The landscape of lncRNAs in cell granules: Insights into their significance in cancer.

Cellular compartmentalization, achieved through membrane-based compartments, is a fundamental aspect of cell biology that contributes to the evolutionary success of cells. While organelles have traditionally been the focus of research, membrane-less organelles (MLOs) are emerging as critical players, exhibiting distinct morphological features and unique molecular compositions. Recent research highlights the pivotal role of long noncoding RNAs (lncRNAs) in MLOs and their involvement in various cellular processes across different organisms. In the context of cancer, dysregulation of MLO formation, influenced by altered lncRNA expression, impacts chromatin organization, oncogenic transcription, signaling pathways, and telomere lengthening. This review synthesizes the current understanding of lncRNA composition within MLOs, delineating their functions and exploring how their dysregulation contributes to human cancers. Environmental challenges in tumorigenesis, such as nutrient deprivation and hypoxia, induce stress granules, promoting cancer cell survival and progression. Advancements in biochemical techniques, particularly single RNA imaging methods, offer valuable tools for studying RNA functions within live cells. However, detecting low-abundance lncRNAs remains challenging due to their limited expression levels. The correlation between lncRNA expression and pathological conditions, particularly cancer, should be explored, emphasizing the importance of single-cell studies for precise biomarker identification and the development of personalized therapeutic strategies. This article is categorized under: RNA Export and Localization > RNA Localization RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.

Stress-induced phosphoprotein 1: how does this co-chaperone influence the metastasis steps?

In several cancer types, metastasis is associated with poor prognosis, survival, and quality of life, representing a life risk more significant than the primary tumor itself. Metastasis is a multi-step process that spreads tumor cells from primary sites to surrounding or distant organs, originating secondary tumors. The interconnected steps that drive metastasis depend of several capabilities that enable cells to detach from the primary tumor, acquire motility and migrate through the basal membrane; invade and spread through the vascular system, and finally settle and originate a new tumor. Recently, stress-induced phosphoprotein 1 (STIP1) has emerged as a protein capable of driving tumor cells through these metastasis steps by mediating several biological processes and signaling pathways. This protein is mainly known for its function as a co-chaperone, acting as a scaffold for the interaction of its client heat-shock proteins Hsp70/90 chaperones; however, it is also known that STIP1 can act independently of chaperones to activate downstream phosphorylation pathways. The over-expression of STIP1 has been reported across various cancer types, identifying it as a potential biomarker for predicting patient prognosis and monitoring the progression of metastasis. Here, we present a discussion on how this co-chaperone mediates the initial steps of metastasis (cell adhesion loss, epithelial-to-mesenchymal transition, and angiogenesis), highlighting the biological mechanisms in which STIP1 plays a vital role, also presenting an overview of the current knowledge regarding its clinical relevance.

Organohalogen compounds in a hotspot for chemical pollution: Assessment in free-ranging Atlantic spotted dolphins (Stenella frontalis).

The assessment of chemical pollution in free-ranging living mammals is viable using remote biopsies and portrays a comprehensive scenario of environmental health. The Southwestern Atlantic Ocean holds incredible biodiversity, but it is under the constant and invisible threat of persistent organic pollutants (POPs) of anthropogenic origin, such as pesticides, brominated flame retardants, and industrial-use compounds (e.g., PCBs). Thus, this study aimed to assess the bioaccumulation of POPs (PCBs, DDTs, HCB, mirex and PBDEs) and natural organobromine compounds (MeO-BDEs) using gas-chromatography coupled to mass spectrometry in biopsy samples of Atlantic spotted dolphins (Stenella frontalis, n = 20) that inhabit and forage both inside and in adjacent areas to degraded (Guanabara Bay) and conserved (Ilha Grande Bay) coastal bays in the Southeastern Brazil. Among the studied compounds, PCBs were predominant in the contamination profile with median concentration of 97.0 µg.g-1 lipid weight (lw), followed by the sum of the p,p' isomers of DDT, DDD, and DDE of 11.0 µg.g-1 lw, the brominated flame retardants PBDEs of 1.6 µg.g-1 lw, and the other organochlorine pesticides mirex of 0.78 µg.g-1 lw, and HCB of 0.049 µg.g-1 lw. The MeO-BDEs were detected with a median concentration of 22.8 µg.g-1 lw. 85 % of the Atlantic spotted dolphins analyzed in this study presented PCB concentration that exceeded even the less conservative threshold limits for adverse health effects (41 µg.g-1 lw). This study shows that despite the conservation status of preserved bays, cetacean species foraging in these locations are still under increased threat. Hence chemical pollution demands local and global efforts to be mitigated.

Targeting EphA2: a promising strategy to overcome chemoresistance and drug resistance in cancer.

Erythropoietin-producing hepatocellular A2 (EphA2) is a vital member of the Eph tyrosine kinase receptor family and has been associated with developmental processes. However, it is often overexpressed in tumors and correlates with cancer progression and worse prognosis due to the activation of its noncanonical signaling pathway. Throughout cancer treatment, the emergence of drug-resistant tumor cells is relatively common. Since the early 2000s, researchers have focused on understanding the role of EphA2 in promoting drug resistance in different types of cancer, as well as finding efficient and secure EphA2 inhibitors. In this review, the current knowledge regarding induced resistance by EphA2 in cancer treatment is summarized, and the types of cancer that lead to the most cancer-related deaths are highlighted. Some EphA2 inhibitors were also investigated. Regardless of whether the cancer treatment has reached a drug-resistance stage in EphA2-overexpressing tumors, once EphA2 is involved in cancer progression and aggressiveness, targeting EphA2 is a promising therapeutic strategy, especially in combination with other target-drugs for synergistic effect. For that reason, monoclonal antibodies against EphA2 and inhibitors of this receptor should be investigated for efficacy and drug toxicity.

Biomarker potential of the LEF1/TCF family members in breast cancer: Bioinformatic investigation on expression and clinical significance.

The LEF1/TCF transcription factor family is related to the development of diverse tissue types, including the mammary tissue, and dysregulation of its expression and function has been described to favor breast tumorigenesis. However, the clinical and biological relevance of this gene family in breast cancer is still poorly understood. Here, we used bioinformatics approaches aiming to reduce this gap. We investigated its expression patterns in molecular and immune breast cancer subtypes; its correlation with immune cell infiltration, and its prognostic values in predicting outcomes. Also, through regulons construction, we determined the genes whose expression is influenced by these transcription factors, and the pathways in which they are involved. We found that LEF1 and TCF3 are over-expressed in breast tumors regarding non-tumor samples, while TCF4 and TCF7 are down-expressed, with the gene's methylation status being associated with its expression dysregulation. All four transcription factors presented significance at the diagnostic and prognostic levels. LEF1, TCF4, and TCF7 presented a significant correlation with immune cell infiltration, being associated with the immune subtypes of less favorable outcomes. Altogether, this research contributes to a more accurate understanding of the expression and clinical and biomarker significance of the LEF1/TCF transcription factors in breast cancer.

Screening of Exosome-Derived Proteins and Their Potential as Biomarkers in Diagnostic and Prognostic for Pancreatic Cancer.

In the oncological area, pancreatic cancer is one of the most lethal diseases, with 5-year survival rising just 10% in high-development countries. This disease is genetically characterized by KRAS as a driven mutation followed by SMAD4, CDKN2, and TP53-associated mutations. In clinical aspects, pancreatic cancer presents unspecific clinical symptoms with the absence of screening and early plasmatic biomarker, being that CA19-9 is the unique plasmatic biomarker having specificity and sensitivity limitations. We analyzed the plasmatic exosome proteomic profile of 23 patients with pancreatic cancer and 10 healthy controls by using Nanoscale liquid chromatography coupled to tandem mass spectrometry (NanoLC-MS/MS). The pancreatic cancer patients were subdivided into IPMN and PDAC. Our findings show 33, 34, and 7 differentially expressed proteins when comparing the IPMN vs. control, PDAC-No treatment vs. control, and PDAC-No treatment vs. IPMN groups, highlighting proteins of the complement system and coagulation, such as C3, APOB, and SERPINA. Additionally, PDAC with no treatment showed 11 differentially expressed proteins when compared to Folfirinox neoadjuvant therapy or Gemcitabine adjuvant therapy. So here, we found plasmatic exosome-derived differentially expressed proteins among cancer patients (IPMN, PDAC) when comparing with healthy controls, which could represent alternative biomarkers for diagnostic and prognostic evaluation, supporting further scientific and clinical studies on pancreatic cancer.

Fatal toxoplasmosis in a captive squirrel monkey (Saimiri boliviensis) in Portugal.

New World monkeys are especially vulnerable to develop severe clinical manifestations and succumb to acute toxoplasmosis. This study aimed to describe the histopathological findings and genotypic characterization of the Toxoplasma gondii strain involved in a lethal case occurring in a zoo-housed black-capped squirrel monkey (Saimiri boliviensis) in Portugal. Cyst-like structures suggestive of Sarcocystidae parasites and acute injuries in liver and brain were observed by light microscopy examination. By immunohistochemistry, calprotectin, T. gondii antigen and Iba1 antigen had a positive signaling in lung, liver and brain tissues. Toxoplasma gondii B1, ITS1 and 529 repetitive element fragments amplifications together with the genotyping of 13 microsatellite markers confirmed a systemic T. gondii infection linked to a non-clonal type II strain. This description is consistent to the majority T. gondii strains circulating in Europe.

High-throughput proteomics of breast cancer subtypes: Biological characterization and multiple candidate biomarker panels to patients' stratification.

BACKGROUND AND AIMS: The actual classification of breast tumors in subtypes represents an attempt to stratify patients into clinically cohesive groups, nevertheless, clinicians still lack reproducible and reliable protein biomarkers for breast cancer subtype discrimination. In this study, we aimed to access the differentially expressed proteins between these tumors and its biological implications, contributing to the subtype's biological and clinical characterization, and with protein panels for subtype discrimination. METHODS: In our study, we applied high-throughput mass spectrometry, bioinformatic, and machine learning approaches to investigate the proteome of different breast cancer subtypes. RESULTS: We identified that each subtype depends on different protein expression patterns to sustain its malignancy, and also alterations in pathways and processes that can be associated with each subtype and its biological and clinical behaviors. Regarding subtype biomarkers, our panels achieved performances with at least 75% of sensibility and 92% of specificity. In the validation cohort, the panels obtained acceptable to outstanding performances (AUC = 0.740 to 1.00). CONCLUSIONS: In general, our results expand the accuracy of breast cancer subtypes' proteomic landscape and improve the understanding of its biological heterogeneity. In addition, we identified potential protein biomarkers for the stratification of breast cancer patients, improving the repertoire of reliable protein biomarkers. SIGNIFICANCE: Breast cancer is the most diagnosed cancer type worldwide and the most lethal cancer in women. As a heterogeneous disease, breast cancer tumors can be classified into four major subtypes, each presenting particular molecular alterations, clinical behaviors, and treatment responses. Thus, a pivotal step in patient management and clinical decisions is accurately classifying breast tumor subtypes. Currently, this classification is made by the immunohistochemical detection of four classical markers (estrogen receptor, progesterone receptor, HER2 receptor, and the Ki-67 index); however, it is known that these markers alone do not fully discriminate the breast tumor subtypes. Also, the poor understanding of the molecular alterations of each subtype leads to a challenging decision-making process regarding treatment choice and prognostic determination. This study, through high-throughput label-free mass-spectrometry data acquisition and downstream bioinformatic analysis, advances in the proteomic discrimination of breast tumors and achieves an in-depth characterization of the subtype's proteomes. Here, we indicate how the variations in the subtype's proteome can influence the tumor's biological and clinical differences, highlighting the variation in the expression pattern of oncoproteins and tumor suppressor proteins between subtypes. Also, through our machine-learning approach, we propose multi-protein panels with the potential to discriminate the breast cancer subtypes. Our panels achieved high classification performance in our cohort and in the independent validation cohort, demonstrating their potential to improve the current tumor discrimination system as complements to the classical immunohistochemical classification.

Major regulators of the multi-step metastatic process are potential therapeutic targets for breast cancer management.

Metastasis is a multi-step process that leads to the dissemination of tumor cells to new sites and, consequently, to multi-organ neoplasia. Although most lethal breast cancer cases are related to metastasis occurrence, little is known about the dysregulation of each step, and clinicians still lack reliable therapeutic targets for metastasis impairment. To fill these gaps, we constructed and analyzed gene regulatory networks for each metastasis step (cell adhesion loss, epithelial-to-mesenchymal transition, and angiogenesis). Through topological analysis, we identified E2F1, EGR1, EZH2, JUN, TP63, and miR-200c-3p as general hub-regulators, FLI1 for cell-adhesion loss specifically, and TRIM28, TCF3, and miR-429 for angiogenesis. Applying the FANMOD algorithm, we identified 60 coherent feed-forward loops regulating metastasis-related genes associated with distant metastasis-free survival prediction. miR-139-5p, miR-200c-3p, miR-454-3p, and miR-1301-3p, among others, were the FFL's mediators. The expression of the regulators and mediators was observed to impact overall survival and to go along with metastasis occurrence. Lastly, we selected 12 key regulators and observed that they are potential therapeutic targets for canonical and candidate antineoplastics and immunomodulatory drugs, like trastuzumab, goserelin, and calcitriol. Our results highlight the relevance of miRNAs in mediating feed-forward loops and regulating the expression of metastasis-related genes. Altogether, our results contribute to understanding the multi-step metastasis complexity and identifying novel therapeutic targets and drugs for breast cancer management.

Comprehensive analysis of the large and small ribosomal proteins in breast cancer: Insights on proteomic and transcriptomic expression patterns, regulation, mutational landscape, and prognostic significance.

Several evidence has demonstrated the involvement of the ribosomal proteins (RPs) in many malignancies, however, the function and clinical relevance of the RPs in breast cancer remains unclear. The present study aims to contribute to the understanding of the role of the RPs in breast tumorigenesis and its clinical implications in the field of biomarker discovery and outcome prediction. We investigated the proteomic and transcriptomic expression of the RPs in non-tumor and tumor tissues of different breast cancer subtypes, and integrated bioinformatics approaches and online databases to comprehensively evaluate the potential functions, regulatory networks, mutational landscape, and prognostic values of the ribosomal proteins in breast cancer. Our results show that 33 RPs have deregulated expression in breast cancer and its subtypes and that 26 RPs have potential as prognostic markers in a subtype-dependent way, with mutations in RP genes being frequent in breast tumors and related to overall survival and relapse-free status. Our RP gene regulatory network indicates the transcription factors MYC, ETS1, and SPI1, and the miRNAs has-let-7c-5p, has-mir-20b-5p, and has-mir-4668-3p as regulators of the RPs expression in breast cancer. The RPs were associated with several clinicopathological parameters of breast cancer and predicted to be involved in ribosomal-independent mechanisms such as regulation of the SLITS-ROBO pathway. This study comprehensively investigated the ribosomal proteins in breast cancer, suggesting that the RPs have clinical potential as biomarkers of diagnostic and prognostic, also providing an in-depth view of the RPs significance in breast cancer.

Impact of manual correction over automated segmentation of spectral domain optical coherence tomography.

OBJECTIVE: To study the automated segmentation of retinal layers using spectral domain optical coherence tomography (OCT) and the impact of manual correction over segmentation mistakes. METHODS: This was a retrospective, cross-sectional, comparative study that compared the automated segmentation of macular thickness using Spectralis™ OCT technology (Heidelberg Engineering, Heidelberg, Germany) versus manual segmentation in eyes with no macular changes, macular cystoid edema (CME), and choroidal neovascularization (CNV). Automated segmentation of macular thickness was manually corrected by two independent examiners and reanalyzed by them together in case of disagreement. RESULTS: In total, 306 eyes of 254 consecutive patients were evaluated. No statistically significant differences were noted between automated and manual macular thickness measurements in patients with normal maculas, while a statistically significant difference was found in central thickness in patients with CNV and with CME. Segmentation mistakes in macular OCTs were present in 5.3% (5 of 95) in the normal macula group, 16.4% (23 of 140) in the CME group, and 66.2% (47 of 71) in CNV group. The difference between automated and manual macular thickness was higher than 10% in 1.4% (2 of 140) in the CME group and in 28.17% (20 of 71) in the CNV group. Only one case in the normal group had a higher than 10% segmentation error (1 of 95). CONCLUSION: The evaluation of automated segmented OCT images revealed appropriate delimitation of macular thickness in patients with no macular changes or with CME, since the frequency and magnitude of the segmentation mistakes had low impact over clinical evaluation of the images. Conversely, automated macular thickness segmentation in patients with CNV showed a high frequency and magnitude of mistakes, with potential impact on clinical analysis.

Toxoplasma gondii in cetaceans of Brazil: a histopathological and immunohistochemical survey.

Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. In cetaceans, T. gondii infection is a significant cause of morbidity and mortality. Despite the worldwide range and broad cetacean host record of T. gondii infection, there is limited information on toxoplasmosis in cetaceans from the Southern hemisphere. We investigated the occurrence of T. gondii by histopathology and immunohistochemistry in tissue samples of 185 animals comprising 20 different cetacean species from Brazil. Three out of 185 (1.6%) animals presented T. gondii-associated lesions: a captive killer whale Orcinus orca, a free-ranging common bottlenose dolphin Tursiops truncatus and a free-ranging Guiana dolphin Sotalia guianensis. The main lesions observed in these animals were necrotizing hepatitis, adrenalitis and lymphadenitis associated with protozoal cysts or extracellular tachyzoites presenting immunolabeling with anti-T. gondii antibodies. This study widens the spectrum of species and the geographic range of this agent in Brazil, and provides the first reports of T. gondii infection in a captive killer whale and in a free-ranging common bottlenose dolphin in South America.

Age, sex and storage time influence hair cortisol levels in a wild mammal population.

The measurement of hair cortisol is increasingly used to understand the effect of natural and anthropogenic stressors on wild animals, but it is potentially confounded by individual, seasonal and sex-dependant variations in baseline cortisol secretion. This study validated an enzyme-linked immunoassay for hair cortisol measurement and characterized its baseline variation in a wild population of Egyptian mongoose. The analysis encompassed individuals of both sexes and all ages, across a range of geographic, environmental and seasonal conditions that the species experiences in Portugal allowing us to account for spatial, temporal and biological factors that contribute to hair cortisol variation. Our results showed that age, sex and storage time had an effect on hair cortisol, but season did not. Hair cortisol was higher in early stage juveniles compared to other age cohorts, in males when compared to females, and decreased with longer storage time. By identifying the factors that influence baseline hair cortisol in this wild population, we establish the basis for its application as an indicator of the effect of natural and anthropogenic stressors.

Toxoplasma gondii in cetaceans of Brazil: a histopathological and immunohistochemical survey / Toxoplasma gondii em cetáceos do Brasil: estudo histopatológico e imuno-histoquímico

Abstract Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. In cetaceans, T. gondii infection is a significant cause of morbidity and mortality. Despite the worldwide range and broad cetacean host record of T. gondii infection, there is limited information on toxoplasmosis in cetaceans from the Southern hemisphere. We investigated the occurrence of T. gondii by histopathology and immunohistochemistry in tissue samples of 185 animals comprising 20 different cetacean species from Brazil. Three out of 185 (1.6%) animals presented T. gondii-associated lesions: a captive killer whale Orcinus orca, a free-ranging common bottlenose dolphin Tursiops truncatus and a free-ranging Guiana dolphin Sotalia guianensis. The main lesions observed in these animals were necrotizing hepatitis, adrenalitis and lymphadenitis associated with protozoal cysts or extracellular tachyzoites presenting immunolabeling with anti-T. gondii antibodies. This study widens the spectrum of species and the geographic range of this agent in Brazil, and provides the first reports of T. gondii infection in a captive killer whale and in a free-ranging common bottlenose dolphin in South America.

Resumo Toxoplasmose é uma doença parasitária causada pelo protozoário Toxoplasma gondii. A infecção por T. gondii é uma causa significativa de morbidade e mortalidade, nos cetáceos. Apesar da abrangência mundial e amplo registro de espécies de cetáceos infectadas por T. gondii, informações sobre toxoplasmose em cetáceos do hemisfério sul são limitadas. Neste estudo pesquisou-se por meio de histopatologia e imuno-histoquímica a ocorrência de T. gondii em amostras de tecido de 185 animais, compreendendo 20 diferentes espécies de cetáceos que ocorrem no Brasil. Três dos 185 (1,6%) animais apresentaram lesões associadas a T. gondii: uma orca Orcinus orca mantida em cativeiro, um golfinho-nariz-de-garrafa Tursiops truncatus e um boto-cinza Sotalia guianensis de vida livre. As principais lesões observadas nesses animais foram hepatite, adrenalite e linfadenite necrotizantes associadas a cistos protozoários ou taquizoítos extracelulares, marcados com anticorpos anti-T. gondii. O presente estudo amplia o espectro de espécies susceptíveis a esse agente e o seu alcance geográfico no Brasil, fornecendo o primeiro relato da infecção por T. gondii em uma orca mantida em cativeiro e em um golfinho-nariz-de-garrafa de vida livre na América do Sul.

Cetacean movements in coastal waters of the southwestern Atlantic ocean / Movimentos de cetáceos pelas águas costeiras do sudoeste do oceano Atlântico

Abstract: Cetaceans were monitored along ca. 700 km of the southeast coast of Brazil (22°S to 25°S) from 1995 to 2014 using photo-identification. The objective of this study was to identify any presence of long-distance movements for monitored cetacean species and discuss implications. Data on long-range movements of four of the monitored species are presented after the analysis of 321,765 photographs taken for individual identification. Seven individuals from four populations of Guiana dolphins (Sotalia guianensis) considered resident to particular estuaries or bays were reported in dispersal involving movement between pairs of protected areas over long-range distances varying between 86 and 135 km. Three cataloged rough-toothed dolphins (Steno bredanensis), first seen in Guanabara Bay, Rio de Janeiro state (22°46'S) in November 2011, were sighted 240 km southwards as members of the same group in coastal waters of São Paulo state (23°46'S) in July 2014. Water depth for those sightings ranged from 16 to 52.7 m; local sightings of rough-toothed dolphins in Brazil have frequently been in shallow waters, but the species global distribution is usually associated with deeper waters. In a 27-day interval in the spring of 2012, a group of 16 orcas (Orcinus orca) travelled ca. 277 km in shallow coastal waters ranging from 20 to 30 m deep. Orcas are commonly observed between November and February in southeast Brazil, probably in search for prey. In summer months between 2012 and 2014, three Bryde's whales (Balaenoptera edeni) sighted in waters ranging from 14 to 49 m deep, moved between 218 and 327 km. Bryde's whales are usually found in local coastal waters where they spend summer months feeding on sardines. To date, these are the longest estimated movements reported to S. guianensis, S. bredanensis, O. orca and B. edeni in the Southwestern Atlantic Ocean.

Resumo: Cetáceos foram monitorados em cerca de 700 km da costa sudeste do Brasil (22°S a 25°S) entre 1995 e 2014 com o uso da fotoidentificação. O objetivo deste estudo foi de identificar quaisquer presenças de movimentos de longa distância de indivíduos das espécies monitoradas e discutir suas implicações. Dados de movimentos de longa distância de quatro das espécies monitoradas são apresentados após a análise de 321.765 fotos obtidas para identificações individuais. Sete indivíduos de quatro populações de boto-cinza (Sotalia guianensis) consideradas residentes a estuários e baías particulares foram reportados em movimentos de dispersão envolvendo pares de áreas protegidas em distâncias que variaram entre 86 e 135 km. Três golfinhos-de-dentes-rugosos (Steno bredanensis) catalogados e avistados primeiramente na Baía de Guanabara, Rio de Janeiro (22°46'S), em novembro de 2011, foram avistados 240 km mais ao sul como membros de um mesmo grupo nas águas costeiras do Estado de São Paulo (23°46'S) em julho de 2014. A profundidade da água onde essas avistagens aconteceram variou entre 16 e 52,7 m; avistagens de golfinhos-de-dentes-rugosos têm sido efetuadas em águas rasas na costa sudeste do Brasil, embora a distribuição global da espécie esteja associada a águas profundas. Em um intervalo de 27 dias na primavera de 2012, um grupo de 16 orcas (Orcinus orca) se desclocou cerca de 277 km em águas rasas variando entre 20 e 30 m. Orcas são comumente avistadas entre novembro e fevereiro no sudeste do Brasil, possivelmente em busca de presas. Nos meses de verão entre 2012 e 2014, três baleias-de-Bryde (Balaenoptera edeni) avistadas em águas de 14 a 49 m de profundidade, moveram-se entre 218 e 327 km. baleias-de-Bryde são encontradas em águas costeiras locais onde passam os meses de verão se alimentando de sardinhas. Até o presente momento, esses são os deslocamentos estimados como os de maiores distâncias observados para S. guianensis, S. bredanensis, O. orca and B. edeni no Atlântico Sudoeste.

Exfoliation syndrome associated with LOXL1 gene polymorphisms in a Black patient from Latin America: a case report / Síndrome de esfoliação associada a polimorfismos do gene LOXL1 em paciente negro da América Latina: relato de caso

ABSTRACT A 89-year-old Black female with a 6-year history of advanced open-angle glaucoma was referred to the Glaucoma Service of the Ophthalmology Department - Federal University of São Paulo (UNIFESP). Best-corrected visual acuity was 20/400 in the right eye and 20/60 in the left eye. Pseudoexfoliation material was observed at the iris border, angle, and the anterior lens surface. Anterior biomicroscopy revealed exfoliation material forming an evident peripheral zone and a central disc separated by a clear intermediate zone on the anterior lens surface OU. Gonioscopy showed an open-angle Sampaolesis's line and whitish material deposits OU. Fundus examination revealed a cup-to-disc ratio of 1.0 OU with peripapillary atrophy. Genetic analysis for single nucleo­tide polymorphisms of the lysyl oxidase-like 1 gene linked to exfoliation syndrome identified two such single nucleotide polymorphisms, rs1048661 and rs216524.

RESUMO Uma mulher negra de 89 anos com um histórico de seis anos de glaucoma avançado de ângulo aberto avançado foi encaminhada ao Serviço de Glaucoma do Departamento de Oftalmologia da Universidade Federal de São Paulo (UNIFESP). A acuidade visual melhor corrigida era 20/400 no olho direito e 20/60 no olho esquerdo. Material pseudo-exfoliativo foi observado na borda iriana, ângulo e superfície anterior do cristalino. A biomicroscopia de segmento anterior demonstrou material exfoliativo formando uma zona periférica evidente e um disco central separado por uma zona intermediária livre na cápsula anterior do cristalino. A gonioscopia mostrou uma linha de Sampaolesi de ângulo aberto e depósitos esbranquiçados. O exame de fundo de olho revelou disco óptico com escavação total em ambos os olhos com atrofia peripapilar. A análise genética para polimorfismos de nucleotídeo único do gene semelhante à lysyl oxidase-like 1 ligado à síndrome de esfoliação identificou dois desses polimorfismos de nucleotídeo único, rs1048661 e rs216524.

Levels and profiles of chlorinated and brominated contaminants in Southern Hemisphere humpback whales, Megaptera novaeangliae.

The study documents the levels and profiles of selected contaminants [polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs) and methoxylated PBDEs (MeO-PBDEs)] in blubber biopsy samples collected from humpback whales (Megaptera novaeangliae) in Antarctic Peninsula waters. In addition, we investigated year-to-year and sex-related differences in the bioaccumulation patterns. Except for hexachlorobenzene (HCB), whose concentrations were in the same range as those found in whales from the Northern Hemisphere, levels of all other compounds were lower in Southern Hemisphere whales compared to literature data on animals from the Arctic and subarctic region. The mean contribution to the sum of all anthropogenic organohalogen compounds (ΣOHC) decreased in the following order ΣPCBs (44%)>HCB (31%)>ΣDDXs (13%)>ΣCHLs (4.6%)>ΣHCHs (4.4%)>ΣPBDEs (0.9%). The predominant compounds within each chemical class were: PCBs 153, 149, 101 and 138; p,p'-DDE; γ-HCH; trans-nonachlor; PBDEs 99 and 47. The most dominant MeO-PBDE congener was 6-MeO-BDE 47. As samples were collected during three consecutive summer seasons, year-to-year trends could be assessed indicating a significant decrease from 2000 to 2003 for ΣCHL levels. Higher ΣPBDE concentrations and higher values of the ΣPBDE / ΣMeO-PBDE ratio, as well as higher ratios between the two MeO-BDEs (2'-MeO-BDE 68/6-MeO-BDE 47) were found in females compared to males. Higher ΣMeO-PBDE concentrations and higher values of the ratios between the lower chlorinated and the higher chlorinated PCBs were found in males than in females. In addition, five out of six significant differences found through discriminant function analysis were gender-related. The literature reports both feeding in mid- to low-latitudes and sex-related differences in migration patterns for humpback whales from the Southern Hemisphere, indicating that the hypothesis of dietary differences between males and females cannot be excluded. Nevertheless, additional studies are required for further investigation of this hypothesis.

Enterobacteria identification and detection of diarrheagenic Escherichia coli in a Port Complex

The Port Complex of Maranhão (PCM) is the second largest port complex in Brazil, receiving ships with large volumes of ballast water. To evaluate the microbiological quality of its waters, physicochemical parameters (pH and salinity), the number of coliforms (thermotolerants and totals), and the presence of enterobacterias and diarrheagenic Escherichia coli strains were analyzed. In order to identify the presence of E. coli virulence genes target regions of the stx, elt, est, aggR, CVD432, ipaH and eae nucleotide sequences were studied. The presence of totals and thermotolerants coliforms were positive. Analyzing the salinity parameter, a significant increase in total coliforms was observed during the rainy season. We identified the species Escherichia coli, Proteus mirabilis, Citrobacter freundii, Proteus vulgaris, Klebsiella pneumoniae, Klebsiella ozaenae, Morganella morganii, Enterobacter cloacae and Edwardsiella tarda. Out of the 51 E. coli isolated, two were positive for the elt gene and one was positive for the CVD432 sequence, features of enterotoxigenic and enteroaggregative strains, respectively. This study reveals that the PCM is contaminated by enterobacteria and diarrheagenic E.coli thus providing evidence regarding the risk of these bacteria being carried by ships to other countries, and draws attention to the input of fecal bacteria brought by ships in the port waters of Maranhão.

Non-Hodgkin’s Lymphoma: Five-year Survival in a Historical Cohort of Patients who Underwent Stem Cell Transplantationin Brazil / Linfoma No-Hodgkin: Supervivencia de Cinco Años en una Cohorte Histórica dePacientes Sometidos a Trasplante de Células Madre en Brasil / Linfoma Não-Hodgkin: Sobrevida de Cinco Anos em uma Coorte Histórica dePacientes Submetidos a Transplante de Células-Tronco no Brasil

Introduction: Several studies have shown the benefits of stem cell transplantation in the treatment of Non-Hodgkin’s lymphoma. Objective: To evaluate survival and associated factors in transplanted Non-Hodgkin’s lymphoma patients in Brazil. Method: We conducted a retrospective analysis of 100 adult patients with Non-Hodgkin’s lymphoma transplanted in a national reference center for hematopoietic stem cell transplantation between 1997 and 2009. Data was obtained from medical charts and included besides socio-demographic and lifestyle variables, others relatedto diagnosis and transplantation. The five-year survival probability was estimated using the Kaplan-Meier method and differences between curves were tested with the log-rank test, assuming statistical significance level of 5%. Cox regression was performed for multivariate analysis. Results: Median age at diagnosis was 43 years (17-65) and 45 years (18-66) at transplantation. Median time between diagnosis and transplantation was 17 months (4-173). The probability of survival at 5 years was 50.8% with a median survival time of 22.5 months. In multivariate analysis, evidence of disease 12 months after transplant (HR: 4.49; 95% CI 2.15-9.39), chemo-sensitivity to the last regimenbefore transplant (HR: 2.92; 95% CI 1.35-6.32) and advanced stage at diagnosis (HR: 1.96, 95% CI 1.02-3.80)were prognostic factors for survival. Conclusion: Median age at transplantation in this cohort was similar to that of other studies but median time between diagnosis and transplantation was higher. Although overall survival (5 years) approached that reported in other studies, different treatment protocols and specific characteristics of each populationlimit comparisons

Morphological and anatomical characterization of the digestive tract of Centropomus parallelus and C. undecimalis / Caracterização Morfológica e Anatômica do Tubo Digestório de Centropomus parallelus e C. undecimalis

Centropomus parallelus and C. undecimalis are the most common species of Centropomidae in Brazil. Some authors attribute their failure to grow under in artificial conditions due to limited knowledge on the morphological and functional development of their digestive system and on nutrition requirements of both species. Current research characterizes histologically and histochemically the digestive tract of C. parallelus and C. undecimalis to provide a histophysiological assessment for studies related to their nutritional needs. In the esophagus, the mucous cells in the epithelium stained positively for PAS and AB. In the stomach, positive reactions to PAS and negative to AB respectively occurred on surface and mucous cells in the epithelium and in the lamina propria. In the intestine, goblet cells showed ratio similarity, with mucus being positive in AB and PAS. A greater concentration of these cells existed in the middle and distal intestine, with a greater increase of secretions when compared to those in the proximal intestine. Results show that C. parallelus and C.undecimalis display the main features of the digestive tract of carnivorous fish, a well-developed stomach and a relatively short intestine. In fact, they give insights for future studies on the mechanisms related to the species's digestive and absorptive physiology.

Centropomus parallelus e C. undecimalis são as espécies mais comuns de Centropomidae no Brasil. Alguns autores atribuem o insucesso no seu cultivo devido ao escasso conhecimento sobre o desenvolvimento morfológico e funcional do sistema digestório, assim como o desconhecimento das exigências nutricionais das espécies. Dessa forma realizou-se o presente trabalho, com o objetivo de caracterizar histológica e histoquimicamente o tubo digestório de C. parallelus e C. undecimalis, para estudos histofisiológicos relacionados às necessidades nutricionais deste peixe. No esôfago, as células mucosas, presentes no epitélio coraram-se positivamente tanto em PAS como em AB. No estômago, as células superficiais e mucosas presentes no epitélio e na lâmina própria respectivamente, apresentaram reações positivas em PAS e negativa em AB. No intestino as células caliciformes apresentaram similaridade na proporção entre os mucos sendo positivos tanto em PAS como em AB; nos intestinos médio e distal observou-se uma maior concentração destas células, resultando em uma quantidade maior de secreções em comparação ao intestino proximal. Através dos resultados observados, conclui-se que o C. parallelus e C. undecimalis exibem as principais características do trato digestório de peixes carnívoros, como um estômago bem desenvolvido e um intestino relativamente curto. Estes resultados darão subsídios para futuros estudos sobre mecanismos da fisiologia digestiva e absortiva desta espécie.