Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner.

Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD + can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD + precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known. Here we investigate the effect of long-term administration of NMN on the health, cancer burden, frailty and lifespan of male and female mice. Without increasing tumor counts or severity in any tissue, NMN treatment of males and females increased activity, maintained more youthful gene expression patterns, and reduced overall frailty. Reduced frailty with NMN treatment was associated with increases in levels of Anerotruncus colihominis, a gut bacterium associated with lower inflammation in mice and increased longevity in humans. NMN slowed the accumulation of adipose tissue later in life and improved metabolic health in male but not female mice, while in females but not males, NMN increased median lifespan by 8.5%, possible due to sex-specific effects of NMN on NAD + metabolism. Together, these data show that chronic NMN treatment delays frailty, alters the microbiome, improves male metabolic health, and increases female mouse lifespan, without increasing cancer burden. These results highlight the potential of NAD + boosters for treating age-related conditions and the importance of using both sexes for interventional lifespan studies.

Incidental Adrenal Masses: A Case Report of an Adrenal Oncocytoma.

A 59-year-old woman underwent an abdominal and pelvic computed tomography (CT) scan to rule out non-obstructive urolithiasis. The patient was asymptomatic, with the exception of occasional bilateral low back pain. A physical examination did not reveal any notable findings. The CT scan revealed the presence of an incidental solid left adrenal lesion, which displaced the body of the pancreas and the left kidney. The lesion measured 7 cm × 6.5 cm and exhibited a rounded morphology with well-defined margins. It showed progressive and heterogeneous contrast uptake. Additionally, magnetic resonance imaging (MRI) was performed, confirming the presence of an adrenal lesion with intense and heterogeneous hypersignal on T2. The lesion also demonstrated heterogeneous and persistent enhancement in a dynamic study. Furthermore, there were some indistinct and non-specific hypointense areas identified on both T1 and T2 sequences. The lesion exhibited moderately restricted diffusion. Although the imaging features were non-specific, there were no indications of invasion or distant metastasis, which made a benign large adrenal mass the most likely diagnosis. Non-functioning pheochromocytoma, lipid-poor adrenal adenoma, as well as metastasis or primary adrenal carcinoma, were considered differential diagnoses. The patient underwent an elective adrenalectomy, during which the identified lesion was completely resected. The patient's postoperative recovery was uneventful, and she was discharged three days after the procedure. Subsequent histopathological evaluation revealed an oncocytic neoplasm of the adrenal cortex - specifically, an oncocytoma.

Effect of probiotic therapy on periodontal tissues and intestinal mucosa of rats with ligature-induced periodontitis / Efeito da terapia probiótica nos tecidos periodontais e mucosa intestinal de ratos com periodontite induzida por ligadura

INTRODUCTION: As periodontitis is caused by dysbiotic biofilm, it is believed that therapy with probiotics can act to control the mechanisms of adhesion and colonization, competing with invading microorganisms. OBJECTIVE: Evaluate probiotic therapy effect on periodontal tissues and intestinal mucosa of rats with ligature-induced periodontitis. METHODS: 32 Wistar rats were divided into four groups (n=8): Control Group (CG); Periodontal disease (PD); Probiotic (PROB); PD + probiotic (PDPRO). PD and PDPRO received a ligature over the first lower molars and PROB and PDPRO the probiotic Lactobacillus acidophilus based were given orally for 44 days. The animals were euthanized and the blood was collected for evaluation of triglyceride and cholesterol concentrations. The hemimandibles were collected for histomorphometric and radiographic analysis. The duodenum was removed for morphological evaluation and gingival tissue around the molars was collected for analysis of IL-17. RESULTS: The ANOVA one-way test was used followed by Tukey Test. PDPRO had a significantly lower bone loss than the PD (p<0.05) and a smaller number of osteoclasts on PDPRO when compared to the PD. As for IL-17, there was a decrease in the PDPRO when compared to the PD. The histomorphometry of the duodenum showed that there was a significant increase in the width of the villi in PROB only. CONCLUSION: The therapy with probiotics was effective to avoid the development of periodontitis by reducing alveolar bone loss and inflammation modulation and increasing the width of the duodenum villi, which may help to restabilize the balance of the gastrointestinal tract.

INTRODUÇÃO: Como a periodontite é causada por biofilme disbiótico, acredita-se que a terapia com probióticos possa atuar no controle dos mecanismos de adesão e colonização, competindo com microrganismos invasores. OBJETIVO: Avaliar o efeito da terapia probiótica nos tecidos periodontais e mucosa intestinal de ratos com periodontite induzida por ligadura. MÉTODOS: 32 ratos Wistar foram divididos em quatro grupos (n=8): Grupo Controle (GC); Doença periodontal (PD); Probiótico (PROB); PD + probiótico (PDPRO). PD e PDPRO receberam ligadura sobre os primeiros molares inferiores e PROB e PDPRO, o probiótico à base de Lactobacillus acidophilus dado via oral por 44 dias. Os animais foram sacrificados e o sangue coletado para avaliação das concentrações de triglicerídeos e colesterol total. As hemimandíbulas foram coletadas para análise histomorfométrica e radiográfica. O duodeno foi removido para avaliação morfológica e o tecido gengival ao redor dos molares foi coletado para análise de IL-17. RESULTADOS: Foi usado Teste ANOVA seguido pelo Teste de Tukey. PDPRO teve uma perda óssea significativamente menor do que o PD (p<0.05) e um menor número de osteoclastos no PDPRO quando comparado ao PD. Já para IL-17, houve diminuição do PDPRO em relação ao PD. A histomorfometria do duodeno mostrou que houve aumento significativo da largura das vilosidades no PROB somente. CONCLUSÃO: A terapia com probiótico foi eficaz para evitar o desenvolvimento de periodontite por reduzir a perda óssea alveolar e a modulação da inflamação e aumentar a largura das vilosidades duodenais, o que pode ajudar a estabilizar o equilíbrio do trato gastrointestinal.

Incidence and clinical results of tendinous injuries in calcaneus and pilon fractures.

PURPOSE: The aims of this study were: (1) to define the incidence of tendinous injuries in calcaneus and pilon fractures with different fracture severity and (2) to determine the clinical impact of such injuries. STUDY DESIGN AND METHODS: CT-scans of 121 patients with calcaneus and pilon fractures were retrospectively analyzed over a 4-year period. The tendinous injuries were identified and correlated with the type of fracture (location and classification). Clinical analysis was performed using the American Orthopedic Foot and Ankle Society (AOFAS) and SF-36 (Short Form-36 Health Survey) scores. RESULTS: Tendinous injuries were observed in 36% of all CT-scans analyzed, with the most common injury being incarceration (n = 20) and dislocation (n = 24). Calcaneus fractures sanders type 3/4 were 9 times more prone to tendon injury (p < 0.001; OR 8.67; 95% CI 2.49-30.24). Pilon fractures Ruedi-Allgower type 2/3 were 8 times more prone to tendon injury (p = 0.005; OR 7.5; 95% CI 1.72-32.80). No significant differences (p > 0.05) were found in AOFAS and SF-36 scores between patients with/without tendon injuries for fractures with the same severity. CONCLUSION: The incidence of tendon injuries in calcaneus/pilon fractures is high and may be underreported. Calcaneus fractures are prone to peroneal tendon injury. In pilon fractures, it is important to look for tibialis posterior tendon injury, especially entrapment. The presence of tendinous injuries does not affect function and pain for the same type of calcaneus and pilon fractures at the long term. LEVEL OF EVIDENCE: Level 3 retrospective study.

Interface trabalho-tratamento hemodialítico em pacientes com insuficiência renal crônica: revisão de escopo / Interfaz trabajo-tratamiento hemodialítico en pacientes con insuficiencia renal crónica: revisión de alcance / Work-hemodialysis treatment interface in patients with chronic kidney disease: a scoping review

Resumo Objetivo Analisar as evidências científicas sobre o impacto do tratamento hemodialítico no trabalho de pacientes com insuficiência renal crônica. Métodos Revisão de escopo realizada por meio de buscas em cinco bases de dados: PubMed, LILACS, CINAHL, PsyInfo e Scopus. Foram incluídos estudos publicados entre 2010 e 2020, nos idiomas português, espanhol e inglês, de abordagem qualitativa ou quantitativa, com pacientes em tratamento hemodialítico para insuficiência renal crônica, que tivessem foco no trabalho, emprego ou produtividade. Resultados Os 18 estudos incluídos na revisão mostram o impacto do tratamento hemodialítico na relação com o trabalho e as razões associadas à desempregabilidade. Tais razões envolvem características sociodemográficas, debilidade física, tratamento e apoio familiar e do empregador. Conclusão Após o início da hemodiálise, nota-se o comprometimento da capacidade funcional tanto física como psicológica dos pacientes, sendo necessárias alterações nos hábitos de vida em decorrência das restrições impostas pela insuficiência renal crônica e da diminuição da produtividade.

Resumen Objetivo Analizar las evidencias científicas sobre el impacto del tratamiento hemodialítico en el trabajo de pacientes con insuficiencia renal crónica. Métodos Revisión de alcance realizada mediante búsquedas en cinco bases de datos: PubMed, LILACS, CINAHL, PsyInfo y Scopus. Se incluyeron estudios publicados entre 2010 y 2020, en idioma portugués, español e inglés, de enfoque cualitativo o cuantitativo, con pacientes bajo tratamiento hemodialítico por insuficiencia renal crónica, que estuvieran centrados en el trabajo, empleo o productividad. Resultados Los 18 estudios incluidos en la revisión muestran el impacto del tratamiento hemodialítico en la relación con el trabajo y las razones asociadas al desempleo. Estas razones incluyen características sociodemográficas, debilidad física, tratamiento y apoyo familiar y del empleador. Conclusión Después del inicio de la hemodiálisis, se observa la capacidad funcional de los pacientes comprometida, tanto la física como la psicológica, por lo que los cambios en los hábitos de vida se hacen necesarios como consecuencia de las restricciones impuestas por la insuficiencia renal crónica y de la reducción de la productividad.

Abstract Objective To analyze the scientific evidence on the impact of hemodialysis treatment on the work of patients with chronic kidney disease. Methods This is a scoping review carried out through searches in five databases: PubMed, LILACS, CINAHL, PsyInfo and Scopus. We included studies published between 2010 and 2020, in Portuguese, Spanish and English, with a qualitative or quantitative approach, with patients undergoing hemodialysis for chronic kidney failure, who focused on work, employment or productivity. Results The 18 studies included in the review show the impact of hemodialysis treatment on the relationship with work and the reasons associated with unemployment. Such reasons involve sociodemographic characteristics, physical weakness, treatment and family and employer support. Conclusion After starting hemodialysis, we identified impairment in patients' functional capacity, both physical and psychological, requiring changes in life habits due to restrictions imposed by chronic kidney disease and decreased productivity.

Potent and Specific Activators for Mitochondrial Sirtuins Sirt3 and Sirt5.

Sirtuins are NAD+-dependent protein deacylases involved in metabolic regulation and aging-related diseases. Specific activators for seven human Sirtuin isoforms would be important chemical tools and potential therapeutic drugs. Activators have been described for Sirt1 and act via a unique N-terminal domain of this isoform. For most other Sirtuin isoforms, including mitochondrial Sirt3-5, no potent and specific activators have yet been identified. We here describe the identification and characterization of 1,4-dihydropyridine-based compounds that either act as pan Sirtuin activators or specifically stimulate Sirt3 or Sirt5. The activators bind to the Sirtuin catalytic cores independent of NAD+ and acylated peptides and stimulate turnover of peptide and protein substrates. The compounds also activate Sirt3 or Sirt5 in cellular systems regulating, e.g., apoptosis and electron transport chain. Our results provide a scaffold for potent Sirtuin activation and derivatives specific for Sirt3 and Sirt5 as an excellent basis for further drug development.

Incidental Liver Lesions in children: A practical and evidence-based approach.

Incidental liver lesions are increasingly being discovered in the context of the increased use of ultrasound studies and the majority are benign. In children, although individually rare, the differential diagnosis is broad and therefore a systematic approach is of utmost importance to reduce the radiological and disease burden in children and their families. This review article collected current evidence and provides fundamental information for the clinician regarding specific differential diagnoses and unique imaging features of benign liver lesions in children. Ultimately, we propose a practical stepwise approach mainly involving clinical and radiological workup. Laboratory tests and histopathological examination may be necessary in the presence of red flags or in indeterminate lesions.

Exposure to glyphosate-based herbicide during early stages of development increases insulin sensitivity and causes liver inflammation in adult mice offspring

ABSTRACT Objective: To investigate the effect of pre and postnatal exposure to a glyphosate-based herbicide on glucose metabolism and liver histology in adult F1 mice offspring. Methods: Female mice (C57Bl/6) received 0.5% of glyphosate (Roundup Original DI®) in drinking water or purified water (Glyphosate Group and Control Group respectively) during pregnancy and lactation. Offspring (F1) were submitted to glucose and insulin tolerance tests and euthanized on postnatal day 150. Body and plasma parameters, and liver histology were analyzed. Results: Exposure to glyphosate reduced maternal body weight gain during pregnancy and lactation, with no impacts on litter size. Pre and postnatal exposure to glyphosate did not affect body parameters but increased glucose tolerance on postnatal day 60. In spite of glucose tolerance normalization by postnatal day 143, this effect was associated with higher insulin sensitivity relative to mice in the Control-F1 Group. Mice in the Glyphosate-F1 Group had mild and moderate lobular inflammation in the liver. Conclusion: Maternal exposure to glyphosate affected insulin sensitivity and caused hepatic inflammation in adult F1 mice offspring.

What is the state of the art of computer vision-assisted cytology? A Systematic Literature Review.

Cytology is a low-cost and non-invasive diagnostic procedure employed to support the diagnosis of a broad range of pathologies. Cells are harvested from tissues by aspiration or scraping, and it is still predominantly performed manually by medical or laboratory professionals extensively trained for this purpose. It is a time-consuming and repetitive process where many diagnostic criteria are subjective and vulnerable to human interpretation. Computer Vision technologies, by automatically generating quantitative and objective descriptions of examinations' contents, can help minimize the chances of misdiagnoses and shorten the time required for analysis. To identify the state-of-art of computer vision techniques currently applied to cytology, we conducted a Systematic Literature Review, searching for approaches for the segmentation, detection, quantification, and classification of cells and organelles using computer vision on cytology slides. We analyzed papers published in the last 4 years. The initial search was executed in September 2020 and resulted in 431 articles. After applying the inclusion/exclusion criteria, 157 papers remained, which we analyzed to build a picture of the tendencies and problems present in this research area, highlighting the computer vision methods, staining techniques, evaluation metrics, and the availability of the used datasets and computer code. As a result, we identified that the most used methods in the analyzed works are deep learning-based (70 papers), while fewer works employ classic computer vision only (101 papers). The most recurrent metric used for classification and object detection was the accuracy (33 papers and 5 papers), while for segmentation it was the Dice Similarity Coefficient (38 papers). Regarding staining techniques, Papanicolaou was the most employed one (130 papers), followed by H&E (20 papers) and Feulgen (5 papers). Twelve of the datasets used in the papers are publicly available, with the DTU/Herlev dataset being the most used one. We conclude that there still is a lack of high-quality datasets for many types of stains and most of the works are not mature enough to be applied in a daily clinical diagnostic routine. We also identified a growing tendency towards adopting deep learning-based approaches as the methods of choice.

Measuring PGC-1α and Its Acetylation Status in Mouse Primary Myotubes.

Metabolic flexibility is vital for organisms to respond to and survive changes in energy availability. A critical metabolic flexibility regulator is peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), which regulates various transcription factors and nuclear receptors that, in turn, regulate mitochondrial homeostasis and fatty acid oxidation. PGC-1α is itself regulated, with one of the significant modes of regulation being acetylation. Thus, measuring the acetylation status of PGC-1α is a critical indicator of cells' metabolic flexibility. In this chapter, we describe a method of evaluating PGC-1α acetylation in primary mouse myotubes. This method can also be used with other cell types and tissues.

Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment.

Currently, no pharmacotherapy has been proven effective in treating photoreceptor degeneration in patients. Discovering readily available and safe neuroprotectants is therefore highly sought after. Here, we investigated nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), in a retinal detachment (RD) induced photoreceptor degeneration. NMN administration after RD resulted in a significant reduction of TUNEL+ photoreceptors, CD11b+ macrophages, and GFAP labeled glial activation; a normalization of protein carbonyl content (PCC), and a preservation of the outer nuclear layer (ONL) thickness. NMN administration significantly increased NAD+ levels, SIRT1 protein expression, and heme oxygenase-1 (HO-1) expression. Delayed NMN administration still exerted protective effects after RD. Mechanistic in vitro studies using 661W cells revealed a SIRT1/HO-1 signaling as a downstream effector of NMN-mediated protection under oxidative stress and LPS stimulation. In conclusion, NMN administration exerts neuroprotective effects on photoreceptors after RD and oxidative injury, suggesting a therapeutic avenue to treating photoreceptor degeneration.

The Soluble Adenylyl Cyclase Inhibitor LRE1 Prevents Hepatic Ischemia/Reperfusion Damage Through Improvement of Mitochondrial Function.

Hepatic ischemia/reperfusion (I/R) injury is a leading cause of organ dysfunction and failure in numerous pathological and surgical settings. At the core of this issue lies mitochondrial dysfunction. Hence, strategies that prime mitochondria towards damage resilience might prove applicable in a clinical setting. A promising approach has been to induce a mitohormetic response, removing less capable organelles, and replacing them with more competent ones, in preparation for an insult. Recently, a soluble form of adenylyl cyclase (sAC) has been shown to exist within mitochondria, the activation of which improved mitochondrial function. Here, we sought to understand if inhibiting mitochondrial sAC would elicit mitohormesis and protect the liver from I/R injury. Wistar male rats were pretreated with LRE1, a specific sAC inhibitor, prior to the induction of hepatic I/R injury, after which mitochondria were collected and their metabolic function was assessed. We find LRE1 to be an effective inducer of a mitohormetic response based on all parameters tested, a phenomenon that appears to require the activity of the NAD+-dependent sirtuin deacylase (SirT3) and the subsequent deacetylation of mitochondrial proteins. We conclude that LRE1 pretreatment leads to a mitohormetic response that protects mitochondrial function during I/R injury.

Histopathological alterations in gills of a fish (Astyanax bifasciatus) in neotropical streams: negative effects of riparian forest reduction and presence of pesticides.

The reduction of riparian vegetation around aquatic environments causes several physicochemical alterations and favors the entry of pesticides via surface runoff. Such changes have negative effects on aquatic organisms. In this study, we evaluated histopathological alterations in gills of Astyanax bifasciatus to test the hypothesis that more severe histopathological alterations occur in gills of fish from streams with higher agricultural impact from the surrounding area. The specimens were collected by electrofishing in seven streams of the lower Iguaçu basin between August 2015 and February 2016. The gills were processed according to routine histological methods and examined by light microscopy. The histopathological alterations, mainly stage II (lamellar aneurysm and total fusion of lamellae), were observed in fish collected in streams with higher agricultural activity. In these streams, the histopathological index indicated slight to moderate organ lesions. In contrast, in streams with more vegetation cover, fish collected presented stage I histopathological alterations (lamellar edema and lamellar hyperplasia), and the HI indicated normal functioning of the gills. In addition, chloride and acid mucous cells were more abundant in the gills of fish collected in rural streams. Our findings demonstrate that more severe histopathological alterations were registered in fish collected from streams with intense agricultural activity in the surrounding area. Therefore, it highlights that vegetation cover around the streams is a positive force for the conservation and health of aquatic organisms.

Mitohormesis and metabolic health: The interplay between ROS, cAMP and sirtuins.

The key role of mitochondria in oxidative metabolism and redox homeostasis explains the link between mitochondrial dysfunction and the development of metabolic disorders. Mitochondria's highly dynamic nature, based on alterations in biogenesis, mitophagy, fusion and fission, allows adjusting sequential redox reactions of the electron transport chain (ETC) and dissipation of the membrane potential by ATP synthase, to different environmental cues. With reactive oxygen species being an inevitable by-product of oxidative phosphorylation (OXPHOS), alterations on mitochondrial oxidative rate with a consequent excessive load of reactive oxygen species have been traditionally associated with pathological conditions. However, reactive oxygen species have also been suggested as promoters of mitohormesis, a process in which low, non-cytotoxic concentrations of reactive oxygen species promote mitochondrial homeostasis. Therefore, signaling systems involved in the regulation of mitochondrial homeostasis are attractive candidates for drug development for metabolic diseases triggered by mitochondrial dysfunction. Reversible phosphorylation downstream the cyclic AMP (cAMP) signaling cascade and deacetylation mediated by sirtuins are recognized as major mitochondrial regulators.

Uptake and effects of different concentrations of spherical polymer microparticles on Artemia franciscana.

Artemia cysts have a huge economic importance for the aquaculture sector due to the fact that they are used as live feed for larviculture. Microplastics (MPs) are common and emergent pollutants in the aquatic environments, with unknown and potential long-term effects on planktonic species such as Artemia spp. When used as live feed, Artemia could transfer contaminants to fish along the food chain, with possible adverse effects on human health through their consumption. This study aims to assess the uptake of different concentrations of spherical polymer microparticles (FRM) (1-5 µm diameter) and their associated chronic effects on feeding, growth, mortality, and reproductive success from juvenile to adult stage of brine shrimp Artemia franciscana. Individuals were exposed for 44 days to 0.4, 0.8 and 1.6 mg.L-1 of FRM. No significant detrimental effects on growth, ingestion and mortality rates of A. franciscana were observed in all tested conditions. However, reproductive success was strongly affected by the increase of MP concentrations. The results of the present study showed that A. franciscana juveniles and adults were able to survive different experimental MP concentrations, but their reproductive success and progeny were significantly impacted by exposure to FRM particles.

Dolops carvalhoi as a vector of Epistylis sp. between cultivated and wild specimens of Oreochromis niloticus in Brazil / Dolops carvalhoi como vetor de Epistylis sp. entre espécimes cultivados e silvestres de Oreochromis niloticus no Brasil

Abstract Epistyliasis has been characterized as an emergent disease which has a great impact on fish farms, especially on Oreochromis niloticus production systems. Although epidemiological important, information about the dispersion of these parasites and their mechanical vectors is scarce. The present study reported the cooccurrence of Epistylis sp. as an epibiont of Dolops carvalhoi, a parasitic crustacean of cultivated/wild specimens (from accidental release) of O. niloticus from a cage fish farm area in the Ilha Solteira Reservoir, Grande River, SP, Brazil. The co-occurrence of Epistylis sp. and D. carvalhoi, and their epibiont relationship registered in this study suppose that the Epistylis may use the crustaceans for dispersion and as mechanical vectors for the dissemination of diseases in wild and cultivated hosts. Moreover, exchange of parasites between wild and cultivated hosts is possible, considering both organisms (protozoan and argulid). Furthermore, the results of the present study demonstrate the need to monitor the areas adjacent to cage fish farms as a preventive measure for the dispersion of pathogens. This is the first report of epibiosis between Epistylis sp. and argulid parasites of cultivated and wild O. niloticus, contributing to knowledge about host-parasite specificity, geographical distribution, dispersion of etiological agents and epidemiology in aquaculture.

Resumo Epistilíase tem sido caracterizada como uma doença emergente de grande impacto nas pisciculturas, especialmente em sistemas de produção de Oreochromis niloticus. Embora seja importante epidemiologicamente, informações sobre a dispersão desses parasitas e seus vetores mecânicos são escassos. O presente estudo relata a coocorrência de Epistylis sp. como um epibionte de Dolops carvalhoi, um crustáceo parasita de espécimes cultivados e silvestres (de escapes acidentais) de O. niloticus em área de piscicultura de tanques-rede no reservatório de Ilha Solteira, Rio Grande, SP, Brasil. A coocorrência de Epistylis sp. e D. carvalhoi, e sua relação epibionte registrada neste estudo, supõem que Epistylis sp. possa utilizar os crustáceos para dispersão e como vetores mecânicos para a disseminação de doenças em hospedeiros silvestres e cultivados. Além disso, a troca de parasitas entre hospedeiros silvestres e cultivados é possível, considerando ambos os organismos (protozoários e argulídeos). Os resultados deste estudo, também demonstram a necessidade de monitorar as áreas adjacentes às pisciculturas como medida preventiva para a dispersão de patógenos. Este é o primeiro relato de epibiose entre Epistylis sp. e parasitas argulídeos de O. niloticus cultivados e silvestres, contribuindo para o conhecimento da especificidade parasitária do hospedeiro, distribuição geográfica, dispersão de agentes etiológicos e epidemiologia na aquicultura.

Histopathological alterations in Astyanax bifasciatus (Teleostei: Characidae) correlated with land uses of surroundings of streams

This study evaluated gills and liver of Astyanax bifasciatus as histological biomarkers for biomonitoring of streams along areas with different land uses. The fish were collected by electrofishing in six streams in the basin of the lower Iguaçu River. The objective was to correlate the presence and degree of histopathological alterations of gills and liver with the environmental variables among streams along different land uses. The low frequency of histopathological alterations found in fish from the forest streams suggested normal organ functioning. In fish from the rural and urban streams, the histopathological alterations occurred were in higher frequency, indicated light to moderate damage in gills and liver of fish from the rural streams, and moderate to severe damage in liver of fish from urban streams. The histopathological alterations in gills (lamellar aneurysm) and livers (vascular congestion) verified in impacted streams were significantly more frequent and severe. It was possible to distinguish streams along different land uses, suggesting that these histopathological alterations can be used as biomarkers for biomonitoring studies. The health integrity of fish from streams in forest areas further reinforces the importance of maintaining preservation areas in basins under intensive land use.(AU)

Esse estudo avaliou brânquias e fígado de Astyanax bifasciatus como biomarcadores histológicos para biomonitoramento de riachos em áreas com diferentes usos do solo. Os peixes foram coletados por pesca elétrica em seis riachos na bacia do baixo rio Iguaçu. O objetivo foi correlacionar a presença e o grau de alterações histopatológicas em brânquias e fígado com as variáveis ambientais entre riachos com diferentes usos do solo. A baixa frequência de alterações histopatológicas encontradas em peixes de riachos florestados indicou funcionamento normal do órgão. Em peixes de riachos rurais e urbanos, as alterações histopatológicas encontradas foram em maior frequência, indicando danos leves para moderados em brânquias e fígado de peixes dos riachos rurais, e danos moderados para severos em fígado de peixes de riachos urbanos. As alterações histopatológicas em brânquias (aneurisma lamelar) e fígados (congestão vascular) observadas nos riachos impactados foram significativamente mais frequentes e severas. Foi possível distinguir os riachos com diferente uso do solo, sugerindo que estas alterações histopatológicas podem ser usadas como biomarcadores para estudos de biomonitoramento. A integridade da saúde dos peixes dos riachos nas áreas florestadas reforça ainda mais a importância de manter áreas de preservação nas bacias com intenso uso do solo.(AU)

Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly.

The molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and to control spindle checkpoint signaling. In this study, we describe the molecular mechanism used by the Rod-Zw10-Zwilch complex and the adaptor Spindly to recruit dynein to kinetochores in Caenorhabditis elegans embryos and human cells. We show that Rod's N-terminal ß-propeller and the associated Zwilch subunit bind Spindly's C-terminal domain, and we identify a specific Zwilch mutant that abrogates Spindly and dynein recruitment in vivo and Spindly binding to a Rod ß-propeller-Zwilch complex in vitro. Spindly's N-terminal coiled-coil uses distinct motifs to bind dynein light intermediate chain and the pointed-end complex of dynactin. Mutations in these motifs inhibit assembly of a dynein-dynactin-Spindly complex, and a null mutant of the dynactin pointed-end subunit p27 prevents kinetochore recruitment of dynein-dynactin without affecting other mitotic functions of the motor. Conservation of Spindly-like motifs in adaptors involved in intracellular transport suggests a common mechanism for linking dynein to cargo.

The role of sex hormones and steroid receptors on female reproductive cancers.

Sex steroids have been widely described to be associated with a number of human diseases, including hormone-dependent tumors. Several studies have been concerned about the factors regulating the availability of sex steroids and its importance in the pathophysiological aspects of the reproductive cancers in women. In premenopausal women, large fluctuations in the concentration of circulating estradiol (E2) and progesterone (P4) orchestrate many events across the menstrual cycle. After menopause, the levels of circulating E2 and P4 decline but remain at high concentration in the peripheral tissues. Notably, there is a strong relationship between circulating sex hormones and female reproductive cancers (e.g. ovarian, breast, and endometrial cancers). These hormones activate a number of specific signaling pathways after binding either to estrogen receptors (ERs), especially ERα, ERα36, and ERß or progesterone receptors (PRs). Importantly, the course of the disease will depend on particular transactivation pathway. Identifying ER- or PR-positive tumors will benefit patients in terms of proper endocrine therapy. Based on hormonal responsiveness, effective prevention methods for ovarian, breast, and endometrial cancers represent a special opportunity for women at risk of malignancies. Hormone replacement therapy (HRT) might significantly increase the risk of these cancer types, and endocrine treatments targeting ER signaling may be helpful against E2-dependent tumors. This review will present the role of sex steroids and their receptors associated with the risk of developing female reproductive cancers, with emphasis on E2 levels in pre and postmenopausal women. In addition, new therapeutic strategies for improving the survival rate outcomes in women will be addressed.