bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of high dimensional data using pre-defined set and subset information, with applications to genomic data
Authors: Guo Wenge , Yang Mingan , Xing Chuanhua , Peddada Shyamal D 
Published: July 2012

AbstractBackgroundBased on available biological information, genomic data can often be partitioned into pre-defined sets (e.g. pathways) and subsets within sets. Biologists are often interested in determining whether some pre-defined sets of variables (e.g. genes) are differentially expressed under varying experimental conditions. Several procedures are available in the literature for making such determinations, however, they do not take into account information regarding the subsets within each set. Secondly, variables (e.g. genes) belonging to a set or a subset are potentially correlated, yet such information is often ignored and univariate methods are used. This may result in loss of power and/or inflated false positive rate.ResultsWe introduce a multiple testing-based methodology which makes use of available information regarding biologically relevant subsets within each pre-defined set of variables while exploiting the underlying dependence structure among the variables. Using this methodology, a biologist may not only determine whether a set of variables are differentially expressed between two experimental conditions, but may also test whether specific subsets within a significant set are also significant.ConclusionsThe proposed methodology; (a) is easy to implement, (b) does not require inverting potentially singular covariance matrices, and (c) controls the family wise error rate (FWER) at the desired nominal level, (d) is robust to the underlying distribution and covariance structures. Although for simplicity of exposition, the methodology is described for microarray gene expression data, it is also applicable to any high dimensional data, such as the mRNA seq data, CpG methylation data etc.
CalpB modulates border cell migration in Drosophila egg chambers
Authors: Kókai Endre , Páldy Ferencz Sándor , Somogyi Kálmán , Chougule Anil , Pál Margit , Kerekes Éva , Deák Péter , Friedrich Péter , Dombrádi Viktor , Ádám Géza 
Published: July 2012

Abstract

Background
Calpains are calcium regulated intracellular cysteine proteases implicated in a variety of physiological functions and pathological conditions. The Drosophila melanogaster genome contains only two genes, CalpA and CalpB coding for canonical, active calpain enzymes. The movement of the border cells in Drosophila egg chambers is a well characterized model of the eukaryotic cell migration. Using this genetically pliable model we can investigate the physiological role of calpains in cell motility.

Results
We demonstrate at the whole organism level that CalpB is implicated in cell migration, while the structurally related CalpA paralog can not fulfill the same function. The downregulation of the CalpB gene by mutations or RNA interference results in a delayed migration of the border cells in Drosophila egg chambers. This phenotype is significantly enhanced when the focal adhesion complex genes encoding for α-PS2 integrin ( if), β-PS integrin ( mys) and talin ( rhea) are silenced. The reduction of CalpB activity diminishes the release of integrins from the rear end of the border cells. The delayed migration and the reduced integrin release phenotypes can be suppressed by expressing wild-type talin-head in the border cells but not talin-headR367A, a mutant form which is not able to bind β-PS integrin. CalpB can cleave talin in vitro, and the two proteins coimmunoprecipitate from Drosophila extracts.

Conclusions
The physiological function of CalpB in border cell motility has been demonstrated in vivo. The genetic interaction between the CalpB and the if, mys, as well as rhea genes, the involvement of active talin head-domains in the process, and the fact that CalpB and talin interact with each other collectively suggest that the limited proteolytic cleavage of talin is one of the possible mechanisms through which CalpB regulates cell migration.
Adaptive evolution of Toll-like receptor 5 in domesticated mammals
Authors: Smith Sarah A , Jann Oliver C , Haig David , Russell George C , Werling Dirk , Glass Elizabeth J , Emes Richard D 
Published: July 2012

Abstract

Background
Previous studies have proposed that mammalian toll like receptors (TLRs) have evolved under diversifying selection due to their role in pathogen detection. To determine if this is the case, we examined the extent of adaptive evolution in the TLR5 gene in both individual species and defined clades of the mammalia.

Results
In support of previous studies, we find evidence of adaptive evolution of mammalian TLR5. However, we also show that TLR5 genes of domestic livestock have a concentration of single nucleotide polymorphisms suggesting a specific signature of adaptation. Using codon models of evolution we have identified a concentration of rapidly evolving codons within the TLR5 extracellular domain a site of interaction between host and the bacterial surface protein flagellin.

Conclusions
The results suggest that interactions between pathogen and host may be driving adaptive change in TLR5 by competition between species. In support of this, we have identified single nucleotide polymorphisms (SNP) in sheep and cattle TLR5 genes that are co-localised and co-incident with the predicted adaptive codons suggesting that adaptation in this region of the TLR5 gene is on-going in domestic species.
Reassessment of the function of somatolactin alpha in lipid metabolism using medaka mutant and transgenic strains
Authors: Sasano Yuko , Yoshimura Asami , Fukamachi Shoji 
Published: July 2012

Abstract

Background
Somatolactin alpha (SLa) is a fish-specific peptide hormone secreted from the pituitary. In medaka, SLa functions to darken the skin color and lack of SLa makes it pale. Transcription of SLa is enhanced or suppressed when fish are kept in dark or bright conditions, respectively, indicating SLa’s important role in background acclimation of the skin color. Bizarrely, however, the lack of SLa seems to cause the additional defect of increased triglycerides in organs, which could not be rescued (decreased) by its overexpression.

Results
To assess this enigmatic result, we investigated genetic (the SLa, Slc45a2, r, and Y genes) and nongenetic (age, fasting, water temperature, and background color) effects on hepatic triglycerides. These experiments found that percent hepatic triglycerides quickly change in response to external/internal environments. Effects of SLa seemed to be much less obvious, although it may increase the proportion of hepatic triglycerides at least during certain breeding conditions or under certain genetic backgrounds.

Conclusions
The present results do not exclude the possibility that SLa takes part in lipid metabolism or other physiological processes. However, we suggest that skin-color regulation is the only definite role of SLa so far demonstrated in this species.
Genomic and transcriptomic insights into the thermo-regulated biosynthesis of validamycin in Streptomyces hygroscopicus 5008
Authors: Wu Hang , Qu Shuang , Lu Chenyang , Zheng Huajun , Zhou Xiufen , Bai Linquan , Deng Zixin 
Published: July 2012

Abstract

Background

Streptomyces hygroscopicus 5008 has been used for the production of the antifungal validamycin/jinggangmycin for more than 40 years. A high yield of validamycin is achieved by culturing the strain at 37°C, rather than at 30°C for normal growth and sporulation. The mechanism(s) of its thermo-regulated biosynthesis was largely unknown.

Results
The 10,383,684-bp genome of strain 5008 was completely sequenced and composed of a linear chromosome, a 164.57-kb linear plasmid, and a 73.28-kb circular plasmid. Compared with other Streptomyces genomes, the chromosome of strain 5008 has a smaller core region and shorter terminal inverted repeats, encodes more α/β hydrolases, major facilitator superfamily transporters, and Mg2+/Mn2+-dependent regulatory phosphatases. Transcriptomic analysis revealed that the expression of 7.5% of coding sequences was increased at 37°C, including biosynthetic genes for validamycin and other three secondary metabolites. At 37°C, a glutamate dehydrogenase was transcriptionally up-regulated, and further proved its involvement in validamycin production by gene replacement. Moreover, efficient synthesis and utilization of intracellular glutamate were noticed in strain 5008 at 37°C, revealing glutamate as the nitrogen source for validamycin biosynthesis. Furthermore, a SARP-family regulatory gene with enhanced transcription at 37°C was identified and confirmed to be positively involved in the thermo-regulation of validamycin production by gene inactivation and transcriptional analysis.

Conclusions
Strain 5008 seemed to have evolved with specific genomic components to facilitate the thermo-regulated validamycin biosynthesis. The data obtained here will facilitate future studies for validamycin yield improvement and industrial bioprocess optimization.
Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model
Authors: Ajayi Abiodun , Yu Xin , Lindberg Staffan , Langel Ülo , Ström Anna-Lena 
Published: July 2012

Abstract

Background
Spinocerebellar ataxia type 7 (SCA7) is one of nine inherited neurodegenerative disorders caused by polyglutamine (polyQ) expansions. Common mechanisms of disease pathogenesis suggested for polyQ disorders include aggregation of the polyQ protein and induction of oxidative stress. However, the exact mechanism(s) of toxicity is still unclear.

Results
In this study we show that expression of polyQ expanded ATXN7 in a novel stable inducible cell model first results in a concomitant increase in ROS levels and aggregation of the disease protein and later cellular toxicity. The increase in ROS could be completely prevented by inhibition of NADPH oxidase (NOX) complexes suggesting that ATXN7 directly or indirectly causes oxidative stress by increasing superoxide anion production from these complexes. Moreover, we could observe that induction of mutant ATXN7 leads to a decrease in the levels of catalase, a key enzyme in detoxifying hydrogen peroxide produced from dismutation of superoxide anions. This could also contribute to the generation of oxidative stress. Most importantly, we found that treatment with a general anti-oxidant or inhibitors of NOX complexes reduced both the aggregation and toxicity of mutant ATXN7. In contrast, ATXN7 aggregation was aggravated by treatments promoting oxidative stress.

Conclusion
Our results demonstrates that oxidative stress contributes to ATXN7 aggregation as well as toxicity and show that anti-oxidants or NOX inhibition can ameliorate mutant ATXN7 toxicity.
Developmental trajectory of the endocannabinoid system in human dorsolateral prefrontal cortex
Authors: Long Leonora E , Lind Jonna , Webster Maree , Weickert Cynthia Shannon 
Published: July 2012

Abstract

Background
Endocannabinoids provide control over cortical neurotransmission. We investigated the developmental expression of key genes in the endocannabinoid system across human postnatal life and determined whether they correspond to the development of markers for inhibitory interneurons, which shape cortical development. We used microarray with qPCR validation and in situ hybridisation to quantify mRNA for the central endocannabinoid receptor CB1R, endocannabinoid synthetic enzymes (DAGLα for 2-arachidonylglycerol [2-AG] and NAPE-PLD for anandamide), and inactivating enzymes (MGL and ABHD6 for 2-AG and FAAH for anandamide) in human dorsolateral prefrontal cortex (39 days - 49 years).

Results
CB1R mRNA decreases until adulthood, particularly in layer II, after peaking between neonates and toddlers. DAGLα mRNA expression is lowest in early life and adulthood, peaking between school age and young adulthood. MGL expression declines after peaking in infancy, while ABHD6 increases from neonatal age. NAPE-PLD and FAAH expression increase steadily after infancy, peaking in adulthood.

Conclusions
Stronger endocannabinoid regulation of presynaptic neurotransmission in both supragranular and infragranular cortical layers as indexed through higher CB1R mRNA may occur within the first few years of human life. After adolescence, higher mRNA levels of the anandamide synthetic and inactivating enzymes NAPE-PLD and FAAH suggest that a late developmental switch may occur where anandamide is more strongly regulated after adolescence than earlier in life. Thus, expression of key genes in the endocannabinoid system changes with maturation of cortical function.
Cold-acclimation limits low temperature induced photoinhibition by promoting a higher photochemical quantum yield and a more effective PSII restoration in darkness in the Antarctic rather than the Andean ecotype of Colobanthus quitensis Kunt Bartl (Cariophyllaceae)
Authors: Bascuñán-Godoy Luisa , Sanhueza Carolina , Cuba Marely , Zuñiga Gustavo E , Corcuera Luis J , Bravo León A 
Published: July 2012

Abstract

Background
Ecotypes of Colobanthus quitensis Kunt Bartl (Cariophyllaceae) from Andes Mountains and Maritime Antarctic grow under contrasting photoinhibitory conditions, reaching differential cold tolerance upon cold acclimation. Photoinhibition depends on the extent of photodamage and recovery capability. We propose that cold acclimation increases resistance to low-temperature-induced photoinhibition, limiting photodamage and promoting recovery under cold. Therefore, the Antarctic ecotype (cold hardiest) should be less photoinhibited and have better recovery from low-temperature-induced photoinhibition than the Andean ecotype. Both ecotypes were exposed to cold induced photoinhibitory treatment (PhT). Photoinhibition and recovery of photosystem II (PSII) was followed by fluorescence, CO2 exchange, and immunoblotting analyses.

Results
The same reduction (25%) in maximum PSII efficiency (Fv/Fm) was observed in both cold-acclimated (CA) and non-acclimated (NA) plants under PhT. A full recovery was observed in CA plants of both ecotypes under dark conditions, but CA Antarctic plants recover faster than the Andean ecotype.
Under PhT, CA plants maintain their quantum yield of PSII, while NA plants reduced it strongly (50% and 73% for Andean and Antarctic plants respectively). Cold acclimation induced the maintenance of PsaA and Cyt b6/f and reduced a 41% the excitation pressure in Antarctic plants, exhibiting the lowest level under PhT. xCold acclimation decreased significantly NPQs in both ecotypes, and reduced chlorophylls and D1 degradation in Andean plants under PhT.
NA and CA plants were able to fully restore their normal photosynthesis, while CA Antarctic plants reached 50% higher photosynthetic rates after recovery, which was associated to electron fluxes maintenance under photoinhibitory conditions.

Conclusions
Cold acclimation has a greater importance on the recovery process than on limiting photodamage. Cold acclimation determined the kinetic and extent of recovery process under darkness in both C. quitensis ecotypes. The greater recovery of PSII at low temperature in the Antarctic ecotype was related with its ability to maintain PsaA, Cyt b6/f and D1 protein after photoinhibitory conditions. This is probably due to either a higher stability of these polypeptides or to the maintenance of their turnover upon cold acclimation. In both cases, it is associated to the maintenance of electron drainage from the intersystem pool, which maintains QA more oxidized and may allow the synthesis of ATP and NADPH necessaries for the regeneration of ribulose 1,5-bisphosphate in the Calvin Cycle. This could be a key factor for C. quitensis success under the harsh conditions and the short growing period in the Maritime Antarctic.
Is single reading with computer-aided detection (CAD) as good as double reading in mammography screening? A systematic review
Authors: Azavedo Edward , Zackrisson Sophia , Mejàre Ingegerd , Heibert Arnlind Marianne 
Published: July 2012

Abstract

Background
In accordance with European guidelines, mammography screening comprises independent readings by two breast radiologists (double reading). CAD (computer-aided detection) has been suggested to complement or replace one of the two readers (single reading + CAD).
The aim of this systematic review is to address the following question: Is the reading of mammographic x-ray images by a single breast radiologist together with CAD at least as accurate as double reading?

Methods
The electronic literature search included the databases Pub Med, EMBASE and The Cochrane Library. Two independent reviewers assessed abstracts and full-text articles.

Results
1049 abstracts were identified, of which 996 were excluded with reference to inclusion and exclusion criteria; 53 full-text articles were assessed for eligibility. Finally, four articles were included in the qualitative analysis, and one in a GRADE synthesis.

Conclusions
The scientific evidence is insufficient to determine whether the accuracy of single reading + CAD is at least equivalent to that obtained in standard practice, i.e. double reading where two breast radiologists independently read the mammographic images.
Chronic kidney disease among high school students of Kinshasa
Authors: Bukabau Justine B , Makulo Jean-Robert R , Pakasa Nestor M , Cohen Eric P , Lepira François B , Kayembe Patrick K , Nseka Nazaire M , Sumaili Ernest K 
Published: July 2012

AbstractBackgroundChronic kidney disease (CKD) is a major worldwide health problem. However, its burden among adolescents and young adults is unknown, especially in sub-Saharan Africa. The aim of this study was to investigate its prevalence in the school environment. The concordance of usual formulas used to estimate renal function was also assessed.MethodsIn an epidemiological cross sectional study, a random sample of 524 pupils (263 boys, mean age of 18.7 ± 1.4 years) from school environment of Kinshasa were studied. Recorded parameters of interest were anthropometric, proteinuria, serum creatinine and estimated glomerular filtration rate (eGFR) according to the Schwartz formula using uncalibrated creatinine levels from one random measurement. CKD was defined as the presence of kidney damage (daily proteinuria ≥ 300 mg) and/or reduced kidney function (eGFR < 60 ml/min/1.73 m2). Concordances between eGFR according to Schwartz, Cockcroft-Gault (C-G) indexed for BSA and modification of diet in renal disease (MDRD) study equations were computed using the kappa coefficient.ResultsThe prevalence of CKD by the Schwartz formula was 1.5%. By stage, 0.8% had CKD stage 1 (proteinuria with normal eGFR) and 0.8% had CKD stage 3 (eGFR, 30 to 59 ml/min/1.73 m2). The prevalence of proteinuria ≥ 300 mg/day was 1% (one case had 2.7g/day). Agreement between eGFR according to Schwartz formula and the MDRD formula was excellent (kappa: 88.8%). Although correlations between all formulas were excellent (0.99; 0.87, and 0.89), agreement was poor between eGFR according to Schwartz and C-G indexed BSA equation (kappa: 52.7%) and, poorer with C-G unadjusted for BSA (kappa: 26.9%).ConclusionIn the large African city of Kinshasa, 2% of high school students have CKD. This high prevalence rate emphasizes the need for appropriate detection and prevention measures in this vulnerable young age population group.
Trend analysis of hospital admissions attributable to tobacco smoking, Northern Territory Aboriginal and non-Aboriginal populations, 1998 to 2009
Authors: Pircher Sabine LM , Li Shu Qin , Guthridge Steven L 
Published: July 2012

Abstract

Background
Tobacco smoking is a well-recognised risk factor for many diseases [1]. This study assesses the extent of smoking-attributable hospitalisation in the Northern Territory (NT) Aboriginal and non-Aboriginal populations, and examines smoking-attributable hospitalisation trends for the years 1998/99 to 2008/09.

Methods
Hospital discharge data were used for the analysis. The proportion of conditions attributable to tobacco smoking was calculated using the aetiological fraction method. Age-adjusted smoking-attributable hospitalisation rates were calculated to describe the impact of tobacco smoking on the health of Territorians. A negative binominal regression model was applied to examine trends in smoking-attributable hospitalisations.

Results
Aboriginal Territorians were found to have higher rates of smoking-attributable hospitalisation, with Aboriginal males more than three times and Aboriginal females more than four times more likely to be hospitalised for smoking-attributable conditions than their non-Aboriginal counterparts. The age-adjusted hospitalisation rate for Aboriginal males increased by 31% and for Aboriginal females by 18% during the study period. There were more modest increases for NT non-Aboriginal males and females (5% and 17% respectively). The increase among Aboriginal males occurred up until 2005/06 followed by moderation in the trend. There were small reductions in smoking-attributable hospitalisation rates among all populations in younger age groups (less than 25 years).

Conclusions
Aboriginal Territorians experience much higher smoking-attributable hospitalisation rates than non-Aboriginal Territorians. The scale of the smoking burden and suggestion of recent moderation among Aboriginal men reinforce the importance of tobacco control interventions that are designed to meet the needs of the NT’s diverse population groups. Preventing smoking and increasing smoking cessation rates remain priorities for public health interventions in the NT.
Fighting parasites and predators: How to deal with multiple threats?
Authors: Hesse Olivia , Engelbrecht Wolfgang , Laforsch Christian , Wolinska Justyna 
Published: July 2012

AbstractBackgroundAlthough inducible defences have been studied extensively, only little is known about how the presence of parasites might interfere with these anti-predator adaptations. Both parasites and predators are important factors shaping community structure and species composition of ecosystems. Here, we simultaneously exposedDaphnia magnato predator cues (released by the tadpole shrimp,Triops, or by a fish) and spores of the yeast parasiteMetschnikowiasp. to determine how life history and morphological inducible defences against these two contrasting types of predators are affected by infection.ResultsThe parasite suppressed someTriops-induced defences:Daphnialost the ability to produce a greater number of larger offspring, a life-history adaptation toTriopspredation. In contrast, the parasite did not suppress inducible defences against fish: induction (resulting in smaller body length of the mothers as well as of their offspring) and infection acted additively on the measured traits. Thus, fish-induced defences may be less costly than inducible defences against small invertebrate predators likeTriops; the latter defences could no longer be expressed when the host had already invested in fighting off the parasite.ConclusionsIn summary, our study suggests that as specific inducible defences differ in their costs, some might be suppressed if a target prey is additionally infected. Therefore, adding parasite pressure to predator–prey systems can help to elucidate the costs of inducible defences.