bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive characterisation of the fibre composition and properties of a limb (Flexor digitorum superficialis, membri thoraci) and a trunk (Psoas major) muscle in cattle
Authors: Moreno-Sánchez Natalia , Díaz Clara , Carabaño María J , Rueda Julia , Rivero José-Luis L
Published: December 2008

Background

The fibre type attributes and the relationships among their properties play an important role in the differences in muscle capabilities and features. Comprehensive characterisation of the skeletal muscles should study the degree of association between them and their involvement in muscle functionality. The purposes of the present study were to characterise the fibre type composition of a trunk (Psoas major, PM) and a limb (Flexor digitorum, membri thoraci, FD) muscle in the bovine species and to study the degree of coordination among contractile, metabolic and histological properties of fibre types. Immunohistochemical, histochemical and histological techniques were used.

Results

The fibre type composition was delineated immunohistochemically in calf muscle samples, identifying three pure (I, IIA, and IIX) and two hybrid type fibres (I+IIA, and IIAX). Most of the fibres in FD were types I and IIA, while pure IIX were absent. All fibre types were found in PM, the IIX type being the most frequent. Compared to other species, small populations of hybrid fibres were detected. The five fibre types, previously identified, were ascribed to three different acid and alkaline mATPase activity patterns. Type I fibres had the highest oxidative capacity and the lowest glycolytic capacity. The reverse was true for the IIX fibres, whereas the type IIA fibres showed intermediate properties. Regarding the histological properties, type I fibres tended to be more capillarised than the II types. Correlations among contractile, metabolic and histological features on individual fibres were significantly different from zero (r values varied between -0.31 and 0.78). Hybrid fibre values were positioned between their corresponding pure types, and their positions were different regarding their metabolic and contractile properties.

Conclusion

Coordination among the contractile, metabolic and histological properties of fibres has been observed. However, the magnitude of the correlation among them is always below 0.8, suggesting that the properties of muscles are not fully explained by the fibre composition. These results support the concept that, to some extent, muscle plasticity can be explained by the fibre type composition, and by the properties derived from their metabolic and histological profiles.
A class frequency mixture model that adjusts for site-specific amino acid frequencies and improves inference of protein phylogeny
Authors: Wang Huai-Chun , Li Karen , Susko Edward , Roger Andrew J
Published: December 2008

Background

Widely used substitution models for proteins, such as the Jones-Taylor-Thornton (JTT) or Whelan and Goldman (WAG) models, are based on empirical amino acid interchange matrices estimated from databases of protein alignments that incorporate the average amino acid frequencies of the data set under examination (e.g JTT + F). Variation in the evolutionary process between sites is typically modelled by a rates-across-sites distribution such as the gamma (Γ) distribution. However, sites in proteins also vary in the kinds of amino acid interchanges that are favoured, a feature that is ignored by standard empirical substitution matrices. Here we examine the degree to which the pattern of evolution at sites differs from that expected based on empirical amino acid substitution models and evaluate the impact of these deviations on phylogenetic estimation.

Results

We analyzed 21 large protein alignments with two statistical tests designed to detect deviation of site-specific amino acid distributions from data simulated under the standard empirical substitution model: JTT+ F + Γ. We found that the number of states at a given site is, on average, smaller and the frequencies of these states are less uniform than expected based on a JTT + F + Γ substitution model. With a four-taxon example, we show that phylogenetic estimation under the JTT + F + Γ model is seriously biased by a long-branch attraction artefact if the data are simulated under a model utilizing the observed site-specific amino acid frequencies from an alignment. Principal components analyses indicate the existence of at least four major site-specific frequency classes in these 21 protein alignments. Using a mixture model with these four separate classes of site-specific state frequencies plus a fifth class of global frequencies (the JTT + cF + Γ model), significant improvements in model fit for real data sets can be achieved. This simple mixture model also reduces the long-branch attraction problem, as shown by simulations and analyses of a real phylogenomic data set.

Conclusion

Protein families display site-specific evolutionary dynamics that are ignored by standard protein phylogenetic models. Accurate estimation of protein phylogenies requires models that accommodate the heterogeneity in the evolutionary process across sites. To this end, we have implemented a class frequency mixture model (cF) in a freely available program called QmmRAxML for phylogenetic estimation.
Assembling an arsenal, the scorpion way
Authors: Kozminsky-Atias Adi , Bar-Shalom Adi , Mishmar Dan , Zilberberg Noam
Published: December 2008

Background

For survival, scorpions depend on a wide array of short neurotoxic polypeptides. The venoms of scorpions from the most studied group, the Buthida, are a rich source of small, 23–78 amino acid-long peptides, well packed by either three or four disulfide bridges that affect ion channel function in excitable and non-excitable cells.

Results

In this work, by constructing a toxin transcripts data set from the venom gland of the scorpion Buthus occitanus israelis, we were able to follow the evolutionary path leading to mature toxin diversification and suggest a mechanism for leader peptide hyper-conservation. Toxins from each family were more closely related to one another than to toxins from other species, implying that fixation of duplicated genes followed speciation, suggesting early gene conversion events. Upon fixation, the mature toxin-coding domain was subjected to diversifying selection resulting in a significantly higher substitution rate that can be explained solely by diversifying selection. In contrast to the mature peptide, the leader peptide sequence was hyper-conserved and characterized by an atypical sub-neutral synonymous substitution rate. We interpret this as resulting from purifying selection acting on both the peptide and, as reported here for the first time, the DNA sequence, to create a toxin family-specific codon bias.

Conclusion

We thus propose that scorpion toxin genes were shaped by selective forces acting at three levels, namely (1) diversifying the mature toxin, (2) conserving the leader peptide amino acid sequence and intriguingly, (3) conserving the leader DNA sequences.
Acidic pH shock induces the expressions of a wide range of stress-response genes
Authors: Kim Yoon Jung , Moon Myung Hee , Song Jae Yang , Smith Colin P , Hong Soon-Kwang , Chang Yong Keun
Published: December 2008

Background

Environmental signals usually enhance secondary metabolite production in Streptomycetes by initiating complex signal transduction system. It is known that different sigma factors respond to different types of stresses, respectively in Streptomyces strains, which have a number of unique signal transduction mechanisms depending on the types of environmental shock. In this study, we wanted to know how a pH shock would affect the expression of various sigma factors and shock-related proteins in S. coelicolor A3(2).

Results

According to the results of transcriptional and proteomic analyses, the major number of sigma factor genes were upregulated by an acidic pH shock. Well-studied sigma factor genes of sigH (heat shock), sigR (oxidative stress), sigB (osmotic shock), and hrdD that play a major role in the secondary metabolism, were all strongly upregulated by the pH shock. A number of heat shock proteins including the DnaK family and chaperones such as GroEL2 were also observed to be upregulated by the pH shock, while their repressor of hspR was strongly downregulated. Oxidative stress-related proteins such as thioredoxin, catalase, superoxide dismutase, peroxidase, and osmotic shock-related protein such as vesicle synthases were also upregulated in overall.

Conclusion

From these observations, an acidic pH shock was considered to be one of the strongest stresses to influence a wide range of sigma factors and shock-related proteins including general stress response proteins. The upregulation of the sigma factors and shock proteins already found to be related to actinorhodin biosynthesis was considered to have contributed to enhanced actinorhodin productivity by mediating the pH shock signal to regulators or biosynthesis genes for actinorhodin production.
Microarray-based estimation of SNP allele-frequency in pooled DNA using the Langmuir kinetic model
Authors: Yin Bin-Cheng , Li Honghua , Ye Bang-Ce
Published: December 2008

Background

High throughput genotyping of single nucleotide polymorphisms (SNPs) for genome-wide association requires technologies for generating millions of genotypes with relative ease but also at a reasonable cost and with high accuracy. In this work, we have developed a theoretical approach to estimate allele frequency in pooled DNA samples, based on the physical principles of DNA immobilization and hybridization on solid surface using the Langmuir kinetic model and quantitative analysis of the allelic signals.

Results

This method can successfully distinguish allele frequencies differing by 0.01 in the actual pool of clinical samples, and detect alleles with a frequency as low as 2%. The accuracy of measuring known allele frequencies is very high, with the strength of correlation between measured and actual frequencies having an r2 = 0.9992. These results demonstrated that this method could allow the accurate estimation of absolute allele frequencies in pooled samples of DNA in a feasible and inexpensive way.

Conclusion

We conclude that this novel strategy for quantitative analysis of the ratio of SNP allelic sequences in DNA pools is an inexpensive and feasible alternative for detecting polymorphic differences in candidate gene association studies and genome-wide linkage disequilibrium scans.
Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblasts
Authors: Lovas Agnes , Radke Dörte , Albrecht Daniela , Yilmaz Z Buket , Möller Ulrich , Habenicht Andreas JR , Weih Falk
Published: December 2008

Background

Lymphotoxin signaling via the lymphotoxin-β receptor (LTβR) has been implicated in biological processes ranging from development of secondary lymphoid organs, maintenance of spleen architecture, host defense against pathogens, autoimmunity, and lipid homeostasis. The major transcription factor that is activated by LTβR crosslinking is NF-κB. Two signaling pathways have been described, the classical inhibitor of NF-κB α (IκBα)-regulated and the alternative p100-regulated pathway that result in the activation of p50-RelA and p52-RelB NF-κB heterodimers, respectively.

Results

Using microarray analysis, we investigated the transcriptional response downstream of the LTβR in mouse embryonic fibroblasts (MEFs) and its regulation by the RelA and RelB subunits of NF-κB. We describe novel LTβR-responsive genes that were regulated by RelA and/or RelB. The majority of LTβR-regulated genes required the presence of both RelA and RelB, revealing significant crosstalk between the two NF-κB activation pathways. Gene Ontology (GO) analysis confirmed that LTβR-NF-κB target genes are predominantly involved in the regulation of immune responses. However, other biological processes, such as apoptosis/cell death, cell cycle, angiogenesis, and taxis were also regulated by LTβR signaling. Moreover, LTβR activation inhibited expression of a key adipogenic transcription factor, peroxisome proliferator activated receptor-γ (pparg), suggesting that LTβR signaling may interfere with adipogenic differentiation.

Conclusion

Microarray analysis of LTβR-stimulated fibroblasts provided comprehensive insight into the transcriptional response of LTβR signaling and its regulation by the NF-κB family members RelA and RelB.
Lipopolysaccharide (LPS) potentiates hydrogen peroxide toxicity in T98G astrocytoma cells by suppression of anti-oxidative and growth factor gene expression
Authors: Yue Gang , Shi Guanfang , Azaro Marco A , Yang Qifeng , Hu Guohong , Luo Minjie , Yin Kingsley , Nagele Robert G , Fine Daniel H , Yang Jin-Ming , Li Honghua
Published: December 2008

Background

Lipopolysaccharide (LPS) is a cell wall component of Gram-negative bacteria with proved role in pathogenesis of sepsis. Brain injury was observed with both patients dead from sepsis and animal septic models. However,in vitroadministration of LPS has not shown obvious cell damage to astrocytes and other relative cell lines while it does cause endothelial cell deathin vitro. These observations make it difficult to understand the role of LPS in brain parenchymal injury.

Results

To test the hypothesis that LPS may cause biological changes in astrocytes and make the cells to become vulnerable to reactive oxygen species, a recently developed highly sensitive and highly specific system for large-scale gene expression profiling was used to examine the gene expression profile of a group of 1,135 selected genes in a cell line, T98G, a derivative of human glioblastoma of astrocytic origin. By pre-treating T98G cells with different dose of LPS, it was found that LPS treatment caused a broad alteration in gene expression profile, but did not cause obvious cell death. However, after short exposure to H2O2, cell death was dramatically increased in the LPS pretreated samples. Interestingly, cell death was highly correlated with down-regulated expression of antioxidant genes such as cytochrome b561, glutathione s-transferase a4 and protein kinase C-epsilon. On the other hand, expression of genes encoding growth factors was significantly suppressed. These changes indicate that LPS treatment may suppress the anti-oxidative machinery, decrease the viability of the T98G cells and make the cells more sensitive to H2O2stress.

Conclusion

These results provide very meaningful clue for further exploring and understanding the mechanism underlying astrocyte injury in sepsisin vivo, and insight for why LPS could cause astrocyte injuryin vivo, but notin vitro. It will also shed light on the therapeutic strategy of sepsis.
Buffering by gene duplicates: an analysis of molecular correlates and evolutionary conservation
Authors: Hannay Kevin , Marcotte Edward M , Vogel Christine
Published: December 2008

Background

One mechanism to account for robustness against gene knockouts or knockdowns is through buffering by gene duplicates, but the extent and general correlates of this process in organisms is still a matter of debate. To reveal general trends of this process, we provide a comprehensive comparison of gene essentiality, duplication and buffering by duplicates across seven bacteria (Mycoplasma genitalium, Bacillus subtilis, Helicobacter pylori, Haemophilus influenzae, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Escherichia coli), and four eukaryotes (Saccharomyces cerevisiae (yeast), Caenorhabditis elegans (worm), Drosophila melanogaster (fly), Mus musculus (mouse)).

Results

In nine of the eleven organisms, duplicates significantly increase chances of survival upon gene deletion (P-value ≤ 0.05), but only by up to 13%. Given that duplicates make up to 80% of eukaryotic genomes, the small contribution is surprising and points to dominant roles of other buffering processes, such as alternative metabolic pathways. The buffering capacity of duplicates appears to be independent of the degree of gene essentiality and tends to be higher for genes with high expression levels. For example, buffering capacity increases to 23% amongst highly expressed genes in E. coli. Sequence similarity and the number of duplicates per gene are weak predictors of the duplicate's buffering capacity. In a case study we show that buffering gene duplicates in yeast and worm are somewhat more similar in their functions than non-buffering duplicates and have increased transcriptional and translational activity.

Conclusion

In sum, the extent of gene essentiality and buffering by duplicates is not conserved across organisms and does not correlate with the organisms' apparent complexity. This heterogeneity goes beyond what would be expected from differences in experimental approaches alone. Buffering by duplicates contributes to robustness in several organisms, but to a small extent – and the relatively large amount of buffering by duplicates observed in yeast and worm may be largely specific to these organisms. Thus, the only common factor of buffering by duplicates between different organisms may be the by-product of duplicate retention due to demands of high dosage.
Environmental rRNA inventories miss over half of protistan diversity
Authors: Jeon Sunok , Bunge John , Leslin Chesley , Stoeck Thorsten , Hong Sunhee , Epstein Slava S
Published: December 2008

Background

The main tool to discover novel microbial eukaryotes is the rRNA approach. This approach has important biases, including PCR discrimination against certain rRNA gene species, which makes molecular inventories skewed relative to the source communities. The degree of this bias has not been quantified, and it remains unclear whether species missed from clone libraries could be recovered by increasing sequencing efforts, or whether they cannot be detected in principle. Here we attempt to discriminate between these possibilities by statistically analysing four protistan inventories obtained using different general eukaryotic PCR primers.

Results

We show that each PCR primer set-specific clone library is not a sample from the community diversity but rather from a fraction of this diversity. Therefore, even sequencing such clone libraries to saturation would only recover that fraction, which, according to the parametric models, varies between 17 ± 4% to 49 ± 10%, depending on the set of primers. The pooled data is thus qualitatively richer than individual libraries, even if normalized to the same sequencing effort.

Conclusion

The use of a single pair of primers leads to significant underestimation of the true community richness at all levels of taxonomic hierarchy. The majority of available protistan rRNA gene surveys likely sampled less than half of the target diversity, and might have completely missed the rest. The use of multiple PCR primers reduces this bias but does not necessarily eliminate it.
Association between Ngb polymorphisms and ischemic stroke in the Southern Chinese Han population
Authors: Lin Yi , Fang Ling , Xue Xie-Hua , Murong Shen-Xing , Wang Ning , Wu Zhi-Ying
Published: December 2008

Background

Neuroglobin (Ngb), one of novel members of the globin superfamily, is expressed predominantly in brain neurons, and appears to modulate hypoxic-ischemic insults. The mechanisms underlying Ngb-mediated neuronal protection are still unclear. For it is one of the candidate protective factors for ischemic stroke, we conducted a case-control study to clarify the association of Ngb polymorphisms with ischemic stroke in the Southern Chinese Han population.

Methods

355 cases and 158 controls were recruited. With brain imaging, cases were subdivided into large-artery atherosclerosis (LVD) and small-vessel occlusion (SVD) stroke. PCR amplified all the four exons of Ngb and flanking intron sequence for each exon. Genotyping for Ngb was achieved by direct sequencing and mismatched PCR-RFLP. Polymorphisms were studied both individually and as haplotypes in each group and subgroup which subdivided according to gender or age.

Results

Two intronic polymorphisms 89+104 c>t and 322-110 (6a)>5a were identified. The allele frequency of 89+104 t was decreased in stroke cases. The protective effect seems to be more pronounced in subgroups of female patients and age > 60 years. Also, we have confirmed decreased LDL-C level and reduced hypertension and hypercholesterolemia in 89+104 t allele carriers. In contrast, the 322-110 (6a)>5a genotype distribution was similar between cases and controls. However, the haplotype 89+104 c>t/322-110 (6a)>5a was related with LVD and SVD stroke. The haplotype c-5a was more frequent in both LVD and SVD groups while t-6a was more frequent in controls.

Conclusion

Ngb polymorphism 89+104 t had protective effects on LVD and SVD in the Southern Chinese Han population. A "hitchhiking" effect was observed for the 89+104 t/322-110 (6a) genotype combination especially for LVD.
Conventional and molecular cytogenetics of human non-medullary thyroid carcinoma: characterization of eight cell line models and review of the literature on clinical samples
Authors: Ribeiro Franclim Ricardo , Meireles Ana Margarida , Rocha Ana Sofia , Teixeira Manuel Rodrigues
Published: December 2008

Background

Cell lines are often poorly characterized from a genetic point of view, reducing their usefulness as tumor models. Our purpose was to assess the genetic background of eight commonly used human thyroid carcinoma models and to compare the findings with those reported for primary tumors of the gland.

Methods

We used chromosome banding analysis and comparative genomic hybridization to profile eight non-medullary thyroid carcinoma cell lines of papillary (TPC-1, FB2, K1 and B-CPAP), follicular (XTC-1) or anaplastic origin (8505C, C643 and HTH74). To assess the representativeness of the findings, we additionally performed a thorough review of cytogenetic (n = 125) and DNA copy number information (n = 270) available in the literature on clinical samples of thyroid carcinoma.

Results

The detailed characterization of chromosomal markers specific for each cell line revealed two cases of mistaken identities: FB2 was shown to derive from TPC-1 cells, whereas K1 cells have their origin in cell line GLAG-66. All cellular models displayed genomic aberrations of varying complexity, and recurrent gains at 5p, 5q, 8q, and 20q (6/7 cell lines) and losses at 8p, 13q, 18q, and Xp (4/7 cell lines) were seen. Importantly, the genomic profiles were compatible with those of the respective primary tumors, as seen in the meta-analysis of the existing literature data.

Conclusion

We provide the genomic background of seven independent thyroid carcinoma models representative of the clinical tumors of the corresponding histotypes, and highlight regions of recurrent aberrations that may guide future studies aimed at identifying target genes. Our findings further support the importance of routinely performing cytogenetic studies on cell lines, to detect cross-contamination mishaps such as those identified here.
Gambling problems in the family – A stratified probability sample study of prevalence and reported consequences
Authors: Wenzel Hanne Gro , Øren Anita , Bakken Inger Johanne
Published: December 2008

Background

Prior studies on the impact of problem gambling in the family mainly include help-seeking populations with small numbers of participants. The objective of the present stratified probability sample study was to explore the epidemiology of problem gambling in the family in the general population.

Methods

Men and women 16–74 years-old randomly selected from the Norwegian national population database received an invitation to participate in this postal questionnaire study. The response rate was 36.1% (3,483/9,638). Given the lack of validated criteria, two survey questions ("Have you ever noticed that a close relative spent more and more money on gambling?" and "Have you ever experienced that a close relative lied to you about how much he/she gambles?") were extrapolated from the Lie/Bet Screen for pathological gambling. Respondents answering "yes" to both questions were defined as Concerned Significant Others (CSOs).

Results

Overall, 2.0% of the study population was defined as CSOs. Young age, female gender, and divorced marital status were factors positively associated with being a CSO. CSOs often reported to have experienced conflicts in the family related to gambling, worsening of the family's financial situation, and impaired mental and physical health.

Conclusion

Problematic gambling behaviour not only affects the gambling individual but also has a strong impact on the quality of life of family members.
A Plasmodium yoelii soluble factor inhibits the phenotypic maturation of dendritic cells
Authors: Orengo Jamie M , Wong Kurt A , Ocaña-Morgner Carlos , Rodriguez Ana
Published: December 2008

Background

Infection with the protozoan parasitePlasmodiumis the cause of malaria.Plasmodiuminfects host erythrocytes causing the pathology of the disease.Plasmodium-infected erythrocytes can modulate the maturation of dendritic cells (DCs) and alter their capacity to activate T cells.

Methods

Mice infected withPlasmodium yoeliiand isolatedP. yoelii-infected erythrocytes were used to study their effect on the maturation of mouse dendritic cells.

Results

DCs are not able to mature in response to LPS injection during the late stage ofP. yoeliiinfection in mice, indicating impaired functionality of these cellsin vivo.P. yoelii-infected erythrocytes inhibit the maturation of DCsin vitroin a dose-dependent manner, which is consistent with the inhibition found during late infection when parasite burden is highest. The inhibition of DC maturation and the cytokine secretion profile of DCs are modulated by soluble factors released byP. yoelii-infected erythrocytes. A small, heat-stable, non-hydrophobic molecule ofP. yoelii-infected erythrocytes rapidly inhibits the LPS induced phenotypic maturation of DCs in a reversible manner.

Conclusion

These findings add evidence to the malaria associated immune suppressionin vivoandin vitroand provide insight into the nature and mechanism of thePlasmodiumfactor(s) responsible for altering DC functions.
Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability
Authors: Lam Prudence B , Burga Laura N , Wu Bryan P , Hofstatter Erin W , Lu Kun Ping , Wulf Gerburg M
Published: December 2008

Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself.

Methods

Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence.

Results

Sixty-four samples (28.7%) stained positive for Her2 (IHC 3+), and 54% (122/223) of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5%) were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2 degradation, which could be prevented by treatments with the proteasome inhibitor ALLnL.

Conclusion

Pin1 is a novel regulator of erbB2 that modulates the ubiquitin-mediated degradation of erbB2. The overexpression of Pin1 in a majority of Her2-overexpressing breast cancer may contribute to maintain erbB2 levels. Pin1 inhibition alone and in conjunction with mTOR inhibition suppresses the growth of Her2+ breast cancer cells.
A paraneoplastic manifestation of metastatic breast cancer responding to endocrine therapy: a case report
Authors: Wood Joanna P , Haynes Andrew P , Cheung KL
Published: December 2008

Background

Many cancers are known to be associated with paraneoplastic syndromes. These syndromes are usually treated by chemotherapy with or without immunosupression but they often respond poorly. There are no published reviews on response to endocrine treatment.

Case presentation

We report a case of a patient presenting with papillitis, myositis and sensory peripheral neuropathy 18 months before a diagnosis of metastatic oestrogen receptor positive breast cancer was confirmed. The patient was treated with anastrozole which led not only to a decrease of her tumour burden but also to an improvement in her biochemical markers and amelioration of her clinical symptoms.

Conclusion

This case is an example of breast cancer presenting with paraneoplastic manifestations. It took several months to establish the cause of symptoms in this patient thus illustrating the need for physicians to maintain a high index of suspicion for paraneoplastic syndromes in women presenting with unusual neurological symptoms with no obvious cause.

It is a unique case as it illustrates how treatment with an aromatase inhibitor leading to cancer regression can result in an improvement in the paraneoplastic symptoms.
Changes in the reproductive function and developmental phenotypes in mice following intramuscular injection of an activin betaA-expressing plasmid
Authors: Kim Mi-Nyeu , Park Moon Nyeo , Jung Hoi Kyung , Cho Chunghee , Mayo Kelly E , Cho Byung-Nam
Published: December 2008

Background

The TGF-beta family protein activin has numerous reported activities with some uncertainty in the reproductive axis and development. The precise roles of activin in in vivo system were investigated using a transient gain of function model.

Methods

To this end, an expression plasmid, pCMV-rAct, with the activin betaA cDNA fused to the cytomegalovirus promoter, was introduced into muscle of the female adult mice by direct injection.

Results

Activin betaA mRNA was detected in the muscle by RT-PCR and subsequent Southern blot analysis. Activin betaA was also detected, and western blot analysis revealed a relatively high level of serum activin with correspondingly increased FSH. In the pCMV-rAct-injected female mice, estrus stage within the estrous cycle was extended. Moreover, increased numbers of corpora lutea and a thickened granulosa cell layer with a small antrum in tertiary follicles within the ovary were observed. When injected female mice were mated with males of proven fertility, a subset of embryos died in utero, and most of those that survived exhibited increased body weight.

Conclusion

Taken together, our data reveal that activin betaA can directly influence the estrous cycle, an integral part of the reproduction in female mice and activin betaA can also influence the embryo development as an endocrine fashion.
Evolution of a polymodal sensory response network
Authors: Srinivasan Jagan , Durak Omer , Sternberg Paul W
Published: December 2008

Background

Avoidance of noxious stimuli is essential for the survival of an animal in its natural habitat. Some avoidance responses require polymodal sensory neurons, which sense a range of diverse stimuli, whereas other stimuli require a unimodal sensory neuron, which senses a single stimulus. Polymodality might have evolved to help animals quickly detect and respond to diverse noxious stimuli. Nematodes inhabit diverse habitats and most nematode nervous systems are composed of a small number of neurons, despite a wide assortment in nematode sizes. Given this observation, we speculated that cellular contribution to stereotyped avoidance behaviors would also be conserved between nematode species. The ASH neuron mediates avoidance of three classes of noxious stimuli in Caenorhabditis elegans. Two species of parasitic nematodes also utilize the ASH neuron to avoid certain stimuli. We wanted to extend our knowledge of avoidance behaviors by comparing multiple stimuli in a set of free-living nematode species.

Results

We used comparative behavioral analysis and laser microsurgery to examine three avoidance behaviors in six diverse species of free-living nematodes. We found that all species tested exhibit avoidance of chemo-, mechano- and osmosensory stimuli. In C. elegans, the bilaterally symmetric polymodal ASH neurons detect all three classes of repellant. We identified the putative ASH neurons in different nematode species by their anatomical positions and showed that in all six species ablation of the ASH neurons resulted in an inability to avoid noxious stimuli. However, in the nematode Pristionchus pacificus, the ADL neuron in addition to the ASH neuron contributed to osmosensation. In the species Caenorhabditis sp. 3, only the ASH neuron was required to mediate nose touch avoidance instead of three neurons in C. elegans. These data suggest that different species can increase or decrease the contribution of additional, non-ASH sensory neurons mediating osmosensation and mechanosensation.

Conclusion

The overall conservation of ASH mediated polymodal nociception suggests that it is an ancestral evolutionarily stable feature of sensation. However, the finding that contribution from non-ASH sensory neurons mediates polymodal nociception in some nematode species suggests that even in conserved sensory behaviors, the cellular response network is dynamic over evolutionary time, perhaps shaped by adaptation of each species to its environment.
Hardwiring of fine synaptic layers in the zebrafish visual pathway
Authors: Nevin Linda M , Taylor Michael R , Baier Herwig
Published: December 2008

Background

Neuronal connections are often arranged in layers, which are divided into sublaminae harboring synapses with similar response properties. It is still debated how fine-grained synaptic layering is established during development. Here we investigated two stratified areas of the zebrafish visual pathway, the inner plexiform layer (IPL) of the retina and the neuropil of the optic tectum, and determined if activity is required for their organization.

Results

The IPL of 5-day-old zebrafish larvae is composed of at least nine sublaminae, comprising the connections between different types of amacrine, bipolar, and ganglion cells (ACs, BCs, GCs). These sublaminae were distinguished by their expression of cell type-specific transgenic fluorescent reporters and immunohistochemical markers, including protein kinase Cβ (PKC), parvalbumin (Parv), zrf3, and choline acetyltransferase (ChAT). In the tectum, four retinal input layers abut a laminated array of neurites of tectal cells, which differentially express PKC and Parv. We investigated whether these patterns were affected by experimental disruptions of retinal activity in developing fish. Neither elimination of light inputs by dark rearing, nor a D, L-amino-phosphono-butyrate-induced reduction in the retinal response to light onset (but not offset) altered IPL or tectal lamination. Moreover, thorough elimination of chemical synaptic transmission with Botulinum toxin B left laminar synaptic arrays intact.

Conclusion

Our results call into question a role for activity-dependent mechanisms – instructive light signals, balanced on and off BC activity, Hebbian plasticity, or a permissive role for synaptic transmission – in the synaptic stratification we examined. We propose that genetically encoded cues are sufficient to target groups of neurites to synaptic layers in this vertebrate visual system.
Comparison of temporal changes in psychological distress after hematopoietic stem cell transplantation among the underlying diseases of Japanese adult patients
Authors: Fukuo Wataru , Yoshiuchi Kazuhiro , Takimoto Yoshiyuki , Sakamoto Noriyuki , Kikuchi Hiroe , Hachizuka Maki , Inada Shuji , Nannya Yasuhito , Kumano Keiki , Takahashi Tsuyoshi , Kurokawa Mineo , Akabayashi Akira
Published: December 2008

Background

Although hematopoietic stem cell transplantation (HSCT) can potentially cure some hematological malignancies, patients who undergo HSCT experience psychological distress. However, there have been few studies on the short-term influence of HSCT on psychological distress.

Methods

The subjects were 71 patients with hematological malignancies who underwent HSCT: 33 with acute leukemia, 19 with chronic leukemia, nine with myelodysplastic syndrome, and 10 with malignant lymphoma. Psychological distress was assessed prior to HSCT and on the seventh day after HSCT using the Profile of Mood States (POMS).

Results

With regard to Anger-Hostility, the interaction of time (pre- and post-HSCT) and group (the four groups) was significant in male patients (p = 0.04), but not in female patients. With regard to the other subscales of POMS, there was no significant main effect or interaction in male or female patients.

Conclusion

It may be important to provide psychological support to patients throughout the period of HSCT in consideration of differences in mood changes associated with the underlying disease and patient sex in order to provide efficient psychiatric intervention for both better psychiatric and survival outcomes.
Cytomegalovirus-associated splenic infarcts in a female patient with Factor V Leiden mutation: a case report
Authors: Atzmony Lihi , Saar Nili , Chundadze Tamar , Arbel Yaron , Justo Dan , Mashav Noa
Published: December 2008

Introduction

Cytomegalovirus-associated thrombosis has rarely been reported in the medical literature, and if so, mainly in immunocompromized patients.

Case presentation

We report the case of a 36-year-old Caucasian woman with acute cytomegalovirus infection presenting with spontaneous splenic infarcts. Trans-esophageal echocardiography did not show any vegetations or mural thrombi. The patient was also found to be heterozygous for the Factor V Leiden mutation. Anticoagulation treatment was considered but ruled out since cytomegalovirus was the obvious trigger for thrombosis in this patient. To the best of our knowledge, this is only the third report to date of cytomegalovirus-associated splenic infarcts.

Conclusion

This case report serves as additional evidence for the role of cytomegalovirus in thrombosis.
Atypical manifestation of late onset limb girdle muscular dystrophy presenting with recurrent falling and shoulder dysfunction: a case report
Authors: Schofer Markus Dietmar , Patzer Thilo , Quante Markus
Published: December 2008

Introduction

Myopathies can be sub-classified into congenital, hereditary, mitochondrial, and secondary myopathies.

Congenital myopathies are usually diagnosed post partal or in early childhood. Manifestation in adolescence is uncommon and most cases occur as sporadic mutations. Therefore, there is a risk of under diagnosing this disease in middle-aged patients showing pain, dysfunction, recurrent trauma or falls, where muscle atrophy is seen as a secondary injury.

Case presentation

Our report is about a 54 year old Caucasian woman with an extended history of pain, loss of function and weakness in her right shoulder. The clinical picture showed a frozen right shoulder. The main finding was a marked limb-muscle atrophy of both delta- und biceps-muscles and a rotator cuff tear that had developed over years. Previous medical consultations attributed the atrophy to recurrent falls, shoulder dysfunction and pain. Conservative treatment (analgesics, physiotherapy, training) had failed.

The familiar anamnesis was free of any neurological diseases or other genetic diseases.

MRI showed a sub-total proximal muscular limb atrophy and a rotator cuff tear in both shoulders. An incision-biopsy of the right delta- and biceps-muscle revealed a chronical myopathy. The level of creatinkinasis was expected to be high but measurements showed values only slightly above normal. Immunohistochemistry, eventually revealed a mild form of LGMD (type 2I). Due to the pattern of symptoms and diagnostic results we described the case as atypical LGMD.

Conclusion

Our case presents a phenotype of a late onset of limb girdle muscular dystrophy syndrome associated with shoulder pain and dysfunction and recurrent falls. This kind of disease is not very common. In particular, muscle atrophy in the elderly is generally seen as a secondary injury. This case should remind us of the importance of a differential diagnosis of a late onset of muscular dystrophy-syndrome in the elderly, since an early diagnosis offers more treatment options, therefore preventing a rapid progression.
Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparumpopulation divergence
Authors: Neafsey Daniel E , Schaffner Stephen F , Volkman Sarah K , Park Daniel , Montgomery Philip , Milner Danny A , Lukens Amanda , Rosen David , Daniels Rachel , Houde Nathan , Cortese Joseph F , Tyndall Erin , Gates Casey , Stange-Thomann Nicole , Sarr Ousmane , Ndiaye Daouda , Ndir Omar , Mboup Soulyemane , Ferreira Marcelo U , Moraes Sandra do Lago , Dash Aditya P , Chitnis Chetan E , Wiegand Roger C , Hartl Daniel L , Birren Bruce W , Lander Eric S , Sabeti Pardis C , Wirth Dyann F
Published: December 2008

Background

The malaria parasite Plasmodium falciparum exhibits abundant genetic diversity, and this diversity is key to its success as a pathogen. Previous efforts to study genetic diversity in P. falciparum have begun to elucidate the demographic history of the species, as well as patterns of population structure and patterns of linkage disequilibrium within its genome. Such studies will be greatly enhanced by new genomic tools and recent large-scale efforts to map genomic variation. To that end, we have developed a high throughput single nucleotide polymorphism (SNP) genotyping platform for P. falciparum.

Results

Using an Affymetrix 3,000 SNP assay array, we found roughly half the assays (1,638) yielded high quality, 100% accurate genotyping calls for both major and minor SNP alleles. Genotype data from 76 global isolates confirm significant genetic differentiation among continental populations and varying levels of SNP diversity and linkage disequilibrium according to geographic location and local epidemiological factors. We further discovered that nonsynonymous and silent (synonymous or noncoding) SNPs differ with respect to within-population diversity, inter-population differentiation, and the degree to which allele frequencies are correlated between populations.

Conclusions

The distinct population profile of nonsynonymous variants indicates that natural selection has a significant influence on genomic diversity in P. falciparum, and that many of these changes may reflect functional variants deserving of follow-up study. Our analysis demonstrates the potential for new high-throughput genotyping technologies to enhance studies of population structure, natural selection, and ultimately enable genome-wide association studies in P. falciparum to find genes underlying key phenotypic traits.
Analysis of mammalian gene batteries reveals both stable ancestral cores and highly dynamic regulatory sequences
Authors: Ettwiller Laurence , Budd Aidan , Spitz François , Wittbrodt Joachim
Published: December 2008

Background

Changes in gene regulation are suspected to comprise one of the driving forces for evolution. To address the extent of cis-regulatory changes and how they impact on gene regulatory networks across eukaryotes, we systematically analyzed the evolutionary dynamics of target gene batteries controlled by 16 different transcription factors.

Results

We found that gene batteries show variable conservation within vertebrates, with slow and fast evolving modules. Hence, while a key gene battery associated with the cell cycle is conserved throughout metazoans, the POU5F1 (Oct4) and SOX2 batteries in embryonic stem cells show strong conservation within mammals, with the striking exception of rodents. Within the genes composing a given gene battery, we could identify a conserved core that likely reflects the ancestral function of the corresponding transcription factor. Interestingly, we show that the association between a transcription factor and its target genes is conserved even when we exclude conserved sequence similarities of their promoter regions from our analysis. This supports the idea that turnover, either of the transcription factor binding site or its direct neighboring sequence, is a pervasive feature of proximal regulatory sequences.

Conclusions

Our study reveals the dynamics of evolutionary changes within metazoan gene networks, including both the composition of gene batteries and the architecture of target gene promoters. This variation provides the playground required for evolutionary innovation around conserved ancestral core functions.
Anisotropy of experimentally compressed kaolinite-illite-quartz mixtures
Authors: Voltolini Marco , Wenk Hans-Rudolf , Mondol Nazmul Haque , Bjørlykke Knut , Jahren Jens
Published: December 2008

The anisotropy of physical properties is a well-known characteristic of many clay-bearing rocks. This anisotropy has important implications for elastic properties of rocks and must be considered in seismic modeling. Preferred orientation of clay minerals is an important factor causing anisotropy in clay-bearing rocks such as shales and mudstones that are the main cap rocks of oil reservoirs. The preferred orientation of clays depends mostly on the amount of clays and the degree of compaction. To study the effect of these parameters, we prepared several samples compressing (at two effective vertical stresses) a mixture of clays (illite and kaolinite) and quartz (silt) with different clay/quartz ratios. The preferred orientation of the phases was quantified with Rietveld analysis on synchrotron hard X-ray images. Pole figures for kaolinite and illite display a preferred orientationof clay platelets perpendicular to the compaction direction, increasing in strength with clay content and compaction pressure. Quartz particles have a random orientation distribution. Aggregate elastic properties can be estimated by averaging the single-crystal properties over the orientation distribution obtained from the diffraction data analysis. Calculated P-wave velocity anisotropy ranges from 0% (pure quartz sample) to 44% (pure clay sample, highly compacted), but calculated velocities are much higher than measured velocities. This is attributed to uncertainties about single-crystal elastic properties and oriented micropores and limited grain contacts that are not accounted for in the model. In this work, we present an effective method to obtain quantitative data, helping to evaluate the role of clay percentage and compaction pressure on the anisotropy of elastic properties of clay-bearing rocks.