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CITED2 and the modulation of the hypoxic response in cancer

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World Journal of Clinical Oncology 2020年第5期11卷 260-274页

作者： Mónica T Fernandes Sofia M Calado leonardo mendes-silva JoséBraganca School of Health Universidade do AlgarveCampus of GambelasFaro 8005-139Portugal Centre for Biomedical Research Universidade do AlgarveCampus of GambelasFaro 8005-139Portuga Algarve Biomedical Centre Faro 8005-139Portugal Department of Biomedical Sciences and Medicine Universidade do AlgarveCampus of GambelasFaro 8005-139Portugal

CITED2(CBP/p300-interacting transactivator with Glu/Asp-rich C-terminal domain,2)is a ubiquitously expressed protein exhibiting a high affinity for the CH1 domain of the transcriptional co-activators CBP/p300,for which it competes with hypoxia-inducible factors(HIFs).CITED2 is particularly efficient in the inhibition of HIF-1α-dependent transcription in different contexts,ranging from organ development and metabolic homeostasis to tissue regeneration and immunity,being also potentially involved in various other physiological *** addition,CITED2 plays an important role in inhibiting HIF in some diseases,including kidney and heart diseases and type *** the particular case of cancer,CITED2 either functions by promoting or suppressing cancer development depending on the context and type of *** instance,CITED2 overexpression promotes breast and prostate cancers,as well as acute myeloid leukemia,while its expression is downregulated to sustain colorectal cancer and hepatocellular *** addition,the role of CITED2 in the maintenance of cancer stem cells reveals its potential as a target in non-small cell lung carcinoma and acute myeloid leukemia,for *** besides the wide body of evidence linking both CITED2 and HIF signaling to carcinogenesis,little data is available regarding CITED2 role as a negative regulator of HIF-1αspecifically in ***,comprehensive studies exploring further the interactions of these two important mediators in cancer-specific models are sorely needed and this can potentially lead to the development of novel targeted therapies.

关键词： Cancer Cancer stem cell CBP/p300 CITED2 Hypoxia-inducible factors 1α

How far have we come?Review of main public policies to reduce landslide impacts in Brazil

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Journal of Mountain Science 2024年第9期21卷 2891-2904页

作者： Bianca Carvalho VIEIRA Tiago Damas MARTINS Telma mendes da silva JoséEduardo BONINI Department of Geography University of São PauloAvenida Professor Lineu Prestes 05508-000Brazil Cities Institute Federal University of São PauloAvenida Jacu-Pêssego 08260-001Brazil Department of Geography Federal University of Rio de JaneiroAvenida Athos da Silveira Ramos 21941-916Brazil

During the rainy season in Brazil,landslides can have catastrophic consequences,including loss of life,damage to urban infrastructure and significant economic ***,more than eight million people in Brazil live in disaster-prone *** objective of this article is to present a chronological review of the principal policies and programmes at the national,state,and municipal levels,with an emphasis on their key actions aimed at mitigating the impact of disasters related to natural hazards,particularly *** analysis was based on official records of public policies from the national,state,and municipal *** results show that several initiatives were initially developed at the local and regional ***,it was not until the late 1980s that a comprehensive organisation of civil protection at the national level emerged as a response *** is possible to highlight three phases(understanding,coexistence,and prevention)of institutional action focused on risk management in the face of *** the growing knowledge of risk scenarios,disasters continue to occur in Brazil on an annual basis,revealing several obstacles to reducing their impact,particularly given the social and economic disparities between Brazilian regions and the applicability of public policies that must overcome the limitations of each municipality.

关键词： Disasters Risk Mitigation Prevention Legislation Civil Defense Natural Hazards

A remote sensing approach to estimate the load bearing capacity of soil

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Information Processing in Agriculture 2024年第1期11卷 109-116页

作者： Italo Rômulo mendes de Souza Edson Eyji Sano Renato Paiva de Lima Anderson Rodrigo da silva Statistics and Geoprocessing Laboratory Instituto Federal GoianoGeraldo Silva Nascimento RoadKm 2.575790-000 UrutaíGoiásBrazil Embrapa Cerrados BR-020 RoadKm 18Mailbox 0822373310-970 PlanaltinaDFBrazil Department of Soil Science ‘Luiz de Queiroz’College of AgricultureUniversity of São PauloAv.Pádua Dias235-AgronomiaPiracicabaSP 13418-900Brazil

Preconsolidation pressure(σp)of soil can be considered as an indicator of the Load Bearing Capacity(LBC),which is the tolerated surface pressure before compaction,often caused by the traffic of agricultural *** this pioneering study,a remote sensing approach was introduced to estimate LBC throughσp from soils of the“Rio Preto”Hydrographic Basin,Bahia State,Brazil,in a monthly time lapse from 2016 to ***,σp is measured by a laborious and time demanding laboratory analysis,making it unfeasible to map large *** innovative methodology of this work consists of combining active–passive satellite data on soil moisture and pedotransfer functions of clay content and water matric potential to obtain geo-located estimates ofσ*** were analysed under different classes of soil use,land cover and slope;95%confidence intervals were built for the time series of mean values of LBC for each *** overall seasonal variation in LBC estimates is similar in areas with annual crops,grasslands and natural vegetation,and flat areas are less affected by soil moisture variations over the year(between seasons).LBC decreased,in general,at about 0.5%a year in flat ***,these areas demand attention,since they occupy 86%of the Basin and are mostly subjected to agricultural soil management and surface pressure by heavy machinery.

关键词： Soil compaction SMAP Preconsolidation stress Brazilian Cerrado

Spatial analysis of Dengue through the reproduction numbers relating to socioeconomic features:Case studies on two Brazilian urban centers

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Infectious Disease Modelling 2024年第1期9卷 142-157页

作者： Ana T.C.silva Rejane C.Dorn Lívia R.Tomás leonardo B.L.Santos Lacita M.Skalinski Suani T.R.Pinho Departamento de Física Universidade Estadual de Feira de SantanaAv.Transnordestinas/n.Novo HorizonteFeira de Santana44036-900BABrazil Instituto de Física Universidade Federal da BahiaRua Barão de Jeremoabo s/nCampus Universitário de OndinaSalvador40170-115BABrazil Centro Nacional de Monitoramento e Alertas de Desastres Naturais(CEMADEN) Estrada Dr.Altino Bondensan500São Josédos Campos12247-016SPBrazil Universidade Estadual de Santa Cruz Campus Soane Nazaréde AndradeRodovia Jorge AmadoKm 16SalobrinhoIlhéus45662-900BABrazil Instituto de Saúde Coletiva Universidade Federal da BahiaR.Basílio da Gamas/n-CanelaSalvador40110-140BABrazil Instituto Nacional de Ciência e Tecnologia-Sistemas Complexos Virtual InstitutionBrazil

The study of the propagation of infectious diseases in urban centers finds a close connection with their population's social characteristics and *** work performs a spatial analysis of dengue cases in urban centers based on the basic reproduction numbers,R0,and incidence by planning areas(PAs),as well as their correlations with the Human Development Index(HDI)and the number of *** analyzed dengue epidemics in 2002 at two Brazilian urban centers,Belo Horizonte(BH)and Rio de Janeiro(RJ),using PAs as spatial *** results reveal heterogeneous spatial scenarios for both cities,with very weak correlations between R0 and both the number of trips and the HDI;in BH,the values of R0 show a less spatial heterogeneous pattern than in *** BH,there are moderate correlations between incidence and both the number of trips and the HDI;meanwhile,they weakly correlate for ***,the absence of strong correlations between the considered measures indicates that the transmission process should be treated considering the city as a whole.

关键词： Dengue Mathematical mode lBasic reproduction number Urban mobility Urban indices

Gravity-Driven Listric Growth Fault and Sedimentation in the Lagoa do Peixe, Rio Grande do Sul Coastal Plain, Brazil

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Open Journal of Geology 2024年第4期14卷 594-616页

作者： Bruno silva da Fontoura Adelir José Strieder Iran Carlos Stalliviere Corrêa Paulo Rogério mendes Instituto de Geociê ncias UFRGS Porto Alegre Brazil Engenharia Geoló gica Centro de Engenharias UFPel Pelotas Brasil HIDROSERV— Servi&#231os Geol&#243gicos e Geof&#237sicos Ltda. Porto Alegre Brazil

High frequency, high resolution GPR surveys are successfully applied to investigate near-surface stratification architecture of sedimentary units in coastal plains and to define their depositional conditions. However, low frequency GPR surveys to investigate fault-related depositional systems at greater depths are scarce. This survey was designed investigate a > 100 km long linear escarpment that controls the northwest margin of the Lagoa do Peixe, an important lagoon in Rio Grande do Sul Coastal Plain (RGSCP, Brazil). The traditional approach points that RGSCP was developed by juxtaposition of four lagoons/barrier systems as consequence of sea level changes;no deformational structure is admitted to exist before. The low frequency GPR (50 MHz, RTA antenna) and geological surveys carried out in the RGSCP showed the existence of a large, gravity-driven listric growth fault controlling the Lagoa do Peixe escarpment and hangingwall sedimentation. The radargrams in four subareas along the Lagoa do Peixe Growth Fault could be interpreted following the seismic expression of rift-related depositional systems. The radargrams enabled to distinguish three main lagoonal deposition radarfacies. The lower lagoonal radarfacies is a convex upward unit, thicker close to growth fault;the radarfacies geometry indicates that fault displacement rate surpasses the sedimentation rate, and its upper stratum is aged ~3500 l4C years BP. The second lagoonal radarfacies is a triangular wedge restricted to the lagoon depocenter, whose geometry indicates that fault displacement and the sedimentation rates kept pace. The upper lagoonal radarfacies is being deposited since 1060 ± 70 l4C years BP, under sedimentation rate higher than fault displacement rate. The results indicate that low frequency GPR surveys can help in investigating fault-related depositional systems in coastal zones. They also point to a new approach in dealing with RGSCP stratigraphy.

关键词： GPR (Ground-Penetrating Radar) Growth Fault Sedimentation Radarfacies Coastal Plain

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

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World Journal of Clinical Oncology 2024年第5期15卷 587-590页

作者： leonardo S Lino-silva Sabrina B Martínez-Villavicencio Luisa Fernanda Rivera-Moncada Department of Pathology Oncology National Cancer Institute(Mexico)TlalpanMexico City 14080Mexico

In this editorial,we comment on the article by Wang et *** manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic *** results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response *** authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation ***,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response *** essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for *** findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient *** the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

关键词： Primary central nervous system lymphoma Zanubrutinib Bruton’s tyrosine kinase Prognosis Myeloid differentiation primary response 88 gene Cluster of differentiation 79B gene

Gravity Fault Subsidence and Beach Ridges Progradation in Quinta-Cassino (RS) Coastal Plain, Brazil

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Open Journal of Geology 2024年第2期14卷 177-195页

作者： Bruno silva da Fontoura Adelir José Strieder Iran Carlos Stalliviere Corrêa Paulo Rogério mendes Alexandre Felipe Bruch Angélica Cirolini Programa de Pós-Graduaç &#227o em Geoci&#234ncias (PPGeo) Instituto de Geoci&#234ncias UFRGS Porto Alegre Brazil Engenharia Geológica Centro de Engenharias UFPel Pra&#231a Domingos Rodrigues 2 Pelotas Brasil HIDROSERV-Serviç os Geológicos e Geofísicos Ltda. Rua Senegal 152 Porto Alegre Brazil Colégio Politécnico UFSM Santa Maria Brasil

Ground penetrating radar (GPR) surveys have being applied to investigate very near-surface stratification of sedimentary units in coastal plains and to define their depositional conditions. This paper presents, however, low-frequency GPR survey to investigate fault-related depositional systems at greater depths. The Quinta-Cassino area in the Rio Grande do Sul Coastal Plain (RGSCP, Brazil) shows a wide strandplain that is made off by very long, continuous, and linear geomorphic features (beach ridges). This strandplain extends for ~70 km southward. The beach ridges show low-angle truncations against the Quinta escarpment, and also truncations in the strandplain. The traditional approach points that RGSCP was developed by juxtaposition of four lagoons/barrier systems as consequence of sea level changes;previous model assumes that no deformational episode occurred in RGSCP. The geophysical and geological surveys carried out in this area showed the existence of listric fault controlling the beach ridges in the escarpments and hanging-wall blocks. The radargrams could distinguish Pleistocene basement unit anticlockwise rotation, thickening of beach ridges radarfacies close to listric normal faults, and horst structures. These deformational features indicate that the extensional zone of a large-scale gravity-driven structure controlled the mechanical subsidence, the Holocene sedimentation and its stratigraphic and geomorphic features in the Quinta-Cassino area to build up an asymmetric delta. The results point to a new approach in dealing with RGSCP Holocene evolution.

关键词： Gravity Tectonics Normal Faults Ground Penetrating Radar Survey Beach-Ridges Progradation

In Silico and in Vitro Analysis of Pyrazolone Derivatives against Zika Virus and Identification of Potential NS5 Methyltransferase Inhibitors by Molecular Docking

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Journal of Biosciences and Medicines 2024年第7期12卷 214-229页

作者： Luciene Soares silva Tiago Soares Barbosa Maria Leonisa Sanchez-Nuñez Aldenise Mont Serrat Rosa da silva Vitor Won-Held Rabelo leonardo dos Santos Corrêa Amorim leonardo Alves Miceli Percilene Fazolin Vegi Alice Bernardino Helena Carla Castro Izabel Christina Nunes de Palmer Paixão Science and Biotechnology Graduate Program Department of Cellular and Molecular Biology Institute of Biology Fluminense Federal University Niteri Brazil Science and Biotechnology Graduate Program Department of Cellular and Molecular Biology Institute of Biology Fluminense Federal University Niterói Brazil Laboratory of Antibiotics Biochemistry Teaching and Molecular Modeling Institute of Biology Fluminense Federal University Niterói Brazil Laboratory of Organic Chemistry at the Institute of Chemistry Institute of Biology Fluminense Federal University Niterói Brazil

Zika virus (ZIKV), a mosquito-borne flavivirus, has been associated with benign infections for decades. However, it has become a public health concern due to its association with severe fetal and neurological complications. Although many efforts have been made to control ZIKV infection, approved vaccines or antiviral drugs are still lacking. Consequently, the development of new effective anti-ZIKV agents is urgently needed. In this context, we investigated the antiviral potential of pyrazolone derivatives against ZIKV replication using in silico and in vitro methods. The four pyrazolone derivatives evaluated (1a, 1b, 1c, and 1d) inhibited over 50% of ZIKV replication with low cytotoxicity. Among them, compound 1b exhibited the most potent activity (EC50 = 4.3 μM) and the highest selectivity (SI = 342). Mechanism of action studies indicated that these compounds act at early stages of virus replication, and compound 1b can also directly inactivate ZIKV particles. Molecular docking studies suggested that these compounds can bind to and block the activity of ZIKV NS5 methyltransferase. Finally, pharmacokinetic and toxicological predictions have reinforced the safety and drug-like profiles of these derivatives. In conclusion, the pyrazolone scaffold proved to be valuable for anti-ZIKV drug development, and the derivatives studied deserve further investigation.

关键词： Zika Pyrazolone NS5 Methyltransferase Antivirals

Obtaining 2D Soil Geotechnical Profiles from Cokriging Interpolation of Sample Data and Electrical Resistivity Tomography (ERT)—Applications in Mass Movements Studies

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International Journal of Geosciences 2024年第7期15卷 525-548页

作者： Cassiano Antonio Bortolozo Noel Howley Andy Legg Tristan Pryer Danielle silva de Paula Tatiana Sussel Gonçalves mendes Daniel Metodiev Marcio Roberto Magalhães de Andrade Silvio Jorge Coelho Simões Maiconn Vinicius de Moraes Marcio Augusto Ernesto de Moraes Luana Albertani Pampuch Rodolfo Moreda mendes Harideva Marturano Egas Institute of Science and Technology So Paulo State University (UNESP) So Jos dos Campos Brazil Cemaden-National Center for Monitoring and Early Warning of Natural Disasters General Coordination of Research and Development So Jos dos Campos Brazil Institute for Mathematical Innovation University of Bath Bath UK Department of Mathematical Sciences University of Bath Bath UK

Brazil annually faces significant challenges with mass movements, particularly in areas with poorly constructed housing, inadequate engineering, and lacking sanitation infrastructure. Campos do Jordão, in São Paulo state, is a city currently grappling with these issues. This paper details a study conducted within a pilot area in Campos do Jordão, where geophysical surveys and geotechnical borehole data were integrated. The geophysical surveys provided 2D profiles, and samples were collected to analyse soil moisture and plasticity. These datasets were combined using a Cokriging-based model to produce an accurate representation of the subsurface conditions. The enhanced modelling of subsurface variability facilitates a deeper understanding of soil behavior, which can be used to improve landslide risk assessments. This approach is innovative, particularly within the international context where similar studies often do not address the complexities associated with urban planning deficits such as those observed in some areas of Brazil. These conditions, including the lack of proper sanitation and irregular housing, significantly influence the geological stability of the region, adding layers of complexity to subsurface assessments. Adapting geotechnical evaluation methods to local challenges offers the potential to increase the efficacy and relevance of geological risk management in regions with similar socio-economic and urban characteristics.

关键词： Mass Movements Geophysics ERT Geotechnical Surveys Campos do Jordão Cokriging