Artigos - Genética - IBB

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Behind Base J: The Roles of JBP1 and JBP2 on Trypanosomatids
(2023-03-01) Assis, Luiz Henrique de Castro [UNESP]; de Paiva, Stephany Cacete [UNESP]; Cano, Maria Isabel Nogueira [UNESP]; Universidade Estadual Paulista (UNESP)
β-D-glucopyranosyloxymethiluracil (Base J) is a modified thymidine base found in kinetoplastids and some related organisms. Interestingly, Base J distribution into the genome can vary depending on the organism and its life stage. Base J is reported to be found mostly at telomeric repeats, on inactive variant surface glycoproteins (VSG’s) expression sites (e.g., T. brucei), in RNA polymerase II termination sites and sub-telomeric regions (e.g., Leishmania). This hypermodified nucleotide is synthesized in two steps with the participation of two distinct thymidine hydroxylases, J-binding protein 1 and 2 (JBP1 and JBP2, respectively) and a β-glucosyl transferase. A third J-binding protein, named JBP3, was recently identified as part of a multimeric complex. Although its structural similarities with JBP1, it seems not to be involved in J biosynthesis but to play roles in gene expression regulation in trypanosomatids. Over the years, with the characterization of JBP1 and JBP2 mutant lines, Base J functions have been targeted and shone a light on that matter, showing genus-specific features. This review aims to explore Base J’s reported participation as a regulator of RNA polymerase II transcription termination and to summarize the functional and structural characteristics and similarities of the remarkable JBP proteins in pathogenic trypanosomatids.
Metabolism and Signaling of Plant Mitochondria in Adaptation to Environmental Stresses
(2022-10-01) Barreto, Pedro [UNESP]; Koltun, Alessandra; Nonato, Juliana; Yassitepe, Juliana; Maia, Ivan de Godoy [UNESP]; Arruda, Paulo; Universidade Estadual Paulista (UNESP); Universidade Estadual de Campinas (UNICAMP); Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA)
The interaction of mitochondria with cellular components evolved differently in plants and mammals; in plants, the organelle contains proteins such as ALTERNATIVE OXIDASES (AOXs), which, in conjunction with internal and external ALTERNATIVE NAD(P)H DEHYDROGENASES, allow canonical oxidative phosphorylation (OXPHOS) to be bypassed. Plant mitochondria also contain UNCOUPLING PROTEINS (UCPs) that bypass OXPHOS. Recent work revealed that OXPHOS bypass performed by AOXs and UCPs is linked with new mechanisms of mitochondrial retrograde signaling. AOX is functionally associated with the NO APICAL MERISTEM transcription factors, which mediate mitochondrial retrograde signaling, while UCP1 can regulate the plant oxygen-sensing mechanism via the PRT6 N-Degron. Here, we discuss the crosstalk or the independent action of AOXs and UCPs on mitochondrial retrograde signaling associated with abiotic stress responses. We also discuss how mitochondrial function and retrograde signaling mechanisms affect chloroplast function. Additionally, we discuss how mitochondrial inner membrane transporters can mediate mitochondrial communication with other organelles. Lastly, we review how mitochondrial metabolism can be used to improve crop resilience to environmental stresses. In this respect, we particularly focus on the contribution of Brazilian research groups to advances in the topic of mitochondrial metabolism and signaling.
Human chromosome telomeres
(2021-06-07) Barbé-Tuana, Florencia; Grun, Lucas Kich; Pierdoná, Vinícius; de Oliveira, Beatriz Cristina Dias [UNESP]; Paiva, Stephany Cacete [UNESP]; Shiburah, Mark Ewusi [UNESP]; da Silva, Vítor Luiz [UNESP]; Morea, Edna Gicela Ortiz [UNESP]; Fontes, Verônica Silva [UNESP]; Cano, Maria Isabel Nogueira [UNESP]; Pontifical Catholic University of Rio Grande do Sul (PUCRS); PUCRS; Federal University of Rio Grande do Sul (UFRGS); Universidade Estadual Paulista (UNESP)
Telomeres are specialized sequences at the end of linear chromosomes. Its conserved structure and function among eukaryotic cells suggest important evolutionary functions. Telomere dynamics play major roles in chromosomal integrity, stability, cellular replication and aging, performing crucial genome protective functions. In the majority of somatic cells, telomeres shorten in each round of cell replication. Whereas short telomeres are a trigger for apoptosis, accelerated attrition is a hallmark of aging, present in senescent and tumoral cells. Compensation for erosion in germinal and progenitor cells is accomplished by the telomerase enzyme, composed of a catalytic (TERT) and a RNA template (TR) subunits. Telomerase activity is tightly controlled with reactivation central for tumoral transformation. Clinical evidence suggests that telomeres' shortening that causally contributes to the establishment of specific progeria syndromes phenotypes are telomeropathies. In other cases, aging is accompanied by an abrupt telomere shortening in the context of chronic diseases, proposing telomeres length as an important biological pace marker for progression of various pathologies and aging. Because cancer cells reactivate TERT to compensate for telomeric loss, in the last decades, telomerase and the telomeres biology field have been subject to intense research in search for therapeutical targets for cancer. This chapter mainly focuses on basic telomere description and synthesis accomplished by the reverse transcriptase telomerase and its regulation. A final section addresses the understanding of telomeres in health and its contribution to cancer with therapeutic potentials for targeted inhibition.
Genetics of acheiropodia (“the handless and footless families of Brazil”): VIII. Penetrance and expressivity
(1975-01-01) Freire‐Maia, Ademar; Faculdade de Ciências Médicas e Biológicas
The acheiropodia data are shown to be consistent with the hypothesis of a fully penetrant gene in the homozygous state. The expressivity is shown to be generally constant, with some minor variation between individuals as well as between the two sides of the same affected person. Copyright © 1975, Wiley Blackwell. All rights reserved
Extending records of albinism and skin disorders in American cownose rays to southeastern Brazil
(2023-01-01) Rodrigues, Alexandre [UNESP]; Shkola, Wesley; Rangel, Bianca S.; Universidade Estadual Paulista (UNESP); líder da equipe Kapiloton; Universidade de São Paulo (USP)
Albinism is a genetic condition expressed as a lack of integumentary and retinal melanin. Although documented across many vertebrate species, albinism and other skin disorders are rarely observed in elasmobranchs (sharks and rays). The present study describes the first confirmed case of albinism in American cownose ray (Rhinoptera bonasus), and three other juveniles of the species with undetermined skin disorders observed in São Paulo, southeastern Brazil. Pigmentation disorders have already been observed in American cownose rays from the North Atlantic, including two cases of leucism and a possible albinism. Based on the results, it was discussed the possible consequences of albinism for the ray survival as well as the possible causes for the undetermined skin disorders.
Investigating an Unknown Biodiversity: Evidence of Distinct Lineages of the Endemic Chola Guitarfish Pseudobatos percellens Walbaum, 1792 in the Western Atlantic Ocean
(2023-03-01) Cruz, Vanessa P. [UNESP]; Rotundo, Matheus M.; Charvet, Patrícia; Boza, Beatriz R. [UNESP]; Souza, Bruno C. [UNESP]; Cerqueira, Najila N. C. D. [UNESP]; Oliveira, Claudio [UNESP]; Lessa, Rosângela; Foresti, Fausto [UNESP]; Universidade Estadual Paulista (UNESP); UNISANTA; Universidade Federal do Ceará; Universidade Federal Rural de Pernambuco
Anthropogenic actions have affected marine species for a long time, through overexploitation of natural stocks and habitat degradation, influencing the life strategies of several taxa, especially rays and sharks, which have suffered significant population declines in recent years. Therefore, conservation actions and stock management have become paramount. In this regard, chola guitarfish, Pseudobatos percellens, distributed throughout the Brazilian coast, is often commercially fished by local artisanal fleets or as by-catch in shrimp trawl fisheries. Therefore, this study aimed to understand the genetic diversity of P. percellens throughout the Brazilian coast, using single nucleotide polymorphisms (SNPs). Genetic analyses employing 3329 SNPs revealed a hidden biodiversity within P. percellens, with at least one lineage occurring in the Northern and Northeastern regions and another distributed in the Southeastern/Southern Brazilian coast, with high genetic differentiation between them. However, the Discriminant Analysis of Principal Components (DAPC) indicated the presence of in fact three lineages distributed in these regions that must still be better investigated. Therefore, to ensure adequate conservation of chola guitarfish biodiversity, populations must be managed separately along the Brazilian coast. Furthermore, the need for a taxonomic review for this group is noted.
Nuclear and Kinetoplast DNA Replication in Trypanosomatids
(Bentham Science Publ, 2017-01-01) Silva, Marcelo S. da; Viviescas, Maria Alejandra [UNESP]; Pavani, Raphael Souza; Ortiz, Edna Gicela [UNESP]; Storti, Camila B. [UNESP]; Cano, Maria Isabel N. [UNESP]; DaSilva, M. S.; Cano, MIN; Butantan Inst; Universidade Estadual Paulista (UNESP)
Trypanosomatids are among the most primitive eukaryotes and therefore exhibit both conserved and unique non-conserved features in the DNA replication machinery. In eukaryotes, nuclear DNA replication is preceded by the assembly of the pre-replication complex (pre-RC), which is coordinated by the six-subunit origin recognition complex (ORC), which together with the Cdc6 and Cdt1 proteins play a central role in the loading of the hetero-hexamer Mcm(2-7). In the domain Archaea there are no Cdt1 protein homologs, Mcm is a homo-hexamer, which is recruited by a protein that shows homology with ORC, and Cdc6 (called Orc/ Cdc6). Curiously, trypanosomatid pre-RC differs from others eukaryotes in this context, and it appears more similar to that of Archaea, presenting a homolog of protein Orc/Cdc6 and no homologs of Cdt1, in addition to present Mcm as a hetero-hexamer complex. The completion of DNA replication, at trypanosomatid telomeres, apparently is similar to other eukaryotes, although the processing of the leading and lagging telomeres required to generate the 3' overhangs, which serves as telomerase substrate, remains unknown. With the generation of overhangs at the ends of the chromosomes, telomeres are frequently extended by the action of telomerase, whose control also remains unknown. It is worth mentioning that DNA replication in trypanosomatids initiates almost simultaneously in the nucleus and the kinetoplast, suggesting that regulation of DNA synthesis in the two DNA-containing organelles may be coordinated. The kinetoplast DNA (kDNA) consists of mini- and maxicircles, which are replicated by many proteins whose mechanisms of action remain unclear. This chapter aims to review and discuss the complex DNA replication mechanisms that act independently in the kinetoplast and the nucleus, as well as some fascinating peculiarities exclusive to trypanosomatids protozoa group.
Homeostasis of DNA Integrity
(Crc Press-taylor & Francis Group, 2018-01-01) Segatto, Marcela; Nogueira Cano, Maria Isabel [UNESP]; DelMoral, A. M.; Goni, G. Z.; Fac Brasileira Multivix Vitoria; Universidade Estadual Paulista (UNESP)
Gene-associated markers as a genomic and transcriptomic resource for a highly migratory and apex predator shark (Isurus oxyrinchus)
(2022-09-01) Domingues, Rodrigo R.; Mastrochirico-Filho, Vito Antonio [UNESP]; Mendes, Natalia J. [UNESP]; Hashimoto, Diogo T. [UNESP]; Coelho, Rui; Antunes, Agostinho; Foresti, Fausto [UNESP]; Mendonça, Fernando F.; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Universidade Estadual Paulista (UNESP); Instituto Português do Mar e da Atmosfera–IPMA; Universidade do Algarve; University of Porto
The shortfin mako, Isurus oxyrinchus, is an oceanic pelagic shark species found worldwide in tropical and subtropical waters. It is frequently caught by pelagic longline fisheries, but despite its commercial importance and ecological significance, little is still known about its biology and ecology at the molecular level. Therefore, we combined two massive parallel sequencing approaches, double digest restriction site-associated DNA sequencing (ddRAD) and RNA sequencing (RNAseq), for single nucleotide polymorphism (SNP) discovery in the shortfin mako. The ddRAD yielded a total of 82,676 putative SNPs. For RNAseq, a total of 129,663 putative SNPs were found. After the stricter filtering procedure, 405 SNPs from ddRAD and 1165 SNPs from RNAseq were retained and suitable for further analysis. Annotation analysis of SNPs from ddRAD revealed a total of 55 gene associated SNP markers, of which 32 SNPs (58.2%) are associated with diseases and defense responses, 9 SNPs (16.4%) are associated with developmental process, and 3 SNPs (5.4%) are present in genes involved in the reproductive function. For RNAseq, 739 SNPs were annotated and associated to relevant functions amongst which 10 SNPs (0.53%) were related with reproduction, 6 SNPs (0.32%) with growth, and 9 (0.48%) with locomotion. Overall, the genotyping of the SNPs was followed by the validation of 255 SNPs from ddRAD and 646 for RNAseq in 31 individuals from the Atlantic and Indian oceans. Our results provide valuable sequence resources for future population genomics analysis, comparative genomics, phylogenomics, and molecular evolution of the globally endangered shortfin mako shark.
DNA Barcoding and Species Delimitation for Dogfish Sharks Belonging to the Squalus Genus (Squaliformes: Squalidae)
(2022-07-01) Ariza, Ailton A. [UNESP]; Adachi, Aisni M. C. L. [UNESP]; Roque, Pollyana; Hazin, Fabio H. V.; Vianna, Marcelo; Rotundo, Matheus M.; Delpiani, Sergio M.; de Astarloa, Juan M. Díaz; Delpiani, Gabriela; Oliveira, Claudio [UNESP]; Foresti, Fausto [UNESP]; Cruz, Vanessa P. [UNESP]; Universidade Estadual Paulista (UNESP); Universidade Federal Rural de Pernambuco; Universidade Federal do Rio de Janeiro (UFRJ); Universidade Santa Cecília; Instituto de Investigaciones Marinas y Costeras; CABA AAJ
The Squalus genus comprises a group of small demersal sharks occurring circumglobally, popularly known as dogfish sharks. This genus exhibits a conserved morphology, thus making correct morphological identification difficult. Considering these taxonomic problems and the scarcity of molecular data, the present study aimed to identify Squalus genus MOTUs, using DNA barcoding for species delimitation via ABGD (automatic barcode gap discovery), PTP (Poisson tree process), and GMYC (general mixed Yule coalescent) employing the mitochondrial COI gene. A total of 69 sequences were generated from samples obtained from the American coast in both the Atlantic and Pacific Oceans. The ABGD analysis was the most conservative among the three applied delimitations, indicating three taxonomic units, while the PTP analysis revealed nine MOTUs, with two conflicting units noted between S. clarkae + S. mitsukurii and S. albicaudus + S. cubensis. The GMYC analysis indicated an excessive division, with S. acanthias and S. mitsukurii subdivided into six MOTUs each and S. blainville, into four. These findings demonstrated that Squalus presents a complex of previously defined species, with misidentified samples deposited in databases leading to difficulties in analyzing the real distribution and diversity of species belonging to this genus. Thus, further efforts to highlight possible new species are recommended.
B Chromosomes in Psalidodon scabripinnis (Characiformes, Characidae) Species Complex
(Mdpi, 2022-09-01) Silva, Duilio M. Z. A. [UNESP]; Castro, Jonathan P.; Goes, Caio A. G. [UNESP]; Utsunomia, Ricardo [UNESP]; Vidal, Mateus R. [UNESP]; Nascimento, Cristiano N. [UNESP]; Lasmar, Lucas F. [UNESP]; Paim, Fabilene G. [UNESP]; Soares, Leticia B. [UNESP]; Oliveira, Claudio [UNESP]; Porto-Foresti, Fabio [UNESP]; Artoni, Roberto F.; Foresti, Fausto [UNESP]; Universidade Estadual Paulista (UNESP); Universidade Federal de São Carlos (UFSCar); Universidade Estadual de Ponta Grossa (UEPG); Fed Rural Univ Rio Janeiro
Simple Summary For more than a century, B chromosomes have been investigated in several eukaryotic species. These supernumerary genomic elements behave as parasites or provide fitness benefits to the hosts. They are mostly composed of repetitive DNA, but they also have protein-coding genes. B chromosomes are associated with differential gene expression and phenotypic effects. This makes them one of the most interesting genomic elements to investigate. Fish species of the Psalidodon genus harbor a great diversity of B chromosomes. Recent studies showed they share a common ancestor, persisting in the genus for a long time and enduring speciation processes. In the Psalidodon scabripinnis species complex, B chromosomes express their own genes, mostly related to cell cycle and gonad differentiation. Moreover, these B chromosomes are associated with functional effects, e.g., cell cycle extension. Here, we review the current knowledge regarding these elements in the P. scabripinnis species complex and propose a chromosome speciation model facilitated by the B chromosome manipulation of the cell machinery. B chromosomes are extra-genomic components of cells found in individuals and in populations of some eukaryotic organisms. They have been described since the first observations of chromosomes, but several aspects of their biology remain enigmatic. Despite being present in hundreds of fungi, plants, and animal species, only a small number of B chromosomes have been investigated through high-throughput analyses, revealing the remarkable mechanisms employed by these elements to ensure their maintenance. Populations of the Psalidodon scabripinnis species complex exhibit great B chromosome diversity, making them a useful material for various analyses. In recent years, important aspects of their biology have been revealed. Here, we review these studies presenting a comprehensive view of the B chromosomes in the P. scabripinnis complex and a new hypothesis regarding the role of the B chromosome in the speciation process.
The Long Non-Coding RNA SNHG12 as a Mediator of Carboplatin Resistance in Ovarian Cancer via Epigenetic Mechanisms
(2022-04-01) Abildgaard, Cecilie; Do Canto, Luisa Matos; Rainho, Cláudia Aparecida [UNESP]; Marchi, Fabio Albuquerque; Calanca, Naiade [UNESP]; Waldstrøm, Marianne; Steffensen, Karina Dahl; Rogatto, Silvia Regina; Lillebaelt University Hospital of Southern Denmark; Universidade Estadual Paulista (UNESP); CIPE—C. Camargo Cancer Center; University of Southern Denmark
Genetic and epigenetic changes contribute to intratumor heterogeneity and chemotherapy resistance in several tumor types. LncRNAs have been implicated, directly or indirectly, in the epigenetic regulation of gene expression. We investigated lncRNAs that potentially mediate carboplatin-resistance of cell subpopulations, influencing the progression of ovarian cancer (OC). Four carboplatin-sensitive OC cell lines (IGROV1, OVCAR3, OVCAR4, and OVCAR5), their derivative resistant cells, and two inherently carboplatin-resistant cell lines (OVCAR8 and Ovc316) were subjected to RNA sequencing and global DNA methylation analysis. Integrative and cross-validation analyses were performed using external (The Cancer Genome Atlas, TCGA dataset, n = 111 OC samples) and internal datasets (n = 39 OC samples) to identify lncRNA candidates. A total of 4255 differentially expressed genes (DEGs) and 14529 differentially methylated CpG positions (DMPs) were identified comparing sensitive and resistant OC cell lines. The comparison of DEGs between OC cell lines and TCGA-OC dataset revealed 570 genes, including 50 lncRNAs, associated with carboplatin resistance. Eleven lncRNAs showed DMPs, including the SNHG12. Knockdown of SNHG12 in Ovc316 and OVCAR8 cells increased their sensitivity to carboplatin. The results suggest that the lncRNA SNHG12 contributes to carboplatin resistance in OC and is a potential therapeutic target. We demonstrated that SNHG12 is functionally related to epigenetic mechanisms.
Comprehensive In Silico Analysis and Transcriptional Profiles Highlight the Importance of Mitochondrial Dicarboxylate Carriers (DICs) on Hypoxia Response in Both Arabidopsis thaliana and Eucalyptus grandis
(2022-01-01) Barreto, Pedro [UNESP]; Arcuri, Mariana L. C. [UNESP]; Lima, Rômulo Pedro Macêdo [UNESP]; Marino, Celso Luis [UNESP]; Maia, Ivan G. [UNESP]; Universidade Estadual Paulista (UNESP)
Plant dicarboxylate carriers (DICs) transport a wide range of dicarboxylates across the mitochondrial inner membrane. The Arabidopsis thaliana DIC family is composed of three genes (AtDIC1, 2 and 3), whereas two genes (EgDIC1 and EgDIC2) have been retrieved in Eucalyptus grandis. Here, by combining in silico and in planta analyses, we provide evidence that DICs are partially redundant, important in plant adaptation to environmental stresses and part of a low-oxygen response in both species. AtDIC1 and AtDIC2 are present in most plant species and have very similar gene structure, developmental expression patterns and absolute expression across natural Arabidopsis accessions. In contrast, AtDIC3 seems to be an early genome acquisition found in Brassicaceae and shows relatively low (or no) expression across these accessions. In silico analysis revealed that both AtDICs and EgDICs are highly responsive to stresses, especially to cold and submergence, while their promoters are enriched for stress-responsive transcription factors binding sites. The expression of AtDIC1 and AtDIC2 is highly correlated across natural accessions and in response to stresses, while no correlation was found for AtDIC3. Gene ontology enrichment analysis suggests a role for AtDIC1 and AtDIC2 in response to hypoxia, and for AtDIC3 in phosphate starvation. Accordingly, the investigated genes are induced by submergence stress in A. thaliana and E. grandis while AtDIC2 overexpression improved seedling survival to submergence. Interestingly, the induction of AtDIC1 and AtDIC2 is abrogated in the erfVII mutant that is devoid of plant oxygen sensing, suggesting that these genes are part of a conserved hypoxia response in Arabidopsis.
Brazilian green propolis: A novel tool to improve the cytotoxic and immunomodulatory action of docetaxel on MCF-7 breast cancer cells and on women monocyte
(2022-01-01) de Oliveira Cardoso, Eliza [UNESP]; Santiago, Karina Basso [UNESP]; Conti, Bruno José [UNESP]; Conte, Fernanda Lopes [UNESP]; Tasca, Karen Ingrid [UNESP]; Romagnoli, Graziela Gorete; de Assis Golim, Marjorie [UNESP]; Rainho, Cláudia Aparecida [UNESP]; Bastos, Jairo Kenupp; Sforcin, José Maurício [UNESP]; Universidade Estadual Paulista (UNESP); Oeste Paulista University (UNOESTE); Universidade de São Paulo (USP)
Docetaxel (DTX) is used against breast cancer despite its side effects such as toxicity and immunosuppression. Here we investigated the cytotoxic and immunomodulatory effects of the ethanol solution extract of propolis (EEP) in combination with DTX on MCF-7 breast cancer cells and on women's monocyte. The cytotoxic potential of EEP + DTX was assessed by MTT assay and the type of tumor cell death was evaluated by flow cytometry. The effects of EEP + DTX on the migration and invasion of MCF-7 cells were analyzed. Cytokine production by monocytes was assessed by ELISA and the expression of cell surface markers was evaluated by flow cytometry. We also assessed the fungicidal activity of monocytes against Candida albicans and the generation of reactive oxygen species (ROS). Finally, the impact of the supernatants of treated monocytes in the viability, migration, and invasiveness of tumor cells was assessed. EEP enhanced the cytotoxicity of DTX alone against MCF-7 cells by inducing necrosis and inhibiting their migratory ability. EEP + DTX exerted no cytotoxic effects on monocytes and stimulated HLA-DR expression, TNF-α, and IL-6 production, exerted an immunorestorative action in the fungicidal activity, and reduced the oxidative stress. Our findings have practical implications and reveal new insights for complementary medicine.
Systemic treatment of penile squamous cell carcinoma—hurdles and hopes of preclinical models and clinical regimens: a narrative review
(2021-10-01) Thomas, Anita; do Canto Alvim, Luisa Matos; Rainho, Claudia Aparecida [UNESP]; Juengel, Eva; Blaheta, Roman Alexander; Spiess, Philippe E.; Rogatto, Silvia Regina; Tsaur, Igor; University Medicine Mainz; University of Southern Denmark; Universidade Estadual Paulista (UNESP); Goethe University Hospital Frankfurt; Moffitt Cancer Center
Despite contemporary research efforts, the prognosis of penile squamous cell carcinoma (PeSCC) has not significantly improved over the past decade. Despite frequently encountered patient-related delayed medical consultations impairing outcomes, several other aspects contribute to the lack of advancement in the treatment of this condition. One essential reason is that translational research, a prerequisite for the clinically successful disease management, is still at an early stage in PeSCC as compared to many other malignancies. Preclinical experimental models are indispensable for the evaluation of tumor biology and identification of genomic alterations. However, since neither commercial PeSCC cell lines are available nor xenograft models sustainably established, such analyses are challenging in this field of research. In addition, systemic therapies are less effective and toxic without decisive breakthroughs over recent years. Current systemic management of PeSCC is based on protocols that have been investigated in small series of only up to 30 patients. Thus, there is an unmet medical need for new approaches necessitating research efforts to develop more efficacious systemic strategies. This review aims to highlight the current state of knowledge in the molecular alterations involved in the etiology and ensuing steps for cancer progression, existing preclinical models of translational research, clinically relevant systemic protocols, and ongoing clinical trials.
Physical, functional and biochemical features of Nanoskin® bacterial cellulose scaffold as a potential carrier for cell transference
(2022-02-01) Viveiros, Magda Massae Hata [UNESP]; Rainho, Cláudia Aparecida [UNESP]; Ramirez, Jofer Andree Zamame [UNESP]; Kaneno, Ramon [UNESP]; Silva, Márcia Guimarães [UNESP]; Ximenes, Valdecir Farias [UNESP]; de Olyveira, Gabriel Molina; Basmaji, Pierre; Di Girolamo, Nick; Schellini, Silvana Artioli [UNESP]; Universidade Estadual Paulista (UNESP); Innovatecs Biotechnological Research and Development; University of New South Wales
We evaluated the feasibility of Nanoskin®, a bacterial cellulose (BC) nanofiber membrane, as a potential scaffold for cell transference therapy. Nanoskin® does not induce lymphocyte proliferation, but it does not kill lymphocytes. Human mesenchymal stem cells (MSCs) and lymphocytes produced significantly elevated amounts of interleukin (IL)-10 (p = 0.0005; p = 0.02) when in contact with Nanoskin®. In conclusion, the Nanoskin® can be a promising biomaterial for use as a cell carrier-scaffold in cell transference therapies.
DNA barcode regions for differentiating Cattleya walkeriana and C. loddigesii
(2017-01-01) Rivera-Jiménez, Hernando [UNESP]; Rossini, Bruno César [UNESP]; Tambarussi, Evandro Vagner [UNESP]; Veasey, Elizabeth Ann; Ibanes, Bruna; Marino, Celso Luis [UNESP]; Universidade Estadual Paulista (UNESP); Universidade Estadual do Centro-Oeste; Universidade de São Paulo (USP)
Growers appreciate Cattleya walkeriana and C. loddigesii due to striking shape and rarity. Thus, this study aimed to evaluate the feasibility of DNA barcode regions, namely ITS1, ITS2 and rpoC1, to discriminate between C. walkeriana and C. loddigesii species. DNA barcode regions were successfully amplified using primers designed to amplify plants. We also included sequences from public databases in order to test if these regions were able to discriminate C. walkeriana and C. loddigesii from other Cattleya species. These regions, and their combinations, demonstrated that the ITS1+ITS2 had the highest average interspecific distance (11.1%), followed by rpoC1 (1.06%). For species discrimination, ITS1+ITS2 provided the best results. The combined data set of ITS1+ITS2+rpoC1 also discriminated both species, but did not result in higher rates of discrimination. These results indicate that ITS region is the best option for molecular identification of these two species and from some other species of this genus.
Persistência e liberação de macronutrientes e silício da fitomassa de crotalária em função da fragmentação
(2012-08-06) da Costa, Claudio Hideo Martins [UNESP]; Crusciol, Carlos Alexandre Costa [UNESP]; Soratto, Rogério Peres [UNESP]; Ferrari Neto, Jayme [UNESP]; Universidade Estadual Paulista (UNESP)
The persistence of straw, as well as the dynamics of nutrients release of it, are important aspects to consider in the choice of plants for composition of crop rotations in a no tillage system. Thus, the objective of this work was to evaluate the decomposition rate and macronutrients and silicon (Si) release from sunn hemp (Crotalaria juncea L.) phytomass, as a function of management, with and without fragmentation. A randomized blocks design, with four replications, in a factorial 2×6, constituted by two aboveground phytomass management after 75 days after emergence (with and without mechanical fragmentation) and six sampling times (0, 18, 32, 46, 74 and 91 days after management (DAM)), were evaluated the decomposition rate and nutrient release from sunn hemp biomass. The mechanical fragmentation of sunn hemp straw did not change the decomposition and macronutrients release. The maximum release rates occurred 0-18 DAM. Potassium is the most rapidly available nutrient, while the silicon is more slowly released to the ground. Over time there has been increasing Si content in the straw.
Studies of the human sex ratio and factors influencing family size in Botucatu, Brazil
(1977-01-01) Gray, Elmer; Bortolozzi, Jehud [UNESP]; Western Kentucky University; Universidade Estadual Paulista (UNESP)
Yeast Double Transporter Gene Deletion Library for Identification of Xenobiotic Carriers in Low or High Throughput
(2021-12-01) Almeida, Ludimila Dias; Silva, Ali Salim Faraj; Mota, Daniel Calixto; Vasconcelos, Adrielle Ayumi; Camargo, Antônio Pedro; Pires, Gabriel Silva; Furlan, Monique; Da Cunha Freire, Helena Martins Ribeiro; Klippel, Angélica Hollunder [UNESP]; Silva, Suélen Fernandes [UNESP]; Zanelli, Cleslei Fernando [UNESP]; Carazzolle, Marcelo Falsarella; Oliver, Stephen G.; Bilsland, Elizabeth; Universidade Estadual de Campinas (UNICAMP); Universidade Estadual Paulista (UNESP); University of Cambridge
The routes of uptake and efflux should be considered when developing new drugs so that they can effectively address their intracellular targets. As a general rule, drugs appear to enter cells via protein carriers that normally carry nutrients or metabolites. A previously developed pipeline that searched for drug transporters using Saccharomyces cerevisiae mutants carrying single-gene deletions identified import routes for most compounds tested. However, due to the redundancy of transporter functions, we propose that this methodology can be improved by utilizing double mutant strains in both low- and high-throughput screens. We constructed a library of over 14,000 strains harboring double deletions of genes encoding 122 nonessential plasma membrane transporters and performed low- and high-throughput screens identifying possible drug import routes for 23 compounds. In addition, the high-throughput assay enabled the identification of putative efflux routes for 21 compounds. Focusing on azole antifungals, we were able to identify the involvement of the myo-inositol transporter, Itr1p, in the uptake of these molecules and to confirm the role of Pdr5p in their export.

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