A Dutch guideline for the treatment of scoliosis in neuromuscular disorders

Background

Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care.

Methods

The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence.

Results

For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands.

Conclusion

In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders.     

Singular value decomposition-based regression identifies activation of endogenous signaling pathways in vivo

Background

The physical organization and chromosomal localization of genes within genomes is known to play an important role in their function. Most genes arise by duplication and move along the genome by random shuffling of DNA segments. Higher order structuring of the genome occurs in eukaryotes, where groups of physically linked genes are co-expressed. However, the contribution of gene duplication to gene order has not been analyzed in detail, as it is believed that co-expression due to recent duplicates would obscure other domains of co-expression.

Results

We have catalogued ordered duplicated genes in Drosophila melanogaster, and found that one in five of all genes is organized as tandem arrays. Furthermore, among arrays that have been spatially conserved over longer periods than would be expected on the basis of random shuffling, a disproportionate number contain genes encoding developmental regulators. Using in situ gene expression data for more than half of the Drosophila genome, we find that genes in these conserved clusters are co-expressed to a much higher extent than other duplicated genes.

Conclusions

These results reveal the existence of functional constraints in insects that retain copies of genes encoding developmental and regulatory proteins as neighbors, allowing their co-expression. This co-expression may be the result of shared cis-regulatory elements or a shared need for a specific chromatin structure. Our results highlight the association between genome architecture and the gene regulatory networks involved in the construction of the body plan.     

Abundance,Species Composition and Spatial Distribution of Planktonic Rotifers and Crustaceans in Lake Ziway (Rift Valley,Ethiopia)

Species composition, abundance, and spatial distribution of rotifer and crustacean zooplankton were studied in Lake Ziway from late April to early July 2004. A total of 49 rotifer species was recorded, with Anuraeopsis fissa, Brachionus angularis, Filinia novaezealandiae, and Trichocerca ruttneri being numerically dominant. Variation in abundance was extremely high, ranging from 2 to 1000+ individuals per litre. There was no significant difference in the distribution of rotifer species between inshore and offshore regions. Crustacean species richness was low, with only five cladoceran and three copepod species occurring in the open water. Moina micrura and Diaphanosoma excisum dominated the cladoceran community, whereas Thermocyclops decipiens was the dominant copepod. Although numerically dominant (75%), rotifers accounted for less than 30% of mean total zooplankton biomass. Peak abundance of crustaceans was observed in May and June, following the onset of the rainy season and increased phytoplankton production. Variation in the spatial distribution of crustacean species was neither observed horizontally between inshore and offshore areas nor vertically in the highly turbid and wind exposed deeper part of the lake. On the other hand, Moina micrura varied significantly in size between inshore and offshore areas. Adult M. micrura dominated offshore, whereas juveniles were more abundant inshore, suggesting a predominantly littoral selective predation on large and adult crustaceans by fish. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors

Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.     

Modeling genetic inheritance of copy number variations

Copy number variations (CNVs) are being used as genetic markers or functional candidates in gene-mapping studies. However, unlike single nucleotide polymorphism or microsatellite genotyping techniques, most CNV detection methods are limited to detecting total copy numbers, rather than copy number in each of the two homologous chromosomes. To address this issue, we developed a statistical framework for intensity-based CNV detection platforms using family data. Our algorithm identifies CNVs for a family simultaneously, thus avoiding the generation of calls with Mendelian inconsistency while maintaining the ability to detect de novo CNVs. Applications to simulated data and real data indicate that our method significantly improves both call rates and accuracy of boundary inference, compared to existing approaches. We further illustrate the use of Mendelian inheritance to infer SNP allele compositions in each of the two homologous chromosomes in CNV regions using real data. Finally, we applied our method to a set of families genotyped using both the Illumina HumanHap550 and Affymetrix genome-wide 5.0 arrays to demonstrate its performance on both inherited and de novo CNVs. In conclusion, our method produces accurate CNV calls, gives probabilistic estimates of CNV transmission and builds a solid foundation for the development of linkage and association tests utilizing CNVs.     

Prospects for sustainable use and development of wild food plants in Ethiopia

Field and herbarium studies on wild flowering plants of Ethiopia furnished 203 species consumed by the community. These account for about 3% of the higher plant species in the country and comprise herbs (37%), shrubs (32%), and trees (31%). Species with edible fruits contributed to 61.6%, leaves 27.7%, stems 14.4%, roots 13.3%, and seeds 10.3%. About 15% are considered famine foods. Forest habitats gave 102 species, woodlands 99, grasslands 83, bushlands 52, rocky and dry areas 47, cultivated places 41, riverbanks 31, and roadsides/ disturbed areas 25. The altitudinal distribution gave 148 species between 1500-2400 m, 144 below 1500 m and 81 above 2400 m a.s.l. Some species are wild and others slightly or strongly associated with humans, revealing a living analogue of the wild-semiwild-domesticated continuum. Full-scale ethnobotanical studies, implementing appropriate conservation measures and domesticating and integrating promising taxa into existing crops are favored for the purpose of diversification of food sources, ensuring food security, and maintenance of biodiversity and environmental integrity.     

N-acetylglucosamine and glucosamine-containing arabinogalactan proteins control somatic embryogenesis

In plants, complete embryos can develop not only from the zygote, but also from somatic cells in tissue culture. How somatic cells undergo the change in fate to become embryogenic is largely unknown. Proteins, secreted into the culture medium such as endochitinases and arabinogalactan proteins (AGPs) are required for somatic embryogenesis. Here we show that carrot (Daucus carota) AGPs can contain glucosamine and N-acetyl-D-glucosaminyl and are sensitive to endochitinase cleavage. To determine the relevance of this observation for embryogenesis, an assay was developed based on the enzymatic removal of the cell wall from cultured cells. The resulting protoplasts had a reduced capacity for somatic embryogenesis, which could be partially restored by adding endochitinases to the protoplasts. AGPs from culture medium or from immature seeds could fully restore or even increase embryogenesis. AGPs pretreated with chitinases were more active than untreated molecules and required an intact carbohydrate constituent for activity. AGPs were only capable of promoting embryogenesis from protoplasts in a short period preceding cell wall reformation. Apart from the increase in embryogenesis, AGPs can reinitiate cell division in a subpopulation of otherwise non-dividing protoplasts. These results show that chitinase-modified AGPs are extracellular matrix molecules able to control or maintain plant cell fate.     

Identification of differentially expressed genes in high-density oligonucleotide arrays accounting for the quantification limits of the technology

In DNA microarray analysis, there is often interest in isolating a few genes that best discriminate between tissue types. This is especially important in cancer, where different clinicopathologic groups are known to vary in their outcomes and response to therapy. The identification of a small subset of gene expression patterns distinctive for tumor subtypes can help design treatment strategies and improve diagnosis. Toward this goal, we propose a methodology for the analysis of high-density oligonucleotide arrays. The gene expression measures are modeled as censored data to account for the quantification limits of the technology, and two gene selection criteria based on contrasts from an analysis of covariance (ANCOVA) model are presented. The model is formulated in a hierarchical Bayesian framework, which in addition to making the fit of the model straightforward and computationally efficient, allows us to borrow strength across genes. The elicitation of hierarchical priors, as well as issues related to parameter identifiability and posterior propriety, are discussed in detail. We examine the performance of our proposed method on simulated data, then present a detailed case study of an endometrial cancer dataset.     

The role of sulphidogenesis in anaerobic treatment phase of tannery wastewater treatment in advanced integrated wastewater pond system

An outdoor experiment was conducted to study the competitionbetween Sulphate Reducing Bacteria (SRB) and Methanogenic Archaea (MA) in anaerobictreatment phase of tannery wastewater treatment in pilot-scale Advanced FacultativePond (AFP). The relative electron flow towards sulphate reduction was higher (59–83%) than towardsmethanogenesis (17–41%), although the COD recovery within thereactor varied between 15 and 90%. The results also demonstrated that the flow of electrons towards SRBincreased with increase of the sulphate concentration and decrease of the COD : SO₄ ⁼ ratio.     

Helicobacter pylori-selective antibacterials based on inhibition of pyrimidine biosynthesis

We report the discovery of a class of pyrazole-based compounds that are potent inhibitors of the dihydroorotate dehydrogenase of Helicobacter pylori but that do not inhibit the cognate enzymes from Gram-positive bacteria or humans. In culture these compounds inhibit the growth of H. pylori selectively, showing no effect on other Gram-negative or Gram-positive bacteria or human cell lines. These compounds represent the first examples of H. pylori-specific antibacterial agents. Cellular activity within this structural class appears to be due to dihydroorotate dehydrogenase inhibition. Minor structural changes that abrogate in vitro inhibition of the enzyme likewise eliminate cellular activity. Furthermore, the minimum inhibitory concentrations of these compounds increase upon addition of orotate to the culture medium in a concentration-dependent manner, consistent with dihydroorotate dehydrogenase inhibition as the mechanism of cellular inhibition. The data presented here suggest that targeted inhibition of de novo pyrimidine biosynthesis may be a valuable mechanism for the development of antimicrobial agents selective for H. pylori.