Cdkn2a inactivation promotes malignant transformation of mouse immature thymocytes before the β-selection checkpoint

CDKN2A deletion is the most frequent genetic alteration in T-cell acute lymphoblastic leukemia (T-ALL), occurring across all molecular and immunophenotypic subtypes. CDKN2A encodes two functionally unrelated tumor suppressor proteins, ARF and INK4a, which are critical regulators of cell cycle and proliferation. Arf has been reported to suppress T-ALL development in post−b-selection thymocytes, but whether CDKN2A acts as a tumor suppressor gene in immature, pre−b-selection thymocytes remains to be elucidated. Resorting to a Rag2-deficient model of T-ALL, driven by the ETV6:: JAK2 fusion, we report that Cdkn2a haploinsufficiency at early stages of T-cell development facilitates leukemia developmentPPBI-POCI-01-0145-FEDER-022122; POCI-01-0145-FEDER-007274; NORTE01-0145-FEDER-000029info:eu-repo/semantics/publishedVersio

Distribution models of deep-sea elasmobranchs in the Azores, Mid-Atlantic Ridge, to inform spatial planning

Elasmobranchs inhabiting depths beyond 200 m are extremely susceptible to overexploitation but are extracted by fisheries around the world either as target species or as bycatch. There is little information available to formulate management strategies to reduce elasmobranch-fishery interactions in the deep sea. In European Union waters, prohibiting the catches of deep-sea elasmobranchs has provided the necessary impetus to study by-catch avoidance of these threatened species. We used over 20 years of fisheries-independent and fisheries-dependent data to model the spatial distribution of 15 species of deep-sea elasmobranchs (12 sharks and 3 rays) captured frequently in the Exclusive Economic Zone of the Azores Archipelago (Mid-Atlantic Ridge) to explore spatial management to reduce unwanted catches of these species. We applied Generalised Additive Models to predict the probability of presence of 15 species, as well as the abundance of 6 of those species, within the Azores EEZ and neighbouring seamounts (up to 2000 m depth), using environmental and operational variables as predictors. Our results identified that depth is most influential in determining the distribution of these sharks and rays, in addition to seafloor topography. Distinctive bathymetric features such as seamounts and ridges were highlighted as areas where the probability of presence of the greatest number of species overlapped. Although not related to habitat, gear type influenced the capture probability of certain species, with the artisanal handline, gorazeira, having lower captures than bottom longline. Our results support using depth-based, area-based, and gear-based tactics to design management measures to reduce elasmobranch bycatch, for more sustainable deep-sea fisheries.Postprint2,42

Association between Polymorphisms in Antioxidant Genes and Inflammatory Bowel Disease

Inflammation is the driving force in inflammatory bowel disease (IBD) and its link to oxidative stress and carcinogenesis has long been accepted. The antioxidant system of the intestinal mucosa in IBD is compromised resulting in increased oxidative injury. This defective antioxidant system may be the result of genetic variants in antioxidant genes, which can represent susceptibility factors for IBD, namely Crohn's disease (CD) and ulcerative colitis (UC). Single nucleotide polymorphisms (SNPs) in the antioxidant genes SOD2 (rs4880) and GPX1 (rs1050450) were genotyped in a Portuguese population comprising 436 Crohn's disease and 367 ulcerative colitis patients, and 434 healthy controls. We found that the AA genotype in GPX1 is associated with ulcerative colitis (OR = 1.93, adjusted P-value = 0.037). Moreover, we found nominal significant associations between SOD2 and Crohn's disease susceptibility and disease subphenotypes but these did not withstand the correction for multiple testing. These findings indicate a possible link between disease phenotypes and antioxidant genes. These results suggest a potential role for antioxidant genes in IBD pathogenesis and should be considered in future association studies.info:eu-repo/semantics/publishedVersio

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the “alternative mechanism of telomere lengthening” (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target

Viabilidade econômica do cultivo de abacaxi no arenito Caiuá, região noroeste do Estado do Paraná = Economic feasibility of pineapple culture in the Caiuá sandstone area, northwestern Paraná State

A área da região noroeste do Estado do Paraná, sobre o arenito Caiuá, carece de opções de exploração agrícola economicamente viáveis. Assim, o abacaxi apresenta-se como opção de cultivo, entretanto, necessitando de maiores estudos referentes à sua exploraçãonesta região. O presente trabalho teve por objetivo avaliar a viabilidade socioeconômica do cultivo desta frutífera na região de Umuarama, Estado do Paraná em relação às principais regiões fornecedoras de abacaxi para o Estado. Para tanto, visitaram-se três propriedades nos municípios de Umuarama, Cafezal do Sul e Cruzeiro do Oeste, objetivando levantar os coeficientes técnicos desta atividade e seus indicadores de lucratividade. A região analisada apresenta boa capacidade competitiva em relação às regiões tradicionalmente produtoras (Frutal, Estado de Minas Gerais e Guaraçaí, Estado de São Paulo), principalmente pela proximidade do mercado consumidor. O abacaxi é uma excelente opção de cultivo no contexto da agricultura familiar.The northwestern region of the state of Paraná, in the Caiuásandstone area, lacks options for economically feasible agricultural exploration. Thus, pineapple appears as a growth option, needing further studies regarding its exploration in that region. Thepresent review aimed to evaluate the feasibility of this culture and analyze the competitiveness of this region of Umuarama, Paraná State, compared to the state’s main pineapple supplying regions. For this purpose, three producers in Umuarama, Cafezal do Sul and Cruzeiro do Oeste were visited, in order to survey the technical coefficient of this culture and its profit indicators. The analyzed region presents a good and competitive capacity compared to other traditional fruitproducers, mainly due to the proximity of consumer markets. Pineapple is an excellent choice of culture in the familiar agricultural context

Viabilidade econômica do cultivo de abacaxi no arenito Caiuá, região noroeste do Estado do Paraná

A área da região noroeste do Estado do Paraná, sobre o arenito Caiuá, carece de opções de exploração agrícola economicamente viáveis. Assim, o abacaxi apresenta-se como opção de cultivo, entretanto, necessitando de maiores estudos referentes à sua exploração nesta região. O presente trabalho teve por objetivo avaliar a viabilidade socioeconômica do cultivo desta frutífera na região de Umuarama, Estado do Paraná em relação às principais regiões fornecedoras de abacaxi para o Estado. Para tanto, visitaram-se três propriedades nos municípios de Umuarama, Cafezal do Sul e Cruzeiro do Oeste, objetivando levantar os coeficientes técnicos desta atividade e seus indicadores de lucratividade. A região analisada apresenta boa capacidade competitiva em relação às regiões tradicionalmente produtoras (Frutal, Estado de Minas Gerais e Guaraçaí, Estado de São Paulo), principalmente pela proximidade do mercado consumidor. O abacaxi é uma excelente opção de cultivo no contexto da agricultura familiar.The northwestern region of the state of Paraná, in the Caiuá sandstone area, lacks options for economically feasible agricultural exploration. Thus, pineapple appears as a growth option, needing further studies regarding its exploration in that region. The present review aimed to evaluate the feasibility of this culture and analyze the competitiveness of this region of Umuarama, Paraná State, compared to the state's main pineapple supplying regions. For this purpose, three producers in Umuarama, Cafezal do Sul and Cruzeiro do Oeste were visited, in order to survey the technical coefficient of this culture and its profit indicators. The analyzed region presents a good and competitive capacity compared to other traditional fruit producers, mainly due to the proximity of consumer markets. Pineapple is an excellent choice of culture in the familiar agricultural context

Challenges in avoiding deep-water shark bycatch in Azorean hook-And-line fisheries [Dataset]

Table A. Summary of the European Union fishing opportunities regulations since 2005, regarding deep-water sharks for Portugal in area X (Azores EEZ). Quota in tonnes (t); * = bycatch only; 10%* = bycatch of up to 10% of 2009 allowed; idem for 3%; 0 = zero TAC; b = only for the longline fishery targeting black scabbardfish; X = fishing prohibition; Y = Yes, included in the regulation; N = not included.Peer reviewe