bluuebunny/crossref_metadata_2025 huggingface dataset:
Could Ca2+ sensitizers rescue patients from chronic congestive heart failure?
Authors: Endoh M
Published: February 2007

Attempts to ameliorate cardiac contractile dysfunction by Ca2+ mobilizers, such as catecholamines, phosphodiesterase (PDE) inhibitors and digitalis, play an important role in pharmacotherapy for congestive heart failure (CHF), but these agents possess disadvantages in causing Ca2+ overload resulting in arrhythmogenicity and damage to cardiomyocytes. Ca2+ sensitizers that act directly on contractile proteins are free from the risk of Ca2+ overload and they could improve haemodynamic parameters with minimum increase in energy expenditure even under pathological conditions, including acidosis and stunned myocardium. Beneficial effects of levosimendan (that acts by combination of Ca2+ sensitization and PDE inhibition) on CHF due to hypertensive cardiomyopathy in Dahl/Rapp rats as reported in this issue demonstrate the potential of oral levosimendan in long‐term treatment of chronic CHF. Since chronic CHF in clinical settings is much more complex, careful analysis of clinical outcomes will be required to establish the therapeutic relevance of Ca2+ sensitizers in the treatment of chronic CHF.

British Journal of Pharmacology (2007) 150, 826–828. doi:10.1038/sj.bjp.0707163
Anti‐rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen‐induced arthritis in rodents
Authors: Lin H‐S , Hu C‐Y , Chan H‐Y , Liew Y‐Y , Huang H‐P , Lepescheux L , Bastianelli E , Baron R , Rawadi G , Clément‐Lacroix P
Published: February 2007

Background and purpose:

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Histone deacetylase inhibitors (HDACi), a new class of anti‐cancer agents, have recently been reported to exhibit potent anti‐inflammatory activities. A proof of concept study was carried out with suberoylanilide hydroxamic acid (SAHA) and MS‐275, two HDACi currently undergoing clinical investigations for various oncological indications.

Experimental approach:

The anti‐rheumatic effects of SAHA and MS‐275 were assessed in both mouse and rat collagen induced arthritis (CIA) models.

Key results:

SAHA exhibited moderate prophylactic efficacy. It attenuated paw swelling due to inflammation, decreased bone erosion in both mice and rats and reduced slightly the RA‐induced bone resorption in rats. However, SAHA could not inhibit the onset of arthritis. In contrast, MS‐275 displayed dramatic anti‐rheumatic activities. In prophylactic intervention, high doses of MS‐275 prevented bone erosion and markedly delayed the onset of arthritis; at low doses, MS‐275 strongly attenuated paw swelling, bone erosion, and bone resorption associated with RA. Furthermore, the therapeutic efficacy of MS‐275 was also documented. After the onset of arthritis, it could stop the disease progression and joint destruction. An anti inflammatory effect of MS‐275 was also confirmed through its capacity to decrease serum IL‐6 and IL‐1β levels in the CIA induced mouse model. The anti‐rheumatic activity of MS‐275 was also confirmed through histological observation. No synovial hyperplasia, pannus formation, cartilage or bone destruction were observed in the high dose prophylactic intervention in mice.

Conclusion and implication:

This study strongly supported HDACi as an innovative therapeutic strategy for RA.

British Journal of Pharmacology (2007) 150, 862–872. doi:10.1038/sj.bjp.0707165
HDAC inhibitors as anti‐inflammatory agents
Authors: Adcock I M
Published: February 2007

Diverse cellular functions including the regulation of inflammatory gene expression, DNA repair and cell proliferation are regulated by changes in the acetylation status of histones and non‐histone proteins. Many human diseases, particularly cancer, have been associated with altered patterns of histone acetylation. Furthermore, abnormal expression and activation of histone acetyltransferases, which act as transcriptional co‐activators, has been reported in inflammatory diseases. Histone deacetylase (HDAC) inhibitors have been developed clinically for malignancies due to their effects on apoptosis. More recently, in vitro and in vivo data indicates that HDAC inhibitors may be anti‐inflammatory due to their effects on cell death acting through acetylation of non‐histone proteins. Although there are concerns over the long‐term safety of these agents, they may prove useful particularly in situations where current anti‐inflammatory therapies are suboptimal.

British Journal of Pharmacology (2007) 150, 829–831. doi:10.1038/sj.bjp.0707166
FTY720 suppresses interleukin‐1β‐induced secretory phospholipase A2 expression in renal mesangial cells by a transcriptional mechanism
Authors: Xin C , Ren S , Eberhardt W , Pfeilschifter J , Huwiler A
Published: February 2007

Background and purpose:

FTY720 is a potent immunomodulatory prodrug that is converted to its active phosphorylated form by a sphingosine kinase. Here we have studied whether FTY720 mimicked the action of sphingosine‐1‐phosphate (S1P) and exerted an anti‐inflammatory potential in renal mesangial cells.

Experimental approach:

Prostaglandin E2 (PGE2) was quantified by an enzyme‐linked immunosorbent‐assay. Secretory phospholipase A2 (sPLA2) protein was detected by Western blot analyses. mRNA expression was determined by Northern blot analysis and sPLA2‐promoter activity was measured by a luciferase‐reporter‐gene assay.

Key results:

Stimulation of cells for 24 h with interleukin‐1β (IL‐1β) is known to trigger increased PGE2 formation which coincides with an induction of the mRNA for group‐IIA‐sPLA2 and protein expression. FTY720 dose‐dependently suppressed IL‐1β‐induced IIA‐sPLA2 protein secretion and activity in the supernatant. This effect is due to a suppression of cytokine‐induced sPLA2 mRNA expression which results from a reduced promoter activity. As a consequence of suppressed sPLA2 activity, PGE2 formation is also reduced by FTY720. Mechanistically, the FTY720‐suppressed sPLA2 expression results from an activation of the TGFβ/Smad signalling cascade since inhibition of the TGFβ receptor type I by a specific kinase inhibitor reverses the FTY720‐mediated decrease of sPLA2 protein expression and sPLA2 promoter activity.

Conclusions and implications:

In summary, our data show that FTY720 was able to mimic the anti‐inflammatory activity of TGFβ and blocked cytokine‐triggered sPLA2 expression and subsequent PGE2 formation. Thus, FTY720 may exert additional in vivo effects besides the well reported immunomodulation and its anti‐inflammatory potential should be considered.

British Journal of Pharmacology (2007) 150, 943–950. doi:10.1038/sj.bjp.0707171
The ‘specific’ tyrosine kinase inhibitor genistein inhibits the enzymic hydrolysis of anandamide: implications for anandamide uptake
Authors: Thors L , Alajakku K , Fowler C J
Published: February 2007

Background and Purpose:

The cellular uptake of anandamide is reduced by inhibitors of fatty acid amide hydrolase (FAAH) and by agents disrupting endocytotic mechanisms. However, it is not clear if these events occur over the same time frame and if they occur to the same extent in different cells. We have therefore investigated the effects of such compounds in three cell lines of different origins using different assay incubation times and temperatures.

Experimental approach:

FAAH activity and cellular uptake of anandamide was measured using anandamide, radio‐labelled either in the ethanolamine or arachidonoyl part of the molecule.

Key results:

The FAAH inhibitor URB597 inhibited the uptake of anandamide into C6 glioma, RBL2H3 basophilic leukaemia cells and P19 embryonic carcinoma cells at incubation time 4 min. However, a time‐dependent and temperature‐sensitive residual uptake remained after URB597 treatment. The combination of progesterone and nystatin reduced the uptake, but also decreased the amount of anandamide retained by the wells. Genistein inhibited anandamide uptake in a manner that was not additive to that of URB597. However, genistein was a potent competitive inhibitor of FAAH (Kivalue 8 μM).

Conclusions and implications:

The reduction of anandamide uptake by genistein can be explained by its ability to inhibit FAAH with a potency which overlaps that for inhibition of tyrosine kinase. The FAAH‐ resistant but time‐dependent uptake of anandamide is seen in all three cell lines studied and is thus presumably a generally occurring process.

British Journal of Pharmacology(2007)150,951–960. doi:10.1038/sj.bjp.0707172
New potent and selective cytochrome P450 2B6 (CYP2B6) inhibitors based on three‐dimensional quantitative structure‐activity relationship (3D‐QSAR) analysis
Authors: Korhonen L E , Turpeinen M , Rahnasto M , Wittekindt C , Poso A , Pelkonen O , Raunio H , Juvonen R O
Published: February 2007

Background and purpose:

The cytochrome P450 2B6 (CYP2B6) enzyme metabolises a number of clinically important drugs. Drug‐drug interactions resulting from inhibition or induction of CYP2B6 activity may cause serious adverse effects. The aims of this study were to construct a three‐dimensional structure‐activity relationship (3D‐QSAR) model of the CYP2B6 protein and to identify novel potent and selective inhibitors of CYP2B6 forin vitroresearch purposes.

Experimental approach:

The inhibition potencies (IC50values) of structurally diverse chemicals were determined with recombinant human CYP2B6 enzyme. Two successive models were constructed using Comparative Molecular Field Analysis (CoMFA).

Key results:

Three compounds proved to be very potent and selective competitive inhibitors of CYP2B6in vitro(IC50<1μM): 4‐(4‐chlorobenzyl)pyridine (CBP), 4‐(4‐nitrobenzyl)pyridine (NBP), and 4‐benzylpyridine (BP). A complete inhibition of CYP2B6 activity was achieved with 0.1μM CBP, whereas other CYP‐related activities were not affected. Forty‐one compounds were selected for further testing and construction of the final CoMFA model. The created CoMFA model was of high quality and predicted accurately the inhibition potency of a test set (n=7) of structurally diverse compounds.

Conclusions and implications:

Two CoMFA models were created which revealed the key molecular characteristics of inhibitors of the CYP2B6 enzyme. The final model accurately predicted the inhibitory potencies of several structurally unrelated compounds. CBP, BP and NBP were identified as novel potent and selective inhibitors of CYP2B6 and CBP especially is a suitable inhibitor forin vitroscreening studies.

British Journal of Pharmacology(2007)150,932–942. doi:10.1038/sj.bjp.0707173
5‐HT4receptor agonists increase sAPPα levels in the cortex and hippocampus of male C57BL/6j mice
Authors: Cachard‐Chastel M , Lezoualc'h F , Dewachter I , Deloménie C , Croes S , Devijver H , Langlois M , Van Leuven F , Sicsic S , Gardier A M
Published: February 2007

Background and purpose:

A strategy to treat Alzheimer's disease (AD) is to increase the soluble form of amyloid precursor protein (sAPPα), a promnesic protein, in the brain. Because strong evidence supports beneficial effects of 5‐hydroxytryptamine 5‐HT4receptor agonists in memory and learning, we investigated the role of 5‐HT4receptors on APP processing in 8 weeks‐old male C57BL/6j mice.

Experimental approach:

Mice were given, subcutaneously, prucalopride or ML 10302 (s.c.), two highly selective 5‐HT4receptor agonists and, up to 240 min later, the hippocampus and cortex were analysed by Western blot for sAPPα determination.

Key results:

Prucalopride (5 or 10 mg kg‐1) significantly increased sAPPαlevels in the hippocampus and cortex, but did not modify the expression level of APP mRNA as detected by quantitative RT‐PCR. A selective 5‐HT4receptor antagonist, GR125487 (1 mg kg‐1, s.c.) inhibited prucalopride induced‐ increase in sAPPα levels. In addition, levels of sAPPα were increased by ML10302 only at 20 mg kg‐1and was limited to the cortex. Also, prucalopride increased sAPPα levels in the cortex of a transgenic mouse model of AD, expressing the London mutation of APP. Furthermore, the combined injection of a selective acetylcholinesterase inhibitor, donepezil and prucalopride induced a synergic increase in sAPPα levels in the cortex and hippocampus.

Conclusions and implications:

Our results demonstrate that the 5‐HT4receptor plays a key role in the non‐amyloidogenic pathway of APP metabolismin vivoand give support to the beneficial use of 5‐HT4agonists for AD treatment.

British Journal of Pharmacology(2007)150,883–892. doi:10.1038/sj.bjp.0707178
Explicit symplectic integrators of molecular dynamics algorithms for rigid-body molecules in the canonical, isobaric-isothermal, and related ensembles
Authors: Okumura Hisashi , Itoh Satoru G. , Okamoto Yuko
Published: February 2007

The authors propose explicit symplectic integrators of molecular dynamics (MD) algorithms for rigid-body molecules in the canonical and isobaric-isothermal ensembles. They also present a symplectic algorithm in the constant normal pressure and lateral surface area ensemble and that combined with the Parrinello-Rahman algorithm. Employing the symplectic integrators for MD algorithms, there is a conserved quantity which is close to Hamiltonian. Therefore, they can perform a MD simulation more stably than by conventional nonsymplectic algorithms. They applied this algorithm to a TIP3P pure water system at 300K and compared the time evolution of the Hamiltonian with those by the nonsymplectic algorithms. They found that the Hamiltonian was conserved well by the symplectic algorithm even for a time step of 4fs. This time step is longer than typical values of 0.5–2fs which are used by the conventional nonsymplectic algorithms.
Pulsed time-of-flight radar for fiber-optic strain sensing
Authors: Lyöri Veijo , Kilpelä Ari , Duan Guoyong , Mäntyniemi Antti , Kostamovaara Juha
Published: February 2007

This article describes a fiber-optic interrogation device based on the pulsed time-of-flight technique. The apparatus is capable of measuring time delays between wideband reflectors, such as connectors, along a fiber path with a precision of about 280fs (rms value) and a spatial resolution of about 3ns (0.30m) in a measurement time of 25ms. Potential application areas include measuring integral strain and its derivatives such as cracks, deflections, and displacements, particularly in large civil engineering and composite structures. The operation and basic blocks of the measurement system are presented in detail together with measurement results obtained in laboratory and field conditions. It is shown that by using a fiber loop sensor with a reference fiber, it is possible to achieve a strain precision below 1μstrain and a measurement frequency of 4Hz. System performance proved adequate for the study of both static and dynamic phenomena in a bridge deck.
The role of point defects in the physical properties of nonstoichiometric ceria
Authors: Duncan Keith L. , Wang Yanli , Bishop Sean R. , Ebrahimi Fereshteh , Wachsman Eric D.
Published: February 2007

Explicit, analytical expressions have been derived for the dependence of electrical conductivity, chemical expansion, and elastic modulus on point defect concentration and oxygen partial pressure using a consistent approach. In developing the model, expressions were first derived for the functional dependence of defect concentration on the oxygen partial pressure for fluorite oxides. Expressions for the chemical expansion, elastic modulus, and electrical conductivity as functions of defect concentration are then derived and verified with experimental data for ceria (CeO2−δ) with consistently good fits. The same values for the material constants were used in all of the fits, further validating our approach.
Cubic InN growth on sapphire (0001) using cubic indium oxide as buffer layer
Authors: Lozano J. G. , Morales F. M. , García R. , González D. , Lebedev V. , Wang Ch. Y. , Cimalla V. , Ambacher O.
Published: February 2007

Cubic InN layers were grown by molecular beam epitaxy on buffer layers of indium oxide prepared onto sapphire (0001) substrates. The structure was analyzed by means of electron diffraction and transmission electron microscopy. The intermediate indium oxide layer presents a body centered cubic (bcc) structure, with bcc-In2O3(001)‖Al2O3(0001) plane relationship. Thereupon, a zinc-blende phase of InN (001) was grown with a reticular misfit of 1.6% and a significant reduction of mismatch-related defects. This good coherence offers a promising expectation to obtain high quality cubic InN layers superior to other highly mismatched cubic substrates used previously.
Room temperature negative differential resistance of CdF2∕CaF2 double-barrier resonant tunneling diode structures grown on Si(100) substrates
Authors: Kanazawa Tohru , Fujii Ryo , Wada Takafumi , Suzuki Yusuke , Watanabe Masahiro , Asada Masahiro
Published: February 2007

The authors have demonstrated the crystal growth of CaF2∕CdF2∕CaF2 multilayered heterostructures on Si(100) substrates as double-barrier resonant tunneling diode structures by a low-temperature growth technique. Current-voltage characteristics were investigated and the authors observed negative differential resistance (NDR) characteristics at room temperature. The peak-to-valley current ratio was 2–8, and 13 at maximum, and peak current density was 80–90A∕cm2. The quantum-well layer thickness dependence of NDR peak voltages is also discussed on the basis of qualitative analytical model using the Esaki-Tsu formula.
Collective spin modes in monodimensional magnonic crystals consisting of dipolarly coupled nanowires
Authors: Gubbiotti G. , Tacchi S. , Carlotti G. , Singh N. , Goolaup S. , Adeyeye A. O. , Kostylev M.
Published: February 2007

Magnetization dynamics of dipolarly coupled nanowire arrays has been studied by Brillouin light scattering. Measurements performed in uniformly magnetized wires as a function of the transferred wave vector demonstrated the existence of several discrete collective modes, propagating through the structure with a periodic dispersion curve encompassing several Brillouin zones relative to the artificial spatial periodicity. This experimental evidence has been quantitatively explained by a theoretical model which permits the calculation of the dispersion relation for collective modes in patterned arrays through the numerical solution of an eigenvalue problem for an integral operator.
Growth competition during glancing angle deposition of nanorod honeycomb arrays
Authors: Zhou C. M. , Gall D.
Published: February 2007

Arrays of Ta nanorods were grown by glancing angle deposition (GLAD) onto honeycomb Cr nanodot patterns that were evaporated onto Si substrates through a self-assembled monolayer of SiO2 nanospheres. Statistical size analyses from arrays of rods with variable average length l and width w, with 210nm⩽l⩽650nm and 109nm⩽w⩽304nm, show that the distribution in w broadens with increasing l and decreasing w, but remains approximately constant with a fixed l∕w ratio. This is attributed to an intercolumnar growth competition that exacerbates nanorod size fluctuations but scales with rod size. These results suggest that the overall nanostructure shapes during low-temperature GLAD are independent of material-specific length scales and are, therefore, completely controlled by the geometric shadowing.
Drosera × sidjamesii (Droseraceae): systematics and ecology of a natural hybrid from Western Australia
Authors: Lowrie Allen , Conran John G.
Published: February 2007

The natural hybrid Drosera × sidjamesii Lowrie & Conran from Lake Gnangarra north of Perth, Western Australia is described and defined as a cross between D. nitidula Planch. subsp. omissa Marchant & Lowrie auct. non Diels and D. pulchella Lehm., between which it shows a high degree of intermediacy for almost all characters. Cytological examination of the hybrid and its parents confirms that the former at 2n = 46 is a combination of the 2n = 28 in D. nitidula subsp. omissa and 2n = 18 in D. pulchella. The hybrid grows along a narrow ecotone between the parental species, largely on sandy peat and along a presumed soil moisture/elevation gradient caused by the nearby lake. Nevertheless, within this ecotone the hybrid is significantly more frequent than either parental species, with D. pulchella mainly growing in peat soils closer to the lake and D. nitidula subsp. omissa on white sand further from the water. Field observations of morphotypes also suggest that the hybrid has arisen several times at the site, and that a limited number of plants at the site are becoming fertile and setting seed.
Molecular taxonomic clarification of Ptilotus exaltatus and Ptilotus nobilis (Amaranthaceae)
Authors: Lee Kok K. , Harrison Dion K. , Johnston Margaret E. , Williams Richard R.
Published: February 2007

A complete botanical key for the genus Ptilotus R.Brown (family Amarathaceae) has not yet been published. Identifying the 100 or more Ptilotus species using morphological characters has been difficult because plants often exhibit slight morphological differences and intermediate characteristics common to several species, subspecies, varieties and forms. Ptilotus exaltatus Nees and P. nobilis (Lindl) F.Muell share many morphological characteristics, but are classified as different species predominantly based on inflorescence colour. The current study involved a molecular phylogenetic analysis of 14 Ptilotus species using sequence data from the internal transcribed spacer (ITS) regions ITS 1 and ITS 2 within the 18S–26S nuclear rDNA. Of the 39 accessions analysed, all except those identified as P. exaltatus and P. nobilis clustered according to their respective species based on their morphological taxonomy. In contrast, all 18 P. exaltatus and P. nobilis accessions formed a distinct monophyletic clade with 99% bootstrap values and a low level of sequence variation (GD = 0.002). Taking into account the lack of reliable morphological characters for separating P. exaltatus and P. nobilis, together with the ITS sequence data showing little genetic divergence or genetic structure, we propose that P. exaltatus and P. nobilis are conspecific.
A new system for determining which plant species are indigenous in Australia
Authors: Bean Anthony R.
Published: February 2007

An examination of Floras and related literature from various countries of the world has revealed a wide range of interpretations and concepts for indigenous plants. Nevertheless, an indigenous plant species has been universally defined as one that was not deliberately or accidentally introduced by man. An important recent addendum to the ‘indigenous’ definition is that it must disperse from an area where it is considered native. Particularly problematic are the so-called ‘pantropical’ or ‘cosmopolitan’ plants. These species are usually invasive and abundant, but most could not have crossed major barriers without the assistance of humans, and hence should be regarded as non-native species throughout much of their range. The accurate assessment of the alien or indigenous status of these and other taxa has been hampered by a lack of knowledge about their geographic origins and dispersal ability. Australian botanists have frequently adhered to a concept of indigenous plants being any that were thought to be present before European settlement in their region of interest – 1788 for the Sydney area, and as late as the 1850s for northern Australia. This definition is unrealistic and unworkable, especially when considering the ‘pantropical’ species. The transport of plants by maritime traders and explorers into the Indonesian and west Pacific areas has occurred for at least the past 3000 years. European colonisation in those areas from the 16th century accelerated plant introductions. Some of those plant species undoubtedly made their way to Australia before European settlement. This paper presents explicit definitions for indigenous (native) or alien (exotic, introduced, non-indigenous) plant species in Australia. A system of assessment using a combination of ecological, phytogeographical and historical criteria (the EPH system) allows the determination of ‘origin status’ for individual species. As a case study, data are presented for 40 plant species of disputed origin status. These species are assessed against the criteria, and a recommended origin status given for Australian occurrences.
Rising HIV notifications in Australia: accounting for the increase in people living with HIV and implications for the HIV transmission rate
Authors: Ginige Samitha , Chen Marcus Y. , Hocking Jane S. , Grulich Andrew E. , Fairley Christopher K.
Published: February 2007

Background: To describe the changes in notification rates for HIV, as a proportion of people living with HIV infection, in Australia. Methods: Notification data on HIV and AIDS-related deaths published by the National Centre in HIV Epidemiology and Clinical Research were obtained and analysed for the period of 1988–2004. Results: The annual HIV notification rate per 100 people living with HIV fell significantly between 1988 and 1999 for all HIV cases and for men who have sex with men (MSM) specifically (P < 0.01). However, although there was an increase in HIV notifications between 2000 and 2004 (P = 0.01 for all HIV cases and P = 0.06 for MSM), the notification rate per 100 people living with HIV remained relatively stable (P = 0.6 for all HIV cases and P = 0.4 for MSM). Conclusions: These data suggest that despite significant rises in notifications for HIV, the effective reproductive rate for HIV has remained relatively stable since 1999.
Sex, love and gender norms: sexual life and experience of a group of young people in Ho Chi Minh City, Vietnam
Authors: Nguyen Hoa Ngan , Liamputtong Pranee
Published: February 2007

This paper discusses the impacts of gender norms on the sexual life and experience of a group of young Vietnamese people. It is based on a qualitative study on sexuality and abortion among young people in Ho Chi Minh City, Vietnam. There were two general attitudes towards premarital sex. One view supported young people in a serious, loving relationship engaging in sex before marriage; the other opposed premarital sex because it affected the reputation of girls and their families. These general attitudes were similar to the views on virginity: one group believed strongly in girls maintaining their virginity and the other group emphasised love, emotion and trust, not virginity, as the most important criteria for marriage. Among women there were more supporters than opponents of the traditional view of premarital sex and virginity. Premarital sex was more acceptable for young people in a serious, loving relationship with certain commitment to marriage. Young men considered sex a way to express their love and to become more intimate. Women’s view was that premarital sex only occurred within a serious, loving relationship or when there was a serious commitment to marriage. It is clear that young people’s sexual life is shaped and constrained by gender norms through political interventions, sexual education and moral judgements. Under the pressure of these norms, young people face many difficulties in order to fulfill a safe and satisfying sexual life.
Psychosocial factors influencing the disclosure of sexually transmissible infection diagnoses among female adolescents
Authors: Cunningham Shayna D. , Meyers Todd , Kerrigan Deanna , Ellen Jonathan M.
Published: February 2007

Background: Individuals diagnosed with a sexually transmissible infection (STI) often face psychosocial concerns through which they must navigate to arrive at disclosure decisions. The objective of this study was to qualitatively explore the decision-making process for disclosure of STI diagnoses to sex partners among adolescent females in Baltimore City, MD. Methods: Semi-structured interviews were conducted with 21 African American adolescent females who tested positive for chlamydia and/or gonorrhoea in the previous 3 months. Three individuals also provided audio diaries in which they tape recorded a daily journal discussing their lives and experiences with STIs. Results: Female adolescents often do not notify all potentially infected sex partners or tell sex partners all of the STIs to which they may have been exposed. Although participants recognised the importance of informing their sex partner(s) of their STI diagnosis, there were other competing psychosocial factors that influenced their decisions to disclose, such as perceptions of the social consequences of having an STI including fear of stigmatisation and loss of relationship. Such concerns appear to vary by disease and partner type as well as previous STI experience. Conclusions: To increase disclosure of STI diagnoses, clinic counselling strategies to encourage partner notification should seek to engage patients in a dialogue regarding their fears related to their diagnoses, how this might affect their relationships with different types of partners and the individual and social meanings their specific STI diagnosis(es) might hold.
The sources of treatment of sexually transmissible infections in a rural community in central Thailand
Authors: Prempree Preecha , Detels Roger , Ungkasrithongkul Mongkol , Meksawasdichai Sittichai , Panthong Samreng , Ungpanich Varaporn
Published: February 2007

Background: Sexually transmissible infection (STI) rates in Thailand declined from 1986 to 1994, but levelled off until 2002. This study documents the distribution of STI cases attending major treatment venues and the quality of treatment in a rural area. Methods: A cross sectional study was conducted in January and June 2001 in all 42 health-care facilities in the study district, including the hospital STI and outpatient clinics, private clinics, local health centres and pharmacies. Quality of care was assessed by documenting appropriate syndromic treatment according to the World Health Organization Syndromic Case Management Guidelines. Results: Over half of STI patients (60%) sought treatment from pharmacies (35%) and health centres (25%), the facilities least capable of accurately diagnosing and treating STI. Only 0–59% were adequately treated. Conclusions: The quality of services needs to be improved and innovative strategies developed and implemented to address the problems of acceptability, stigmatisation, access and quality of STI services in Thailand.
Sexual health of homeless youth: prevalence and correlates of sexually transmissible infections
Authors: Tyler Kimberly A. , Whitbeck Les B. , Chen Xiaojin , Johnson Kurt
Published: February 2007

Background: The study examined risk factors for having ever contracted sexually transmissible infections (STI) among a high-risk sample in midwestern USA. Methods: A cross sectional survey was conducted among 428 homeless youth aged 16–19 years. Assessed correlates included child maltreatment, street exposure, sexual histories, street experiences and substance use. Results: Multivariate analyses revealed that males were 86% less likely to have had STI compared with females (adjusted odds ratio [AOR] = 0.14; 95% confidence interval [CI] = 0.06–0.31). Blacks were almost four times more likely (AOR = 3.71; 95% CI = 1.80–7.63) and other races were over two times more likely (AOR = 2.25; 95% CI = 1.08–4.67) to have had STI compared with whites. For every one unit increase in the number of times youth ran away, there was a 3% increase in the likelihood of ever having had an STI (AOR = 1.03; 95% CI = 1.01–1.06). For every one unit increase in frequency of condom use there was a 61% decrease in the likelihood of an STI (AOR = 1.39; 95% CI = 1.10–1.76). Finally, youth who traded sex were approximately 2.5 times more likely to have had STI compared with youth who did not trade sex (AOR = 2.36; 95% CI = 1.04–5.34). None of the remaining correlates approached multivariate significance. Conclusions: The amount of time youth spend on the street, their sexual practices, and their subsistence strategies are important correlates of STI and females and non-whites are particularly vulnerable among this high-risk population.
Correlates of intent to be vaccinated against human papillomavirus: an exploratory study of college-aged women
Authors: Crosby Richard , Schoenberg Nancy , Hopenhayn Claudia , Moore Greg , Melhan William
Published: February 2007

This study identified correlates of human papillomavirus (HPV) vaccine acceptance among college-aged women. Data were collected by self-administered questionnaire. In multivariate analyses, women having vaginal sex (past 12 months) were nearly four times more likely to indicate acceptance (P = 0.0001). Those reporting ever having a sexually transmissible infection (STI; P = 0.03) and those indicating ever having an abnormal Pap test (P = 0.03) were more likely to indicate acceptance. Thus, three forms of ‘exposure’ (having sex, having an STI or abnormal Pap) may be linked to vaccine acceptance among young women attending universities. The findings suggest that opportunities may exist for clinic-based HPV vaccine promotion among this population of women.
The presentation of anogenital cancers as sexually transmissible infection: a case for vigilance
Authors: Markos A. R.
Published: February 2007

The recent outbreaks of sexually transmissible infections (STI) provoke professional concern and public anxiety. There is sporadically published literature reporting cases of vulval, penile and anal cancers presenting at genitourinary medicine clinics. The recent referral of a series of cases, by medical practitioners, as anogenital warts, which were later diagnosed as vulval, penile and anal cancers, is alarming. The cases reflect the current state of apprehension between patients and medical professionals regarding STI.
Linking pattern formation to cell-type specification: Dichaete and Ind directly repress
achaete
gene expression in the
Drosophila
CNS
Authors: Zhao Guoyan , Boekhoff-Falk Grace , Wilson Beth A. , Skeath James B.
Published: February 2007

Mechanisms regulating CNS pattern formation and neural precursor formation are remarkably conserved between
Drosophila
and vertebrates. However, to date, few direct connections have been made between genes that pattern the early CNS and those that trigger neural precursor formation. Here, we use
Drosophila
to link directly the function of two evolutionarily conserved regulators of CNS pattern along the dorsoventral axis, the homeodomain protein Ind and the Sox-domain protein Dichaete, to the spatial regulation of the proneural gene
achaete
(
ac
) in the embryonic CNS. We identify a minimal
achaete
regulatory region that recapitulates half of the wild-type
ac
expression pattern in the CNS and find multiple putative Dichaete-, Ind-, and Vnd-binding sites within this region. Consensus Dichaete sites are often found adjacent to those for Vnd and Ind, suggesting that Dichaete associates with Ind or Vnd on target promoters. Consistent with this finding, we observe that Dichaete can physically interact with Ind and Vnd. Finally, we demonstrate the
in vivo
requirement of adjacent Dichaete and Ind sites in the repression of
ac
gene expression in the CNS. Our data identify a direct link between the molecules that pattern the CNS and those that specify distinct cell-types.
PPARγ1 attenuates cytosol to membrane translocation of PKCα to desensitize monocytes/macrophages
Authors: von Knethen Andreas , Soller Mathias , Tzieply Nico , Weigert Andreas , Johann Axel M. , Jennewein Carla , Köhl Roman , Brüne Bernhard
Published: February 2007

Recently, we provided evidence that PKCα depletion in monocytes/macrophages contributes to cellular desensitization during sepsis. We demonstrate that peroxisome proliferator–activated receptor γ (PPARγ) agonists dose dependently block PKCα depletion in response to the diacylglycerol homologue PMA in RAW 264.7 and human monocyte–derived macrophages. In these cells, we observed PPARγ-dependent inhibition of nuclear factor-κB (NF-κB) activation and TNF-α expression in response to PMA. Elucidating the underlying mechanism, we found PPARγ1 expression not only in the nucleus but also in the cytoplasm. Activation of PPARγ1 wild type, but not an agonist-binding mutant of PPARγ1, attenuated PMA-mediated PKCα cytosol to membrane translocation. Coimmunoprecipitation assays pointed to a protein–protein interaction of PKCα and PPARγ1, which was further substantiated using a mammalian two-hybrid system. Applying PPARγ1 mutation and deletion constructs, we identified the hinge helix 1 domain of PPARγ1 that is responsible for PKCα binding. Therefore, we conclude that PPARγ1-dependent inhibition of PKCα translocation implies a new model of macrophage desensitization.
Translation attenuation by PERK balances ER glycoprotein synthesis with lipid-linked oligosaccharide flux
Authors: Shang Jie , Gao Ningguo , Kaufman Randal J. , Ron David , Harding Heather P. , Lehrman Mark A.
Published: February 2007

Endoplasmic reticulum (ER) homeostasis requires transfer and subsequent processing of the glycan Glc3Man9GlcNAc2 (G3M9Gn2) from the lipid-linked oligosaccharide (LLO) glucose3mannose9N-acetylglucosamine2-P-P-dolichol (G3M9Gn2-P-P-Dol) to asparaginyl residues of nascent glycoprotein precursor polypeptides. However, it is unclear how the ER is protected against dysfunction from abnormal accumulation of LLO intermediates and aberrant N-glycosylation, as occurs in certain metabolic diseases. In metazoans phosphorylation of eukaryotic initiation factor 2α (eIF2α) on Ser51 by PERK (PKR-like ER kinase), which is activated by ER stress, attenuates translation initiation. We use brief glucose deprivation to simulate LLO biosynthesis disorders, and show that attenuation of polypeptide synthesis by PERK promotes extension of LLO intermediates to G3M9Gn2-P-P-Dol under these substrate-limiting conditions, as well as counteract abnormal N-glycosylation. This simple mechanism requires eIF2α Ser51 phosphorylation by PERK, and is mimicked by agents that stimulate cytoplasmic stress-responsive Ser51 kinase activity. Thus, by sensing ER stress from defective glycosylation, PERK can restore ER homeostasis by balancing polypeptide synthesis with flux through the LLO pathway.
Critical role of the extracellular signal–regulated kinase–MAPK pathway in osteoblast differentiation and skeletal development
Authors: Ge Chunxi , Xiao Guozhi , Jiang Di , Franceschi Renny T.
Published: February 2007

The extracellular signal–regulated kinase (ERK)–mitogen-activated protein kinase (MAPK) pathway provides a major link between the cell surface and nucleus to control proliferation and differentiation. However, its in vivo role in skeletal development is unknown. A transgenic approach was used to establish a role for this pathway in bone. MAPK stimulation achieved by selective expression of constitutively active MAPK/ERK1 (MEK-SP) in osteoblasts accelerated in vitro differentiation of calvarial cells, as well as in vivo bone development, whereas dominant-negative MEK1 was inhibitory. The involvement of the RUNX2 transcription factor in this response was established in two ways: (a) RUNX2 phosphorylation and transcriptional activity were elevated in calvarial osteoblasts from TgMek-sp mice and reduced in cells from TgMek-dn mice, and (b) crossing TgMek-sp mice with Runx2+/− animals partially rescued the hypomorphic clavicles and undemineralized calvaria associated with Runx2 haploinsufficiency, whereas TgMek-dn; Runx2+/− mice had a more severe skeletal phenotype. This work establishes an important in vivo function for the ERK–MAPK pathway in bone that involves stimulation of RUNX2 phosphorylation and transcriptional activity.
Membrane chaperone Shr3 assists in folding amino acid permeases preventing precocious ERAD
Authors: Kota Jhansi , Gilstring C. Fredrik , Ljungdahl Per O.
Published: February 2007

The yeast endoplasmic reticulum (ER) membrane-localized chaperone Shr3 plays a critical role in enabling amino acid permeases (AAPs) to fold and attain proper structures required for functional expression at the plasma membrane. In the absence of Shr3, AAPs specifically accumulate in the ER, where despite the correct insertion of their 12 transmembrane segments (TMSs), they aggregate forming large molecular weight complexes. We show that Shr3 prevents aggregation and facilitates the functional assembly of independently coexpressed N- and C-terminal fragments of the general AAP Gap1. Shr3 interacts with and maintains the first five TMSs in a conformation that can posttranslationally assemble with the remaining seven TMSs. We also show that Doa10- and Hrd1-dependent ER-associated degradation (ERAD) pathways redundantly degrade AAP aggregates. In combination, doa10Δ hrd1Δ mutations stabilize AAP aggregates and partially suppress amino acid uptake defects of shr3 mutants. Consequently, in cells with impaired ERAD, AAPs are able to attain functional conformations independent of Shr3. These findings illustrate that folding and degradation are tightly coupled processes during membrane protein biogenesis.
Notch signaling is necessary for epithelial growth arrest by TGF-β
Authors: Niimi Hideki , Pardali Katerina , Vanlandewijck Michael , Heldin Carl-Henrik , Moustakas Aristidis
Published: February 2007

Transforming growth factor β (TGF-β) and Notch act as tumor suppressors by inhibiting epithelial cell proliferation. TGF-β additionally promotes tumor invasiveness and metastasis, whereas Notch supports oncogenic growth. We demonstrate that TGF-β and ectopic Notch1 receptor cooperatively arrest epithelial growth, whereas endogenous Notch signaling was found to be required for TGF-β to elicit cytostasis. Transcriptomic analysis after blocking endogenous Notch signaling uncovered several genes, including Notch pathway components and cell cycle and apoptosis factors, whose regulation by TGF-β requires an active Notch pathway. A prominent gene coregulated by the two pathways is the cell cycle inhibitor p21. Both transcriptional induction of the Notch ligand Jagged1 by TGF-β and endogenous levels of the Notch effector CSL contribute to p21 induction and epithelial cytostasis. Cooperative inhibition of cell proliferation by TGF-β and Notch is lost in human mammary cells in which the p21 gene has been knocked out. We establish an intimate involvement of Notch signaling in the epithelial cytostatic response to TGF-β.
Human embryonic stem cells for brain repair?
Authors: Zhang Su-Chun , Li Xue-Jun , Austin Johnson M , Pankratz Matthew T
Published: February 2007

Cell therapy has been perceived as the main or ultimate goal of human embryonic stem (ES) cell research. Where are we now and how are we going to get there? There has been rapid success in devising
in vitro
protocols for differentiating human ES cells to neuroepithelial cells. Progress has also been made to guide these neural precursors further to more specialized neural cells such as spinal motor neurons and dopamine-producing neurons. However, some of the
in vitro
produced neuronal types such as dopamine neurons do not possess all the phenotypes of their
in vivo
counterparts, which may contribute to the limited success of these cells in repairing injured or diseased brain and spinal cord in animal models. Hence, efficient generation of neural subtypes with correct phenotypes remains a challenge, although major hurdles still lie ahead in applying the human ES cell-derived neural cells clinically. We propose that careful studies on neural differentiation from human ES cells may provide more immediate answers to clinically relevant problems, such as drug discovery, mechanisms of disease and stimulation of endogenous stem cells.
Brain micro-ecologies: neural stem cell niches in the adult mammalian brain
Authors: Riquelme Patricio A , Drapeau Elodie , Doetsch Fiona
Published: February 2007

Neurogenesis persists in two germinal regions in the adult mammalian brain, the subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal formation. Within these two neurogenic niches, specialized astrocytes are neural stem cells, capable of self-renewing and generating neurons and glia. Cues within the niche, from cell–cell interactions to diffusible factors, are spatially and temporally coordinated to regulate proliferation and neurogenesis, ultimately affecting stem cell fate choices. Here, we review the components of adult neural stem cell niches and how they act to regulate neurogenesis in these regions.
Molecular epidemiological analysis of Japanese encephalitis virus in China
Authors: Wang Huan Yu , Takasaki Tomohiko , Fu Shi Hong , Sun Xiao Hong , Zhang Hai Lin , Wang Zhao Xiao , Hao Zong Yu , Zhang Jia Ke , Tang Qing , Kotaki Akira , Tajima Shigeru , Liang Xiao Feng , Yang Wei Zhong , Kurane Ichiro , Liang Guo Dong
Published: February 2007

Sixty-two new Japanese encephalitis virus (JEV) isolates were obtained from mosquitoes, biting midges, human cerebrospinal fluid and human blood samples in China during 2002–2005. The E and prM genes were sequenced and phylogenetic analyses were performed with 38 JEV other isolates from China and 36 JEV strains from other countries. Phylogenetic trees based on the E and prM gene sequences were similar. The results indicate that: (i) recent JEV isolates from China are divided into two genotypes, genotype 1 and genotype 3; (ii) recent JEV isolates from China are grouped into the same clusters within genotypes 1 and 3; and (iii) genotype 1 JEV strains have been isolated in China since 1979, whilst genotype 3 JEV strains were isolated before the 1970s. The results suggest that genotype 1 JEV was introduced to China around 1979 and that JEV strains belonging to genotypes 1 and 3 circulate in China.
Intracellular localization and effects of individually expressed human parechovirus 1 non-structural proteins
Authors: Krogerus Camilla , Samuilova Olga , Pöyry Tuija , Jokitalo Eija , Hyypiä Timo
Published: February 2007

Human parechovirus 1 (HPEV-1) has many unique features compared with other picornaviruses and it has been shown that the replication complex formed during HPEV-1 infection is different from that of other picornaviruses. Here, the intracellular localization and functional effects of individually expressed HPEV-1 non-structural proteins were studied. The 2A and 3D proteins were found diffusely in the cytoplasm and nucleus of the cell. The 3A and 3AB proteins were observed to co-localize with the markers for the Golgi apparatus, whereas 2B co-localized with markers for the endoplasmic reticulum and the 2C and 2BC proteins were observed mainly on the surface of lipid droplets. The 2C protein, which has been implicated in replication-complex formation in enterovirus-infected cells, was not able to induce vesicles similar to those seen in HPEV-1-infected cells when expressed individually. However, in superinfected cells, the fusion protein was able to relocate to the virus replication complexes. Similar to other picornaviruses, HPEV-1 was found to interfere with cellular secretion, but this function could not be ascribed to any of the individually expressed non-structural proteins.