bluuebunny/crossref_metadata_2025 huggingface dataset:
Dormant forms of Mycobacterium smegmatis with distinct morphology
Authors: Anuchin Aleksey M. , Mulyukin Andrey L. , Suzina Natalya E. , Duda Vitaly I. , El-Registan Galina I. , Kaprelyants Arseny S.
Published: March 2009

Cultivation of Mycobacterium smegmatis cells in a nitrogen-limited minimal medium (SR-1) followed by prolonged storage at room temperature without shaking resulted in the gradual accumulation of morphologically distinct ovoid forms characterized by (i) low metabolic activity; (ii) elevated resistance to antibiotics and to heat treatment; and (iii) inability to produce colonies on standard agar plates (non-platable cells). Detailed microscopic examination confirmed that ovoid cells possessed an intact cell envelope, specific fine structure and large electron-transparent bodies in the cytoplasm. Cell staining with Nile red and analysis of the lipid content by TLC revealed the presence of significant amounts of apolar lipids in these bodies. The ovoid forms could be stored for significant periods (up to 5 months) and resuscitated afterwards in a modified Sauton's medium. Importantly, resuscitation of ovoid cells was accompanied by their transformation into the typical rod-shaped cells. We suggest that the observed ovoid cells represent dormant forms, resembling morphologically distinct cells of Mycobacterium tuberculosis previously isolated from tuberculosis patients and infected animals.
The roles of the nitrate reductase NarGHJI, the nitrite reductase NirBD and the response regulator GlnR in nitrate assimilation of Mycobacterium tuberculosis
Authors: Malm Sven , Tiffert Yvonne , Micklinghoff Julia , Schultze Sonja , Joost Insa , Weber Isabel , Horst Sarah , Ackermann Birgit , Schmidt Mascha , Wohlleben Wolfgang , Ehlers Stefan , Geffers Robert , Reuther Jens , Bange Franz-Christoph
Published: March 2009

Mycobacterium tuberculosis can utilize various nutrients including nitrate as a source of nitrogen. Assimilation of nitrate requires the reduction of nitrate via nitrite to ammonium, which is then incorporated into metabolic pathways. This study was undertaken to define the molecular mechanism of nitrate assimilation in M. tuberculosis. Homologues to a narGHJI-encoded nitrate reductase and a nirBD-encoded nitrite reductase have been found on the chromosome of M. tuberculosis. Previous studies have implied a role for NarGHJI in nitrate respiration rather than nitrate assimilation. Here, we show that a narG mutant of M. tuberculosis failed to grow on nitrate. A nirB mutant of M. tuberculosis failed to grow on both nitrate and nitrite. Mutant strains of Mycobacterium smegmatis mc2155 that are unable to grow on nitrate were isolated. The mutants were rescued by screening a cosmid library from M. tuberculosis, and a gene with homology to the response regulator gene glnR of Streptomyces coelicolor was identified. A ΔglnR mutant of M. tuberculosis was generated, which also failed to grow on nitrate, but regained its ability to utilize nitrate when nirBD was expressed from a plasmid, suggesting a role of GlnR in regulating nirBD expression. A specific binding site for GlnR within the nirB promoter was identified and confirmed by electrophoretic mobility shift assay using purified recombinant GlnR. Semiquantitative reverse transcription PCR, as well as microarray analysis, demonstrated upregulation of nirBD expression in response to GlnR under nitrogen-limiting conditions. In summary, we conclude that NarGHJI and NirBD of M. tuberculosis mediate the assimilatory reduction of nitrate and nitrite, respectively, and that GlnR acts as a transcriptional activator of nirBD.
The Spo0E phosphatase of Bacillus subtilis is a substrate of the FtsH metalloprotease
Authors: Le Ai Thi Thuy , Schumann Wolfgang
Published: March 2009

In the absence of the ATP-dependent metalloprotease FtsH, the sporulation frequency ofBacillus subtiliscells is reduced by several orders of magnitude. This indicates that FtsH has to degrade or to regulate the steady-state level of one or more proteins that interfere with successful sporulation. Here, we show that the amount of the master regulator protein Spo0A is reduced in anftsHknockout and the small amounts of Spo0A protein present are inactive. Phosphorylation of Spo0A occurs through a phosphorelay. Four negative regulators have been identified here which directly interfere with the phosphorelay throughftsH, namely the phosphatases RapA, RapB, RapE and Spo0E. If a null allele in any one of them was combined with anftsHknockout, the sporulation frequency was increased by two to three orders of magnitude, but remained below 1 %. When purified Spo0E was incubated with FtsH, partial degradation of the phosphatase was observed. In contrast, two mutant versions of Spo0E with truncated C-termini remained stable. Transfer of the C-terminal 25 aa of Spo0E to a shorter homologue of Spo0E, YnzD, which is not a substrate of FtsH, conferred instability. When a mutant Spo0A was produced that was active in the absence of phosphorylation, spores were formed at a normal rate in anftsHknockout, indicating thatftsHis needed only during phase 0.
Relaxed control of sugar utilization in Lactobacillus brevis
Authors: Kim Jae-Han , Shoemaker Sharon P. , Mills David A.
Published: March 2009

Prioritization of sugar consumption is a common theme in bacterial growth and a problem for complete utilization of five and six carbon sugars derived from lignocellulose. Growth studies show that Lactobacillus brevis simultaneously consumes numerous carbon sources and appears to lack normal hierarchical control of carbohydrate utilization. Analysis of several independent L. brevis isolates indicated that co-utilization of xylose and glucose is a common trait for this species. Moreover, carbohydrates that can be used as a single carbon source are simultaneously utilized with glucose. Analysis of the proteome of L. brevis cells grown on glucose, xylose or a glucose/xylose mixture revealed the constitutive expression of the enzymes of the heterofermentative pathway. In addition, fermentative mass balances between mixed sugar inputs and end-products indicated that both glucose and xylose are simultaneously metabolized through the heterofermentative pathway. Proteomic and mRNA analyses revealed that genes in the xyl operon were expressed in the cells grown on xylose or on glucose/xylose mixtures but not in those grown on glucose alone. However, the expression level of XylA and XylB proteins in cells grown on a glucose/xylose mixture was reduced 2.7-fold from that observed in cells grown solely on xylose. These results suggest that regulation of xylose utilization in L. brevis is not stringently controlled as seen in other lactic acid bacteria, where carbon catabolite repression operates to prioritize carbohydrate utilization more rigorously.
Energetic limits to metabolic flexibility: responses of Saccharomyces cerevisiae to glucose–galactose transitions
Authors: van den Brink J. , Akeroyd M. , van der Hoeven R. , Pronk J. T. , de Winde J. H. , Daran-Lapujade P.
Published: March 2009

Glucose is the favoured carbon source forSaccharomyces cerevisiae, and the Leloir pathway for galactose utilization is only induced in the presence of galactose during glucose-derepressed conditions. The goal of this study was to investigate the dynamics of glucose–galactose transitions. To this end, well-controlled, glucose-limited chemostat cultures were switched to galactose-excess conditions. Surprisingly, galactose was not consumed upon a switch to galactose excess under anaerobic conditions. However, the transcripts of the Leloir pathway were highly increased upon galactose excess under both aerobic and anaerobic conditions. Protein and enzyme-activity assays showed that impaired galactose consumption under anaerobiosis coincided with the absence of the Leloir-pathway proteins. Further results showed that absence of protein synthesis was not caused by glucose-mediated translation inhibition. Analysis of adenosine nucleotide pools revealed a fast decrease of the energy charge after the switch from glucose to galactose under anaerobic conditions. Similar results were obtained when glucose–galactose transitions were analysed under aerobic conditions with a respiratory-deficient strain. It is concluded that under fermentative conditions, the energy charge was too low to allow synthesis of the Leloir proteins. Hence, this study conclusively shows that the intracellular energy status is an important factor in the metabolic flexibility ofS. cerevisiaeupon changes in its environment.
Lipotoxin F of Pseudomonas aeruginosa is an AlgU-dependent and alginate-independent outer membrane protein involved in resistance to oxidative stress and adhesion to A549 human lung epithelia
Authors: Damron F. Heath , Napper Jennifer , Teter M. Allison , Yu Hongwei D.
Published: March 2009

Chronic lung infection with P. aeruginosa and excessive neutrophil-associated inflammation are major causes of morbidity and mortality in patients with cystic fibrosis (CF). Overproduction of an exopolysaccharide known as alginate leads to the formation of mucoid biofilms that are resistant to antibiotics and host defences. Alginate overproduction or mucoidy is controlled by a stress-related ECF sigma factor AlgU/T. Mutation in the anti-sigma factor MucA is a known mechanism for conversion to mucoidy. Recently, we showed that inactivation of a kinase (KinB) in nonmucoid strain PAO1 results in overproduction of alginate. Here, we report the initial characterization of lipotoxin F (LptF, PA3692), an OmpA-like outer membrane protein that exhibited increased expression in the mucoid PAO1kinB mutant. The lipotoxin family of proteins has been previously shown to induce inflammation in lung epithelia, which may play a role in CF disease progression. Expression of LptF was observed to be AlgU-dependent and upregulated in CF isolates. Deletion of lptF from the kinB mutant had no effect on alginate production. Deletion of lptF from PAO1 caused a differential susceptibility to oxidants that can be generated by phagocytes. The lptF and algU mutants were more sensitive to hypochlorite than PAO1. However, the lptF mutant displayed increased resistance to hydrogen peroxide. LptF also contributed to adhesion to A549 human lung epithelial cells. Our data suggest that LptF is an outer membrane protein that may be important for P. aeruginosa survival in harsh environments, including lung colonization in CF.
Effects of etanercept on urine neopterin levels in patients with psoriasis in a controlled, open‐label study
Authors: KOC Erol , TUNCA Mustafa , AKGUL Emin Ozgur , AKAR Ahmet , KURT Yasemin , KURUMLU Zafer , ERBIL Kemal , KILIC Selim
Published: March 2009

Neopterin is an immunological marker of cellular immune activation. Etanercept is a tumor necrosis factor‐α (TNF‐α) antagonist that decreases excessive levels of TNF‐α associated with inflammatory disease down to physiological levels. The objective of this study was to investigate urine neopterin levels in psoriatic patients treated with etanercept, to study the effect of etanercept as a TNF‐α blocker on urine neopterin levels. Urine neopterin levels and urine neopterin/creatinine ratios were measured by high‐performance liquid chromatography in 22 patients with psoriasis before and after treatment with etanercept. Results were compared with a group of 20 healthy volunteers, and 20 patients with inflammatory skin diseases as control groups. Urine neopterin levels, neopterin/creatinine ratios and Psoriasis Area and Severity Index (PASI) scores were evaluated at baseline, and the 12th and 24th week after treatment. Urine neopterin levels were significantly elevated in the psoriatic group compared with control and inflammatory skin diseases groups (P < 0.05). Urine neopterin levels were significantly reduced after etanercept treatment. Statistically we did not find any correlation between neopterin levels and PASI scores. Our findings indicate that urine neopterin concentrations may reflect the disease activity in psoriasis, and may be used as a marker for monitoring disease activity and response to treatment with etanercept in psoriatic patients.
Patent ductus arteriosus flow patterns in the treatment of congenital diaphragmatic hernia
Authors: Okamoto Shinya , Ikawa Hiromichi , Fukumoto Hironori , Masuyama Hiroaki , Konuma Kunio , Kohno Miyuki , Nakamura Tsuneyuki , Takahashi Hiroaki
Published: March 2009

Background:  Congenital diaphragmatic hernia (CDH) mortality still remains high, due to lung hypoplasia and persistent pulmonary hypertension of the neonate (PPHN). Effective management of PPHN and time of operation are quite important to the improvement of CDH treatment. In order to determine the optimal time for operation, we monitored PPHN with cardiac ultrasound.

Methods:  PPHN was assessed with three parameters: patent ductus arteriosus flow patterns (PDAFP), %left ventricular diameter at diastole, and left ventricular fraction of shortening (LVFS). Four patients with an antenatal diagnosis were treated under this protocol. Diaphragm repair was performed when PDAFP became left to right shunt dominant and the pre‐ and postoperative course was analyzed with regular chart reviews.

Results:  The alveolar‐arterial oxygen difference levels of four patients were 590, 335, 613 and 530 mmHg, and operations were carried out when the patients were 2, 2, 3 and 2 days old, respectively. In three of the four patients (all except case 3) the PDAFP changed from right to left shunt dominant or bidirectional (BD), to left to right shunt dominant within 48 h. The %left ventricular diameter at diastole was relatively stable around the time of operation. The LVFS of all patients decreased after the operation. Only the LVFS of case 3 decreased temporarily to less than 30% (which indicates poor left ventricular function) but recovered. No patients needed extracorporeal membrane oxygenation support. All patients survived the procedure and were extubated. Case 3, who took 10 days to become left to right shunt dominant after the operation, needed home oxygenation therapy for 10 months.

Conclusions:  PDAFP was a reliable marker of PPHN on a high‐frequency oscillatory ventilator to determine the optimal time for the operation for CDH. The optimal time for operation is supposed to be the time when PDAFP become left to right shunt dominant.
Normal thiopurine methyltransferase phenotype testing in a Crohn disease patient with azathioprine induced myelosuppression
Authors: Leung M. , Piatkov I. , Rochester C. , Boyages S. C. , Leong R. W. L.
Published: March 2009

Severe cytopenias in patients with autoimmune conditions treated with azathioprine are well‐recognized. Thiopurine methyltransferase (TPMT) enzymatic activity is subject to individual and ethnic variability. Patients with low TPMT activity (poor metabolizers) are at high risk of developing severe and potentially fatal haematopoietic toxicity. Studies have shown that essentially all TPMT‐deficient patients will develop haematopoietic toxicity on administration of conventional thiopurine dosages (6‐mercaptopurine, azathioprine). Therefore, screening for TPMT polymorphisms in patients before prescribing thiopurine drugs has been proposed. However, despite normalin vitroenzymatic activity, cytopenia may still occurin vivo. This is the case report of an Asian patient with Crohn disease harbouring a rare TPMT mutation on DNA sequencing, who developed neutropenic sepsis and anaemia after a flare of Crohn disease. The report illustrates the importance of monitoring for cytopenia in the setting of active inflammatory disease despite prior normal phenotyping, the role of predictive pharmacogenetics and the limitations of TPMT phenotype assays that may result in misclassification of at‐risk patients.
Effects of cholinesterase inhibition in supraspinal and spinal neural pathways on the micturition reflex in rats
Authors: Masuda Hitoshi , Chancellor Michel B. , Kihara Kazunori , Sakai Yasuyuki , Koga Fumitaka , Azuma Hiroshi , De Groat William C. , Yoshimura Naoki
Published: March 2009

OBJECTIVE

To investigate whether activation of brain and spinal cholinergic pathways affects the micturition reflex in rats.

MATERIALS AND METHODS

The effects of intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of neostigmine as a cholinesterase inhibitor and oxotremorine‐M (OXO‐M) as a muscarinic acetylcholine receptor (mAChRs) agonist, on the micturition reflex were evaluated by infusion cystometrography (CMG) in urethane‐anaesthetized untreated rats or rats pretreated with capsaicin.

RESULTS

Neostigmine injected i.c.v. increased bladder capacity (BC) and pressure threshold (PT) dose‐dependently, with an increase in maximum voiding pressure (MVP) and a decrease in voiding efficiency (VE) at higher doses. Also, neostigmine injected i.t. increased the BC and PT dose‐dependently without changing MVP or VE, and these effects were not apparent in capsaicin‐pretreated rats. In both routes, atropine as an antagonist of mAChRs, but not mecamylamine as a nicotinic‐AChR antagonist, almost completely antagonized the effects of neostigmine. The rank order of potencies of the antagonists for increasing effects of BC induced by 1 nmol of neostigmine was: pirenzepine (an M1mAChR antagonist) = atropine > 4‐DAMP (an M3mAChR antagonist) >> methoctramine (an M2mAChR antagonist) and tropicamide (an M4mAChR antagonist) via the i.c.v. route; and atropine > methoctramine > pirenzepine > tropicamide and 4‐DAMP via the i.t. route, respectively. OXO‐M injected via i.c.v. and i.t. had the same effects on BC, PT, MVP and VE as neostigmine by i.c.v. and i.t., respectively.

CONCLUSIONS

These results indicate that activation of muscarinic cholinergic mechanisms by the cholinesterase inhibitor in the brain and spinal cord can inhibit the micturition reflex, mainly by affecting afferent pathways. These mAChR‐induced inhibitory effects seem to be mediated through M1/M3receptor subtypes in the brain, while in the spinal cord, the M1/M2receptor subtypes might be involved in inhibitory effects, which are mediated via inhibition of mechanoceptive C‐fibre afferent pathways.
GRN 3′UTR+78 C>T is not associated with risk for Parkinson’s disease
Authors: Jasinska‐Myga B. , Wider C. , Opala G. , Krygowska‐Wajs A. , Barcikowska M. , Czyzewski K. , Baker M. , Rademakers R. , Uitti R. J. , Farrer M. J. , Ross O. A. , Wszolek Z. K.
Published: March 2009

Background and purpose:  A single nucleotide polymorphism in the 3′‐untranslated region of the progranulin gene (GRN; 3′UTR+78C>T; rs5848) was reported to alter the risk for frontotemporal lobar degeneration with ubiquitin‐positive inclusions (FTLD‐U). rs5848 is located within a micro‐RNA binding site and affects the expression of GRN.

Methods:  As FTLD‐U patients often present with parkinsonism, we investigated the association of GRN rs5848 and risk of Parkinson’s disease in two Caucasian patient–control series (n = 1413) from the US and Poland.

Results:  No association was observed between rs5848 and susceptibility to Parkinson’s disease (individual series and combined analysis).

Conclusions:  This finding shows that GRN rs5848 does not affect the risk of Parkinson’s disease in the US and Polish populations.
Epidemiology of ALS in Padova district, Italy, from 1992 to 2005
Authors: Cima V. , Logroscino G. , D’Ascenzo C. , Palmieri A. , Volpe M. , Briani C. , Pegoraro E. , Angelini C. , Soraru G.
Published: March 2009

Background and purpose:  Several studies have reported an increase in ALS incidence in recent years but population‐based studies in Europe do not confirm this trend. To analyze ALS incidence over time we conducted a retrospective incidence study in the Padova district of Italy (1992 to 2005). We had previously conducted a survey in the same area in the years 1980–1991.

Methods:  We used the archives of all the neurological wards of the Padova district to identify all subjects with a discharge diagnosis of ALS or motor neuron disease and resident in the Padova district.

Results:  We ascertained 182 patients (85 males and 97 females; male:female ratio 0.88:1) over the 14‐year study period. The annual incidence rates adjusted by sex and age increased from 1.31/100000/year in the years 1992–1994 to 1.92/100000/year in the years 2004–2005.

Conclusions:  This study confirmed an ALS incidence increase over the last 25 years in the Padova district. The increase in incidence may be partially explained by the ageing of the general population rather than by an improved diagnostic assessment.
Shame and guilt in preschool depression: evidence for elevations in self‐conscious emotions in depression as early as age 3
Authors: Luby Joan , Belden Andy , Sullivan Jill , Hayen Robin , McCadney Amber , Spitznagel Ed
Published: March 2009

Background: Empirical findings from two divergent bodies of literature illustrate that depression can arise in the preschool period and that the complex self‐conscious emotions of guilt and shame may develop normatively as early as age 3. Despite these related findings, few studies have examined whether the emotions of shame and guilt are salient in early childhood depression. This is important to further understand the emotional characteristics of preschool depression. Based on the hypothesis that preschool depression would be uniquely associated with higher levels of shame and maladaptive guilt, these emotions were investigated in a sample that included depressed, anxious, and disruptive disordered preschoolers as well as healthy peers using multiple methods.

Method: Structured psychiatric diagnoses were derived in a sample ofN= 305 preschoolers ascertained from community sites. Preschoolers’ tendency to experience shame and guilt were explored using a story stem completion task coded by raters blind to symptoms and diagnosis of the subjects. Guilt experience and reparation behaviors were also measured using parent report.

Results: Based on preschooler’s emotion themes during the narrative tasks, gender, age, and depression severity predicted unique and significant portions of the variance in preschoolers’ expressions of shame. Parent report measures revealed that increasing depression severity was associated with children’s more frequent experiences of guilt feelings and less frequent attempts at guilt reparation (maladaptive guilt).

Conclusions: Findings demonstrated that high levels of shame and maladaptive guilt were related to preschool onset depression when using observational measures of children’s internal representations of their self‐conscious emotions as well as parent report. These findings demonstrate continuity of these core emotions of depression as early as age 3. These findings suggest that guilt and shame should be explored in clinical assessments of young children and may be an important focus for future studies of the developmental psychopathology of depression.
Relationships between Sensitivity to Agricultural Intensification and Ecological Traits of Insectivorous Mammals and Arthropods
Authors: JENNINGS NANCY , POCOCK MICHAEL J. O.
Published: March 2009

Abstract: We tested the hypothesis that variation in the sensitivity of animals to habitat change is explained by ecological traits (life‐history traits, trophic level, and mobility). We measured the sensitivity of insectivorous mammals (shrews and bats) and their prey (arthropods active at the soil surface and nocturnal aerial arthropods) to three aspects of agricultural intensification in a matched‐pair experimental design: increased use of agrochemicals (comparison of organic and conventional cereal crops, with pairing for the size of the boundary hedge), change in grassland management from hay to silage (with pairing for the size of the boundary hedge), and increased field size due to hedgerow loss (with boundary‐field comparisons as a proxy). We assessed the sensitivity of taxa as the difference in their relative abundance between pairs of high‐ and low‐intensity sites for each aspect of agricultural intensification. We used phylogenetically informed analyses to explore cross‐species relationships between our measures of sensitivity and seven ecological traits of animals (e.g., trophic level, mobility, and reproductive rate). Several traits were related to the sensitivity of animals to agricultural intensification. These traits were mainly associated with fast life histories (high reproductive output and low trophic level) and low mobility. Trophic level of adults was related to sensitivity to habitat change for all three aspects of agricultural intensification, but the direction of the relationship differed between the three aspects of intensification. The significance of the relationship between other ecological traits and sensitivity to intensification varied for the three aspects of agricultural intensification. Our results show that some ecological traits can be used to preselect taxa that are predicted to be sensitive to habitat change, and their sensitivity can be tested empirically for use as biotic indicator taxa. Understanding which traits are related to sensitivity to habitat change is vital because sensitivity is important in determining a taxon's ability to survive in dynamic environments.
Membrane array–based differential profiling of platelets during storage for 52 miRNAs associated with apoptosis
Authors: Kannan Meganathan , Mohan Ketha V. Krishna , Kulkarni Sandhya , Atreya Chintamani
Published: March 2009

BACKGROUND: Enucleated platelets (PLTs) utilize posttranscriptional gene (mRNA) regulation (PTGR) for their normal morphologic and physiologic functions, which are altered in their ex vivo storage, also collectively referred to as storage lesions. While cellular micro‐RNAs (miRNAs) play a significant role in posttranscriptional gene (mRNA) regulation by binding to their target mRNAs, comprehensive analysis of apoptosis‐associated miRNAs and global changes in their profiles during PLT storage have not been evaluated to date.

STUDY DESIGN AND METHODS: In this report room temperature–stored PLTs of Days 0, 2, and 9 were analyzed by differential profiling for 52 apoptosis‐associated human miRNAs. After total RNA extraction from the samples, a membrane array–based miRNA analysis was carried out. Prediction of target genes was performed by bioinformatics‐based approaches.

RESULTS: Our analysis revealed that during storage, Let‐7a, ‐7c, ‐7e, ‐7f, ‐7g, and ‐7i miRNA profiles of the PLTs were barely detectable, while levels of miR‐150, ‐151, ‐152, ‐184, ‐188, ‐196a, ‐197, and ‐202 remained at high levels in PLTs. The rest of the miRNA levels were in between. However, two miRNAs, Let‐7b and miR‐16, distinctly demonstrated an increasing trend while miR‐7 and miR‐145 showed a decreasing profile during PLT storage. For these four miRNAs, we also identified their potential target mRNAs.

CONCLUSIONS: Overall, these results confirm the fact that miRNAs do exist in PLTs, and among 52 apoptosis‐specific miRNAs studied, only a few selected miRNAs did perturb during PLT storage. Future experimental evaluation of these miRNA–target mRNA interactions will provide new insights into the molecular mechanisms of PLT storage–associated lesions.
Regulation of extracellular matrix genes by arecoline in primary gingival fibroblasts requires epithelial factors
Authors: Thangjam G. S. , Agarwal P. , Balapure A. K. , Girish Rao S. , Kondaiah P.
Published: March 2009

Background and Objective:  Oral submucous fibrosis, a disease of collagen disorder, has been attributed to arecoline present in the saliva of betel quid chewers. However, the molecular basis of the action of arecoline in the pathogenesis of oral submucous fibrosis is poorly understood. The basic aim of our study was to elucidate the mechanism underlying the action of arecoline on the expression of genes in oral fibroblasts.

Material and Methods:  Human keratinocytes (HaCaT cells) and primary human gingival fibroblasts were treated with arecoline in combination with various pathway inhibitors, and the expression of transforming growth factor‐beta isoform genes and of collagen isoforms was assessed using reverse transcription–polymerase chain reaction analysis.

Results:  We observed the induction of transforming growth factor‐beta2 by arecoline in HaCaT cells and this induction was found to be caused by activation of the M‐3 muscarinic acid receptor via the induction of calcium and the protein kinase C pathway. Most importantly, we showed that transforming growth factor‐beta2 was significantly overexpressed in oral submucous fibrosis tissues (p = 0.008), with a median of 2.13 (n = 21) compared with 0.75 (n = 18) in normal buccal mucosal tissues. Furthermore, arecoline down‐regulated the expression of collagens 1A1 and 3A1 in human primary gingival fibroblasts; however these collagens were induced by arecoline in the presence of spent medium of cultured human keratinocytes. Treatment with a transforming growth factor‐beta blocker, transforming growth factor‐beta1 latency‐associated peptide, reversed this up‐regulation of collagen, suggesting a role for profibrotic cytokines, such as transforming growth factor‐beta, in the induction of collagens.

Conclusion:  Taken together, our data highlight the importance of arecolineinduced epithelial changes in the pathogenesis of oral submucous fibrosis.
A Comparison of Three Different Attachment Systems for Mandibular Two‐Implant Overdentures: One‐Year Report
Authors: Kleis Wilfried K. , Kämmerer Peer W. , Hartmann Sinsa , Al‐Nawas Bilal , Wagner Wilfried
Published: March 2009

Background: There is a lack of clinical studies on the self‐aligning attachment system (Locator®; Zest Anchors, Inc. homepage, Escondido, CA, USA) for two‐implant‐retained overdentures in the edentulous mandible. Therefore, a comparison of the Locator with two traditional designs (a rotational gold matrix and a rubber O‐ring type) in clinical 1‐year use was conducted.

Materials and Methods: From 2003 to 2007, 60 patients received two Osseotite® TG Standard implants (BIOMET 3i Implant Innovations, Palm Beach Gardens, FL, USA) in the intraforaminal area of the edentulous mandible. The implants were left unloaded for 3.5 months, randomized to three different attachment systems, and loaded through a mandibular overdenture. Twenty‐three patients received a self‐aligning attachment system (Locator) and 33 patients a ball attachment (Dal‐Ro®[BIOMET 3i Implant Innovations]n = 25; TG‐O‐Ring®[Cendres & Metaux SA, Biel‐Bienne, Switzerland]n = 8). After 12 months of delivery of the overdentures, the oral situation was evaluated: prosthodontic maintenance and biologic complications, subjective patients' experience, and oral health‐related life quality (Oral Health Impact Profile [OHIP‐G 49]).

Results: After 1‐year of clinical service, 8 of 120 implants were lost (9.6%). The Locator system brought up 34 prosthetic complications, especially the need for change of the male parts or activation because of loss of retention. The TG‐O‐Ring patients showed 14 complications, most of them the change of the O‐Rings. The patients with the Dal‐Ro abutment had seven minor complications in 12 months of clinical use. Biologic complications and patients' oral health‐related life quality showed no significant difference among the three experimental groups.

Conclusions: Prosthodontic maintenance was restricted to loss of retention for all systems. Within the observation period of this study, the self‐aligning attachment system showed a higher rate of maintenance than the ball attachments. The patients' oral health‐related life qualities as well as the biologic parameters do not differ when using the three abutment systems.
Are There Enough Doctors in My Rural Community? Perceptions of the Local Physician Supply
Authors: Biola Holly , Pathman Donald E.
Published: March 2009

ABSTRACT: 
Purpose: To assess whether people in the rural Southeast perceive that there is an adequate number of physicians in their communities, assess how these perceptions relate to county physician‐to‐population (PtP) ratios, and identify other factors associated with the perception that there are enough local physicians. Methods: Adults (n = 4,879) from 150 rural counties in eight southeastern states responded through a telephone survey. Agreement or disagreement with the statement “I feel there are enough doctors in my community” constituted the principal outcome. Weighted chi‐square analysis and a generalized estimating equation (GEE) assessed the strength of association between perceptions of an adequate physician workforce and county PtP ratios, individual characteristics, attitudes about and experiences with medical care, and other county characteristics. Findings: Forty‐nine percent of respondents agreed there were enough doctors in their communities, 46% did not agree, and 5% were undecided. Respondents of counties with higher PtP ratios were only somewhat more likely to agree that there were enough local doctors (Pearson's correlation coefficient = 0.09, P < .001). Multivariate analyses revealed that perceiving that there were enough local physicians was more common among men, those 65 and older, whites, and those with lower regard for physician care. Perceptions that the local physician supply was inadequate were more common for those who had longer travel distances, problems with affordability, and little confidence in their physicians. Perceptions of physician shortages were more common in counties with higher poverty rates. Conclusions: County PtP ratios only partially account for rural perceptions that there are or are not enough local physicians. Perceptions of an adequate local physician workforce are also related to how much people value physicians’ care and whether they face other barriers to care.
Reverse Engineering of Gene Networks with LASSO and Nonlinear Basis Functions
Authors: Gustafsson Mika , Hörnquist Michael , Lundström Jesper , Björkegren Johan , Tegnér Jesper
Published: March 2009

The quest to determine cause from effect is often referred to as reverse engineering in the context of cellular networks. Here we propose and evaluate an algorithm for reverse engineering a gene regulatory network from time‐series and steady‐state data. Our algorithmic pipeline, which is rather standard in its parts but not in its integrative composition, combines ordinary differential equations, parameter estimations by least angle regression, and cross‐validation procedures for determining the in‐degrees and selection of nonlinear transfer functions. The result of the algorithm is a complete directed network, in which each edge has been assigned a score from a bootstrap procedure. To evaluate the performance, we submitted the outcome of the algorithm to the reverse engineering assessment competition DREAM2, where we used the data corresponding to the InSilico1 and InSilico2 networks as input. Our algorithm outperformed all other algorithms when inferring one of the directed gene‐to‐gene networks.
Ethical Issues in the Treatment of Severe Brain Injury
Authors: Bernat James L.
Published: March 2009

Technological developments in functional neuroimaging have important ethical implications for the care of brain‐injured patients. Patterns of fMRI and PET responses to stimuli may help clarify if a patient is utterly unaware, and thereby enhance a physician's confidence in reaching an accurate diagnosis of vegetative state or minimally conscious state. The analysis of similar responses may enhance a physician's confidence in pronouncing an accurate prognosis for functional recovery and help avoid committing the fallacy of the self‐fulfilling prophesy. Surrogate decision making is necessary to secure consent for treatment decision in brain‐injured patients and should attempt to reproduce the treatment decision the patient would have made. Physicians should manage irreducible clinical uncertainty by sharing their level of certainty of diagnosis and prognosis with the surrogate decision‐maker. Shared decision making between the physician and surrogate is the current formulation of the doctrine of informed consent. Advance care planning can help inform surrogate decision making, but is available less commonly among young, previously healthy brain‐injured patients. Functional neuroimaging technologies also impact on ethical issues of treatment, rehabilitation, and palliation. Families of brain‐injured patients should be compassionately counseled that, despite provocative and highly publicized case reports, these technologies, while promising, are currently investigational and have not been sufficiently validated yet to be available for routine clinical use.
Real Women or Objects of Discourse? The Search for Early Christian Women
Authors: Cobb L. Stephanie
Published: March 2009

Scholarly interest in gender and sexuality in early Christianity, which has typically been tied to an interest in women and women's roles, experiences, and influences, is a relatively new addition to the study of early church history. Women and women's issues entered the academy through the women's movement of the 1970s. Early on this scholarship was driven, in part, by a political or theological agenda that sought to empower women of the twentieth century by reconstructing the lives of their foremothers. Often the early studies of women in the church were optimistic that real, historical women could be found within our sources. Soon, however, scholars became more suspicious of the male‐authored texts and turned, instead, to study the social effect of discourses about women. Many scholars, however, are not yet ready to give up investigations of ancient women's lives. Thus the field of early Christian studies is developing a variety of methodologies that offer sophisticated readings of ancient male‐authored texts while still acknowledging the inherent difficulties involved in reconstructing women's lives in early Christian history.
Spectroscopic Properties of Quercetin Derivatives,  Quercetin‐3‐O‐rhamnoside and Quercetin‐3‐O‐rutinoside, in  Hydro‐organic Mixed Solvents
Authors: Liu Hai‐Bo , Yu Daun , Shin Sung Chul , Park Hyoung‐Ryun , Park Jong Keun , Bark Ki‐Min
Published: March 2009

The characteristic fluorescence properties of quercetin‐3‐O‐rhamnoside (QCRM) and quercetin‐3‐O‐rutinoside (QCRT) were studied in CH3OH–H2O and CH3CN–H2O mixed solvents. Although QCRM and QCRT are known as nonfluorescent molecules, significant fluorescence emissions were discovered at 360 nm in CH3OH and CH3CN when they were promoted to the second excited state. The emission band is broad and structureless and the intensity decreases quickly as the H2O composition in the solvent increases. When the amount of H2O exceeds 60% in both mixed solvents, this emission disappears due to the formation of the distorted excited state. This state will be formed due to the strong intermolecular hydrogen bonding between the polar groups of solute and H2O. As the composition of CH3OH or CH3CN in solvent becomes large, the number of molecules having several intramolecular hydrogen bonding increases. Some of these molecules will be changed to a fluorescent species during the decay process, after excitation. The theoretical calculation further supports these results. The change of the lifetimes, quantum yields, and radiative and nonradiative rate constants of molecules was also examined as a function of solvatochromic parameters for CH3OH–H2O and CH3CN–H2O.
A fish bone embedded in the mobile tongue mimicking a neoplasm
Authors: Wang Yan , Li Wen
Published: March 2009

Foreign bodies embedded in a mobile tongue as an enlarged tongue mass are rarely presented to either a laryngologist or a dentist, because such bodies are commonly lodged superficially and are easily removed by the patients themselves or removed by a laryngologist by means of indirect laryngoscope or endoscope. We have described a 63‐year‐old female with an 8‐month history of an enlarged mass in the anterior right tongue. Physical examination demonstrated a mass located in the anterior right tongue without clear margin, with superficially intact mucosa and normal colour. A benign tongue neoplasm was first considered. However, a fish bone totally embedded in the mobile tongue with granuloma formation was encountered during the incisional biopsy operation. Complete removal of the foreign body with granuloma was achieved under general anaesthesia. There was no neuromuscular or neurosensory dysfunction of the tongue in the follow‐up period of 2 years. Although an embedded foreign body in the mobile tongue is a rare condition, it should be considered in the work‐up of a patient with an enlarged tongue mass, with or without a history of swallowing a foreign body.
Adjunctive Chemotherapeutic Suppression of Mutans Streptococci in the Setting of Severe Early Childhood Caries: An Exploratory Study
Authors: Berkowitz Robert J. , Koo Hyun , McDermott Michael P. , Whelehan Mary Therese , Ragusa Patricia , Kopycka‐Kedzierawski Dorota T. , Karp Jeffrey M. , Billings Ronald
Published: March 2009

Objectives: This investigational study assessed the suppressive effect of 10 percent povidone iodine (PI) coupled with elimination of active carious lesions on salivary mutans streptococci (MS) populations in children with severe early childhood caries (S‐ECC). Methods: 77 children (38 females, 39 males) were treated for S‐ ECC in one session; a 0.2 ml PI solution was applied to the dentition after dental surgery was completed and immediately wiped off. The subjects aged from 2 to 5 years (mean = 3.78 years) at baseline. Whole nonstimulated saliva samples were obtained at baseline, 30 days, 60 days, and 90 days post dental surgery. Samples were placed on ice and processed within 2 hours. The MS level in each sample was expressed as colony forming units (CFUs) per ml of saliva. Results: Approximately 50 percent of subjects had a >95 percent reduction in CFU/ml of saliva at each time point after baseline. The percentages of subjects with a >50 percent reduction in MS level were 85 percent at 30 days, 83 percent at 60 days, 84 percent at 90 days. The median (25th, 75th percentiles) CFUs/ml of saliva counts were 8.40 × 105 (1.49 × 105, 5.00 × 106) at baseline (n = 77), 4.12 × 104 (8.40 × 103, 1.89 × 105) at 30 days (n = 74), 4.62 × 104 (7.00 × 103, 1.36 × 105) at 60 days (n = 70), and 5.09 × 104 (1.16 × 104, 1.00 × 105) at 90 days (n = 70). The changes from baseline to 30 days, 60 days, and 90 days were statistically significant (P < 0.0001). Conclusions: PI coupled with dental surgery has a significant suppressive effect on salivary MS levels in the setting of S‐ECC for at least 90 days. These data strongly suggest that treatment with PI may be an important adjunct to dental surgery for S‐ECC.
Oral Mucosal Conditions in Chronic Hepatitis C Brazilian Patients: A Cross‐Sectional Study
Authors: De Mattos Camargo Grossmann Soraya , Teixeira Rosângela , De Aguiar Maria Cássia Ferreira , De Moura Mariela Dutra Gontijo , Do Carmo Maria Auxiliadora Vieira
Published: March 2009

Objective: Our purpose was to carry out an epidemiological study to assess the prevalence of oral mucosal conditions in Brazilian patients with chronic hepatitis C. Methods: A cross‐sectional survey was carried out on 215 patients with chronic hepatitis C who were examined for oral mucosal conditions, including oral mucosal lesions and variations of normality. Results: The prevalence of patients with chronic hepatitis C presenting oral mucosal conditions was 96.3 percent (207 patients). Oral mucosal lesions were present in 147 patients (68.4 percent), whereas variations of normality were observed in 173 patients (80.5 percent). The most common lesions included cheek biting in 42 cases (19.5 percent), candidiasis in 39 cases (18.1 percent), and leukoplakia in 28 cases (13.0 percent). The association of oral lichen planus with hepatitis C virus (HCV) infection proved to be statistically significant (P = 0.002). The most frequent variations of normality included Fordyce's spots in 96 cases (44.7 percent), lingual varicosities in 67 cases (31.2 percent), and fissured tongue in 60 cases (27.9 percent). Conclusion: The prevalence of patients with chronic hepatitis C presenting oral mucosal conditions was 96.3 percent. Despite this high prevalence, only the association between oral lichen planus and hepatitis C showed statistical significance. Considering that HCV infection may be associated with extrahepatic disorders, such as oral manifestations, efforts should be made to clarify the possible relation between oral conditions and HCV infection. This may be helpful in the earlier diagnosis of the infection mainly in asymptomatic patients.
FURTHER EVIDENCE OF LONG MEMORY IN THE SOUTH AFRICAN STOCK MARKET
Authors: Morris Quinton , Van Vuuren Gary , Styger Paul
Published: March 2009

This paper expands and augments the results of the paper by Jefferis and Thupayagale) and tests the efficiency of the South African stock market with Wavelet and Markov Switching Regime analyses of selected shares and the a ALSI 40 data. The Wavelet analysis indicated that most of the individual share prices and the share index time series are mean reverting over the long run and follow a long memory process, offering evidence against weak‐form efficient market hypothesis (EMH). The Markov model modelled the financial and prevalent economic conditions accurately and established the presence of patterns in the historic time series, providing additional support against the weak‐form EMH.
Motivating Retail Marketing Effort: Optimal Contract Design
Authors: Mukhopadhyay Samar K. , Su Xuemei , Ghose Sanjoy
Published: March 2009

We study a distribution channel where a manufacturer relies on a sales agent for selling the product, and for investing in the most appropriate marketing effort. The agent's effort is hard to monitor. In addition, the cost of effort is the agent's private information. These impose challenges to the manufacturer in its endeavor to influence the agent's marketing effort provisions and to allocate profit between the two parties. We propose two contract forms. The franchise fee contract is a two‐part price schedule specifying a variable wholesale price and a fixed franchise fee. The retail price maintenance contract links the allowed retail price that the agent charges customers with total payment to the manufacturer and sales level. Under information asymmetry, for implementing either contract form, the manufacturer needs to offer a menu of contracts, hoping to invoke the “revelation principle” when the agent picks a certain contract from that menu. We show that the two contract forms perform differently, and each party's preference toward a particular contract form is linked with the total reservation profit level and/or the sales agent's cost type. We provide managerial guidelines for the manufacturer in selecting a better contract form under different conditions.
A Model of Consumer Inertia with Applications to Dynamic Pricing
Authors: Su Xuanming
Published: March 2009

This paper introduces a decision model of consumer inertia. Consumers exhibit inertia when they have an inherent bias to delay purchases. Inertia may induce consumers to wait even when it is optimal to buy immediately. We embed our decision model within a dynamic pricing context. There is a firm that sells a fixed capacity over two time periods to an uncertain number of both rational and inertial consumers. We find that consumer inertia has both positive and negative effects on profits: it decreases demand (in period one) but intensifies competition among consumers for the product (in period two). We show that our model of inertia is consistent with well‐established behavioral regularities, such as loss aversion and probability weighting in the sense of prospect theory, and hyperbolic time preferences. We offer practical recommendations for firms to influence the level of consumer inertia. These include offering returns policies (to mitigate potential consumer losses), providing decision aids (to avoid perception errors), and offering flexible payment options (to lower transaction costs).