bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide analysis of gene expression during Xenopus tropicalis tadpole tail regeneration
Authors: Love Nick R , Chen Yaoyao , Bonev Boyan , Gilchrist Michael J , Fairclough Lynne , Lea Robert , Mohun Timothy J , Paredes Roberto , Zeef Leo AH , Amaya Enrique
Published: November 2011

Background

The molecular mechanisms governing vertebrate appendage regeneration remain poorly understood. Uncovering these mechanisms may lead to novel therapies aimed at alleviating human disfigurement and visible loss of function following injury. Here, we explore tadpole tail regeneration in Xenopus tropicalis, a diploid frog with a sequenced genome.

Results

We found that, like the traditionally used Xenopus laevis, the Xenopus tropicalis tadpole has the capacity to regenerate its tail following amputation, including its spinal cord, muscle, and major blood vessels. We examined gene expression using the Xenopus tropicalis Affymetrix genome array during three phases of regeneration, uncovering more than 1,000 genes that are significantly modulated during tail regeneration. Target validation, using RT-qPCR followed by gene ontology (GO) analysis, revealed a dynamic regulation of genes involved in the inflammatory response, intracellular metabolism, and energy regulation. Meta-analyses of the array data and validation by RT-qPCR and in situ hybridization uncovered a subset of genes upregulated during the early and intermediate phases of regeneration that are involved in the generation of NADP/H, suggesting that these pathways may be important for proper tail regeneration.

Conclusions

The Xenopus tropicalis tadpole is a powerful model to elucidate the genetic mechanisms of vertebrate appendage regeneration. We have produced a novel and substantial microarray data set examining gene expression during vertebrate appendage regeneration.
Evolution of anterior Hox regulatory elements among chordates
Authors: Natale Alfonso , Sims Carrie , Chiusano Maria L , Amoroso Alessandro , D'Aniello Enrico , Fucci Laura , Krumlauf Robb , Branno Margherita , Locascio Annamaria
Published: November 2011

Background

The Hox family of transcription factors has a fundamental role in segmentation pathways and axial patterning of embryonic development and their clustered organization is linked with the regulatory mechanisms governing their coordinated expression along embryonic axes. Among chordates, of particular interest are the Hox paralogous genes in groups 1-4 since their expression is coupled to the control of regional identity in the anterior nervous system, where the highest structural diversity is observed.

Results

To investigate the degree of conservation in cis-regulatory components that form the basis of Hox expression in the anterior nervous system, we have used assays for transcriptional activity in ascidians and vertebrates to compare and contrast regulatory potential. We identified four regulatory sequences located near the CiHox1, CiHox2 and CiHox4 genes of the ascidian Ciona intestinalis which direct neural specific domains of expression. Using functional assays in Ciona and vertebrate embryos in combination with sequence analyses of enhancer fragments located in similar positions adjacent to Hox paralogy group genes, we compared the activity of these four Ciona cis-elements with a series of neural specific enhancers from the amphioxus Hox1-3 genes and from mouse Hox paralogous groups 1-4.

Conclusions

This analysis revealed that Kreisler and Krox20 dependent enhancers critical in segmental regulation of the hindbrain appear to be specific for the vertebrate lineage. In contrast, neural enhancers that function as Hox response elements through the action of Hox/Pbx binding motifs have been conserved during chordate evolution. The functional assays reveal that these Hox response cis-elements are recognized by the regulatory components of different and extant species. Together, our results indicate that during chordate evolution, cis-elements dependent upon Hox/Pbx regulatory complexes, are responsible for key aspects of segmental Hox expression in neural tissue and appeared with urochordates after cephalochordate divergence.
Microsatellite distribution on sex chromosomes at different stages of heteromorphism and heterochromatinization in two lizard species (Squamata: Eublepharidae: Coleonyx elegans and Lacertidae: Eremias velox)
Authors: Pokorná Martina , Kratochvíl Lukáš , Kejnovský Eduard
Published: November 2011

Background

The accumulation of repetitive sequences such as microsatellites during the differentiation of sex chromosomes has not been studied in most squamate reptiles (lizards, amphisbaenians and snakes), a group which has a large diversity of sex determining systems. It is known that the Bkm repeats containing tandem arrays of GATA tetranucleotides are highly accumulated on the degenerated W chromosomes in advanced snakes. Similar, potentially homologous, repetitive sequences were found on sex chromosomes in other vertebrates. Using FISH with probes containing all possible mono-, di-, and tri-nucleotide sequences and GATA, we studied the genome distribution of microsatellite repeats on sex chromosomes in two lizard species (the gecko Coleonyx elegans and the lacertid Eremias velox) with independently evolved sex chromosomes. The gecko possesses heteromorphic euchromatic sex chromosomes, while sex chromosomes in the lacertid are homomorphic and the W chromosome is highly heterochromatic. Our aim was to test whether microsatellite distribution on sex chromosomes corresponds to the stage of their heteromorphism or heterochromatinization. Moreover, because the lizards lie phylogenetically between snakes and other vertebrates with the Bkm-related repeats on sex chromosomes, the knowledge of their repetitive sequence is informative for the determination of conserved versus convergently evolved repetitive sequences across vertebrate lineages.

Results

Heteromorphic sex chromosomes of C. elegans do not show any sign of microsatellite accumulation. On the other hand, in E. velox, certain microsatellite sequences are extensively accumulated over the whole length or parts of the W chromosome, while others, including GATA, are absent on this heterochromatinized sex chromosome.

Conclusion

The accumulation of microsatellite repeats corresponds to the stage of heterochromatinization of sex chromosomes rather than to their heteromorphism. The lack of GATA repeats on the sex chromosomes of both lizards suggests that the Bkm-related repeats on sex chromosomes in snakes and other vertebrates evolved convergently. The comparison of microsatellite sequences accumulated on sex chromosomes in E. velox and in other eukaryotic organisms suggests that historical contingency, not characteristics of particular sequences, plays a major role in the determination of which microsatellite sequence is accumulated on the sex chromosomes in a particular lineage.
QTL detection for Aeromonas salmonicida resistance related traits in turbot (Scophthalmus maximus)
Authors: Rodríguez-Ramilo Silvia T , Toro Miguel A , Bouza Carmen , Hermida Miguel , Pardo Belén G , Cabaleiro Santiago , Martínez Paulino , Fernández Jesús
Published: November 2011

Background

Interactions between fish and pathogens, that may be harmless under natural conditions, often result in serious diseases in aquaculture systems. This is especially important due to the fact that the strains used in aquaculture are derived from wild strains that may not have had enough time to adapt to new disease pressures. The turbot is one of the most promising European aquaculture species. Furunculosis, caused by the bacterium Aeromonas salmonicida, produces important losses to turbot industry. An appealing solution is to achieve more robust broodstock, which can prevent or diminish the devastating effects of epizooties. Genomics strategies have been developed in turbot to look for candidate genes for resistance to furunculosis and a genetic map with appropriate density to screen for genomic associations has been also constructed. In the present study, a genome scan for QTL affecting resistance and survival to A. salmonicida in four turbot families was carried out. The objectives were to identify consistent QTL using different statistical approaches (linear regression and maximum likelihood) and to locate the tightest associated markers for their application in genetic breeding strategies.

Results

Significant QTL for resistance were identified by the linear regression method in three linkage groups (LGs 4, 6 and 9) and for survival in two LGs (6 and 9). The maximum likelihood methodology identified QTL in three LGs (5, 6 and 9) for both traits. Significant association between disease traits and genotypes was detected for several markers, some of them explaining up to 17% of the phenotypic variance. We also identified candidate genes located in the detected QTL using data from previously mapped markers.

Conclusions

Several regions controlling resistance to A. salmonicida in turbot have been detected. The observed concordance between different statistical methods at particular linkage groups gives consistency to our results. The detected associated markers could be useful for genetic breeding strategies. A finer mapping will be necessary at the detected QTL intervals to narrow associations and around the closely associated markers to look for candidate genes through comparative genomics or positional cloning strategies. The identification of associated variants at specific genes will be essential, together with the QTL associations detected in this study, for future marker assisted selection programs.
Identification of novel maize miRNAs by measuring the precision of precursor processing
Authors: Jiao Yinping , Song Weibin , Zhang Mei , Lai Jinsheng
Published: November 2011

Background

miRNAs are known to play important regulatory roles throughout plant development. Until recently, nearly all the miRNAs in maize were identified by comparative analysis to miRNAs sequences of other plant species, such as rice and Arabidopsis.

Results

To find new miRNA in this important crop, small RNAs from mixed tissues were sequenced, resulting in over 15 million unique sequences. Our sequencing effort validated 23 of the 28 known maize miRNA families, including 49 unique miRNAs. Using a newly established criterion, based on the precision of miRNA processing from precursors, we identified 66 novel miRNAs in maize. These miRNAs can be grouped into 58 families, 54 of which have not been identified in any other species. Five new miRNAs were validated by northern blot. Moreover, we found targets for 23 of the 66 new miRNAs. The targets of two of these newly identified miRNAs were confirmed by 5'RACE.

Conclusion

We have implemented a novel method of identifying miRNA by measuring the precision of miRNA processing from precursors. Using this method, 66 novel miRNAs and 50 potential miRNAs have been identified in maize.
Characterization of heterogeneous vancomycin-intermediate resistance, MIC and accessory gene regulator (agr) dysfunction among clinical bloodstream isolates of staphyloccocus aureus
Authors: Harigaya Yoriko , Ngo Dung , Lesse Alan J , Huang Vanthida , Tsuji Brian T
Published: November 2011

Background

The development of hVISA has been associated with vancomycin clinical failures and is commonly misidentified in clinical microbiology laboratories. Therefore, the objectives of this present study was to improve the reliability of methodologies and criteria for identifying hVISA, evaluate the prevalence of hVISA among clinical bloodstream isolates of S. aureus and determine if there exists a relationship between accessory gene regulator (agr) dysfunction and the hVISA phenotype.

Methods

The presence of hVISA in 220 clinical S. aureus isolates (121 MSSA, 99 MRSA) from bloodstream infections was examined by CLSI broth microdilution, Macro & Standard Etest. Isolates which were classified as hVISA by Macro Etest, were additionally evaluated using a modified PAP-AUC method using a modified starting inoculum of 1010 CFU/mL, and growth on brain heart infusion agar with 4 mg/L vancomycin (BHIV4) at 108 and 1010 CFU/mL, and agr function was assessed by delta-hemolysin production.

Results

Broth microdilution MIC50/90 of S.aureus and hVISA was 1.0/2.0 and 1.5/2.0 mg/L (p= 0.02), respectively. Macro Etest identified 12 (5.5%) hVISA isolates; higher among MRSA (9.1%) versus MSSA (2.5%) (p = 0.03). The mean modified PAP-AUC ratios (> 0.8) of 7 MRSA strains and 3 MSSA strains were significantly different (p = 0.001). 58% of hVISA strains were found to be agr dysfunctional when 21% of MRSA strains were agr dysfunctional. hVISA was detected among S. aureus bloodstream isolates, which were classified as susceptible among clinical microbiology laboratories.

Conclusions

Evaluating the correlation between Etest MICs and modified PAP-AUC ratio values will add further improvement of discriminating hVISA, and agr dysfunction may be predictive of strains which display a greater predilection to display the hVISA phenotype.
Validation of metabolic syndrome using medical records in the SUN cohort
Authors: Barrio-Lopez Maria Teresa , Bes-Rastrollo Maira , Beunza Juan Jose , Fernandez-Montero Alejandro , Garcia-Lopez Martin , Martinez-Gonzalez Miguel Angel
Published: November 2011

Background

The objective of this study was to evaluate the validity of self reported criteria of Metabolic Syndrome (MS) in the SUN (Seguimiento Universidad de Navarra) cohort using their medical records as the gold standard.

Methods

We selected 336 participants and we obtained MS related data according to Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF). Then we compared information on the self reported diagnosis of MS and MS diagnosed in their medical records. We calculated the proportion of confirmed MS, the proportion of confirmed non-MS and the intraclass correlation coefficients for each component of the MS.

Results

From those 336 selected participants, we obtained sufficient data in 172 participants to confirm or reject MS using ATP III criteria. The proportion of confirmed MS was 91.2% (95% CI: 80.7- 97.1) and the proportion of confirmed non-MS was 92.2% (95% CI: 85.7-96.4) using ATP III criteria. The proportion of confirmed MS using IDF criteria was 100% (95% CI: 87.2-100) and the proportion of confirmed non-MS was 97.1% (95% CI: 85.1-99.9). Kappa Index was 0.82 in the group diagnosed by ATP III criteria and 0.97 in the group diagnosed by IDF criteria. Intraclass correlation coefficients for the different component of MS were: 0.93 (IC 95%:0.91- 0.95) for BMI; 0.96 (IC 95%: 0.93-0.98) for waist circumference; 0.75 (IC 95%: 0.66-0.82) for fasting glucose; 0.50 (IC 95%:0.35-0.639) for HDL cholesterol; 0.78 (IC 95%: 0.70-0.84) for triglycerides; 0.49 (IC 95%:0.34-0.61) for systolic blood pressure and 0.55 (IC 95%: 0.41-0.65) for diastolic blood pressure.

Conclusions

Self-reported MS based on self reported components of the SM in a Spanish cohort of university graduates was sufficiently valid as to be used in epidemiological studies.
Efficient production of chimeric Human papillomavirus 16 L1 protein bearing the M2e influenza epitope in Nicotiana benthamiana plants
Authors: Matić Slavica , Rinaldi Riccardo , Masenga Vera , Noris Emanuela
Published: November 2011

Background

Human papillomavirus 16 (HPV-16) L1 protein has the capacity to self-assemble into capsomers or virus-like particles (VLPs) that are highly immunogenic, allowing their use in vaccine production. Successful expression of HPV-16 L1 protein has been reported in plants, and plant-produced VLPs have been shown to be immunogenic after administration to animals.

Results

We investigated the potential of HPV-16 L1 to act as a carrier of two foreign epitopes from Influenza A virus: (i) M2e2-24, ectodomain of the M2 protein (M2e), that is highly conserved among all influenza A isolates, or (ii) M2e2-9, a shorter version of M2e containing the N-terminal highly conserved epitope, that is common for both M1 and M2 influenza proteins. A synthetic HPV-16 L1 gene optimized with human codon usage was used as a backbone gene to design four chimeric sequences containing either the M2e2-24 or the M2e2-9 epitope in two predicted surface-exposed L1 positions. All chimeric constructs were transiently expressed in plants using the Cowpea mosaic virus-derived expression vector, pEAQ-HT. Chimeras were recognized by a panel of linear and conformation-specific anti HPV-16 L1 MAbs, and two of them also reacted with the anti-influenza MAb. Electron microscopy showed that chimeric proteins made in plants spontaneously assembled in higher order structures, such as VLPs of T = 1 or T = 7 symmetry, or capsomers.

Conclusions

In this study, we report for the first time the transient expression and the self-assembly of a chimeric HPV-16 L1 bearing the M2e influenza epitope in plants, representing also the first record of a successful expression of chimeric HPV-16 L1 carrying an epitope of a heterologous virus in plants. This study further confirms the usefulness of human papillomavirus particles as carriers of exogenous epitopes and their potential relevance for the production in plants of monovalent or multivalent vaccines.
Leaf extracts from Nitraria retusa promote cell population growth of human cancer cells by inducing apoptosis
Authors: Boubaker Jihed , Bhouri Wissem , Sghaier Mohamed Ben , Bouhlel Ines , Skandrani Ines , Ghedira Kamel , Chekir-Ghedira Leila
Published: November 2011

Background

In this report the phytochemical profile of Nitraria. Retusa (N. Retusa) leaf extracts were identified and their ability to induce apoptosis in human chronic myelogenous erythroleukaemia (K562) was evaluated.

Methods

Apoptosis of the human chronic myelogenous erythroleukaemia (K562) was evidenced by investigating DNA fragmentation, PARP cleavage and caspases 3 and 8 inducing activities, in the presence of N. retusa extracts.

Results

Our study revealed that the tested extracts from N. Retusa contain many useful bioactive compounds. They induced in a time-dependent manner the apoptosis the tested cancerous our cell line. This result was confirmed by ladder DNA fragmentation profile and PARP cleavage, as well as a release in caspase-3 and caspase-8 level.

Conclusion

Our results indicate that the tested compounds have a significant antiproliferative effect which may be due to their involvement in the induction of the extrinsic apoptosic pathway.
The effect of short-term canola oil ingestion on oxidative stress in the vasculature of stroke-prone spontaneously hypertensive rats
Authors: Papazzo Annateresa , Conlan Xavier , Lexis Louise , Lewandowski Paul
Published: November 2011

Background

This study aimed to determine if 25 days of canola oil intake in the absence of excess dietary salt or together with salt loading affects antioxidant and oxidative stress markers in the circulation. A further aim was to determine the mRNA expression of NADPH oxidase subunits and superoxide dismutase (SOD) isoforms in the aorta of stroke-prone spontaneously hypertensive (SHRSP) rats.

Methods

Male SHRSP rats, were fed a defatted control diet containing 10% wt/wt soybean oil or a defatted treatment diet containing 10% wt/wt canola oil, and given tap water or water containing 1% NaCl. Blood was collected at the end of study for analysis of red blood cell (RBC) antioxidant enzymes, RBC and plasma malondialdehyde (MDA), plasma 8-isoprostane and plasma lipids. The aorta was removed and the mRNA expression of NOX2, p22
phox
, CuZn-SOD, Mn-SOD and EC-SOD were determined.

Results

In the absence of salt, canola oil reduced RBC SOD and glutathione peroxidase, and increased total cholesterol and LDL cholesterol compared with soybean oil. RBC glutathione peroxidase activity was significantly lower in both the salt loaded groups compared to the soybean oil only group. In addition, RBC MDA and plasma HDL cholesterol were significantly higher in both the salt loaded groups compared to the no salt groups. Plasma MDA concentration was higher and LDL cholesterol concentration lower in the canola oil group loaded with salt compared to the canola oil group without salt. The mRNA expression of NADPH oxidase subunits and SOD isoforms were significantly reduced in the canola oil group with salt compared to canola oil group without salt.

Conclusion

In conclusion, these results indicate that canola oil reduces antioxidant status and increases plasma lipids, which are risk factors for cardiovascular disease. However, canola oil in combination with salt intake increased MDA, a marker of lipid peroxidation and decreased NAPDH oxidase subunits and aortic SOD gene expression.
Autonomic nervous system and lipid metabolism: findings in anxious-depressive spectrum and eating disorders
Authors: Pistorio Elisabetta , Luca Maria , Luca Antonina , Messina Vincenzo , Calandra Carmela
Published: November 2011

Objective

To correlate lipid metabolism and autonomic dysfunction with anxious-depressive spectrum and eating disorders. To propose the lipid index (LI) as a new possible biomarker.

Methods

95 patients and 60 controls were enrolled from the University Psychiatry Unit of Catania and from general practitioners (GPs). The patients were divided into four pathological groups: Anxiety, Depression, Anxious-Depressive Disorder and Eating Disorders [Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) official/appendix criteria]. The levels of the cholesterol, triglycerides and apolipoproteins A and B were determined. The LI, for each subject, was obtained through a mathematical operation on the values of the cholesterol and triglycerides levels compared with the maximum cut-off of the general population. The autonomic functioning was tested with Ewing battery tests. Particularly, the correlation between heart rate variability (HRV) and lipid metabolism has been investigated.

Results

Pathological and control groups, compared among each other, presented some peculiarities in the lipid metabolism and the autonomic dysfunction scores. In addition, a statistically significant correlation has been found between HRV and lipid metabolism.

Conclusions

Lipid metabolism and autonomic functioning seem to be related to the discussed psychiatric disorders. LI, in addition, could represent a new possible biomarker to be considered.
Orthogonal Stability of an Additive-Quadratic Functional Equation
Authors: Park Choonkil
Published: November 2011

Using the fixed point method and using the direct method, we prove the Hyers-Ulam stability of an orthogonally additive-quadratic functional equation in orthogonality spaces.

(2010) Mathematics Subject Classification: Primary 39B55; 47H10; 39B52; 46H25.
Robust video super resolution algorithm using measurement validation method and scene change detection
Authors: Kim Minjae , Ku Bonhwa , Chung Daesung , Shin Hyunhak , Han David K , Ko Hanseok
Published: November 2011

Explicit motion estimation is considered a major factor in the performance of classical motion-based super resolution (SR) algorithms. To reconstruct video frames sequentially, we applied a dynamic SR algorithm based on the Kalman recursive estimator. Our approach includes a novel measurement validation process to attain robust image reconstruction results under inexplicit motion estimation. In our method, the suitability for high-resolution pixel estimation is determined by the accuracy of motion estimation. We measured the accuracy of the image registration result using the Mahalanobis distance between the input low-resolution frame and the motion compensated high-resolution estimation. We also incorporate an effective scene change detection method dedicated to the proposed SR approach for minimizing erroneous results when abrupt scene changes occur in the video frames. According to the ratio of well-aligned pixels (i.e., motion is compensated accurately) to the total number of pixels, we are able to detect sudden changes of scene and context in the input video. Representative experiments on synthetic and real video data show robust performance of the proposed algorithm in terms of its reconstruction quality even with errors in the estimated motion.
Post-traumatic hypoxia exacerbates neurological deficit, neuroinflammation and cerebral metabolism in rats with diffuse traumatic brain injury
Authors: Yan Edwin B , Hellewell Sarah C , Bellander Bo-Michael , Agyapomaa Doreen A , Morganti-Kossmann M Cristina
Published: November 2011

Background

The combination of diffuse brain injury with a hypoxic insult is associated with poor outcomes in patients with traumatic brain injury. In this study, we investigated the impact of post-traumatic hypoxia in amplifying secondary brain damage using a rat model of diffuse traumatic axonal injury (TAI). Rats were examined for behavioral and sensorimotor deficits, increased brain production of inflammatory cytokines, formation of cerebral edema, changes in brain metabolism and enlargement of the lateral ventricles.

Methods

Adult male Sprague-Dawley rats were subjected to diffuse TAI using the Marmarou impact-acceleration model. Subsequently, rats underwent a 30-minute period of hypoxic (12% O2/88% N2) or normoxic (22% O2/78% N2) ventilation. Hypoxia-only and sham surgery groups (without TAI) received 30 minutes of hypoxic or normoxic ventilation, respectively. The parameters examined included: 1) behavioural and sensorimotor deficit using the Rotarod, beam walk and adhesive tape removal tests, and voluntary open field exploration behavior; 2) formation of cerebral edema by the wet-dry tissue weight ratio method; 3) enlargement of the lateral ventricles; 4) production of inflammatory cytokines; and 5) real-time brain metabolite changes as assessed by microdialysis technique.

Results

TAI rats showed significant deficits in sensorimotor function, and developed substantial edema and ventricular enlargement when compared to shams. The additional hypoxic insult significantly exacerbated behavioural deficits and the cortical production of the pro-inflammatory cytokines IL-6, IL-1β and TNF but did not further enhance edema. TAI and particularly TAI+Hx rats experienced a substantial metabolic depression with respect to glucose, lactate, and glutamate levels.

Conclusion

Altogether, aggravated behavioural deficits observed in rats with diffuse TAI combined with hypoxia may be induced by enhanced neuroinflammation, and a prolonged period of metabolic dysfunction.
Effect of L-carnitine on the hepatic transcript profile in piglets as animal model
Authors: Keller Janine , Ringseis Robert , Priebe Steffen , Guthke Reinhard , Kluge Holger , Eder Klaus
Published: November 2011

Background

Carnitine has attracted scientific interest due to several health-related effects, like protection against neurodegeneration, mitochondrial decay, and oxidative stress as well as improvement of glucose tolerance and insulin sensitivity. The mechanisms underlying most of the health-related effects of carnitine are largely unknown.

Methods

To gain insight into mechanisms through which carnitine exerts its beneficial metabolic effects, we fed piglets either a control or a carnitine supplemented diet, and analysed the transcriptome in the liver.

Results

Transcript profiling revealed 563 genes to be differentially expressed in liver by carnitine supplementation. Clustering analysis of the identified genes revealed that most of the top-ranked annotation term clusters were dealing with metabolic processes. Representative genes of these clusters which were significantly up-regulated by carnitine were involved in cellular fatty acid uptake, fatty acid activation, fatty acid β-oxidation, glucose uptake, and glycolysis. In contrast, genes involved in gluconeogenesis were down-regulated by carnitine. Moreover, clustering analysis identified genes involved in the insulin signaling cascade to be significantly associated with carnitine supplementation. Furthermore, clustering analysis revealed that biological processes dealing with posttranscriptional RNA processing were significantly associated with carnitine supplementation.

Conclusion

The data suggest that carnitine supplementation has beneficial effects on lipid and glucose homeostasis by inducing genes involved in fatty acid catabolism and glycolysis and repressing genes involved in gluconeogenesis.
Inductive specification and axonal orientation of spinal neurons mediated by divergent bone morphogenetic protein signaling pathways
Authors: Perron Jeanette C , Dodd Jane
Published: November 2011

Background

Bone morphogenetic protein (BMP)7 evokes both inductive and axon orienting responses in dorsal interneurons (dI neurons) in the developing spinal cord. These events occur sequentially during the development of spinal neurons but in these and other cell types such inductive and acute chemotactic responses occur concurrently, highlighting the requirement for divergent intracellular signaling. Both type I and type II BMP receptor subtypes have been implicated selectively in orienting responses but it remains unclear how, in a given cell, divergence occurs. We have examined the mechanisms by which disparate BMP7 activities are generated in dorsal spinal neurons.

Results

We show that widely different threshold concentrations of BMP7 are required to elicit the divergent inductive and axon orienting responses. Type I BMP receptor kinase activity is required for activation of pSmad signaling and induction of dI character by BMP7, a high threshold response. In contrast, neither type I BMP receptor kinase activity nor Smad1/5/8 phosphorylation is involved in the low threshold orienting responses of dI axons to BMP7. Instead, BMP7-evoked axonal repulsion and growth cone collapse are dependent on phosphoinositide-3-kinase (PI3K) activation, plausibly through type II receptor signaling. BMP7 stimulates PI3K-dependent signaling in dI neurons. BMP6, which evokes neural induction but does not have orienting activity, activates Smad signaling but does not stimulate PI3K.

Conclusions

Divergent signaling through pSmad-dependent and PI3K-dependent (Smad-independent) mechanisms mediates the inductive and orienting responses of dI neurons to BMP7. A model is proposed whereby selective engagement of BMP receptor subunits underlies choice of signaling pathway.
Distribution of HPV genotypes in cervical intraepithelial lesions and cervical cancer in Tanzanian women
Authors: Vidal Adriana C , Murphy Susan K , Hernandez Brenda Y , Vasquez Brandi , Bartlett John A , Oneko Olola , Mlay Pendo , Obure Joseph , Overcash Francine , Smith Jennifer S , van der Kolk Mike , Hoyo Cathrine
Published: November 2011

Background

Infection with human papillomavirus (HPV) is associated with uterine cervical intraepithelial neoplasia (CIN) and invasive cancers (ICC). Approximately 80% of ICC cases are diagnosed in under-developed countries. Vaccine development relies on knowledge of HPV genotypes characteristic of LSIL, HSIL and cancer; however, these genotypes remain poorly characterized in many African countries. To contribute to the characterization of HPV genotypes in Northeastern Tanzania, we recruited 215 women from the Reproductive Health Clinic at Kilimanjaro Christian Medical Centre. Cervical scrapes and biopsies were obtained for cytology and HPV DNA detection.

Results

79 out of 215 (36.7%) enrolled participants tested positive for HPV DNA, with a large proportion being multiple infections (74%). The prevalence of HPV infection increased with lesion grade (14% in controls, 67% in CIN1 cases and 88% in CIN2-3). Among ICC cases, 89% had detectable HPV. Overall, 31 HPV genotypes were detected; the three most common HPV genotypes among ICC were HPV16, 35 and 45. In addition to these genotypes, co-infection with HPV18, 31, 33, 52, 58, 68 and 82 was found in 91% of ICC. Among women with CIN2-3, HPV53, 58 and 84/83 were the most common. HPV35, 45, 53/58/59 were the most common among CIN1 cases.

Conclusions

In women with no evidence of cytological abnormalities, the most prevalent genotypes were HPV58 with HPV16, 35, 52, 66 and 73 occurring equally. Although numerical constraints limit inference, findings that 91% of ICC harbor only a small number of HPV genotypes suggests that prevention efforts including vaccine development or adjuvant screening should focus on these genotypes.
Full-term extrauterine abdominal pregnancy: a case report
Authors: Dahab Amal A , Aburass Rahma , Shawkat Wasima , Babgi Reem , Essa Ola , Mujallid Razaz H
Published: November 2011

Introduction

Extrauterine abdominal pregnancy is extremely rare and is frequently missed during antenatal care. This is a report of a full-term extrauterine abdominal pregnancy in a primigravida who likely had a ruptured ectopic pregnancy with secondary implantation and subsequently delivered a healthy baby.

Case presentation

A 23-year-old, Middle Eastern, primigravida presented at 14 weeks gestation with intermittent suprapubic pain and dysuria. An abdominal ultrasound examination showed a single viable fetus with free fluid in her abdomen. A follow-up examination at term showed a breech presentation and the possibility of a bicornute uterus with the fetus present in the left horn of her uterus. Our patient underwent Cesarean delivery under general anesthesia and was found to have a small intact uterus with the fetus lying in her abdomen and surrounded by an amniotic fluid-filled sac. The baby was extracted uneventfully, but the placenta was implanted in the left broad ligament and its removal resulted in massive intraoperative bleeding that necessitated blood and blood products transfusion and the administration of Factor VII to control the bleeding. Both the mother and newborn were discharged home in good condition.

Conclusions

An extrauterine abdominal pregnancy secondary to a ruptured ectopic pregnancy with secondary implantation could be missed during antenatal care and continue to term with good maternal and fetal outcome. An advanced extrauterine pregnancy should not result in the automatic termination of the pregnancy.
L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function
Authors: Xia Yunqiu , Li Qing , Zhong Weizhen , Dong Jing , Wang Zhulin , Wang Chunbo
Published: November 2011

Background

There are an increasing number of patients suffering from fatty liver caused by type 2 diabetes. We intended to study the preventive and therapeutic effect of L-carnitine (LC) on nonalcoholic fatty liver disease (NAFLD) in streptozotocin (STZ)-induced type 2 diabetic mice and to explore its possible mechanism.

Methods

Thirty male Kungming mice were randomly divided into five groups: control group, diabetic group, pre-treatment group (125 mg/kg BW), low-dose (125 mg/kg BW) therapeutic group and high-dose (250 mg/kg BW) therapeutic group. The morphology of hepatocytes was observed by light and electron microscopy. LC and ALC (acetyl L-carnitine) concentrations in the liver were determined by high-performance liquid chromatography (HPLC). Moreover, liver weight, insulin levels and free fatty acid (FFA) and triglyceride (TG) levels in the liver and plasma were measured.

Results

Average liver LC and ALC levels were 33.7% and 20% lower, respectively, in diabetic mice compared to control mice (P < 0.05). After preventive and therapeutic treatment with LC, less hepatocyte steatosis, clearer crista and fewer glycogen granules in the mitochondria were observed. Decreased liver weight, TG levels, and FFA concentrations (P < 0.05) in the liver were also observed after treatment with LC in diabetic mice. Moreover, liver LC and ALC levels increased upon treatment with LC, whereas the ratio of LC and ALC decreased significantly (P < 0.01).

Conclusion

LC supplements ameliorated fatty liver in type 2 diabetic mice by increasing fatty acid oxidation and decreasing the LC/ALC ratio in the liver. Therefore, oral administration of LC protected mitochondrial function in liver.
Effects of cattle rustling and household characteristics on migration decisions and herd size amongst pastoralists in Baringo District, Kenya
Authors: Kaimba George K , Njehia Bernard K , Guliye Abdi Y
Published: November 2011

Pastoral communities in arid and semi-arid lands (ASALs) of Kenya depend on livestock for their livelihood. However, these ASALs are characterized by temporal and spatial climatic variation, making availability of resources uneven. Mobility is a key strategy used by pastoralists to efficiently utilize available resources, notably pasture and water. This strategy is being interrupted by a vicious cycle of livestock rustling/raiding. This study was conducted to elucidate the effects of livestock rustling and other household characteristics on migration decisions and herd size amongst pastoralists in Baringo District in Kenya. A sample of 110 pastoralists were interviewed using a structured questionnaire. Binary probit model was used to explain the probability of migrating while ordinary least square was used to explain effects on herd size.

Gender and age of the household head are significant (P < 0.1 and P < 0.05, respectively) determinants of migration, whereas both also significantly (P < 0.1) influenced herd size. Intensity of rustling, and loss of livestock to drought and/or disease also significantly (P < 0.01) influence the decision to migrate. Level of education had significant (P < 0.1) and negative influence on herd size, whereas size of household had significant (P < 0.01) and positive impact on herd size. Non-livestock income had significant (P < 0.05) and negative influence on migration and herd size.

The practice of livestock rustling, rampant amongst pastoralist communities in Kenya and sometimes occurs across borders, influences pastoralists' decision to migrate and also their herd sizes. It destabilizes communities and undermines their normal livelihood strategies, thus contributing to increased poverty. Increasing the level of development in pastoral areas and formulation of appropriate policies will help in controlling the rustling menace.
Sensitization of epithelial growth factor receptors by nicotine exposure to promote breast cancer cell growth
Authors: Nishioka Takashi , Kim Hyun-Seok , Luo Ling-Yu , Huang Yi , Guo Jinjin , Yan Chen Chang
Published: November 2011

Introduction

Tobacco smoke is known to be the main cause of lung, head and neck tumors. Recently, evidence for an increasing breast cancer risk associated with tobacco smoke exposure has been emerging. We and other groups have shown that nicotine, as a non-conventional carcinogen, has the potential to facilitate cancer genesis and progression. However, the underlying mechanisms by which the smoke affects the breast, rather than the lung, remain unclear. Here, we examine possible downstream signaling pathways of the nicotinic acetylcholine receptor (nAChR) and their role in breast cancer promotion.

Methods

Using human benign MCF10A and malignant MDA-MB-231 breast cells and specific inhibitors of possible downstream kinases, we identified nAChR effectors that were activated by treatment with nicotine. We further tested the effects of these effector pathways on the regulation of E2F1 activation, cell cycle progression and on Bcl-2 expression and long-term cell survival.

Results

In this study, we demonstrated a novel signaling mechanism by which nicotine exposure activated Src to sensitize epidermal growth factor receptor (EGFR)-mediated pathways for breast cancer cell growth promotion. After the ligation of nAChR with nicotine, EGFR was shown to be activated and then internalized in both MCF10A and MDA-MB-231 breast cancer cells. Subsequently, Src, Akt and ERK1/2 were phosphorylated at different time points following nicotine treatment. We further demonstrated that through Src, the ligation of nicotine with nAChR stimulated the EGFR/ERK1/2 pathway for the activation of E2F1 and further cell progression. Our data also showed that Akt functioned directly downstream of Src and was responsible for the increase of Bcl-2 expression and long-term cell survival.

Conclusions

Our study reveals the existence of a potential, regulatory network governed by the interaction of nicotine and nAChR that integrates the conventional, mitogenic Src and EGFR signals for breast cancer development.
Effect of changing water salinity on complex conductivity spectra of sandstones
Authors: Weller Andreas , Breede Katrin , Slater Lee , Nordsiek Sven
Published: November 2011

We analyzed the influence of pore fluid composition on the complex electrical conductivity of three sandstones with differing porosity and permeability. The fluid electrical conductivity ([Formula: see text]) of sodium and calcium chloride solutions was gradually increased from 25 mS/m to 2300 mS/m. The expected linear relation between [Formula: see text] and the real component of electrical conductivity ([Formula: see text]) of the saturated samples was observed. The imaginary component ([Formula: see text]) exhibits a steeper increase at lower salinities that flattens at higher salinities. For a glauconitic sandstone and a high porosity Bunter sandstone, [Formula: see text] approaches an asymptotic value at high salinities. Sodium cations result in larger values of [Formula: see text] than calcium cations in solutions of equal concentration. Debye decomposition was used to determine normalized chargeability ([Formula: see text]) and average relaxation time ([Formula: see text]) from spectral data. The behavior of [Formula: see text] is comparable to [Formula: see text] as both parameters measure the polarizability. At lower salinity, the relation between [Formula: see text] and [Formula: see text] approximates a power law with an exponent of [Formula: see text]. The average relaxation time shows only a weak dependence on [Formula: see text]. The normalized chargeability of sandstone samples can be described by the product of the pore space related internal surface and a quantity characterizing the polarizability of the mineral-fluid interface that depends on fluid chemistry. We introduce a new parameter, the specific polarizability, describing this dependence. We propose relations between polarizability and fluid chemistry that could be used to estimate pore space internal surface across samples of varying [Formula: see text]. We observe a consistent maximum polarizability for quartz dominated siliceous material.
Longitudinal Patient-Reported Performance Status Assessment in the Cancer Clinic Is Feasible and Prognostic
Authors: Suh Sang-Yeon , LeBlanc Thomas W. , Shelby Rebecca A. , Samsa Gregory P. , Abernethy Amy P.
Published: November 2011

The enhanced resolution provided by patient-reported performance status, as measured by the Patient Care Monitor, allows for the detection of changes in trajectory over time, potentially serving as an early-warning system to trigger clinical interventions.
Advance Care Planning With Your Patients
Authors: Gesme Dean H. , Wiseman Marian
Published: November 2011

Studies have shown that patients want their doctor to talk to them about their advance care plans, and they want that discussion sooner rather than later.
Multimorbidity: An Issue of Growing Importance for Oncologists
Authors: Ritchie Christine S. , Kvale Elizabeth , Fisch Michael J.
Published: November 2011

Recognition of the impact of multiple co-occurring conditions on a patient's cancer care plan and development of strategies to address the challenges associated with multimorbidity will enable oncologists to provide higher quality, patient-centered care.
Integration of Inventory and Pricing Decisions with Costly Price Adjustments
Authors: Chen Xin , Zhou Sean X. , Chen Youhua (Frank)
Published: November 2011

Motivated by the widespread adoption of dynamic pricing in industry and the empirical evidence of costly price adjustments, in this paper we consider a periodic-review inventory model with price adjustment costs that consist of both fixed and variable components. In each period, demand is stochastic and price-dependent. The firm needs to coordinate the pricing and inventory replenishment decisions in each period to maximize its total discounted profit over a finite planning horizon. We develop the general model and characterize the optimal policies for two special scenarios, namely, a model with inventory carryover and no fixed price-change costs and a model with fixed price-change costs and no inventory carryover. Finally, we propose an intuitive heuristic policy to tackle the general system whose optimal policy is expected to be very complicated. Our numerical studies show that this heuristic policy performs well.
An Interior Point Constraint Generation Algorithm for Semi-Infinite Optimization with Health-Care Application
Authors: Oskoorouchi Mohammad R. , Ghaffari Hamid R. , Terlaky Tamás , Aleman Dionne M.
Published: November 2011

We propose an interior point constraint generation (IPCG) algorithm for semi-infinite linear optimization (SILO) and prove that the algorithm converges to an ε-solution of SILO after a finite number of constraints is generated. We derive a complexity bound on the number of Newton steps needed to approach the updated μ-center after adding multiple violated constraints and a complexity bound on the total number of constraints that is required for the overall algorithm to converge.

We implement our algorithm to solve the sector duration optimization problem arising in Leksell Gamma Knife® Perfexion™ (Elekta, Stockholm Sweden) treatment planning, a highly specialized treatment for brain tumors. Using real patient data provided by the Department of Radiation Oncology at Princess Margaret Hospital in Toronto, Ontario, Canada, we show that our algorithm can efficiently handle problems in real-life health-care applications by providing a quality treatment plan in a timely manner.

Comparing our computational results with MOSEK, a commercial software package, we show that the IPCG algorithm outperforms the classical primal-dual interior point methods on sector duration optimization problem arising in Perfexion™ treatment planning. We also compare our results with that of a projected gradient method. In both cases we show that IPCG algorithm obtains a more accurate solution substantially faster.