Evolution of plant RNA polymerase IV/V genes: evidence of subneofunctionalization of duplicated NRPD2/NRPE2-like paralogs in Viola (Violaceae)

<p>Abstract</p> <p>Background</p> <p>DNA-dependent RNA polymerase IV and V (Pol IV and V) are multi-subunit enzymes occurring in plants. The origin of Pol V, specific to angiosperms, from Pol IV, which is present in all land plants, is linked to the duplication of the gene encoding the largest subunit and the subsequent subneofunctionalization of the two paralogs (<it>NRPD1 </it>and <it>NRPE1</it>). Additional duplication of the second-largest subunit, <it>NRPD2/NRPE2</it>, has happened independently in at least some eudicot lineages, but its paralogs are often subject to concerted evolution and gene death and little is known about their evolution nor their affinity with Pol IV and Pol V.</p> <p>Results</p> <p>We sequenced a ~1500 bp <it>NRPD2/E2</it>-like fragment from 18 <it>Viola </it>species, mostly paleopolyploids, and 6 non-<it>Viola </it>Violaceae species. Incongruence between the <it>NRPD2/E2</it>-like gene phylogeny and species phylogeny indicates a first duplication of <it>NRPD2 </it>relatively basally in Violaceae, with subsequent sorting of paralogs in the descendants, followed by a second duplication in the common ancestor of <it>Viola </it>and <it>Allexis</it>. In <it>Viola</it>, the mutation pattern suggested (sub-) neofunctionalization of the two <it>NRPD2/E2</it>-like paralogs, <it>NRPD2/E2-a </it>and <it>NRPD2/E2-b</it>. The <it>d</it>_<it>N</it>/<it>d</it>_{<it>S </it>}ratios indicated that a 54 bp region exerted strong positive selection for both paralogs immediately following duplication. This 54 bp region encodes a domain that is involved in the binding of the Nrpd2 subunit with other Pol IV/V subunits, and may be important for correct recognition of subunits specific to Pol IV and Pol V. Across all <it>Viola </it>taxa 73 <it>NRPD2/E2</it>-like sequences were obtained, of which 23 (32%) were putative pseudogenes - all occurring in polyploids. The <it>NRPD2 </it>duplication was conserved in all lineages except the diploid MELVIO clade, in which <it>NRPD2/E2-b </it>was lost, and its allopolyploid derivates from hybridization with the CHAM clade, section <it>Viola </it>and section <it>Melanium</it>, in which <it>NRPD2/E2-a </it>occurred in multiple copies while <it>NRPD2/E2-b </it>paralogs were either absent or pseudogenized.</p> <p>Conclusions</p> <p>Following the relatively recent split of Pol IV and Pol V, our data indicate that these two multi-subunit enzymes are still in the process of specialization and each acquiring fully subfunctionalized copies of their subunit genes. Even after specialization, the <it>NRPD2/E2</it>-like paralogs are prone to pseudogenization and gene conversion and <it>NRPD2 </it>and <it>NRPE2 </it>copy number is a highly dynamic process modulated by allopolyploidy and gene death.</p

The impact of the COVID-19 pandemic on cancer diagnosis based on pathology notifications : A comparison across the Nordic countries during 2020

The severity of the COVID-19 pandemic and subsequent mitigation strategies have varied across the Nordic countries. In a joint Nordic population-based effort, we compared patterns of new cancer cases and notifications between the Nordic countries during 2020. We used pathology notifications to cancer registries in Denmark, the Faroe Islands, Finland, Iceland, Norway and Sweden to determine monthly numbers of pathology notifications of malignant and in situ tumours from January to December 2020 compared to 2019 (2017-2019 for Iceland and the Faroe Islands). We compared new cancer cases per month based on unique individuals with pathology notifications. In April and May 2020, the numbers of new malignant cases declined in all Nordic countries, except the Faroe Islands, compared to previous year(s). The largest reduction was observed in Sweden (May: -31.2%, 95% CI -33.9, -28.3), followed by significant declines in Finland, Denmark and Norway, and a nonsignificant decline in Iceland. In Denmark, Norway, Sweden and Finland the reporting rates during the second half of 2020 rose to almost the same level as in 2019. However, in Sweden and Finland, the increase did not compensate for the spring decline (annual reduction -6.2% and -3.6%, respectively). Overall, similar patterns were observed for in situ tumours. The COVID-19 pandemic led to a decline in rates of new cancer cases in Sweden, Finland, Denmark and Norway, with the most pronounced reduction in Sweden. Possible explanations include the severity of the pandemic, temporary halting of screening activities and changes in healthcare seeking behaviour.Peer reviewe

U.S. Billion-ton Update: Biomass Supply for a Bioenergy and Bioproducts Industry

The Report, Biomass as Feedstock for a Bioenergy and Bioproducts Industry: The Technical Feasibility of a Billion-Ton Annual Supply (generally referred to as the Billion-Ton Study or 2005 BTS), was an estimate of “potential” biomass within the contiguous United States based on numerous assumptions about current and future inventory and production capacity, availability, and technology. In the 2005 BTS, a strategic analysis was undertaken to determine if U.S. agriculture and forest resources have the capability to potentially produce at least one billion dry tons of biomass annually, in a sustainable manner—enough to displace approximately 30% of the country’s present petroleum consumption. To ensure reasonable confidence in the study results, an effort was made to use relatively conservative assumptions. However, for both agriculture and forestry, the resource potential was not restricted by price. That is, all identified biomass was potentially available, even though some potential feedstock would more than likely be too expensive to actually be economically available. In addition to updating the 2005 study, this report attempts to address a number of its shortcoming

Meeting report: discussions and preliminary findings on extracellular RNA measurement methods from laboratories in the NIH Extracellular RNA Communication Consortium

Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA-containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in-person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field

Social hållbarhet : En undersökning av de möjligheter och utmaningar som leverantörer av varor till bygg- och fastighetsbranschen står inför i arbetet med social hållbarhet

Social sustainability is a concept in which relevance is prevailing within the construction industry. In 2016 there shall be a new EU constitution that shall require mandatory sustainability reporting for companies and organisations and new regulations that precedes the current regulation on working environments. The purpose of the regulations is to promote a virtuous working environment and avert the risk of illness due to organisational and social conditions within the work environment. As a consequence, companies need to increase their socially sustainable requirements where primary focus has been on economic sustainability and environmental sustainability. Byggvarubedömningen are a non-profit association that through assessments examine products used within construction practices and the real estate industry with a focus on chemical content of materials and their adverse effects on the environment. Byggvarubedömningen are to implement social criteria’s within their assessments on behalf of their investors which consists of builders, real estate companies and various other participants within the construction industry. The purpose of this report is to investigate how suppliers of products in the construction and real estate industry, which are members of Byggvarubedömningen, work with social sustainability in the current situation. This report highlights social sustainability aspects that align with basic human rights. The goal of this report is to observe difficulties and challenges suppliers of products in the construction and real estate industry faces within social sustainability work and with requirements defined in the supply chain. In conclusion the report shall provide a basis for further studies in the field of the construction industry since there is a current shortage in similar surveys regarding social sustainability. Information has been collected through semi-structured interviews from companies that supply products to the construction and real estate industry to increase a greater understanding of the significance of social sustainability work for the industry. Literature studies about the concept social sustainability and underlying reasons for the introduction of social criteria’s have been made to collect more information about why the subject is relevant today. The results of the survey show that suppliers' work with social sustainability are of varying degree and it is possible to discern clear difficulties, but also benefits of developing a work on social sustainability. The survey also shows that all companies participating in the study have a positive attitude towards having their products being assessed in terms of social sustainability in the future. Major companies expressed that it would be difficult to track their products processes all the way to the extraction of raw materials, whilst the smaller companies informed that it would not be as onerous. &amp; Further studies with more extensive interviews should be conducted to generate a more detailed comparison between product groups and also generate a broader understanding of the situation in the construction industry today

Early intervention : A study of special need teachers’ training methods for children at risk of early reading difficulties

The aim of the study was to investigate how schools identify primary school children with early reading difficulties and what kind of early intervention special education teachers use to support these students. This study also investigates early interventions that special education teachers con­sider to be effective. Ten special education teachers were interviewed regarding early intervention. The result showed that the schools use several screenings from within the age group of 6-9 year olds. The special education teachers can at an early stage identify primary school children with difficulties in their reading and they use a range of different interventions. It is found in this study that an intense period of individual tuition is the intervention that most special education teachers think leads to good results for primary school children with difficulties in their early reading. That finding is also supported in previous research. It is clear that special education teachers and special education teachers need more time for early intervention. The teachers' opportunities for doing this should be reviewed

Monoclonal antibodies and cytokines for therapy of patients with advanced colorectal carcinoma : a clinical and immunological study

There is a great need for developing and improving treatment alternatives in colorectal carcinoma (CRC). The tumour associated antigen (TAA) GA733/CO17-1A is expressed by more than 90% of all CRCs, on the majority of both primary and metastatic CRC cells. This antigen can be utilised as a target structure for passive as well as active immunotherapy. Mouse MAb17-1A has been produced against this antigen and shown to induce clinical responses in patients. The clinical effect might be improved by adding cytokines, which might augment immune effector functions utilised by MAb. In this study we have analysed clinical and immunological in vivo functions of patients with advanced CRC treated with a combination of the MAb 17-1A, GM-CSF and IL-2. The first analysis concerned the clinical effect of IL-2 alone, without MAb. Low doses of IL-2 were given in combination with IFN-[alpha] to 15 patients with metastatic CRC. No patient showed a major response. Six patients had a stable disease. In the subsequent study the clinical response and immune effector functions were analysed when IL-2 was added to a combination of MAb/GM-CSF, the so far best treatment regimen. 20 patients with metastatic CRC were included in this study. One patient obtained a partial remission and 2 patients stable disease. The therapeutic effect did not seem to be improved when IL-2 was added to MAb/GM-CSF therapy, which was in contrast to expectations from preclinical data. There might be a tendency to a lower response rate and impaired survival for MAb/GM-CSF/IL-2 treated patients as compared to patients treated with MAb/GM-CSF. When analysing different in vivo effects a suppressed human anti-mouse (HAMA) and antiidiotypic antibody (Ab2) response as well as an impaired antibody dependent cellular cytotoxicity (ADCC) was observed. There was also a tendency to reduction of the frequency and severity of allergic reactions in MAb/GM-CSF/IL-2 treated patients as compared to MAb/GM-CSF treated patients. A highly significant increase in neopterin and sIL-2R serum concentration was noted in the MAb/GM-CSF/IL-2 treatment group as compared to the MAb/GM-CSF group. These data may indicate induction of immune suppression when IL-2 was added to MAb/GM-CSF. Increases in neopterin and sIL-2R concentrations may reflect activation of cellular immune responses mainly involving macrophages and lymphocytes. High concentrations of these serum markers might indicate generation of oxidative stress. Induction of cytokine antibodies has earlier been shown to hamper the clinical responses of biotherapeutic agents. This study revealed differences in immunogenicity between different preparations of GM-CSF and that neutralising anti-GM-CSF antibodies had biological implications. Furthermore, it was obvious that non-neutralising IL-2 antibodies had a profound impact on IL-2 pharmacokinetics. In IL-2 antibody positive patients a decreased cytokine induced increment of leukocytes was observed. As the use of therapeutic cytokines is increasing it seems to be of particular importance to establish the optimal biological doses of different cytokines as well as to carefully evaluate the induction of cytokine antibodies to be able to use cytokines rationally in the clinic

Circumpolar phylogeography of the northern pike (Esox lucius) and its relationship to the Amur pike (E. reichertii)

Background: Freshwater fishes of the genus Esox are found throughout the Holarctic region. The northern pike (E. lucius) has a circumpolar distribution whereas the assumed sister species the Amur pike (E. reichertii) is only found in the Amur region. The genetic structure and post-glacial dispersal of these species are not well known. Here, we use sequence variation at two mitochondrial DNA regions (cytb and D-loop) to investigate the phylogeography, infer location of glacial refugia and investigate the time of divergence and potential demographic expansion of the various clades detected. Results: The two species did not share haplotypes implying long-term isolation with no gene flow, and divergence of the taxa were estimated at 4.55 Myr. The northern pike mtDNA haplotypes revealed three main lineages. One of the northern pike mtDNA lineages was found throughout the entire Holarctic region suggesting transcontinental dispersal from a single refugium. The three lineages exhibited a star phylogeny, indicating population expansion following isolation in separate glacial refugia. Estimated time of divergence of these lineages was 0.18 ¿ 0.26 Myr. Conclusions: The precise location of the glacial refugia is uncertain, but our data suggests an Asian origin. The expansion of the circumpolar lineage is estimated to be around the end of the second glacial, implying that the current distribution is due to a recent recolonization from an east-Asian refugium. All three northern pike mtDNA lineages occurred sympatrically in Europe, possibly due to secondary contact. Two of the lineages probably originated from different European refugia, one in the Danube-region and one in Western Europe, the latter seems to be the primary source for recolonization of northern Europe