bluuebunny/crossref_metadata_2025_split huggingface dataset:
The RHNumtS compilation: Features and bioinformatics approaches to locate and quantify Human NumtS
Authors: Lascaro Daniela , Castellana Stefano , Gasparre Giuseppe , Romeo Giovanni , Saccone Cecilia , Attimonelli Marcella 
Published: August 2009

AbstractBackgroundTo a greater or lesser extent, eukaryotic nuclear genomes contain fragments of their mitochondrial genome counterpart, deriving from the random insertion of damaged mtDNA fragments. NumtS (Nuclear mt Sequences) are not equally abundant in all species, and are redundant and polymorphic in terms of copy number. In population and clinical genetics, it is important to have a complete overview of NumtS quantity and location. Searching PubMed for NumtS or Mitochondrial pseudo-genes yields hundreds of papers reporting Human NumtS compilations produced byin silicoor wet-lab approaches. A comparison of published compilations clearly shows significant discrepancies among data, due both to unwise application of Bioinformatics methods and to a not yet correctly assembled nuclear genome. To optimize quantification and location of NumtS, we produced a consensus compilation of Human NumtS by applying various bioinformatics approaches.ResultsLocation and quantification of NumtS may be achieved by applying database similarity searching methods: we have applied various methods such as Blastn, MegaBlast and BLAT, changing both parameters and database; the results were compared, further analysed and checked against the already published compilations, thus producing the Reference Human Numt Sequences (RHNumtS) compilation. The resulting NumtS total 190.ConclusionThe RHNumtS compilation represents a highly reliable reference basis, which may allow designing a lab protocol to test the actual existence of each NumtS. Here we report preliminary results based on PCR amplification and sequencing on 41 NumtS selected from RHNumtS among those with lower score. In parallel, we are currently designing the RHNumtS database structure for implementation in the HmtDB resource. In the future, the same database will host NumtS compilations from other organisms, but these will be generated only when the nuclear genome of a specific organism has reached a high-quality level of assembly.
Integrative analysis of RUNX1 downstream pathways and target genes
Authors: Michaud Joëlle , Simpson Ken M , Escher Robert , Buchet-Poyau Karine , Beissbarth Tim , Carmichael Catherine , Ritchie Matthew E , Schütz Frédéric , Cannon Ping , Liu Marjorie , Shen Xiaofeng , Ito Yoshiaki , Raskind Wendy H , Horwitz Marshall S , Osato Motomi , Turner David R , Speed Terence P , Kavallaris Maria , Smyth Gordon K , Scott Hamish S 
Published: August 2009

AbstractBackgroundTheRUNX1transcription factor gene is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It is also responsible for a familial platelet disorder with predisposition to acute myeloid leukemia (FPD-AML). The disruption of the largely unknown biological pathways controlled by RUNX1 is likely to be responsible for the development of leukemia. We have used multiple microarray platforms and bioinformatic techniques to help identify these biological pathways to aid in the understanding of why RUNX1 mutations lead to leukemia.ResultsHere we report genes regulated either directly or indirectly by RUNX1 based on the study of gene expression profiles generated from 3 different human and mouse platforms. The platforms used were global gene expression profiling of: 1) cell lines with RUNX1 mutations from FPD-AML patients, 2) over-expression of RUNX1 and CBFβ, and 3) Runx1 knockout mouse embryos using either cDNA or Affymetrix microarrays. We observe that our datasets (lists of differentially expressed genes) significantly correlate with published microarray data from sporadic AML patients with mutations in eitherRUNX1or its cofactor,CBFβ. A number of biological processes were identified among the differentially expressed genes and functional assays suggest that heterozygousRUNX1point mutations in patients with FPD-AML impair cell proliferation, microtubule dynamics and possibly genetic stability. In addition, analysis of the regulatory regions of the differentially expressed genes has for the first time systematically identified numerous potential novel RUNX1 target genes.ConclusionThis work is the first large-scale study attempting to identify the genetic networks regulated by RUNX1, a master regulator in the development of the hematopoietic system and leukemia. The biological pathways and target genes controlled by RUNX1 will have considerable importance in disease progression in both familial and sporadic leukemia as well as therapeutic implications.
The human gastric pathogen Helicobacter pylori has a potential acetone carboxylase that enhances its ability to colonize mice
Authors: Brahmachary Priyanka , Wang Ge , Benoit Stéphane L , Weinberg Michael V , Maier Robert J , Hoover Timothy R 
Published: August 2009

Abstract

Background

Helicobacter pylori colonizes the human stomach and is the etiological agent of peptic ulcer disease. All three H. pylori strains that have been sequenced to date contain a potential operon whose products share homology with the subunits of acetone carboxylase (encoded by acxABC) from Xanthobacter autotrophicus strain Py2 and Rhodobacter capsulatus strain B10. Acetone carboxylase catalyzes the conversion of acetone to acetoacetate. Genes upstream of the putative acxABC operon encode enzymes that convert acetoacetate to acetoacetyl-CoA, which is metabolized further to generate two molecules of acetyl-CoA.

Results
To determine if the H. pylori acxABC operon has a role in host colonization the acxB homolog in the mouse-adapted H. pylori SS1 strain was inactivated with a chloramphenicol-resistance (cat) cassette. In mouse colonization studies the numbers of H. pylori recovered from mice inoculated with the acxB:cat mutant were generally one to two orders of magnitude lower than those recovered from mice inoculated with the parental strain. A statistical analysis of the data using a Wilcoxin Rank test indicated the differences in the numbers of H. pylori isolated from mice inoculated with the two strains were significant at the 99% confidence level. Levels of acetone associated with gastric tissue removed from uninfected mice were measured and found to range from 10–110 μmols per gram wet weight tissue.

Conclusion
The colonization defect of the acxB:cat mutant suggests a role for the acxABC operon in survival of the bacterium in the stomach. Products of the H. pylori acxABC operon may function primarily in acetone utilization or may catalyze a related reaction that is important for survival or growth in the host. H. pylori encounters significant levels of acetone in the stomach which it could use as a potential electron donor for microaerobic respiration.
Enhancing bile tolerance improves survival and persistence of Bifidobacterium and Lactococcus in the murine gastrointestinal tract
Authors: Watson Debbie , Sleator Roy D , Hill Colin , Gahan Cormac GM 
Published: August 2009

AbstractBackgroundThe majority of commensal gastrointestinal bacteria used as probiotics are highly adapted to the specialised environment of the large bowel. However, unlike pathogenic bacteria; they are often inadequately equipped to endure the physicochemical stresses of gastrointestinal (GI) delivery in the host. Herein we outline a patho-biotechnology strategy to improve gastric delivery and host adaptation of a probiotic strainBifidobacterium breveUCC2003 and the generally regarded as safe (GRAS) organismLactococcus lactisNZ9000.ResultsIn vitrobile tolerance of both strains was significantly enhanced (P< 0.001), following heterologous expression of theListeria monocytogenesbile resistance mechanism BilE. Strains harbouringbilEwere also recovered at significantly higher levels (P< 0.001), than control strains from the faeces and intestines of mice (n= 5), following oral inoculation. Furthermore, aB. brevestrain expressingbilEdemonstrated increased efficacy relative to the wild-type strain in reducing oralL. monocytogenesinfection in mice.ConclusionCollectively the data indicates that bile tolerance can be enhanced inBifidobacteriumandLactococcusspecies through rational genetic manipulation and that this can significantly improve delivery to and colonisation of the GI tract.
Diversity of the parB and repA genes of the Burkholderia cepacia complex and their utility for rapid identification of Burkholderia cenocepacia
Authors: Drevinek Pavel , Baldwin Adam , Dowson Christopher G , Mahenthiralingam Eshwar 
Published: August 2009

Abstract

Background

Burkholderia cenocepacia is the most prominent species of the B. cepacia complex (Bcc), a group of nine closely related and difficult to identify bacteria that cause serious infections in patients with cystic fibrosis. Despite its clinical relevance, identification of B. cenocepacia as a single species is unavailable, as it splits by a widely used recA gene-based PCR identification method into discrete phylogenetic subgroups IIIA, IIIB, IIIC and IIID. With the aim of identifying gene targets suitable for unified detection of B. cenocepacia strains, we examined sequence polymorphisms in the repA and parB genes. These essential genes are involved in the replication and partitioning of bacterial replicons, hence we also had the opportunity for the first time to investigate the evolution of the multireplicon (three chromosome) structure of Bcc genomes.

Results
Alignment of the repA and parB genes from publicly available Bcc genome sequences enabled the design of primers for their amplification and sequence analysis. Multilocus sequencing typing, a highly discriminatory method for Bcc species and strain discrimination, was used to select strains of unique sequence types (STs) that spanned the known Bcc genetic diversity. Sequence datasets of repA (83 isolates, 67 STs) and parB (120 isolates, 95 STs) genes from the second chromosome were aligned and examined phylogenetically to identify polymorphisms suitable for identification of B. cenocepacia. In contrast to parB, the Bcc repA sequences demonstrated distinct clustering of B. cenocepacia from other species, which enabled the design a species-specific multiplex PCR. The novel single-reaction B. cenocepacia detection method was tested on a panel of 142 different Bcc strains (142 STs) and distinguished recA groups IIIA, IIIB and IIID, from all other Bcc members with 100% sensitivity and 93% specificity.

Conclusion
The repA-based multiplex PCR is a useful aid to the rapid identification of the most clinically relevant B. cenocepacia recA subgroups IIIA, IIIB and IIID. Phylogenetic analysis of repA and parB genes demonstrated that acquisition of the second and third replicons of Bcc genomes occurred prior to their differentiation into discrete species and that the sharing of replicons across species had not occurred.
The Kv2.1 K+ channel targets to the axon initial segment of hippocampal and cortical neurons in culture and in situ
Authors: Sarmiere Patrick D , Weigle Cecile M , Tamkun Michael M 
Published: August 2009

Abstract

Background
The Kv2.1 delayed-rectifier K+ channel regulates membrane excitability in hippocampal neurons where it targets to dynamic cell surface clusters on the soma and proximal dendrites. In the past, Kv2.1 has been assumed to be absent from the axon initial segment.

Results
Transfected and endogenous Kv2.1 is now demonstrated to preferentially accumulate within the axon initial segment (AIS) over other neurite processes; 87% of 14 DIV hippocampal neurons show endogenous channel concentrated at the AIS relative to the soma and proximal dendrites. In contrast to the localization observed in pyramidal cells, GAD positive inhibitory neurons within the hippocampal cultures did not show AIS targeting. Photoactivable-GFP-Kv2.1-containing clusters at the AIS were stable, moving <1 μm/hr with no channel turnover. Photobleach studies indicated individual channels within the cluster perimeter were highly mobile (FRAP τ = 10.4 ± 4.8 sec), supporting our model that Kv2.1 clusters are formed by the retention of mobile channels behind a diffusion-limiting perimeter. Demonstrating that the AIS targeting is not a tissue culture artifact, Kv2.1 was found in axon initial segments within both the adult rat hippocampal CA1, CA2, and CA3 layers and cortex.

Conclusion
In summary, Kv2.1 is associated with the axon initial segment both in vitro and in vivo where it may modulate action potential frequency and back propagation. Since transfected Kv2.1 initially localizes to the AIS before appearing on the soma, it is likely multiple mechanisms regulate Kv2.1 trafficking to the cell surface.
Heat shock protein 90: translation from cancer to Alzheimer's disease treatment?
Authors: Luo Wenjie , Rodina Anna , Chiosis Gabriela 
Published: August 2009

Abstract
Both malignant transformation and neurodegeneration, as it occurs in Alzheimer's disease, are complex and lengthy multistep processes characterized by abnormal expression, post-translational modification, and processing of certain proteins. To maintain and allow the accumulation of these dysregulated processes, and to facilitate the step-wise evolution of the disease phenotype, cells must co-opt a compensatory regulatory mechanism. In cancer, this role has been attributed to heat shock protein 90 (Hsp90), a molecular chaperone that maintains the functional conformation of multiple proteins involved in cell-specific oncogenic processes. In this sense, at the phenotypic level, Hsp90 appears to serve as a biochemical buffer for the numerous cancer-specific lesions that are characteristic of diverse tumors. The current review proposes a similar role for Hsp90 in neurodegeneration. It will present experimentally demonstrated, but also hypothetical, roles that suggest Hsp90 can act as a regulator of pathogenic changes that lead to the neurodegenerative phenotype in Alzheimer's disease.
Epidemiology of constipation in Europe and Oceania: a systematic review
Authors: Peppas George , Alexiou Vangelis G , Mourtzoukou Eleni , Falagas Matthew E 
Published: August 2009

Abstract

Background
We aimed to review the literature regarding the epidemiology of constipation in Europe and Oceania and the associated prevalence/risk factors.

Methods
Two reviewers performed PubMed searches and a hand search of references. A study was considered eligible for inclusion if it reported data about the prevalence of constipation in any population, free of other gastrointestinal disorders, in Europe and Oceania. Studies were evaluated for quality. Data regarding the setting, type of study, definition of constipation, study population, prevalence of constipation, factors associated with increased odds for constipation, and the female to male ratio, were collected.

Results
The 21 reviewed studies depict prevalence rates in 34 different population groups ranging widely from a low 0.7% to a high 81%. In the general population of Europe the mean value of the reported constipation rates is 17,1 % and the median value 16.6%. Among the studies conducted in Oceania, the mean value of constipation prevalence was 15.3%. Female gender, age and socioeconomic and educational class seem to have major effect on constipation prevalence. A number of various other risk factors are, less clearly, associated with constipation.

Conclusion
This systematic review depicts the high prevalence and related risk factors of a disorder that decreases the health-related quality of life and has major economic consequences.
A survey of knowledge, attitudes and practices towards avian influenza in an adult population of Italy
Authors: Di Giuseppe Gabriella , Abbate Rossella , Albano Luciana , Marinelli Paolo , Angelillo Italo F 
Published: August 2009

AbstractBackgroundSeveral public health strategic interventions are required for effective prevention and control of avian influenza (AI) and it is necessary to create a communication plan to keep families adequately informed on how to avoid or reduce exposure. This investigation determined the knowledge, attitudes, and behaviors relating to AI among an adult population in Italy.MethodsFrom December 2005 to February 2006 a random sample of 1020 adults received a questionnaire about socio-demographic characteristics, knowledge of transmission and prevention about AI, attitudes towards AI, behaviors regarding use of preventive measures and food-handling practices, and sources of information about AI.ResultsA response rate of 67% was achieved. Those in higher socioeconomic classes were more likely to identify the modes of transmission and the animals' vehicles for AI. Those older, who knew the modes of transmission and the animals' vehicles for AI, and who still need information, were more likely to know that washing hands soap before and after touching raw poultry meat and using gloves is recommended to avoid spreading of AI through food. The risk of being infected was significantly higher in those from lower socioeconomic classes, if they did not know the definition of AI, if they knew that AI could be transmitted by eating and touching raw eggs and poultry foods, and if they did not need information. Compliance with the hygienic practices during handling of raw poultry meat was more likely in those who perceived to be at higher risk, who knew the hygienic practices, who knew the modes of transmission and the animals' vehicles for AI, and who received information from health professionals and scientific journals.ConclusionRespondents demonstrate no detailed understanding of AI, a greater perceived risk, and a lower compliance with precautions behaviors and health educational strategies are strongly needed.
Emergence of unusual human rotavirus strains in Salento, Italy, during 2006–2007
Authors: De Donno Antonella , Grassi Tiziana , Bagordo Francesco , Idolo Adele , Cavallaro Alessandra , Gabutti Giovanni ,   the Collaborative Group for the surveillance of Rotavirus Infection
Published: August 2009

Abstract

Background
In recent years, rotavirus genotyping by RT-PCR has provided valuable information about the diversity of rotaviruses (RV) circulating throughout the world.
The purpose of the present study was to monitor the prevalence of the different G and P genotypes of rotaviruses circulating in Salento and detect any uncommon or novel types.

Methods
During the period from January 2006 to December 2007, a total of 243 rotavirus positive stool samples were collected from children with diarrhoea admitted to four Hospitals in the province of Lecce (Copertino, Galatina, Gallipoli and Tricase).
All the specimens were tested for RV by real time PCR and genotyped for VP7 (G-type) and VP4 (P-type) gene by reverse transcription (RT) and multiplex PCR using different type specific primers.

Results
In course of this study we identified 4 common G&P combinations viz. G2P[8], G1P[8], G2P[4] and G9P[8] amongst 59.8% of the typeable rotavirus positives.
Rotavirus G2P[8] was recognized as the most widespread genotype during the sentinel-based survey in Salento.
The detection of other novel and unusual strains, such as G2P[10], G4P[10], G8P[4], G9P[11] and G10P[8] is noteworthy.
Furthermore, a significant number of mixed infections were observed during the survey period but G3P[8] rotaviruses were not detected.

Conclusion
This study highlights the genetic diversity among rotaviruses isolated from children in Salento and the emergence of some novel strains. Therefore, it is highly essential to continuously monitor for these strains so as to assess the impact of vaccines on RV strains circulating in Salento and understand the effect of strain variation on efficacy of presently available vaccines.
Antiviral resistance during pandemic influenza: implications for stockpiling and drug use
Authors: Arino Julien , Bowman Christopher S , Moghadas Seyed M 
Published: August 2009

Abstract

Background
The anticipated extent of antiviral use during an influenza pandemic can have adverse consequences for the development of drug resistance and rationing of limited stockpiles. The strategic use of drugs is therefore a major public health concern in planning for effective pandemic responses.

Methods
We employed a mathematical model that includes both sensitive and resistant strains of a virus with pandemic potential, and applies antiviral drugs for treatment of clinical infections. Using estimated parameters in the published literature, the model was simulated for various sizes of stockpiles to evaluate the outcome of different antiviral strategies.

Results
We demonstrated that the emergence of highly transmissible resistant strains has no significant impact on the use of available stockpiles if treatment is maintained at low levels or the reproduction number of the sensitive strain is sufficiently high. However, moderate to high treatment levels can result in a more rapid depletion of stockpiles, leading to run-out, by promoting wide-spread drug resistance. We applied an antiviral strategy that delays the onset of aggressive treatment for a certain amount of time after the onset of the outbreak. Our results show that if high treatment levels are enforced too early during the outbreak, a second wave of infections can potentially occur with a substantially larger magnitude. However, a timely implementation of wide-scale treatment can prevent resistance spread in the population, and minimize the final size of the pandemic.

Conclusion
Our results reveal that conservative treatment levels during the early stages of the outbreak, followed by a timely increase in the scale of drug-use, will offer an effective strategy to manage drug resistance in the population and avoid run-out. For a 1918-like strain, the findings suggest that pandemic plans should consider stockpiling antiviral drugs to cover at least 20% of the population.