bluuebunny/crossref_metadata_2025_split huggingface dataset:
P53 apoptosis mediator PERP: localization, function and caspase activation in uveal melanoma
Authors: Davies Lyndsay , Gray Donna , Spiller Dave , White Mike R. H. , Damato Bertil , Grierson Ian , Paraoan Luminita 
Published: November 2008

Abstractp53 apoptosis effector related to PMP‐22 (PERP) is a transcriptional target gene of p53 tumour suppressor that is specifically induced during apoptosis and not during cell cycle arrest. In primary uveal melanoma (UM), the most common intraocular malignancy in adults that has a reportedly unaffected signalling pathway upstream of and including p53, PERP expression is down‐regulated in the metastatic monosomy 3‐type tumours, compared with the less aggressive disomy 3‐type tumours. Here, we demonstrate experimentally, by the use of full‐length PERP‐green fluorescent protein (GFP) fusions and real‐time confocal microscopy, the intracellular targeting and plasma membrane localization of PERP in living UM cells and show that expression of PERP induces caspase‐mediated apoptosis in UM cells. Induction of PERP expression in GFP‐PERP‐transfected UM cells leads to increased levels of cleaved caspase‐8 forms, as well as to reduction of its full‐length substrate Bid, but not to detectable processing of caspase‐9. The levels of mature caspase‐8, ‐9 and ‐3 proteins significantly correlate with PERP expression levels in primary UMs. Transcriptional profiling of PERP and caspase‐8 in tumour specimens indicates that the positive association of PERP and caspase‐8 proteins is a consequence of post‐translational processing, most likely at the level of caspase‐8 cleavage, and not of increased transcription of pro‐caspase‐8. We conclude that PERP expression leads to activation of an extrinsic receptor‐mediated apoptotic pathway, with a possible subsequent engagement of the intrinsic apoptotic pathway. The findings underline the apoptotic pathway mediated by PERP as a critical mechanism employed by UM tumours to modulate susceptibility to apoptosis.
Analysis of molecular determinants of PRL‐3
Authors: Pascaru Mihaela , Tanase Carmen , Vacaru Andrei M. , Boeti Patricia , Neagu Elena , Popescu Irinel , Szedlacsek Stefan E. 
Published: November 2008

AbstractIn order to analyse whether a C‐terminal polybasic sequence represents a nuclear localization signal (NLS) we obtained several truncated and mutant forms of protein of regerating liver (PRL)‐3 and evaluated their subcellular localization as compared to the wild‐type form. Our results invalidate the hypothesis that this is an NLS. We also analysed the influence of the C‐ and N‐terminal residues on the phosphatase activity of PRL‐3. Our results provide in vitro evidence that the C‐terminal CAAX motif, besides directing the protein farnesylation, plays an additional regulatory role by inhibiting the catalytic efficiency of PRL‐3. Taking into account the results we obtained, as well as reported data, we propose a hypothetical molecular mechanism for the nucleocytoplasmic localization and transfer of PRL‐3.
Intrusive luxation of permanent incisors in Norwegians aged 6–17 years: a retrospective study of treatment and outcome
Authors: Wigen Tove Irene , Agnalt Reidun , Jacobsen Ingeborg 
Published: November 2008

Abstract –  Background/Aim:  External replacement resorption (ankylosis‐related) is a severe complication leading eventually to tooth loss. Little information exists regarding the influence of variables such as degree of intrusion or treatment method on the development of replacement resolution in intruded permanent incisors. The aim of this study was to report the most frequently involved age group, the preferred type of treatment, and the type and frequency of healing complications. Special attention was paid to the effect of treatment on the occurrence of replacement resorption.Material and Methods:  Fifty‐one intruded permanent incisors were studied in 20 boys and 19 girls aged 6 to 17 years. Only three patients were over 12 years of age. Complete intrusion had occurred in 21 teeth, and 31 teeth were classified as immature. Re‐eruption was awaited for 37 teeth. The remaining teeth were repositioned orthodontically (7 teeth) or surgically (7 teeth).Results:  Re‐eruption occurred in 35 out of 37 teeth over a period of 3–12 months. After a mean observation period of 4 years ranging from 1–12 years, retained pulp vitality was recorded in 22 teeth (43%). Pulp necrosis had developed in 57%, inflammatory resorption in 26% and replacement resorption in 12%. Whereas all inflammatory resorptions were arrested after long‐term calcium hydroxide treatment, replacement resorption always led to complete root resorption. In the analysis all orthodontic and surgical repositioned teeth were combined into an active treatment group. The non‐active treatment group consisted of teeth allowed to re‐erupt. The distribution of replacement resorption was significantly lower in teeth allowed to re‐erupt than in teeth repositioned actively.Conclusions:  The best treatment of intruded incisors in 6–12 year‐old children is to await re‐eruption. Should endodontic treatment be required before re‐eruption has occurred, a gingivectomy can be performed to gain access to the root canal.
Pulp and periodontal healing of laterally luxated permanent teeth: results after 4 years
Authors: Ferrazzini Pozzi Elena C. , Von Arx Thomas 
Published: November 2008

Abstract –  Aim:  To evaluate the pulp and periodontal healing of laterally luxated permanent teeth.Material and methods:  Patients presenting with lateral luxation of permanent teeth during 2001–2002 were enrolled in this clinical study. Laterally luxated teeth were repositioned and splinted with a TTS/composite resin splint for 4 weeks. Immediate (prophylactic) root‐canal treatment was performed in severely luxated teeth with radiographically closed apices. All patients received tetracycline for 10 days. Re‐examinations were performed after 1, 2, 3, 6, 12 and 48 months.Results:  All 47 laterally luxated permanent teeth that could be followed over the entire study period survived. In 10 teeth (21.3%), a prophylactic root‐canal treatment was performed within 2 weeks following injury. The remaining 37 teeth showed the following characteristics at the 4‐year re‐examination: 19 teeth (51.4%) had pulp survival (no clinical or radiographic signs or symptoms), nine teeth (24.3%) presented with pulp canal calcification, and pulp necrosis was seen in another nine teeth (24.3%), within the first year after trauma. None of the teeth with a radiographically open apex at the time of lateral luxation showed complications. External root resorption was only seen in one tooth.Conclusions:  Laterally luxated permanent teeth with incomplete root formation have a good prognosis, with all teeth surviving in this study. The most frequent complication was pulp necrosis that was only seen in teeth with closed apices.
Dental trauma in an Australian rural centre
Authors: Lam Raymond , Abbott Paul , Lloyd Christopher , Lloyd Carmel , Kruger Estie , Tennant Marc 
Published: November 2008

Abstract –  Background/Aim:  There is little epidemiological research regarding dental trauma in Australia. Previous research has largely focused on specific sub‐populations with data not necessarily applicable to a general rural Australian population. Studies from other countries have presented variable data and the relevance of their findings to the Australian setting is questionable. The aim of this study was to investigate the prevalence, causes and presentation of dental trauma in a large rural centre in Australia.Materials and methods:  A retrospective analysis was performed of the dental records of 323 consecutive patients who had attended a private general dental practice in Bunbury, Western Australia following an injury to their teeth and/or mouths during the period from May 2000 to December 2005 (inclusive). Injuries were classified using the Andreasen system (1994). Data analysis was carried out using spss software and Chi‐Square tests were performed with the level of significance set at 5%.Results:  There were 528 teeth injured and eight patients had only soft tissue injuries. Males (68.1%) significantly outnumbered females (31.9%) and the ages ranged from 10 months to 78 years. The highest number of injuries occurred in children and adolescents, specifically the 0‐ to 4‐year age group followed by the 5‐ to 9‐year age and 10‐ to 14‐year age groups. Trauma was most frequently the result of falls, accidents while playing and participating in sports activities.Conclusions:  The maxillary central incisors were the most commonly injured teeth in both the primary and permanent dentitions. Uncomplicated crown fractures were the most common injury followed by luxations and subluxations. No significant differences in frequency were reported for the different days of the week, the different months or seasons of the year. Only one‐third of the patients presented for dental treatment within 24 h of the injury while the remainder delayed seeking treatment for varying times up to 1 year.
Post‐flood field investigations in upland catchments after major flash floods: proposal of a methodology and illustrations
Authors: Gaume E. , Borga M. 
Published: November 2008

AbstractPost‐event survey and investigation is one way to gain experience on natural hazards. The importance of the systematisation and standardisation of such investigations and re‐analysis is progressively recognised in all the geophysical sciences as shown by the growing number of scientific papers and programs on the subject. But how to proceed in the case of a flash floods, what type of data should be collected for what type of analyses and to explore which particular issues? To give a first answer to these questions, a methodology for post‐flash flood field investigations has been developed under the EC FLOODsite project and tested under the EC HYDRATE project. This paper presents shortly the principles of this methodology and illustrates its application for the study of two major flash floods that occurred in November 1999 and September 2002 in the South of France.
Helping Children in the Child Welfare Systems Heal from Trauma: A Systems Integration Approach
Authors: Kletzka Nicole Taylor , Siegfried Christine 
Published: November 2008

ABSTRACTNumerous organizations touch the lives of children and their families following incidents of maltreatment, including family/dependency courts, child welfare agencies, foster parent associations, foster care agencies or substitute care facilities, mental health agencies, and others. The way these organizations work together is critically important. They have the potential to promote child safety and reduce the harmful impact of maltreatment on children, but also, unfortunately, at times their actions may worsen the traumatic experience for children and their families. The National Child Traumatic Stress Network conducted a survey of 53 child‐serving organizations in 10 states, to assess the ways the organizations gather and share trauma‐related information and the basic training about child trauma their staffs receive. The goal was to determine how the various service systems, including the courts, communicate with each other about trauma and the extent to which, alone or in combination, they promote children's healing following traumatic events. The survey results point to a need to improve collaboration on issues associated with child maltreatment and trauma. Judges can be important leaders in bringing about necessary changes. Recommendations for judges and courts are included.
Children Who Have Been Traumatized: One Court's Response
Authors: Howard Judge Michael L. , Tener Robin R. 
Published: November 2008

ABSTRACTA court that is trauma‐informed can assist with the process of identifying children in need of trauma‐focused services and can provide education and direction to families frustrated by prior treatment failures. The unique role of the juvenile court judge as a community convener offers an opportunity to increase community awareness about the impact of trauma, and to promote the adoption of evidence‐based treatment for trauma victims. This article outlines the way that increased trauma awareness and trauma screening within a family court system mobilized the development of effective resources for children and families affected by trauma.
Children with Sexual Behavior Problems
Authors: Swisher Lisa M. , Silovsky Jane F. , Stuart Judge Roger H. , Pierce Keri 
Published: November 2008

ABSTRACTJudges are encountering more cases (both dependent and delinquent) involving juveniles under the age of 12 who have acted out sexually. The youth's own trauma history and protection issues often complicate the cases. This article reviews the research about treatment for children with sexual behavior problems (SBP) and discusses guidelines for making placement decisions in order to assist judges to determine an appropriate level of response in cases of children with SBP. To this end, information about typical sexual development with strategies for determining whether a sexual behavior is problematic or developmentally appropriate is provided. Children with SBP are contrasted with adolescent and adult sexual offenders. Assessment and treatment guidelines based on the current state of clinical research are provided, noting that a number of treatments have demonstrated efficacy with SBP in children. Information to facilitate decision making regarding residential placement, school participation, and family reunification is provided. Public policy should be based on scientific results and reflect the very low risk posed by children with SBP when making decisions about application of the Adam Walsh Act and national lifetime registries in general.
Variation in
Salmonella enterica
Serovar Typhi IncHI1 Plasmids during the Global Spread of Resistant Typhoid Fever
Authors: Phan Minh-Duy , Kidgell Claire , Nair Satheesh , Holt Kathryn E. , Turner Arthur K. , Hinds Jason , Butcher Philip , Cooke Fiona J. , Thomson Nicholas R. , Titball Richard , Bhutta Zulfiqar A. , Hasan Rumina , Dougan Gordon , Wain John 
Published: November 2008

ABSTRACT

A global collection of plasmids of the IncHI1 incompatibility group from
Salmonella enterica
serovar Typhi were analyzed by using a combination of DNA sequencing, DNA sequence analysis, PCR, and microarrays. The IncHI1 resistance plasmids of serovar Typhi display a backbone of conserved gene content and arrangement, within which are embedded preferred acquisition sites for horizontal DNA transfer events. The variable regions appear to be preferred acquisition sites for DNA, most likely through composite transposition, which is presumably driven by the acquisition of resistance genes. Plasmid multilocus sequence typing, a molecular typing method for IncHI1 plasmids, was developed using variation in six conserved loci to trace the spread of these plasmids and to elucidate their evolutionary relationships. The application of this method to a collection of 36 IncHI1 plasmids revealed a chronological clustering of plasmids despite their difference in geographical origins. Our findings suggest that the predominant plasmid types present after 1993 have not evolved directly from the earlier predominant plasmid type but have displaced them. We propose that antibiotic selection acts to maintain resistance genes on the plasmid, but there is also competition between plasmids encoding the same resistance phenotype.
Klebsiella pneumoniae
OmpA Confers Resistance to Antimicrobial Peptides
Authors: Llobet Enrique , March Catalina , Giménez Paloma , Bengoechea José A. 
Published: November 2008

ABSTRACT

A
Klebsiella pneumoniae ompA
mutant was more susceptible to antimicrobial peptides (APs) than the wild type. Susceptibility did not result from surface changes other than the absence of OmpA. Our data suggest that OmpA is implicated in the activation of yet-unknown systems dedicated to ameliorating AP cytotoxicity.
Targeting Type III Secretion in
Yersinia pestis
Authors: Pan Ning J. , Brady Michael J. , Leong John M. , Goguen Jon D. 
Published: November 2008

ABSTRACT

Yersinia pestis
, the causative agent of plague, utilizes a plasmid-encoded type III secretion system (T3SS) to aid it with its resistance to host defenses. This system injects a set of effector proteins known as Yops (
Yersinia
outer proteins) into the cytosol of host cells that come into contact with the bacteria. T3SS is absolutely required for the virulence of
Y. pestis
, making it a potential target for new therapeutics. Using a novel and simple high-throughput screening method, we examined a diverse collection of chemical libraries for small molecules that inhibit type III secretion in
Y. pestis
. The primary screening of 70,966 compounds and mixtures yielded 421 presumptive inhibitors. We selected eight of these for further analysis in secondary assays. Four of the eight compounds effectively inhibited Yop secretion at micromolar concentrations. Interestingly, we observed differential inhibition among Yop species with some compounds. The compounds did not inhibit bacterial growth at the concentrations used in the inhibition assays. Three compounds protected HeLa cells from type III secretion-dependent cytotoxicity. Of the eight compounds examined in secondary assays, four show good promise as leads for structure-activity relationship studies. They are a diverse group, with each having a chemical scaffold not only distinct from each other but also distinct from previously described candidate type III secretion inhibitors.
Real-Time Monitoring of Human Enterovirus (HEV)-Infected Cells and Anti-HEV 3C Protease Potency by Fluorescence Resonance Energy Transfer
Authors: Tsai Meng-Tian , Cheng Yun-Hsiang , Liu Yu-Ning , Liao Nien-Chien , Lu Wen-Wen , Kung Szu-Hao 
Published: November 2008

ABSTRACT

A real-time assay system that allows monitoring of intracellular human enterovirus (HEV) protease activity was established using the principle of fluorescence resonance energy transfer (FRET). It was accomplished by engineering cells to constitutively express a genetically encoded FRET probe. The FRET-based probe was designed to contain an enterovirus 71 3C protease (3C
pro
) cleavage motif flanked by the FRET pair composed of green fluorescent protein 2 and red fluorescent protein 2 (DsRed2). Efficient FRET from the stable line was detected in a real-time manner by fluorescence microscopy, and the disruption of FRET was readily monitored upon HEV infection. The level of the repressed FRET was proportional to the input virus titer and the infection duration as measured by the fluorometric method. The FRET biosensor cell line was also responsive to other related HEV serotypes, but not to the phylogenetically distant herpes simplex virus, which was confirmed by Western blot analysis. The FRET biosensor was then utilized to develop a format for the determination of antiviral susceptibility, as the reduced FRET appeared to reflect viral replication. Evaluations of the FRET biosensor system with representative HEV serotypes demonstrated that their susceptibilities to a 3C
pro
inhibitor, rupintrivir, were all accurately determined. In summary, this novel FRET-based system is a means for rapid detection, quantification, and drug susceptibility testing for HEVs, with potential for the development of a high-throughput screening assay.
Discovery of a Small-Molecule Inhibitor of β-1,6-Glucan Synthesis
Authors: Kitamura Akihiro , Someya Kazuhiko , Hata Masato , Nakajima Ryohei , Takemura Makoto 
Published: November 2008

ABSTRACT

It is possible that antifungal drugs with novel modes of action will provide favorable options to treat fungal infections. In the course of our screening for antifungal compounds acting on the cell wall, a pyridobenzimidazole derivative with unique activities, named D75-4590, was discovered. During treatment of
Saccharomyces cerevisiae
with D75-4590, (i) incorporation of [
14
C]glucose into the β-1,6-glucan component was selectively reduced, (ii) proteins released from the cell had lost the β-1,6-glucan moiety, and (iii) cells tended to clump, resulting in impaired cell growth. Genetic analysis of a D75-4590-resistant mutant of
S. cerevisiae
indicated that its primary target was Kre6p, which is considered to be one of the β-1,6-glucan synthases. These results strongly suggest that D75-4590 is a specific inhibitor of β-1,6-glucan synthesis. D75-4590 showed potent activities against various
Candida
species. It inhibited hyphal elongation of
C. albicans
as well.
KRE6
is conserved in various fungi, but no homologue has been found in mammalian cells. These lines of evidence indicate that D75-4590 is a promising lead compound for novel antifungal drugs. To our knowledge, this is the first report of a β-1,6-glucan inhibitor.
Characterization and Sequence Analysis of Extended-Spectrum-β-Lactamase-Encoding Genes from
Escherichia coli, Klebsiella pneumoniae
, and
Proteus mirabilis
Isolates Collected during Tigecycline Phase 3 Clinical Trials
Authors: Jones C. Hal , Tuckman Margareta , Keeney David , Ruzin Alexey , Bradford Patricia A. 
Published: November 2008

ABSTRACT

In concert with the development of novel β-lactams and broad-spectrum cephalosporins, bacterially encoded β-lactamases have evolved to accommodate the new agents. This study was designed to identify, at the sequence level, the genes responsible for the extended-spectrum-β-lactamase (ESBL) phenotypes of
Escherichia coli, Klebsiella pneumoniae
, and
Proteus mirabilis
isolates collected during the global tigecycline phase 3 clinical trials. PCR assays were developed to identify and clone the
bla
TEM
,
bla
SHV
,
bla
OXA
, and
bla
CTX
genes from clinical strains. Isolates were also screened for AmpC genes of the
bla
CMY
,
bla
ACT
,
bla
FOX
, and
bla
DHA
families as well as the
bla
KPC
genes encoding class A carbapenemases.
E. coli, K. pneumoniae
, and
P. mirabilis
isolates with ceftazidime MICs of ≥2 μg/ml were designated possible ESBL-producing pathogens and were then subjected to a confirmatory test for ESBLs by use of Etest. Of 272 unique patient isolates, 239 were confirmed by PCR and sequencing to carry the genes for at least one ESBL, with 44% of the positive isolates harboring the genes for multiple ESBLs. In agreement with current trends for ESBL distribution,
bla
CTX-M
-type β-lactamase genes were found in 83% and 71% of the ESBL-positive
E. coli
and
K. pneumoniae
isolates, respectively, whereas
bla
SHV
genes were found in 41% and 28% of the ESBL-positive
K. pneumoniae
and
E. coli
isolates, respectively. Ninety-seven percent of the
E. coli
and
K. pneumoniae
isolates were tigecycline susceptible (MIC
90
= 2 μg/ml), warranting further studies to define the therapeutic utility of tigecycline against strains producing ESBLs in a clinical setting.