bluuebunny/crossref_metadata_2025 huggingface dataset:
Current management strategies and therapeutic targets in chronic constipation
Authors: Emmanuel Anton
Published: October 2010

Constipated patients who are refractory to simple lifestyle interventions will usually resort to laxatives, whether prescribed or over the counter. Clinical trial evidence is scarce for older medications such as laxatives, especially with a condition as chronic and subjective as constipation. Newer polyethylene glycol-based laxatives have been investigated under rigorous clinical trial settings, but comparisons between different laxatives are not available. Newer prokinetic agents, targeting peristalsis, intestinal secretion and the colonic flora, have been developed for laxative refractory constipation. This review focuses on the evidence for each of these agents, and the relative indications for each of them.
Nutrient Intake of Rural Preschool Children in Southwest Nigeria
Authors: Agbon Chineze , Okeke Elizbeth , Omotayo Akin
Published: October 2010

Stunting, adolescent fractures, and osteoporosis later in life are all public health problems that may be eradicated with adequate nutrient intake in preschool diets. Preschool children’s nutrient consumption was studied using the weighed food intake method. Demographic data were obtained using a questionnaire. A total of 116 preschool children in 9 villages formed the population for the study. Data were analyzed using EPI Info version 3.3.2 and the SPSS software package. The preschoolers’ mean intake of protein (17.0 g) and energy (1068 kcal) was lower than Food and Agricultural Organization of the United Nations (FAO)/World Health Organization (WHO)—recommended intake, and calcium (474 mg) was lower than the Food and Nutrition Board—recommended intake. Zinc intake (9.9 mg) marginally met basal dietary requirements for zinc as recommended by WHO in a low-bioavailability diet. When subjects were separated according to age group, the nutrient intake of protein and calcium increased with age, but it was not statistically different (P < .05). Zinc consumption by children between the ages of 2 and 3 years was statistically lower (P < .05) than the consumption by the children between the ages of 3 to 4 years and 4 to 5 years. The energy intake in children aged 2 to 4 years was significantly lower (P < .05) than the intake of children aged 4 to 5 years. By the end of preschool age, the consumption of all nutrients was low, except for zinc, which marginally met the basal requirement of the subjects.
Population genetics of foxtail millet and its wild ancestor
Authors: Wang Chunfang , Chen Jinfeng , Zhi Hui , Yang Lu , Li Wei , Wang Yongfang , Li Haiquan , Zhao Baohua , Chen Mingsheng , Diao Xianmin
Published: October 2010

Background

Foxtail millet (Setaria italica (L.) P. Beauv.), one of the most ancient domesticated crops, is becoming a model system for studying biofuel crops and comparative genomics in the grasses. However, knowledge on the level of genetic diversity and linkage disequilibrium (LD) is very limited in this crop and its wild ancestor, green foxtail (Setaria viridis (L.) P. Beauv.). Such information would help us to understand the domestication process of cultivated species and will allow further research in these species, including association mapping and identification of agricultural significant genes involved in domestication.

Results

In this study, we surveyed DNA sequence for nine loci across 50 accessions of cultivated foxtail millet and 34 of its wild progenitor. We found a low level of genetic diversity in wild green foxtail (θ = 0.0059), θ means Watterson's estimator of θ. Despite of a 55% loss of its wild diversity, foxtail millet still harbored a considerable level of diversity (θ = 0.0027) when compared to rice and sorghum (θ = 0.0024 and 0.0034, respectively). The level of LD in the domesticated foxtail millet extends to 1 kb, while it decayed rapidly to a negligible level within 150 bp in wild green foxtail. Using coalescent simulation, we estimated the bottleneck severity at k = 0.6095 when ρ/θ = 1. These results indicated that the domestication bottleneck of foxtail millet was more severe than that of maize but slightly less pronounced than that of rice.

Conclusions

The results in this study establish a general framework for the domestication history of foxtail millet. The low level of genetic diversity and the increased level of LD in foxtail millet are mainly caused by a population bottleneck, although gene flow from foxtail millet to green foxtail is another factor that may have shaped the pattern of genetic diversity of these two related gene pools. The knowledge provided in this study will benefit future population based studies in foxtail millet.
Dynamic transcriptomic profiles of zebrafish gills in response to zinc supplementation
Authors: Zheng Dongling , Kille Peter , Feeney Graham P , Cunningham Phil , Handy Richard D , Hogstrand Christer
Published: October 2010

Background

Dietary zinc supplementation may help to promote growth, boost the immune system, protect against diabetes, and aid recovery from diarrhoea. We exploited the zebrafish (Danio rerio) gill as a unique vertebrate ion transporting epithelium model to study the time-dependent regulatory networks of gene-expression leading to homeostatic control during zinc supplementation. This organ forms a conduit for zinc uptake whilst exhibiting conservation of zinc trafficking components.

Results

Fish were maintained with either zinc supplemented water (4.0 μM) and diet (2023 mg zinc kg-1) or water and diet containing Zn2+ at 0.25 μM and 233 mg zinc kg-1, respectively. Gill tissues were harvested at five time points (8 hours to 14 days) and transcriptome changes analysed in quintuplicate using a 16 K microarray with results anchored to gill Zn2+ influx and whole body nutrient composition (protein, carbohydrate, lipid, elements). The number of regulated genes increased up to day 7 but declined as the fish acclimated. In total 525 genes were regulated (having a fold-change more than 1.8 fold change and an adjusted P-value less than 0.1 which is controlling a 10% False discovery rate, FDR) by zinc supplementation, but little overlap was observed between genes regulated at successive time-points. Many genes displayed cyclic expression, typical for homeostatic control mechanisms. Annotation enrichment analysis revealed strong overrepresentation of "transcription factors", with specific association evident with "steroid hormone receptors". A suite of genes linked to "development" were also statistically overrepresented. More specifically, early regulation of genes was linked to a few key transcription factors (e.g. Mtf1, Jun, Stat1, Ppara, Gata3) and was followed by hedgehog and bone morphogenic protein signalling.

Conclusions

The results suggest that zinc supplementation reactivated developmental pathways in the gill and stimulated stem cell differentiation, a response likely reflecting gill remodelling in response to its altered environment. This provides insight to the role of zinc during cell differentiation and illustrates the critical nature of maintaining zinc status. The study also highlights the importance of temporal transcriptomics analysis in order resolve the discrete elements of biological processes, such as zinc acclimation.
A second generation genetic linkage map of Japanese flounder (Paralichthys olivaceus)
Authors: Castaño-Sánchez Cecilia , Fuji Kanako , Ozaki Akiyuki , Hasegawa Osamu , Sakamoto Takashi , Morishima Kagayaki , Nakayama Ichiro , Fujiwara Atsushi , Masaoka Tetsuji , Okamoto Hiroyuki , Hayashida Kengo , Tagami Michihira , Kawai Jun , Hayashizaki Yoshihide , Okamoto Nobuaki
Published: October 2010

Background

Japanese flounder (Paralichthys olivaceus) is one of the most economically important marine species in Northeast Asia. Information on genetic markers associated with quantitative trait loci (QTL) can be used in breeding programs to identify and select individuals carrying desired traits. Commercial production of Japanese flounder could be increased by developing disease-resistant fish and improving commercially important traits. Previous maps have been constructed with AFLP markers and a limited number of microsatellite markers. In this study, improved genetic linkage maps are presented. In contrast with previous studies, these maps were built mainly with a large number of codominant markers so they can potentially be used to analyze different families and populations.

Results

Sex-specific genetic linkage maps were constructed for the Japanese flounder including a total of 1,375 markers [1,268 microsatellites, 105 single nucleotide polymorphisms (SNPs) and two genes]; 1,167 markers are linked to the male map and 1,067 markers are linked to the female map. The lengths of the male and female maps are 1,147.7 cM and 833.8 cM, respectively. Based on estimations of map lengths, the female and male maps covered 79 and 82% of the genome, respectively. Recombination ratio in the new maps revealed F:M of 1:0.7. All linkage groups in the maps presented large differences in the location of sex-specific recombination hot-spots.

Conclusions

The improved genetic linkage maps are very useful for QTL analyses and marker-assisted selection (MAS) breeding programs for economically important traits in Japanese flounder. In addition, SNP flanking sequences were blasted against Tetraodon nigroviridis (puffer fish) and Danio rerio (zebrafish), and synteny analysis has been carried out. The ability to detect synteny among species or genera based on homology analysis of SNP flanking sequences may provide opportunities to complement initial QTL experiments with candidate gene approaches from homologous chromosomal locations identified in related model organisms.
Expansion and subfunctionalisation of flavonoid 3',5'-hydroxylases in the grapevine lineage
Authors: Falginella Luigi , Castellarin Simone D , Testolin Raffaele , Gambetta Gregory A , Morgante Michele , Di Gaspero Gabriele
Published: October 2010

Background

Flavonoid 3',5'-hydroxylases (F3'5'Hs) and flavonoid 3'-hydroxylases (F3'Hs) competitively control the synthesis of delphinidin and cyanidin, the precursors of blue and red anthocyanins. In most plants,F3'5'Hgenes are present in low-copy number, but in grapevine they are highly redundant.

Results

The first increase inF3'5'Hcopy number occurred in the progenitor of the eudicot clade at the time of the γ triplication. Further proliferation ofF3'5'Hs has occurred in one of the paleologous loci after the separation of Vitaceae from other eurosids, giving rise to 15 paralogues within 650 kb. Twelve reside in 9 tandem blocks of ~35-55 kb that share 91-99% identity. The second paleologousF3'5'Hhas been maintained as an orphan gene in grapevines, and lacks orthologues in other plants. DuplicateF3'5'Hs have spatially and temporally partitioned expression profiles in grapevine. The orphanF3'5'Hcopy is highly expressed in vegetative organs. More recent duplicateF3'5'Hs are predominately expressed in berry skins. They differ only slightly in the coding region, but are distinguished in the structure of the promoter. Differences incis-regulatory sequences of promoter regions are paralleled by temporal specialisation of gene transcription during fruit ripening. Variation in anthocyanin profiles consistently reflects changes in theF3'5'HmRNA pool across different cultivars. MoreF3'5'Hcopies are expressed at high levels in grapevine varieties with 93-94% of 3'5'-OH anthocyanins. In grapevines depleted in 3'5'-OH anthocyanins (15-45%), fewerF3'5'Hcopies are transcribed, and at lower levels. Conversely, only two copies of the gene encoding the competing F3'H enzyme are present in the grape genome; one copy is expressed in both vegetative and reproductive organs at comparable levels among cultivars, while the other is transcriptionally silent.

Conclusions

These results suggest that expansion and subfunctionalisation ofF3'5'Hs have increased the complexity and diversification of the fruit colour phenotype among red grape varieties.
Reference gene selection for quantitative reverse transcription-polymerase chain reaction normalization during in vitro adventitious rooting in Eucalyptus globulus Labill
Authors: de Almeida Márcia R , Ruedell Carolina M , Ricachenevsky Felipe K , Sperotto Raul A , Pasquali Giancarlo , Fett-Neto Arthur G
Published: October 2010

Background

Eucalyptus globulusand its hybrids are very important for the cellulose and paper industry mainly due to their low lignin content and frost resistance. However, rooting of cuttings of this species is recalcitrant and exogenous auxin application is often necessary for good root development. To date one of the most accurate methods available for gene expression analysis is quantitative reverse transcription-polymerase chain reaction (qPCR); however, reliable use of this technique requires reference genes for normalization. There is no single reference gene that can be regarded as universal for all experiments and biological materials. Thus, the identification of reliable reference genes must be done for every species and experimental approach. The present study aimed at identifying suitable control genes for normalization of gene expression associated with adventitious rooting inE. globulusmicrocuttings.

Results

By the use of two distinct algorithms,geNormandNormFinder, we have assessed gene expression stability of eleven candidate reference genes inE. globulus:18S, ACT2, EF2, EUC12, H2B, IDH, SAND, TIP41, TUA, UBIand33380. The candidate reference genes were evaluated in microccuttings rootedin vitro, in presence or absence of auxin, along six time-points spanning the process of adventitious rooting. Overall, the stability profiles of these genes determined with each one of the algorithms were very similar. Slight differences were observed in the most stable pair of genes indicated by each program:IDHandSANDforgeNorm, andH2BandTUAforNormFinder. Both programs indentifiedUBIand18Sas the most variable genes. To validate these results and select the most suitable reference genes, the expression profile of theARGONAUTE1gene was evaluated in relation to the most stable candidate genes indicated by each algorithm.

Conclusion

Our study showed that expression stability varied between putative reference genes tested inE. globulus. Based on theAGO1relative expression profile obtained using the genes suggested by the algorithms,H2BandTUAwere considered as the most suitable reference genes for expression studies inE. globulusadventitious rooting.UBIand18Swere unsuitable for use as controls in qPCR related to this process. These findings will enable more accurate and reliable normalization of qPCR results for gene expression studies in this economically important woody plant, particularly related to rooting and clonal propagation.
A direct comparison of strategies for combinatorial RNA interference
Authors: Lambeth Luke S , Van Hateren Nick J , Wilson Stuart A , Nair Venugopal
Published: October 2010

Background

Combinatorial RNA interference (co-RNAi) is a valuable tool for highly effective gene suppression of single and multiple-genes targets, and can be used to prevent the escape of mutation-prone transcripts. There are currently three main approaches used to achieve co-RNAi in animal cells; multiple promoter/shRNA cassettes, long hairpin RNAs (lhRNA) and miRNA-embedded shRNAs, however, the relative effectiveness of each is not known. The current study directly compares the ability of each co-RNAi method to deliver pre-validated siRNA molecules to the same gene targets.

Results

Double-shRNA expression vectors were generated for each co-RNAi platform and their ability to suppress both single and double-gene reporter targets were compared. The most reliable and effective gene silencing was achieved from the multiple promoter/shRNA approach, as this method induced additive suppression of single-gene targets and equally effective knockdown of double-gene targets. Although both lhRNA and microRNA-embedded strategies provided efficient gene knockdown, suppression levels were inconsistent and activity varied greatly for different siRNAs tested. Furthermore, it appeared that not only the position of siRNAs within these multi-shRNA constructs impacted upon silencing activity, but also local properties of each individual molecule. In addition, it was also found that the insertion of up to five promoter/shRNA cassettes into a single construct did not negatively affect the efficacy of each individual shRNA.

Conclusions

By directly comparing the ability of shRNAs delivered from different co-RNA platforms to initiate knockdown of the same gene targets, we found that multiple U6/shRNA cassettes offered the most reliable and predictable suppression of both single and multiple-gene targets. These results highlight some important strengths and pitfalls of the currently used methods for multiple shRNA delivery, and provide valuable insights for the design and application of reliable co-RNAi.
Prevalence and novelty of PRPF31 mutations in French autosomal dominant rod-cone dystrophy patients and a review of published reports
Authors: Audo Isabelle , Bujakowska Kinga , Mohand-Saïd Saddek , Lancelot Marie-Elise , Moskova-Doumanova Veselina , Waseem Naushin H , Antonio Aline , Sahel José-Alain , Bhattacharya Shomi S , Zeitz Christina
Published: October 2010

Background

Rod-cone dystrophies are heterogeneous group of inherited retinal disorders both clinically and genetically characterized by photoreceptor degeneration. The mode of inheritance can be autosomal dominant, autosomal recessive or X-linked. The purpose of this study was to identify mutations in one of the genes, PRPF31, in French patients with autosomal dominant RP, to perform genotype-phenotype correlations of those patients, to determine the prevalence of PRPF31 mutations in this cohort and to review previously identified PRPF31 mutations from other cohorts.

Methods

Detailed phenotypic characterization was performed including precise family history, best corrected visual acuity using the ETDRS chart, slit lamp examination, kinetic and static perimetry, full field and multifocal ERG, fundus autofluorescence imaging and optic coherence tomography. For genetic diagnosis, genomic DNA of ninety families was isolated by standard methods. The coding exons and flanking intronic regions of PRPF31 were PCR amplified, purified and sequenced in the index patient.

Results

We showed for the first time that 6.7% cases of a French adRP cohort have a PRPF31 mutation. We identified in total six mutations, which were all novel and not detected in ethnically matched controls. The mutation spectrum from our cohort comprises frameshift and splice site mutations. Co-segregation analysis in available family members revealed that each index patient and all affected family members showed a heterozygous mutation. In five families incomplete penetrance was observed. Most patients showed classical signs of RP with relatively preserved central vision and visual field.

Conclusion

Our studies extended the mutation spectrum of PRPF31 and as previously reported in other populations, it is a major cause of adRP in France.
Expression profiling in canine osteosarcoma: identification of biomarkers and pathways associated with outcome
Authors: O'Donoghue Liza E , Ptitsyn Andrey A , Kamstock Debra A , Siebert Janet , Thomas Russell S , Duval Dawn L
Published: October 2010

Background

Osteosarcoma (OSA) spontaneously arises in the appendicular skeleton of large breed dogs and shares many physiological and molecular biological characteristics with human OSA. The standard treatment for OSA in both species is amputation or limb-sparing surgery, followed by chemotherapy. Unfortunately, OSA is an aggressive cancer with a high metastatic rate. Characterization of OSA with regard to its metastatic potential and chemotherapeutic resistance will improve both prognostic capabilities and treatment modalities.

Methods

We analyzed archived primary OSA tissue from dogs treated with limb amputation followed by doxorubicin or platinum-based drug chemotherapy. Samples were selected from two groups: dogs with disease free intervals (DFI) of less than 100 days (n = 8) and greater than 300 days (n = 7). Gene expression was assessed with Affymetrix Canine 2.0 microarrays and analyzed with a two-tailed t-test. A subset of genes was confirmed using qRT-PCR and used in classification analysis to predict prognosis. Systems-based gene ontology analysis was conducted on genes selected using a standard J5 metric. The genes identified using this approach were converted to their human homologues and assigned to functional pathways using the GeneGo MetaCore platform.

Results

Potential biomarkers were identified using gene expression microarray analysis and 11 differentially expressed (p < 0.05) genes were validated with qRT-PCR (n = 10/group). Statistical classification models using the qRT-PCR profiles predicted patient outcomes with 100% accuracy in the training set and up to 90% accuracy upon stratified cross validation. Pathway analysis revealed alterations in pathways associated with oxidative phosphorylation, hedgehog and parathyroid hormone signaling, cAMP/Protein Kinase A (PKA) signaling, immune responses, cytoskeletal remodeling and focal adhesion.

Conclusions

This profiling study has identified potential new biomarkers to predict patient outcome in OSA and new pathways that may be targeted for therapeutic intervention.
PDGF-B-driven gliomagenesis can occur in the absence of the proteoglycan NG2
Authors: Terrile Marta , Appolloni Irene , Calzolari Filippo , Perris Roberto , Tutucci Evelina , Malatesta Paolo
Published: October 2010

Background

In the last years, the transmembrane proteoglycan NG2 has gained interest as a therapeutic target for the treatment of diverse tumor types, including gliomas, because increases of its expression correlate with dismal prognosis. NG2 has been shown to function as a co-receptor for PDGF ligands whose aberrant expression is common in gliomas. We have recently generated a glioma model based on the overexpression of PDGF-B in neural progenitors and here we investigated the possible relevance of NG2 during PDGF-driven gliomagenesis.

Methods

The survival curves of NG2-KO mice overexpressing PDGF-B were compared to controls by using a Log-rank test. The characteristics of tumors induced in NG2-KO were compared to those of tumors induced in wild type mice by immunostaining for different cell lineage markers and by transplantation assays in adult mice.

Results

We showed that the lack of NG2 does not appreciably affect any of the characterized steps of PDGF-driven brain tumorigenesis, such as oligodendrocyte progenitor cells (OPC) induction, the recruitment of bystander OPCs and the progression to full malignancy, which take place as in wild type animals.

Conclusions

Our analysis, using both NG2-KO mice and a miRNA based silencing approach, clearly demonstrates that NG2 is not required for PDGF-B to efficiently induce and maintain gliomas from neural progenitors. On the basis of the data obtained, we therefore suggest that the role of NG2 as a target molecule for glioma treatment should be carefully reconsidered.
Increased accumulation of hypoxia-inducible factor-1α with reduced transcriptional activity mediates the antitumor effect of triptolide
Authors: Zhou Zhao-Li , Luo Zhi-Guo , Yu Bing , Jiang Yi , Chen Yi , Feng Jian-Ming , Dai Mei , Tong Lin-Jiang , Li Zheng , Li Yuan-Chao , Ding Jian , Miao Ze-Hong
Published: October 2010

Background

Hypoxia-inducible factor-1α (HIF-1α), a critical transcription factor to reduced O2 availability, has been demonstrated to be extensively involved in tumor survival, aggressive progression, drug resistance and angiogenesis. Thus it has been considered as a potential anticancer target. Triptolide is the main principle responsible for the biological activities of the Traditional Chinese Medicine tripterygium wilfordii Hook F. Triptolide possesses great chemotherapy potential for cancer with its broad-spectrum anticancer, antiangiogenesis, and drug-resistance circumvention activities. Numerous biological molecules inhibited by triptolide have been viewed as its possible targets. However, the anticancer action mechanisms of triptolide remains to be further investigated. Here we used human ovarian SKOV-3 cancer cells as a model to probe the effect of triptolide on HIF-1α.

Results

Triptolide was observed to inhibit the proliferation of SKOV-3 cells, and meanwhile, to enhance the accumulation of HIF-1α protein in SKOV-3, A549 and DU145 cells under different conditions. Triptolide did not change the kinetics or nuclear localization of HIF-1α protein or the 26 S proteasome activity in SKOV-3 cells. However, triptolide was found to increase the levels of HIF-1α mRNA. Unexpectedly, the HIF-1α protein induced by triptolide appeared to lose its transcriptional activity, as evidenced by the decreased mRNA levels of its target genes including VEGF, BNIP3 and CAIX. The results were further strengthened by the lowered secretion of VEGF protein, the reduced sprout outgrowth from the rat aorta rings and the inhibitory expression of the hypoxia responsive element-driven luciferase reporter gene. Moreover, the silencing of HIF-1α partially prevented the cytotoxicity and apoptosis triggered by triptolide.

Conclusions

The potent induction of HIF-1α protein involved in its cytotoxicity, together with the suppression of HIF-1 transcriptional activity, indicates the great therapeutic potential of triptolide as an anticancer drug. Meanwhile, our data further stress the possibility that HIF-1α functions in an unresolved nature or condition.
Improving the interpretation of quality of life evidence in meta-analyses: the application of minimal important difference units
Authors: Johnston Bradley C , Thorlund Kristian , Schünemann Holger J , Xie Feng , Murad Mohammad Hassan , Montori Victor M , Guyatt Gordon H
Published: October 2010

Systematic reviews of randomized trials that include measurements of health-related quality of life potentially provide critical information for patient and clinicians facing challenging health care decisions. When, as is most often the case, individual randomized trials use different measurement instruments for the same construct (such as physical or emotional function), authors typically report differences between intervention and control in standard deviation units (so-called "standardized mean difference" or "effect size"). This approach has statistical limitations (it is influenced by the heterogeneity of the population) and is non-intuitive for decision makers. We suggest an alternative approach: reporting results in minimal important difference units (the smallest difference patients experience as important). This approach provides a potential solution to both the statistical and interpretational problems of existing methods.
Estradiol, progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles
Authors: Wen Xuesong , Li Dong , Tozer Amanda J , Docherty Suzanne M , Iles Ray K
Published: October 2010

Background

The production of sex steroids by follicular cells is proposed to be influenced by the maturity of the incumbent oocyte. Thus steroid levels may reflect suitability of an oocyte for IVF. We examined follicular fluids and granulosa cell production of steroid from IVF patients in order to test the relationship between steroid levels and fertilization.

Methods

Follicular fluid and granulosa cells were extracted from 206 follicles of 35 women undergoing controlled ovarian stimulation. Follicular fluid was assayed for estradiol, progesterone and testosterone. Granulosa cells were cultured from individual follicles and their culture media assayed for production of these hormones after 24 hrs in vitro. Levels of steroids were correlated with follicular diameter, oocyte recovery and subsequent fertilization.

Results

Follicular fluid levels of progesterone were 6100 times higher than that of estradiol, and 16,900 times higher that of testosterone. Despite the size of follicle triggered after controlled luteinisation, the levels of progesterone and testosterone were maintained at relatively constant levels (median 98.1 micromoles/L for progesterone, and 5.8 nanomoles/L for testosterone). However, estradiol levels were slightly lower in the larger follicles (follicular diameter 10-15 mm, median 25.3 nanomoles/L; follicles > = 15 mm, median 15.1 nanomoles/L; linear correlation r = -0.47, p < 0.0001). With respect to oocyte recovery, no steroid showed a significant association in follicular fluid levels. Similarly no difference in follicular fluid steroid levels was found for those oocytes that did or did not fertilize. Significant quantities of progesterone were produced by the granulosa cells but production was constant regardless of the size of follicle from which the cells originated. Estradiol levels were only detectable in 10 of 121 cultures examined, and testosterone in none. Interestingly, when an oocyte was present follicular estradiol levels correlated with progesterone levels. However, when absent, follicular estradiol levels correlated with testosterone levels but not with progesterone.

Conclusions

The principle steroid product of luteinized pre-ovulatory granulosa is progesterone, a differentiation triggered by the gonadotropin surge. However, absolute steroid levels are associated with follicular size, not oocyte maturation/ability to fertilize.
Distinct modulation of microglial amyloid β phagocytosis and migration by neuropeptidesi
Authors: Fleisher-Berkovich Sigal , Filipovich-Rimon Talia , Ben-Shmuel Sarit , Hülsmann Claudia , Kummer Markus P , Heneka Michael T
Published: October 2010

Microglial activation plays an integral role in the development and course of neurodegeneration. Although neuropeptides such as bradykinin (BK), somatostatin (SST), and endothelin (ET) are known to be important mediators of inflammation in the periphery, evidence of a similar function in brain is scarce. Using immunocytochemistry, we demonstrate the expression of receptors for BK (B1, B2 subtypes), ET (ETA, ETB subtypes) and SST (SST 2, 3, 4 subtypes) in primary microglia and microglial cell lines. Exposure of BV2 and N9, as well as primary microglial cells to BK or SST increased Aβ uptake in a concentration-dependent manner, whereas endothelin decreased Aβ uptake. This was caused by increased phagocytosis of Aβ since the rate of intracellular Aβ degradation remained unaffected. All neuropeptides increased chemotactic activity of microglia. In addition, BK reduced Aβ-induced expression of proinflammatory genes including iNOS and COX-2. ET decreased the Aβ-induced expression of monocyte chemoattractant protein 1 and interleukin-6. These results suggest that neuropeptides play an important role in chemotaxis and Aβ clearance and modulate the brain's response to neuroinflammatory processes.
Cerebrovascular expression of proteins related to inflammation, oxidative stress and neurotoxicity is altered with aging
Authors: Tripathy Debjani , Yin Xiangling , Sanchez Alma , Luo Jinhua , Martinez Joseph , Grammas Paula
Published: October 2010

Background

Most neurodegenerative diseases are age-related disorders; however, how aging predisposes the brain to disease has not been adequately addressed. The objective of this study is to determine whether expression of proteins in the cerebromicrovasculature related to inflammation, oxidative stress and neurotoxicity is altered with aging.

Methods

Brain microvessels are isolated from Fischer 344 rats at 6, 12, 18 and 24 months of age. Levels of interleukin (IL)-1β and IL-6 RNA are determined by RT-PCR and release of cytokines into the media by ELISA. Vessel conditioned media are also screened by ELISA for IL-1α, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α, (TNFα), and interferon γ (IFNγ). Immunofluorescent analysis of brain sections for IL-1β and IL-6 is performed.

Results

Expression of IL-1β and IL-6, both at RNA and protein levels, significantly (p < 0.01) decreases with age. Levels of MCP-1, TNFα, IL-1α, and IFNγ are significantly (p < 0.05-0.01) lower in 24 month old rats compared to 6 month old animals. Immunofluorescent analysis of brain vessels also shows a decline in IL-1β and IL-6 in aged rats. An increase in oxidative stress, assessed by increased carbonyl formation, as well as a decrease in the antioxidant protein manganese superoxide dismutase (MnSOD) is evident in vessels of aged animals. Finally, addition of microvessel conditioned media from aged rats to neuronal cultures evokes significant (p < 0.001) neurotoxicity.

Conclusions

These data demonstrate that cerebrovascular expression of proteins related to inflammation, oxidative stress and neurotoxicity is altered with aging and suggest that the microvasculature may contribute to functional changes in the aging brain.
Factors that predict fertility desires for people living with HIV infection at a support and treatment centre in Kabale, Uganda
Authors: Kakaire Othman , Osinde Michael O , Kaye Dan K
Published: October 2010

Background

Studies from different contexts worldwide indicate that HIV positive patients manifest high-risk sexual behavior characterized by fertility intentions, multiple sexual partners, non-use of contraceptives and non-disclosure of HIV status to their sex partners. The objective was to analyze fertility desires among persons living with HIV at a treatment centre in Kabale Hospital, Southwestern Uganda.

Methods

From January to August 2009, we interviewed 400 HIV positive patients seeking care using an interviewer-administered questionnaire. We assessed socio-demographic variables, reproductive history, sexuality and fertility desires. At bivariate and multivariate analysis, characteristics of participants who reported or did not report desire to have a child in the near future were compared.

Results

Of the 400 respondents, (25.3%) were male, 47.3% were aged 25-34 years, over 85% were currently married or had ever been married, and the 62% had primary level of education or less. Over 17% had produced a child since the HIV diagnosis was made, and 28.6% reported that they would like to have a child in the near future. Age of the respondent, being single (versus being ever-married) and whether any of the respondents' children had died were inversely associated with fertility intentions.

Conclusion

Factors inversely associated with fertility intentions were age of the respondent, marital status and whether any of the respondents' children had died. Use of antiretroviral therapy was not associated with fertility intentions.
Moving towards Supraspinal TRPV1 Receptors for Chronic Pain Relief
Authors: Palazzo Enza , Luongo Livio , de Novellis Vito , Berrino Liberato , Rossi Francesco , Maione Sabatino
Published: October 2010

Transient receptor potential vanilloid type 1 (TRPV1) receptor is a non selective ligand-gated cation channel activated by capsaicin, heat, protons and endogenous lipids termed endovanilloids. As well as peripheral primary afferent neurons and dorsal root ganglia, TRPV1 receptor is also expressed in spinal and supraspinal structures such as those belonging to the endogenous antinociceptive descending pathway which is a circuitry of the supraspinal central nervous system whose task is to counteract pain. It includes periaqueductal grey (PAG) and rostral ventromedial medulla (RVM) whose activation leads to analgesia. Such an effect is associated with a glutamate increase and the activation of OFF and inhibition of ON cell population in the rostral ventromedial medulla (RVM). Activation of the antinociceptive descending pathway via TPRV1 receptor stimulation in the PAG may be a novel strategy for producing analgesia in chronic pain. This review will summarize the more recent insights into the role of TRPV1 receptor within the antinociceptive descending pathway and its possible exploitation as a target for new pain-killer agents in chronic pain conditions, with particular emphasis on the most untreatable pain state: neuropathic pain.
Altered resting-state connectivity in subjects at ultra-high risk for psychosis: an fMRI study
Authors: Shim Geumsook , Oh Jungsu S , Jung Wi Hoon , Jang Joon Hwan , Choi Chi-Hoon , Kim Euitae , Park Hye-Yoon , Choi Jung-Seok , Jung Myung Hun , Kwon Jun Soo
Published: October 2010

Background

Individuals at ultra-high risk (UHR) for psychosis have self-disturbances and deficits in social cognition and functioning. Midline default network areas, including the medial prefrontal cortex and posterior cingulate cortex, are implicated in self-referential and social cognitive tasks. Thus, the neural substrates within the default mode network (DMN) have the potential to mediate self-referential and social cognitive information processing in UHR subjects.

Methods

This study utilized functional magnetic resonance imaging (fMRI) to investigate resting-state DMN and task-related network (TRN) functional connectivity in 19 UHR subjects and 20 matched healthy controls. The bilateral posterior cingulate cortex was selected as a seed region, and the intrinsic organization for all subjects was reconstructed on the basis of fMRI time series correlation.

Results

Default mode areas included the posterior/anterior cingulate cortices, the medial prefrontal cortex, the lateral parietal cortex, and the inferior temporal region. Task-related network areas included the dorsolateral prefrontal cortex, supplementary motor area, the inferior parietal lobule, and middle temporal cortex. Compared to healthy controls, UHR subjects exhibit hyperconnectivity within the default network regions and reduced anti-correlations (or negative correlations nearer to zero) between the posterior cingulate cortex and task-related areas.

Conclusions

These findings suggest that abnormal resting-state network activity may be related with the clinical features of UHR subjects. Neurodevelopmental and anatomical alterations of cortical midline structure might underlie altered intrinsic networks in UHR subjects.
Follicular dendritic cell sarcoma: a report of six cases and a review of the Chinese literature
Authors: Wang Haiwei , Su Zhansan , Hu Zhongliang , Wen Jifang , Liu Baoan
Published: October 2010

Goals

The main purpose of this study is to broaden the clinicopathological spectrum and increase recognition of follicular dendritic cell sarcoma (FDCS) through analysis of the clinical and pathological features of 50 cases.

Methods

The clinicopathological features of total 50 cases of FDCS were analyzed including a review of 44 cases reported in Chinese literature before October 2009 and six original cases from the pathology files conducted by the authors.

Results

The youngest patient came under observation in this study is only seven years old. Including the cases contributed by the authors, our literary review indicated that male dominated the tumor cases (M: F = 3: 2). 28 cases (56%) present with this disease in extranodal sites. Tumor cells demonstrated positive staining for the follicular dendritic cell markers CD21 (47/49), CD35 (43/45), CD23 (20/23) and CD68 (23/25). In situ hybridization for Epstein-Barr virus-encoded RNA was performed in 10 cases. Nevertheless, EBV expression was absent in all these cases. The follow-up analysis of all cases shows that 26 (81.2%) patients were alive and disease free; 6 (18.8%) patients were alive with recurrent disease or metastasis; and nobody had died of this disease at the time of last follow-up.

Conclusions

The diagnosis of the FDCS is based on the findings of morphology and immunohistochemistry. The FDCS occurred in China should be viewed and treated as a low-grade sarcoma, and the role of the EBV in the pathogenesis of this tumor is still uncertain. There is a possibility that the tumor might be racial or geographic correlated, because most cases were reported from Eastern Asia area; it's particular the case of the liver or spleen tumor.
Retrieval of the Alzheimer's amyloid precursor protein from the endosome to the TGN is S655 phosphorylation state-dependent and retromer-mediated
Authors: Vieira Sandra I , Rebelo Sandra , Esselmann Hermann , Wiltfang Jens , Lah James , Lane Rachel , Small Scott A , Gandy Sam , da Cruz e Silva Edgar F , da Cruz e Silva Odete AB
Published: October 2010

Background

Retrograde transport of several transmembrane proteins from endosomes to the trans-Golgi network (TGN) occurs via Rab 5-containing endosomes, mediated by clathrin and the recently characterized retromer complex. This complex and one of its putative sorting receptor components, SorLA, were reported to be associated to late onset Alzheimer's disease (AD). The pathogenesis of this neurodegenerative disorder is still elusive, although accumulation of amyloidogenic Abeta is a hallmark. This peptide is generated from the sucessive β- and γ- secretase proteolysis of the Alzheimer's amyloid precursor protein (APP), events which are associated with endocytic pathway compartments. Therefore, APP targeting and time of residence in endosomes would be predicted to modulate Abeta levels. However, the formation of an APP- and retromer-containing protein complex with potential functions in retrieval of APP from the endosome to the TGN had, to date, not been demonstrated directly. Further, the motif(s) in APP that regulate its sorting to the TGN have not been characterized.

Results

Through the use of APP-GFP constructs, we show that APP containing endocytic vesicles targeted for the TGN, are also immunoreactive for clathrin-, Rab 5- and VPS35. Further, they frequently generate protruding tubules near the TGN, supporting an association with a retromer-mediated pathway. Importantly, we show for the first time, that mimicking APP phosphorylation at S655, within the APP 653YTSI656 basolateral motif, enhances APP retrieval via a retromer-mediated process. The phosphomimetic APP S655E displays decreased APP lysosomal targeting, enhanced mature half-life, and decreased tendency towards Abeta production. VPS35 downregulation impairs the phosphorylation dependent APP retrieval to the TGN, and decreases APP half-life.

Conclusions

We reported for the first time the importance of APP phosphorylation on S655 in regulating its retromer-mediated sorting to the TGN or lysosomes. Significantly, the data are consistent with known interactions involving the retromer, SorLA and APP. Further, these findings add to our understanding of APP targeting and potentially contribute to our knowledge of sporadic AD pathogenesis representing putative new targets for AD therapeutic strategies.
Public perception of mental health in Iraq
Authors: Sadik Sabah , Bradley Marie , Al-Hasoon Saad , Jenkins Rachel
Published: October 2010

Background

People who suffer from mental illness, the professionals who treat them, and indeed the actual concept of mental illness are all stigmatised in public perception and often receive very negative publicity. This paper looks at Iraq, which has a population of 30 million who are mainly Moslem. Mental health services and professionals have historically been sparse in Iraq with 1 psychiatrist per 300,000 before 2003 falling to 1 per million until recently and 1 primary care centre (40 Healthcare Workers including 4 General Practitioners) to 35,000 population, compared with 1 GP per 1700 population in the UK.

Methods

We aimed to assess public attitudes and perceptions to mental illness. Participants were asked to complete a questionnaire (additional file 1), which was designed specifically for Iraqi contexts and was made available in 2 languages. The survey was carried out in 500 participants' homes across 2 districts of Baghdad.

Results

The response rate of the survey was 86.4%. The paper shows respondents views on the aetiology of mental illness, perceptions of people with mental illness and attitudes towards care and treatment of people with mental illness.

Conclusions

This survey of public attitudes towards mental illness in Iraq has shown that community opinion about the aetiology of mental illness is broadly compatible with scientific evidence, but understanding of the nature of mental illness, its implications for social participation and management remains negative in general.
Clinical characteristics of depression among adolescent females: a cross-sectional study
Authors: Khalil Afaf H , Rabie Menan A , Abd-El-Aziz Mohamed F , Abdou Tarek A , El-Rasheed Amany H , Sabry Walaa M
Published: October 2010

Background

Adolescents rarely seek psychiatric help; they even hesitate to disclose their feelings to their parents. However; the adolescents especially the females experience depressive symptoms more frequently than general population. Do they experience classic depressive symptoms? Are there symptoms specific to this subpopulation?

Aim of the study

Through this study, the authors aimed to estimate the prevalence of depressive disorders in Egyptian adolescent female students. They also expected a characteristic profile of symptoms for the adolescent females. However available literature provides no guidance in the description of this profile of symptoms.

Methods

A number of 602 adolescent females were interviewed, and subjected to General Health Questionnaire (GHQ); Children Depression Inventory (CDI), Structured Clinical Interview for DSM-IV Axis-I Disorders (SCID-I), then Hamilton Rating Scale for Depression (Ham-D). Results were analyzed by the use of SPSS-15.

Results

The study revealed the prevalence of depression in the sample of the study to be 15.3% (measured by CDI), and 13.3% (measured by SCID-I). Fatigue was the most common presenting depressive symptom (81.3%), in addition to other emotional, cognitive and physiological symptoms. Suicidal ideations were the most common suicidal symptoms in depressed adolescent females (20%), with 2.5% serious suicidal attempts.

Conclusions

The somatic symptoms were by far the most common presenting symptom for female adolescents suffering from depressive disorders. Depressive phenomena including unexplained fatigue, decreased energy, psychomotor changes, lack of concentration, weight changes and suicidal ideations may be the presenting complaints instead of the classic sad mood.
Investigation of Toll-like receptors in the pathogenesis of fibrotic and granulomatous disorders: a bronchoalveolar lavage study
Authors: Margaritopoulos Giorgos A , Antoniou Katerina M , Karagiannis Kostas , Samara Katerina D , Lasithiotaki Ismini , Vassalou Evi , Lymbouridou Rena , Koutala Helen , Siafakas Nikos M
Published: October 2010

Background and aim

Toll-like receptors (TLRs), a key component of innate immunity, have recently been implicated in the pathogenesis of interstitial lung diseases (ILDs). As the involvement of TLRs has not yet been fully elucidated, the aim of the current study was to examine the expression of various TLRs in the bronchoalveolar lavage fluid (BALF) of patients with ILDs.

Patients and Methods

We studied prospectively three groups of patients: (1) one group of 35 patients with fibrotic disorders, 16 with idiopathic pulmonary fibrosis (IPF) and 19 with fibrotic interstitial pneumonias associated with collagen tissue disorders (CTD-IPs); (2) one group of 14 patients with pulmonary sarcoidosis; and (3) 11 normal subjects. We evaluated TLR expression with flow cytometry and mRNA expression with real-time PCR.

Results

An overexpression of TLR-3 mRNA was found in fibrotic disorders (CTD-IPs/IPF) in comparison with sarcoidosis (mean ± SD, 1.104 ± 1.087 versus 0.038 ± 0.03;P= 0.04). Additionally, TLR-3 mRNA was increased in CTD-IPs in comparison with IPF (P= 0.001), sarcoidosis (P= 0.002) and controls (P= 0.05). An upregulation in TLR-7 and -9 mRNA expression was detected in IPF (P= 0.05) and sarcoidosis (P= 0.05), respectively, when compared to controls. A higher percentage of TLR-9-expressing cells was found in BALF of CTD-IPs when compared to IPF (mean ± SD, 36.7 ± 7.06 versus 14.85 ± 3.82;P= 0.025).

Conclusion

We observed distinct profiles of TLR expression in fibrotic and granulomatous disorders. It is likely that they could play a key role in the pathogenesis of these diseases and represent future therapeutic targets.