Plasmodium vivax, the most widespread Plasmodium species in the world. This species has been neglected and understudied for a long time, due to its lower mortality in comparison with Plasmodium falciparum. A renewed interest has emerged in the past decade with the discovery of antimalarial drug resistance and of severe and even fatal human cases. Nonetheless, today there are still significant gaps in our understanding of the population genetics and evolutionary history of P. vivax, particularly because of a lack of genetic data from Africa. To address these gaps, we genotyped 14 microsatellite loci in 834 samples obtained from 28 locations in 20 countries from around the world. We discuss the worldwide population genetic structure and diversity and the evolutionary origin of P. vivax in the world and its introduction into the Americas. This study demonstrates the importance of conducting genome-wide analyses of P. vivax in order to unravel its complex evolutionary history.More than 200 million malaria clinical cases are reported each year due to  Plasmodium species infecting humans, P. vivax is the most prevalent parasite outside Africa. To date, there has been less research on this species than for Plasmodium falciparum, a more lethal species, principally because of the lack of an in vitro culture system and also because P. vivax is considered relatively benign. Nevertheless, P. vivax is responsible for severe and incapacitating clinical symptoms with significant effects on human health. The emergence of new drug resistance and the discovery of severe and even fatal cases due to P. vivax question the benign status of P. vivax malaria. In recent years, there has been increased interest in characterizing the distribution of genetic variation in P. vivax. However, these studies either generated genetic information from a regional geographic scale or combine genetic datasets generated in different molecular platforms, which is known to generate biased results. In this study, we used a single genotyping platform to genotype 14 microsatellite markers in 834 samples of P. vivax obtained from 28 locations in 20 countries from around the world, including several populations from East and West Africa. We discuss the worldwide population genetic structure and the evolutionary origins of P. vivax, as well as its introduction into the Americas.Among the five  Plasmodium parasites are the agents responsible for malaria, one of the worst scourges of mankind, with almost 600,000 infant deaths and about 200 million clinical cases reported each year)ilibrium . In contilibrium . P. vivar others  Tables. observed , indicatulations , which cAt a worldwide scale, populations tend to group together according to their geographic locations but the relationships between populations of different geographic origins are far less obvious Figs  and 4. OP. vivax as well as the effect of more recent demographic events like population contraction, expansion or founding events.The variations of genetic diversity and genetic differentiation observed among populations at a worldwide scale are likely the consequence of the history of colonisation of the world by P. vivax and its spread throughout the world: the “Out of Asia” scenario and the “Out of Africa” scenario. Although these two hypotheses were based on different lines of evidence, the “Out of Africa” hypothesis has enjoyed renewed interest in recent years following the discovery of parasites closely related to P. vivax in African apes (named P. vivax-like) and the observation that human P. vivax diversity appears to be nested within that of the P. vivax-like parasites. This discovery has led some researchers to suggest that human strains of P. vivax originated following the transfer of parasites from African great apes to humans [P. vivax in sub-Saharan human populations, associated to the absence at the surface of their red blood cells of the Duffy antigen (i.e. Duffy negativity), suggesting that the Duffy-negative mutation was selected a long time ago in response to P. vivax infection [P. vivax was inferred from just a few nuclear genes and partial mitochondrial genomes and is consistent with several alternative scenarios. Indeed, such phylogenetic patterns can also be obtained because of incomplete lineage sorting or because of a lack of phylogenetic signal for the sequences used, two phenomena that are frequent when species have recently diverged (which is the case for P. vivax and P. vivax-like). We recently showed, comparing P. vivax-like genomes to those of P. vivax, that incongruent phylogenies may be obtained when one limits the analyses to a single or a couple of genes [P. vivax, with the high genetic diversity obtained in current Asian P. vivax parasite populations in comparison to the rest of worldwide P. vivax parasites? This pattern of genetic diversity is the opposite for P. falciparum, which has a well-established African origin [P. vivax [P. vivax among Plasmodium parasite species infecting mostly wild Asian monkeys (about fifteen monkey species’) also calls into question the “Out of Africa” hypothesis.Two scenarios have been proposed to explain the origin of o humans ,33. The nfection . Howeverof genes . Second,n origin . Indeed,P. vivax . FinallyP. vivax at a worldwide scale, then our results based on microsatellite markers, would be more congruent with an Asian origin and a spread from Asia of the current populations of P. vivax found worldwide in humans. Genetic diversity and allelic richness are highest in South-East Asian P. vivax populations and decrease from South East Asia to East Africa  are clearly insufficient to disentangle the impact of recent and ancient demographic events on the distribution of P. vivax genetic variability. More extensive analyses of the population genetic structure of these parasites, using whole genome data and some tests of demographic scenarios, might be necessary to resolve the origin and evolution of these parasites.One may nevertheless advocate that some of these genetic patterns (e.g. the decrease of genetic diversity from Asia to Africa) could also be the consequence of the current differences in population size of the P. vivax populations from South America  and Central America (Mexico and Honduras)  appear to be more closely related to some African populations (the Mauritanian P. vivax population), thus suggesting a double origin of P. vivax in America (Asian and African). Moreover, we found that American P. vivax populations harbour low levels of genetic variation. These results are consistent with a scenario in which American P. vivax populations were introduced from multiple sources. This possibility of introduction from multiple locations has already been mentioned in several recent studies based on the analysis of different kinds of genetic markers [P. vivax populations contributed to the current diversity of P. vivax observed in South America [P. vivax dated between 1942 and 1944 that European isolates were closely related to the most common present-day American haplotype [P. vivax likely entered the American continent during the post Columbian contact [P. vivax parasites seem to be characterized by a recent history through multiple introductions and the next steps will be to identify the sources of introduction and to date such events.Within the Americas, a separation is observed between onduras) . When coonduras) , it seem markers ,38. Rodr America . Gelaberaplotype . This su contact . To concP. vivax populations. The highest genetic diversity is again observed in South East Asian P. vivax populations in comparison to the populations of the rest of the world, which argues again the suggested African origin of current human P. vivax. Concerning the colonization of the American continent, results obtained in our study seem to suggest a double origin from Africa (or Europe) and Asia, as already suggested by different studies [P. vivax are needed, including the study of ancient European P. vivax strains.This study confirmed the worldwide genetic structure of  studies ,37–39. IS1 FigFST computed using an island model. Red: area including the highest 5% neutral FST. Yellow: area including the lowest 5% neutral FST.The microsatellite markers suspected to be under positive selection (MS3 and MS6) are displayed. Grey: area including 95% of the neutral (PDF)Click here for additional data file.S2 FigRed and orange dots indicate the bootstrap values, ranging from 0.9 to 1, and from 0.6 to 0.89 respectively. The only difference detectable is that the AFR+MRT cluster is associated to the Central American populations when considering the full microsatellite markers set, whereas it is distinct when getting rid of the two markers detected under positive selection (MS3 and MS6). AFR: Central African Republic + Cameroon + Togo; ARM: Armenia; AZE: Azerbaijan; BAN: Bandarban; BAY: Bay Islands; CAM: Camopi; CAY: Cayenne; COX: Cox’s Bazar; ETH: Ethiopia; HLF: New Halfa; HND: Honduras; IND: India; IRN: Iran; KGR: Khagrachari; KHA: Khartoum; MEX: Mexico; MRT: Mauritania; PAK: Pakistan; PER: Peru; STG: Saint Gorges de l’Oyapock; THA: Thailand; TMY: Thailand/Myanmar; TUR: Turkey; VEN: Venezuela. In yellow are represented Asian countries, in purple Middle-east countries, in grey African countries and in green American countries.(PDF)Click here for additional data file.S3 FigIn yellow are represented Asian countries, in purple Middle-east countries, in grey African countries and in green American countries.(PDF)Click here for additional data file.S4 FigIn yellow are represented Asian countries, in purple Middle-east countries, in grey African countries and in green American countries.(PDF)Click here for additional data file.S5 FigST). A. Asian/Middle East continent and B. American continent. Mantel tests gave P-values < 0.05 for both continents tested.Pairwise geographic along landmasses plotted against pairwise genetic differentiation (F(PDF)Click here for additional data file.S1 TableAll isolates were genotyped by us for the 14 microsatellite loci. NA: non-available information.(DOCX)Click here for additional data file.S2 TableFor markers on the same chromosome, distances are enough to limit any physical linkage: MS2, MS5 and MS6 are at a minimum at 0.15Mb apart from each others; MS7 and MS8 are 1.14Mb appart; MS12 and MS15 are 1.04Mb appart.(DOCX)Click here for additional data file.S3 TableFor microsatellite genotypes, blank cases correspond to the absence of readable amplification/genotype.(DOCX)Click here for additional data file.S4 TableAFR: Central African Republic + Cameroon + Togo; ARM: Armenia; AZE: Azerbaijan; BAN: Bandarban; BAY: Bay Islands; CAM: Camopi; CAY: Cayenne; COX: Cox’s Bazar; ETH: Ethiopia; HLF: New Halfa; HND: Honduras; IND: India; IRN: Iran; KGR: Khagrachari; KHA: Khartoum; MEX: Mexico; MRT: Mauritania; PAK: Pakistan; PER: Peru; STG: Saint Gorges de l’Oyapock; THA: Thailand; TMY: Thailand/Myanmar; TUR: Turkey; VEN: Venezuela.(DOCX)Click here for additional data file.S5 TableARM: Armenia; AZE: Azerbaijan; BAN: Bandarban; BAY: Bay Islands; CAM: Camopi; CAY: Cayenne; COX: Cox’s Bazar; ETH: Ethiopia; HLF: New Halfa; HND: Honduras; IND: India; IRN: Iran; KGR: Khagrachari; KHA: Khartoum; MEX: Mexico; MRT: Mauritania; PAK: Pakistan; PER: Peru; STG: Saint Gorges de l’Oyapock; THA: Thailand; TMY: Thailand/Myanmar; TUR: Turkey; VEN: Venezuela.(DOCX)Click here for additional data file.S6 TableP-value < 0.008 (Bonferroni correction).*(DOCX)Click here for additional data file.S7 TableAll significant values are indicated in bold . AFR: Cantral African Republic + Cameroon + Togo; ARM: Armenia; AZE: Azerbaijan; BAN: Bandabar; BAY: Bay Islands; CAM: Camopi; CAY: Cayenne; COX: Cox’s Bazar; ETH: Ethiopia; HLF: New Halfa; HND: Honduras; IND: India; IRN: Iran; KGR: Khagrachari; KHA: Khartoum; MEX: Mexico; MRT: Mauritania; PAK: Pakistan; PER: Peru; STG: Saint Georges de l’Oyapock; THA: Thailand; TMY: Thailand/Myanmar; TUR: Turkey; VEN: Venezuela.(DOCX)Click here for additional data file.


In “Recommendations From the Twitter Hashtag #DoctorsAreDickheads: Qualitative Analysis :e17595), the authors noted three errors.In the originally published manuscript, the fourth sentence of the second paragraph of the Introduction section read:The term originated from a professional YouTube video maker, who posted a video on Twitter explaining that she had been diagnosed with Ehlers-Danlos syndrome and postural orthostatic hypotension syndrome (POTS).This has been changed to:The term originated from a professional YouTube video maker, who posted a video on Twitter explaining that she had been diagnosed with Ehlers-Danlos syndrome and postural orthostatic tachycardia syndrome (POTS).a originally read:In Table 2, footnote POTS: postural orthostatic hypotension syndrome.This has been changed to:POTS: postural orthostatic tachycardia syndrome.The Abbreviations section originally included the following:POTS: postural orthostatic hypotension syndrome.This has been changed to:POTS: postural orthostatic tachycardia syndrome.These corrections will appear in the online version of the paper on the JMIR Publications website on November 9, 2020, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories.


Correction to:Movement Ecology (2023) 11:2010.1186/s40462-023-00378-1Following publication of the original article , the autThe statement in the ‘Availability of data and materials’ section originally read: We will make our data publicly available upon publication.The statement should read: The datasets generated for this study are available on request to the corresponding author.The original article  has been


In the manuscript “Isolated and combined association of excessive screen time and physical inactivity with negative self-rated health in adolescents”, DOI: 10.1590/1984-0462/2023/41/2022077, published in the Rev Paul Pediatr. 2023;41:e2022077:On the top of the first page:Where it reads:Jean Carlos Parmigiani de MarcoIt should read:Jean Carlos Parmigiani De Marco


Correction to: BMC Health Services Research (2023) 23:71110.1186/s12913-023-09725-9Following publication of the original article , the autThe incorrect author name is: Zahra Hadian ShiaziThe correct author name is: Zahra Hadian ShiraziThe author group has been updated above and the original article  has been


There are errors in the Funding section. The correct Funding statement is: Specific grant number: GST03 Initials of authors who received award: AvS Specific grant number: EDU/0500057415 Initials of authors who received award: AvS, HYFull names of commercial companies that funded the study or authors: no commercial company funded the study or authors.Work preparatory to this meta-analysis was funded by the Organization for Economic Cooperation and Development (Contract Reference: EDU/0500057415).The systematic literature search and the coding for this meta-analysis was funded by the Global TIES for Children Research Center at New York University Abu Dhabi (GST03).https://nyuad.nyu.edu/en/research/faculty-labs-and-projects/global-ties-for-children.htmlURL to sponsor’ website: The funders (other than the named authors) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


J Pediatr 2022;241:203; Open Forum Infect Dis 2022;9(2):ofac492.626) that residents trained in a structured communication strategy called AIMS  demonstrated specific behaviors of interest during live and virtual encounters with standardized patients (SPs) portraying vaccine-hesitant parents. The current study was conducted to determine if those behaviors were prioritized long after completion of training.We previously showed  or standard of care training ; blinding was maintained after training and until the time of the current study. Subjects were invited to complete an online survey wherein 10 possible communication behaviors were ranked from highest priority to lowest priority . Respondents were considered to have prioritized AIMS behaviors if they ranked each of the 3 AIMS items in the top 5; the ability of this measure to detect prioritization of AIMS behaviors was assessed by surveying unblinded residents who underwent AIMS training in the prior 2 weeks . Differences between groups were assessed using Chi-square tests for proportions. We hypothesized that a higher proportion of subjects in the AIMS Group would prioritize AIMS behaviors compared to subjects in the Control Group.p-value = 0.003). However, only 19% of the 32 residents in the AIMS Group met criteria for prioritization of AIMS behaviors .Characteristics of study participants are shown in Figure 3. Seventy-seven percent of the 31 residents in the Validation Group met criteria for prioritization of AIMS behaviors, compared with only 38% of the 32 subjects in the Control Group (AIMS communication behaviors are ranked highly shortly after training, but this prioritization is not retained over time. Future studies of the utility of structured vaccine hesitancy communication strategies should incorporate repetition and spaced retrieval to enhance retention and ensure deployment in practice.Shanna M. Barton, MD, M.Sc., Sanofi Pasteur: Grant/Research Support Gary S. Marshall, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|GSK: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi: Honoraria|Seqirus: Advisor/Consultant|Seqirus: Grant/Research Support|Seqirus: Honoraria


Journal of Pharmaceutical Health Care and Sciences (2023) 9:1310.1186/s40780-023-00281-2The original publication of this article contained an incorrect title.The correct and incorrect title are listed below, the original article has been updated.Rhabdomyolysis caused by interaction between rosuvastatin and vadadustat: a case control studyRhabdomyolysis caused by interaction between rosuvastatin and vadadustat: a case report


Correction: Journal of Orthopaedic Surgery and Research (2022) 17:544 10.1186/s13018-022-03434-5Following publication of the original article , the autThe incorrect author name is: Jingxing ZhaoThe correct author name is: Jingxin ZhaoThe author group has been updated above and the original article  has been


Caption: Section of the digestive gland of a cockle infected with Marteilia cochillia.Credit: Dr. Antonio Villalba.


To the editor,We thank Dr. Sasaki, Dr. Suzaki, and Dr. Ueki for their interest and comments on the letter entitled “Predictive significance of Charcot‐Leyden crystal structures for nasal polyp recurrence”,However, we readily acknowledge that detection of CLCs by H&E staining has some issues as proposed by Ueki et al. First, we believe that the most critical factor determining staining success is the optimal eosin pH value. Actually, many commercial eosin solutions could detect eosinophils perfectly but not CLCs. It should also be noted that CLCs identified by H&E staining may be interfered by other eosinophilic components, which can be improved by optimizing the eosin solution pH value. Second, CLCs count may vary depending on the different fields of view. In fact, CLCs are preferentially detected in the nasal mucosa tissue that is in close proximity to denuded epithelium and eosinophil degranulation.Yurong Bai: Data curation (lead); Formal analysis (lead); Methodology (lead); Writing – original draft (lead). Wenyi Chen: Data curation ; Methodology ; Validation . Weifeng Kong: Methodology (supporting); Software; . Xin Luo: Methodology (supporting); Software (supporting). Jingyuan Chen: Methodology (supporting); Software . Xinyue Wang: Methodology (supporting); Software . Qingwu Wu: Methodology (supporting); Software . Jianning Chen: Methodology (supporting); Resources . Qintai Yang: Funding acquisition (supporting); Investigation ; Project administration ; writing – review & editing . Yana Zhang: Conceptualization (lead); Funding acquisition (lead); Investigation ; Project administration (lead); Resources (lead); Supervision (lead); writing – original draft (supporting); writing – review and editing (lead).None.The National Natural Science Foundation of China (NSFC), Grant/Award Numbers: 8217114, U20A20399, 82271148; the Natural Science Foundation of Guangdong Province, Grant/Award Number: 2022A1515011787; the Science and Technology Program of Guangzhou, Grant/Award Number: 202201020402; the Key‐area Research and Development Program of Guangzhou Province, Grant/Award Number: 2020B0101130015; Fundamental Research Funds for the Central University, Sun Yat‐sen University, Grant/Award Number: 23qnpy141


Penicillium roqueforti.Caption: A slice of a French Termignon blue cheese naturally colonized by Credit: Tatiana Giraud.


Correction: Journal of Medical Case Reports (2023) 17:434 10.1186/s13256-023-04160-0Following publication of the original article , an erroThe section currently reads:FundingNo fund received for this article.The section should read:FundingFunding Open Access funding provided by the Qatar National Library.The funding section has been updated above and the original article  has been


Septic shock studies have identified that delay to the initial antimicrobial administration is the strongest predictor of survival. With every hour of delay mortality increases by 7.6%. The time from the written antibiotic order to intravenous administration or “hang-time” can be several hours due to logistics within the hospital. As the optimization of the antibiotic administration involves the participation of a team in the ICU, Antimicrobial Stewardship Programs (ASP) play an important role in reducing this gap. The present study sought to determine the time between the prescription and the infusion of the antibiotic in 7 Latin American ICU that are implementing ASPs.Prevalence study between 2021-2022 in 7 hospitals . Hang-time was defined as the time elapsed from the written antibiotic order to actual IV administration. Hang-time compliant was defined as antibiotic administration within an elapsed time of 1 h from the written antibiotic order. Any patient with a suspected infection in the ICU , who had a first dose of the antibiotic was included. Patients with incomplete medical records or who died before the administration of the first dose were excluded. For the descriptive analysis, the average of the time difference between the formulation versus the administration of the treatment was determined, as well as the adherence to the administration of the antibiotic in the first hour after being formulated.1207 prescriptions were evaluated. The most common diagnose was sepsis and septic shock from urinary and pulmonary source. Hangtime adherence was 38.5% (22.5%-74.0%). The time range was 2 to 1080 minutes.HANGTIME RESULTS BY COUNTRYThe administration of antibiotics during the first hour in ICU patients was not an adherent practice despite being a risk factor for mortality. A stewardship process improvement protocol with physicians, pharmacists, and nursing collaboration has been developed to improve the hang-time of antibiotics in patients with sepsis. ASPs with limited resources should consider implementing hang-time protocols. Phase 2 will measure compliance of the hang-time protocol and mortality.Christian Pallares, MD, MSc, 3M: Advisor/Consultant|3M: Honoraria|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Westquímica: Advisor/Consultant|Westquímica: Grant/Research Support|Westquímica: Honoraria Jorge Chaverri, n/a, Pfizer: Advisor/Consultant|Pfizer: Honoraria María Virginia Villegas, n/a, MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Westquímica: Advisor/Consultant|Westquímica: Grant/Research Support|Westquímica: Honoraria


Correction to: Current Hypertension Reports 10.1007/s11906-023-01264-2The article “Does Renal Denervation a Reasonable Treatment Option in Hemodialysis-Dependent Patient with Resistant Hypertension? A Narrative Review”, was originally published electronically on the publisher’s internet portal on 6 September 2023 with error on the tagging of the author names (first names and last names were interchanged) and affiliation of the third author.First Name: AlbertoLast Name: MazzaAuthor 1First Name: FabioLast Name: Dell'AvvocataAuthor 2First Name: GioiaLast Name: TorinAuthor 3First Name: FrancescaLast Name: BulighinAuthor 4First Name: YuriLast Name: BattagliaAuthor 5First Name: FulvioLast Name: FioriniAuthor 6The correct tagging of the author names are as follows:Gioia Torin (third author) should be affiliated to ESH Excellence Hpertension Centre and Dept. of Internal Medicine, Santa Maria della Misericordia General Hospital, AULSS 5 Polesana, Rovigo, Italy.The original article has been corrected.


Correction to: BMC Health Services Research (2023) 23:106910.1186/s12913-023-10066-wFollowing publication of the original article , the autThe incorrect author name is: Branden McCormack.The correct author name is: Brendan McCormack.The author group has been updated above and the original article  has been


Details of correction: reverse order of first and second authors.Existing text: Federica Turati, Marta RossiCorrected text should read: Marta Rossi, Federica Turati


Correction to: Acta Neuropathologica Communications (2023) 11:11110.1186/s40478-023-01609-7Following publication of the original article , the autThe incorrect author names are: Laura Kuhlman and Andrew Mackling.The correct author names are: Laura Kuhlmann and Andrew Macklin.The author group has been updated above and the original article  has been


Caption: An infant of Macaca mulatta vestita is groveling on adult‐female monkey's back in Jiacha Gorge on the Yarlung Zangbo River, Tibet, China.Credit: Dayong Li.


Following publication of the original article , we haveOriginally published phrase:From top left: All-cause deaths; deaths from external causes; deaths from neoplasms; deaths from diseases of the nervous system and the sense organs. From bottom left: Deaths from circulatory diseases; deaths from mental and behavioural disorders; deaths from diseases of the respiratory system; deaths from other causes.Corrected caption phrase:Panel a: all-cause deaths; Panel b: deaths from external causes; Panel c: deaths from neoplasms; Panel d: deaths from diseases of the nervous system and the sense organs; Panel e: deaths from circulatory diseases; Panel f: deaths from mental and behavioural disorders; Panel g: deaths from diseases of the respiratory system; Panel h: Deaths from other causes.The original article has been corrected.


BJS Open 2023;7: https://doi.org/10.1093/bjsopen/zrad024This is a correction to: Bin Li and others, Surgical treatment of hilar cholangiocarcinoma: retrospective analysis. Fig. 2. This is the correct version:In the originally published version of this article, there were errors in the use of ‘>’ and ‘<’ symbols in the RLV/TLV presentation of the site area in instead of:The figure has been emended in the article.


There were multiple errors in the Author Contributions statement. The Author Contributions statement should read: "Conceived and designed the experiments: SJD LAS DPB CJK. Performed the experiments: SJD LAS DPB CJK.Analyzed the data: SJD TP LAS DPB CJK. Wrote the paper: SJD MIT TP LAS DPB CJK."


HLA genes. In this study, we sought to use SNP genotyping in a large patient collection to identify sJIA susceptibility loci.Systemic juvenile idiopathic arthritis (sJIA) is a complex inflammatory disease whose etiology remains unknown. sJIA is distinguished from other forms of juvenile idiopathic arthritis (JIA) by its characteristic features including requisite quotidian fever and salmon-colored, evanescent skin rash, but also by an absence of autoantibodies. Based on its unique phenotype among JIA subtypes, it has been suggested that sJIA may be autoinflammatory rather than autoimmune in nature, and consistent with this, sJIA is distinct among JIA subtypes for its inconsistently detectable association with p below 0.001, producing a dataset of 690,672 SNPs in 576 cases and 426 controls. To address population stratification, we employed principal components (PC) analysis to identify and exclude samples with differing genetic backgrounds. We excluded 60 sJIA samples on this basis, reducing the size of the collection for final analysis to 516 cases and 426 controls. After correcting for the top 10 PCs, the genomic inflation factor reflected minimal population stratification (λGC = 1.01).We genotyped 576 children fulfilling ILAR criteria for systemic arthritis and 366 control subjects free of sJIA or autoimmune disease. The collection included 205 cases and 210 controls from Cincinnati Children’s Hospital, 185 cases from the repository at University of Manchester, 56 cases and 60 controls from University of Genova, 54 cases from Hacettepe University, 42 cases from the University of Utah, 34 cases from Stanford University, and 96 controls from Istanbul University. SNP genotyping was performed using Illumina Omni1M Quad v1.0 beadchips and iScan platform. Omni1M beadchip data from 60 unrelated CEU HapMap individuals were obtained through Illumina’s iControlDB. SNP associations were evaluated using SNP & Variation Suite 7, excluding SNPs with call rates below 95%, minor allele frequencies below 0.05, or Hardy-Weinberg Equilibrium HLA-DRB1 with PC-corrected associations that exceeded a stringent threshold for genome-wide significance (p < 5 x 10-8). These SNPs were part of a larger group of 45 SNPs with p < 5 x 10-5 in the MHC class II gene cluster. The effect size of the sJIA-associated SNPs ranged from odds ratios of 1.45 to 1.65. Notably, the effect size of this association is modest, relative to the effect of associated HLA genes in other JIA subtypes and other autoimmune diseases. Figure We identified 12 SNPs within MHC of sJIA patients, albeit with more modest effect sizes than those detected in other JIA subtypes. This suggests at least some contribution of autoimmunity to the pathogenesis of this complex disorder.A large collaborative effort to identify sJIA patients and a careful genetic matching strategy have allowed us to clearly detect an association signal within the class II region of the Michael Ombrello: None; Elaine F. Remmers: None; Alexei A. Grom: None; Wendy Thomson: None; Alberto Martini: None; Marco Gattorno: None; Seza Ozen: None; Ahmet Gul: None; John F. Bohnsack: None; Andrew S. Zeft: None; Elizabeth D. Mellins: None; Jane L. Park: None; Claudio Len: None; Colleen Satorius: None; Ricardo A.G. Russo: None; Terri H. Finkel: None; Rae S.M. Yeung: None; Rayfel Schneider: None; Sampath Prahalad: None; David N. Glass: None; Roger C. Allen: None; Nico Wulffraat: None; Pierre Quartier: None; Maria Odete E. Hilario: None; Kevin Murray: None; Sheila Oliveira: None; Jordi Anton: None; Anne Hinks: None; Eleftheria Zeggini: None; Carl Langefeld: None; Susan Thompson: None; Jeffrey Chaitow: None; Justine Ellis: None; Davinder Singh: None; Andre Cavalvanti: None; Blanca Bica: None; Flavio Sztajnbok: None; Hakon Hakonarson: None; Katherine A. Siminovitch: None; Kirsten Minden: None; Peter Haas: None; Tobias Schwarz: None; Daniel L. Kastner: None; Patricia Woo: None.


AbstractTettigettalnamariae Quartau & Boulard 1995 is recorded for the first time in Spain. Thought to be endemic to Portugal (occurring in the southern province of Algarve), the present paper adds its distribution to southern Spain, being an Iberian endemism. The acoustic signals of the new specimens collected were recorded in different localities of Huelva province, in Andalusia during August 2012. According to their present known distribution, specimens of Tettigettalnamariae tend to be sparsely distributed in small range populations in southern Iberian Peninsula, favouring wooded areas with Pinuspinea. Hemiptera: Cicadoidea) constitute a successful group of insects where males typically communicate during pair formation and courtship through acoustic distinctive signals  have been described and recorded so far in Portugal only . Identification was based on the collection of specimens and the recording of male acoustic signals typical of the species.As an outcome of intensive fieldwork in Portugal and Spain for species of the genus The field survey was conducted daily from 10:00 h to 19:00 h during sunny weather with temperatures ranging from 29° to 32° C. Searches were conducted by car while driving at a reduced speed, allowing the detection of the songs of calling males. Their acoustic signals were recorded at the collecting site using a Marantz PMD 661 Portable SD recorder (20 Hz – 24 kHz) connected to a Telinga Pro 7 Dat-mic microphone (Twin Science) following the procedures given in Faculty of Sciences, University of Lisbon (FCUL). Collected specimens were stored dry and a front leg was preserved in 100% ethanol for DNA isolation.Geographical coordinates were determined with a GPS  for each site where male songs were heard and where specimens were collected. Species confirmation was accomplished with time and frequency analysis of sound recordings using the software Avisoft Sas-Lab Pro  as in prQuartau & Boulard, 1995Type status:Other material. Occurrence: recordedBy: Raquel Mendes; individualCount: 3; sex: male; Location: country: Espana; stateProvince: Andaluzia; verbatimLocality: Cartaya; verbatimLatitude: 37°15'44.2"N; verbatimLongitude: 7°07'48.9"W; Event: samplingProtocol: Acoustic recording; eventDate: 2012-08-15T17:00Z; Record Level: collectionID: 3372;3373;3374; institutionCode: FCUL; collectionCode: Entomology_PCSType status:Other material. Occurrence: recordedBy: Raquel Mendes; Vera Nunes; individualCount: 3; sex: male; Location: country: Espana; stateProvince: Andaluzia; verbatimLocality: Cartaya; verbatimLatitude: 37°15'44.2"N; verbatimLongitude: 7°07'48.9"W; Event: samplingProtocol: Acoustic recording; eventDate: 2012-08-15T18:00Z; Record Level: collectionID: 3375;3376;3377; institutionCode: FCUL; collectionCode: Entomology_PCSType status:Other material. Occurrence: recordedBy: Vera Nunes; individualCount: 1; sex: male; Location: country: Espana; stateProvince: Andaluzia; verbatimLocality: Cartaya; verbatimLatitude: 37°15'44.2"N; verbatimLongitude: 7°07'48.9"W; Event: samplingProtocol: Sweep net capture; eventDate: 2012-08-15T17:45Z; Record Level: collectionID: 3378; institutionCode: FCUL; collectionCode: Entomology_PCSType status:Other material. Occurrence: recordedBy: Raquel Mendes; Vera Nunes; individualCount: 1; sex: male; Location: country: Espana; stateProvince: Andaluzia; verbatimLocality: Moguer; verbatimLatitude: 37°12'30.7"N; verbatimLongitude: 6°46'46.1"W; Event: samplingProtocol: Acoustic recording; eventDate: 2012-08-16T11:50Z; Record Level: collectionID: 3379; institutionCode: FCUL; collectionCode: Entomology_PCSType status:Other material. Occurrence: recordedBy: Raquel Mendes; Vera Nunes; individualCount: 1; sex: male; Location: country: Espana; stateProvince: Andaluzia; verbatimLocality: Moguer; verbatimLatitude: 37°12'30.7"N; verbatimLongitude: 6°46'46.1"W; Event: samplingProtocol: Acoustic recording; eventDate: 2012-08-16T14:40Z; Record Level: collectionID: 3380; institutionCode: FCUL; collectionCode: Entomology_PCSType status:Other material. Occurrence: recordedBy: Vera Nunes; individualCount: 1; sex: male; Location: country: Espana; stateProvince: Andaluzia; verbatimLocality: Almonte; verbatimLatitude: 37°13'43.0"N; verbatimLongitude: 6°33'51.1"W; Event: samplingProtocol: Acoustic recording; eventDate: 2012-08-16T15:45Z; Record Level: collectionID: 3382; institutionCode: FCUL; collectionCode: Entomology_PCSTettigettalnamariae specimens in Spain.Our analysis of the morphological and acoustic data confirmed the presence of Tettigettalnamariae tending to favour wooded areas of Pinuspinea near the sea in the southern Iberian Peninsula (Figs Specimens were collected and recorded in different locations from Huelva province in Andalusia around the following localities: Cartaya, Aljaraque, Moguer, Mazagón, Almonte and Hinojos Table . Recordsula Figs , 2.Tettigettalnamariae specimens have a broad spectrum near 6 - 16.5 kHz with maximum energy around 12 kHz. For time domain variables, our results indicated an echeme duration ranging from 0.02 to 0.10s, with an average value of 0.06s. For the echeme period we found a range of 0.16 to 0.54s and average of 0.32s.Acoustic analysis Table , Fig. 3 Tettigettalnamariae was a Portuguese endemic cicada, seeming to be confined to central Algarve, close to the sea (Tettigettalnamariae given the restricted habitat range of the known populations. The discovery of Tettigettalnamariae populations in Spain means that the species is not confined to the central wooded area of Algarve, close to the sea, having instead a wider distribution extending to Andalusia. The new populations of Tettigettalnamariae reported here constitute an important addition to the scarce knowledge of this rare species. However, Tettigettalnamariae distribution remains heavily fragmented and discontinuous. Consequently the species is still vulnerable to habitat loss caused by changes in land use or forest fires that often jeopardize Pinuspinea woods during the summer, when cicada adult males are active. These threats may cause the decline and eventual extinction of local populations of cicadas and are especially worrying for small range species such as Tettigettalnamariae (Previous studies suggested that  the sea  which isamariae .With the present data, obtained through our 2012 fieldwork, a new cicada species is listed for Spain and a new endemism for Iberia.Cicadetta (e.g.Moreover, the current species list available for the cicadas from Iberian Peninsula are likely to still be incomplete. As the male acoustic signals in cicadas are highly diagnostic for the separation of closely related species , it is qetta e.g.. All thi


Several authors were omitted from the contributions to the "Wrote the paper" section. The correct Author Contributions are: Conceived and designed the experiments: CMC APM DAE EAW KEWJ. Performed the experiments: CMC PMW APM WKR AB. Analyzed the data: ERG CMC PMW RD WKR KEWJ. Contributed reagents/materials/analysis tools: APM WKR DAE KEWJ. Wrote the paper: ERG RAD EAW KEW.


The word "arsenal" was misspelled in the title of the article. The correct title is: "Molecular Evolution of Vertebrate Neurotrophins: Co-Option of the Highly Conserved Nerve Growth Factor Gene into the Advanced Snake Venom Arsenal." The correct Citation is: Sunagar K, Fry BG, Jackson TNW, Casewell NR, Undheim EAB, et al. (2013) Molecular Evolution of Vertebrate Neurotrophins: Co-Option of the Highly Conserved Nerve Growth Factor Gene into the Advanced Snake Venom Arsenal. PLoS ONE 8(11): e81827. doi:10.1371/journal.pone.0081827.


There were errors in the name of the thirteenth author. The correct name is: Nhu Thi Quynh Nguyen.On two occasions in the Abstract, the letter "M" was dropped from words.Introduction: icroscopic Observation Drug Susceptibility (MODS)..." should be "Introduction: Microscopic Observation Drug Susceptibility (MODS)...""Conclusion: ODS is a sensitive..." should be corrected as "Conclusion: MODS is a sensitive..." "


T. harzianum are well known for their biocontrol activity against many plant pathogens. However, there is a lack of studies concerning its use as a biological control agent against F. solani, a pathogen involved in several crop diseases. In this study, we have used subtractive library hybridization (SSH) and quantitative real-time PCR (RT-qPCR) techniques in order to explore changes in T. harzianum genes expression during growth on cell wall of F. solani (FSCW) or glucose. RT-qPCR was also used to examine the regulation of 18 genes, potentially involved in biocontrol, during confrontation between T. harzianum and F. solani.The species of T. harzianum growth on FSCW or glucose. We identified various genes of biotechnological value encoding to proteins which function such as transporters, hydrolytic activity, adherence, appressorium development and pathogenesis. Fifteen genes were up-regulated and sixteen were down-regulated at least at one-time point during growth of T. harzianum in FSCW. During the confrontation assay most of the genes were up-regulated, mainly after contact, when the interaction has been established.Data obtained from two subtractive libraries were compared after annotation using the Blast2GO suite. A total of 417 and 78 readable EST sequence were annotated in the FSCW and glucose libraries, respectively. Functional annotation of these genes identified diverse biological processes and molecular functions required during T. harzianum expressed different genes when grown on FSCW compared to glucose. It provides insights into the mechanisms of gene expression involved in mycoparasitism of T. harzianum against F. solani. The identification and evaluation of these genes may contribute to the development of an efficient biological control agent.This study demonstrates that  Trichoderma harzianum is a soil-borne filamentous fungus that protects crop plants from attack by a range of pathogenic fungi  × 100 [ng Phred . Only se program . The fil)] × 100 .T. harzianum grown in FSCW, and T. harzianum grown in glucose medium. Both conditions were sampled at three different time points . Statistical tests  were performed when appropriate. Eighteen genes potentially involved in biocontrol were selected from the FSCW-library and 10 genes from Glc-library . Amplification efficiency was then calculated from the given slopes in the IQ5 Optical system Software v2.0 [The expression levels of 28 genes were estimated from the threshold cycle using the 2T method . In ordeare v2.0 . All calF. solani cell wall library; Glc-library: Glucose library.asm: acid sphingomielinase; aoc: amine oxidase; aqp: aquaporin; cfem: eight cysteine-containing domain; chk1: checkpoint-like protein; chit: chitinase 33; cpox: coproporphyrinogen oxidase; CWDE: Cell Wall Degrading Enzymes; Duf: duf895 domain membrane protein; Endo: Endochitinase 42; Eno: Enolase; Exo: Exo-rhamnogalacturonase; Gapd: Glyceraldehyde 3- phosphate dehydrogenase; Glyc: Glycosyl hydrolase; hsp98: heat shock protein; ht: hexose transporter-like protein; mbl2: mbl2-like secreted; norA: norsolorinic acid reductase; ptr2: peptide transporter; psd: phosphatidylserine decarboxylase family protein; pld: phospholipase d; pdc: pyruvate decarboxylase; qid: QID74 protein; sag: senescence-associated protein; ser: serine protease; sck1: serine threonine-protein kinase; c2h2: zinc finger domain protein; zt: zinc-regulated transporter; bgn: β-1,3-endoglucanase; FSCW-library: No competing financial interests exist.PMV, ASS and SJLS performed the construction of the cDNA gene libraries and sequenced the ESTs. PMV and ASGC designed the bioinformatics analysis. PMV and RNS performed the RT-PCR analyses and evaluation of the data. PMV drafted the manuscript. ASGC and CJU were responsible for the experimental design and revised the manuscript. All authors approved the final version of the paper.Relative expression profiles of genes identified in Trichoderma harzianum (FSCW and Glc libraries) at different times of exposure to Fusarium solani cell wall. The data is presented with log scale for better visualization.Click here for fileRelative expression profiles of genes identified T. harzianum during interaction with F. solani. The data is presented with log scale for better visualization.Click here for file


This study describes the natural history of Barth syndrome (BTHS).The medical records of all patients with BTHS living in France were identified in multiple sources and reviewed.TAZ mutations were observed in 15 pedigrees. The estimated incidence of BTHS was 1.5 cases per million births (95%CI: 0.2–2.3). The median age at presentation was 3.1 weeks , and the median age at last follow-up was 4.75 years . Eleven patients died at a median age of 5.1 months; 9 deaths were related to cardiomyopathy and 2 to sepsis. The 5-year survival rate was 51%, and no deaths were observed in patients ≥3 years. Fourteen patients presented with cardiomyopathy, and cardiomyopathy was documented in 20 during follow-up. Left ventricular systolic function was very poor during the first year of life and tended to normalize over time. Nineteen patients had neutropenia. Metabolic investigations revealed inconstant moderate 3-methylglutaconic aciduria and plasma arginine levels that were reduced or in the low-normal range. Survival correlated with two prognostic factors: severe neutropenia at diagnosis (<0.5 × 109/L) and birth year. Specifically, the survival rate was 70% for patients born after 2000 and 20% for those born before 2000.We identified 16 BTHS pedigrees that included 22 patients. This survey found that BTHS outcome was affected by cardiac events and by a risk of infection that was related to neutropenia. Modern management of heart failure and prevention of infection in infancy may improve the survival of patients with BTHS without the need for heart transplantation. T studies ,14,22-27database . AllelicNotably, both in our cohort and in other BTHS patients , 3-methyFinally, the natural course of this disease illustrates the benefits of an interdisciplinary approach. In particular, a diagnosis of cardiomyopathy in a newborn or infant should lead to repeated tests to determine whether low ANC is present. The reverse is also true: It may be worth adding cardiac evaluation to the workup of the diagnosis of a chronic neutropenia suspected to be congenital. This diagnostic work-up should be performed in close cooperation with geneticists and metabolic disease specialists.TAZ gene; UPN: Unique patient number; WBC: White blood cell countACE-I: Angiotensin-converting enzyme inhibitor; ALC: Absolute lymphocyte count; AMC: Absolute monocyte count; ANC: Absolute neutrophil count; BSF: Barth Syndrome Foundation; BTHS: Barth syndrome; CBC: Complete blood count; CL: Cardiolipin; DCM: Dilated cardiomyopathy; GCSF: Granulocyte colony-stimulating factor; G6PC3: Glucose-6-phosphatase catalytic subunit 3 gene; Hb: Haemoglobin; HCM: Hypertrophic cardiomyopathy; IUGR: Intrauterine growth retardation; LV: Left ventricle; LVEDD: Left ventricle end diastolic diameter; LVEF: Left ventricle ejection fraction; LVNC: Left ventricular noncompaction; MLCL: Monolysocardiolipin; PCR: Polymerase chain reaction; QTc: Corrected QT interval; SD: Standard deviation; SF: Shortening fraction; TAZ: The authors declare no competing interests.A steering committee that included JD, DB, ASL, CO, AC and MR planned the study. ASL and RT carried out the molecular genetic studies, and CO and AC carried out the metabolic studies. DB analysed the data pertaining to the cardiac evaluations. CR collected the data and drafted the manuscript. JD was responsible for the statistical analysis and for the organization of the French SCN registry. All authors read and approved the final manuscript.Review of all published studies about Barth syndrome patients.Click here for fileFamily trees showing the 16 Barth syndrome pedigrees reported in this study.Click here for file


There were errors in the Author Contributions section. The correct contributions are: Conceived and designed the experiments: WS JF. Performed the experiments: WS. Analyzed the data: WS. Interpreted the data: JF. Designed the simulations: CK WL. Performed and analyzed the simulations: CK. Wrote the paper: WS CK JF.


During early vertebrate development, various small non-coding RNAs (sRNAs) such as MicroRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs) are dynamically expressed for orchestrating the maternal-to-zygotic transition (MZT). Systematic analysis of expression profiles of zebrafish small RNAome will be greatly helpful for understanding the sRNA regulation during embryonic development.We first determined the expression profiles of sRNAs during eight distinct stages of early zebrafish development by sRNA-seq technology. Integrative analyses with a new computational platform of CSZ  demonstrated an sRNA class transition from piRNAs to miRNAs as development proceeds. We observed that both the abundance and diversity of miRNAs are gradually increased, while the abundance is enhanced more dramatically than the diversity during development. However, although both the abundance and diversity of piRNAs are gradually decreased, the diversity was firstly increased then rapidly decreased. To evaluate the computational accuracy, the expression levels of four known miRNAs were experimentally validated. We also predicted 25 potentially novel miRNAs, whereas two candidates were verified by Northern blots.http://csz.biocuckoo.org.Taken together, our analyses revealed the piRNA to miRNA transition as a conserved mechanism in zebrafish, although two different types of sRNAs exhibit distinct expression dynamics in abundance and diversity, respectively. Our study not only generated a better understanding for sRNA regulations in early zebrafish development, but also provided a useful platform for analyzing sRNA-seq data. The CSZ was implemented in Perl and freely downloadable at:  Small non-coding RNAs (sRNAs) of about 20 ~ 30 nucleotides (nt) play an essential role in a variety of animal developmental processes, such as embryonic, neuronal, muscle, and germline development -3. Microet al. quantitatively analyzed sRNA expression profiles in 256-cell (2.5 hpf), sphere (4 hpf), shield (6 hpf), and 1 dpf (days post fertilization) stages of early zebrafish development . The most widely used radial basis function (RBF) was chosen. The penalty parameter C and RBF kernel parameter γ were exhaustively searched as 8.0 and 0.03125, respectively.The LIBSVM package was used for training , while others are called false positives (FP). Among the predicted negative results obtained by ZmirP, real negatives are called true negatives (TN), while the others are called false negatives (FN). In a classification problem, the specificity (Sp), sensitivity (Sn), accuracy (Ac) and Mathew’s correlation coefficient (MCC) are most widely used to evaluate the prediction system. They are defined as:Among the predicted positive results obtained by ZmirP, the real positives are called true positives  (AB type) were maintained under standard library conditions and the embryonic stages in this study were as described .k-nearest neighbors; ZmirP: Zebrafish miRNA prediction; CSZ: Characterization of small RNAome for zebrafish; RBF: Radial basis function; TP: True positive; FP: False positive; TN: True negative; Sp: Specificity; Sn: Sensitivity; Ac: Accuracy; MCC: Mathew’s correlation coefficient; ROC: Receiver Operating Characteristic; qRT-PCR: quantitative real-time PCR; RPM: reads per million; Non-repeat-associated piRNAs: piRNAs that were not annotated as repeat sequences; Repeat-associated piRNAs: piRNAs that could be mapped to repetitive sequences.sRNAs: small non-coding RNAs; miRNAs: MicroRNAs; piRNAs: Piwi-interacting RNAs; pri-miRNAs: primary miRNA molecules; dsRNAs: double-stranded RNAs; RISC: RNA-induced silencing complex; hpf: hours post fertilization; MZT: Maternal-to-zygotic transition; NGS: Next-generation sequencing; dpf: days post fertilization; triplet elements: local structure-sequence features; SVMs: Support vector machines; RF: Random forest; MFE: Minimum of free energy; kNN: The authors declare that they have no competing interests.YX and HJ designed the project; YY, YX developed the algorithm and analyzed data; QY, LM and QJ performed experiments; WD, ZL, YZ and JR extensively shared and discussed data; YX, YY and QY wrote the manuscript. All authors read and approved the final manuscript.The detailed data statistics for different type of reads in eight libraries.Click here for fileThe 218 known zebrafish miRNAs identified from the sRNA-seq data, with corresponding mappable reads.Click here for fileThe 25 predicted miRNAs.Click here for fileThe secondary structures of 25 potentially novel miRNAs.Click here for fileThe piRNA clusters identified from the sRNA-seq data.Click here for fileThe distribution of different types of sRNAs in data from Wei’s data . (A) TheClick here for file


There were errors in the published Author Contributions. The correct Author Contributions are: Conceived and designed the experiments: WAB AV TLH DJG. Performed the experiments: WAB MS HZ. Analyzed the data: WAB AV TLH DAK DJG. Contributed reagents/materials/analysis tools: TLH DAK DJG. Wrote the paper: WAB.


AbstractCasuarinicolaaustralis Taylor, 2010 is reported for the first time, based on new material from Auckland. This is also the first record of the genus from New Zealand.The presence in New Zealand of the triozid  Casuarinicolaaustralis Taylor, 2010 was described from Australia, where it is the most common and widespread member of its genus, being widely distributed in New South Wales, Queensland, South Australia, Victoria and Western Australia. Like its congeners, it is restricted to host trees of the genus Casuarina. Casuarinicolaaustralis occurs on all Australian species of Casuarina, including Casuarinacunninghamiana and Casuarinaglauca. Both these species of Casuarina are exotic and present in the wild in New Zealand, according to the New Zealand Organisms Register (NZOR), as well as present in cultivation. Casuarinicola has not been reported (by name) previously from N.Z.Taylor, 2010Type status:Other material. Occurrence: recordedBy: Stephen Thorpe; sex: 1 male, 1 female; Location: country: New Zealand; verbatimLocality: Mechanics Bay, Auckland City; verbatimElevation: 0-5 m; verbatimLatitude: 36.8474938105S; verbatimLongitude: 174.7869624545E; Event: eventDate: 6 January 2013; Record Level: institutionCode: Auckland MuseumType status:Other material. Occurrence: recordedBy: Stephen Thorpe; individualCount: 1; sex: female; Location: country: New Zealand; verbatimLocality: Felton Mathew Avenue, Saint Johns, Auckland; verbatimLatitude: 36.8741794382S; verbatimLongitude: 174.8506522179E; Event: eventDate: 2013-02-20; Record Level: institutionCode: Auckland MuseumType status:Other material. Occurrence: recordedBy: Stephen Thorpe; individualCount: many; sex: males, females; Location: country: New Zealand; verbatimLocality: Thomas Bloodworth Park, Auckland; verbatimElevation: 0-5 m; verbatimLatitude: 36.8652411423S; verbatimLongitude: 174.7900235653E; Event: eventDate: 2013-02-26; Record Level: institutionCode: Auckland MuseumCasuarinaglauca trees growing in the vicinity of Ports of Auckland at Mechanics Bay. A few psylloids were observed, including a pair in copula, which I collected. The specimens will be vouchered in Auckland Museum. They are easily identified as Casuarinicolaaustralis Taylor in Casuarinicolaaustralis therein, except only that the second and third bands on the female fore wings of my specimen are narrowly joined. Such minor variation is entirely expected for insect colour patterns, and the pattern is still by far closest to that of typical Casuarinicolaaustralis than it is to any other species of Casuarinicola. I can find no other differences. I therefore recommend that Casuarinicolaaustralis be added to the New Zealand Organisms Register (NZOR) as present in the wild. Its "origin" is "exotic". Subsequently, on 20 Feb 2013, a further female specimen was found on a Casuarina tree in the Auckland suburb of Saint Johns. The second and third bands on the fore wings are separated, though narrowly (Fig. Casuarina trees at Thomas Bloodworth Park, Auckland. Several pairs were observed in copula. One female was collected. It has the second and third bands of one forewing joined, and of the other narrowly separated. On Casuarina in Auckland, there is also an apparently undescribed Australian species of Trioza, which is more common and widespread than Casuarinicolaaustralis.On 6 Jan 2013, I examined some


AbstractMicrogasterdeductor Nixon (1968) are recorded from the Nearctic (Canada and the United States) and the Palaearctic (Sweden), expanding significantly the range of the species. Microgasterdeductor seems to be widely distributed in boreal areas of the Holarctic, and it is characterized by unique morphological  and molecular (COI) traits. Preliminary evidence, to be corroborated when more data is available, suggests that the species might have shifted northwards between 1950 and the present day.Four new localities for the species  Microgasterdeductor Nixon (1968) is a very distinctive microgastrine wasp , and can be easily separated from all Holarctic species of Microgaster based on its tarsal claws, which have a lobe (Microgasterdeductor could be more widely distributed in sub-Arctic or Arctic areas of the Holarctic (Europe and North America).e a lobe  Fig. 2)Microgaste a lobe . Howevere a lobe . That loMicrogasterdeductor is recorded from four additional localities, three in the Nearctic and one in the Palaearctic, which expand significantly the known range of the species. Morphological and molecular data that serve as diagnostic tools are presented, and the potential of a shift northwards of the species distribution is briefly discussed.Here http://www.boldsystems.org/).All the specimens studied for this paper are deposited in the Canadian National Collection of Insects (CNC), Ottawa, Canada. The only exception is one female deposited in the Biodiversity Institute of Ontario, which was not examined directly. Instead it was studied based on a single photo  and associated DNA barcode, both freely available as public data in the Barcode of Life Data Systems (BOLD)  were examined, although no specimen of Microgasterdeductor was found in those samples.Additionally, 40 specimens of The historical data on the distribution of the species was extracted from the original references  and compNixon, 1968Type status:Holotype. Occurrence: individualCount: 1; sex: female; Location: country: Finland; stateProvince: Lapland; verbatimLocality: Ivalo; Record Level: institutionCode: BMNHType status:Paratype. Occurrence: individualCount: 2; sex: 1 female, 1 male; Location: country: Finland; stateProvince: Lapland; verbatimLocality: Ivalo; Record Level: institutionCode: BMNHType status:Paratype. Occurrence: individualCount: 1; sex: female; Location: country: Sweden; stateProvince: Lapland; verbatimLocality: Torneträsk; Record Level: institutionCode: BMNHType status:Other material. Occurrence: recordedBy: Jose Fernández-Triana; individualCount: 3; sex: 1 female, 2 males; Location: country: United States; stateProvince: Alaska; verbatimLocality: Unalakleet; verbatimLatitude: 63.878889; verbatimLongitude: -160.789722; Event: eventDate: 27 Jun 1961, 28 Jun 1961, 4 Jul 1961; Record Level: institutionCode: CNCType status:Other material. Occurrence: recordedBy: Jose Fernández-Triana; individualCount: 4; sex: females; Location: country: Sweden; stateProvince: Lapland; verbatimLocality: Abisko; verbatimLatitude: 68.35; verbatimLongitude: 18.816667; Event: eventDate: 29 Jul 1951, 9 Aug 1951, 15 Aug 1951; Record Level: institutionCode: CNCType status:Other material. Occurrence: recordedBy: Jose Fernández-Triana; individualCount: 1; sex: female; Location: country: Sweden; stateProvince: Lapland; verbatimLocality: Abisko; verbatimElevation: 400 m; verbatimLatitude: 68.35; verbatimLongitude: 18.816667; Event: eventDate: 31 Jul 1960; Record Level: institutionCode: CNCType status:Other material. Occurrence: recordedBy: Jose Fernández-Triana; individualCount: 1; sex: female; Location: country: Canada; stateProvince: Northwest Territories; verbatimLocality: Tuktoyaktuk; verbatimLatitude: 66.4445; verbatimLongitude: -133.032; Event: samplingProtocol: Sweeping; eventDate: 14 Jul 2010; Record Level: institutionCode: CNCType status:Other material. Occurrence: recordedBy: Jose Fernández-Triana; individualCount: 1; sex: female; Location: country: Canada; stateProvince: Yukon Territory; verbatimLocality: Herschel Island; verbatimLatitude: 69.571; verbatimLongitude: -138.902; Event: eventDate: 29 Jul 2008; Record Level: institutionCode: BIOType status:Other material. Occurrence: recordedBy: Jose Fernández-Triana; individualCount: 35; Location: country: Canada; stateProvince: Manitoba; verbatimLocality: 23 km E of Churchill; verbatimLatitude: 58.734; verbatimLongitude: -93.82; Event: eventDate: 12 Jul 1952, 18 Jul 1952, 23 Jul 1952, 28 Jul 1952, 29 Jul 1952, 3 Aug 1952, 5 Aug 1952; Record Level: institutionCode: CNCType status:Other material. Occurrence: recordedBy: Jose Fernández-Triana; individualCount: 6; Location: country: Canada; stateProvince: Manitoba; verbatimLocality: Warkworth Creek nr. Churchill; verbatimLatitude: 58.375; verbatimLongitude: -93.875; Event: eventDate: 29 Jun 1952, 7 Jul 1952, 3 Aug 1952; Record Level: institutionCode: CNCMicrogasterdeductor in the Nearcitc include three localities: Unalakleet, Alaska (United States), and Tuktoyaktuk, Northwest Territories and Herschel Island, Yukon Territory (Canada). They expand considerably the distribution of the species in the Holarctic, and the Alaskan record suggests the possibility that the species might also be in Siberia, Russia . The new record in the Palaearctic is from Abisko in Sweden, a locality very close to that of Torneträsk, where one of the paratypes, included by Nixon  but in others the pale spot is reduced  differed from Microgasterdeductor by 46 base pairs (7%). Full data of the sequences and specimens can be freely accessed in BOLD from the public projects with codes CNCAS, HARC and WOMIA. The nucleotide sequence of the full barcode of Microgasterdeductor, in FASTA format is:The two specimens recently collected (2008 and 2010) rendered full DNA barcodes – a section of 658 base pairs of the mitochondrial COI gene. Among the material collected in Churchill in 1952, one specimen rendered about half a barcode (320 base pairs), and for another 33 specimens short sequences of 129-144 base pairs were obtained. All sequences were identical, with the shorter ones perfectly matching the corresponding section of the full barcode obtained from the two recent specimens. The closest sequences in BOLD  species that this wasp parasitizes.Based on the studied molecular and morphological data, Microgasterdeductor, seems to suggest that its range might have shifted northwards recently. For example, the species was the most commonly collected Microgastrinae in Churchill during a period of intense study of insects in the area around the 1950's. However, it has never been found there again, in spite of even more intense collecting efforts carried out in the same locality between 2006–2011 , this project has not recovered the species either]. Conversely, the only two recent records of Microgasterdeductor correspond to Canadian localities at 69–70°N, which had similarly been sampled in the 1940–1960 without finding any record of the species. These two localities are 6–10° north of the Canadian collections from the 1950–1960.The relatively scarce information about historical (1950–1960) and present (2008–2010) distribution of 006–2011 . Similardeductor ; also, bHowever, both historical and current day distribution patterns are likely to be biased by incomplete sampling efforts. The study of more specimens and more localities will be necessary before reaching any conclusions on this topic.


There was an error in the Author Contributions. The correct Author Contributions are: Designed the experiments: JRK RKK SB. Performed the experiments: SB. Analyzed the data: JRK RKK SB. Contributed reagents/materials/analysis tools: SB RKK JRK. Wrote the paper: JRK RKK SB. This research work is the part of PhD thesis (SB) under the supervision of JRK RKK.


There was an error in the Author Contributions Statement. The Author Contributions Statement should read: "Conceived and designed the experiments: WG SD LP. Performed the experiments: WG HY SD. Analyzed the data: WG DW. Contributed reagents/materials/analysis tools: WG HY. Wrote the paper: WG HY."


Clostridium sticklandii belongs to a cluster of non-pathogenic proteolytic clostridia which utilize amino acids as carbon and energy sources. Isolated by T.C. Stadtman in 1954, it has been generally regarded as a "gold mine" for novel biochemical reactions and is used as a model organism for studying metabolic aspects such as the Stickland reaction, coenzyme-B12- and selenium-dependent reactions of amino acids. With the goal of revisiting its carbon, nitrogen, and energy metabolism, and comparing studies with other clostridia, its genome has been sequenced and analyzed.C. sticklandii is one of the best biochemically studied proteolytic clostridial species. Useful additional information has been obtained from the sequencing and annotation of its genome, which is presented in this paper. Besides, experimental procedures reveal that C. sticklandii degrades amino acids in a preferential and sequential way. The organism prefers threonine, arginine, serine, cysteine, proline, and glycine, whereas glutamate, aspartate and alanine are excreted. Energy conservation is primarily obtained by substrate-level phosphorylation in fermentative pathways. The reactions catalyzed by different ferredoxin oxidoreductases and the exergonic NADH-dependent reduction of crotonyl-CoA point to a possible chemiosmotic energy conservation via the Rnf complex. C. sticklandii possesses both the F-type and V-type ATPases. The discovery of an as yet unrecognized selenoprotein in the D-proline reductase operon suggests a more detailed mechanism for NADH-dependent D-proline reduction. A rather unusual metabolic feature is the presence of genes for all the enzymes involved in two different CO2-fixation pathways: C. sticklandii harbours both the glycine synthase/glycine reductase and the Wood-Ljungdahl pathways. This unusual pathway combination has retrospectively been observed in only four other sequenced microorganisms.C. sticklandii genome and additional experimental procedures have improved our understanding of anaerobic amino acid degradation. Several specific metabolic features have been detected, some of which are very unusual for anaerobic fermenting bacteria. Comparative genomics has provided the opportunity to study the lifestyle of pathogenic and non-pathogenic clostridial species as well as to elucidate the difference in metabolic features between clostridia and other anaerobes.Analysis of the  Clostridium consists of a large group of Gram-positive, anaerobic bacteria which belong to the Firmicute phylum . The genome annotation and features are available at http://www.genoscope.cns.fr/agc/microscope/Anaeroscope.The genome sequence reported in this article has been deposited in the EMBL database [EMBL:Rhodobacter capsulatus nitrogen fixation; Sec: selenocysteine; SLP: substrate-level phosphorylation; THF: tetrahydrofolate; WGS: whole genome shotgun.ATP: adenosine triphosphate; CoA or CoASH: coenzyme A; ETP: electron-transport phosphorylation; fd: ferredoxin; FMN: flavin mononucleotide; gcv-system: glycine cleavage system; LC-MS: Liquid Chromatography-Mass Spectrometry; MaGe: Magnifying Genomes; NADH: reduced nicotinamide adenine dinucleotide; NADPH: reduced nicotinamide adenine dinucleotide phosphate; Ppase: pyrophosphatase; Rnf: protein involved in AK, NF and GNC performed genome and comparative analysis and coordinated experimental procedures. SC carried out the growth experiments. ST analysed amino acid utilization by LC-MS. NP contributed to the experimental procedures. AL contributed to elaboration of the clostridial database Anaeroscope. MG constructed shotgun library for sequencing. VB carried out the assembly and finishing of the genome. EP performed bioinformatic analyses. ST, AL and VB participated in writing sections of the manuscript. MS, DL, and JW critically reviewed the manuscript. GNC and JRA contributed to writing of the manuscript. AK and NF wrote the manuscript. All authors read and approved the final manuscript.C. sticklandii compared with other clostridiaGenomic and metabolic features of . All data are extracted from the MaGe annotations except those of Clostridium sporogenes, which are from the NCBI database. C.stick: Clostridium sticklandii DSM 519; C.acet: Clostridium acetobutylicum ATCC 824; C.beij: Clostridium beijerinckii NCIMB 8052; C.botu: Clostridium botulinum A Hall; C.diff: Clostridium difficile 630; C.kluv: Clostridium kluyveri DSM 555; C.novy: Clostridium novyi NT; C.perf: Clostridium perfringens ATCC 13124; C.phyt: Clostridium phytofermentans ISDg; C.teta: Clostridium tetani E88; C.ther: C. thermocellum ATCC 27405; C.spor: C. sporogenes ATCC 1557; A.meta: Alkaliphilus metalliredigens QYMF; A.orem: Alkaliphilus oremlandii OhILAs; M.ther: Moorella thermoacetica ATCC 39073. *2-ketoacid ferredoxin oxidoreductases.Click here for fileC. sticklandii synteny conservation and Bidirectional Best Hit percentages with the most closely related clostrial species. Synteny conservation is given by the percentage of CDS in synteny between C. sticklandii and the complete sequenced genomes.Click here for fileC. sticklandii, their protein symbols and their corresponding labelsCharacteristic gene products of . This is a listing of all genes/proteins that are discussed in the text.Click here for fileComparative analysis of amino acid degradation pathways in several clostridial species. Blast searches (criteria: 30% identity over at least 80% of the length of the reference protein) were performed to determine the presence of the key enzymes in the microorganisms. All protein sequences were taken from C. sticklandii with two exceptions: the sequence of methylaspartate mutase was from Clostridium cochlearium, and that of 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans. C.stick: Clostridium sticklandii DSM 519; C.acet: Clostridium acetobutylicum ATCC 824; C.beij: Clostridium beijerinckii NCIMB 8052; C.botu: Clostridium botulinum A Hall; C.diff: Clostridium difficile 630; C.kluv: Clostridium kluyveri DSM 555; C.novy: Clostridium novyi NT; C.perf: Clostridium perfringens ATCC 13124; C.phyt: Clostridium phytofermentans ISDg; C.teta: Clostridium tetani E88; C.ther: C. thermocellum ATCC 27405; C.spor: C. sporogenes ATCC 15579; A.meta: Alkaliphilus metalliredigens QYMF; A.orem: Alkaliphilus oremlandii OhILAs; M.ther: Moorella thermoacetica ATCC 39073; C.coch: Clostridium cochlearium; A.ferm: Acidaminococcus fermentans DSM 20731. The genome of Clostridium cochlearium is not yet sequenced.Click here for fileLC-MS analyses of amino acid utilization during growth. For each amino acid, its presence in the medium was checked at different growth phases (colour graphs). The growth kinetic is represented by a yellow graph. Citrulline, ornithine, alanine and aspartate (indicated by a black frame) were not added to the medium. They appeared as intermediates or products of metabolism from other amino acids. Since the utilization of methionine was not discussed in the article, the graph for this amino acid is not shown.Click here for fileC. sticklandii in three types of media with different amino acid compositionCell growth of . Graph 1: medium containing amino acids that are catabolized in the exponential phase ; Graph 2: medium containing amino acids that are catabolized in the exponential and stationary phase ; Graph 3: the amino acid combination of this medium is equivalent to the second medium, complemented with amino acids apparently not metabolized . Tyrosine was added to each medium.Click here for fileComparison of the D-proline reductase gene cluster from different clostridial species. White arrows indicate hypothetical proteins or those presumed not to be involved in the D-proline reductase reaction. The letter "U" indicates the presence of selenocysteine. In Clostridium botulinum A Hall, a part of the cluster is duplicated.Click here for filePresence of characteristic enzymes of the glycine synthase (Gcv proteins)/glycine reductase (Grd proteins) and Wood-Ljungdahl (CODH proteins) pathway in microbial genomes. Complete and WGS microbial genomes  were scanned for some selected characteristic orthologous genes coding for carbon monoxide dehydrogenase/acetyl-CoA synthetase (Wood-Ljungdahl pathway), glycine reductase (Stickland reaction), and the glycine synthase (gcv-system) using a blastx search with stringent criteria (40% of positive residues over at least 80% of the length of the reference protein). For each target genome, the presence/absence of each protein was summarized in a 1/0 vector. Those WGS microbial genomes which do not contain all genes of both pathways are omitted.Click here for file


Representing species-specific proteins and protein complexes in ontologies that are both human- and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes.http://pir.georgetown.edu/pro/.We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at PRO is a unique database resource for species-specific protein complexes. PRO facilitates robust annotation of variations in composition and function contexts for protein complexes within and between species. Logical and semantic access to related protein forms is critical for advancing bioinformatics approaches to representing, modeling, and reasoning about complex biological systems at the genomic and cellular level . The Prointeractions in that they are continuant entities, i.e. they endure or continue to exist through time. Interactions, in contrast, are occurrent entities, i.e. they occur in time through successive temporal phases. The explicit representation of protein complexes in PRO--defining each member of the complex at the level of its isoform, variant, or modified form--provides the ability to represent complex biological knowledge as it is emerging in the experimental research community in structures that are both human readable and accessible to algorithmic approaches.The PRO has three components informally referred to as ProForm, ProEvo, and ProComp . ProFormspecific classes of protein complexes, while GO, in most instances, represents the species-independent classes of protein complexes; within PRO, the latter are referred to by using GO identifiers. The UniProt Knowledgebase (UniProtKB) comment: Category = organism-complex. Entities of this type are disposed to have the enzymatic activity described by EC:6.4.1.4.synonym: "beta-methylcrotonyl-CoA carboxylase (mouse)" EXACT synonym: "MCC (mouse)" EXACT is_a: GO:0002169! 3-methylcrotonyl-CoA carboxylase complex, mitochondrialhas_part PR:000025354 {cardinality = "1"} ! methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial (mouse)relationship: has_part PR:000025357 {cardinality = "1"} ! methylcrotonoyl-CoA carboxylase beta chain, mitochondrial (mouse)relationship: relationship: only_in_taxon taxon:10090 ! Mus musculusSerine palmitoyltransferase  catalyzes the key reaction in the biosynthesis of sphingolipids. In many eukaryotic species, this enzyme is a heterodimer consisting of two subunits, SPTLC1 and SPTLC2. Recently, it was shown that in human cells, SPTLC1 and SPTLC2 form a complex with a third subunit, SPTLC3, with a resulting molecular mass of 480 kDa . SPTLC1 A serine palmitoyltransferase complex is also found in gram-negative sphingolipid-containing bacteria. Unusually, the outer membranes of these bacteria contain glycosphingolipid (GSL) instead of lipopolysaccharide, and SPT catalyzes the first step of the GSL biosynthetic pathway in these organisms. But, as opposed to the human SPT complex, bacterial SPT complex is homodimeric -21. In shas_part relation to the corresponding classes of protein components. The functional human complex classes have an is_a relationship to the serine C-palmitoyltransferase complex class in GO (GO:0017059). The complex core has an is_a relationship to GO:0043234 (protein complex) as there is currently not a more specific complex class in GO.The representation of SPT complexes in PRO shown below and illustrated in Figure [Term]id: PR:000026144name: serine palmitoyltransferase complex core 1 (human)def: "A serine palmitoyltransferase complex that is heterodimeric consisting of one subunit of serine palmitoyltransferase 1 and serine palmitoyltransferase 2. These components are encoded in the genome of human." [PRO:CNA]is_a: GO:0043234 ! protein complexrelationship: has_part PR:000026141 {cardinality = "1"} ! serine palmitoyltransferase 1 (human)relationship: has_part PR:000026142 {cardinality = "1"} ! serine palmitoyltransferase 2 (human)relationship: only_in_taxon taxon:9606 ! Homo sapiens[Term]id: PR:000026155name: serine palmitoyltransferase complex A (human)def: "A serine palmitoyltransferase complex consisting of an unknown combination of the serinepalmitoyltransferase subunits 1-3. The stoichiometry is a tetramer composed of the serinepalmitoyltransferase core complexes 1 and/or 2." comment: Category = organism-complex. Entities of this type are disposed to have the enzymatic activity described by EC:2.3.1.50.is_a: GO:0017059 ! serine C-palmitoyltransferase complexrelationship: has_part PR:000026141 {cardinality = "4"}! serine palmitoyltransferase 1 (human)relationship: has_part PR:000026142 ! serine palmitoyltransferase 2 (human)relationship: has_part PR:000026143 ! serine palmitoyltransferase 3 (human)relationship: only_in_taxon taxon:9606 ! Homo sapiensThe protein complex stanza for the bacterial SPT complex PR:000026169) is shown below. The bacterial and human complexes differ in composition def: "A homodimeric serine palmitoyltransferase complex that is composed of bacterial serine palmitoyltransferase encoded in the genome of Sphingobacterium multivorum." comment: Category = organism-complex. Entities of this type are disposed to have the enzymatic activity described by EC:2.3.1.50.is_a: GO:0002179 ! homodimeric serine palmitoyltransferase complexrelationship: has_part PR:000026168 {cardinality = "2"} ! bacterial serine palmitoyltransferase isoform 1 (Sphingobacterium multivorum)relationship: only_in_taxon taxon:28454 ! Sphingobacterium multivorum+ as a cofactor in the oxidative decarboxylation of isocitrate and one utilizes NAD+. The NAD+-dependent IDH is a mitochondrial protein complex in the citric acid cycle; it consists of three subunits , each of which is encoded by a single gene. The mouse alpha subunit gene encodes two different protein isoforms by alternative splicing. ProComp can distinguish between complexes that differ in the isoform of one of the constituents. As illustrated below (in bold), the protein complex stanzas from PRO describe two types of IDH complexes that differ only in the type of isoform of the alpha subunit. Both classes of isoform-specific protein complexes shown below (PR:000026072 and PR:000026073) are subclasses of the mouse-specific protein complex class (PR:000026071) which, in turn, is a subclass of the species-independent complex class defined in GO (GO:0005962).There are three types of isocitrate dehydrogenases (IDHs) in mammals; two IDHs utilize NADP[Term]id: PR:000026071name: mitochondrial isocitrate dehydrogenase complex (NAD+) (mouse)definition: A mitochondrial isocitrate dehydrogenase complex using NAD+ whose components are encoded in the genome of mouse [PRO:hjd]is_a:GO:0005962 ! mitochondrial isocitrate dehydrogenase complex (NAD+)relationship: has_part PR:000025358 ! isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial (mouse)relationship: has_part PR:000025359 ! isocitrate dehydrogenase [NAD] subunit beta, mitochondrial (mouse)relationship: has_part PR:000025360 ! isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial (mouse)relationship: only_in_taxon taxon:10090! Mus musculus[Term]id: PR:000026072name: mitochondrial isocitrate dehydrogenase complex (NAD+) A (mouse)def: A mitochondrial isocitrate dehydrogenase complex using NAD+ whose components are encoded in the genome of mouse containing isoform 1 of subunit alpha" [PRO:hjd]is_a:PR: 000026071! mitochondrial isocitrate dehydrogenase complex (NAD+) (mouse)relationship: has_part PR:000025355 ! isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial isoform 1 (mouse)relationship: has_part PR:000025359 ! isocitrate dehydrogenase [NAD] subunit beta, mitochondrial (mouse)relationship: has_part PR:000025360 ! isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial (mouse)relationship: only_in_taxon taxon:10090 ! Mus musculus[Term]id: PR:000026073name:mitochondrial isocitrate dehydrogenase complex (NAD+) B (mouse)def: A mitochondrial isocitrate dehydrogenase complex using NAD+ whose components are encoded in the genome of mouse containing isoform 2 of subunit alpha" [PRO:hjd]is_a:PR: 000026071! mitochondrial isocitrate dehydrogenase complex (NAD+) (mouse)relationship: has_part PR:000025356 ! isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial isoform 2 (mouse)relationship: has_part PR:000025359 ! isocitrate dehydrogenase [NAD] subunit beta, mitochondrial (mouse)relationship: has_part PR:000025360 ! isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial (mouse)relationship: only_in_taxon taxon:10090! Mus musculushas_part statements that refer to "either-or" classes of proteins are used to represent uncertainty in a compact form with no loss of information. The union_of statement (highlighted by bold text in the stanza below) indicates which genes could code for a particular protein component. The union_of tag appears in the appropriate protein component stanzas, not in the protein complex stanza. These tags are shown below (as comments) for illustration purposes only.Cytochrome c oxidase, also known as Complex IV (EC 1.9.3.1), is a large transmembrane protein complex located in the inner mitochondrial membrane. Its function is sequestration of free radicals, coupled to the transport of protons across the inner mitochondrial membrane, which creates the proton gradient used by mitochondrial ATP synthase during ATP production. Although the function of Complex IV is well understood, the exact composition of the complex is not certain due to apparent genetic redundancy. Complex IV is composed of 13 polypeptides: three encoded in the mitochondrial genome, and ten encoded in the nuclear genome . The unc[Term]id: PR:000026295name: respiratory chain complex IV (mouse)def: A mitochondrial respiratory chain complex IV whose components are encoded in the genome of mouse. is_a: GO:0005751 ! mitochondrial respiratory chain complex IVrelationship: has_part PR:000025364 {cardinality = "1"} ! cytochrome oxidase subunit 1, mitochondrial (mouse)relationship: has_part PR:000025366 {cardinality = "1"} ! cytochrome oxidase subunit 2, mitochondrial (mouse)relationship: has_part PR:000025367 {cardinality = "1"} ! cytochrome oxidase subunit 3, mitochondrial (mouse)relationship: has_part PR:000026286 complex IV component 4 (mouse)! union_of: PR:000025368 ! Cox4i1! union_of: PR:000025369 ! Cox4i2relationship: has_part PR:000026294 {cardinality = "1"} ! cytochrome c oxidase subunit 5A, mitochondrial, transit peptide removed form (mouse)relationship: has_part PR:000025371 {cardinality = "1"} ! cytochrome c oxidase subunit 5B (mouse)relationship: has_part PR:000026287 {cardinality = "1"} ! complex IV component 6a (mouse)! union_of: PR:000025372 ! Cox6a1! union_of: PR:000025373 ! Cox6a2relationship: has_part PR:000026288 {cardinality = "1"} ! complex IV component 6b (mouse)! union_of: PR:000025374 ! Cox6b1! union_of: PR:000025375 ! Cox6b2relationship: has_part PR:000025376 {cardinality = "1"} ! cytochrome c oxidase subunit 6C (mouse)relationship: has_part PR:000026289 {cardinality = "1"} ! complex IV component 7A (mouse)! union_of: PR:000025377 ! Cox7a1! union_of: PR:000025378 ! Cox7a2! union_of: PR:000025379 ! Cox7a2lrelationship: has_part PR:000027496 {cardinality = "1"} ! complex IV component 7B (mouse)! union of PR:000027491 ! Cox7b! union of PR:000027489 ! Cox7b2relationship: has_part PR:000025383 {cardinality = "1"} ! cytochrome c oxidase subunit 7C, mitochondrial (mouse)relationship: has_part PR:000026290 {cardinality = "1"} ! complex IV component 8 (mouse)! union_of: PR:000025380 ! Cox8a! union_of: PR:000025381 ! Cox8b! union_of: PR:000025382 ! Cox8crelationship: only_in_taxon taxon:10090 ! Mus musculusWhile not illustrated in the use cases above, many PRO complexes have species-specific protein types of modified isoforms. A few examples are: (i) PR:000025933 smad2-smad4 protein complex 1 (human), which contains active phosphorylated form of smad2 (MAD homolog 2), (ii) PR:000026035 myc-max acetylated complex (human), where both myc (myelocytomatosis oncogene) and max (Max protein) are acetylated, and (iii) PR:000027084 IRF3-P:IRF7-P complex (human), which contains the active phosphorylated forms of IRF3 (interferon regulatory factor 3) and IRF7 (interferon regulatory factor 7).http://purl.obolibrary.org/obo/PR_000026144 is shown in Figure The web display of the ProComp stanza for the human SPT complex described above in Use Case 2 http://www.geneontology.org/GO.format.gaf-1_0.shtml. The PAF format consists of a standard header and 20 tab-delimited columns .The ProComp ontology provides species-specific, accessioned protein complex entities that support robust, context-specific annotation of protein biology . ComprehMCC; EC 6.4.1.4). Knowledge that mutations in human genes that encode the protein components of the MCC complex: MCCC1  and MCCC2 (subunit beta), cause methylcrotonylglycinuria type I (OMIM #210200) and methylcrotonylglycinuria type II (OMIM #210210), respectively, are represented in the PAF file  subunit is required for their proper functioning ,28. In mhttp://obi-ontology.org/) group on the development and application of an evidence code ontology to describe the evidence used to support protein complex assertions in ProComp, and with developers of the curation tools to enable capturing such evidence with appropriate granularity. Second, our current work records only protein monomer components of complexes facilitated by an interface that makes selection of the monomers and their identifiers manageable. However, as we note, protein complexes (such as Complex IV in Use Case 4) are known to have lipid, heme, and other co-factors as components. Extensions to our curation tools will be developed in order to select and include such components, identifiers for which are provided by, e.g., the Chemical Entities of Biological Interest (CheBI) ontology [has_agent and is_agent_in relations in our annotations to connect, provisionally, proteins with representation of sequence variation from the Sequence Ontology. However this does not agree with the formal definition in which these relations connect processes with their participants [has_part to relate a protein complex to its components and uses cardinality restriction to represent stoichiometry. However, because has_part is a transitive relation, the ontology falls outside OWL2-DL making it not possible to use standard reasoners. Thus, we are evaluating the possibility of replacing has_part with a new relation that is a non-transitive sub-property of the has_part relation. Finally, we will implement closure axioms that would more clearly define the number and kind of complex components. For example, our representation of Complex IV allows that there might be additional protein components because of the open world assumption. A closure axiom would assert that exactly 13 of the components of this complex are proteins, while still allowing that there might be other kinds of components.Improvements in the PRO ontology and annotation have come to light by our work on the use cases described in this manuscript. We outline a number of known issues that serve as the basis for future work. First, while the assertions in stanzas within PRO are intended to be backed by evidence, the distinction between experimental and inferential evidence (both legitimate) is not yet captured clearly. This is especially true in cases where the evidence for composition and stochiometry for protein complexes is derived from orthologous proteins and complexes in other organisms. Usefully recording such information, as we recognize is important, was hampered by deficits in our curation tools that made it impossible to record evidence for individual relations or, more specifically, cardinality. We are working with the Ontology for Biomedical Investigations  or text . Searches can be restricted to specific modified forms , database, or membership in a complex. PRO entries can also be accessed via hypertext links on gene detail pages in the Mouse Genome Informatics (MGI) database and from MouseCyc, Reactome, and EcoCyc. PRO (Release 20) contains 168 complexes drawn from Reactome (human), MouseCyc (mouse), EcoCyc (E. coli) and direct submissions from collaborating research groups. OBO Edit, an open source ontology editing tool http://oboedit.org/[The Protein Ontology resource can be accessed on-line edit.org/, can be http://purl.obolibrary.org/obo/pr.owl).Existing conversion tools allow for OBO-formatted ontologies to be converted into Web ontology language (OWL) ,33. The The authors declare that they have no competing interests.CJB, HD, AE, AR and PD researched and created protein complex stanzas for mouse and human. DN CA, and AR validated the ontology stanza formats and created the appropriate records in the PRO database. NR built software infrastructure to facilitate semi-automated acquisition of protein complex data from contributing databases. All authors contributed to the development of the formalisms to represent the classes of protein complexes illustrated in this manuscript. All authors participated in the writing of the manuscript. All authors read and approved the manuscript.


The 7th author's correct name is: Diane Wallace Taylor.The correct author contributions are: Conceived and designed the experiments: KLS ALC RGFL RJIL PG MEM DWT SJR KCK. Performed the experiments: KLS ALC. Analyzed the data: KLS ALC. Contributed reagents/materials/analysis tools: RGFL DWT MEM SJR KCK. Wrote the paper: KLS ALC KCK. Constructive review of manuscript: DWT MEM SJR.


The CIGS NCs of approximately 17 nm in diameter were homogeneously blended with P3HT layer to form an active layer of a photovoltaic device. The blend ratios of CIGS NCs to P3HT, solvent effects on thin film morphologies, interface between P3HT/CIGS NCs and post-production annealing of devices were investigated, and the best performance of photovoltaic devices was measured under AM 1.5 simulated solar illumination (100 mW/cm2).This work presents the systematic studies of bulk hybrid heterojunction solar cells based on CuSe Photovoltaic (PV) devices, converting photon into electricity as an elegant and clean renewable energy, have attracted tremendous attentions on research and developments. Among emerging PV technologies, organic photovoltaic devices (OPV) composed of polymer matrices can be considered as promising third-generation solar cell due to its exceptional mechanical flexibility for versatile applications ,2. Moreo2-Phenyl-C61 butyric acid methyl ester; PCE: Power-conversion efficiency; PEDOT/PSS: Poly-poly(styrenesulfonate); XRD: Powder X-ray diffraction; FTIR: Fourier transform infrared spectroscopy; HRTEM: High-resolution transmission electron microscopy; PL: Photoluminescence; FWHM: Full width at half maximum; Jsc: Short-circuit current; Voc: Opened circuit voltage; FF: Fill factor; OLA: Oleylamine; PYR: Pyridine.CIGS: CuSeThe authors declare that they have no competing interests.YKL carried out the device fabrication and drafted the manuscript; SHC synthesized the CIGS nanocrystals; HFH provided useful solutions to the experimental issues and helped to revise the draft; HYT participated in the design of the study; YTY participated in the sequence alignment and helped to draft the manuscript; YLC carried out the TEM analysis, conceived the study, and organized the final version of the paper. All authors read and approved the final manuscript.


The author contributions provided in the HTML and PDF versions of the article contain author initials from a different paper. The following are the correct author contributions for this article:Conceived and designed the experiments: BZ YYH QY. Performed the experiments: BZ YYH QY SWZ YW YXC DRX. Analyzed the data: YYH QY SWZ YW YXC DRX. Contributed reagents/materials/analysis tools: YYH QY SWZ YW YXC DRX. Wrote the paper: YYH QY.


There was an error in the author contributions section of the article. A correct version of the section is available below.Conceived and designed the experiments: AC JD LY. Performed the experiments: AC. Analyzed the data: AC. Wrote the manuscript: AC JD LY.