bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tripartite chimeric pseudogene from the genome of rice blast fungus Magnaporthe grisea suggests double template jumps during long interspersed nuclear element (LINE) reverse transcription
Authors: Gogvadze Elena , Barbisan Crystel , Lebrun Marc-Henri , Buzdin Anton 
Published: October 2007

Abstract

Background
A systematic survey of loci carrying retrotransposons in the genome of the rice blast fungus Magnaporthe grisea allowed the identification of novel non-canonical retropseudogenes. These elements are chimeric retrogenes composed of DNA copies from different cellular transcripts directly fused to each other. Their components are copies of a non protein-coding highly expressed RNA of unknown function termed WEIRD and of two fungal retrotransposons: MGL and Mg-SINE. Many of these chimeras are transcribed in various M. grisea tissues and during plant infection. Chimeric retroelements with a similar structure were recently found in three mammalian genomes. All these chimeras are likely formed by RNA template switches during the reverse transcription of diverse LINE elements.

Results
We have shown that in M. grisea template switching occurs at specific sites within the initial template RNA which contains a characteristic consensus sequence. We also provide evidence that both single and double template switches may occur during LINE retrotransposition, resulting in the fusion of three different transcript copies. In addition to the 33 bipartite elements, one tripartite chimera corresponding to the fusion of three retrotranscripts (WEIRD, Mg-SINE, MGL-LINE) was identified in the M. grisea genome. Unlike the previously reported two human tripartite elements, this fungal retroelement is flanked by identical 14 bp-long direct repeats. The presence of these short terminal direct repeats demonstrates that the LINE enzymatic machinery was involved in the formation of this chimera and its integration in the M. grisea genome.

Conclusion
A survey of mammalian genomic databases also revealed two novel tripartite chimeric retroelements, suggesting that double template switches occur during reverse transcription of LINE retrotransposons in different eukaryotic organisms.
Gene profile analysis of osteoblast genes differentially regulated by histone deacetylase inhibitors
Authors: Schroeder Tania M , Nair Aswathy K , Staggs Rodney , Lamblin Anne-Francoise , Westendorf Jennifer J 
Published: October 2007

Abstract

Background
Osteoblast differentiation requires the coordinated stepwise expression of multiple genes. Histone deacetylase inhibitors (HDIs) accelerate the osteoblast differentiation process by blocking the activity of histone deacetylases (HDACs), which alter gene expression by modifying chromatin structure. We previously demonstrated that HDIs and HDAC3 shRNAs accelerate matrix mineralization and the expression of osteoblast maturation genes (e.g. alkaline phosphatase, osteocalcin). Identifying other genes that are differentially regulated by HDIs might identify new pathways that contribute to osteoblast differentiation.

Results
To identify other osteoblast genes that are altered early by HDIs, we incubated MC3T3-E1 preosteoblasts with HDIs (trichostatin A, MS-275, or valproic acid) for 18 hours in osteogenic conditions. The promotion of osteoblast differentiation by HDIs in this experiment was confirmed by osteogenic assays. Gene expression profiles relative to vehicle-treated cells were assessed by microarray analysis with Affymetrix GeneChip 430 2.0 arrays. The regulation of several genes by HDIs in MC3T3-E1 cells and primary osteoblasts was verified by quantitative real-time PCR. Nine genes were differentially regulated by at least two-fold after exposure to each of the three HDIs and six were verified by PCR in osteoblasts. Four of the verified genes (solute carrier family 9 isoform 3 regulator 1 (Slc9a3r1), sorbitol dehydrogenase 1, a kinase anchor protein, and glutathione S-transferase alpha 4) were induced. Two genes (proteasome subunit, beta type 10 and adaptor-related protein complex AP-4 sigma 1) were suppressed. We also identified eight growth factors and growth factor receptor genes that are significantly altered by each of the HDIs, including Frizzled related proteins 1 and 4, which modulate the Wnt signaling pathway.

Conclusion
This study identifies osteoblast genes that are regulated early by HDIs and indicates pathways that might promote osteoblast maturation following HDI exposure. One gene whose upregulation following HDI treatment is consistent with this notion is Slc9a3r1. Also known as NHERF1, Slc9a3r1 is required for optimal bone density. Similarly, the regulation of Wnt receptor genes indicates that this crucial pathway in osteoblast development is also affected by HDIs. These data support the hypothesis that HDIs regulate the expression of genes that promote osteoblast differentiation and maturation.
Identification of genes that regulate multiple cellular processes/responses in the context of lipotoxicity to hepatoma cells
Authors: Srivastava Shireesh , Li Zheng , Yang Xuerui , Yedwabnick Matthew , Shaw Stephen , Chan Christina 
Published: October 2007

Abstract

Background
In order to devise efficient treatments for complex, multi-factorial diseases, it is important to identify the genes which regulate multiple cellular processes. Exposure to elevated levels of free fatty acids (FFAs) and tumor necrosis factor alpha (TNF-α) alters multiple cellular processes, causing lipotoxicity. Intracellular lipid accumulation has been shown to reduce the lipotoxicity of saturated FFA. We hypothesized that the genes which simultaneously regulate lipid accumulation as well as cytotoxicity may provide better targets to counter lipotoxicity of saturated FFA.

Results
As a model system to test this hypothesis, human hepatoblastoma cells (HepG2) were exposed to elevated physiological levels of FFAs and TNF-α. Triglyceride (TG) accumulation, toxicity and the genomic responses to the treatments were measured. Here, we present a framework to identify such genes in the context of lipotoxicity. The aim of the current study is to identify the genes that could be altered to treat or ameliorate the cellular responses affected by a complex disease rather than to identify the causal genes. Genes that regulate the TG accumulation, cytotoxicity or both were identified by a modified genetic algorithm partial least squares (GA/PLS) analysis. The analyses identified NADH dehydrogenase and mitogen activated protein kinases (MAPKs) as important regulators of both cytotoxicity and lipid accumulation in response to FFA and TNF-α exposure. In agreement with the predictions, inhibiting NADH dehydrogenase and c-Jun N-terminal kinase (JNK) reduced cytotoxicity significantly and increased intracellular TG accumulation. Inhibiting another MAPK pathway, the extracellular signal regulated kinase (ERK), on the other hand, improved the cytotoxicity without changing TG accumulation. Much greater reduction in the toxicity was observed upon inhibiting the NADH dehydrogenase and MAPK (which were identified by the dual-response analysis), than for the stearoyl-CoA desaturase (SCD) activation (which was identified for the TG-alone analysis).

Conclusion
These results demonstrate the applicability of GA/PLS in identifying the genes that regulate multiple cellular responses of interest and that genes regulating multiple cellular responses may be better candidates for countering complex diseases.
Mitochondrial respiratory chain is involved in insulin-stimulated hydrogen peroxide production and plays an integral role in insulin receptor autophosphorylation in neurons
Authors: Storozhevykh Tatiana P , Senilova Yana E , Persiyantseva Nadezhda A , Pinelis Vsevolod G , Pomytkin Igor A 
Published: October 2007

AbstractBackgroundAccumulated evidence suggests that hydrogen peroxide (H2O2) generated in cells during insulin stimulation plays an integral role in insulin receptor signal transduction. The role of insulin-induced H2O2in neuronal insulin receptor activation and the origin of insulin-induced H2O2in neurons remain unclear. The aim of the present study is to test the following hypotheses (1) whether insulin-induced H2O2is required for insulin receptor autophosphorylation in neurons, and (2) whether mitochondrial respiratory chain is involved in insulin-stimulated H2O2production, thus playing an integral role in insulin receptor autophosphorylation in neurons.ResultsInsulin stimulation elicited rapid insulin receptor autophosphorylation accompanied by an increase in H2O2release from cultured cerebellar granule neurons (CGN). N-acetylcysteine (NAC), a H2O2scavenger, inhibited both insulin-stimulated H2O2release and insulin-stimulated autophosphorylation of insulin receptor. Inhibitors of respiratory chain-mediated H2O2production, malonate and carbonyl cyanide-4-(trifluoromethoxy)-phenylhydrazone (FCCP), inhibited both insulin-stimulated H2O2release from neurons and insulin-stimulated autophosphorylation of insulin receptor. Dicholine salt of succinic acid, a respiratory substrate, significantly enhanced the effect of suboptimal insulin concentration on the insulin receptor autophosphorylation in CGN.ConclusionResults of the present study suggest that insulin-induced H2O2is required for the enhancement of insulin receptor autophosphorylation in neurons. The mitochondrial respiratory chain is involved in insulin-stimulated H2O2production, thus playing an integral role in the insulin receptor autophosphorylation in neurons.
An EST database from saffron stigmas
Authors: D'Agostino Nunzio , Pizzichini Daniele , Chiusano Maria Luisa , Giuliano Giovanni 
Published: October 2007

Abstract

Background
Saffron (Crocus sativus L., Iridaceae) flowers have been used as a spice and medicinal plant ever since the Greek-Minoan civilization. The edible part – the stigmas – are commonly considered the most expensive spice in the world and are the site of a peculiar secondary metabolism, responsible for the characteristic color and flavor of saffron.

Results
We produced 6,603 high quality Expressed Sequence Tags (ESTs) from a saffron stigma cDNA library. This collection is accessible and searchable through the Saffron Genes database http://www.saffrongenes.org. The ESTs have been grouped into 1,893 Clusters, each corresponding to a different expressed gene, and annotated. The complete set of raw EST sequences, as well as of their electopherograms, are maintained in the database, allowing users to investigate sequence qualities and EST structural features (vector contamination, repeat regions). The saffron stigma transcriptome contains a series of interesting sequences (putative sex determination genes, lipid and carotenoid metabolism enzymes, transcription factors).

Conclusion
The Saffron Genes database represents the first reference collection for the genomics of Iridaceae, for the molecular biology of stigma biogenesis, as well as for the metabolic pathways underlying saffron secondary metabolism.
Structural disorder promotes assembly of protein complexes
Authors: Hegyi Hedi , Schad Eva , Tompa Peter 
Published: October 2007

Abstract

Background
The idea that the assembly of protein complexes is linked with protein disorder has been inferred from a few large complexes, such as the viral capsid or bacterial flagellar system, only. The relationship, which suggests that larger complexes have more disorder, has never been systematically tested. The recent high-throughput analyses of protein-protein interactions and protein complexes in the cell generated data that enable to address this issue by bioinformatic means.

Results
In this work we predicted structural disorder for both E. coli and S. cerevisiae, and correlated it with the size of complexes. Using IUPred to predict the disorder for each complex, we found a statistically significant correlation between disorder and the number of proteins assembled into complexes. The distribution of disorder has a median value of 10% in yeast for complexes of 2–4 components (6% in E. coli), but 18% for complexes in the size range of 11–100 proteins (12% in E. coli). The level of disorder as assessed for regions longer than 30 consecutive disordered residues shows an even stronger division between small and large complexes (median values about 4% for complexes of 2–4 components, but 12% for complexes of 11–100 components in yeast). The predicted correlation is also supported by experimental evidence, by observing the structural disorder in protein components of complexes that can be found in the Protein Data Bank (median values 1. 5% for complexes of 2–4 components, and 9.6% for complexes of 11–100 components in yeast). Further analysis shows that this correlation is not directly linked with the increased disorder in hub proteins, but reflects a genuine systemic property of the proteins that make up the complexes.

Conclusion
Overall, it is suggested and discussed that the assembly of protein-protein complexes is enabled and probably promoted by protein disorder.
Pharmacokinetics of recombinant human growth hormone administered by cool.click™ 2, a new needle-free device, compared with subcutaneous administration using a conventional syringe and needle
Authors: Brearley Chris , Priestley Anthony , Leighton-Scott James , Christen Michel 
Published: October 2007

Abstract

Background
Growth hormone (GH) is used to treat growth hormone deficiency (GHD, adult and paediatric), short bowel syndrome in patients on a specialized diet, HIV-associated wasting and, in children, growth failure due to a number of disorders including Turner's syndrome and chronic renal failure, and in children born small for gestational age. Different brands and generic forms of recombinant human growth hormone (r-hGH) are approved for varying indications in different countries. New ways of administering GH are required because the use of a needle and syringe or a device where a patient still has to insert the needle manually into the skin on a daily basis can lead to low adherence and sub-optimal treatment outcomes. The objective of this study was to assess the relative bioavailability of r-hGH (Saizen®, Merck Serono) administered by a new needle-free device, cool.click™ 2, and a standard needle and syringe.

Methods
The study was performed with 38 healthy volunteers who underwent pituitary somatotrope cell down-regulation using somatostatin, according to a randomized, two-period, two-sequence crossover design. Following subcutaneous administration of r-hGH using cool.click™ 2 or needle and syringe, pharmacokinetic parameters were analysed by non-compartmental methods. Bioequivalence was assessed based on log-transformed AUC and Cmax values.

Results
The 90% confidence intervals for test/reference mean ratio of the plasma pharmacokinetic variables Cmax and AUC0-inf were 103.7–118.3 and 97.1–110.0, respectively, which is within the accepted bioequivalence range of 80–125%. r-hGH administered by cool.click™ 2 is, therefore, bioequivalent to administration by needle and syringe with respect to the rate and extent of GH exposure. Treatment using cool.click™ 2 was found to be well tolerated. With cool.click™ 2 the tmax was less (3.0 hours) than for needle and syringe delivery (4.5 hours), p = 0.002 (Friedman test), although this is unlikely to have any clinical implications.

Conclusion
These results demonstrate that cool.click™ 2 delivers subcutaneous r-hGH exposure that is bioequivalent to the conventional mode of injection. The new device has the additional advantage of being needle-free, and should help to increase patient adherence and achieve good therapeutic outcomes from r-hGH treatment.
Patient-provider interaction from the perspectives of type 2 diabetes patients in Muscat, Oman: a qualitative study
Authors: Abdulhadi Nadia , Al Shafaee Mohammed , Freudenthal Solveig , Östenson Claes-Göran , Wahlström Rolf 
Published: October 2007

Abstract
Background
Patients' expectations and perceptions of the medical encounter and interactions are important tools in diabetes management. Some problems regarding the interaction during encounters may be related to a lack of communication skills on the part of either the physician or the patient.
This study aimed at exploring the perceptions of type 2 diabetes patients regarding the medical encounters and quality of interactions with their primary health-care providers.

Methods
Four focus group discussions (two women and two men groups) were conducted among 27 purposively selected patients (13 men and 14 women) from six primary health-care centres in Muscat, Oman. Qualitative content analysis was applied.

Results
The patients identified some weaknesses regarding the patient-provider communication like: unfriendly welcoming; interrupted consultation privacy; poor attention and eye contact; lack of encouraging the patients to ask questions on the providers' side; and inability to participate in medical dialogue or express concerns on the patients' side. Other barriers and difficulties related to issues of patient-centeredness, organization of diabetes clinics, health education and professional competency regarding diabetes care were also identified.

Conclusion
The diabetes patients' experiences with the primary health-care providers showed dissatisfaction with the services. We suggest appropriate training for health-care providers with regard to diabetes care and developing of communication skills with emphasis on a patient-centred approach. An efficient use of available resources in diabetes clinics and distributing responsibilities between team members in close collaboration with patients and their families seems necessary. Further exploration of the providers' work situation and barriers to good interaction is needed. Our findings can help the policy makers in Oman, and countries with similar health systems, to improve the quality and organizational efficiency of diabetes care services.
Sleep in Kcna2 knockout mice
Authors: Douglas Christopher L , Vyazovskiy Vladyslav , Southard Teresa , Chiu Shing-Yan , Messing Albee , Tononi Giulio , Cirelli Chiara 
Published: October 2007

Abstract

Background

Shaker codes for a Drosophila voltage-dependent potassium channel. Flies carrying Shaker null or hypomorphic mutations sleep 3–4 h/day instead of 8–14 h/day as their wild-type siblings do. Shaker-like channels are conserved across species but it is unknown whether they affect sleep in mammals. To address this issue, we studied sleep in Kcna2 knockout (KO) mice. Kcna2 codes for Kv1.2, the alpha subunit of a Shaker-like voltage-dependent potassium channel with high expression in the mammalian thalamocortical system.

Results

Continuous (24 h) electroencephalograph (EEG), electromyogram (EMG), and video recordings were used to measure sleep and waking in Kcna2 KO, heterozygous (HZ) and wild-type (WT) pups (P17) and HZ and WT adult mice (P67). Sleep stages were scored visually based on 4-s epochs. EEG power spectra (0–20 Hz) were calculated on consecutive 4-s epochs. KO pups die by P28 due to generalized seizures. At P17 seizures are either absent or very rare in KO pups (< 1% of the 24-h recording time), and abnormal EEG activity is only present during the seizure. KO pups have significantly less non-rapid eye movement (NREM) sleep (-23%) and significantly more waking (+21%) than HZ and WT siblings with no change in rapid eye movement (REM) sleep time. The decrease in NREM sleep is due to an increase in the number of waking episodes, with no change in number or duration of sleep episodes. Sleep patterns, daily amounts of sleep and waking, and the response to 6 h sleep deprivation are similar in HZ and WT adult mice.

Conclusion

Kv1.2, a mammalian homologue of Shaker, regulates neuronal excitability and affects NREM sleep.
Immune Restoration Syndrome with disseminated Penicillium marneffei and Cytomegalovirus co-infections in an AIDS patient
Authors: Gupta Swati , Mathur Purva , Maskey Dipesh , Wig Naveet , Singh Sarman 
Published: October 2007

Abstract

Background

Penicillium marneffei is a dimorphic fungus, endemic in South-east Asia. The fungus causes severe disease in immunocompromised patients such as AIDS. However, no case of immune restoration disease of Penicillium marneffei is reported in literature from a non-endemic area.

Case Presentation
We report the first case of Penicillium marneffei and Cytomegalovirus infection manifesting as a result of immune restoration one month after initiating HAART. This severely immunocompromised patient had presented with multiple lymphadenopathy, massive hepatosplenomegaly, visual impairment and mild icterus, but no skin lesions. Penicillium marneffei was isolated from lymph node fine-needle aspirates and blood cultures.

Conclusion
In order to diagnose such rare cases, the clinicians, histopathologists and microbiologists alike need to maintain a strong index of suspicion for making initial diagnosis as well as for suspecting immune reconstitution syndrome (IRS) with Penicillium marneffei.
Cloning of full genome sequence of hepatitis E virus of Shanghai swine isolate using RACE method
Authors: Shen Quan , Zhang Wen , Cao Xiangrong , Mou Jing , Cui Li , Hua Xiuguo 
Published: October 2007

Abstract
Genotype 4 hepatitis E virus (HEV) was reportedly transmitted freely between humans and swine in eastern China. The full-length genomic sequence of Shanghai swine isolate (SH-SW-zs1) recovered from feces sample of a pig which was infected with HEV RNA positive swine serum was determined using RT-PCR and RACE (Rapid Amplification of cDNA Ends) methods. The full genome of the SH-SW-zs1 isolate was 7265 nucleotides in length and phylogenetic analysis indicated that this isolate belonged to genotype 4. Comparison of the 3' UTR sequence with the corresponding regions of other 38 HEV strains from different region revealed that the Shanghai swine isolate is 21–49 bp longer than the other stains.
Postprandial ghrelin suppression is exaggerated following major surgery; implications for nutritional recovery
Authors: Nematy Mohsen , Brynes Audrey E , Hornick Philip I , Patterson Michael , Ghatei Mohammad A , Bloom Stephen R , Brett Stephen J , Frost Gary S 
Published: October 2007

Abstract
Meeting patients' nutritional requirements and preventing malnutrition is a challenge following major surgical procedures. The role of ghrelin in nutritional recovery after non-gastrointestinal major surgery is unknown. We used coronary artery bypass grafting (CABG) as an example of anticipated good recovery post major surgery.
Seventeen patients undergoing CABG (mean ± SEM: 70.1 ± 2.2 yrs, BMI 29.1 ± 1.4 kg/m2, 15 male) underwent fasting and postprandial (45 mins after standard test breakfast) blood sampling pre-operatively (day 0), post-operatively (day 6) and at follow-up (day 40). Changes in food intake, biochemical and anthropometric markers of nutritional status were recorded. A comparison was made to 17 matched healthy controls (70.6 ± 2.3 yrs, BMI 28.4 ± 1.3 kg/m2).
We observed significantly increased post-operative and follow-up fasting ghrelin concentrations compared with pre-operatively (pre-op. 402 ± 42 pmol/L vs post-op. 642 ± 97 pmol/L vs follow-up 603 ± 94 pmol/L) (ANOVA p < 0.05). Significantly exaggerated postprandial suppression of ghrelin was seen postoperatively and continued until follow-up (Δ pre-op. 10 ± 51 pmol/L vs Δ post-op. -152 ± 43 pmol/L vs Δ follow-up -159 ± 65 pmol/L, p < 0.05). This was associated with a 50% reduction in food intake {post-op. 4.5 ± 0.5 MJ/D (1076 ± 120 kcal/D) compared with estimated requirements 9.9 ± 0.5 MJ/D (2366 ± 120 kcal/D)}, leading to a 4% weight loss and a 5% reduction in muscle arm circumference loss over length of follow up.
Our data support the hypothesis that prolonged changes in fasting and postprandial plasma ghrelin concentrations are associated with impaired nutritional recovery after CABG. These findings reinforce the need to investigate ghrelin in other patients groups undergoing major surgery.