Modeling the economic impact for Chile of an import ban on genetically modified maize.

We estimate producer and consumer surplus changes due to a possible GM maize import ban in Chile, which produces only non-GM grains for internal use. Without foreign non-GM sources, the ban's effect on domestic maize prices would be so significant as to induce Chile to switch from net exporter to net importer of animal products. Fixed factor owners in farm production would benefit significantly, although non-GM maize imports would moderate gains. Total social welfare measures would decline considerably, requiring large offsetting noneconomic benefits for a ban's political viability. Without non-GM imports, internal maize prices would likely eliminate domestic animal product industries; with possible imports, industries and final consumers would suffer, but much less. Currently, the country is a net importer of grain and a net exporter of pork and poultry, and so most welfare losses on the demand side of the market for maize would be in terms of the economic rents generated by the pork and poultry sectors. International competition would protect final consumers to the extent that animal product imports based on GM feed were permitted.

The peroxisome protein translocation machinery is developmentally regulated in the fungus Podospora anserina.

IMPORTANCE: Sexual reproduction allows eukaryotic organisms to produce genetically diverse progeny. This process relies on meiosis, a reductional division that enables ploidy maintenance and genetic recombination. Meiotic differentiation also involves the renewal of cell functioning to promote offspring rejuvenation. Research in the model fungus Podospora anserina has shown that this process involves a complex regulation of the function and dynamics of different organelles, including peroxisomes. These organelles are critical for meiosis induction and play further significant roles in meiotic development. Here we show that PEX13-a key constituent of the protein conduit through which the proteins defining peroxisome function reach into the organelle-is subject to a developmental regulation that almost certainly involves its selective ubiquitination-dependent removal and that modulates its abundance throughout meiotic development and at different sexual differentiation processes. Our results show that meiotic development involves a complex developmental regulation of the peroxisome protein translocation system.

The constraints of allotopic expression.

Allotopic expression is the functional transfer of an organellar gene to the nucleus, followed by synthesis of the gene product in the cytosol and import into the appropriate organellar sub compartment. Here, we focus on mitochondrial genes encoding OXPHOS subunits that were naturally transferred to the nucleus, and critically review experimental evidence that claim their allotopic expression. We emphasize aspects that may have been overlooked before, i.e., when modifying a mitochondrial gene for allotopic expression━besides adapting the codon usage and including sequences encoding mitochondrial targeting signals━three additional constraints should be considered: (i) the average apparent free energy of membrane insertion (µΔGapp) of the transmembrane stretches (TMS) in proteins earmarked for the inner mitochondrial membrane, (ii) the final, functional topology attained by each membrane-bound OXPHOS subunit; and (iii) the defined mechanism by which the protein translocator TIM23 sorts cytosol-synthesized precursors. The mechanistic constraints imposed by TIM23 dictate the operation of two pathways through which alpha-helices in TMS are sorted, that eventually determine the final topology of membrane proteins. We used the biological hydrophobicity scale to assign an average apparent free energy of membrane insertion (µΔGapp) and a "traffic light" color code to all TMS of OXPHOS membrane proteins, thereby predicting which are more likely to be internalized into mitochondria if allotopically produced. We propose that the design of proteins for allotopic expression must make allowance for µΔGapp maximization of highly hydrophobic TMS in polypeptides whose corresponding genes have not been transferred to the nucleus in some organisms.

Nuclear transport and subcellular localization of the dystrophin Dp71 and Dp40 isoforms in the PC12 cell line.

The shortest dystrophins, Dp71 and Dp40, are transcribed from the DMD gene through an internal promoter located in intron 62. These proteins are the main product of the DMD gene in the nervous system and have been involved in various functions related to cellular differentiation and proliferation as well as other cellular processes. Dp71 mRNA undergoes alternative splicing that results in different Dp71 protein isoforms. The subcellular localization of some of these isoforms in the PC12 cell line has been previously reported, and a differential subcellular distribution was observed, which suggests a particular role for each isoform. With the aim of obtaining information on their function, this study identified factors involved in the nuclear transport of Dp71 and Dp40 isoforms in the PC12 cell line. Cell cultures were treated with specific nuclear import/export inhibitors to determine the Dp71 isoform transport routes. The results showed that all isoforms of Dp71 and Dp40 included in the analysis have the ability to enter the cell nucleus through α/ß importin, and the main route of nuclear export for Dp71 isoforms is through the exportin CRM1, which is not the case for Dp40.

Risk assessment procedures in Argentina for the safe import, quarantine and release of biological control agents against pests.

The decision to import and release biological control agents is a national one that may involve various authorities. It will be overseen by the national plant protection organisation that implements the responsibilities described in the International Plant Protection Convention. This article provides an overview of the decision processes and roles of these authorities in Argentina. Argentina has a long history of coordination with the other Southern Cone nations on plant protection and other technical sanitary and phytosanitary matters associated with trade. This article reports on 25 years of evaluation, import and release of exotic biological control agents. Not a single import with a permit has faced rejection on the basis of phytosanitary requirements. This record highlights the region's commitment to integrated pest management approaches that rely on international shipments of live insects and other beneficial organisms.

La décision d'importer et d'autoriser des lâchers d'agents de lutte biologique est du ressort national, avec la participation de plusieurs autorités compétentes. Elle est supervisée par l'organisation nationale de protection des végétaux, qui est chargée d'exercer les responsabilités prévues au titre de la Convention internationale pour la protection des végétaux. Les auteurs donnent une vue d'ensemble des procédures décisionnelles et des fonctions respectives des autorités compétentes en Argentine. L'Argentine et les autres nations du Cône Sud ont une longue histoire commune de coordination de la protection des végétaux et d'autres questions sanitaires et phytosanitaires en lien avec les échanges internationaux. Les auteurs font le point sur 25 années d'évaluations, d'importations et de lâchers d'agents de lutte biologique exotiques dans le pays. Aucune importation ayant fait l'objet d'une autorisation préalable n'a été rejetée pour des motifs de conformité phytosanitaire. Ce constat souligne l'engagement fort de la région en faveur de méthodes intégrées de gestion des nuisibles reposant sur le transport international d'insectes vivants et d'autres organismes utiles.

La de importar y liberar al medio agentes de control biológico es una decisión de carácter nacional en la que pueden intervenir diversas autoridades y que supervisará la organización nacional de protección fitosanitaria encargada de trasladar a la práctica las responsabilidades enunciadas en la Convención Internacional de Protección Fitosanitaria. Los autores presentan a grandes líneas los procesos decisorios y las funciones de dichas autoridades en la Argentina, país que tiene una larga trayectoria de coordinación con otras naciones del Cono Sur en materia de protección de los vegetales y otras cuestiones técnicas de índole sanitaria y fitosanitaria ligadas al comercio. Los autores dan cuenta de 25 años de evaluación, importación y liberación al medio de agentes exóticos de control biológico. En ese tiempo, ni una sola importación provista de permiso ha sido denegada en aplicación de requisitos fitosanitarios. Semejante historial pone de relieve el compromiso de la región con fórmulas de gestión integrada de plagas que reposan en los envíos internacionales de insectos vivos y otros organismos beneficiosos.

Chlorpyrifos should be banned in agriculture and livestock production in Colombia

Chlorpyrifos (CPF) is a pesticide widely used in Colombia´s agriculture, including crops, farm animals and pets, despite it has been banned for use in the European Union and the United States. Studies demonstrate that even low blood levels of CPF -which do not inhibit blood acetylcholinesterase- can lead to child developmental and neurological disorders such as smaller head circumference and brain alterations, and psychomotor and cognitive deficits related to learning ability, attention and memory. In adults, CPF is an endocrine disruptor and breast carcinogen. High direct and indirect economic costs have been associated with CPF exposure. Not only farmers and their families -who have the highest exposures- but the general population consuming crops sprayed with CPF are also at risk. For these reasons CPF was recently banned by the European Union (2020) and the USA (2021). Pesticide regulation policies vary greatly depending on which and how scientific studies are used to assess health risks. Pesticide evaluations funded by the chemical industry should be rectified to avoid conflicts of interest. Furthermore, political alignment with the interests of the industry should not take precedence over independent scientific evidence. It is discouraging, to say the least, that until stricter health laws are passed in Colombia, CPFs and related pesticides will continue to be imported from those countries that have already banned them. Colombian scientists should raise their voice to challenge blind acceptance of profits over unintended consequences, and efforts to prevent pesticide´s abuse should be encouraged.

El clorpirifos (CPF) es un pesticida ampliamente utilizado en la agricultura de Colombia, incluidos cultivos, animales de granja y mascotas, a pesar de haber sido prohibido en la Unión Europea y Estados Unidos. Los estudios han demostrado que incluso niveles bajos de CPF en sangre -que no inhiben la acetilcolinesterasa sanguínea- pueden provocar trastornos neurológicos y del desarrollo infantil, como menor circunferencia de la cabeza y alteraciones cerebrales, y déficits psicomotores y cognitivos relacionados con la capacidad de aprendizaje, la atención y la memoria. En adultos, el CPF es un disruptor endocrino y causante de cáncer de mama. Altos costos económicos directos e indirectos se han asociado con la exposición al CPF. No solo los trabajadores agrícolas y sus familias, que están más expuestos, sino también la población en general que consume cultivos rociados con CPF también están en riesgo. Por estas razones el CPF fue prohibido recientemente por la Unión Europea (2020) y los EE. UU. (2021). Las políticas de regulación de plaguicidas varían mucho según los estudios científicos escogidos para evaluar los riesgos para la salud. Las evaluaciones de plaguicidas financiadas por la industria química deben rectificarse para evitar conflictos de interés. Además, ante la evidencia científica independiente no debería prevalecer la alineación política con los intereses de dicha industria. Es desalentador, por decir lo menos, que hasta que se aprueben leyes de salud más estrictas en Colombia se seguirán importando CPF y pesticidas relacionados desde aquellos países que ya los han prohibido. Los científicos colombianos deben alzar la voz para desafiar la aceptación ciega de ganancias por encima de las consecuencias no deseadas en salud pública, y se deben alentar los esfuerzos para prevenir el abuso de pesticidas.

Clorpirifós (CPF) é um pesticida registrado amplamente utilizado na agricultura colombiana, incluindo lavouras, animais de fazenda e animais de estimação, apesar de ter sido proibido na União Europeia e nos Estados Unidos. Estudos têm demonstrado que mesmo níveis baixos de CPF no sangue -que não inibem a acetilcolinesterase sanguínea-podem levar a distúrbios neurológicos e de desenvolvimento em crianças, como menor perímetro cefálico e alterações cerebrais, além de déficits psicomotores e cognitivos relacionados à capacidade de aprendizagem, atenção e memoria. Em adultos, o CPF é um desregulador endócrino e cancerígeno da mama. Altos custos econômicos diretos (devido ao tratamento) e indiretos (devido à perda de produtividade) têm sido associados à exposição ao CPF. Não apenas os trabalhadores agrícolas e suas famílias, que têm as maiores exposições, mas a população em geral que consome culturas pulverizadas com CPF também estão em risco. Por essas razões, o CPF foi recentemente proibido pela União Europeia (2020) e pelos EUA (2021). As políticas de regulamentação de pesticidas variam muito, dependendo de quais (e como) os estudos científicos são usados para avaliar os riscos à saúde. As avaliações de pesticidas financiadas pela indústria química devem ser retificadas para evitar conflitos de interesse. Além disso, o alinhamento político com os interesses da indústria não deve ter precedência sobre as evidências científicas independentes. É desanimador - para dizer o mínimo - que até que leis de saúde mais rígidas sejam aprovadas na Colômbia, o CPF e tóxicos relacionados continuarão a ser importados dos países que já os proibiram.

Positively charged amino acids at the N terminus of select mitochondrial proteins mediate early recognition by import proteins αß'-NAC and Sam37.

A major challenge in eukaryotic cells is the proper distribution of nuclear-encoded proteins to the correct organelles. For a subset of mitochondrial proteins, a signal sequence at the N terminus (matrix-targeting sequence [MTS]) is recognized by protein complexes to ensure their proper translocation into the organelle. However, the early steps of mitochondrial protein targeting remain undeciphered. The cytosolic chaperone nascent polypeptide-associated complex (NAC), which in yeast is represented as the two different heterodimers αß-NAC and αß'-NAC, has been proposed to be involved during the early steps of mitochondrial protein targeting. We have previously described that the mitochondrial outer membrane protein Sam37 interacts with αß'-NAC and together promote the import of specific mitochondrial precursor proteins. In this work, we aimed to detect the region in the MTS of mitochondrial precursors relevant for their recognition by αß'-NAC during their sorting to the mitochondria. We used targeting signals of different mitochondrial proteins (αß'-NAC-dependent Oxa1 and αß'-NAC-independent Mdm38) and fused them to GFP to study their intracellular localization by biochemical and microscopy methods, and in addition followed their import kinetics in vivo. Our results reveal the presence of a positively charged amino acid cluster in the MTS of select mitochondrial precursors, such as Oxa1 and Fum1, which are crucial for their recognition by αß'-NAC. Furthermore, we explored the presence of this cluster at the N terminus of the mitochondrial proteome and propose a set of precursors whose proper localization depends on both αß'-NAC and Sam37.

The plastome of Melocactus glaucescens Buining & Brederoo reveals unique evolutionary features and loss of essential tRNA genes.

MAIN CONCLUSION: The plastome of Melocactus glaucescens shows unique rearrangements, IR expansion, and unprecedented gene losses in Cactaceae. Our data indicate tRNA import from the cytosol to the plastids in this species. Cactaceae represents one of the richest families in keystone species of arid and semiarid biomes. This family shows various specific features comprehending morphology, anatomy, and metabolism, which allow them to grow under unfavorable environmental conditions. The subfamily Cactoideae contains the most divergence of species, which are highly variable in growth habit and morphology. This subfamily includes the endangered species Melocactus glaucescens (tribe Cereeae), which is a cactus endemic to the biome Caatinga in Brazil. Aiming to analyze the plastid evolution and develop molecular markers, we sequenced and analyzed in detail the plastome of M. glaucescens. Our analyses revealed that the M. glaucescens plastome is the most divergent among the species of the family Cactaceae sequenced so far. We characterized here unique rearrangements, expanded IRs containing an unusual set of genes, and several gene losses. Some genes related to the ndh complex were lost during the plastome evolution, while others have lost their functionality. Additionally, the loss of three tRNA genes (trnA-UGC, trnV-UAC, and trnV-GAC) suggests tRNA import from the cytosol to the plastids in M. glaucescens. Moreover, we identified high gene divergence, several putative positive signatures, and possible unique RNA-editing sites. Furthermore, we mapped 169 SSRs in the plastome of M. glaucescens, which are helpful to access the genetic diversity of natural populations and conservation strategies. Finally, our data provide new insights into the evolution of plastids in Cactaceae, which is an outstanding lineage adapted to extreme environmental conditions and a notorious example of the atypical evolution of plastomes.

Is the mitochondrion a promising drug target in trypanosomatids?

The trypanosomatids Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are etiological agents of important neglected tropical diseases, affecting millions of people worldwide, and the drugs available for these diseases present several limitations. Novel efficient and nontoxic drugs are necessary as an alternative to the current chemotherapy. The unique mitochondrion of trypanosomatids and its peculiar features turn this organelle a potential drug target. Several phenotypic studies describe the damage in the parasite mitochondrial ultrastructure, but the molecular target is unknown. Few reports demonstrated the electron transport system (ETS) as a target due to the high similarities to mammalian orthologues, hence ETS is not a good candidate for drug intervention. On the other hand, antioxidant enzymes, such as trypanothione reductase, and an alternative oxidase (AOX) seem to be interesting targets; however no high active inhibitors were developed up to now. Finally, due to the remarkable differences to mammalian machinery, together with the high biological importance for the parasite survival, the mitochondrial import system stands out as a very promising target in trypanosomatids. Archaic translocase of the outer membrane (ATOM) and translocase of the inner membrane (TIM) complexes, which mediate both protein and tRNA import, composed by specific subunits of these parasites, could be excellent candidates, deserving studies focused on the development of specific drugs.

Commodity risk assessment of Ullucus tuberosus tubers from Peru.

The European Commission requested the EFSA Panel on Plant Health to prepare and deliver risk assessments for commodities listed in Commission Implementing Regulation (EU) 2018/2019 as 'High risk plants, plant products and other objects. This Scientific Opinion covers plant health risks posed by tubers of Ullucus tuberosus imported from Peru, taking into account the available scientific information, including the technical information provided by Peru. The relevance of an EU quarantine pest for this opinion was based on evidence that: (i) the pest is present in Peru, (ii) U. tuberosus is a host of the pest and (iii) the pest can be associated with the commodity. The relevance of any other pest, not regulated in the EU, was based on evidence that: (i) the pest is present in Peru (ii) the pest is absent in the EU; (iii) U. tuberosus is a host of the pest; (iv) the pest can be associated with the commodity and (v) the pest may have an impact and can pose a potential risk for the EU territory. There are five pests i.e. one insect (Amathynetoides nitidiventris), two nematodes (Atalodera andina and Nacobbus aberrans) and two viruses (the Andean potato latent virus (APLV) and the potato virus T (PVT)) that fulfilled all relevant criteria were selected for further evaluation. For the five pests, the risk mitigation measures proposed in the technical dossier from Peru were evaluated taking into account the possible limiting factors. For each of the five pests, an expert judgement is given on the likelihood of pest freedom taking into consideration the risk mitigation measures acting on the pest, including uncertainties associated with the assessment. The degree of pest freedom varies among the pests evaluated, with PVT being the pest most frequently expected on the imported commodities. The Expert Knowledge Elicitation indicated, with 95% certainty, that between 9,157 and 10,000 tubers out of 10,000 would be free of PVT.

The impact of agriculture trade and exchange rate on economic growth of Pakistan: an NARDL and asymmetric analysis approach / O impacto do comércio agrícola e da taxa decâmbio no crescimento econômico do Paquistão: uma abordagem de análise NARDL e assimétrica

This study contributes to the extant literature on the nexus among agriculture export, import exchange rate and economic growth in Pakistan. We used annual time series data for 1980-2017 and employ the Non-linear Autoregressive Distributed Lag (NARDL) model. The NARDL testing results affirms asymmetric co-integration among the variables. The study main results show: (i) Co-integration test for long run the positive shocks in export and import have positive significant while exchange rate has positive effect the economic growth. (ii) Co-integration test for short run the positive shocks in import has positive significant and while Export and exchange rate have negative significant effect on economic growth. The symmetrical results show: (i) Export has unidirectional granger causality (ii) Exchange rate has bidirectional granger causality (iii) Import has not ganger causality with economic growth. In addition, the results demonstrated that causality relationship can help out policy maker to design such policies which are useful to economic growth of Pakistan, which could further promote foreign trade to gain the maximum level of economic growth.(AU)

Este estudo contribui para a literatura existente sobre o nexo entre exportação agrícola, taxa de câmbio de importação e crescimento econômico no Paquistão. Utilizamos dados de séries temporais anuais para 1980-2017 e empregamos o modelo Não-linear Autoregressive Distributed Lag (NARDL). Os resultados dos testes NARDL afirmam a co-integração assimétrica entre as variáveis. Os principais resultados do estudo mostram: (i) no teste de co-integração de longo prazo, os choques positivos nas exportações e importações têm uma significância positiva, enquanto a taxa de câmbio afeta positivamente o crescimento econômico; (ii) Teste de co-integração para curto prazo, os choques positivos nas importações são positivos significativos e, enquanto a exportação e a taxa de câmbio têm um efeito negativo significativo no crescimento econômico. Os resultados simétricos mostram: (i) a exportação tem causalidade unidirecional sobre o crescimento ; (ii) a taxa de câmbio tem causalidade bidirecional sobre o crescimento ; (iii) a importação não tem causalidade sobre o crescimento econômico. Além disso, os resultados demonstraram que a relação de causalidade pode ajudar o formulador de políticas a elaborar políticas úteis ao crescimento econômico do Paquistão, o que poderia promover ainda mais o comércio exterior para obter o nível máximo de crescimento econômico.(AU)

From cytosol to mitochondria: the beginning of a protein journey.

Mitochondrial protein import is one of the key processes during mitochondrial biogenesis that involves a series of events necessary for recognition and delivery of nucleus-encoded/cytosol-synthesized mitochondrial proteins into the organelle. The past research efforts have mainly unraveled how membrane translocases ensure the correct protein sorting within the different mitochondrial subcompartments. However, early steps of recognition and delivery remain relatively uncharacterized. In this review, we discuss our current understanding about the signals on mitochondrial proteins, as well as in the mRNAs encoding them, which with the help of cytosolic chaperones and membrane receptors support protein targeting to the organelle in order to avoid improper localization. In addition, we discuss recent findings that illustrate how mistargeting of mitochondrial proteins triggers stress responses, aiming to restore cellular homeostasis.

The impact of agriculture trade and exchange rate on economic growth of Pakistan: an NARDL and asymmetric analysis approach / O impacto do comércio agrícola e da taxa decâmbio no crescimento econômico do Paquistão: uma abordagem de análise NARDL e assimétrica

ABSTRACT: This study contributes to the extant literature on the nexus among agriculture export, import exchange rate and economic growth in Pakistan. We used annual time series data for 1980-2017 and employ the Non-linear Autoregressive Distributed Lag (NARDL) model. The NARDL testing results affirms asymmetric co-integration among the variables. The study main results show: (i) Co-integration test for long run the positive shocks in export and import have positive significant while exchange rate has positive effect the economic growth. (ii) Co-integration test for short run the positive shocks in import has positive significant and while Export and exchange rate have negative significant effect on economic growth. The symmetrical results show: (i) Export has unidirectional granger causality (ii) Exchange rate has bidirectional granger causality (iii) Import has not ganger causality with economic growth. In addition, the results demonstrated that causality relationship can help out policy maker to design such policies which are useful to economic growth of Pakistan, which could further promote foreign trade to gain the maximum level of economic growth.

RESUMO: Este estudo contribui para a literatura existente sobre o nexo entre exportação agrícola, taxa de câmbio de importação e crescimento econômico no Paquistão. Utilizamos dados de séries temporais anuais para 1980-2017 e empregamos o modelo Não-linear Autoregressive Distributed Lag (NARDL). Os resultados dos testes NARDL afirmam a co-integração assimétrica entre as variáveis. Os principais resultados do estudo mostram: (i) no teste de co-integração de longo prazo, os choques positivos nas exportações e importações têm uma significância positiva, enquanto a taxa de câmbio afeta positivamente o crescimento econômico; (ii) Teste de co-integração para curto prazo, os choques positivos nas importações são positivos significativos e, enquanto a exportação e a taxa de câmbio têm um efeito negativo significativo no crescimento econômico. Os resultados simétricos mostram: (i) a exportação tem causalidade unidirecional sobre o crescimento ; (ii) a taxa de câmbio tem causalidade bidirecional sobre o crescimento ; (iii) a importação não tem causalidade sobre o crescimento econômico. Além disso, os resultados demonstraram que a relação de causalidade pode ajudar o formulador de políticas a elaborar políticas úteis ao crescimento econômico do Paquistão, o que poderia promover ainda mais o comércio exterior para obter o nível máximo de crescimento econômico.

Identification of a putative nuclear localization signal in the tumor suppressor maspin sheds light on its nuclear import regulation.

The tumor suppressor activity of maspin (mammary serine protease inhibitor) has been associated with its nuclear localization. In this study we explore the regulation of maspin nuclear translocation. An in vitro nuclear import assay suggested that maspin can passively enter the nucleus. However, in silico analysis identified a putative maspin nuclear localization signal (NLS), which was able to mediate the nuclear translocation of a chimeric protein containing this NLS fused to five green fluorescent protein molecules in tandem (5GFP). Dominant-negative Ran-GTPase mutants RanQ69L or RanT24N suppressed this process. Unexpectedly, the full-length maspin fused to 5GFP failed to enter the nucleus. As maspin's putative NLS is partially hidden in its three-dimensional structure, we suggest that maspin nuclear transport could be conformationally regulated. Our results suggest that maspin nuclear translocation involves both passive and active mechanisms.

Identification of a nuclear localization signal and importin beta members mediating NUAK1 nuclear import inhibited by oxidative stress.

NUAK1 is a serine/threonine kinase member of the AMPK-α family. NUAK1 regulates several processes in tumorigenesis; however, its regulation and molecular targets are still poorly understood. Bioinformatics analysis predicted that the majority of NUAK1 localizes in the nucleus. However, there are no studies about the regulation of NUAK1 subcellular distribution. Here, we analyzed NUAK1 localization in several human cell lines, mouse embryo fibroblasts, and normal mouse tissues. We found that NUAK1 is located in the nucleus and also in the cytoplasm. Through bioinformatics analysis and studies comparing subcellular localization of wild type and NUAK1 mutants, we identified a conserved bipartite nuclear localization signal at the N-terminal domain of NUAK1. Based on mass spectrometry analysis, we found that NUAK1 interacts with importin-ß members including importin-ß1 (KPNB1), importin-7 (IPO7), and importin-9 (IPO9). We confirmed that importin-ß members are responsible for NUAK1 nuclear import through the inhibition of importin-ß by Importazole and the knockdown of either IPO7 or IPO9. In addition, we found that oxidative stress induces NUAK1 cytoplasmic accumulation, indicating that oxidative stress affects NUAK1 nuclear transport. Thus, our study is the first evidence of an active nuclear transport mechanism regulating NUAK1 subcellular localization. These data will lead to investigations of the molecular targets of NUAK1 according to its subcellular distribution, which could be new biomarkers or targets for cancer therapies.

DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway.

MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed.

Outro olhar sobre a vigilância sanitária de produtos no Brasil: a legislação de controle sanitário das importações em foco / Another look at sanitary surveillance of products in Brazil: the sanitary control legislation of imports in focus

Resumo Este artigo tem como objeto a regulamentação adotada pelo Brasil no que tange ao controle sanitário da importação de produtos sob vigilância sanitária. O estudo incorporou os aspectos políticos, técnicos, econômicos e institucionais envolvidos no controle das importações. Destaca-se, ainda, a identificação de atores que se mostraram relevantes na formulação e na implantação das normas. Nesta perspectiva, foi realizado estudo singular do conjunto das normatizações publicadas entre 1996 e 2013 editadas desde a antiga Secretaria de Vigilância Sanitária até a Anvisa. Como resultado, foram selecionadas cinco normas para análise, bem como suas alterações posteriores, caracterizando um estudo qualitativo de caráter exploratório, executado com base na análise temática de conteúdo. O exame desse material permitiu traçar uma trajetória do controle sanitário das importações, possibilitando destacar as condicionantes para as alterações dos regulamentos e os efeitos produzidos por estas. Observou-se que tanto a elaboração quanto os posteriores desdobramentos das normatizações foram influenciados pelas mudanças políticas e econômicas observadas no país e no mundo, sofrendo a determinação de organismos internacionais e de atores intra e extra-institucionais, que conduziram a restrições no controle de produtos importados. O estudo permitiu conhecer melhor a prática da vigilância sanitária, no âmbito da importação.

Abstract This article focuses on the regulation adopted by Brazil in relation to health inspection of imports of goods under sanitary surveillance. The study incorporated the political, technical, economic and institutional aspects involved in the sanitary control of imports. Noteworthy is also the identification of actors relevant in the formulation and implementation of standards. In this perspective, we performed singular study of all norms published between 1996 and 2013 edited from the former Health Surveillance Secretariat to the National Sanitary Surveillance Agency (Anvisa). As a result, five standards were selected for analysis as well as its subsequent amendments, featuring a qualitative exploratory study based on thematic content analysis. The examination of this material allowed to draw a trajectory of sanitary control of imports, which unfolded from the analysis of standards, allowing highlight the conditions for changes in regulations and the effects of such changes. It was observed that both the elaboration and later developments of norms were influenced by political and economic changes observed in the country and the world, suffering the determination of international organizations and intra and extra-institutional actors, which led to restrictions in the health control products imported. The study allowed a better understanding of the practice of sanitary surveillance in the import scope.

Profile of the Illegal Import of Products of Animal Origin to Brazilian Cities at the Border with Argentina and Uruguay.

International food transit is a risk to public and animal health when not subject to legal importation sanitation procedures. Due to the extensive border area, illegal food import in Brazil is a common practice, especially in Rio Grande do Sul (RS), a state that borders with Argentina and Uruguay. The objective of this study was to evaluate the profile of Brazilians living in cities in RS that border with Argentina (BR-AR) or Uruguay (BR-UR) regarding the practice of illegal import of products of animal origin and to determine associations between the population characteristics and illegal import. A questionnaire with information related to the personal profile, habits of acquisition of imported food, and knowledge of health risks deriving from the consumption of the imported products was elaborated. The questionnaire was administered in six cities in RS (three cities bordering Argentina and three cities bordering Uruguay) and responses were obtained from 744 individuals. The variables city, sex, level of education, and knowledge were subjected to the chi-square test to verify the association between these variables and food import. Part of the interviewees admitted to illegally importing products of animal origin at both BR-AR (65.17%) and BR-UR (76.28%) borders. Dairy products were the main imported goods, followed by raw and processed meat. The study revealed that illegal import is common at the frontier region of RS, especially that of products of animal origin, dairy, and raw and processed meat. Although illegal importation occurs at all the cities under study, it was higher at the BR-UR border. Also, knowledge of the health risks influences the decision to import food or not.

Identification of karyopherins involved in the nuclear import of RNA exosome subunit Rrp6 in Saccharomyces cerevisiae.

The exosome is a conserved multiprotein complex essential for RNA processing and degradation. The nuclear exosome is a key factor for pre-rRNA processing through the activity of its catalytic subunits, Rrp6 and Rrp44. In Saccharomyces cerevisiae, Rrp6 is exclusively nuclear and has been shown to interact with exosome cofactors. With the aim of analyzing proteins associated with the nuclear exosome, in this work, we purified the complex with Rrp6-TAP, identified the co-purified proteins by mass spectrometry, and found karyopherins to be one of the major groups of proteins enriched in the samples. By investigating the biological importance of these protein interactions, we identified Srp1, Kap95, and Sxm1 as the most important karyopherins for Rrp6 nuclear import and the nuclear localization signals recognized by them. Based on the results shown here, we propose a model of multiple pathways for the transport of Rrp6 to the nucleus.

αß'-NAC cooperates with Sam37 to mediate early stages of mitochondrial protein import.

The mitochondrial proteome is mostly composed of nuclear-encoded proteins. Such polypeptides are synthesized with signals that guide their intracellular transport to the surface of the organelle and later within the different mitochondrial subcompartments until they reach their functional destination. It has been suggested that the nascent-polypeptide associated complex (NAC) - a cytosolic chaperone that recognizes nascent chains on translationally active ribosomes - has a role in the import of nuclear-encoded mitochondrial proteins. However, the molecular mechanisms that regulate the NAC-mediated cotranslational import are still not clear. Here, we show that a particular NAC heterodimer formed by subunits α and ß' in Saccharomyces cerevisiae is specifically involved in the process of mitochondrial import and functionally cooperates with Sam37, an outer membrane protein subunit of the sorting and assembly machinery complex. Mutants in both components display growth defects, incorrectly accumulate precursor forms of mitochondrial proteins in the cytosol, and have an altered mitochondrial protein content. We propose that αß'-NAC and Sam37 are members of the system that recognizes mitochondrial proteins at early stages of their synthesis, escorting them to the import machinery of mitochondria.