bluuebunny/crossref_metadata_2025 huggingface dataset:
From annuals to perennials: phylogeny of subtribe Castillejinae (Orobanchaceae)
Authors: Tank David C. , Olmstead Richard G.
Published: April 2008

Variation in life history strategies is a fundamental question in evolutionary biology, and the cooccurrence of annual and perennial habits in Castilleja and Castillejinae provides the opportunity to study the evolution of plant life history in a phylogenetic context. Molecular phylogenetic analysis of two chloroplast (rps16 and trnL/F) and two nuclear ribosomal (internal and external transcribed spacers) DNA regions support the monophyly of subtribe Castillejinae (Orobanchaceae). A well‐supported phylogeny of the six genera (Castilleja [∼180 spp.], Clevelandia [1 sp.], Cordylanthus [18 spp.], Ophiocephalus [1 sp.], Orthocarpus [9 spp.], and Triphysaria [5 spp.]) comprising the subtribe is presented, and morphological synapomorphies are identified for the major lineages recovered. Orthocarpus and Triphysaria are both monophyletic; Cordylanthus is biphyletic. Clevelandia and Ophiocephalus are derived from within Castilleja. The perennial Castilleja clade (∼160 spp.) is derived from a grade of annual taxa including Castilleja sect. Oncorhynchus (16 spp.), Cordylanthus, Orthocarpus, and Triphysaria. This suggests that the perennial habit evolved a single time from an annual ancestral lineage that persisted throughout the diversification of Castillejinae, contrary to classical interpretations of life history evolution in plants. Given the prevalence of polyploidy among perennial Castilleja species, perenniality may have played an important role in the origin and establishment of polyploidy in Castilleja.
Progress in secondary stroke prevention
Authors: Romano Jose G. , Sacco Ralph L.
Published: April 2008

Objectives

There are about 200,000 recurrent strokes each year in the United States. In addition, a large proportion of strokes are preceded by a transient ischemic attack. Therefore, secondary stroke prevention strategies are of great importance.

Methods

Select ongoing and recently completed studies were reviewed, with emphasis on those completed since the publication of secondary prevention guidelines. Ongoing studies that have the potential to modify existing recommendations are also mentioned.

Results

This review discusses recently completed and ongoing studies that have the potential to impact clinical practice. The topics discussed include hypertension, dyslipidemia, extracranial carotid and intracranial atherosclerotic disease, and antithrombotic therapy.

Interpretation

Recent studies have provided evidence that impact secondary stroke prevention. Ann Neurol 2008;63:418–427
Effects of coagulation processes on properties of epoxidized natural rubber
Authors: Zong‐Qiang Zeng , He‐Ping Yu , Qi‐Fang Wang , Guang Lu
Published: April 2008

The epoxidized natural rubber (ENR) with epoxy group contents of 48.4% were coagulated with ethanol and steam and the structures, processing performances, antioxidative behaviors, cure characteristics, and dynamic mechanical properties were analyzed using infrared spectroscopy, rubber processing analyzer, thermogravimetric analyzer, rheometer, and dynamic thermomechanical analyzer, respectively. The results indicate that the ENR coagulated with ethanol (ENR‐e) exhibits a compact structure and the contents of residual low‐molecular‐weight matters are higher than those of unconsolidated ENR coagulated with steam (ENR‐s). Therefore, the processing performance and antioxidative behavior as well as the curing characteristics of ENR‐e compound are poorer than those of ENR‐s. Although the mechanical properties and wet skid resistance of ENR‐s vulcanizate are poorer than those of ENR‐e, the heat build‐up or rolling resistance of ENR‐s is better than that of ENR‐e. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Unique Microanatomy of Ileal Peyer's Patches of the One Humped Camel (Camelus dromedarius) is not Age‐Dependent
Authors: Zidan Mohamed , Pabst Reinhard
Published: April 2008

The Peyer's patches (PP) have been intensely investigated in several species because this is an important entry site for antigens and infectious agents. There are many PP in the jejunum, and in some species such as ruminants, carnivores, and omnivores, a different continuous PP is found in the terminal ileum. This PP disappears with age in these species studied. So far the ileal PP (IPP) has only been examined in the camel by light microscopy. Therefore, the localization of ileal Peyer's patches in the dromedary camel at different ages, as well as the histology and ultrastructures were now investigated. The IPP were characteristically seen as dark rose‐colored isolated structures in the shape of a cup, arranged in three irregular rows. The central row was antimesenteric. Each patch was formed by several mainly elongated dome regions flanked by intestinal villi. In cross‐sections these domes appeared as short, wide villi. The domes were formed from lymphoid follicles covered with a typical dome‐associated epithelium of enterocytes and M cells without any goblet cells. The M cells showed variable appearance depending on the functional status. The lymphoid follicles expressed clear germinal centers. High endothelial venules were localized in the interfollicular region. In contrast to other species the IPP were still present with a comparable macroscopic and histological structure in camels of 25 years of age. Anat Rec, 291:1023–1028, 2008. © 2008 Wiley‐Liss, Inc.
Effectiveness of medial‐wedge insole treatment for valgus knee osteoarthritis
Authors: Rodrigues Priscilla T. , Ferreira Ana F. , Pereira Rosa M. R. , Bonfá Eloísa , Borba Eduardo F. , Fuller Ricardo
Published: April 2008

Objective

To assess the efficacy of medial‐wedge insoles in valgus knee osteoarthritis (OA).

Methods

Thirty consecutive women with valgus‐deformity knee OA ≥8 degrees were randomized into 2 groups: medial insole (insoles with 8‐mm medial elevation at the rearfoot [n = 16]) and neutral insole (similar insole without elevation [n = 14]). Both groups also wore ankle supports. A blinded examiner assessed pain on movement, at rest, and at night with a visual analog scale (VAS), the Lequesne index, and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index. Femorotibial, talocalcaneal, and talar tilt angles were evaluated at baseline and after 8 weeks of insole use.

Results

Significant reductions in the medial insole group were observed for pain on movement (mean ± SD VAS pre‐ and postintervention 8.1 ± 1.5 versus 4.2 ± 2.4; P = 0.001), at rest (5.1 ± 2.3 versus 2.7 ± 2.4; P = 0.002), and at night (6.1 ± 2.7 versus 3.1 ± 2.1; P = 0.001). In addition, a decrease in Lequesne (14.7 ± 3.4 versus 9.6 ± 3.8; P = 0.001) and WOMAC scores (74.1 ± 14.2 versus 56.1 ± 14.9; P = 0.001) was observed for the medial insole group. In the neutral insole group, a significant reduction was observed only for night pain (mean ± SD VAS pre‐ and postintervention 5.8 ± 2.4 versus 4.6 ± 2.4; P = 0.019). An increase in femorotibial angle (169.0 ± 3.4 versus 170.8 ± 3.7; P = 0.001) occurred only in the medial insole group. Moreover, the difference in measured femorotibial angles pre‐ and postintervention was 1.84 ± 1.42 versus −0.18 ± 0.67 (P < 0.001) for the medial and neutral insole groups.

Conclusion

The use of medial‐wedge insoles was highly effective in reducing pain at rest and on movement and promoted a functional improvement of valgus knee OA.
Reducing joint loading in medial knee osteoarthritis: Shoes and canes
Authors: Kemp Georgina , Crossley Kay M. , Wrigley Tim V. , Metcalf Ben R. , Hinman Rana S.
Published: April 2008

Objective

Increased medial knee loading is associated with a much higher risk of disease progression in knee osteoarthritis (OA). Interventions that can reduce medial knee joint load have the potential to slow disease progression over time. We evaluated the effects of shoes and a cane on knee load in people with knee OA.

Methods

Forty people with medial knee OA underwent 3‐dimensional gait analysis to measure their peak knee adduction moment, an indicator of medial knee joint load. Results when walking in bare feet were compared with those obtained when walking in their own usual shoes. Twenty participants also underwent testing using a cane, and results were compared with walking unaided.

Results

Compared with barefoot, walking in shoes was associated with a significant increase in the peak knee adduction moment (mean ± SD N × m/BW × H% 3.49 ± 0.84 versus 3.77 ± 0.90; P < 0.001), although there was considerable individual variation. The use of a cane resulted in a 10% decrease in the knee adduction moment (mean ± SD N × m/BW × H% 3.76 ± 0.95 versus 3.38 ± 0.68; P = 0.001).

Conclusion

Wearing shoes increases medial knee joint load compared with walking barefoot. Given the variable response to shoes observed, further research is required to ascertain which shoe types might be optimal for those with knee OA. The use of a cane significantly reduces medial knee loading and has the potential to reduce the risk of disease progression in knee OA.
Long‐Wavelength Fluorescence from 2‐Aminopurine‐Nucleobase Dimers in DNA
Authors: Bonnist Eleanor Y. M. , Jones Anita C.
Published: April 2008

When 2‐aminopurine (2AP) is substituted for adenine in DNA, it is widely accepted that its fluorescence spectrum is essentially unchanged from that of the free fluorophore. We show that 2AP in DNA exhibits long‐wavelength emission and excitation bands, in addition to the familiar short‐wavelength spectra, as a result of formation of a ground‐state heterodimer with an adjacent, π‐stacked, natural base. The observation of dual emission from 2AP in a variety of oligodeoxynucleotide duplexes and single strands demonstrates the generality of this phenomenon. The photophysical and conformational properties of the long‐wavelength‐emitting 2AP‐nucleobase dimer are examined. Analogous long‐wavelength fluorescence is seen when 2AP π‐stacks with aromatic amino acid sidechains in the active sites of methyltransferase enzymes during DNA nucleotide flipping.
Heck Reactions of 6‐ and 2‐Halopurines
Authors: Tobrman Tomáš , Dvořák Dalimil
Published: April 2008

Under the conditions of the Heck reaction, 9‐benzyl‐6‐iodopurine affords mainly the corresponding 6,6′‐dimer, the Heck product being formed only in low yield (≤12 %). With 7‐benzyl‐6‐iodopurine the dimerization is suppressed and the Heck product is obtained in 32–91 % yield. 9‐Substituted 6‐chloro‐2‐iodopurines react smoothly, giving 2‐alkenyl‐6‐chloropurines in 71–97 % isolated yields. The reaction proceeds with alkenes bearing electron‐withdrawing substituents (like CO2Bu, COCH3, CN) and Ph, while vinyl acetate and dodec‐1‐ene are unreactive. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Nuclear proteome analysis of undifferentiated mouse embryonic stem and germ cells
Authors: Buhr Nicolas , Carapito Christine , Schaeffer Christine , Kieffer Emmanuelle , Van Dorsselaer Alain , Viville Stéphane
Published: April 2008

Embryonic stem cells (ESCs) and embryonic germ cells (EGCs) provide exciting models for understanding the underlying mechanisms that make a cell pluripotent. Indeed, such understanding would enable dedifferentiation and reprogrammation of any cell type from a patient needing a cell therapy treatment. Proteome analysis has emerged as an important technology for deciphering these biological processes and thereby ESC and EGC proteomes are increasingly studied. Nevertheless, their nuclear proteomes have only been poorly investigated up to now. In order to investigate signaling pathways potentially involved in pluripotency, proteomic analyses have been performed on mouse ESC and EGC nuclear proteins. Nuclei from ESCs and EGCs at undifferentiated stage were purified by subcellular fractionation. After 2‐D separation, a subtractive strategy (subtracting culture environment contaminating spots) was applied and a comparison of ESC, (8.5 day post coïtum (dpc))‐EGC and (11.5 dpc)‐EGC specific nuclear proteomes was performed. A total of 33 ESC, 53 (8.5 dpc)‐EGC, and 36 (11.5 dpc)‐EGC spots were identified by MALDI‐TOF‐MS and/or nano‐LC‐MS/MS. This approach led to the identification of two isoforms (with and without N‐terminal acetylation) of a known pluripotency marker, namely developmental pluripotency associated 5 (DPPA5), which has never been identified before in 2‐D gel‐MS studies of ESCs and EGCs. Furthermore, we demonstrated the efficiency of our subtracting strategy, in association with a nuclear subfractionation by the identification of a new protein (protein arginine N‐methyltransferase 7; PRMT7) behaving as proteins involved in pluripotency.
Polydrug use, cannabis, and psychosis‐like symptoms
Authors: Van Dam Nicholas T , Earleywine Mitch , DiGiacomo Greg
Published: April 2008

Objective

To examine psychosis‐like symptoms in users of legal and illicit drugs.

Methods

Schizotypal Personality Questionnaire (SPQ) scores were compared in groups of people with different exposure to cannabis, with the use of other drugs serving as a covariate. Supplemental analyses compared users of legal and illicit drugs with cannabis use as a covariate.

Results

Weekly (n = 111) and monthly (n = 136) cannabis users had higher scores on the SPQ than former (n = 143) and non‐users (n = 81). The use of other drugs accounted for the links between cannabis and schizotypy. Lifetime use of psychomotor stimulant drugs plus ecstasy accounted for associations between cannabis and scores on the SPQ and its different subscales. Dividing groups by type of drug use revealed that those who used only cannabis and legal drugs (CLDs) (n = 126) were no different from those who used only legal drugs (LDs) (n = 74) but both groups scored significantly lower on the SPQ than polydrug users (n = 247). When controlling for marijuana use in the last month, the significant difference across drug use groups remained.

Conclusions

The results suggest that research on marijuana and schizotypy requires careful assessment of the use of other drugs, especially psychomotor stimulants and ecstasy. Copyright © 2008 John Wiley & Sons, Ltd.
Characterization of BASP1‐mediated neurite outgrowth
Authors: Korshunova Irina , Caroni Pico , Kolkova Kateryna , Berezin Vladimir , Bock Elisabeth , Walmod Peter S.
Published: April 2008

The brain acid‐soluble protein BASP1 (CAP‐23, NAP‐22) belongs to the family of growth‐associated proteins, which also includes GAP‐43, a protein recently shown to regulate neural cell adhesion molecule (NCAM)‐mediated neurite outgrowth. Here, the effects of BASP1 overexpression were investigated in PC12E2 cells and primary hippocampal neurons. BASP1 overexpression stimulated neurite outgrowth in both cell types. The effects of BASP1 and trans‐homophilic NCAM interactions were additive, and BASP1‐induced neurite outgrowth was not inhibited by ectopic expression of cytoplasmic NCAM domains. Furthermore, inhibition of signaling via the fibroblast growth factor receptor, Src‐family nonreceptor tyrosine kinases, protein kinase C, or GSK3β, and expression of constructs of the cytoskeletal proteins spectrin and tau inhibited NCAM‐ but not BASP1‐induced neurite outgrowth. Expression of BASP1 mutated at the serine‐5 phosphorylation site stimulated neurite outgrowth to a degree comparable to that observed in response to overexpression of wild‐type BASP1, whereas expression of BASP1 mutated at the myristoylation site at glycine‐1 completely abrogated the stimulatory effects of the protein on neurite outgrowth. Finally, coexpression experiments with dominant negative and wild‐type versions of GAP‐43 and BASP1 demonstrated that the two proteins could substitute for each other with respect to induction of NCAM‐independent neurite outgrowth, whereas BASP1 was unable to replace the stimulatory effect of GAP‐43 on NCAM‐mediated neurite outgrowth. These observations demonstrate that BASP1 and GAP‐43 have overlapping, but not identical, functions in relation to neurite outgrowth and indicate that the main function of BASP1 is to regulate the organization and morphology of the plasma membrane. © 2008 Wiley‐Liss, Inc.
Age‐related decreases in NAD(P)H and glutathione cause redox declines before ATP loss during glutamate treatment of hippocampal neurons
Authors: Parihar Mordhwaj S. , Kunz Elizabeth A. , Brewer Gregory J.
Published: April 2008

Age‐related glutamate excitotoxicity depends in an unknown manner on active mitochondria, which are key determinants of the cellular redox potential. Compared with embryonic and middle‐aged neurons, old‐aged rat hippocampal neurons have a lower resting reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and a lower redox ratio (NAD(P)H/flavin adenine nucleotide). Glutamate treatment resulted in an initial increase in NAD(P)H concentrations in all ages, followed by a profound calcium‐dependent, age‐related decline in NAD(P)H concentration and redox ratio. With complex I of the electron transport chain inhibited by rotenone, treatment with glutamate or ionomycin only resulted in the increase in NAD(P)H fluorescence. High‐performance liquid chromatography analysis of adenine nucleotides in brain extracts showed 50% less nicotinamide adenine dinucleotide (NADH) and almost twice as much oxidized nicotinamide adenine dinucleotide, demonstrating a more oxidized ratio in old than middle‐aged brain. Resting glutathione content also declined with age and further decreased with glutamate treatment without accompanying changes in adenosine triphosphate levels. We conclude that age does not affect production of NADH by dehydrogenases but that old‐aged neurons consume more NADH and glutathione, leading to a catastrophic decline in redox ratio. © 2008 Wiley‐Liss, Inc.
Huperzine A attenuates mitochondrial dysfunction after middle cerebral artery occlusion in rats
Authors: Zheng Chun Yan , Zhang Hai Yan , Tang Xi Can
Published: April 2008

Mitochondrial dysfunction has been proved to contribute to ischemia‐induced brain damage. In this study, which used a rat middle cerebral artery occlusion (MCAO) model, the protective effects of huperzine A (HupA) against mitochondrial dysfunction and brain damage were investigated. MCAO for 45 min followed by 4 hr of reperfusion significantly impaired the activities of mitochondrial respiratory chain enzymes (complex I, complex II–III, and complex IV) and α‐ketoglutarate dehydrogenase, increased the production of reactive oxygen species (ROS), and induced mitochondrial swelling. Pretreatment of HupA at 0.1 mg/kg significantly preserved respiratory chain enzyme activities, decreased ROS production, and attenuated mitochondrial swelling. It could also significantly attenuate the neurological deficits (after 4 or 24 hr reperfusion) and reduce infarct volumes (after 24 hr reperfusion). Moreover, HupA protected isolated nonsynaptosomal mitochondria from calcium‐induced damage in vitro by preserving mitochondrial membrane potential and decreasing ROS production. Overall, the present study indicates that HupA can ameliorate MCAO‐induced mitochondrial dysfunction, and this might partially contribute to its protective effect on brain damage after 24 hr of reperfusion. © 2008 Wiley‐Liss, Inc.
Antipsychotic drugs up‐regulate tryptophan hydroxylase in ADF neurons of Caenorhabditis elegans: Role of calcium‐calmodulin‐dependent protein kinase II and transient receptor potential vanilloid channel
Authors: Donohoe Dallas R. , Phan Thang , Weeks Kathrine , Aamodt Eric J. , Dwyer Donard S.
Published: April 2008

Antipsychotic drugs produce acute behavioral effects through antagonism of dopamine and serotonin receptors, and long‐term adaptive responses that are not well understood. The goal of the study presented here was to use Caenorhabditis elegans to investigate the molecular mechanism or mechanisms that contribute to adaptive responses produced by antipsychotic drugs. First‐generation antipsychotics, trifluoperazine and fluphenazine, and second‐generation drugs, clozapine and olanzapine, increased the expression of tryptophan hydroxylase‐1::green fluorescent protein (TPH‐1::GFP) and serotonin in the ADF neurons of C. elegans. This response was absent or diminished in mutant strains lacking the transient receptor potential vanilloid channel (TRPV; osm‐9) or calcium/calmodulin‐dependent protein kinase II (CaMKII; unc‐43). The role of calcium signaling was further implicated by the finding that a selective antagonist of calmodulin and a calcineurin inhibitor also enhanced TPH‐1::GFP expression. The ADF neurons modulate foraging behavior (turns/reversals off food) through serotonin production. We found that short‐term exposure to the antipsychotic drugs altered the frequency of turns/reversals off food. This response was mediated through dopamine and serotonin receptors and was abolished in serotonin‐deficient mutants (tph‐1) and strains lacking the SER‐1 and MOD‐1 serotonin receptors. Consistent with the increase in serotonin in the ADF neurons induced by the drugs, drug withdrawal after 24‐hr treatment was accompanied by a rebound in the number of turns/reversals, which demonstrates behavioral adaptation in serotonergic systems. Characterization of the cellular, molecular, and behavioral adaptations to continuous exposure to antipsychotic drugs may provide insight into the long‐term clinical effects of these medications. © 2008 Wiley‐Liss, Inc.
Interactive roles of fibroblast growth factor 2 and neurotrophin 3 in the sequence of migration, process outgrowth, and axonal differentiation of mouse cochlear ganglion cells
Authors: Hossain Waheeda A. , D'Sa Chrystal , Morest D. Kent
Published: April 2008

A growth factor may have different actions depending on developmental stage. We investigated this phenomenon in the interactions of fibroblast growth factor 2 (FGF2) and neurotrophins on cochlear ganglion (CG) development. The portions of the otocyst fated to form the CG and cochlear epithelium were cocultured at embryonic day 11 (E11). Cultures were divided into groups fed with defined medium, with or without FGF2 and neurotrophin supplements, alone or in combination, for 7 days. We measured the number of migrating neuroblasts and distances migrated, neurite outgrowth, and axonlike processes. We used immunohistochemistry to locate neurotrophin 3 (NT3) and its high‐affinity receptor (TrkC) in the auditory system, along with FGF2 and its R1 receptor, at comparable developmental stages in vitro and in situ from E11 until birth (P1) in the precursors of hair cells, support cells, and CG cells. Potential sites for interaction were localized to the nucleus, perikaryal cytoplasm, and cell surfaces, including processes and growth cones. Time‐lapse imaging and quantitative measures support the hypothesis that FGF2 alone or combined with neurotrophins promotes migration and neurite outgrowth. Synergism or antagonism between NT3 and other factors suggest interactions at the receptor level. Formation of axons, endings, and synaptic vesicle protein 2 were increased by interactions of NT3 and FGF2. Similar experiments with a mutant overexpressor for FGF2 suggest that endogenous FGF2 supports migration and neurite outgrowth of CG neuroblasts as well as proliferation, leading to accelerated development. The findings suggest interactive and sequential roles for FGF2 and NT3. © 2008 Wiley‐Liss, Inc.
Runx2 is expressed in human glioma cells and mediates the expression of galectin‐3
Authors: Vladimirova Valentina , Waha Andreas , Lückerath Katharina , Pesheva Penka , Probstmeier Rainer
Published: April 2008

Runx2 is a member of the Runx family of transcription factors (Runx1–3) with a restricted expression pattern. It has so far been detected predominantly in skeletal tissues where, inter alia, it regulates the expression of the β‐galactoside‐specific lectin galectin‐3. Here we show that, in contrast to Runx3, Runx1 and Runx2 are expressed in a variety of human glioma cells. Runx2 expression pattern in these cells correlated completely with that of galectin‐3, but not with that of other galectins. A similar correlation in the expression pattern of galectin‐3 and Runx2 transcripts was detected in distinct types of 70 primary neural tumors, such as glioblastoma multiforme, but not in others, such as gangliocytomas. In glioma cells, Runx2 is directly involved in the regulation of galectin‐3 expression, as shown by RNAi and transcription factor binding assays demonstrating that Runx2 interacts with a Runx2‐binding motif present in the human galectin‐3 promoter. Knockdown of Runx2 was thus accompanied by a reduction of both galectin‐3 mRNA and protein levels by at least 50%, dependent on the glial tumor cell line tested. Reverse transcriptase–polymerase chain reaction analyses, aimed at finding other potential target genes of Runx2 in glial tumor cells, revealed the presence of bone sialoprotein, osteocalcin, osteopontin, and osteoprotegerin. However, their expression patterns only partially overlap with that of Runx2. These data suggest a functional contribution of Runx‐2‐regulated galectin‐3 expression to glial tumor malignancy. © 2008 Wiley‐Liss, Inc.
Swedish amyloid precursor protein mutation increases cell cycle‐related proteins in vitro and in vivo
Authors: Ahn Kwang‐Woo , Joo Yuyoung , Choi Yoori , Kim Minji , Lee Sang Hyoung , Cha Seok‐Ho , Suh Yoo‐Hun , Kim Hye‐Sun
Published: April 2008

Reactivation of the cell cycle, including DNA replication, might play a major role in Alzheimer's disease. In this study, we report that the expressions of Swedish double mutation of amyloid precursor protein (Swe‐APP) or of the APP intracellular domain (AICD) into nerve growth factor (NGF)‐differentiated PC12 cells or rat primary cortical neurons increased mRNA and protein levels of cyclin D1 and cyclin B1. Treatment with lithium chloride (a glycogen synthase kinase‐3β inhibitor) down‐regulated cyclin B1 induced by Swe‐APP expression but up‐regulated cyclin D1 expression induced by Swe‐APP, suggesting that glycogen synthase kinase‐3β activity is involved in these expression changes of cyclins D1 and B1. Swe‐APP, which is a prevailing cause of familial Alzheimer's disease, is well known to increase amyloid beta peptide production both in vitro and in vivo, but the underlying molecular means whereby it leads to the pathogenesis of AD remains unknown. The finding that cyclin D1 and B1 expressions were up‐regulated by Swe‐APP in in vitro cultured cells was substantiated in the brain tissues of Tg2576 mice, which harbor the Swe‐APP mutation. These results suggest that some disturbances in cell cycle regulation may be involved in Swe‐APP or AICD‐induced neurodegeneration and that these contribute to the pathogenesis of AD. © 2008 Wiley‐Liss, Inc.
Preconditioning with cobalt chloride or desferrioxamine protects oligodendrocyte cell line (MO3.13) from tumor necrosis factor‐α‐mediated cell death
Authors: Yao Song‐yi , Soutto Mohammed , Sriram Subramaniam
Published: April 2008

Hypoxia‐inducible factor‐1α (HIF‐1α) is a transcription factor induced under hypoxic conditions. HIF‐1α promotes the expression of genes encoding proteins that increase the cellular supply of oxygen and promote survival in periods of cellular stress and availability of cellular energy. We examined the effect of desferrioxamine (DFO) and cobalt chloride (CoCl2), two agents known to increase the stability of HIF‐1α, and its effect on the survivability of an oligodendroglial cell line, MO3.13, when cultured with tumor necrosis factor‐α (TNFα). Our studies showed that, unlike a murine microglial cell line (BV‐2), MO3.13 cells do not induce HIF‐1α in the presence of TNFα. MO3.13 cells do stabilize HIF‐1α in the presence of DFO or CoCl2. When MO3.13 cell were preconditioned with either DFO or CoCl2, addition of TNFα further increased protein levels of HIF‐1α. The mechanisms that underlie the increase in protein levels of HIF ‐1α seen, following addition of TNFα in preconditioned cells is due to an increase in transcription of the HIF‐1α gene. Increased cellular levels of HIF‐1α is associated with improved survival of MO3.13 cells, when cultured with TNFα after a period of preconditioning by DFO or CoCl2. These studies suggest that compoundsthat increase HIF‐1α can function as neuroprotective agents in inflammatory disorders of the CNS. © 2008 Wiley‐Liss, Inc.
Early increase of Nox4 NADPH oxidase and superoxide generation following endothelin‐1‐induced stroke in conscious rats
Authors: McCann Sarah K. , Dusting Gregory J. , Roulston Carli L.
Published: April 2008

Oxidative stress contributes to the progression of brain injury following ischemic stroke and reperfusion. NADPH oxidase is a well‐established source of superoxide in vascular disease, but its contribution to tissue injury following ischemic stroke has yet to be fully elucidated. Here we show the spatiotemporal profile of NADPH oxidase subunits Nox2 and Nox4 and concurrent superoxide generation following stroke induced by middle cerebral artery constriction in conscious rats. Nox2 mRNA was progressively up‐regulated in both the ipsilateral cortex and the striatum from 6 hr to 7 days poststroke and reperfusion. Nox4 mRNA was also up‐regulated transiently in the cortex at 6 hr poststroke but returned to control levels after this time. In situ detection of superoxide generation with dihydroethidium fluorescence revealed an increase in superoxide within the ischemic core at 6 hr poststroke that was mostly colocalized with the neuronal marker NeuN. By 24 hr, this increase in superoxide production had spread to the boundary zone of the infarct, whereas it disappeared in the ischemic core as neuronal numbers declined. Subsequently, superoxide within the ischemic core again increased at 7 days and was mostly colocalized with the activated microglia/macrophage marker OX‐42. Immunoreactivity to Nox2 followed the same spatiotemporal pattern as that of OX‐42 immunostaining poststroke. Clearly, NADPH oxidase is an important mediator of oxidative stress and contributes to the progression of brain damage beyond the infarct core, via the activation of two catalytic subunits, Nox2 and Nox4. Selectively blocking these subunits might be useful for intervening in the progression of stroke brain injury. © 2008 Wiley‐Liss, Inc.
Protective effects of ischemic postconditioning compared with gradual reperfusion or preconditioning
Authors: Gao Xuwen , Ren Chuancheng , Zhao Heng
Published: April 2008

We examined the temporal factors of postconditioning, assessed whether gradual reperfusion reduces infarcts, and compared postconditioning's protection with that of both rapid and delayed preconditioning. Focal ischemia was generated by permanent occlusion of the leftdistal middle cerebral artery (dMCA) combined with 30 min of occlusion of both common carotid arteries (CCA) in rats. Postconditioning was performed by repetitive brief release and occlusion of CCA after 30 min of CCA occlusion. Gradual reperfusion was generated by controlled release of the bilateral CCA. We confirmed that postconditioning disrupted the early reperfusion but improved cerebral blood flow (CBF) thereafter. Postconditioning with three cycles, but not with 10 cycles, of 30 sec CCA release and 10 sec CCA occlusion (30s/10s) reduced infarction measured at 2 days after stroke. In addition, postconditioning with 10 cycles, but not with three cycles, of 10s/10s reduced infarction but it lost protection when initiated at 3 min after reperfusion. In addition, gradual reperfusion also reduced infarction. Moreover, both rapid and delayed preconditioning conducted 60 min and 3 days before stroke reduced infarct sizes. However, no additional protection was detected when postconditioning was combined with either rapid or delayed preconditioning. In conclusion, gradual reperfusion reduced infarction; postconditioning's protection depended on the number of cycles and duration of each cycle of reperfusion and occlusion and the onset time of postconditioning; postconditioning's protection was comparable to that of rapid preconditioning but not as robust as that of delayed preconditioning. © 2008 Wiley‐Liss, Inc.
Age‐dependent time course of cerebral brain‐derived neurotrophic factor, nerve growth factor, and neurotrophin‐3 in APP23 transgenic mice
Authors: Schulte‐Herbrüggen O. , Eckart S. , Deicke U. , Kühl A. , Otten U. , Danker‐Hopfe H. , Abramowski D. , Staufenbiel M. , Hellweg R.
Published: April 2008

Neurotrophins, including brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin‐3 (NT‐3), have repeatedly been shown to be involved in the pathophysiology of Alzheimer's disease (AD). Recent studies have claimed that these neurotrophic factors are important tools for therapeutic intervention in neurodegenerative diseases. So far, little is known about the age‐ and disease‐modulated time course of cerebral neurotrophins. Therefore, we have studied protein concentrations of BDNF, NGF, and NT‐3 in different brain areas and sciatic nerve, a neurotrophin‐transporting peripheral nerve, in a well‐characterized AD model of amyloid precursor protein‐overexpressing rodents (APP23 mice) at the ages of 5.0, 10.5, and 20.0 months. In APP23 mice, there was a significant increase of BDNF and NGF in the frontal and occipital cortices (for BDNF also in the striatum) of old 20.0‐month‐old mice (with respect to median values up to 8.2‐fold), which was highly correlated with amyloid concentrations of these brain areas. Median values of NGF and NT‐3 showed up to a 6.0‐fold age‐dependent increase in the septum that was not detectable in APP23 mice. Hippocampus, olfactory bulb, and cerebellum (except NT‐3) did not show substantial age‐ or genotype‐related regulation of neurotrophins. In the sciatic nerve, BDNF and NGF levels are increased in5‐month‐old APP23 mice and decrease with age to control levels. In conclusion, APP23 mice show a genotype‐dependent increase of cortical BDNF and NGF that is highly correlated with amyloid concentrations and may reflect an amyloid‐related glia‐derived neurotrophin secretion or an altered axonal transport of these neurotrophic factors. © 2008 Wiley‐Liss, Inc.
High throughput screening and antioxidant assay of dibenzo[a,c]cyclooctadiene lignans in modified‐ultrasonic and supercritical fluid extracts of Schisandra chinensis Baill by liquid chromatography–mass spectrometry and a free radical‐scavenging method
Authors: Wang Ming‐Chih , Lai Yih‐Cherng , Chang Chia‐Lin
Published: April 2008

Dibenzo[a,c]cyclooctadiene lignans of Schisandra chinensis Baill are well known because of their hepatoprotective activity, antioxidant activity, and anticancer effect. For the isolation of the dibenzo[a,c]cyclooctadiene lignans of Schisandra chinensis Baill two extraction methods were used: modified‐ultrasonic extraction and supercritical fluid extraction. A specific and fast analytical method for structure identification is established for quality control because structure elucidation could be accomplished by means of liquid chromatography–mass spectrometry (LC–MS) technologies. The separation and identification of the compounds were completed by: (i) a water–acetonitrile gradient system using a C18 reversed‐phase column; (ii) UV detection at 225 nm; (iii) MS/MS experiments with electrospray ionization interface (ESI) ion trap mass spectrometry in the positive mode. Normalized collision energy was used to obtain fragment ions of structural relevance in the LC–MS/MS. These results provided a reliable LC–MS/MS method for the determination of the dibenzo[a,c]cyclooctadiene lignans from Schisandra chinensis Baill. Finally, we also detected 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) scavenging effects (%) of the modified‐ultrasonic and supercritical fluid extracts of Schisandra chinensis Baill compared with 6‐hydroxy‐2,5,7,8‐tetramethylchroman‐2‐carboxylic acid (Trolox). The antioxidant activities of the modified‐ultrasonic and supercritical fluid extracts were lower than that of trolox.
Comparison of supercritical fluid and Soxhlet extractions for the isolation of nitro compounds from soils
Authors: Bajerová Petra , Eisner Aleš , Ježová Věra , Adam Martin , Ventura Karel
Published: April 2008

Supercritical fluid extraction (SFE) with CO2, a clean and rapid alternative to conventional Soxhlet extraction, was investigated for the extraction of nitro compounds from soil samples. Quantitative extraction by SFE was accomplished at a pressure of 25 MPa and an extraction temperature of 60°C, for 30 min in dynamic mode and using acetonitrile as modifier, and the results were comparable with those obtained by acetonitrile Soxhlet extraction (3 h) for all soil samples. Extracts from these two procedures were analyzed by gas chromatography coupled with mass spectrometry. Quantitative reproducibility for SFE extracts was acceptable (RSD 2–10%), and the quantity of solvent was reduced from 160 mL for Soxhlet extraction to 5 mL in the case of SFE.
Effect of Vulcanization Ingredients on the Intercalation‐Exfoliation Process of Layered Silicate in an Acrylonitrile Butadiene Rubber Matrix
Authors: Das Amit , Jurk René , Stöckelhuber Klaus Werner , Heinrich Gert
Published: April 2008

The effect of both sulfur and peroxide curing on the intercalation and exfoliation process of layered silicate was studied to find a suitable vulcanization package for acrylonitrile butadiene rubber. X‐ray diffraction and transmission electron microscopy studies showed that proper selection of a curing package could lead the layered silicates to have excellent dispersion in intercalated form. The curing characteristics, physical properties, dynamic mechanical properties, and thermogravimetric analysis of layered silicate‐acrylonitrile butadiene rubber nanocomposites were explored. Finally, the effect of different types of zinc accelerators in sulfur vulcanization process was investigated on the intercalation‐exfoliation process of the layered silicates.

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A Versatile Method for Adjusting Thermoresponsivity: Synthesis and ‘Click’ Reaction of an Azido End‐Functionalized Poly(N‐isopropylacrylamide)
Authors: Narumi Atsushi , Fuchise Keita , Kakuchi Ryohei , Toda Atsushi , Satoh Toshifumi , Kawaguchi Seigou , Sugiyama Kenji , Hirao Akira , Kakuchi Toyoji
Published: April 2008

The 2‐chloropropionamide derivative featuring an azido group is used as the initiator for the ATRP of N‐isopropylacrylamide (NIPAM) with copper(I) chloride (CuCl) and tris[2‐(dimethylamino)ethyl]amine (Me6TREN) to produce the PNIPAM end‐functionalized with an azido group. Subsequently, the ‘click’ reaction between the azido end‐group and acetylene derivatives is demonstrated to produce PNIPAM in which the end‐groups are modified by the phenyl, 4‐phenoxyphenyl, butyl, octyl, carboxylic acid, and hydroxymethyl groups. The resulting PNIPAM derivatives show a LCST that ranges from 34.8 to 44.6 °C depending on the introduced end‐group.

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Bovine endometrial legumain and TIMP‐2 regulation in response to presence of a conceptus
Authors: Ledgard A.M. , Lee R.S.‐F. , Peterson A.J.
Published: April 2008

The precise mechanism of placentation in the bovine species where a restricted trophoblast invasion occurs to form the synepitheliochorial placenta is not fully understood. This study initially investigated the conceptus–maternal interactions in the peri‐attachment period by comparing the proteins present at Days 16 and 18 in uterine luminal fluid (ULF) of pregnant with nonpregnant cows using 2‐D gel electrophoresis. Nine protein spots were identified that were present in greater amounts in pregnant compared to nonpregnant ULF: carbonic anhydrase, ezrin, heat shock protein 70, isocitrate dehydrogenase, nucleoside diphosphate kinase, peroxiredoxin 1, purine nucleoside phosphorylase, thioredoxin and triosephosphate isomerase and four proteins that were less abundant in ULF from the gravid compared to the nongravid horns or nonpregnant uteri: cystatin E/M, legumain, retinol‐binding protein (RBP) and tissue inhibitor of matrix metalloproteinase 2 (TIMP‐2). Successful placentation requires the remodelling of the endometrial surface therefore uterine mRNA and protein expression of legumain, a protease activator, and TIMP‐2, a protease inhibitor, was examined in detail during the oestrous cycle and from Days 13 to 31 of pregnancy. Both mRNAs were up‐regulated in the endometrium during the luteal phase of the oestrous cycle and during early pregnancy. Although legumain and TIMP‐2 mRNA expression levels were similar between uterine horns at the same day of pregnancy, the amount of protein differed between gravid and nongravid horns possibly modulated by interferon‐tau or by other factors produced by the conceptus. These events at the conceptus–maternal interface may provide localised control of protease activity necessary for controlling trophoblast invasion of the endometrium. Mol. Reprod. Dev. 76: 65–74, 2009. © 2008 Wiley‐Liss, Inc.
High frequency of copy‐neutral LOH in MUTYH‐associated polyposis carcinomas
Authors: Middeldorp A , van Puijenbroek M , Nielsen M , Corver WE , Jordanova ES , ter Haar N , Tops CMJ , Vasen HFA , Lips EH , van Eijk R , Hes FJ , Oosting J , Wijnen J , van Wezel T , Morreau H
Published: April 2008

Genetic instability is known to drive colorectal carcinogenesis. Generally, a distinction is made between two types of genetic instability: chromosomal instability (CIN) and microsatellite instability (MIN or MSI). Most CIN tumours are aneuploid, whereas MSI tumours are considered near‐diploid. However, for MUTYH‐associated polyposis (MAP) the genetic instability involved in the carcinogenesis remains unclear, as near‐diploid adenomas, aneuploid adenomas and near‐diploid carcinomas have been reported. Remarkably, our analysis of 26 MAP carcinomas, using SNP arrays and flow sorting, showed that these tumours are often near‐diploid (52%) and mainly contain chromosomal regions of copy‐neutral loss of heterozygosity (LOH) (71%). This is in contrast to sporadic colon cancer, where physical loss is the main characteristic. The percentage of chromosomal gains (24%) is comparable to sporadic colorectal cancers with CIN. Furthermore, we verified our scoring of copy‐neutral LOH versus physical loss in MAP carcinomas by two methods: fluorescence in situ hybridization, and LOH analysis using polymorphic markers on carcinoma fractions purified by flow sorting. The results presented in this study suggest that copy‐neutral LOH is an important mechanism in the tumorigenesis of MAP. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Psychosocial risk factors of pain among employees
Authors: Saastamoinen Peppiina , Laaksonen Mikko , Leino‐Arjas Päivi , Lahelma Eero
Published: April 2008

The study of psychosocial risk factors of pain among employees has typically focused on Karasek's job‐demand‐control model. The aim of the study was to examine the own and independent associations of job strain, organizational justice, workplace bullying, and work–home interface with pain.

Data were collected through a postal survey to all 40, 45, 50, 55, and 60‐year‐old employees of the City of Helsinki in 2001 and 2002 (response rate 66%, N=5819, 80% women). Pain was measured with a three category outcome: no pain, acute pain or chronic pain. Adjustment was made for age, education, physical working conditions, BMI, smoking, and alcohol consumption.

Among women, all psychosocial variables were associated with both acute and chronic pain when adjusted for confounders only. When psychosocial factors were additionally adjusted for each other, high job strain and both dimensions of work–home interface remained associated with both types of pain and repeatedly occurring bullying at workplace showed association with acute pain. Among men, when adjusted for confounders only, all psychosocial variables were associated with acute and chronic pain, except for family‐to‐work conflicts among those with acute pain. When adjusted mutually for all psychosocial variables, only bullying was associated with acute pain. Job strain and organizational justice showed associations with chronic pain.

Future studies would benefit from a broad psychosocial framework. Investments to healthier psychosocial working environments are needed to tackle pain related problems among employees.
Can rate of recovery be predicted in patients with acute low back pain? Development of a clinical prediction rule
Authors: Hancock Mark J. , Maher Christopher G. , Latimer Jane , Herbert Rob D. , McAuley James H.
Published: April 2008

Some patients with low back pain recover quickly while others continue to experience pain beyond 3 months. The primary aim of this study was to develop a simple prediction rule to help clinicians identify patients with acute low back pain likely to recover at different rates. The secondary aim was to compare a clinician's prognosis judgement to the prediction rule. The study sample included 239 patients with acute low back pain who participated in a randomised controlled trial. The primary outcome was days to recovery from pain. Potential prognostic factors were initially tested for univariate association with recovery using Cox regression (p<0.1). Continuous prognostic factors with a significant association were dichotomised using a median split. Significantly associated prognostic factors were then included in a multivariate forward stepwise Cox regression. We then separated participants into strata according to the number of predictors in the final model for which they were positive. Our results suggest that a clinical prediction rule using three simple prognostic factors was able to differentiate between patients who recover quickly and those who recover slowly. Patients with lower than average initial pain intensity, shorter duration of symptoms and fewer previous episodes recovered more quickly (HR=3.5, 95% CI, 1.8–7.0) than patients without these characteristics. Therapists were able to predict patients likely to recover at different rates, (HR=1.6, 95% CI, 1.2–2.1), however, they did not perform as well as the clinical prediction rule. The rule requires validation in a different sample of patients.
Down‐regulation of Notch‐dependent transcription by Akt in vitro
Authors: Song Jieun , Park Sungwoo , Kim Minsoon , Shin Incheol
Published: April 2008

The effect of Akt on Notch intracellular domain (NICD)‐mediated transcription was investigated. Transfection experiments revealed that constitutively active Akt down‐regulates NICD‐dependent transcription. Kinase inactive dominant negative Akt did not affect NICD transcriptional activity, indicating that Akt kinase activity is responsible for the down‐regulation. Studies using histone deacetylase (HDAC) and silencing mediator of retinoid and thyroid hormone receptor (SMRT) revealed that modulation of NICD transcriptional activity is not mediated by an HDAC‐dependent mechanism or recruitment of the co‐repressor SMRT. Akt inhibited proper nuclear localization of NICD, and phosphorylated NICD both in vitro and caused its hyperphosphorylation in vivo. These results may suggest possible regulation of NICD transcriptional activity by Akt‐mediated phosphorylation and subsequent inhibition of proper nuclear localization of NICD.
Directional sensing during chemotaxis
Authors: Janetopoulos Christopher , Firtel Richard A.
Published: April 2008

Cells have the innate ability to sense and move towards a variety of chemoattractants. We investigate the pathways by which cells sense and respond to chemoattractant gradients. We focus on the model system Dictyostelium and compare our understanding of chemotaxis in this system with recent advances made using neutrophils and other mammalian cell types, which share many molecular components and signaling pathways with Dictyostelium. This review also examines models that have been proposed to explain how cells are able to respond to small differences in ligand concentrations between the anterior leading edge and posterior of the cell. In addition, we highlight the overlapping functions of many signaling components in diverse processes beyond chemotaxis, including random cell motility and cell division.