bluuebunny/crossref_metadata_2025 huggingface dataset:
JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate
Authors: Hübner Anette , Mulholland David J. , Standen Claire L. , Karasarides Maria , Cavanagh-Kyros Julie , Barrett Tamera , Chi Hongbo , Greiner Dale L. , Tournier Cathy , Sawyers Charles L. , Flavell Richard A. , Wu Hong , Davis Roger J.
Published: July 2012

The c-Jun NH
2
-terminal kinase (JNK) signal transduction pathway is implicated in cancer, but the role of JNK in tumorigenesis is poorly understood. Here, we demonstrate that the JNK signaling pathway reduces the development of invasive adenocarcinoma in the phosphatase and tensin homolog (
Pten
) conditional deletion model of prostate cancer. Mice with JNK deficiency in the prostate epithelium (
ΔJnk ΔPten
mice) develop androgen-independent metastatic prostate cancer more rapidly than control (
ΔPten
) mice. Similarly, prevention of JNK activation in the prostate epithelium (
ΔMkk4 ΔMkk7 ΔPten
mice) causes rapid development of invasive adenocarcinoma. We found that JNK signaling defects cause an androgen-independent expansion of the immature progenitor cell population in the primary tumor. The JNK-deficient progenitor cells display increased proliferation and tumorigenic potential compared with progenitor cells from control prostate tumors. These data demonstrate that the JNK and PTEN signaling pathways can cooperate to regulate the progression of prostate neoplasia to invasive adenocarcinoma.
Lysosomal calcium homeostasis defects, not proton pump defects, cause endo-lysosomal dysfunction in PSEN-deficient cells
Authors: Coen Katrijn , Flannagan Ronald S. , Baron Szilvia , Carraro-Lacroix Luciene R. , Wang Dong , Vermeire Wendy , Michiels Christine , Munck Sebastian , Baert Veerle , Sugita Shuzo , Wuytack Frank , Hiesinger Peter Robin , Grinstein Sergio , Annaert Wim
Published: July 2012

Presenilin (PSEN) deficiency is accompanied by accumulation of endosomes and autophagosomes, likely caused by impaired endo-lysosomal fusion. Recently, Lee et al. (2010. Cell. doi: http://dx.doi.org/10.1016/j.cell.2010.05.008) attributed this phenomenon to PSEN1 enabling the transport of mature V0a1 subunits of the vacuolar ATPase (V-ATPase) to lysosomes. In their view, PSEN1 mediates the N-glycosylation of V0a1 in the endoplasmic reticulum (ER); consequently, PSEN deficiency prevents V0a1 glycosylation, compromising the delivery of unglycosylated V0a1 to lysosomes, ultimately impairing V-ATPase function and lysosomal acidification. We show here that N-glycosylation is not a prerequisite for proper targeting and function of this V-ATPase subunit both in vitro and in vivo in Drosophila melanogaster. We conclude that endo-lysosomal dysfunction in PSEN−/− cells is not a consequence of failed N-glycosylation of V0a1, or compromised lysosomal acidification. Instead, lysosomal calcium storage/release is significantly altered in PSEN−/− cells and neurons, thus providing an alternative hypothesis that accounts for the impaired lysosomal fusion capacity and accumulation of endomembranes that accompanies PSEN deficiency.
Z-line formins promote contractile lattice growth and maintenance in striated muscles of C. elegans
Authors: Mi-Mi Lei , Votra SarahBeth , Kemphues Kenneth , Bretscher Anthony , Pruyne David
Published: July 2012

Muscle contraction depends on interactions between actin and myosin filaments organized into sarcomeres, but the mechanism by which actin filaments incorporate into sarcomeres remains unclear. We have found that, during larval development in Caenorhabditis elegans, two members of the actin-assembling formin family, CYK-1 and FHOD-1, are present in striated body wall muscles near or on sarcomere Z lines, where barbed ends of actin filaments are anchored. Depletion of either formin during this period stunted growth of the striated contractile lattice, whereas their simultaneous reduction profoundly diminished lattice size and number of striations per muscle cell. CYK-1 persisted at Z lines in adulthood, and its near complete depletion from adults triggered phenotypes ranging from partial loss of Z line–associated filamentous actin to collapse of the contractile lattice. These results are, to our knowledge, the first genetic evidence implicating sarcomere-associated formins in the in vivo organization of the muscle cytoskeleton.
c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling
Authors: Fontana Xavier , Hristova Mariya , Da Costa Clive , Patodia Smriti , Thei Laura , Makwana Milan , Spencer-Dene Bradley , Latouche Morwena , Mirsky Rhona , Jessen Kristjan R. , Klein Rüdiger , Raivich Gennadij , Behrens Axel
Published: July 2012

The AP-1 transcription factor c-Jun is a master regulator of the axonal response in neurons. c-Jun also functions as a negative regulator of myelination in Schwann cells (SCs) and is strongly reactivated in SCs upon axonal injury. We demonstrate here that, after injury, the absence of c-Jun specifically in SCs caused impaired axonal regeneration and severely increased neuronal cell death. c-Jun deficiency resulted in decreased expression of several neurotrophic factors, and GDNF and Artemin, both of which encode ligands for the Ret receptor tyrosine kinase, were identified as novel direct c-Jun target genes. Genetic inactivation of Ret specifically in neurons resulted in regeneration defects without affecting motoneuron survival and, conversely, administration of recombinant GDNF and Artemin protein substantially ameliorated impaired regeneration caused by c-Jun deficiency. These results reveal an unexpected function for c-Jun in SCs in response to axonal injury, and identify paracrine Ret signaling as an important mediator of c-Jun function in SCs during regeneration.
Dominance of the CD4+ T helper cell response during acute resolving hepatitis A virus infection
Authors: Zhou Yan , Callendret Benoît , Xu Dan , Brasky Kathleen M. , Feng Zongdi , Hensley Lucinda L. , Guedj Jeremie , Perelson Alan S. , Lemon Stanley M. , Lanford Robert E. , Walker Christopher M.
Published: July 2012

Hepatitis A virus (HAV) infection typically resolves within 4–7 wk but symptomatic relapse occurs in up to 20% of cases. Immune mechanisms that terminate acute HAV infection, and prevent a relapse of virus replication and liver disease, are unknown. Here, patterns of T cell immunity, virus replication, and hepatocellular injury were studied in two HAV-infected chimpanzees. HAV-specific CD8+ T cells were either not detected in the blood or failed to display effector function until after viremia and hepatitis began to subside. The function of CD8+ T cells improved slowly as the cells acquired a memory phenotype but was largely restricted to production of IFN-γ. In contrast, CD4+ T cells produced multiple cytokines when viremia first declined. Moreover, only CD4+ T cells responded during a transient resurgence of fecal HAV shedding. This helper response then contracted slowly over several months as HAV genomes were eliminated from liver. The findings indicate a dominant role for CD4+ T cells in the termination of HAV infection and, possibly, surveillance of an intrahepatic reservoir of HAV genomes that decays slowly. Rapid contraction or failure to sustain such a CD4+ T cell response after resolution of symptoms could increase the risk of relapsing hepatitis A.
Resource Burden Associated with Contact Precautions for Methicillin-ResistantStaphylococcus aureusand Vancomycin-Resistant Enterococcus: The Patient Access Managers' Perspective
Authors: Shenoy Erica S. , Walensky Rochelle P. , Lee Hang , Orcutt Benjamin , Hooper David C.
Published: July 2012

We surveyed patient access managers on the impact of contact precautions (CP) for methicillin-resistantStaphylococcus aureus(MRSA) and vancomycin-resistant enterococcus (VRE) on time to bed assignment, and we investigated the factors influencing infection control policies allowing for discontinuation of CP. The majority of respondents reported an increase in time to bed assignment for patients with a history of MRSA and/or VRE infection or colonization.
Chinks in the Armor: Activation Patterns of Hollow-Bore Safety-Engineered Sharp Devices
Authors: Black Lisa , Parker Ginger , Jagger Janine
Published: July 2012

A retrospective review of secondary injury data was used to evaluate the characteristics of percutaneous injuries from safety-engineered sharp devices. Injury rates and safety device activation rates differed by healthcare provider type. Approximately 22.8%–32% of injuries could have been prevented had an available safety feature been activated after use.
Nasal Swab Screening for Methicillin-Resistant Staphylococcus aureus—How Well Does It Perform? A Cross-Sectional Study
Authors: Matheson Ann , Christie Peter , Stari Traiani , Kavanagh Kim , Gould Ian M. , Masterton Robert , Reilly Jacqui S.
Published: July 2012

Objective.

To determine the proportion of methicillin-resistant Staphylococcus aureus (MRSA) detections identified by nasal swabbing using agar culture in comparison with multiple body site testing using agar and nutrient broth culture.

Design.

Cross-sectional study.

Patients.

Adult patients admitted to 36 general specialty wards of 2 large hospitals in Scotland.

Methods.

Patients were screened for MRSA via multiple body site swabs (nasal, throat, axillary, perineal, and wound/invasive device sites) cultured individually on chromogenic agar and pooled in nutrient broth. Combined results from all sites and cultures provided a gold-standard estimate of true MRSA prevalence.

Results.

This study found that nasal screening performed better than throat, axillary, or perineal screening but at best identified only 66% of true MRSA carriers against the gold standard at an overall prevalence of 2.9%. Axillary screening performed least well. Combining nasal and perineal swabs gave the best 2-site combination (82%). When combined with realistic screening compliance rates of 80%–90%, nasal swabbing alone probably detects just over half of true colonization in practice. Swabbing of clinically relevant sites (wounds, indwelling devices, etc) is important for a small but high-prevalence group.

Conclusions.

Nasal swabbing is the standard method in many locations for MRSA screening. Its diagnostic efficiency in practice appears to be limited, however, and the resource implications of multiple body site screening have to be balanced against a potential clinical benefit whose magnitude and nature remains unclear.
“What the Eyes Don't See, the Heart Doesn't Grieve Over”: Epidemiology and Risk Factors for Bloodstream Infections following Cardiac Catheterization
Authors: Dicks Kristen V. , Staheli Russell , Anderson Deverick J. , Miller Becky A. , Jones W. Schuyler , Harrison J. Kevin , Sexton Daniel J. , Moehring Rebekah W. , Chen Luke F.
Published: July 2012

No standard definition exists for surveillance and characterization of the epidemiology of bloodstream infections (BSIs) after cardiac catheterization (CC) procedures. We proposed a novel case definition and determined the epidemiology and risk factors of BSIs after CC procedure using this new definition.
Effectiveness of Multifaceted Hand Hygiene Interventions in Long-Term Care Facilities in Hong Kong: A Cluster-Randomized Controlled Trial
Authors: Ho Mei-lin , Seto Wing-hong , Wong Lai-chin , Wong Tin-yau
Published: July 2012

Objective.

To determine the effectiveness of World Health Organization (WHO) multimodal strategy in promoting hand hygiene (HH) among healthcare workers (HCWs) in long-term care facilities (LTCFs).

Design.

Cluster-randomized controlled trial.

Setting.

Eighteen homes for the elderly in Hong Kong were randomly allocated to 2 intervention arms and a control arm. Direct observation of HH practice was conducted by trained nurses. Either handrubbing with alcohol-based handrub (ABHR) or handwashing with liquid soap and water was counted as a compliant action. Disease notification data during 2007–2010 were used to calculate incidence rate ratio (IRR).

Participants.

Managers and HCWs of the participating homes.

Interventions.

The WHO multimodal strategy was employed. All intervention homes were supplied with ABHR (WHO formulation I), ABHR racks, pull reels, HH posters and reminders, a health talk, video clips, training materials, and performance feedback. The only difference was that intervention arms 1 and 2 were provided with slightly powdered and powderless gloves, respectively.

Results.

A total of 11,669 HH opportunities were observed. HH compliance increased from 27.0% to 60.6% and from 22.2% to 48.6% in intervention arms 1 and 2, respectively. Both intervention arms showed increased HH compliance after intervention compared to controls, at 21.6% compliance (both P < .001). Provision of slightly powdered versus powderless gloves did not have any significant impact on ABHR usage. Respiratory outbreaks (IRR, 0.12; 95% confidence interval [CI], 0.01–0.93; P = .04) and methicillin-resistant Staphylococcus aureus infections requiring hospital admission (IRR, 0.61; 95% CI, 0.38–0.97; P = .04) were reduced after intervention.

Conclusions.

A promotion program applying the WHO multimodal strategy was effective in improving HH among HCWs in LTCFs.
AutoBind: automatic extraction of protein–ligand-binding affinity data from biological literature
Authors: Chang Darby Tien-Hao , Ke Chao-Hsuan , Lin Jung-Hsin , Chiang Jung-Hsien
Published: July 2012

Motivation: Determination of the binding affinity of a protein–ligand complex is important to quantitatively specify whether a particular small molecule will bind to the target protein. Besides, collection of comprehensive datasets for protein–ligand complexes and their corresponding binding affinities is crucial in developing accurate scoring functions for the prediction of the binding affinities of previously unknown protein–ligand complexes. In the past decades, several databases of protein–ligand-binding affinities have been created via visual extraction from literature. However, such approaches are time-consuming and most of these databases are updated only a few times per year. Hence, there is an immediate demand for an automatic extraction method with high precision for binding affinity collection.

Result: We have created a new database of protein–ligand-binding affinity data, AutoBind, based on automatic information retrieval. We first compiled a collection of 1586 articles where the binding affinities have been marked manually. Based on this annotated collection, we designed four sentence patterns that are used to scan full-text articles as well as a scoring function to rank the sentences that match our patterns. The proposed sentence patterns can effectively identify the binding affinities in full-text articles. Our assessment shows that AutoBind achieved 84.22% precision and 79.07% recall on the testing corpus. Currently, 13 616 protein–ligand complexes and the corresponding binding affinities have been deposited in AutoBind from 17 221 articles.

Availability: AutoBind is automatically updated on a monthly basis, and it is freely available at http://autobind.csie.ncku.edu.tw/ and http://autobind.mc.ntu.edu.tw/. All of the deposited binding affinities have been refined and approved manually before being released.

Contact:  jchiang@mail.ncku.edu.tw

Supplementary Information:  Supplementary data are available at Bioinformatics online.
A Novel Effector Protein, MJ-NULG1a, Targeted to Giant Cell Nuclei Plays a Role inMeloidogyne javanicaParasitism
Authors: Lin Borong , Zhuo Kan , Wu Ping , Cui Ruqiang , Zhang Lian-Hui , Liao Jinling
Published: July 2012

Secretory effector proteins expressed within the esophageal glands of root-knot nematodes (Meloidogyne spp.) are thought to play key roles in nematode invasion of host roots and in formation of feeding sites necessary for nematodes to complete their life cycle. In this study, a novel effector protein gene designated as Mj-nulg1a, which is expressed specifically within the dorsal gland of Meloidogyne javanica, was isolated through suppression subtractive hybridization. Southern blotting and BLAST search analyses showed that Mj-nulg1a is unique for Meloidogyne spp. A real-time reverse-transcriptase polymerase chain reaction assay showed that expression of Mj-nulg1a was upregulated in parasitic second-stage juveniles and declined in later parasitic stages. MJ-NULG1a contains two putative nuclear localization signals and, consistently, in planta immunolocalization analysis showed that MJ-NULG1a was localized in the nuclei of giant cells during nematode parasitism. In planta RNA interference targeting Mj-nulg1a suppressed the expression of Mj-nulg1a in nematodes and attenuated parasitism ability of M. javanica. In contrast, transgenic Arabidopsis expressing Mj-nulg1a became more susceptible to M. javanica infection than wild-type control plants. These results depict a novel nematode effector that is targeted to giant cell nuclei and plays a critical role in M. javanica parasitism.
First Report of a Group 16SrI-B Phytoplasma Associated with Gardenia jasminoides in China
Authors: Sun X. C. , Zhao W. J.
Published: July 2012

Gardenia jasminoides J. Ellis, (also known as common gardenia, cape jasmine, or cape jessamine) is a fragrant flowering evergreen tropical plant, a favorite in gardens worldwide. G. jasminoides were found with small, seriously yellowed leaves, stunted growth, and witches'-broom in a green belt on the Southwest University campus in October 2011. The incidence was lower than 2%. In another green belt, G. jasminoides with only slightly yellowing leaves were found. The incidence was about 5%. Five months later, most seriously yellowed leaves withered. However, no withered leaf was observed among the slightly yellowing leaves. Leaf samples from each symptomatic plant, together with asymptomatic plants from the same belt, were collected for total DNA extraction using a modified cetyltrimethylammoniumbromide method (1). The resulting DNA extracts were analyzed by a nested PCR assay using the phytoplasma 16S rRNA gene primer pairs R16mF2/R16mR1 followed by R16F2n/R16R2 (2). DNA fragments of 1.2 kb that corresponded to 16S rDNA were amplified only from the DNA samples of the five plants with the symptoms mentioned above. The purified nested PCR products were cloned in pGEM-T Easy Vector (Promega) and then sequenced. The resulting 16S rDNA sequences were found to be identical (GenBank Accession No. JQ675713). The consensus sequence was analyzed by the iPhyClassifier online tool ( http://plantpathology.ba.ars.usda.gov/cgi-bin/resource/iphyclassifier.cgi ) and found to share 99.4% similarity with the 16S rDNA sequence of the ‘Candidatus Phytoplasma asteris’ reference strain (GenBank Accession No. M30790) that belongs to the 16SrI-B subgroup (3). The virtual RFLP pattern of the G. jasminoides phytoplasma 16S rDNA gene sequence showed maximum similarity to the reference pattern of NC005303 (similarity coefficient of 1.0). The phylogenetic tree based on the 16S rDNA sequences of phytoplasmas belonging to group 16SrI and other distinct phytoplasma groups also showed that our sequences clustered with members of subgroup 16SrI-B. Subsequently, the presence of the phytoplasmas in symptomatic plants was also confirmed by transmission electron microscopy. Taken together, the phytoplasma was classified as a member of subgroup 16SrI-B. To our knowledge, this is the first report of a subgroup 16SrI-B phytoplasma associated with diseased G. jasminoides in China. G. jasminoides yellowing is often considered to result from nutrient deficiency (especially iron compounds). However, our findings showed that a phytoplasma can cause G. jasminoides yellowing, which should be considered in the control of leaves yellowing.

References: (1) E. Angelini et al. Vitis 40:79, 2001. (2) D. E. Gundersen and I.-M. Lee. Phytopathol. Mediterr. 35:144, 1996. (3) Y. Zhao, et al. Int. J. Syst. Evol. Microbiol. 59:2582, 2009.
Apparent lattice expansion in ordered nanoporous silica during capillary condensation of fluids
Authors: Prass Johannes , Müter Dirk , Erko Maxim , Paris Oskar
Published: July 2012

Ordered nanoporous silica materials containing cylindrical pores on a two-dimensional hexagonal lattice are known to deform upon adsorption and condensation of fluids. These sorption strains can be measured byin situsmall-angle X-ray scattering by analysing the shift of the Bragg peaks from the ordered pore lattice. Besides the real lattice deformation due to the interaction of the solid pore walls with the fluid, a hitherto unexplained apparent lattice expansion is found experimentally in SBA-15 nanoporous silica in a narrow pressure region for three different fluids (pentane, perfluoropentane and water). It is shown that the Bragg peak shift in this region results partly from a subtle contrast effect. The pore form factor changes during capillary condensation owing to the sequential filling of pores according to their diameter. Together with the structure factor from a lattice of finite size, this leads to an effective shift of the Bragg peaks, resulting in the measured apparent lattice strain. Two simple models are presented, which aim to quantitatively describe these apparent strains. The first model employs cylindrical pores with a size distribution on a two-dimensional hexagonal lattice. Filling of pores is achieved by changing the contrast between the pores of a certain size with respect to the surrounding matrix, and the peak shift is calculated from the power spectrum of this lattice. The second model derives analytical expressions for the peak shifts as a function of pore filling fraction by using a Taylor expansion of the pore form factor and a uniform pore size distribution. Both models are able to reproduce the experimental results satisfactorily, providing the possibility to separate these apparent lattice strains from real pore wall deformation in nanoporous materials.
(±)-2,2-Dimethyl-5-oxotetrahydrofuran-3-carboxylic acid (terebic acid): a racemic layered structure
Authors: Santos L. M. , Legendre A. O. , Villis P. C. M. , Viegas Jr C. , Doriguetto A. C.
Published: July 2012

A racemic crystalline form of terebic acid, C7H10O4, which is an important industrial chemical compound, is reported for the first time. The crystal structure is stabilized by O—H...O and C—H...O hydrogen bonds which form racemic double layers parallel to (001).
(E)-4-Amino-N′-(2-hydroxy-5-methoxybenzylidene)benzohydrazide monohydrate
Authors: Kargar Hadi , Kia Reza , Tahir Muhammad Nawaz
Published: July 2012

In the title compound, C15H15N3O3·H2O, the hydazide Schiff base molecule shows anEconformation around the C=N bond. An intramolecular O—H...N hydrogen bond makes anS(6) ring motif. The dihedral angle between the substituted phenyl rings is 23.40 (11)°. The water molecule mediates linking of neighbouring molecules through O—H...(O,O) hydrogen bonds into infinite chains along theaaxis, which are further connected together through N—H...O hydrogen bonds, forming a two-dimensional network parallel to (001). C—H...O interactions aso occur.
(1-Methyl-1H-imidazol-3-ium-2-yl)(phenyl)phosphinate monohydrate
Authors: Sun Yong-Ming , Yang Meng , Zhao Chang-Qiu
Published: July 2012

The title compound, C10H11N2O2P·H2O, contains a tetracoordinate pentavalent P atom. The phosphinate group plays a predominant role in the cohesion of the crystal structure by forming chains along thebaxisviaintermolecular C—H...O hydrogen bonds. These chains are connected by O—H...O and N—H...O hydrogen bonding involving the lattice water.
(Z)-3-Benzyl-1,5-benzothiazepin-4(5H)-one
Authors: Sabari V. , Selvakumar R. , Bakthadoss M. , Aravindhan S.
Published: July 2012

In the crystal structure of the title compound, C16H13NOS, molecules are linked into cyclic centrosymmetricR22(8) dimersviapairs of N—H...O hydrogen bonds. The seven-membered ring adopts a boat conformation.
Bis[μ-bis(diphenylphosphanyl)methane-κ2P:P′]bis[(isoquinoline-κN)silver(I)] bis(trifluoromethanesulfonate)–isoquinoline (1/1)
Authors: Huang Xu , Li Jing , Qiu Qi-Ming , Liu Min , Jin Qiong-Hua
Published: July 2012

The title complex, [Ag2(C25H22P2)2(C9H7N)2](CF3SO3)2·C9H7N, was prepared by the reaction of silver(I) trifluoromethanesulfonate with isoquinoline and bis(diphenylphosphanyl)methane (dppm). The dinuclear molecule is located about a center of inversion and the AgIatom is coordinated by two dppm P atoms and one isoquinoline N atom, forming an eight-membered metalla ring. In addition, in the asymmetric unit, there is a half-molecule of isoquinoline located about a center of inversion. Since this molecule does not possess this symmetry, for one position in the ring there is superposition of both a C atom of a C—H group and the isoquinoline N atom. In the structure, the Ag—P distances [2.4296 (9) and 2.4368 (9) Å] agree with the corresponding distances in related structures, while the Ag—N bond length [2.489 (3) Å] is slightly longer than that in related structures. On the other hand, the P—Ag—P angle [156.44 (3)°] is much larger than the corresponding angles in related structures. The trifluoromethanesulfonate anions do not coordinate to AgIatoms. As is usually found for these anions, the –CF3group is disordered over two orientations [occupancies = 0.57 (12) and 0.43 (12)].
1-(4-Bromophenylsulfonyl)-2-methylnaphtho[2,1-b]furan
Authors: Choi Hong Dae , Seo Pil Ja , Lee Uk
Published: July 2012

In the title compound, C19H13BrO3S, the 4-bromophenyl ring makes a dihedral angle of 64.11 (2)° with the mean plane [r.m.s. deviation = 0.01 (2) Å] of the naphthofuran ring. In the crystal, molecules are linked by weak C—H...O and C—H...π interactions. The crystal structure also exhibits slipped π–π interactions between the central naphthofuran benzene rings of neighbouring molecules [centroid–centroid distance = 3.559 (2), slippage = 1.036 (2) Å], and between the central naphthofuran benzene ring and the furan ring of neighbouring molecules [centroid–centroid distance = 3.655 (2), slippage = 1.136 (2) Å].
Ethylent-15α-[(2-nitrobenzyloxy)methyl]-16-oxobeyeran-20-oate
Authors: Wu Ya , Wang Xia , Gong Jian-hong , Tao Jing-chao
Published: July 2012

In the title compound, C30H41NO6, the three six-membered rings adopt chair conformations and the stereochemistry of theA/BandB/Cring junctions aretrans. The five-membered ringDadopts an envelope conformation, with the methylene C atom as the flap. The title compound was synthesizedviaesterification, Tollens reaction, 1,5-hydride shift from the natural tetracyclic diterpenoid isosteviol
1,4-Diazabicyclo[2.2.2]octane–trans,trans-hexa-2,4-dienedioic acid (1/1)
Authors: Moon Suk-Hee , Park Ki-Min
Published: July 2012

The title 1:1 co-crystal, C6H12N2·C6H6O4, the dicarboxylic acid molecule is close to planar [r.m.s. deviation from the mean plane = 0.07 (1) Å]. In the crystal, the two molecules are arranged alternately and are linked by O—H...N hydrogen bonds, leading to the formation of a chain along the [20-1] direction. The chains are assembled into a two-dimensional framework parallel to the (102) plane through weak C—H...O hydrogen bonds between the two types of molecules.
N-(2,4-Difluorophenyl)-5-methyl-1,2-oxazole-4-carboxamide hemihydrate
Authors: Yu Jian-Guang , Zhu Hai-Xi , Qiu Jiang-Kai , Wang De-Cai , Xu Hong
Published: July 2012

In the title compound, C11H8F2N2O2·0.5H2O, the dihedral angle between the benzene and isoxazole rings is 8.08 (3)°. In the crystal, the components are linked by O—H...N and N—H...O hydrogen bonds, in which the water molecule acts as both a donor and an acceptor, into a tape with anR44(16) graph-set motif along theaaxis. The water molecule is located on a twofold rotation axis. The methyl H atoms were treated as disordered groups over two sites with a refined site-occupancy ratio of 0.48 (6):0.52 (6).
3-Carboxyphenylboronic acid–theophylline (1/1)
Authors: Dyulgerov Ventsi , Nikolova Rositsa P. , Dimova Louiza T. , Shivachev Boris L.
Published: July 2012

The title two-component molecular crystal [systematic name: 3-(dihydroxyboranyl)benzoic acid–1,3-dimethyl-7H-purine-2,6-dione (1/1)], C7H7BO4·C7H8N4O2, comprises theophylline and 3-carboxyphenylboronic acid molecules in a 1:1 molar ratio. In the crystal, molecules are self-assembled by O—H...O and N—H...N hydrogen bonds, generating layers parallel to (-209). The layers are stacked through π–π [centroid–centroid distance = 3.546 (2) Å] and C—H...π interactions.
Methyl 2-(4-methoxy-3-nitrobenzamido)acetate
Authors: Zhu Xin , Ma Qiujuan
Published: July 2012

The title compound, C11H12N2O6, crystallizes with two independent molecules in the asymmetric unit, which differ slightly in conformation. The dihedral angle between the amide O=C—N plane and the attached benzene ring is 19.5 (3)° in one molecule and 23.4 (3)° in the other. In the crystal, the two independent molecules are connected alternately by N—H...O hydrogen bonds, forming a chain along theaaxis.
2-Hydroxy-3-methoxybenzaldehyde (o-vanillin) revisited
Authors: Shin David , Müller Peter
Published: July 2012

The structure ofortho-vanillin, C8H8O3, has been revisited with modern methods and at low temperature (100 K). The previous structure [Iwasakiet al.(1976).Acta Cryst. B32, 1264–1266] is confirmed, but geometric precision is improved by an order of magnitude. The C atom of the methoxy group lies close to the benzene ring plane, which is the most common geometry for –OMe groups lyingorthoto –OH groups on an aromatic ring. The crystal structure displays one intramolecular O—H...O and three weak intermolecular C—H...O hydrogen bonds.
Potassium morpholine-4-carbodithioate monohydrate
Authors: Mafud Ana C.
Published: July 2012

In the ionic title compound, K+·C5H8NOS2−·H2O, the morpholine ring of the morpholine-4-carbodithioate anion has a chair conformation. The potassium cation is coordinated by four S and four O atoms in a bipyramidal reversed geometry. In the crystal, the three components are linked, generating infinite two-dimensional networks that lie parallel to thebcplane. These layers are linkedviaO—H...S hydrogen bonds, forming a three-dimensional structure.
{μ-2-[(3-Amino-2,2-dimethylpropyl)iminomethyl]-6-methoxyphenolato-1:2κ5O1,O6:N,N′,O1}{2-[(3-amino-2,2-dimethylpropyl)iminomethyl]-6-methoxyphenolato-1κ3N,N′,O1}-μ-azido-1:2κ2N:N-azido-2κN-methanol-2κO-dinickel(II)
Authors: Ghaemi Akbar , Rayati Saeed , Fayyazi Kazem , Ng Seik Weng , Tiekink Edward R. T.
Published: July 2012

Two distinct coordination geometries are found in the binuclear title complex, [Ni2(C13H19N2O2)2(N3)2(CH3OH)], as one Schiff base ligand is pentadentate, coordinatingviathe anticipated oxide O, imine N and amine N atoms (as for the second, tridentate, ligand) but the oxide O is bridging and coordination also occurs through the methoxy O atom. The NiIIatoms are linked by a μ2-oxide atom and one end of a μ2-azide ligand, forming an Ni2ON core. The coordination geometry for the NiIIatom coordinated by the tridentate ligand is completed by the methoxy O atom derived from the pentadentate ligand, with the resulting N3O3donor set defining afacoctahedron. The second NiIIatom has itscis-octahedral N4O2coordination geometry completed by the imine N and amine N atoms of the pentadentate Schiff base ligand, a terminally coordinated azide N and a methanol O atom. The arrangement is stabilized by an intramolecular hydrogen bond between the methanol H and the oxide O atom. Linear supramolecular chains along theaaxis are formed in the crystal packing whereby two amine H atoms from different amine atoms hydrogen bond to the terminal N atom of the monodentate azide ligand.
Girdin locates in centrosome and midbody and plays an important role in cell division
Authors: Mao Jing‐Zhuo , Jiang Ping , Cui Su‐Ping , Ren Ya‐Li , Zhao Jing , Yin Xiu‐Hua , Enomoto Atsushi , Liu Hai‐Jing , Hou Lin , Takahashi Masahide , Zhang Bo
Published: July 2012

Girdin is a downstream effector of epidermal growth factor receptor (EGFR)‐AKTand interacts with actin and microtubule. Increasing evidence confirmed thatGirdin played an important role in cell migration. Here we report thatGirdin also regulates cell division. Overexpression or suppression ofGirdin leads to attenuated cell proliferation. Imaging of mitotic cells revealed thatGirdin is located in the cell division apparatus such as centrosome and midbody. The sub‐cellular localization ofGirdin was dependent on the domains, which interacted with actin or microtubules. Overexpression ofGirdin lead to increased centrosome splitting and amplification. In addition, data show that pAKTalso locates in both the centrosome and midbody, indicating the regulating role ofAKTinGirdin‐mediated cell division. To elucidate the effect ofGirdin on tumor growthin vivo,HeLa cells infected with retrovirus harboring either control orGirdin shRNAs were injected subcutaneously into the immunocompromised nude mice. Downregulation ofGirdin by shRNAmarkedly inhibited the cell growth of subcutaneously transplanted tumors in nude mice. These data demonstrate thatGirdin is important for efficient cell division. Taking our previous data into consideration, we speculate thatGirdin regulates both cell division and cell migration through cytoskeletal molecules.
Admission time is associated with outcome of upper gastrointestinal bleeding: results of a multicentre prospective cohort study
Authors: de Groot N. L. , Bosman J. H. , Siersema P. D. , van Oijen M. G. H. , Bredenoord A. J. ,   on behalf of the RASTA study group
Published: July 2012

Background

It has been suggested that patients presenting with upper gastrointestinal bleeding (UGIB) during the weekend have a worse outcome compared with weekdays, with an increased risk of recurrent bleeding and mortality.

Aim

To investigate the association between timing of admission and adverse outcome after UGIB.

Methods

We prospectively collected data from patients presenting with symptoms suggestive of UGIB to the emergency room of eight participating hospitals. Using standard descriptive statistics and logistic regression analyses, differences in 30‐day mortality, rebleeding rate, and need for angiography and surgical intervention were assessed for week‐ and weekend admissions and time of admission. Moreover, patient‐ and procedure‐related factors were identified that could influence outcome.

Results

In total, 571 patients were included with suspected UGIB. Patient admitted during the weekend had a higher mortality rate than patients admitted during the week [9% vs.3%; adjusted odds ratio 2.68 (95%CI 1.07–6.72)]. Weekend admissions were not associated with other adverse outcomes. Patients admitted during the weekend presented more often with bleeding and had a significantly lower systolic and diastolic blood pressure. No differences were found in procedure‐related factors. Time of admission was not associated with an adverse outcome, although patients admitted during the evening had a significantly longer time to endoscopy (15, 22 and 16 h for day, evening and night admissions respectively, P < 0.01).

Conclusion

Although quality of care did not appear to differ between week/weekend admissions, patients with suspected upper gastrointestinal bleeding admitted during the weekend were at higher risk of an adverse outcome. This might be due to the fact that these patients have more severe haemorrhage.
Apha‐adrenergic receptor blockade increases human REM sleep.
Authors: Oswald I , Thacore VR , Adam K , Brezinova V
Published: July 2012

1 An alpha‐adrenergic receptor blocking agent, thymoxamine (150 mg i.v.) in the early night sleep of young adults increased REM sleep duration and also brief awakenings in the early night, while slow wave sleep, stage 3+4, was diminished. In the later night, however, stage 3+4 sleep was increased. Control experiments demonstrated that thymoxamine (i.v.) was without effect on blood pressure. 2 REM sleep duration may be inversely proportional to noradrenaline available at central alpha‐adrenoceptors, but the control mechanisms for REM sleep appear interdependent with those for NREM sleep.
Studies of the action of some anti‐inflammatory drugs on complement mediated immune haemolysis.
Authors: Whaley K , Sloane DJ
Published: July 2012

1 The effects of various anti‐inflammatory and non‐anti‐inflammatory drugs on complement mediated haemolysis have been studied. Drugs which were significantly protein bound were found to inhibit this form of immune lysis, but only at greater concentrations than achieved therapeutically. 2 Removal of the drugs by prolonged dialysis resulted in restoration of complement activity with the exceptions of phenylbutazone and warfarin sodium. 3 Reconstitution experiments indicated that C2 and some of the later components especially C7 were affected by the drugs. 4 Intra‐articular injections of prednisolone (100 mg) in patients with rheumatoid arthritis, failed to produce significant changes in the synovial fluid complement system. 5 None of the drugs affected the binding of antibody to antigen, or the ability of sensitized sheep cells to fix complement.
Behavioural sequelae of methaqualone in man and in the monkey (Macaca mulatta).
Authors: Borland RG , Nicholson AN , Wright CM
Published: July 2012

1 Residual effects in man of methaqualone hydrochloride (400 mg) were studied by adaptive tracking and by reaction time. Performance was measured at 10 h, 13 h, 16 h, 19 h and 34 h after the overnight ingestion of the drug. There was no evidence of impaired performance on adaptive tracking from 10 h to 19 h, but enhanced performance (P = 0.001) was observed 34 h after ingestion. With reaction time an increase (P = 0.01) was observed 10 h and a decrease (P = 0.05) was observed 19 h after ingestion. 2 Effects in the monkey (Macaca mulatta) of methaqualone (20 and 30 mg/kg body weight) were studied by a delayed matching task in which total response time was measured. No consistent effects on matching behaviour or on total response time were observed 2 h after intraperitoneal injection. 3 The studies suggest that methaqualone hydrochloride may be a valuable hypnotic for occasional use by persons involved in skilled activity.
Beta‐adrenergic receptor blocking drugs, hypertension and plasma renin.
Authors: Morgan TO , Roberts R , Carney SL , Louis WJ , Doyle AE
Published: July 2012

1 Propranolol and pindolol reduced both the blood pressure and plasma renin activity when given chronically to hypertensive patients. 2 There was no correlation between the fall in blood pressure and the fall in plasma renin activity. 3 Neither the basal nor the random plasma renin activity predicted the patients who would respond to beta‐adrenergic receptor blocking drugs. 4 Oral propranolol reduced plasma renin activity but did not reduce blood pressure within 4 h of administration; oral pindolol reduced blood pressure but did not reduce plasma renin activity within 4 h of administration. 5 The reduction of blood pressure by propranolol and pindolol does not seem to be mediated by changes in plasma renin in most patients.
Interactions of orphenadrine and phenobarbitone with chlorpromazine: plasma concentrations and effects in man.
Authors: Loga S , Curry S , Lader M
Published: July 2012

1 Two studies were carried out on acutely psychotic patients receiving chlorpromazine (100 mg) 8‐hourly. 2 In the pilot study on five patients, plasma chlorpromazine concentrations fell over the course of 3 weeks of treatment and parallel changes were noted in the plasma half‐ life of antipyrine, salivation rate and handwriting length. 3 In the main study involving twelve patients treated for 15 weeks, the above findings were confirmed and were interpreted as indicating that chlorpromazine accelerated its own metabolism by inducing liver microsomal oxidising enzymes. No metabolites of chlorpromazine were detected in plasma. 4 The addition of phenobarbitone (50 mg) 8‐hourly for 3 weeks, or orphenadrine (100 mg) 8‐hourly for 3 weeks, resulted in a lowering of plasma chlorpromazine concentrations together with a further shortening of plasma antipyrine half‐life. 5 Physiological effects of the additional treatments suggested that phenobarbitone lessens the effects of chlorpromazine by lowering body concentrations. However, orphenadrine acts more by virtue of its anticholinergic effects. 6 It was concluded that phenobarbitone and orphenadrine should not be prescribed routinely in patients receiving major tranquillisers. The need for the addition of orphenadrine should be assessed in each individual case.
Blood level studies with viloxazine hydrochloride in man.
Authors: Bayliss PF , Case DE
Published: July 2012

1 The pharmacokinetic characteristics of a new antidepressant, viloxazine hydrochloride, (ICI 58,834, Vivalan), have been investigated in four separate studies. 2 In Study 1, blood levels were measured over a period of 24 h after single doses of viloxazine hydrochloride from 10− 100 mg (expressed as base). In Study 2, blood levels were measured over 24 h, during which three single doses of viloxazine hydrochloride (80 mg, expressed as base) were given 4 h apart. In Study 3, blood samples and urine and faeces were collected for 96 h after doses of 40 and 100 mg of [14C] viloxazine hydrochloride (40 muCi). In Study 4, 1 h blood levels were measured at weekly intervals during a comparative clinical trial in which viloxazine was given at a dose of 100 mg four times a day. 3 The half‐life of the drug is in the range 2‐5 h with maximum blood levels occurring in 1‐4 h of the oral dose. Maximum blood levels are proportional to the oral dose given over the range studied (0.76(mug/ml)/(mg/kg)). The drug is very well absorbed orally, only 2% being found in faeces. Repeated dosing at 4 hourly intervals leads to slightly higher blood levels after the second, but not subsequent, doses. No accumulation was seen from week to week in depressed patients. No regular sex difference was seen in the pharmacokinetic characteristics of viloxazine hydrochloride but two females in one study did show a markedly higher maximum blood level and apparently longer half‐life than the males. 4 It is concluded that viloxazine is rapidly and almost totally absorbed after an oral dose, and has a shorter half‐life than the tricyclic antidepressants; therapy with it should be easily controllable.
Immediate effects on human performance of a 1,5‐genzodiazepine (clobazam) compared with the 1,4‐benzodiazepines, chlordiazepoxide hydrochloride and diazepam.
Authors: Borland RG , Nicholson AN
Published: July 2012

1 The immediate effects on human performance of the 1,5‐benzodiazepine, clobazam (20 mg), and the 1,4‐benzodiazepines, chlordiazepoxide hydrochloride (20 mg) and diazepam (10 mg), were studied by adaptive tracking and measurement of reaction time. Each drug was ingested at 09.00 h and performance was measured at 09 h 30 min (0.5 h), 11 h 30 min (2.5 h), 14 h 30 min (5.5 h) and 18 h 30 min (9.5 h after ingestion). 2 With diazepam decrements in performance on adaptive tracking were observed at 0.5 h and 2.5 h and performance was enhanced at 9.5 h after ingestion. With clobazam performance at individual times did not differ significantly from control, but there was evidence of an improvement in performance during the day. There was no evidence of impaired performance on adaptive tracking after chlordiazepoxide hydrochloride. 3 Reaction time was slowed at 0.5 h and 2.5 h after diazepam and chlordiazepoxide hydrochloride. A decrease in reaction time was observed at 9.5 h after diazepam. No changes in reaction time were observed after clobazam. 4 The subjects as a group differentiated correctly between performance decrements on adaptive tracking after diazepam and the absence of performance decrements after clobazam and chlordiazepoxide hydrochloride. The persistence of the decrement in performance after diazepam was accurately assessed. 5 It is evident that the nature and persistence of impaired performance and the ability to appreciate impaired performance vary considerably between the benzodiazepines, and that the choice of a benzodiazepine should include careful consideration of performance sequelae.
A clinical and psychometric evaluation of flurazepam.
Authors: Salkind MR , Silverstone T
Published: July 2012

1 The efficacy of flurazepam (15 mg or 30 mg) as a hypnotic, and the residual effects of each dose were compared with placebo in a double‐ blind cross‐over trial involving thirty patients in a general practice setting. Patients received each medication for one week. Daily self‐ ratings of onset, duration and quality of sleep, together with reports of any untoward effects were made. At the end of each period of medication psychomotor tests (reaction time, pursuit rotor, tapping speed) were administered at 09.00 hours. 2 Both doses of flurazepam were significantly more effective than placebo in inducing sleep, improving the quality of sleep and extending its duration. 3 'Hangover' effects were marked following 30 mg, but not after flurazepam (15 mg). Flurazepam (30 mg, but not 15 mg) significantly impaired performance on the pursuit rotor test and tapping speed. Flurazepam thus appears to be an effective hypnotic drug with the optimum dose for use in general practice being 15 mg at night.
Effect of age, height, weight and sex on serum phenytoin concentration in epileptic patients.
Authors: Houghton GW , Richens A , Leighton M
Published: July 2012

1 Steady‐state serum phenytoin concentrations were measured in adult epileptic patients receiving a maintenance dose of phenytoin (300 mg daily). 2 Serum phenytoin concentration showed a positive correlation with age. 3 Serum phenytoin concentration showed a negative correlation with body weight and with height. Multiple correlation analysis indicated that body weight influenced the concentration to a much greater degree than height. 4 When corrected for body weight and height, the serum phenytoin concentrations in women were lower than those in men, although the difference was not statistically significant. 5 Although each of these factors contributes to the interindividual variation in serum phenytoin concentrations, the contribution of each is small. Other factors, such as genetic differences and the effect of saturation kinetics, are much more important in determining steady‐state concentrations. Adjusting the dose according to the age, weight and height of a patient would achieve only a marginal improvement in therapy.
Effect of phenobarbitone on hepatic drug‐metabolizing enzymes and urinary D‐glucaric acid excretion in man.
Authors: Lecamwasam DS , Franklin C , Turner P
Published: July 2012

1 The activities of some hepatic drug‐metabolizing enzymes representative of the four major pathways for the biotransformation of drugs were estimated in diagnostic wedge biopsy specimens obtained from 22 patients with Hodgkin's disease. Twelve patients (nine males and three females) were not on prolonged pre‐operative treatment with any known inducing drugs. In this group, hexobarbitone oxidase activity, cytochrome P450 and microsomal protein contents were in the same range as those reported by other workers. 2 Ten patients (five males and five females) were pre‐operatively treated with phenobarbitone (90 mg daily) for at least seven days. This resulted in a significant increase of hexobarbitone oxidase activity, cytochrome P450 and microsomal protein contents when the phenobarbitone untreated and treated groups were compared as a whole and provides direct evidence of induction of hepatic mixed function oxidase system. In respect of p‐nitroreductase, 1‐leucyl‐beta‐naphthylamide splitting enzyme and UDP glucuronyl transferase, there was no difference between the treated and untreated groups. 3 When untreated and treated patients were compared, the induction of the hepatic mixed function oxidase system, was associated with a significant increase in urinary D‐glucaric acid excretion. In treated patients, however, there was no correlation between any of the indices studied and post‐phenobarbitone D‐glucaric acid content or the rise in D‐glucaric acid excretion. However, the correlation between cytochrome P450 content and post‐phenobarbitone D‐glucaric acid or the rise in D‐glucaric acid excretion was only just below statistical significance (r = 0.696 and 0.690 respectively, 0.10 greater than P greater than 0.05) whereas in the untreated group there was no correlation (r = 0.231, P greater than 0.60). 4 In two patients, whose phenobarbitone was discontinued for at least six days prior to surgery, all indices studied had returned to untreated values, except for microsomal protein content which remained significantly elevated.