Universal Plant DNA Barcode Loci May Not Work in Complex Groups: A Case Study with Indian Berberis Species

BACKGROUND: The concept of DNA barcoding for species identification has gained considerable momentum in animals because of fairly successful species identification using cytochrome oxidase I (COI). In plants, matK and rbcL have been proposed as standard barcodes. However, barcoding in complex genera is a challenging task. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the species discriminatory power of four reportedly most promising plant DNA barcoding loci (one from nuclear genome--ITS, and three from plastid genome--trnH-psbA, rbcL and matK) in species of Indian Berberis L. (Berberidaceae) and two other genera, Ficus L. (Moraceae) and Gossypium L. (Malvaceae). Berberis species were delineated using morphological characters. These characters resulted in a well resolved species tree. Applying both nucleotide distance and nucleotide character-based approaches, we found that none of the loci, either singly or in combinations, could discriminate the species of Berberis. ITS resolved all the tested species of Ficus and Gossypium and trnH-psbA resolved 82% of the tested species in Ficus. The highly regarded matK and rbcL could not resolve all the species. Finally, we employed amplified fragment length polymorphism test in species of Berberis to determine their relationships. Using ten primer pair combinations in AFLP, the data demonstrated incomplete species resolution. Further, AFLP analysis showed that there was a tendency of the Berberis accessions to cluster according to their geographic origin rather than species affiliation. CONCLUSIONS/SIGNIFICANCE: We reconfirm the earlier reports that the concept of universal barcode in plants may not work in a number of genera. Our results also suggest that the matK and rbcL, recommended as universal barcode loci for plants, may not work in all the genera of land plants. Morphological, geographical and molecular data analyses of Indian species of Berberis suggest probable reticulate evolution and thus barcode markers may not work in this case

Footprint of Positive Selection in Treponema pallidum subsp. pallidum Genome Sequences Suggests Adaptive Microevolution of the Syphilis Pathogen

In the rabbit model of syphilis, infection phenotypes associated with the Nichols and Chicago strains of Treponema pallidum (T. pallidum), though similar, are not identical. Between these strains, significant differences are found in expression of, and antibody responses to some candidate virulence factors, suggesting the existence of functional genetic differences between isolates. The Chicago strain genome was therefore sequenced and compared to the Nichols genome, available since 1998. Initial comparative analysis suggested the presence of 44 single nucleotide polymorphisms (SNPs), 103 small (≤3 nucleotides) indels, and 1 large (1204 bp) insertion in the Chicago genome with respect to the Nichols genome. To confirm the above findings, Sanger sequencing was performed on most loci carrying differences using DNA from Chicago and the Nichols strain used in the original T. pallidum genome project. A majority of the previously identified differences were found to be due to errors in the published Nichols genome, while the accuracy of the Chicago genome was confirmed. However, 20 SNPs were confirmed between the two genomes, and 16 (80.0%) were found in coding regions, with all being of non-synonymous nature, strongly indicating action of positive selection. Sequencing of 16 genomic loci harboring SNPs in 12 additional T. pallidum strains, (SS14, Bal 3, Bal 7, Bal 9, Sea 81-3, Sea 81-8, Sea 86-1, Sea 87-1, Mexico A, UW231B, UW236B, and UW249C), was used to identify “Chicago-“ or “Nichols -specific” differences. All but one of the 16 SNPs were “Nichols-specific”, with Chicago having identical sequences at these positions to almost all of the additional strains examined. These mutations could reflect differential adaptation of the Nichols strain to the rabbit host or pathoadaptive mutations acquired during human infection. Our findings indicate that SNPs among T. pallidum strains emerge under positive selection and, therefore, are likely to be functional in nature

Non-pharmacological care for patients with generalized osteoarthritis: design of a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Non-pharmacological treatment (NPT) is a useful treatment option in the management of hip or knee osteoarthritis. To our knowledge however, no studies have investigated the effect of NPT in patients with generalized osteoarthritis (GOA). The primary aim of this study is to compare the effectiveness of two currently existing health care programs with different intensity and mode of delivery on daily functioning in patients with GOA. The secondary objective is to compare the cost-effectiveness of both interventions.</p> <p>Methods/Design</p> <p>In this randomized, single blind, clinical trial with active controls, we aim to include 170 patients with GOA. The experimental intervention consist of six self-management group sessions provided by a multi-disciplinary team (occupational therapist, physiotherapist, dietician and specialized nurse). The active control group consists of two group sessions and four sessions by telephone, provided by a specialized nurse and physiotherapist. Both therapies last six weeks. Main study outcome is daily functioning during the first year after the treatment, assessed on the Health Assessment Questionnaire. Secondary outcomes are health related quality of life, specific complaints, fatigue, and costs. Illness cognitions, global perceived effect and self-efficacy, will also be assessed for a responder analysis. Outcome assessments are performed directly after the intervention, after 26 weeks and after 52 weeks.</p> <p>Discussion</p> <p>This article describes the design of a randomized, single blind, clinical trial with a one year follow up to compare the costs and effectiveness of two non-pharmacological interventions with different modes of delivery for patients with GOA.</p> <p>Trial registration</p> <p>Dutch Trial Register NTR2137</p

Models of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major global health problem and is predicted to become the third most common cause of death by 2020. Apart from the important preventive steps of smoking cessation, there are no other specific treatments for COPD that are as effective in reversing the condition, and therefore there is a need to understand the pathophysiological mechanisms that could lead to new therapeutic strategies. The development of experimental models will help to dissect these mechanisms at the cellular and molecular level. COPD is a disease characterized by progressive airflow obstruction of the peripheral airways, associated with lung inflammation, emphysema and mucus hypersecretion. Different approaches to mimic COPD have been developed but are limited in comparison to models of allergic asthma. COPD models usually do not mimic the major features of human COPD and are commonly based on the induction of COPD-like lesions in the lungs and airways using noxious inhalants such as tobacco smoke, nitrogen dioxide, or sulfur dioxide. Depending on the duration and intensity of exposure, these noxious stimuli induce signs of chronic inflammation and airway remodelling. Emphysema can be achieved by combining such exposure with instillation of tissue-degrading enzymes. Other approaches are based on genetically-targeted mice which develop COPD-like lesions with emphysema, and such mice provide deep insights into pathophysiological mechanisms. Future approaches should aim to mimic irreversible airflow obstruction, associated with cough and sputum production, with the possibility of inducing exacerbations

Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome

Prioritizing congenital syphilis control in south China: a decision analytic model to inform policy implementation.

BACKGROUND: Syphilis is a major public health problem in many regions of China, with increases in congenital syphilis (CS) cases causing concern. The Chinese Ministry of Health recently announced a comprehensive 10-y national syphilis control plan focusing on averting CS. The decision analytic model presented here quantifies the impact of the planned strategies to determine whether they are likely to meet the goals laid out in the control plan. METHODS AND FINDINGS: Our model incorporated data on age-stratified fertility, female adult syphilis cases, and empirical syphilis transmission rates to estimate the number of CS cases associated with prenatal syphilis infection on a yearly basis. Guangdong Province was the focus of this analysis because of the availability of high-quality demographic and public health data. Each model outcome was simulated 1,000 times to incorporate uncertainty in model inputs. The model was validated using data from a CS intervention program among 477,656 women in China. Sensitivity analyses were performed to identify which variables are likely to be most influential in achieving Chinese and international policy goals. Increasing prenatal screening coverage was the single most effective strategy for reducing CS cases. An incremental increase in prenatal screening from the base case of 57% coverage to 95% coverage was associated with 106 (95% CI: 101, 111) CS cases averted per 100,000 live births (58% decrease). The policy strategies laid out in the national plan led to an outcome that fell short of the target, while a four-pronged comprehensive syphilis control strategy consisting of increased prenatal screening coverage, increased treatment completion, earlier prenatal screening, and improved syphilis test characteristics was associated with 157 (95% CI: 154, 160) CS cases averted per 100,000 live births (85% decrease). CONCLUSIONS: The Chinese national plan provides a strong foundation for syphilis control, but more comprehensive measures that include earlier and more extensive screening are necessary for reaching policy goals