Cdc14b regulates mammalian RNA polymerase II and represses cell cycle transcription

Article number: 189 (2011)[EN]Cdc14 is an essential phosphatase in yeast but its role in the mammalian cell cycle remains obscure. We report here that Cdc14b-knockout cells display unscheduled induction of multiple cell cycle regulators resulting in early entry into DNA replication and mitosis from quiescence. Cdc14b dephosphorylates Ser5 at the C-terminal domain (CTD) of RNA polymerase II, a major substrate of cyclin-dependent kinases. Lack of Cdc14b results in increased CTD-Ser5 phosphorylation, epigenetic modifications that mark active chromatin, and transcriptional induction of cell cycle regulators. These data suggest a function for mammalian Cdc14 phosphatases in the control of transcription during the cell cycle

On natural metalinguistic abilities in aphasia: a preliminary study

Natural metalinguistic abilities, which are put into play without explicit instructions, constitute the cognitive basis for a 'reflexive' use of language, a particular manifestation of the executive function when applied to language and verbal behaviour. This reflexive use entails a specific attentional activity by speakers and hearers with regard to linguistic outputs, and an intentional experience-based control over the language use. Putting into play natural metalinguistic abilities can be considered a significant factor for explaining different kinds of adaptive processes. Our results permit us to conclude that an impairment of metalinguistic abilities is involved in aphasia to different degrees. Moreover, the examination of preserved metalinguistic abilities provides an alternative way for assessing the degree of severity of impaired communicative behaviour by people with aphasia. Our procedure, presumably, will also be useful for suggesting new factors when designing therapeutic programmes

Scalability and cost-effectiveness analysis of whole genome-wide association studies on Google Cloud Platform and Amazon Web Services

Objective Advancements in human genomics have generated a surge of available data, fueling the growth and accessibility of databases for more comprehensive, in-depth genetic studies. Methods We provide a straightforward and innovative methodology to optimize cloud configuration in order to conduct genome-wide association studies. We utilized Spark clusters on both Google Cloud Platform and Amazon Web Services, as well as Hail (http://doi.org/10.5281/zenodo.2646680) for analysis and exploration of genomic variants dataset. Results Comparative evaluation of numerous cloud-based cluster configurations demonstrate a successful and unprecedented compromise between speed and cost for performing genome-wide association studies on 4 distinct whole-genome sequencing datasets. Results are consistent across the 2 cloud providers and could be highly useful for accelerating research in genetics. Conclusions We present a timely piece for one of the most frequently asked questions when moving to the cloud: what is the trade-off between speed and cost

Neoplasms and novel gammaherpesviruses in critically endangered captive European minks (Mustela lutreola)

13 Päg. Centro de Investigación en Sanidad Animal (CISA)The European mink (Mustela lutreola) is a riparian mustelid, considered one of the most endangered carnivores in the world. Alpha, beta and gammaherpesviruses described in mustelids have been occasionally associated with different pathological processes. However, there is no information about the herpesviruses species infecting European minks. In this study, 141 samples of swabs (oral, conjunctival, anal), faeces and tissues from 23 animals were analysed for herpesvirus (HV) using a pan-HV-PCR assay. Two different, potentially novel, gammaherpesvirus species were identified in 12 samples from four animals (17.3%), and tentatively named Mustelid gammaherpesvirus-2 (MUGHV-2) and MuGHV-3. Gross examination was performed on dead minks (n = 11), while histopathology was performed using available samples from HV-positive individuals (n = 2), identifying several neoplasms, including B-cell lymphoma (identified by immunohistochemistry) with intralesional syncytia and intranuclear inclusion bodies characteristic of HV (n = 1), pulmonary adenocarcinoma (n = 1), and biliary (n = 1) and preputial (n = 1) cystadenomas, as well as other lesions (e.g., axonal vacuolar degeneration [n = 2] and neuritis [n = 1]). Viral particles, consistent with HVs, were observed by electron microscopy in the mink with neural lymphoma and inclusion bodies. This is the first description of neoplasms and concurrent gammaherpesvirus infection in European minks. The pathological, ultrastructural and PCR findings (MuGHV-2) in the European mink with lymphoma strongly suggest a potential role for this novel gammaherpesvirus in its pathogenesis, as it has been reported in other HV-infected species with lymphoma. The occurrence of neural lymphoma with intralesional syncytia and herpesviral inclusions is, however, unique among mammals. Further research is warranted to elucidate the potential oncogenic properties of gammaherpesviruses in European mink and their epidemiology in the wild population.Innovation Initiative Grant (IIG) of the Edinburgh Fund (University of Edinburgh); Norwegian University of Life Sciences; Generalitat de Catalunya; São Paulo Research Foundation, Grant/Award Number: 2018/20956-08 and 2018/25069-7; University of EdinburghPeer reviewe

Involvement of loops 2 and 3 of alpha-sarcin on its ribotoxic activity

Ribotoxins are a family of fungal ribosome-inactivating proteins displaying highly specific ribonucleolytic activity against the sarcin/ricin loop (SRL) of the larger rRNA, with a-sarcin as its best-characterized member. Their toxicity arises from the combination of this activity with their ability to cross cell membranes. The involvement of a-sarcin's loops 2 and 3 in SRL and ribosomal proteins recognition, as well as in the ribotoxin-lipid interactions involving cell penetration, has been suggested some time ago. In the work presented now different mutants have been prepared in order to study the role of these loops in their ribonucleolytic and lipid-interacting properties. The results obtained confirm that loop 3 residues Lys 111, 112, and 114 are key actors of the specific recognition of the SRL. In addition, it is also shown that Lys 114 and Tyr 48 conform a network of interactions which is essential for the catalysis. Lipid-interaction studies show that this Lys-rich region is indeed involved in the phospholipids recognition needed to cross cell membranes. Loop 2 is shown to be responsible for the conformational change which exposes the region establishing hydrophobic interactions with the membrane inner leaflets and eases penetration of ribotoxins target cells

In vivo testing of novel vaccine prototypes against Actinobacillus pleuropneumoniae

Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is a Gram-negative bacterium that represents the main cause of porcine pleuropneumonia in pigs, causing significant economic losses to the livestock industry worldwide. A. pleuropneumoniae, as the majority of Gram-negative bacteria, excrete vesicles from its outer membrane (OM), accordingly defined as outer membrane vesicles (OMVs). Thanks to their antigenic similarity to the OM, OMVs have emerged as a promising tool in vaccinology. In this study we describe the in vivo testing of several vaccine prototypes for the prevention of infection by all known A. pleuropneumoniae serotypes. Previously identified vaccine candidates, the recombinant proteins ApfA and VacJ, administered individually or in various combinations with the OMVs, were employed as vaccination strategies. Our data show that the addition of the OMVs in the vaccine formulations significantly increased the specific IgG titer against both ApfA and VacJ in the immunized animals, confirming the previously postulated potential of the OMVs as adjuvant. Unfortunately, the antibody response raised did not translate into an effective protection against A. pleuropneumoniae infection, as none of the immunized groups following challenge showed a significantly lower degree of lesions than the controls. Interestingly, quite the opposite was true, as the animals with the highest IgG titers were also the ones bearing the most extensive lesions in their lungs. These results shed new light on A. pleuropneumoniae pathogenicity, suggesting that antibody-mediated cytotoxicity from the host immune response may play a central role in the development of the lesions typically associated with A. pleuropneumoniae infections

Alternative polyadenylation and salicylic acid modulate root responses to low nitrogen availability

Nitrogen (N) is probably the most important macronutrient and its scarcity limits plant growth, development and fitness. N starvation response has been largely studied by transcriptomic analyses, but little is known about the role of alternative polyadenylation (APA) in such response. In this work, we show that N starvation modifies poly(A) usage in a large number of transcripts, some of them mediated by FIP1, a component of the polyadenylation machinery. Interestingly, the number of mRNAs isoforms with poly(A) tags located in protein-coding regions or 5 '-UTRs significantly increases in response to N starvation. The set of genes affected by APA in response to N deficiency is enriched in N-metabolism, oxidation-reduction processes, response to stresses, and hormone responses, among others. A hormone profile analysis shows that the levels of salicylic acid (SA), a phytohormone that reduces nitrate accumulation and root growth, increase significantly upon N starvation. Meta-analyses of APA-affected and fip1-2-deregulated genes indicate a connection between the nitrogen starvation response and salicylic acid (SA) signaling. Genetic analyses show that SA may be important for preventing the overgrowth of the root system in low N environments. This work provides new insights on how plants interconnect different pathways, such as defense-related hormonal signaling and the regulation of genomic information by APA, to fine-tune the response to low N availability

Dilemas e desafios da função docente na sociedade atual: os sentidos da mudança

A abordagem propõe a constatação das exigências de mudança na atualidade, decorrentes do quadro complexo em que se dá a educação escolar hoje para pensar os rumos da atuação/formação do professor. Procurou-se analisar as questões presentes nas tensões vividas pelos docentes no processo pedagógico (curricular), analisando os reflexos do pensamento moderno e pós-moderno na trajetória docente. Em função dessa proposta, são apresentados resultados da investigação desenvolvida com alunos(as) da disciplina de Currículos e Programas do Curso de Pedagogia e posteriormente aprofundada em Projeto de Pesquisa (Prolicen-UFPR) no ano de 2001. Os pesquisadores investigaram professores de escolas públicas de Curitiba e região metropolitana. Buscou-se a leitura de significados, necessidades e opções presentes na condução e moldagem das práticas docentes na atualidade, considerando o conceito de habitus de BOURDIEU e as possibilidades de análise abertas por SACRISTÁN, GIROUX e GRAMSCI. Procurou-se desenredar a função docente da profusão de exigências que lhe são postas hoje, numa contribuição ao redirecionamento das propostas prescritivas de mudança e, sobretudo, de formação do professor

A proposal for a workable analysis of Energy Return on Investment (EROI) in agroecosystems. Part I: Analytical approach

This paper presents a workable approach to the energy analysis of past and present agroecosystems aimed to contribute to their sustainability assessment. This analysis sees the agroecosystem as a set of energy loops between nature and society, and adopts a farm-operator standpoint at landscape level that involves setting specific system boundaries. This in turn entails a specific form to account for energy outputs as well as inputs. According to this conceptual approach, a clear distinction between Unharvested Phytomass, Land Produce and Final Produce is established, and also a sharp divide is adopted between the energy content of internal flows of Biomass Reused and external Societal Inputs when accounting for the amount of Total Inputs Consumed . Treating the conversion of solar radiation into local biomass as a gift of nature, enthalpy values of energy carriers are accounted for net Final Produce going outside as well as for Biomass Reused or Unharvested Phytomass , given that all these flows are evaluated from inside the agroecosystem. On the other hand, the external energy carriers are accounted for as embodied values by adding up direct and indirect energy carriers required to produce or deliver these Societal Inputs to the agroecosystem. The human Labour performed by the farm operators is treated as a special case of external input. It is accounted for the fraction of their energy intake devoted to perform agricultural work, by only using enthalpy or adding transport embodied values depending on the local or external origin of ingredients of the food basket. Following this line of reasoning we propose the definition of two different sets of agroecosystem’s Energy Returns On Energy Inputs (EROIs), depending on whether we use as numerator the Final Produce or the total phytomass harvested and unharvested included in the actual Net Primary Production. By comparing Final EROI with NPP act EROI we can obtain a proxy useful to assess whether the different paths taken by the energy throughputs may undermine or not biodiversity and soil fertility in agroecosystems. Then, by alternatively including or excluding Biomass Reused and External Inputs in the denominator, we split Final EROI into their respective energy returns to either internal or external inputs. This leads to a four interrelated EROIs whose meanings, shortcomings or ambiguities are examined respectively, in order to combine them all to draw the sociometabolic energy profiles of different sorts of agroecosystems along the socio-ecological transitions from traditional organic to industrial farm systems. The conceptual and quantitative relationships between the internal and external returns of Final EROI provide a method to decompose both dimensions in a way that clarifies their respective roles when comparing different agroecosystems, and reveals their capacity for increasing energy yields. This decomposition analysis also facilitates graphing their changing energy profiles through socio-ecological transitions along history. Finally, we suggest other related or derived indicators that can be useful for different purposes. With the bookkeeping proposed the energy analysis of farm systems is widened so as to highlight the role played by the biomass unharvested or internally reused in keeping the ecological services that biodiversity and soil fertility provide. This may also allow to test in agro-forest mosaics the Intermediate Disturbance Hypothesis long debated in ecology, by linking our energy analysis with landscape ecology metrics.Peer ReviewedPostprint (published version