Analysis of Antisense Expression by Whole Genome Tiling Microarrays and siRNAs Suggests Mis-Annotation of Arabidopsis Orphan Protein-Coding Genes

MicroRNAs (miRNAs) and trans-acting small-interfering RNAs (tasi-RNAs) are small (20-22 nt long) RNAs (smRNAs) generated from hairpin secondary structures or antisense transcripts, respectively, that regulate gene expression by Watson-Crick pairing to a target mRNA and altering expression by mechanisms related to RNA interference. The high sequence homology of plant miRNAs to their targets has been the mainstay of miRNA prediction algorithms, which are limited in their predictive power for other kingdoms because miRNA complementarity is less conserved yet transitive processes (production of antisense smRNAs) are active in eukaryotes. We hypothesize that antisense transcription and associated smRNAs are biomarkers which can be computationally modeled for gene discovery.We explored rice (Oryza sativa) sense and antisense gene expression in publicly available whole genome tiling array transcriptome data and sequenced smRNA libraries (as well as C. elegans) and found evidence of transitivity of MIRNA genes similar to that found in Arabidopsis. Statistical analysis of antisense transcript abundances, presence of antisense ESTs, and association with smRNAs suggests several hundred Arabidopsis 'orphan' hypothetical genes are non-coding RNAs. Consistent with this hypothesis, we found novel Arabidopsis homologues of some MIRNA genes on the antisense strand of previously annotated protein-coding genes. A Support Vector Machine (SVM) was applied using thermodynamic energy of binding plus novel expression features of sense/antisense transcription topology and siRNA abundances to build a prediction model of miRNA targets. The SVM when trained on targets could predict the "ancient" (deeply conserved) class of validated Arabidopsis MIRNA genes with an accuracy of 84%, and 76% for "new" rapidly-evolving MIRNA genes.Antisense and smRNA expression features and computational methods may identify novel MIRNA genes and other non-coding RNAs in plants and potentially other kingdoms, which can provide insight into antisense transcription, miRNA evolution, and post-transcriptional gene regulation

Anaerobic microbial communities and their potential for bioenergy production in heavily biodegraded petroleum reservoirs

Most of the oil in low temperature, non‐uplifted reservoirs is biodegraded due to millions of years of microbial activity, including via methanogenesis from crude oil. To evaluate stimulating additional methanogenesis in already heavily biodegraded oil reservoirs, oil sands samples were amended with nutrients and electron acceptors, but oil sands bitumen was the only organic substrate. Methane production was monitored for over 3000 days. Methanogenesis was observed in duplicate microcosms that were unamended, amended with sulfate or that were initially oxic, however methanogenesis was not observed in nitrate‐amended controls. The highest rate of methane production was 0.15 μmol CH4 g−1 oil d−1, orders of magnitude lower than other reports of methanogenesis from lighter crude oils. Methanogenic Archaea and several potential syntrophic bacterial partners were detected following the incubations. GC–MS and FTICR–MS revealed no significant bitumen alteration for any specific compound or compound class, suggesting that the very slow methanogenesis observed was coupled to bitumen biodegradation in an unspecific manner. After 3000 days, methanogenic communities were amended with benzoate resulting in methanogenesis rates that were 110‐fold greater. This suggests that oil‐to‐methane conversion is limited by the recalcitrant nature of oil sands bitumen, not the microbial communities resident in heavy oil reservoirs

Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia

The definitive version is available at www3.interscience.wiley.comExercise in hypoxia is associated with reduced muscle oxidative function and impaired exercise tolerance. We hypothesised that dietary nitrate supplementation (which increases plasma [nitrite] and thus NO bioavailability) would ameliorate the adverse effects of hypoxia on muscle metabolism and oxidative function. In a double-blind, randomised crossover study, nine healthy subjects completed knee-extension exercise to the limit of tolerance (T(lim)), once in normoxia (20.9% O(2); CON) and twice in hypoxia (14.5% O(2)). During 24 h prior to the hypoxia trials, subjects consumed 0.75 L of nitrate-rich beetroot juice (9.3 mmol nitrate; H-BR) or 0.75 L of nitrate-depleted beetroot juice as a placebo (0.006 mmol nitrate; H-PL). Muscle metabolism was assessed using calibrated (31)P-MRS. Plasma [nitrite] was elevated (P < 0.01) following BR (194 ± 51 nm) compared to PL (129 ± 23 nm) and CON (142 ± 37 nM). T(lim) was reduced in H-PL compared to CON (393 ± 169 vs. 471 ± 200 s; P < 0.05) but was not different between CON and H-BR (477 ± 200 s). The muscle [PCr], [P(i)] and pH changed at a faster rate in H-PL compared to CON and H-BR. The [PCr] recovery time constant was greater (P < 0.01) in H-PL (29 ± 5 s) compared to CON (23 ± 5 s) and H-BR (24 ± 5 s). Nitrate supplementation reduced muscle metabolic perturbation during exercise in hypoxia and restored exercise tolerance and oxidative function to values observed in normoxia. The results suggest that augmenting the nitrate-nitrite-NO pathway may have important therapeutic applications for improving muscle energetics and functional capacity in hypoxia

A Canvas for Establishing Global Software Development Collaborations

Jufo-id:80620There is an increasing need and interest for organizations to collaborate with internal and external partners on a global scale for creating software-based products and services. Potential risks and different strategies need to be addressed when setting up such collaborations. Aspects such as cultural and social features, coordination, infrastructure, organizational change processes, or communication issues need to be con- sidered. Although there are already experiences available with respect to setting up global collaborations, they mainly focus on specific areas. It is dicult for companies to quickly assess if they have considered all rele- vant aspects. An overall aid that guides companies in systematically setting up global collaborations is widely missing. In this paper we present a study based on the snowballing method as a systematic approach to literature review. Based on this literature review and inputs from indus- try we investigated what aspects and practices need to be considered when establishing global software development collaborations and how to prioritize them. Based on that we created activity roadmaps that aggregate existing experiences. Reported experiences were structured into nine main aspects each containing extracted successful practices for set- ting up global software development collaborations. As a result we came up with an initial version of a canvas that is proposed as guidance for companies for setting up global collaborations in the software development domain.Peer reviewe

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Identifying ancient water availability through phytolith analysis: An experimental approach.

Water management was critical to the development of complex societies but such systems are often difficult, if not impossible, to recognise in the archaeological record, particularly in prehistoric communities when water management began. This is because early irrigation systems are likely to have been ephemeral and as such would no longer be visible in the archaeological record. We conducted a three year crop growing experiment in Jordan to test the hypothesis that phytoliths (opaline silica bodies formed in plants) can be used to detect the level of past water availability and hence be used as a source of information for inferring past water management. Over a three year period we grew native land races of six-row barley (Hordeum vulgare) and durum wheat (Triticum durum) at three crop growing stations in Jordan with the crops being subjected to different irrigation regimes. Seeds were sown in the autumn and the crops harvested in the spring. The plants were then exported to the University of Reading for phytolith processing. Our results show that while there were unknown factors that influenced phytolith production between years, at the higher levels, the ratio of ‘fixed’ form phytoliths (those formed as a result of genetically determined Silicon uptake) to ‘sensitive’ form phytoliths (those whose Silicon uptake is environmentally controlled) can be used to assess past water availability. Our study is the first large scale experimental project to test this method and take into account multiple variables that can affect phytolith production such as soil composition and chemistry, location, climate and evapotranspiration rates. Results from the cereals grown at two of the crop growing stations, Deir ‘Alla and Ramtha, which received between 100 millimetres and 250 millimetres rainfall per annum, demonstrate that if the ratio of fixed to sensitive phytolith forms is >1, the level of past water availability can be predicted with 80% confidence. Results from the crops grown at the other growing station, Kherbet as-Samra, which received less than 100 millimetres of rainfall per year show that if the ratio of fixed to sensitive forms is >0.5, the level of past water availability can be predicted with 99% confidence. This demonstrates that phytolith analysis can be used as a method to identify past water availability

Phytobiomes are compositionally nested from the ground up

Plant-associated microbes are critical players in host health, fitness and productivity. Despite microbes’ importance in plants, seeds are mostly sterile, and most plant microbes are recruited from an environmental pool. Surprisingly little is known about the processes that govern how environmental microbes assemble on plants in nature. In this study we examine how bacteria are distributed across plant parts, and how these distributions interact with spatial gradients. We sequenced amplicons of bacteria from the surfaces of six plant parts and adjacent soil of Scaevola taccada, a common beach shrub, along a 60 km transect spanning O’ahu island’s windward coast, as well as within a single intensively-sampled site. Bacteria are more strongly partitioned by plant part as compared with location. Within S. taccada plants, microbial communities are highly nested: soil and rhizosphere communities contain much of the diversity found elsewhere, whereas reproductive parts fall at the bottom of the nestedness hierarchy. Nestedness patterns suggest either that microbes follow a source/sink gradient from the ground up, or else that assembly processes correlate with other traits, such as tissue persistence, that are vertically stratified. Our work shines light on the origins and determinants of plant-associated microbes across plant and landscape scales

A comparative study of qualitative and quantitative dynamic models of biological regulatory networks

Backgroun

Long-Stay Psychiatric Patients: A Prospective Study Revealing Persistent Antipsychotic-Induced Movement Disorder

OBJECTIVE: The purpose of this study was to assess the frequency of persistent drug-induced movement disorders namely, tardive dyskinesia (TD), parkinsonism, akathisia and tardive dystonia in a representative sample of long-stay patients with chronic severe mental illness. METHOD: Naturalistic study of 209, mainly white, antipsychotic-treated patients, mostly diagnosed with psychotic disorder. Of this group, the same rater examined 194 patients at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. RESULTS: The frequencies of persistent movement disorders in the sample were 28.4% for TD, 56.2% for parkinsonism, 4.6% for akathisia and 5.7% for tardive dystonia. Two-thirds of the participants displayed at least one type of persistent movement disorder. CONCLUSIONS: Persistent movement disorder continues to be the norm for long-stay patients with chronic mental illness and long-term antipsychotic treatment. Measures are required to remedy this situation