Search

Made available in DSpace on 2022-04-28T19:44:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-16 Paulista University – UNIP São Paulo State University – UNESP Department of General Pathology Institute of Biological Sciences Federal University of Minas Gerais Belo Horizonte Laboratory of Pharmacology and Toxicology Department of Pathology School of Veterinary Medicine and Animal Science University of São Paulo Laboratório de Vetores Virais Centro de Investigação Translacional em Oncologia/LIM24 Instituto do Câncer do Estado de São Paulo Faculdade de Medicina Universidade de São Paulo Departamento de Biologia Estrutural e Funcional Instituto de Biologia Universidade Estadual de Campinas (UNICAMP) Laboratory of Urogenital Carcinogenesis and Immunotherapy University of Campinas Pet Care Oncologic Center – Radiotherapy OncoPet Veterinary Hospital Pontifical Catholic University of Paraná (PUCPR) Vet Cancer – Animal Oncology and Pathology Paulsita University (UNIP) Vet Oncologia Cancer Clinic Department of Veterinary Clinic and Surgery São Paulo State University (UNESP) Specialized Service in Veterinary Oncology (SEOVET) Department of Veterinary Clinic and Surgery Faculty of Agricultural and Veterinary Sciences São Paulo State University Metropolitan University of Santos (UNIMES) Laboratory of Experimental and Comparative Oncology Department of Pathology School of Veterinary Medicine and Animal Science University of São Paulo São Paulo State University – UNESP Department of Veterinary Clinic and Surgery São Paulo State University (UNESP) Department of Veterinary Clinic and Surgery Faculty of Agricultural and Veterinary Sciences São Paulo State University

Recent science education reform proponents explicitly put forward the idea that all students, regardless of culture, gender, race, or socioeconomic status, are capable of understanding and doing science. To address this need, the authors have developed and implemented a field-based urban ecology science program to engage traditionally underrepresented groups, such as minorities and women in real-world science. The authors describe the components of the program and discuss why the program has been successful in providing opportunities for all students to engage in and learn science. Using mixed methods to evaluate the program, they found that it improves student interest in science, supports students in developing a better understanding of scientific methodologies, and improves students' sense of environmental stewardship when compared with students experiencing traditional science instruction over the course of an academic year.

Bohr’s often quoted phrase “reduce experience to order” highlights that studying science is about collecting data through experiences, inferring patterns or relationships in those experiences, and then developing explanations that provide understanding into why certain patterns emerge and others do not. Geospatial technologies offer educators powerful learning resources to engage students in this scientific process. For 3 years, we have been using a range of geospatial technologies including online applications such as Google Earth to powerful desktop applications such as geographic information systems (GIS) to assist teachers who are introducing their students to the rapidly emerging field of urban ecology. Geospatial technologies along with computational modeling tools have proven to be a powerful way to support teachers and students as they critically examine their own neighborhoods.

A via de Reparo por Excisão de Nucleotídeos (NER) é responsável pelo reparo das lesões causadas pela luz ultravioleta (UV) e de outras lesões capazes de distorcer a dupla hélice, bloqueando a replicação e a transcrição. Os pacientes que apresentam as síndromes recessivas raras Xeroderma Pigmentosum (XP), tricotiodistrofia (TTD) e síndrome de Cockayne (CS) possuem mutações em algum dos 11 genes relacionados ao NER e à transcrição basal. Mutações na proteína XPD levam ao surgimento de diferentes fenótipos: XP, TTD, XP/CS ou COFS (Cerebro-Oculo-Facio-Skeletal Syndrome), uma forma rara de CS. Os pacientes XP apresentam alta incidência de câncer de pele, o que não ocorre com os pacientes TTD e CS, além de poderem apresentar perda neuronal progressiva, enquanto todos os CS e TTD apresentam uma diminuição na mielinização do cérebro. As neuropatologias são provavelmente associadas a problemas no reparo de danos endógenos no DNA das células nervosas. Diversos trabalhos mostraram o envolvimento do NER no reparo desses danos, os quais pensava-se serem reparados apenas por outro mecanismo, o Reparo por Excisão de Base. Neste trabalho mostramos que fibroblastos de pacientes XP-D, XP-D/CS e TTD, portadores de mutações em XPD, são sensíveis ao estresse oxidativo induzido pelo tratamento com azul de metileno fotoativado, apresentando bloqueio prolongado no ciclo celular e permanência da sinalização de danos ao DNA. A complementação das diferentes linhagens com o gene XPD/ERCC2 foi capaz de restaurar a sobrevivência celular. Foram detectadas diferenças importantes na capacidade de reparo/retomada da transcrição após danos gerados por estresse oxidativo em DNA plasmidial, além da ativação de vias diferentes de morte celular: fibroblastos XP-D apresentam maior capacidade de reparo e apresentam morte por apoptose após estresse oxidativo, enquanto os fibroblastos XP-D/CS e TTD apresentam menor capacidade de reparo ativação de mais de uma via de morte celular (apoptose e necrose), diferenças que podem estar ligadas ao fenótipo dos pacientes. Mutações no gene codificante para a DNA polimerase n, POLH, estão associadas à forma variante de XP (XP-V). Pol n é uma polimerase especializada na síntese translesão (TLS) de fotoprodutos, além de estar implicada na TLS de outros tipos de lesões como bases oxidadas, e em vias não relacionadas à TLS como a hipermutação somática e à replicação de regiões de DNA com arquiteturas não-canônicas. Neste trabalho mostramos que os fibroblastos de pacientes XP-V apresentam sensibilidade ao estresse oxidativo. Mostramos uma indução da proteína pol n em fibroblastos primários após danos genotóxicos, associada ao aumento da capacidade de lidar com a parada na forquilha de replicação, possibilitando a continuidade da replicação do DNA e ao aumento da sobrevivência celular. Mostramos uma diferença na estabilidade genômica nos genes das imunoglobulinas dos pacientes XP-V idosos em comparação com os pacientes jovens e controles de idade pareada, mostrando que a ausência dessa polimerase pode estar ligada ao aumento da instabilidade genômica nesses genes The Nucleotide Excision Repair (NER) pathway is responsible for the repair of UV photoproducts and other bulky lesions that block both replication and transcription. Patients with the rare recessive disorders Xeroderma Pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne Syndrome (CS) carry mutations in one of the 11 NER genes, linked to repair and basal transcription. Mutations in XPD lead to different phenotypes: XP, TTD, XP/CS or COFS (Cerebro-Oculo-Facio-Skeletal Syndrome), a rare form of CS. XP patients have high incidence of skin cancer, which does not occur in TTD or CS patients, although ther may present neurodegeneration, while all CS and TTD patients have neurodevelopmental symptoms linked to dysmielynation. The pathology of these neurological diseases is probably associated with deficient repair of DNA lesions in nervous cells, generated by endogenous processes. Many groups including ours have demonstrated the involvement of NER in the repair of these lesions, previously thought to be exclusively repaired by Base Excision Repair. In this work we show high sensitivity of both primary and transformed XP-D, XP-D/CS and TTD human fibroblasts in response to oxidative stress generated by photoactivated methylene blue, with prolonged cell cycle arrest and DNA damage signaling. The complementation of the three different cell lines with the XPD/ERCC2 gene was able to restore cell survival. We detected important differences in repair capacity/transcription resumption after damage generated by oxidative stress in plasmid DNA, besides the activation of different cell death pathways: XP-D cells have higher repair capacity and die by apoptosis, while XP-D/CS and TTD cells have little repair capacity and activate more than one death pathway (apoptosis and necrosis). We believe these differences can be related to the patients\' phenotypes. Mutations in DNA polymerase n coding gene, POLH, are associated with the variant form of XP (XP-V). Pol n is a translesion synthesis (TLS) polymerase specialized in the TLS past CPD photoproducts, besides other lesions like oxidized bases, and in other processes like somatic hypermutation and DNA replication in structured regions. In this work we show XP-V human fibroblasts are sensitive to oxidative stress. We detected an induction of pol n after genotoxic stress in primary cells, associated with increased ability to deal with the stalled replication fork, and consequently to DNA replication restart and cell survival. In addition, we detected a difference in genomic stability in immunoglobulin genes in aged XP-V patients in comparison to both young patients and age-matched controls, showing the absence of this polymerase may be linked to increased genomic instability in these genes