bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential expression of p63 isoforms in normal skin and hyperproliferative conditions
Authors: Kim So‐Young , Cho Hyun‐Joo , Kim Dong‐Seok , Choi Hae‐Ryung , Kwon Sun‐Bang , Na Jung‐Im , Jeon Hye‐Chan , Huh Chang‐Hoon , Youn Sang‐Woong , Cho Kwang‐Hyun , Park Kyoung‐Chan
Published: June 2009

Background:  The p63 is regarded as a potential stem cell marker.

Methods:  Expression of p63 isoforms was examined in normal skin and hyperproliferative conditions including psoriasis and artificial skin equivalents (SEs). Rapidly adhering (RA) and slowly adhering (SA) cells were isolated, and Western blotting was performed.

Results:  Expression of p63 (4A4) and p63 (H‐137) is similar in all conditions, although there is some variation in psoriasis. However, expression of p63α (C‐12) is markedly different. In normal skin, p63α (C‐12)‐positive cells were scattered in whole epidermis. But in psoriasis, p63α (C‐12)‐positive cells were observed at the tips of rete ridges. In SEs, p63α (C‐12)‐positive cells were not well observed. Western blot results showed that the RA cells express p63 (4A4) and p63 (H‐137) strongly compared with SA or nonadhering (NA) cells. In contrast, SA or NA cells strongly express p63α (C‐12).

Conclusions:  Results suggest that both p63 (4A4) and p63 (H‐137) can detect epidermal stem cells. But, p63 (H‐137) seemed to be a better marker because p63 (H‐137)‐positive cells were more localized at basal layer. In addition, it can be said that p63α (C‐12) can detect TAp63, which is important in differentiation of epidermis. Furthermore, it is concluded that molecular control of TAp63 is especially disorganized in hyperproliferative condition including psoriasis and SEs.
Fulminant and accelerated presentation of dermatomyositis in two previously healthy young adult males: a potential role for endotheliotropic viral infection
Authors: Magro Cynthia M. , Iwenofu Obiajulu H. , Kearns Mary J. , Nuovo Gerard J. , Dyrsen Molly E. , Segal Jeremy P.
Published: June 2009

Background:  Dermatomyositis (DM) is a prototypic autoimmune syndrome, whereby immune‐based microvascular injury is critical in the pathogenesis of skin lesions and the myopathy. Although not widely recognized or accepted as a pathogenetic trigger, endotheliotropic viral triggers including parvovirus B19 and cytomegalovirus have been linked to DM. At times, the clinical manifestations in DM can be fulminant with acute renal failure because of rhabdomyolysis, respiratory failure and gastrointestinal infarcts.

Methods:  Skin and lung tissues were processed for hematoxylin and eosin, immunohistochemical, immunofluorescent and reverse transcriptase in situ polymerase chain reaction studies.

Case presentation:  We present two cases of fatal DM in previously healthy immunocompetent males. One case had fatal catastrophic respiratory failure from diffuse alveolar damage; herpes simplex virus‐2 RNA was uncovered in lung and skin biopsies during autopsy in the absence of classic cytopathic changes of herpes virus infection. The other case showed a Degos‐like syndrome; parvovirus B19 RNA transcripts were found in cutaneous endothelium of affected skin.

Conclusion:  An accelerated clinical course can occur in the setting of DM in previously healthy patients. A viral‐based etiology should be explored because antiviral therapy may define a critical and potentially lifesaving therapeutic endeavor.
Microbial community analysis of rectal methanogens and sulfate reducing bacteria in two non‐human primate species
Authors: Nakamura Noriko , Leigh Steven R. , Mackie Roderick I. , Gaskins HR
Published: June 2009

Background  Methanogenesis by methanogenic Archaea and sulfate reduction by sulfate reducing bacteria (SRB) are the major hydrogenotrophic pathways in the human colon. Methanogenic status of mammals is suggested to be under evolutionary rather than dietary control. However, information is lacking regarding the dynamics of hydrogenotrophic microbial communities among different primate species.

Methods  Rectal swabs were collected from 10 sooty mangabeys (Cercocebus atys) and 10 baboons (Papio hamadryas). The diversity and abundance of methanogens and SRB were examined using PCR‐denaturing gradient gel electrophoresis (DGGE) and real‐time quantitative PCR (qPCR).

Results  The DGGE results revealed that intestinal Archaea and SRB communities differ between mangabeys and baboons. Phylogenetic analyses of Archaea DGGE bands revealed two distinct clusters with one representing a putative novel order of methanogenic Archaea. The qPCR detected a similar abundance of methanogens and SRB.

Conclusions  Intestinal Archaea and SRB coexist in these primates, and the community patterns are host species‐specific.
Melatonin improves cardiovascular function and ameliorates renal, cardiac and cerebral damage in rats with renovascular hypertension
Authors: Erşahin Mehmet , Şehirli Özer , Toklu Hale Z. , Süleymanoglu Selami , Emekli‐Alturfan Ebru , Yarat Ayşen , Tatlıdede Elif , Yeğen Berrak Ç. , Şener Göksel
Published: June 2009

Abstract: The effect of melatonin was investigated in an angiotensin II‐dependent renovascular hypertension model in Wistar albino rats by placing a renal artery clip (two‐kidney, one‐clip; 2K1C), while sham rats did not have clip placement. Starting either on the operation day or 3 wk after the operation, the rats received melatonin (10 mg/kg/day) or vehicle for the following 6 wk. At the end of the nineth week, after blood pressure (BP) and echocardiographic recordings were obtained, plasma samples were obtained to assay lactate dehydrogenase (LDH), creatine kinase (CK), antioxidant capacity (AOC), asymmetric dimethylarginine (ADMA), and nitric oxide (NOx) levels. In the kidney, heart and brain tissues, malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) and Na+‐K+ATPase activities were determined. 2K1C caused an increase in BP and left ventricular (LV) dysfunction. In hypertensive animals LDH, CK, ADMA levels were increased in plasma with a concomitant reduction in AOC and NOx. Moreover, hypertension caused a significant decrease in tissue SOD, CAT, and Na+, K+‐ATPase activities and glutathione content, while MDA levels and MPO activity were increased in all studied tissues. On the other hand, both melatonin regimens significantly reduced BP, alleviated oxidative injury and improved LV function. In conclusion, melatonin protected against renovascular hypertension‐induced tissue damage and improved cardiac function presumably due to both its direct antioxidant and receptor‐dependent actions, suggesting that melatonin may be of therapeutic use in preventing oxidative stress due to hypertension.
Endosomal Fusion upon SNARE Knockdown is Maintained by Residual SNARE Activity and Enhanced Docking
Authors: Bethani Ioanna , Werner Achim , Kadian Chandini , Geumann Ulf , Jahn Reinhard , Rizzoli Silvio O.
Published: June 2009

SNARE proteins mediate membrane fusion in the secretory pathway of eukaryotic cells. Genetic deletion and siRNA‐based knockdown have been instrumental in assigning given SNAREs to defined intracellular transport steps. However, SNARE depletion occasionally results in barely detectable phenotypes. To understand how cells cope with SNARE loss, we have knocked down several SNAREs functioning in early endosome fusion. Surprisingly, knockdown of syntaxin 13, syntaxin 6 and vti1a, alone or in combinations, did not result in measurable changes of endosomal trafficking or fusion. We found that the residual SNARE levels (typically ∼10%) were sufficient for a substantial amount of SNARE–SNARE interactions. Conversely, in wild‐type cells, most SNARE molecules were concentrated in clusters, constituting a spare pool not readily available for interactions. Additionally, the knockdown organelles exhibited enhanced docking. We conclude that SNAREs are expressed at much higher levels than needed for maintenance of organelle fusion, and that loss of SNAREs is compensated for by the co‐regulation of the docking machinery.
Understory vegetation response to thinning disturbance of varying complexity in coniferous stands
Authors: Ares Adrian , Berryman Shanti D. , Puettmann Klaus J.
Published: June 2009

Question: Can augmented forest stand complexity increase understory vegetation richness and cover and accelerate the development of late‐successional features? Does within‐stand understory vegetation variability increase after imposing treatments that increase stand structural complexity of the overstory? What is the relative contribution of individual stand structural components (i.e. forest matrix, gaps, and leave island reserves) to changes in understory vegetation richness?

Location: Seven study sites in the Coastal Range and Cascades regions of Oregon, USA.

Methods: We examined the effects of thinning six years after harvest on understory plant vascular richness and cover in 40‐ to 60‐year‐old forest stands dominated by Douglas‐fir (Pseudotsuga menziesii). At each site, one unthinned control was preserved and three thinning treatments were implemented: low complexity (LC, 300 trees ha−1), moderate complexity (MC, 200 trees ha−1), and high complexity (HC, variable densities from 100 to 300 trees ha−1). Gaps openings and leave island reserves were established in MC and HC.

Results: Richness of all herbs, forest herbs, early seral herbs and shrubs, and introduced species increased in all thinning treatments, although early seral herbs and introduced species remained a small component. Only cover of early seral herbs and shrubs increased in all thinning treatments whereas forest shrub cover increased in MC and HC. In the understory, we found 284 vascular plant species. After accounting for site‐level differences, the richness of understory communities in thinned stands differed from those in control stands. Within‐treatment variability of herb and shrub richness was reduced by thinning. Matrix areas and gap openings in thinned treatments appeared to contribute to the recruitment of early seral herbs and shrubs.

Conclusions: Understory vegetation richness increased 6 years after imposing treatments, with increasing stand complexity mainly because of the recruitment of early seral and forest herbs, and both low and tall shrubs. Changes in stand density did not likely lead to competitive species exclusion. The abundance of potentially invasive introduced species was much lower compared to other plant groups. Post‐thinning reductions in within‐treatment variability was caused by greater abundance of early seral herbs and shrubs in thinned stands compared with the control. Gaps and low‐density forest matrix areas created as part of spatially variably thinning had greater overall species richness. Increased overstory variability encouraged development of multiple layers of understory vegetation.
Species constancy depends on plot size – a problem for vegetation classification and how it can be solved
Authors: Dengler Jürgen , Löbel Swantje , Dolnik Christian
Published: June 2009

Question: While it is well known that species richness depends on plot size, it is not generally recognised that the same must be true for constancy. Accordingly, many authors use varying plot sizes when classifying vegetation based on the comparison of constancies between groups of plots. We ask whether the constancy‐area relationship follows a general rule, how strong the effect of plot sizes is on constancies, and if it is possible to correct constancies for area.

Location: For empirical evaluation, we use data from plant communities in the Czech Republic, Sweden and Russia.

Methods: To assess the potential influence of differences in plot size on constancies, we develop a mathematical model. Then, we use series of nested plot species richness data from a wide range of community types (herbaceous and forest) to determine the parameters of the derived function and to test how much the shape of the constancy‐area relationship depends on taxa or vegetation types.

Results: Generally, the constancy‐area relationship can be described by C (A)=1−(1−C0)(A/A0)^d, with C being constancy, A area, C0 known constancy on a specific area A0, and d a damping parameter accounting for spatial autocorrelation. As predicted by this function, constancies in plant communities always varied from values near 0% to near 100% if plot sizes were changed sufficiently. For the studied vegetation types, a two‐ to fourfold increase in plot size resulted in a change of conventional constancy classes, i.e. an increase of constancy by 20% or more.

Conclusions: Vegetation classification, which largely relies on constancy values, irrespective of whether traditional or modern fidelity definitions are used, is strongly prone to distorting scale effects when relevés of different plot sizes are combined in studies. The constancy‐area functions presented allow an approximate transformation of constancies to other plot sizes but are flawed by idiosyncrasies in taxa and vegetation types. Thus, we conclude that the best solution for future surveys is to apply uniform plot sizes within a few a priori delimited formations and to determine diagnostic species only within these formations. Finally, we suggest that more detailed analyses of constancy‐area relationships can contribute to a better understanding of species‐area relationships because the latter are the summation of the first for all species.
Trends in NHS primary dental care for older people in England: implications for the future
Authors: Kleinman Eleanor R. , Harper Paul R. , Gallagher Jennifer E.
Published: June 2009

Objective:  To examine trends over time in the National Health Service (NHS) dental service provision for older people in England and consider the implications for future care.

Background:  The number and proportion of older people in the population nationally are increasing and their oral health needs are changing as more people retain teeth into older age.

Materials and methods:  Descriptive analysis of routinely collected activity data for primary dental care in England was undertaken over the 6‐year period, 1999/2000–2004/05. Data were cleaned, grouped into age bands for analysis. Activity rates per head of population were calculated for key aspects of care. Population forecasts and national survey data were used to inform future predictions of care required.

Results:  There was an increase in absolute terms of total items (14.4%) and items per capita (10.7%) between 1999/2000 and 2004/05, with a peak of 15.7 million items claimed in 2003/04. Over the 6‐year period, increases per capita were seen for dental examinations (11.3%), periodontal treatments (8.9%), fillings (1.9%), crowns (14.3%) and extractions (4.9%) amongst older people as a group. In contrast, there was a marked decrease in the episodes of care involving domiciliary care (−46.4%) and upper complete dentures (−32.9%) per capita over this period, items that were most commonly provided for the oldest age‐band (85 years and over). Apart from complete dentures, the demand for care is predicted to increase.

Conclusion:  The volume of primary dental care provided for older people has been increasing at a rate which exceeds population growth, but remains low. Planners and commissioners should urgently review the provision of dental care of older people to ensure that their oral health needs are being met particularly in relation to dentures and domiciliary care.
Non‐surgical treatment of gingival overgrowth induced by nifedipine: a case report on an elderly patient
Authors: De Carvalho Farias Bruna , Cabral Paula Aguiar , Gusmão Estela Santos , Jamelli Sílvia Regina , Cimões Renata
Published: June 2009

doi:10.1111/j.1741‐2358.2009.00273.x
 
Non‐surgical treatment of gingival overgrowth induced by nifedipine: a case report on an elderly patient

Drug‐induced gingival overgrowth (DIGO) is a significant problem for periodontologists and this side effect is frequently associated with three particular drugs: phenytoin, cyclosporin A and nifedipine. A case report of gingival overgrowth induced by nifedipine in an elderly patient treated with non‐surgical periodontal therapy is described. A 75‐year‐old male with generalised gingival overgrowth reported the problem of oral malodour and significant gingival bleeding. The medical history revealed a controlled hypertensive state and Cerebral Vascular Accident (CVA) 3 years prior to consultation. The diagnosis was gingival overgrowth associated with nifedipine, no other risk factors being identified. The patient had been taking nifedipine for 18 months, but after the consultation with the patient’s doctor, nifedipine was suspended, as the hypertension was controlled. Treatment consisted of meticulous oral hygiene instruction, scaling, root surface instrumentation and prophylaxis. Six months after the first intervention, clinical parameters revealed a significant improvement with a considerable reduction in gingival overgrowth, demonstrating the effect of non‐surgical periodontal therapy in severe cases of gingival overgrowth. Non‐surgical treatment of DIGO is a far less invasive technique than surgical approaches and has demonstrated an impressively positive treatment response. It should therefore be considered as a first treatment option for DIGO.
Undergraduate teaching in gerodontology in Leipzig and Zürich – a comparison of different approaches
Authors: Nitschke Ina , Reiber Thomas , Sobotta Bernhard A.J.
Published: June 2009

Objective:  To evaluate undergraduate students’ attitude towards the clinical components of the Leipzig (LPEG) and Zürich (ZPEG) Programmes of Education in Gerodontology.

Background:  Undergraduate student education is the seedbed for conscientious professionals. Extramural clinical education contributes to the formation of positive attitudes. Students in Zürich participate in three clinical activities (in‐house gerodontology clinic, extramural acute geriatrics ward, mobile dental service), in Leipzig they visit a long‐term care facility on six occasions within 4 years.

Methods:  A structured questionnaire with 10 items was administered to students in Leipzig [n = 34, 70.6% female, mean age 25.8 (SD 3.04) years] at the beginning and after completion of gerodontology training and to students in Zürich [n = 33, 48.5% female, mean age 27.0 (SD 3.28) years] on three occasions after clinical training. Students indicated the degree of their agreement with seven statements presented using a 5‐point scale. A choice of responses which characterised the course was offered for assessment.

Results:  Close collaboration with dental tutors, while self‐treating patients in the mobile dental service (mobiDent™) attracted the most positive responses. Ratings from students completing their training in Leipzig were less favourable than their initial responses.

Conclusion:  The lack of a dental service and Leipzig students’ inability to offer treatment in the presence of disease was associated with frustrations. Practical training should go beyond dental examinations at a long‐term care facility and include the opportunity for dental treatment. Personnel and equipment required for mobile treatment exceed resources available at most German dental schools.
Oral health care in long‐term care facilities for elderly people in southern Brazil: a conceptual framework
Authors: Mello Ana Lúcia Schaefer Ferreira de , Erdmann Alacoque Lorenzini , Brondani Mario
Published: June 2009

doi:10.1111/j.1741‐2358.2009.00280.x
 
Oral health care in long‐term care facilities for elderly people in southern Brazil: a conceptual framework

Objective:  To present a theoretical model for understanding oral health care for the elderly in the context of long‐term care institutions (LTCI).

Methods:  Open‐ended individual interviews were conducted with the elderly residing in LTCI, their carers, nursing technicians and nurses, directors of care, dental surgeons and managers of public health services. A grounded theory methodological approach was adopted for data collection and analysis.

Results:  The emerging core category revealed a basic social process: ‘Promoting oral health care for the elderly based on the context of LTCI’. This process was composed of two contradicting yet correlated aspects: the oral health care does not minimise the poor oral epidemiological condition, and at the same time, there was a continued improvement in the oral care expressed by better care practices. These aspects were related to the: attribution of meaning to oral health, social determination of oral health, the ageing process, interactions established in the oral health care practices, oral health care management in LTCI, inclusion of oral health care into the political–organisational dimension and possibility of conjecturing better oral health care practices.

Conclusion:  The core concept of ‘Promotion of oral health care for elderly people based on the context of LTCI’ is capable of explaining the variations in the structure and process of LTCI, as well as in helping to understand the meaning of the oral health care practices for the institutionalised elderly.
Colonisation of soft lining materials by micro‐organisms
Authors: Pavan Sabrina , Dos Santos Paulo Henrique , Filho João Neudenir Arioli , Spolidorio Denise Madalena Palomare
Published: June 2009

doi:10.1111/j.1741‐2358.2009.00300.x
 
Colonisation of soft lining materials by micro‐organisms

Objective:  This study evaluated the in vitro adherence of pathogenic micro‐organisms, Candida albicans, Staphylococcus aureus and Pseudomonas aeruginosa, to soft lining materials and their inhibitory effect on these micro‐organisms.

Materials and Methods:  To measure adherence, specimens of Molloplast B and Ufi Gel P were inoculated [107 colony‐forming units per millimetre (cfu/ml)] with TSB media containing the micro‐organisms. To determine the number of micro‐organisms in the 10−2–10−5 dilutions, 25 μl of the suspension were transferred to plates of selective media. Colony counts of each specimen were quantified (cfu/ml). The surface roughness was measured with a perfilometer to assess the relationship between the adherence of micro‐organisms and surface roughness of each material. For the inhibition test, specimens of materials were placed in agar plates inoculated individually with the micro‐organisms. After 48 h, the inhibition zones around the specimens were measured.

Results:  None of the materials exhibited inhibition zones. The number of cfu/ml of S. aureus and P. aeruginosa were significantly greater than C. albicans for both materials. The Ufi Gel P exhibited greater adherence of C. albicans than Molloplast B. No correlation was observed between the adherence of micro‐organisms and surface roughness.

Conclusion:  The surface roughness of the materials is not the only factor governing micro‐organism adherence.
Longitudinal Associations Between Maternal Work Stress, Negative Work‐Family Spillover, and Depressive Symptoms
Authors: Goodman W. Benjamin , Crouter Ann C. ,   The Family Life Project Key Investigators
Published: June 2009

The current study examined associations over an 18‐month period between maternal work stressors, negative work‐family spillover, and depressive symptoms in a sample of 414 employed mothers with young children living in six predominantly nonmetropolitan counties in the Eastern United States. Results from a one‐group mediation model showed that a less flexible work environment and greater work pressure predicted higher levels of depressive symptoms and, further, that these associations were mediated by perceptions of negative work‐family spillover. Additionally, results from a two‐group mediation model suggested that work pressure predicted greater perceptions of spillover only for mothers employed full‐time. Findings suggest the need for policies that reduce levels of work stress and help mothers manage their work and family responsibilities.
Relationship Quality and Changes in Depressive Symptoms Among Urban, Married African Americans, Hispanics, and Whites
Authors: Fagan Jay
Published: June 2009

Bivariate analyses showed that continuously married urban African American, non‐Hispanic White, and Hispanic fathers and mothers reporting greater marital support and less relational control experienced a decrease in depressive symptoms. Multiple regression showed a stronger association between concurrent marital support and decreased depressive symptoms for mothers than fathers. African American and Hispanic fathers reporting higher levels of spousal relationship support when children were infants reported a larger decrease in depressive symptoms when children were age 3 compared to non‐Hispanic Whites. Relationship control at age 3 was positively related to increased depressive symptoms among all groups except African American fathers and White mothers. African American and Hispanic fathers with marital problems may need additional support services.
A Mediation Model of Interparental Collaboration, Parenting Practices, and Child Externalizing Behavior in a Clinical Sample
Authors: Kjøbli John , Hagen Kristine Amlund
Published: June 2009

The present study examined maternal and paternal parenting practices as mediators of the link between interparental collaboration and children's externalizing behavior. Parent gender was tested as a moderator of the associations. A clinical sample consisting of 136 children with externalizing problems and their families participated in the study. Structural equation modeling was used to test the study hypotheses. Maternal and paternal parenting practices fully mediated the relation between interparental collaboration and externalizing behavior. When the mediated pathways were tested separately, paternal parenting practices functioned as a mediator, whereas maternal parenting practices did not, indicating that the relationship between interparental collaboration, parenting practices and externalizing behavior was moderated by parent gender. The findings suggest that treatments aimed at reducing child externalizing behavior may be strengthened by focusing on interparental collaboration in addition to parenting practices, while also underscoring the need to involve fathers in interventions.
Dyadic Parenting and Children's Externalizing Symptoms
Authors: Meteyer Karen B. , Perry‐Jenkins Maureen
Published: June 2009

We explore dyadic parenting styles and their association with first‐grade children's externalizing behavior symptoms in a sample of 85 working‐class, dual‐earner families. Cluster analysis is used to create a typology of parenting types, reflecting the parental warmth, overreactivity, and laxness of both mothers and fathers in two‐parent families. Three distinct groups emerged: Supportive Parents, Mixed‐Support Parents, and Unsupportive Parents. Results indicate that dyadic parenting styles were related to teacher‐reported externalizing symptoms for boys but not for girls.
Serine hydroxymethyltransferase from Plasmodium vivax is different in substrate specificity from its homologues
Authors: Sopitthummakhun Kittipat , Maenpuen Somchart , Yuthavong Yongyuth , Leartsakulpanich Ubolsree , Chaiyen Pimchai
Published: June 2009

The putative gene of Plasmodium vivax serine hydroxymethyltransferase (PvSHMT; EC 2.1.2.1) was cloned and expressed in Escherichia coli. The purified enzyme was shown to be a dimeric protein with a monomeric molecular mass of 49 kDa. PvSHMT has a maximum absorption peak at 422 nm with a molar absorption coefficient of 6370 m−1·cm−1. The Kd for binding of the enzyme and pyridoxal‐5‐phosphate was 0.14 ± 0.01 μm. An alternative assay for measuring the tetrahydrofolate‐dependent SHMT activity based on the coupled reaction with 5,10‐methylenetetrahydrofolate reductase (EC 1.5.1.20) from E. coli was developed. PvSHMT uses a ternary‐complex mechanism with a kcat value of 0.98 ± 0.06 s−1 and Km values of 0.18 ± 0.03 and 0.14 ± 0.02  mm for l‐serine and tetrahydrofolate, respectively. The optimum pH of the SHMT reaction was 8.0 and an Arrhenius’s plot showed a transition temperature of 19 °C. Besides l‐serine, PvSHMT forms an external aldimine complex with d‐serine, l‐alanine, l‐threonine and glycine. PvSHMT also catalyzes the tetrahydrofolate‐independent retro‐aldol cleavage of 3‐hydroxy amino acids. Although l‐serine is a physiological substrate for SHMT in the tetrahydrofolate‐dependent reaction, PvSHMT can also use d‐serine. In the absence of tetrahydrofolate at high pH, PvSHMT forms an enzyme–quinonoid complex with d‐serine, but not with l‐serine, whereas SHMT from rabbit liver was reported to form an enzyme–quinonoid complex with l‐serine. The substrate specificity difference between PvSHMT and the mammalian enzyme indicates the dissimilarity between their active sites, which could be exploited for the development of specific inhibitors against PvSHMT.
The novel molecule 2‐[5‐(2‐chloroethyl)‐2‐acetoxy‐benzyl]‐4‐(2‐chloroethyl)‐phenyl acetate inhibits phosphoinositide 3‐kinase/Akt/mammalian target of rapamycin signalling through JNK activation in cancer cells
Authors: Ho Ka‐Kei , Rosivatz Evelyn , Gunn Richard M. , Smith Mark E. B. , Stavropoulou Alexandra V. , Rosivatz Erika , Numbere Macba G. , Wong John B. , Lafitte Valerie G. H. , Behrendt Jonathan M. , Myatt Stephen S. , Hailes Helen C. , Woscholski Rüdiger , Lam Eric W.‐F.
Published: June 2009

Screening a compound library of compound 48/80 analogues, we identified 2‐[5‐(2‐chloroethyl)‐2‐acetoxy‐benzyl]‐4‐(2‐chloroethyl)‐phenyl acetate (E1) as a novel inhibitor of the phosphoinositide 3‐kinase/Akt pathway. In order to determine the mechanism of action of E1, we analysed the effect of E1 on components of the phosphoinositide 3‐kinase/Akt/mammalian target of rapamycin (mTOR) pathway. E1 demonstrated dose‐dependent and time‐dependent repression of Akt and mTOR activity in prostate and breast cancer cell lines, PC‐3 and MCF‐7, respectively. Inhibition of Akt and mTOR activity by E1 also coincided with increased c‐Jun NH2‐terminal kinase (JNK) phosphorylation. However, the mode of action of E1 is different from that of the mTOR inhibitor rapamycin. Proliferation and cell cycle analysis revealed that E1 induced cell cycle arrest and cell death in PC‐3 and MCF‐7 cells. Moreover, pretreatment of cancer cells with the JNK inhibitor SP600125 abolished the repression of Akt and mTOR activity by E1, indicating that the inhibition of Akt and mTOR by E1 is mediated through JNK activation. Consistently, E1 repressed Akt and mTOR activity in wild‐type and p38‐null mouse embryonic fibroblasts (MEFs), but not in MEFs lacking JNK1/2, and JNK‐null MEFs were less sensitive to the antiproliferative effects of E1. We further showed that E1 can function cooperatively with suboptimal concentrations of paclitaxel to induce cell death in PC‐3 and MCF‐7 cells. Taken together, these data suggest that E1 induces cancer cell death through the JNK‐dependent repression of Akt and mTOR activity and may provide a valuable compound for further development and research.
Assimilation of excess ammonium into amino acids and nitrogen translocation in Arabidopsis thaliana– roles of glutamate synthases and carbamoylphosphate synthetase in leaves
Authors: Potel Fabien , Valadier Marie‐Hélène , Ferrario‐Méry Sylvie , Grandjean Olivier , Morin Halima , Gaufichon Laure , Boutet‐Mercey Stéphanie , Lothier Jérémy , Rothstein Steven J. , Hirose Naoya , Suzuki Akira
Published: June 2009

This study was aimed at investigating the physiological role of ferredoxin‐glutamate synthases (EC 1.4.1.7), NADH‐glutamate synthase (EC 1.4.1.14) and carbamoylphosphate synthetase (EC 6.3.5.5) in Arabidopsis. Phenotypic analysis revealed a high level of photorespiratory ammonium, glutamine/glutamate and asparagine/aspartate in the GLU1 mutant lacking the major ferredoxin‐glutamate synthase, indicating that excess photorespiratory ammonium was detoxified into amino acids for transport out of the veins. Consistent with these results, promoter analysis and in situ hybridization demonstrated that GLU1 and GLU2 were expressed in the mesophyll and phloem companion cell–sieve element complex. However, these phenotypic changes were not detected in the GLU2 mutant defective in the second ferredoxin‐glutamate synthase gene. The impairment in primary ammonium assimilation in the GLT mutant under nonphotorespiratory high‐CO2 conditions underlined the importance of NADH‐glutamate synthase for amino acid trafficking, given that this gene only accounted for 3% of total glutamate synthase activity. The excess ammonium from either endogenous photorespiration or the exogenous medium was shifted to arginine. The promoter analysis and slight effects on overall arginine synthesis in the T‐DNA insertion mutant in the single carbamoylphosphate synthetase large subunit gene indicated that carbamoylphosphate synthetase located in the chloroplasts was not limiting for ammonium assimilation into arginine. The data provided evidence that ferredoxin‐glutamate synthases, NADH‐glutamate synthase and carbamoylphosphate synthetase play specific physiological roles in ammonium assimilation in the mesophyll and phloem for the synthesis and transport of glutamine, glutamate, arginine, and derived amino acids.
Cinacalcet Treatment in Dialysis Patients with Secondary Hyperparathyroidism: Effects and Open Issues
Authors: Drüeke Tilman B
Published: June 2009

The recent introduction of calcimimetics, a novel class of therapeutic agents, has led to a change in the treatment strategy of secondary hyperparathyroidism in patients with end‐stage renal disease. In initial acute studies in chronic hemodialysis patients, the calcimimetic cinacalcet was shown to reduce plasma intact parathyroid hormone within hours, followed by a rapid, profound decrease in plasma calcium and a minor decrease in plasma phosphorus. Subsequent reports showed that the long‐term administration of cinacalcet to such patients proved to be superior to standard therapy in controlling secondary uremic hyperparathyroidism, in that it was able to induce a decrease in both plasma intact parathyroid hormone and the calcium x phosphorus product, in contrast to the effects of active vitamin D sterols. This allowed the achievement of the guideline treatment targets proposed by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative in a much larger proportion of dialysis patients than standard therapy did. Moreover, the effect of cinacalcet is long‐lasting. An important question is that of cinacalcet's effects on patient outcomes, which is still lacking. A similar lack of information exists for most other treatment modalities given to correct the mineral and bone disorder of chronic kidney disease. A post‐hoc analysis of four clinical trials combined done in hemodialysis patients showed that randomization to cinacalcet led to significant reductions in the risk of parathyroidectomy, fracture, and cardiovascular hospitalization. To obtain a definitive answer to this question, including patient survival, we will have to wait for the results of prospective, randomized controlled trials. In pre‐clinical studies performed in rats with chronic renal failure, the administration of the calcimimetic NPS R‐568 at the time of uremia induction allowed the prevention of parathyroid hyperplasia, and the reversal of already established hyperplasia as well. Perhaps more important from the clinical point of view, NPS R‐568 also appeared to allow reversal of osteitis fibrosa in uremic rats and reduction of aortic calcification and atherosclerosis in uremic rats and mice. In conclusion, the clinical introduction of cinacalcet allows for better control of secondary hyperparathyroidism in dialysis patients as compared to standard therapy, based on surrogate biochemical markers. Hopefully, in the future, this improvement will be shown to be associated with better patient outcomes for the treatment of fractures and cardiovascular morbidity and mortality.
Changes in Interventional Treatment—from the Viewpoint of Percutaneous Ethanol Injection Therapy
Authors: Kitaoka Masafumi
Published: June 2009

The environment surrounding secondary hyperparathyroidism treatment has changed and the transition of the guidelines on selective percutaneous ethanol injection therapy (PEIT) for secondary hyperparathyroidism from 2000 to 2006 has been made. The new guidelines emphasize the point that PEIT is best indicated for patients with one enlarged gland. Among treatments, including local vitamin D injection, selective PEIT and parathyroidectomy, cinacalcet is a potent medical treatment and will be a very effective new post‐treatment intervention. However, it is expected that some patients will require active intervention based on morphological examination even if biochemical control is possible with cinacalcet administration.
Change in Coronary Artery Calcification Score due to Cinacalcet Hydrochloride Administration
Authors: Tsuruta Yoshinari , Ohbayashi Takaaki , Fujii Mikiko , Myochin Hisashi , Mizutani Ryoko , Narita Masayasu , Maeda Kenji
Published: June 2009

We examined the influence of cinacalcet on vascular calcification by measuring the coronary artery calcification score (CACS) in hemodialysis patients who received cinacalcet. The cinacalcet treatment group consisted of eight hemodialysis patients with secondary hyperparathyroidism who received cinacalcet for 7–14 months. The mean CACS change in the treatment group was −0.094/year, showing a decreasing tendency, while that in the control group showed an increasing tendency of 0.034/year. The mean CACS change showed a tendency for improvement in the treatment group, but no significant difference from that in the control group was observed as the number of cases was small (P = 0.102). The results of this study suggest that cinacalcet is effective in preventing the progress of extraosseous calcification.
Impact of Cinacalcet Hydrochloride on Bone Histology in Patients with Secondary Hyperparathyroidism
Authors: Yajima Aiji , Akizawa Tadao , Tsukamoto Yusuke , Kurihara Satoshi , Ito Akemi ,   K Study Group
Published: June 2009

Serum parathyroid hormone (PTH) levels are effectively decreased by cinacalcet hydrochloride (HCl) in patients with secondary hyperparathyroidism. We assessed the impact of cinacalcet HCl on bone histology in these patients. Four hemodialysis patients with secondary hyperparathyroidism (intact PTH ≥ 300 pg/mL) were treated with cinacalcet HCl with low‐doses of vitamin D sterols as well as calcium‐based phosphate binders for 52 weeks. Patients 1, 2, 3 and 4 were aged 55, 65, 61 and 70 years old, and the duration of hemodialysis in the patients was 84, 176, 125 and 216 months, respectively. Serum intact PTH, serum bone metabolism markers and bone histomorphometric parameters were determined before and after 52 weeks of the treatment. Serum intact PTH decreased from 1110, 880, 330 and 980 pg/mL to 233, 80, 88 and 116 pg/mL, respectively, in the four patients after 52 weeks of treatment with cinacalcet HCl. Serum levels of bone metabolism markers and all of the histomorphometric resorption parameters decreased in these patients. In particular, fibrosis volume decreased to 0% in all of the patients. Static formation parameters, including osteoblast surface and osteoid‐related parameters, all decreased after the treatment, indicating an increase of mineralized bone volume during the treatment. Dynamic parameters except for activation frequency decreased after the treatment, indicating significant suppression of bone turnover. Cinacalcet HCl with low‐doses of vitamin D sterols suppressed serum PTH with no significant changes of serum calcium levels. In addition, long‐term administration of cinacalcet HCl improved hyperparathyroid bone diseases in patients with secondary hyperparathyroidism.
Impact of Cinacalcet Hydrochloride on the Achievement of the Japanese Society for Dialysis Therapy (JSDT) Guideline Targets: A post‐hoc Analysis of the KRN1493 Study
Authors: Komaba Hirotaka , Fukagawa Masafumi
Published: June 2009

The Japanese Society for Dialysis Therapy (JSDT) released the Guidelines for the Management of Secondary Hyperparathyroidism in Chronic Dialysis Patients (JSDT guidelines), which set target ranges for calcium (8.4–10.0 mg/dL), phosphorus (3.5–6.0 mg/dL) and intact parathyroid hormone (PTH) (60–180 pg/mL); however, achieving the guideline targets is difficult and challenging. In this post‐hoc analysis, we evaluate the impact of cinacalcet on the achievement of the JSDT targets. After a treatment period of 14 weeks, 26% of the cinacalcet group achieved intact PTH levels within the target ranges (P < 0.001, compared with the control group). A significantly greater proportion achieved the targets for calcium and phosphorus, as compared with control patients (65% vs. 45%, P = 0.015; 68% vs. 47%, P = 0.009, respectively). The proportion of patients in whom serum calcium and phosphorus were controlled to within the target ranges increased from 21% at baseline to 44% (P < 0.001). The combined targets of three parameters were achieved by 17% of cinacalcet‐treated patients, while none of the control patients achieved these parameters simultaneously (P < 0.001). Cinacalcet treatment also efficaciously reduced elevated serum calcium and phosphorus levels. Even in patients with baseline intact PTH levels >500 pg/mL, where parathyroidectomy has been recommended in the JSDT guidelines, 20% of the cinacalcet group achieved the target intact PTH levels. Longer‐term cinacalcet treatment aimed at the JSDT targets may lead to further reductions in PTH secretion. Further studies are required to examine the potential benefit of cinacalcet and to revise the current guidelines relating to adequate use of cinacalcet.
A parsec scale X-ray extended structure from the X-ray binary Circinus X–1
Authors: Soleri P. , Heinz S. , Fender R. , Wijnands R. , Tudose V. , Altamirano D. , Jonker P. G. , van der Klis M. , Kuiper L. , Kaiser C. , Casella P.
Published: June 2009

We present the results of the analysis of two Chandra observations of Circinus X–1 performed in 2007, for a total exposure time of ∼50 ks. The source was observed with the High Resolution Camera during a long X-ray low-flux state of the source. Cir X–1 is an accreting neutron star binary system that exhibits ultra-relativistic arcsec-scale radio jets and an extended arcmin-scale radio nebula. Furthermore, a recent paper has shown an X-ray excess on arcmin-scale prominent on the side of the receding radio jet. In our images, we clearly detect X-ray structures on both the side of the receding and the approaching radio jet. The X-ray emission is consistent with a synchrotron origin. Our detection is consistent with neutron star binaries being as efficient as black hole binaries in producing X-ray outflows, despite their shallower gravitational potential.
A second black hole candidate in a M31 globular cluster is identified with XMM–Newton
Authors: Barnard R. , Kolb U.
Published: June 2009

We use arguments developed in previous work to identify a second black hole candidate associated with an M31 globular cluster (GC), Bo 144, on the basis of X-ray spectral and timing properties. The 2002 XMM–Newton observation of the associated X-ray source (hereafter XBo 144) revealed behaviour that is common to all low-mass X-ray binaries (LMXBs) in the low-hard state. Studies have shown that neutron star LMXBs exhibit this behaviour at 0.01–1000 keV luminosities ≤10 per cent of the Eddington limit (LEdd). However, the unabsorbed 0.3–10 keV luminosity of XBo 144 was ∼0.30 LEdd for a 1.4 M⊙ neutron star, and the 0.01–1000 keV luminosity is expected to be ≳3–7 times higher. We therefore identify XBo 144 as a black hole candidate. Furthermore, it is the second black hole candidate to be consistent with formation via tidal capture of a main sequence donor in a GC; such systems were previously thought non-existent, because the donor was thought to be disrupted during the capture process.
Laboratory evidence for the non-detection of excited nascent H2 in dark clouds
Authors: Congiu E. , Matar E. , Kristensen L. E. , Dulieu F. , Lemaire J. L.
Published: June 2009

There has always been a great deal of interest in the formation of H2 as well as in the binding energy released upon its formation on the surface of dust grains. The present work aims at collecting experimental evidence for how the bond energy budget of H2 is distributed between the reaction site and the internal energy of the molecule. So far, the non-detection of excited nascent H2 in dense quiescent clouds could be a sign that either predictions of emission line intensities are not correct or the de-excitation of the newly formed molecules proceeds rapidly on the grain surface itself. In this Letter, we present experimental evidence that interstellar molecular hydrogen is formed and then rapidly de-excited on the surface of porous water ice mantles. In addition, although we detect ro-vibrationally excited nascent molecules desorbing from a bare non-porous (compact) water ice film, we demonstrate that the amount of excited nascent hydrogen molecules is significantly reduced no matter the morphology of the water ice substrate at 10 K (both on non-porous and on porous water ice) in a regime of high molecular coverage as is the case in dark molecular clouds.
INACTIVATION OF VEROCYTOTOXIGENIC ESCHERICHIA COLI AND LISTERIA MONOCYTOGENES CO‐CULTURED WITH LACTOBACILLUS SAKEI IN A SIMULATED MEAT FERMENTATION MEDIUM
Authors: PAPATHOMOPOULOU K. , KOTZEKIDOU P.
Published: June 2009

The effect of bacteriocin producing Lactobacillus sakei 4413 (an isolate from a Greek dry‐fermented sausage) on inhibition of co‐cultured verocytotoxigenic Escherichia coli or Listeria monocytogenes strains was investigated. In the simulated meat fermentation medium (containing a mixture of nitrogen sources, glucose, sodium chloride and curing agents, with initial pH 6.5) incubated at 25C, L. sakei 4413 produced the highest concentration of bacteriocin in the exponential growth phase, reducing the pH of the medium to 4.3 and producing 0.54% w/v lactic acid. Three primary models (i.e., the Gompertz model, the Baranyi model and the Whiting‐Buchanan model) were evaluated for modeling survival curves of different verocytotoxigenic E. coli and L. monocytogenes strains co‐cultured with L. sakei 4413. The inactivation models evaluated indicated an acceptable degree of goodness‐of‐fit. However, the Whiting‐Buchanan model seems more accurate for fitting microbial inactivation curves, showing the highest R2values and lowest root mean square values in co‐cultures of L. sakei and E. coli or L. monocytogenes. Using the Whiting‐Buchanan model, a 4‐D (99.99%) inactivation of E. coli and L. monocytogenes strains was achieved after 50.9 and 48.7 h, respectively, in co‐cultures with L. sakei 4413 in the simulated meat fermentation medium incubated at 25C. In a synthetic medium containing a mixture of different nitrogen sources (i.e., peptone from meat, meat extract, yeast extract) the effect of temperature and glucose on the inhibitory action of L. sakei 4413 against E. coli O157 EDL‐932 was studied by central composite response surface methodology. The results indicate that the minimum time for a 4‐log decline (11.5 h) for E. coli O157 EDL‐932 in co‐culture with L. sakei 4413 can be achieved at 26C and 2% w/v glucose. The results indicate that L. sakei 4413 could be used as bio‐preservative or starter adjunct in meat fermentations in order to minimize the risk associated with the survival of the above foodborne pathogens.

PRACTICAL APPLICATIONS

The development of indigenous starters is very promising in order to produce fermented sausages with high sanitary and sensory qualities. This work contributes to the development of a starter adjunct from an indigenous L. sakei (isolated from a traditional sausage manufactured by a Greek producer). L. sakei added in a model system inactivates verocytotoxigenic E. coli and L. monocytogenes. As L. sakei strain is well adapted to the meat environment, it will lead to sausages that do not present a sanitary risk.