Kevin , Lee Francis Y.F. , Borzillerri Robert , Lombardo Louis J. , Xie Dianlin , Zhang Yaqun , Klei Herbert E. 
Published: June 2006

Abstract
Chronic myeloid leukemia (CML) is caused by the constitutively activated tyrosine kinase breakpoint cluster (BCR)-ABL. Current frontline therapy for CML is imatinib, an inhibitor of BCR-ABL. Although imatinib has a high rate of clinical success in early phase CML, treatment resistance is problematic, particularly in later stages of the disease, and is frequently mediated by mutations in BCR-ABL. Dasatinib (BMS-354825) is a multitargeted tyrosine kinase inhibitor that targets oncogenic pathways and is a more potent inhibitor than imatinib against wild-type BCR-ABL. It has also shown preclinical activity against all but one of the imatinib-resistant BCR-ABL mutants tested to date. Analysis of the crystal structure of dasatinib-bound ABL kinase suggests that the increased binding affinity of dasatinib over imatinib is at least partially due to its ability to recognize multiple states of BCR-ABL. The structure also provides an explanation for the activity of dasatinib against imatinib-resistant BCR-ABL mutants. (Cancer Res 2006; 66(11): 5790-7)
Involvement of the Paxillin Pathway in JB6 Cl41 Cell Transformation
Authors: Tatsumi Yasuaki , Cho Yong-Yeon , He Zhiwei , Mizuno Hideya , Seok Choi Hong , Bode Ann M. , Dong Zigang 
Published: June 2006

Abstract
Paxillin is a substrate of the Src tyrosine onco-kinase and is involved in cell transformation, cell spreading, migration, and cancer development mediated through the mitogen-activated protein kinase signaling cascades. Here, we showed that paxillin plays a key role in skin cell transformation induced by epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA). To investigate the mechanism of paxillin's role in cell transformation, we established a paxillin knockdown stably transfected cell line by introducing small interfering RNA-paxillin (si-paxillin). The si-paxillin cells displayed a dramatic suppression of cell proliferation and anchorage-independent cell transformation induced by EGF or TPA compared with si-mock control cells. In si-paxillin cells, decreased activator protein-1 (AP-1)–dependent luciferase activity corresponded with suppressed AP-1 DNA binding activity. Importantly, knockdown of paxillin inhibited EGF- or TPA-induced c-Jun phosphorylation at Ser63 and Ser73. Furthermore, total c-Jun protein level was dramatically decreased in si-paxillin cells and was dependent on serum deprivation time. The down-regulation of c-Jun was restored in si-paxillin cells by treatment with the proteasome inhibitor lactacystin but not by the lysosome inhibitor leupeptin. These results clearly provided evidence that paxillin regulates c-Jun protein level and plays a key role in cell transformation most likely through the regulation of c-Jun stability. (Cancer Res 2006; 66(11): 5968-74)
Sulforaphane Causes Autophagy to Inhibit Release of Cytochrome c and Apoptosis in Human Prostate Cancer Cells
Authors: Herman-Antosiewicz Anna , Johnson Daniel E. , Singh Shivendra V. 
Published: June 2006

Abstract
The present study reports a novel response to sulforaphane, a highly promising anticancer constituent of several edible cruciferous vegetables, in PC-3 and LNCaP human prostate cancer cells involving induction of autophagy. Exposure of PC-3 and LNCaP cells to sulforaphane resulted in several specific features characteristic of autophagy, including appearance of membranous vacuoles in the cytoplasm as revealed by transmission electron microscopy and formation of acidic vesicular organelles as revealed by fluorescence microscopy following staining with the lysosomotropic agent acridine orange. The sulforaphane-induced autophagy was associated with up-regulation, processing, and recruitment to autophagosomes of microtubule-associated protein 1 light chain 3 (LC3), which is a mammalian homologue of the yeast autophagy regulating protein Apg8/Aut7p. Treatment of cells with a specific inhibitor of autophagy (3-methyladenine) attenuated localization of LC3 to autophagosomes but exacerbated cytosolic release of cytochrome c as well as apoptotic cell death as revealed by analysis of subdiploid fraction and cytoplasmic histone–associated DNA fragmentation. In conclusion, the present study indicates that induction of autophagy represents a defense mechanism against sulforaphane-induced apoptosis in human prostate cancer cells. To the best of our knowledge, the present study is the first published report to convincingly document induction of autophagy by an isothiocyanate class of dietary chemopreventive agent. (Cancer Res 2006; 66(11): 5828-35)
A Phase I Trial to Determine the Optimal Biological Dose of Celecoxib when Combined with Erlotinib in Advanced Non–Small Cell Lung Cancer
Authors: Reckamp Karen L. , Krysan Kostyantyn , Morrow Jason D. , Milne Ginger L. , Newman Robert A. , Tucker Christopher , Elashoff Robert M. , Dubinett Steven M. , Figlin Robert A. 
Published: June 2006

Abstract
Purpose: Overexpression of cyclooxygenase-2 (COX-2) activates extracellular signal-regulated kinase/mitogen-activated protein kinase signaling in an epidermal growth factor receptor (EGFR) tyrosine kinase inhibition (TKI)–resistant manner. Because preclinical data indicated that tumor COX-2 expression caused resistance to EGFR TKI, a phase I trial to establish the optimal biological dose (OBD), defined as the maximal decrease in urinary prostaglandin E-M (PGE-M), and toxicity profile of the combination of celecoxib and erlotinib in advanced non–small cell lung cancer was done.
Experimental Design: Twenty-two subjects with stage IIIB and/or IV non–small cell lung cancer received increasing doses of celecoxib from 200 to 800 mg twice daily (bid) and a fixed dose of erlotinib. Primary end points included evaluation of toxicity and determination of the OBD of celecoxib when combined with erlotinib. Secondary end points investigate exploratory biological markers and clinical response.
Results: Twenty-two subjects were enrolled, and 21 were evaluable for the determination of the OBD, toxicity, and response. Rash and skin-related effects were the most commonly reported toxicities and occurred in 86%. There were no dose-limiting toxicities and no cardiovascular toxicities related to study treatment. All subjects were evaluated on intent to treat. Seven patients showed partial responses (33%), and five patients developed stable disease (24%). Responses were seen in patients both with and without EGFR-activating mutations. A significant decline in urinary PGE-M was shown after 8 weeks of treatment, with an OBD of celecoxib of 600 mg bid.
Conclusions: This study defines the OBD of celecoxib when combined with a fixed dose of EGFR TKI. These results show objective responses with an acceptable toxicity profile. Future trials using COX-2 inhibition strategies should use the OBD of celecoxib at 600 mg bid.
NR2B Subunit Exerts a Critical Role in Postischemic Synaptic Plasticity
Authors: Picconi Barbara , Tortiglione Anna , Barone Ilaria , Centonze Diego , Gardoni Fabrizio , Gubellini Paolo , Bonsi Paola , Pisani Antonio , Bernardi Giorgio , Di Luca Monica , Calabresi Paolo 
Published: June 2006

Background and Purpose—We characterized the differential effect of the NR2B subunit antagonist ifenprodil in the induction of activity-dependent long-term potentiation (LTP) and of postischemic LTP as well as in the neuronal damage induced by focal ischemia.Methods—Intracellular recordings were obtained from rat corticostriatal slice preparations. High-frequency stimulation of corticostriatal fibers was used as a LTP-inducing protocol. In vitro ischemia was induced by oxygen and glucose deprivation. In vivo ischemia was induced by permanent middle cerebral artery occlusion. Intracellular recordings were also performed in the ischemic penumbra.Results—Antagonists selectively targetingN-methyl-d-aspartate receptors containing the NR2B subunit blocked postischemic LTP without affecting activity-dependent LTP. In a model of focal ischemia, blockade of NR2B subunit in vivo caused reduction of brain damage, amelioration of neurological outcome, and normalization of the synaptic levels of NR2B subunits. Moreover, the antagonism of NR2B subunit was able to rescue the activity-dependent LTP in the ischemic penumbra.Conclusions—We suggest that NR2B subunits contribute to the striatal damage caused by in vivo and in vitro ischemia and play a critical role in the induction of postischemic LTP as well as in the suppression of activity-dependent LTP in the ischemic penumbra.
Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), another myeloproliferative condition characterized by JAK2 V617F mutation
Authors: Szpurka Hadrian , Tiu Ramon , Murugesan Gurunathan , Aboudola Samer , Hsi Eric D. , Theil Karl S. , Sekeres Mikkael A. , Maciejewski Jaroslaw P. 
Published: June 2006

Abstract
JAK2 V617F mutation recently was identified as a pathogenic factor in typical chronic myeloproliferative diseases (CMPD). Some forms of myelodysplastic syndromes (MDS) show a significant overlap with CMPD (classified as MDS/MPD), but the diagnostic assignment may be challenging. We studied blood or bone marrow from 270 patients with MDS, MDS/MPD, and CMPD for the presence of JAK2 V617F mutation using polymerase chain reaction, sequencing, and melting curve analysis. The detection rate of JAK2 V617F mutants for polycythemia vera, chronic idiopathic myelofibrosis, and essential thrombocythemia (n = 103) was similar to the previously reported results. In typical forms of MDS (n = 89) JAK2 V617F mutation was very rare (n = 2). However, a higher prevalence of this mutation was found in patients with MDS/MPD-U (9 of 35). Within this group, most of the patients harboring JAK2 V617F mutation showed features consistent with the provisional MDS/MPD-U entity refractory anemia with ringed sideroblasts and thrombocytosis (RARS-T). Among 9 RARS-T patients, 6 showed the presence of JAK2 V617F mutation, and in 1 patient without mutation, aberrant, positive phospho-STAT5 staining was seen that is typically present in association with JAK2 V617F mutation. In summary, we found that RARS-T reveals a high frequency of JAK2 V617F mutation and likely constitutes another JAK2 mutation-associated form of CMPD.
Immunoglobulin free light chains and solitary plasmacytoma of bone
Authors: Dingli David , Kyle Robert A. , Rajkumar S. Vincent , Nowakowski Grzegorz S. , Larson Dirk R. , Bida John P. , Gertz Morie A. , Therneau Terry M. , Melton L. Joseph , Dispenzieri Angela , Katzmann Jerry A. 
Published: June 2006

AbstractAn abnormal serum immunoglobulin free light chain (FLC) ratio at diagnosis may identify risk of progression to myeloma in patients with solitary bone plasmacytoma (SBP). In the cohort of 116 patients, 43 have progressed to myeloma, with a median time to progression of 1.8 years. The FLC ratio was determined in all 116 patients on serum collected at time of diagnosis and was abnormal in 54 patients (47%). An abnormal FLC ratio was associated with a higher risk of progression to myeloma (P = .039). The risk of progression at 5 years was 44% in patients with an abnormal serum FLC ratio at diagnosis compared with 26% in those with a normal FLC ratio. One to 2 years following diagnosis, a persistent serum M protein level of 5 g/L (0.5 g/dL) or higher was an additional risk factor for progression. A risk stratification model was constructed using the 2 variables of FLC ratio and M protein level: patients with a normal FLC ratio at baseline and M protein level less than 5 g/L (0.5 g/dL) at 1 to 2 years following diagnosis (low risk, n = 31); with either risk factor abnormal (intermediate risk, n = 26); and with both an abnormal FLC ratio and M protein level of 5 g/L (0.5 g/dL) or higher (high risk, n = 18). The corresponding progression rates at 5 years were significantly different in the low, intermediate, and high groups: 13%, 26%, and 62%, respectively (P < .001).
Benchmarking pKa prediction
Authors: Davies Matthew N , Toseland Christopher P , Moss David S , Flower Darren R 
Published: June 2006

Abstract

Background
pKa values are a measure of the protonation of ionizable groups in proteins. Ionizable groups are involved in intra-protein, protein-solvent and protein-ligand interactions as well as solubility, protein folding and catalytic activity. The pKa shift of a group from its intrinsic value is determined by the perturbation of the residue by the environment and can be calculated from three-dimensional structural data.

Results
Here we use a large dataset of experimentally-determined pKas to analyse the performance of different prediction techniques. Our work provides a benchmark of available software implementations: MCCE, MEAD, PROPKA and UHBD. Combinatorial and regression analysis is also used in an attempt to find a consensus approach towards pKa prediction. The tendency of individual programs to over- or underpredict the pKa value is related to the underlying methodology of the individual programs.

Conclusion
Overall, PROPKA is more accurate than the other three programs. Key to developing accurate predictive software will be a complete sampling of conformations accessible to protein structures.
The evolution of activity breaks in the nest cycle of annual eusocial bees: a model of delayed exponential growth
Authors: Mitesser Oliver , Weissel Norbert , Strohm Erhard , Poethke Hans-Joachim 
Published: June 2006

AbstractBackgroundSocial insects show considerable variability not only in social organisation but also in the temporal pattern of nest cycles. In annual eusocial sweat bees, nest cycles typically consist of a sequence of distinct phases of activity (queen or workers collect food, construct, and provision brood cells) and inactivity (nest is closed). Since the flight season is limited to the time of the year with sufficiently high temperatures and resource availability, every break reduces the potential for foraging and, thus, the productivity of a colony. This apparent waste of time has not gained much attention.ResultsWe present a model that explains the evolution of activity breaks by assuming differential mortality during active and inactive phases and a limited rate of development of larvae, both reasonable assumptions. The model predicts a systematic temporal structure of breaks at certain times in the season which increase the fitness of a colony. The predicted pattern of these breaks is in excellent accordance with field data on the nest cycle of the halictidLasioglossum malachurum.ConclusionActivity breaks are a counter-intuitive outcome of varying mortality rates that maximise the reproductive output of primitively eusocial nests.
Giant lipoma arising from deep lobe of the parotid gland
Authors: Wu Che-Wei , Chi Hung-Pin , Chiang Feng-Yu , Hsu Ying-Che , Chan Leong-Perng , Kuo Wen-Rei 
Published: June 2006

Abstract

Background
Lipomas are common benign soft tissue neoplasms but they are found very rarely in the deep lobe of parotid gland. Surgical intervention in these tumors is challenging because of the proximity of the facial nerve, and thus knowledge of the anatomy and meticulous surgical technique are essential.

Case presentation
A 71-year-old female presented with a large asymptomatic mass, which had occupied the left facial area for over the past fifteen years, and she requested surgical excision for a cosmetically better facial appearance. The computed tomography (CT) scan showed a well-defined giant lipoma arising from the left deep parotid gland. The lipoma was successfully enucleated after full exposure and mobilization of the overlying facial nerve branches. The surgical specimen measured 9 × 6 cm in size, and histopathology revealed fibrolipoma. The patient experienced an uneventful recovery, with a satisfying facial contour and intact facial nerve function.

Conclusion
Giant lipomas involving the deep parotid lobe are extremely rare. The high-resolution CT scan provides an accurate and cost-effective preoperative investigative method. Surgical management of deep lobe lipoma should be performed by experienced surgeons due to the need for meticulous dissection of the facial nerve branches. Superficial parotidectomy before deep lobe lipoma removal may be unnecessary in selected cases because preservation of the superficial lobe may contribute to a better aesthetic and functional result.