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

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Mechanisms and management of loss of response to anti-TNF therapy for patients with Crohn's disease: 3-year data from the prospective, multicentre PANTS cohort study

This is the final version. Available from Elsevier via the DOI in this record. Background We sought to report the effectiveness of infliximab and adalimumab over the first 3 years of treatment and to define the factors that predict anti-TNF treatment failure and the strategies that prevent or mitigate loss of response. Methods Personalised Anti-TNF therapy in Crohn’s disease (PANTS) is a UK-wide, multicentre, prospective observational cohort study reporting the rates of effectiveness of infliximab and adalimumab in anti-TNF-naive patients with active luminal Crohn’s disease aged 6 years and older. At the end of the first year, sites were invited to enrol participants still receiving study drug into the 2-year PANTS-extension study. We estimated rates of remission across the whole cohort at the end of years 1, 2, and 3 of the study using a modified survival technique with permutation testing. Multivariable regression and survival analyses were used to identify factors associated with loss of response in patients who had initially responded to anti-TNF therapy and with immunogenicity. Loss of response was defined in patients who initially responded to anti-TNF therapy at the end of induction and who subsequently developed symptomatic activity that warranted an escalation of steroid, immunomodulatory, or anti-TNF therapy, resectional surgery, or exit from study due to treatment failure. This study was registered with ClinicalTrials.gov, NCT03088449, and is now complete. Findings Between March 19, 2014, and Sept 21, 2017, 389 (41%) of 955 patients treated with infliximab and 209 (32%) of 655 treated with adalimumab in the PANTS study entered the PANTS-extension study (median age 32·5 years [IQR 22·1–46·8], 307 [51%] of 598 were female, and 291 [49%] were male). The estimated proportion of patients in remission at the end of years 1, 2, and 3 were, for infliximab 40·2% (95% CI 36·7–43·7), 34·4% (29·9–39·0), and 34·7% (29·8–39·5), and for adalimumab 35·9% (95% CI 31·2–40·5), 32·9% (26·8–39·2), and 28·9% (21·9–36·3), respectively. Optimal drug concentrations at week 14 to predict remission at any later timepoints were 6·1–10·0 mg/L for infliximab and 10·1–12·0 mg/L for adalimumab. After excluding patients who had primary non-response, the estimated proportions of patients who had loss of response by years 1, 2, and 3 were, for infliximab 34·4% (95% CI 30·4–38·2), 54·5% (49·4–59·0), and 60·0% (54·1–65·2), and for adalimumab 32·1% (26·7–37·1), 47·2% (40·2–53·4), and 68·4% (50·9–79·7), respectively. In multivariable analysis, loss of response at year 2 and 3 for patients treated with infliximab and adalimumab was predicted by low anti-TNF drug concentrations at week 14 (infliximab: hazard ratio [HR] for each ten-fold increase in drug concentration 0·45 [95% CI 0·30–0·67], adalimumab: 0·39 [0·22–0·70]). For patients treated with infliximab, loss of response was also associated with female sex (vs male sex; HR 1·47 [95% CI 1·11–1·95]), obesity (vs not obese 1·62 [1·08–2·42]), baseline white cell count (1·06 [1·02–1·11) per 1 × 10⁹ increase in cells per L), and thiopurine dose quartile. Among patients treated with adalimumab, carriage of the HLA-DQA1*05 risk variant was associated with loss of response (HR 1·95 [95% CI 1·17–3·25]). By the end of year 3, the estimated proportion of patients who developed anti-drug antibodies associated with undetectable drug concentrations was 44·0% (95% CI 38·1–49·4) among patients treated with infliximab and 20·3% (13·8–26·2) among those treated with adalimumab. The development of antidrug antibodies associated with undetectable drug concentrations was significantly associated with treatment without concomitant immunomodulator use for both groups (HR for immunomodulator use: infliximab 0·40 [95% CI 0·31–0·52], adalimumab 0·42 [95% CI 0·24–0·75]), and with carriage of HLA-DQA1*05 risk variant for infliximab (HR for carriage of risk variant: infliximab 1·46 [1·13–1·88]) but not for adalimumab (HR 1·60 [0·92–2·77]). Concomitant use of an immunomodulator before or on the day of starting infliximab was associated with increased time without the development of anti-drug antibodies associated with undetectable drug concentrations compared with use of infliximab alone (HR 2·87 [95% CI 2·20–3·74]) or introduction of an immunomodulator after anti-TNF initiation (1·70 [1·11–2·59]). In years 2 and 3, 16 (4%) of 389 patients treated with infliximab and 11 (5%) of 209 treated with adalimumab had adverse events leading to treatment withdrawal. Nine (2%) patients treated with infliximab and two (1%) of those treated with adalimumab had serious infections in years 2 and 3. Interpretation Only around a third of patients with active luminal Crohn’s disease treated with an anti-TNF drug were in remission at the end of 3 years of treatment. Low drug concentrations at the end of the induction period predict loss of response by year 3 of treatment, suggesting higher drug concentrations during the first year of treatment, particularly during induction, might lead to better long-term outcomes. Anti-drug antibodies associated with undetectable drug concentrations of infliximab, but not adalimumab, can be predicted by carriage of HLA-DQA1*05 and mitigated by concomitant immunomodulator use for both drugs.Guts UKCrohn’s and Colitis UKCure Crohn’s ColitisAbbVieMerck Sharp and DohmeNapp PharmaceuticalsPfizerCelltrion Healthcar

Astragalus gooraiensis (Fabaceae), a New Species from Jammu and Kashmir, India

Volume: 17Start Page: 417End Page: 42

Astragalus kongrensis Benth. Ex Baker (Fabaceae), a New Record for Central and North-West Himalayas

Astragalus kongrensis Benth. Ex Baker is reported for the first time from Central (Nepal) and North-West Himalayas (India). Earlier the species was known from East Himalaya (Sikkim-India, Bhutan) and China. The description and illustrations of the species are provided

Astragalus uttaranchalensis (Leguminosae – Papilionoideae), a New Species from the Himalaya in India

A new species of Astragalus, A. uttaranchalensis Chaudhary & Khan (from the Indian Himalayan State Uttaranchal) is described and illustrated. Astragalus uttaranchalensis is closely related to A. emodi Steud., but differs from the latter in shape of stipules, length of inflorescence, number of flowers in each raceme, nature of bracts and size of calyx teeth

Taxonomic and Distributional Notes on Some Astragalus L. (Fabaceae) in India

In this study the revised distribution records of 25 species of Astragalus L. in India has been provided along with correct nomenclature and taxonomic notes. In addition, the relationship, conservation status and Cibachrome photographs of the type materials for some species have also been included wherever found necessary. Based on field and herbarium studies nine species (I. E. A. alitschuri B. Fedtsch, A. charguschanus Freyn, A. contortuplicatus L., A. flemingii Ali, A. iodotropis Boiss. & Hohen, A. pyrrhotrichus Boiss., A. subumbellatus Klotz., A. stocksii Bunge, A. zacharensis Bunge) have been excluded, as they do not occur in the present political boundaries of India of 1971. Those species have also been discussed here which have been recently transferred from Astragalus to some other genera like Ophiocarpus (Bunge) Ikonn., Podolotus Benth. And Podlechiella Maassoumi & Kaz. Osaloo. The present investigation also reveals that about 12 species are not represented in Indian herbaria, while they have been recorded from India based on very old collections housed at different foreign herbaria. A new combination Caragana aegacanthoides (Parker) Chaudhary & Srivastava has been proposed based on Astragalus aegacanthoides Parker

Taxonomic Study of Endemic Species of Astragalus L. (Fabaceae) of India

The goal of the study is to provide a comprehensive taxonomic account of 12 endemic species of Astragalus occurring in India. The north-west Himalayan region harbors more endemic species (11 spp.) than eastern Himalaya where only two species have been noticed from Sikkim. Jammu & Kashmir with seven species occupies first position in the list of endemic species. Five species are strictly confined to Jammu & Kashmir, while two species to Uttaranchal and one species to Sikkim. Only one species (A. tenuicaulis) is found in both the Himalayas, otherwise the elements of both the Himalayas are quite distinct from each other. Most of the endemic species of Astragalus have been observed quite rare in the nature except A. uttaranchalensis. In the present investigation, A. turgidus, a newly described species from Jammu & Kashmir, has been found conspecific to A. kashmirensis. For each species nomenclature, description, distribution, phenology, taxonomic notes, list of the investigated materials, distribution map and figures are given. A new combination A. falconeri var. pilosus (Ali) Chaudhary has been proposed based on A. hoffmeisteri var. pilosus Ali. A new endemic species A. nainitalensis from Kumaon Himalaya has also been described here along with illustrations

Current Status of the Systematics of Astragalus L. (Fabaceae) with Special Reference to the Himalayan Species in India

Astragalus is considered one of the most diverse genera in the family Leguminosae (nom. alt. Fabaceae). Although a large number of works have been carried out on the genus, no monograph is available except some regional accounts and revisions chiefly at sectional level. It may be due to the sheer size of the genus (ca. 3000 spp.) and diverse nature, the genus is quite variable in habit and habitats, size of the plants, nature of indumentums, stipules, leaf rachis, types of inflorescence, relative length of petals, pods etc. Usually, genus is divided into eight to ten subgenera and more than 245 sections. In recently conducted molecular phylogenetic studies it has been shown that none of the subgenera and large sections are monophyletic. However, it has been clearly demonstrated that Astragalus is monophyletic except some outlier species. The chromosome numbers are also quite interesting and significant in Astragalus for its phylogenetic studies. There is a strong correlation between its geographic distribution and chromosome numbers. Currently about 80 species have been recorded from India chiefly from the Himalayas. Except some of our recent publications, not much studies have been carried out on the genus in India after 'The Flora of British India'. Astragalus is not of much economic importance, however, some of its species are well known for commercial gum tragacanth production especially in Iran and China. In India, A. candolleanus is a well known drug as ‘Rudanti’ or ‘Rudravanti’used for tuberculosis, skin diseases, coughs and blood purifier. The aim of this article is to review the entire work carried out on Astragalus and to bring out scattered information at one place for better understanding of the subject and to find out the future prospective of the research in India on the genus