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Lepidoptera are a highly diverse group of herbivorous insects; however, some superfamilies have relatively few species. Two alternative hypotheses for drivers of Lepidoptera diversity are shifts in food plant use or shifts from concealed to external feeding as larvae. Many studies address the former hypothesis but with bias toward externally feeding taxa. One of the most striking examples of species disparity between sister lineages in Lepidoptera is between the concealed-feeding sack-bearer moths (Mimallonoidea), which contain about 300 species, and externally feeding Macroheterocera, which have over 74,000 species. We provide the first dated tree of Mimallonidae to understand the diversification dynamics of these moths in order to fill a knowledge gap pertaining to drivers of diversity within an important concealed-feeding clade. We find that Mimallonidae is an ancient Lepidoptera lineage that originated in the Cretaceous ∼105 million years ago and has had a close association with the plant order Myrtales for the past 40 million years. Diversification dynamics are tightly linked with food plant usage in this group. Reliance on Myrtales may have influenced diversification of Mimallonidae because clades that shifted away from the ancestral condition of feeding on Myrtales have the highest speciation rates in the family.

Merkel cell carcinoma (MCC) of the breast is a very rare and aggressive type of neuroendocrine carcinoma of the breast (NECB) that typically occurs in older and immunocompromised individuals often presenting as a large palpable mass (Albright et al., 20181). Imaging features of MCC are similar to other NECBs, typically appearing as an oval circumscribed mass on mammography and as an irregular mass with increased vascularity on sonography (Jeon et al., 20142). While both MCC and primary NECB demonstrate positive immunostaining for synaptophysin, obtaining immunohistochemical stains for specific markers, such as CK7 and CK20 is imperative to confirm the diagnosis of MCC (Albright et al., 20181). We present a case of a 57-year-old female patient with no personal or family history of breast cancer, who presented for evaluation of a palpable abnormality in her left breast. Initial diagnostic mammogram demonstrated a circumscribed mass in the upper outer quadrant of the left breast corresponding to the palpable area of concern, which correlated to an irregular mass with increased vascularity on targeted ultrasound, similar to other NECBs. Pathologic results after tissue sampling yielded poorly differentiated primary NECB. Following neoadjuvant chemotherapy, the patient underwent a lumpectomy and further immunohistochemical stains of the lumpectomy specimen demonstrated diffusely positive synaptophysin, negative CK7, and positive CK20, consistent with MCC of the breast.

BACKGROUND: Dietary changes, especially declines in traditional food diversity and increases in the consumption of processed foods, have previously been shown to increase the risk of developing cardiovascular diseases. AIM: We evaluated the prevalence and risk factors for metabolic syndrome in four Awajún communities in the Peruvian Amazon. SUBJECTS AND METHODS: A total of 222 participants answered a socioeconomic questionnaire, a 24-hour food recall, and completed a physical examination for metabolic syndrome diagnosis. A Poisson regression with robust variance was used in the statistical analysis of risk factors for metabolic syndrome. RESULTS: We found an overall prevalence of 24% for metabolic syndrome. Being female, increased age, and body mass index were significant risk factors for metabolic syndrome. Surprisingly, risk more than doubled with the ratio of traditional foods. However, this study revealed that there are fewer traditional foods being consumed in this study compared to prior studies among the Awajún. CONCLUSION: We suggest that the unexpected relationship between traditional food consumption and metabolic syndrome may be due to substantial reductions in the diversity of traditional foods. Currently available traditional foods are primarily high in carbohydrates and are supplemented with cheap, non-perishable, and carbohydrate heavy market food items.

Silver (Ag) nanomaterials (NMs) are used in many products, eventually reaching the environment at some life stage and as they can be harmful their impact should be assessed. Although research has focused on Ag NM toxicity, less focus has been on toxicokinetics. The aim of this study was to assess the kinetics of Ag nanomaterial (Ag NM300K) and AgNO3in the soil invertebrateEnchytraeus crypticus. Tests followed OECD guideline 317, with 14 days uptake followed by 14 days elimination in LUFA 2.2 soil. Two sub-lethal concentrations were selected based on enchytraeid sensitivity in a reproduction test (6 and 60 mg Ag per kg for Ag NM300K, and 5 and 45 mg Ag per kg for AgNO3), and spiked soil aged for 3 and 14 days after spiking. Total and 0.01 M CaCl2extractable soil concentrations were evaluated at day 0, 1 and 14 for all the exposures. Overall, enchytraeids showed increasing Ag uptake with time, followed by a decrease when transferred to clean soil. For the lowest exposure concentrations, the difference in Ag uptake rate constants between 3 and 14 days aging was larger (10-fold) for AgNO3than for NM300K (uptake rates being highest for soil aged for 3 days), which was in line with the higher CaCl2-extractable Ag concentrations in AgNO3spiked soil. At the higher exposure concentrations, for AgNO3the difference in Ag uptake rate constants between 3 and 14 days aged soils was 2-fold, with the bioaccumulation factor (BAF) being highest at 3 days aging. For Ag NM300K, the uptake rate constant was low with virtually no elimination, suggesting that body Ag concentrations may keep on increasing with time leading to a higher risk of longer-term exposure compared to the Ag ions. These findings show the importance of understanding the toxicokinetics of ionic and nano forms of silver and other elements, and the key role of aging in determining NM bioavailability.

Radish downy mildew (DM) caused by the oomycete Hyaloperonospora brassicae f. sp. raphani is a serious problem in radish crop, an edible root vegetable of the Brassicaceae family. The objective of this research was to assess radish germplasm for DM resistance and to evaluate the response of different radish organs to the disease under controlled conditions. Forty-four radish accessions were inoculated at cotyledons and true-leaves with H. brassicae isolate R10, collected in cotyledons of field plants. The roots were tested with isolates R10 and R6, this last one collected in roots of field radish. DM symptoms varied with the radish genotype and plant organ analysed. Twenty-seven resistant and partially resistant accessions were identified in all plant stages and are promising sources of resistance to DM, namely 16 commercial varieties, 10 breeding lines, and one landrace. A significant correlation was observed between cotyledon and leaf (1st and 2nd leaves) DM resistance, but low and no correlation was found between the resistance of true-leaves or cotyledons and roots, respectively. Cotyledon and leaf evaluation cannot be used to predict root resistance response in radish. However, cotyledon resistance has its own value because non-infected cotyledons will act as a barrier to slow disease progression to true-leaves and roots. Interesting sources of DM resistance were identified that can be used in radish breeding programs.

The effects of combined exposure to microplastics and contaminants are still not completely understood. To fill this gap, we assessed the effects of polyethylene terephthalate microplastic fibers (100 mg/L; 360 µm average length) on the toxicity of silver nanoparticles (AgNPs; 32 nm) and silver nitrate (AgNO3; 0.1–10 µg Ag/L) to Daphnia magna. Acute immobilization (median effect concentration [EC50]) and cellular energy allocation (CEA; ratio between available energy and energy consumption) were determined in neonates (3 (2.6 and 0.67 µg Ag/L, respectively) was not affected by the presence of microplastic fibers (2.2 and 0.85 µg Ag/L, respectively). No decrease in the available energy was observed: lipid, carbohydrate, and protein contents were unaffected. However, a significant increase in energy consumption was observed in animals exposed to AgNO3 (250% compared with control) and to the combination of microplastic fibers with AgNP (170%) and AgNO3 (260%). The exposure to microplastic fibers alone or in combination with both Ag forms decreased the CEA (values were 55–75% of control values). Our results show that after short-term exposure (48 h), microplastic fibers increased Ag toxicity at a subcellular level (i.e., CEA), but not at the individual level (i.e., immobilization). These results highlight the importance of combining different levels of biological organization to fully assess the ecotoxicological effects of plastics in association with environmental contaminants. Environ Toxicol Chem 2022;41:896–904.

Made available in DSpace on 2021-06-25T10:46:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The aim of this study is to evaluate whether the alterations in glucose metabolism and insulin resistance are mechanisms presented in cardiac remodelling induced by the toxicity of cigarette smoke. Male Wistar rats were assigned to the control group (C; n = 12) and the cigarette smoke-exposed group (exposed to cigarette smoke over 2 months) (CS; n = 12). Transthoracic echocardiography, blood pressure assessment, serum biochemical analyses for catecholamines and cotinine, energy metabolism enzymes activities assay; HOMA index (homeostatic model assessment); immunohistochemistry; and Western blot for proteins involved in energy metabolism were performed. The CS group presented concentric hypertrophy, systolic and diastolic dysfunction, and higher oxidative stress. It was observed changes in energy metabolism, characterized by a higher HOMA index, lower concentration of GLUT4 (glucose transporter 4) and lower 3-hydroxyl-CoA dehydrogenase activity, suggesting the presence of insulin resistance. Yet, the cardiac glycogen was depleted, phosphofructokinase (PFK) and lactate dehydrogenase (LDH) increased, with normal pyruvate dehydrogenase (PDH) activity. The activity of citrate synthase, mitochondrial complexes and ATP synthase (adenosine triphosphate synthase) decreased and the expression of Sirtuin 1 (SIRT1) increased. In conclusion, exposure to cigarette smoke induces cardiac remodelling and dysfunction. The mitochondrial dysfunction and heart damage induced by cigarette smoke exposure are associated with insulin resistance and glucose metabolism changes. Department of Internal Medicine Botucatu Medical School São Paulo State University-UNESP Faculty of Nutrition UFG – Univ Federal de Goiás Department of Chemical and Biological Sciences São Paulo State University-UNESP Department of Pathology and Legal Medicine Ribeirão Preto Medical School University of São Paulo Experimental Research Unit – UNIPEX Botucatu Medical School São Paulo State University-UNESP Department of Internal Medicine Botucatu Medical School São Paulo State University-UNESP Department of Chemical and Biological Sciences São Paulo State University-UNESP Experimental Research Unit – UNIPEX Botucatu Medical School São Paulo State University-UNESP CAPES: 001 FAPESP: 2014/24197-0 FAPESP: 2016/14547-0 FAPESP: 2016/25676-5

Adenomyoepitheliomas (AMEs) of the breast are uncommon and span the morphologic spectrum of benign, atypical, in situ, and invasive forms. In exceptionally rare cases, these tumors metastasize to regional lymph nodes or distant sites. In the era of genomic characterization, data is limited regarding AMEs. The aim of this study was to provide insight into the molecular underpinnings of a spectrum of AMEs. Seven cases of AMEs of the breast (benign-1, atypical-2, in situ-1, invasive-3) were identified in our files. The seven samples were interrogated using the Oncomine Comprehensive Assay v3 (ThermoFisher). Two atypical AMEs and the malignant in situ AME harbored the same gain-of-function PIK3CA mutation. The malignant in situ AME also showed EGFR amplification, not described previously. Both a benign AME and a malignant invasive AME shared the same gain-of-function AKT1 variant. The benign AME also showed a GNAS mutation. Moreover, the same gain-of-function HRAS mutation was present in an atypical AME and a malignant invasive AME. We also identified co-occurring HRAS and PIK3CA mutations in an ER-positive atypical AME, which has not been previously described. No fusion drivers were detected. We describe the molecular characteristics of the spectrum of AME tumors of the breast, which harbor alterations in the PI3K/AKT pathway. Our findings are clinically relevant with respect to the current options of targeted therapy in the rare instances where malignant AME tumors of the breast progress.

As urbanization and urban sprawl increases, habitat for native flora and fauna often becomes threatened. Reestablishing wildlife habitats within designed landscapes has become increasingly popular with horticultural consumers, who are becoming more aware of the benefits of using native plants and the threats of invasive species. Texas wild rice (Zizania texana Hitchc.) is a federally endangered aquatic plant known to occur only in the San Marcos River, Hays County, TX. The objective of this study was to experimentally test the impact of light availability on the vegetative growth of Texas wild rice (TWR) ex situ. The effect of photosynthetically active radiation (PAR) was tested by establishing treatment and control groups of plants in a river raceway located on the campus of Texas State University, San Marcos, TX. At the onset of the experiment, baseline growth data were collected on a random sample of 15 plants to determine starting conditions. The 75 plants within the control and treatment groups were also randomly selected. Two sequential experimental trials were designed involving the same treatment of PAR reductions with 15 TWR plants in the control group (100% of ambient PAR conditions) and 15 within each of four experimental treatment units. Treatments included a reduction in ambient light values at each of the following rates: PAR reduced by 10% (90% ambient light), 20% (80% ambient light), 40% (60% ambient light), and 80% (20% ambient light). Results of the study indicated high shade areas contained reduced areal coverage or complete lack of TWR. There was a significant decrease in both above and below ground biomass, with an 80% reduction in available PAR (20% available ambient light), and other growth parameters of TWR were negatively impacted by reductions in PAR greater than 40% (60% ambient light availability) during the short-term early establishment growth period. Therefore, light availability is a critical environmental factor that must be given consideration when deciding areas of the river to plant TWR for population augmentation.

Made available in DSpace on 2020-12-12T02:08:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-07-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The objective of this study was to evaluate Spondias mombin L. (SM) pulp and its influence on cardiac remodelling after myocardial infarction (MI). Male Wistar rats were assigned to four groups: a sham group (animals underwent simulated surgery) that received standard chow (S; n = 20), an infarcted group that received standard chow (MI; n = 24), an infarcted group supplemented with 100 mg of SM/kg bodyweight/d, (MIS100; n = 23) and an infarcted group supplemented with 250 mg of SM/kg bodyweight/d (MIS250; n = 22). After 3 months of treatment, morphological, functional and biochemical analyses were performed. MI induced structural and functional changes in the left ventricle with worsening systolic and diastolic function, and SM supplementation at different doses did not influence these variables as analysed by echocardiography and an isolated heart study (P >.05). However, SM supplementation attenuated cardiac remodelling after MI, reducing fibrosis (P =.047) and hypertrophy (P =.006). Biomarkers of oxidative stress, inflammatory processes and energy metabolism were further investigated in the myocardial tissue. SM supplementation improved the efficiency of energy metabolism and decreased lipid hydroperoxide in the myocardium [group S (n = 8): 267.26 ± 20.7; group MI (n = 8): 330.14 ± 47.3; group MIS100 (n = 8): 313.8 ± 46.2; group MIS250: 294.3 ± 38.0 nmol/mg tissue; P =.032], as well as decreased the activation of the inflammatory pathway after MI. In conclusion, SM supplementation attenuated cardiac remodelling processes after MI. We also found that energy metabolism, oxidative stress and inflammation are associated with this effect. In addition, SM supplementation at the highest dose is more effective. Internal Medicine Department Botucatu Medical School São Paulo State University (UNESP) School of Nutrition Sciences Faculty of Health Sciences University of Ottawa Chemistry and Biochemistry Department Institute of Biosciences São Paulo State University (UNESP) Internal Medicine Department Botucatu Medical School São Paulo State University (UNESP) Chemistry and Biochemistry Department Institute of Biosciences São Paulo State University (UNESP) FAPESP: 2014/23215-5 FAPESP: 2015/18502-8 FAPESP: 2018/03082-1

Many immunotherapies act by enhancing the ability of cytotoxic T cells to kill tumor cells. Killing depends on T cell recognition of antigens presented by class I major histocompatibility complex (MHC-I) proteins on tumor cells. In this study, we showed that medulloblastomas lacking the p53 tumor suppressor do not express surface MHC-I and are therefore resistant to immune rejection. Mechanistically, this is because p53 regulates expression of the peptide transporter Tap1 and the aminopeptidase Erap1, which are required for MHC-I trafficking to the cell surface. In vitro, tumor necrosis factor (TNF) or lymphotoxin-β receptor agonist can rescue expression of Erap1, Tap1 and MHC-I on p53-mutant tumor cells. In vivo, low doses of TNF prolong survival and synergize with immune checkpoint inhibitors to promote tumor rejection. These studies identified p53 as a key regulator of immune evasion and suggest that TNF could be used to enhance sensitivity of tumors to immunotherapy.

Alpinia spp. play an important ecological role as a source of nectar in the understory of tropical and subtropical forests and many are common. The perennial species Alpinia purpurata (Vieill.) K. Schum. is native to the tropical rainforests of Asia and has been used as an ornamental cut plant because of its lush inflorescences and post-harvest durability. The internal and external morphology, floral biology, and reproductive system of four A. purpurata cultivars were investigated to contribute to studies on the genetic improvement of this species. The inflorescence of A. purpurata is terminal and globose, and has flowers protected by colorful and showy bracts. The white flowers are tubular and bisexual. The floral anthesis of these four cultivars lasted 9 to 12 h, and the pollen viability was above 80% throughout the pre-flowering period in all evaluated cultivars. During anthesis, the stigma and anther crest were receptive because of the presence of stigmatic fluid. Fruiting was observed after hand cross-pollination, whereas no fruiting was recorded in the treatments with spontaneous self-pollination, hand self-pollination or geitonogamy. Natural pollination induced low fruiting, suggesting low pollinator availability in the studied area. The obligatory xenogamy of A. purpurata facilitates the development of new hybrids for the ornamental plant market. RESUMEN Alpinia spp. desempeñan un importante papel ecológico, como fuente de néctar, en el sotobosque de los bosques tropicales y subtropicales, donde muchas de estas especies son comunes. La especie perenne Alpinia purpurata (Vieill.) K. Schum. es nativa de las selvas tropicales de Asia y se ha utilizado como planta de corte ornamental debido a las exuberantes inflorescencias y la durabilidad posterior a la cosecha. Se investigó la morfología interna y externa, la biología floral y el sistema reproductivo de cuatro cultivares de A. purpurata, para apoyar los estudios de mejora genética de la especie. La inflorescencia de A. purpurata es terminal, globosa y tiene flores protegidas por brácteas coloridas y vistosas. Las flores blancas son tubulares bisexuales. La antesis floral de los cuatro cultivares duró entre 9 y 12 h. La viabilidad del polen fue superior al 80% durante todo el período de pre-floración en todos los cultivares evaluados. Durante la antesis, el estigma y la cresta de la antera fueron receptivos. La fructificación de los cultivares se observó después de la polinización cruzada manual. No se registró fructificación en los tratamientos de autopolinización espontánea, autopolinización manual y geitonogamia. La polinización natural indujo baja fructificación, lo que sugiere una baja disponibilidad de polinizadores en el área estudiada. La xenogamia obligatoria de A. purpurata es un facilitador para el desarrollo de nuevos híbridos para el mercado de plantas ornamentales.

Background & Aims Recent evidence has suggested that the intact intestinal epithelial barrier protects our body from a range of immune-mediated diseases. The epithelial layer has an impressive ability to reconstitute and repair upon damage and this process of repair increasingly is seen as a therapeutic target. In vitro models to study this process in primary intestinal cells are lacking. Methods We established and characterized an in vitro model of intestinal damage and repair by applying γ-radiation on small-intestinal organoids. We then used this model to identify novel regulators of intestinal regeneration. Results We identified hepatocyte nuclear factor 4α (HNF4α) as a pivotal upstream regulator of the intestinal regenerative response. Organoids lacking Hnf4a were not able to propagate in vitro. Importantly, intestinal Hnf4a knock-out mice showed impaired regeneration after whole-body irradiation, confirming intestinal organoids as a valuable alternative to in vivo studies. Conclusions In conclusion, we established and validated an in vitro damage–repair model and identified HNF4α as a crucial regulator of intestinal regeneration. Transcript profiling: GSE141515 and GSE141518., Graphical abstract

Made available in DSpace on 2022-04-29T08:33:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-03-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Universidade Estadual Paulista Aim: This study aimed to evaluate the association between serum myostatin levels, hospital mortality, and muscle mass and strength following ST-segment elevation myocardial infarction (STEMI). Methods: This was a prospective observational study. Within 48 hours of admission, bioelectrical impedance and handgrip strength were assessed and blood samples collected for myostatin evaluation. Hospital mortality was recorded. A multiple logistic regression model was also constructed, adjusted by parameters that exhibited significant differences in the univariate analysis, to evaluate the association between myostatin levels and hospital mortality. Results: One hundred and two (102) patients were included: mean age was 60.5±10.6 years, 67.6% were male, and 6.9% died during hospital stay. Univariate analysis showed that patients with lower myostatin levels had higher mortality rates. Serum myostatin levels positively correlated with handgrip strength (r=0.355; p

Made available in DSpace on 2022-04-29T08:30:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-01 Objectives: Doxorubicin is a highly effective chemotherapeutic agent for treating several types of cancer; however, it can induce cardiotoxicity. We evaluated the influence of Pera and Moro orange juices on cardiac remodeling induced by acute administration of doxorubicin in rats. Methods: We allocated 120 male Wistar rats into six groups: control (C), Pera orange juice (PO), Moro orange juice (MO), doxorubicin (D), doxorubicin + Pera orange juice (DPO), and doxorubicin + Moro orange juice (DMO). Groups PO and DPO received Pera orange juice, MO and DMO received Moro orange juice, and C and D received water with maltodextrin (100 g/L) for 4 wk. Subsequently, groups D, DPO, and DMO received 20 mg/kg doxorubicin and C, PO, and MO received saline. Echocardiogram and euthanasia were performed 48 h after doxorubicin injection. Juice and animal-serum flavonoid identification and quantification were evaluated by liquid chromatography/electrospray ionization multistage mass spectrometry. Oxidative stress and myocardial metabolism were evaluated by spectrophotometry. Results: Systolic and diastolic left ventricular dysfunction increased oxidative stress and pathologic changes in myocardial energy metabolism of rats treated with doxorubicin. Intake of both orange juices improved left ventricular function, decreased oxidative stress, and attenuated the myocardial energy metabolism changes. Moro orange juice had a more pronounced effect than Pera orange juice in glutathione peroxidase activity, citrate synthase, and β-hydroxyacyl-CoA dehydrogenase activity. Conclusions: Pera and Moro orange juices attenuated cardiac remodeling induced by doxorubicin, improved myocardial energy metabolism, and attenuated oxidative stress. However, Moro orange juice was more effective than Pera orange juice in modifying energy metabolism. Internal Medicine Department Botucatu Medical School São Paulo State University (UNESP) Chemistry and Biochemistry Department Institute of Biosciences São Paulo State University (UNESP) Department of Food Science and Experimental Nutrition School of Pharmaceutical Science University of São Paulo Internal Medicine Department Botucatu Medical School São Paulo State University (UNESP) Chemistry and Biochemistry Department Institute of Biosciences São Paulo State University (UNESP)

We report the Bombycoidea and Mimallonoidea (Lepidoptera) observed at the the Universidade Federal do Rio Grande do Sul’s (UFRGS) Agronomic Research Station in Eldorado do Sul, Rio Grande do Sul, Brazil from September 7th to November 6th, 2018. This research station is situated in the Campos Sulinos (southern Brazilian grasslands) environment. As part of our inventory, we report the following Bombycoidea: 29 species of Sphingidae, 26 species of Saturniidae, at least seven species of Apatelodidae, and at least four species of Bombycidae. Within Mimallonidae we recorded eight species. New state records include the following Sphingidae: Xylophanes alineae, X. crenulata, and Perigonia stulta; and Mimallonidae: Mimallo grisea and the genus Menevia. Our study represents the first inventory of moths from this location and one of the few from the Campos Sulinos more broadly.

Solar radiation effects on the ecophysiology and biochemical responses of the brown macroalga Macrocystis pyrifera (L.) C. Agardh were evaluated using a mesocosm approach in Southern Chile. Treatments with different radiation attenuations were simulated with three vertical attenuation coefficients: (1) total (Kd = 0.8 m−1), (2) attenuated (Kd = 1.2 m−1), and (3) low (Kd = 1.6 m−1) radiation levels. Nutrient concentration and temperature did not show differences under the three light conditions. Photosynthetic activity was estimated by in vivo chlorophyll a (Chla) fluorescence under the three light treatments as an isolated physical factor in both in situ solar radiation in the field. This was achieved using a pulse amplitude-modulated (PAM) fluorometera—Diving PAM (in situ). Photosynthetic activity and biochemical composition were measured in winter during two daily cycles (1DC and 2DC) in different parts of the thalli of the plant: (1) canopy zone, (2) middle zone, and (3) down zone, associated with different depths in the mesocosm system. Nevertheless, the in situ electron transport rate (ETRin situ) was higher in the exposed thalli of the canopy zone, independent of the light treatment conditions. The concentration of phenolic compounds (PC) increases in the down zone in the first daily cycle, and it was higher in the middle zone in the second daily cycle. The Chla increased in the morning time under total and attenuated radiation in the first daily cycle. Solar radiation increasing at midday prompted the photoinhibition of photosynthesis in the canopy zone but also an increase in productivity and phenol content. Therefore, light attenuation in the water column drove key differences in the photo-physiological responses of M. pyrifera, with the highest productivity occurring in thalli positioned in the canopy zone when exposed to solar irradiance.

Significance HLA alleles have previously been implicated with scleroderma risk, but, in this study, using a European American ancestral cohort and a newly recruited large cohort of African Americans, we comprehensively define the HLA alleles and amino acid residues associated with scleroderma. Scleroderma is characterized by mutually exclusive and specific autoantibodies. We demonstrated ancestry-predominant HLA alleles that were much more strongly associated with autoantibody subsets of scleroderma than with the overall risk of SSc. We bioinformatically predicted immunodominant peptides of self-antigens and demonstrated homology of these peptides with viral protein sequences from Mimiviridae and Phycodnaviridae families. Our findings suggest the hypothesis that scleroderma-specific autoantibodies may arise through molecular mimicry, driven by the interaction of specific viral antigens with corresponding HLA α/β heterodimers., Systemic sclerosis (SSc) is a clinically heterogeneous autoimmune disease characterized by mutually exclusive autoantibodies directed against distinct nuclear antigens. We examined HLA associations in SSc and its autoantibody subsets in a large, newly recruited African American (AA) cohort and among European Americans (EA). In the AA population, the African ancestry-predominant HLA-DRB1*08:04 and HLA-DRB1*11:02 alleles were associated with overall SSc risk, and the HLA-DRB1*08:04 allele was strongly associated with the severe antifibrillarin (AFA) antibody subset of SSc (odds ratio = 7.4). These African ancestry-predominant alleles may help explain the increased frequency and severity of SSc among the AA population. In the EA population, the HLA-DPB1*13:01 and HLA-DRB1*07:01 alleles were more strongly associated with antitopoisomerase (ATA) and anticentromere antibody-positive subsets of SSc, respectively, than with overall SSc risk, emphasizing the importance of HLA in defining autoantibody subtypes. The association of the HLA-DPB1*13:01 allele with the ATA+ subset of SSc in both AA and EA patients demonstrated a transancestry effect. A direct correlation between SSc prevalence and HLA-DPB1*13:01 allele frequency in multiple populations was observed (r = 0.98, P = 3 × 10−6). Conditional analysis in the autoantibody subsets of SSc revealed several associated amino acid residues, mostly in the peptide-binding groove of the class II HLA molecules. Using HLA α/β allelic heterodimers, we bioinformatically predicted immunodominant peptides of topoisomerase 1, fibrillarin, and centromere protein A and discovered that they are homologous to viral protein sequences from the Mimiviridae and Phycodnaviridae families. Taken together, these data suggest a possible link between HLA alleles, autoantibodies, and environmental triggers in the pathogenesis of SSc.

Bipolar disorder (BD) is a common, highly heritable disorder that affects 1–2% of the world’s population. To date, most genetic studies of BD have focused on common gene variation, and while robustly associated loci have been identified, a substantial proportion of the heritability remains missing and could be partially attributable to rare variation. In this study, we apply a de novo paradigm in BD to identify newly arisen variants that have yet to undergo natural selection and may represent highly pathogenic variants. We performed whole genome sequencing of 97 trios of Ashkenazi Jewish descent, selecting “simplex” families with no family history of BD and an early age of onset. We found a total of 6882 de novo variants (an average of 70.9 ± 12.9 S.D. variants per trio), including 107 variants within protein-coding genes. We combined our exonic variations with the results of 79 previously published BD trios, identifying 20 loss-of-function (LoF) and 77 missense damaging de novo variants in BD. These variants showed significant enrichment for constrained genes and for genes located to the postsynaptic density (PSD) (all Bonferroni corrected p

Neurological complications affecting the central nervous system have been reported in adult patients infected by Zika virus (ZIKV) but the underlying mechanisms remain unknown. Here, we report that ZIKV replicates in human and mouse adult brain tissue, targeting mature neurons. ZIKV preferentially targets memory-related brain regions, inhibits hippocampal long-term potentiation and induces memory impairment in adult mice. TNF-α upregulation, microgliosis and upregulation of complement system proteins, C1q and C3, are induced by ZIKV infection. Microglia are found to engulf hippocampal presynaptic terminals during acute infection. Neutralization of TNF-α signaling, blockage of microglial activation or of C1q/C3 prevent synapse and memory impairment in ZIKV-infected mice. Results suggest that ZIKV induces synapse and memory dysfunction via aberrant activation of TNF-α, microglia and complement. Our findings establish a mechanism by which ZIKV affects the adult brain, and point to the need of evaluating cognitive deficits as a potential comorbidity in ZIKV-infected adults., Here, using ex-vivo human adult cortical tissue and a mouse model, the authors investigate the functional consequences of Zika virus (ZIKV) infection in the adult brain, and show that ZIKV causes synapse damage and altered brain function that impacts cognition via activation of innate and inflammatory factors.

Made available in DSpace on 2019-10-06T17:18:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 Debreceni Egyetem BACKGROUND/AIMS: Doxorubicin, a chemotherapy drug used successfully for years, could induce cardiotoxicity. Euterpe oleracea Mart. (açai) is a fruit high in antioxidant properties. The aim of this study was to evaluate doxorubicin-induced cardiotoxicity prevention after açai administration. METHODS: A total of 64 male Wistar rats were allocated into 4 groups: control (C), açai (A), doxorubicin (D) and açai-doxorubicin (DA). Rats received regular chow (C and D groups) or chow supplemented with açai 5% (A and DA groups) for 4 weeks. Subsequently, rats received doxorubicin 20 mg/kg (D and DA groups) or saline (C and A groups). Euthanasia was performed 48 hours after doxorubicin injection. Left ventricular function was evaluated by echocardiography in vivo and by isolated heart study ex vivo. Oxidative stress, myocardial metabolism and nitric oxide metabolite were evaluated by spectrophotometry, MMP-2 activity by zymography and caspase-3 and Bcl-2 protein expression by Western blot. RESULTS: Doxorubicin induced decreases in body weight, food and water ingestion. We observed decreases in left ventricular fractional shortening in rats treated with doxorubicin. Additionally, the same rats showed lower +dP/dt and -dP/dt during isolated heart study than those who did not receive doxorubicin. Doxorubicin injection increased caspase-3 protein expression, myocardium lipid hydroperoxide concentration, MMP-2 activity, phosphofructokinase and lactate dehydrogenase activity, and decreased β-hydroxyacyl-CoA dehydrogenase, pyruvate dehydrogenase, citrate synthase, complex I, complex II and ATP synthase activity in myocardium. Açai supplementation improved left ventricular fractional shortening, decreased myocardium lipid hydroperoxide concentration, MMP-2 activity, and improved β-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, citrate synthase, complex II and ATP synthase enzymatic activities. We did not observe differences in nitric oxide metabolite concentrations between groups. CONCLUSION: Doxorubicin induced left ventricular dysfunction, increases in oxidative stress, changes in myocardium metabolism and MMP-2 activation. Açai supplementation was able to prevent these alterations. Medical School São Paulo State University (Unesp) Institute of Biosciences São Paulo State University (Unesp) Medical School São Paulo State University (Unesp) Institute of Biosciences São Paulo State University (Unesp) Debreceni Egyetem: 2018/03381-9

Background In humans, accumulated adverse experiences during childhood increase the risk of anxiety disorders and attention-deficit/hyperactivity disorder. In rodents, the ventral hippocampus (vHIP) is associated with anxiety regulation, and lesions in this region alter both anxiety-like behavior and activity levels. Neuronal oscillations in the vHIP of the theta frequency range (4–12 Hz) have been implicated in anxious states and derive in part from the activity of inhibitory interneurons in the hippocampus, some of which are enwrapped with perineuronal nets (PNNs), extracellular matrix structures known to regulate plasticity. We sought to investigate the associations among early life stress–induced anxiety and hyperactivity with vHIP neuronal oscillations, inhibitory interneurons, and PNNs in mice. Methods We used repeated maternal separation with early weaning (MSEW) to model accumulated early life adversity in mouse offspring and studied the underlying cellular and electrophysiological changes in the vHIP that are associated with excessive anxiety and hyperactivity. Results We found increased anxiety-like behavior and activity levels in MSEW adult males, along with increased theta power and enhanced theta–gamma coupling in the vHIP. MSEW mice showed reduced intensity of parvalbumin as well as increased PNN intensity around parvalbumin-positive interneurons in the vHIP. We further observed that MSEW increased orthodenticle homeobox protein 2, a transcription factor promoting PNN development, in the choroid plexus, where it is produced, as well as in parvalbumin-positive interneurons, where it is sequestered. Conclusions These findings raise the possibility of causal links among parvalbumin-positive interneurons, PNNs, orthodenticle homeobox protein 2, and MSEW-induced anxiety and hyperactivity.

Currently the area with the inundative release of Cotesia flavipes (Cameron) in the country is approximately 3.5 million hectares per year in regions of tropical and subtropical climate, but there are questions about its efficiency since they are not considered the thermal requirements of the strains used. The objective of the study was to evaluate the biology in different thermal conditions of five C. flavipes strains, from different places of origin. Insects from Parana (Strain PR), Minas Gerais (Strain MG), Alagoas (Strain AL) and two strains from Sao Paulo state (SPI and SPII strains) were submitted to different constant temperatures (10, 15, 18, 20, 22, 25, 30, and 32°C), relative air humidity of 70 ± 10% and 12-h photophase. The duration the egg-adult of C. flavipes was inversely proportional to the temperature in the thermal range of 18 to 30°C. No development occurred at temperatures of 10, 15, and 32°C. The highest survival of the biological cycle (egg-adult) (above 70%) occurred in the thermal range of 25 to 28°C. Also, temperatures from 28 to 30°C characterize significantly more females than males (sex ratio > 0.70). Based on the development of the biological cycle, the threshold temperature (Tt) was similar among the C. flavipes strains (ranging from 9.6 to 11.1°C), providing the thermal constants of 229.4 to 273.9 degree-days. The biological control of Diatraea saccharalis (Fabricius 1794) (Lepidoptera: Crambidae) may be more efficient to use C. flavipes strains more adapted to the thermal conditions of each region.

Microplastic fibers (MF) are released from synthetic textiles during washing and end up in the wastewater. Similarly, silver nanoparticles (AgNP), incorporated in textiles as antimicrobial agents, are released in washing machines, also reaching the wastewater treatment plants. Therefore, both MF and AgNP co-exist in the environment and enter the soil compartment mainly via the application of biosolids. Yet, the combined effect of MF and AgNP has not been studied. Here, we assessed the effects of polyester MF on the toxicity of AgNP and AgNO3 to the earthworm Eisenia andrei and the enchytraeid Enchytraeus crypticus. The organisms were exposed to a range of concentration of AgNP (32, 100, 320, 1000, 3200 mg Ag/kg) and AgNO3 (12.8, 32, 80, 200, 500 mg Ag/kg) in LUFA 2.2 soil in the absence or presence of MF (0.01% DW). Reproduction tests were conducted and the toxicity outcomes compared between soils with and without MF. The exposure to MF caused a decrease in the number of juveniles and changed the biochemical composition of earthworms. Moreover, the presence of MF increased the toxicity of AgNP to earthworm reproduction (EC50 = 165 mg Ag/kg) when compared to AgNP exposure alone (EC50 = 450 mg Ag/kg), but did not alter the toxicity of AgNO3 (EC50 = 40 mg Ag/kg). For enchytraeids, no significant difference in Ag toxicity could be detected when MF was added to the soil for both AgNP and AgNO3. Overall, Ag bioaccumulation was not affected by MF, except for a decrease in earthworm body concentration at the highest Ag soil concentration (3200 mg Ag/kg). Our results suggest that the presence of MF in the soil compartment may be a cause of concern, and that the joint exposure to Ag may be deleterious depending on the Ag form, organism, and endpoint. The present work provides the first evidence that a realistic MF concentration in soil lowers AgNP concentration necessary to provoke reproductive impairment in earthworms. The influence of MF on the risk assessment of AgNP should be considered.

Male butterflies in the hyperdiverse tribe Eumaeini possess an unusually complex and diverse repertoire of secondary sexual characteristics involved in pheromone production and dissemination. Maintaining multiple sexually selected traits is likely to be metabolically costly, potentially resulting in trade-offs in the evolution of male signals. However, a phylogenetic framework to test hypotheses regarding the evolution and maintenance of male sexual traits in Eumaeini has been lacking. Here, we infer a comprehensive, time-calibrated phylogeny from 379 loci for 187 species representing 91% of the 87 described genera. Eumaeini is a monophyletic group that originated in the late Oligocene and underwent rapid radiation in the Neotropics. We examined specimens of 818 of the 1096 described species (75%) and found that secondary sexual traits are present in males of 91% of the surveyed species. Scent pads and scent patches on the wings and brush organs associated with the genitalia were probably present in the common ancestor of Eumaeini and are widespread throughout the tribe. Brush organs and scent pads are negatively correlated across the phylogeny, exhibiting a trade-off in which lineages with brush organs are unlikely to regain scent pads and vice versa. In contrast, scent patches seem to facilitate the evolution of scent pads, although they are readily lost once scent pads have evolved. Our results illustrate the complex interplay between natural and sexual selection in the origin and maintenance of multiple male secondary sexual characteristics and highlight the potential role of sexual selection spurring diversification in this lineage., Proceedings of the Royal Society B: Biological Sciences, 288 (1950), ISSN:0080-4649, ISSN:0950-1193, ISSN:1471-2954, ISSN:0962-8452

Conventional dendritic cells (cDCs) bridge antigen detection to the induction of adaptive immunity, playing crucial roles in host defense. Vanderkerken, Baptista, et al. show that LTα1β2-expressing ILC3s, together with B cells, control the size of the splenic cDC compartment and cDC2 differentiation., The spleen contains a myriad of conventional dendritic cell (cDC) subsets that protect against systemic pathogen dissemination by bridging antigen detection to the induction of adaptive immunity. How cDC subsets differentiate in the splenic environment is poorly understood. Here, we report that LTα1β2-expressing Rorgt+ ILC3s, together with B cells, control the splenic cDC niche size and the terminal differentiation of Sirpα+CD4+Esam+ cDC2s, independently of the microbiota and of bone marrow pre-cDC output. Whereas the size of the splenic cDC niche depended on lymphotoxin signaling only during a restricted time frame, the homeostasis of Sirpα+CD4+Esam+ cDC2s required continuous lymphotoxin input. This latter property made Sirpα+CD4+Esam+ cDC2s uniquely susceptible to pharmacological interventions with LTβR agonists and antagonists and to ILC reconstitution strategies. Together, our findings demonstrate that LTα1β2-expressing Rorgt+ ILC3s drive splenic cDC differentiation and highlight the critical role of ILC3s as perpetual regulators of lymphoid tissue homeostasis.

Made available in DSpace on 2021-06-25T11:00:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Experimental studies have shown the action of green tea in modulating cardiac remodeling. However, the effects of green tea on the cardiac remodeling process induced by doxorubicin (DOX) are not known. Therefore, this study is aimed at evaluating whether green tea extract could attenuate DOX-induced cardiac remodeling, assessed by cardiac morphological and functional changes and associated with the evaluation of different modulators of cardiac remodeling. The animals were divided into four groups: the control group (C), the green tea group (GT), the DOX group (D), and the DOX and green tea group (DGT). Groups C and GT received intraperitoneal sterile saline injections, D and DGT received intraperitoneal injections of DOX, and GT and DGT were fed chow supplemented with green tea extract for 35 days prior to DOX injection. After forty-eight hours, we performed an echocardiogram and euthanasia and collected the materials for analysis. Green tea attenuated DOX-induced cardiotoxicity by increasing cardiac function and decreasing the concentric remodeling. Treatment with DOX increased oxidative stress in the heart, marked by a higher level of lipid hydroperoxide (LH) and lower levels of antioxidant enzymes. Treatment with green tea increased the antioxidant enzymes' activity and decreased the production of LH. Green tea extract increased the expression of Top2-β independent of DOX treatment. The activity of ATP synthase, citrate synthase, and complexes I and II decreased with DOX, without the effects of green tea. Both groups that received DOX presented with a lower ratio of P-akt/T-akt and a higher expression of CD45, TNFα, and intermediate MMP-2, without the effects of green tea. In conclusion, green tea attenuated cardiac remodeling induced by DOX and was associated with increasing the expression of Top2-β and lowering oxidative stress. However, energy metabolism and inflammation probably do not receive the benefits induced by green tea in this model. Internal Medicine Department Botucatu Medical School São Paulo State University (UNESP) Department of Chemical and Biological Sciences São Paulo State University (UNESP) Department of Pathology and Legal Medicine Ribeirão Preto Medical School University of São Paulo (UNESP) Experimental Research Unit (UNIPEX) Botucatu Medical School São Paulo State University (UNESP) Medicine Department São Carlos Federal University Internal Medicine Department Botucatu Medical School São Paulo State University (UNESP) Department of Chemical and Biological Sciences São Paulo State University (UNESP) Department of Pathology and Legal Medicine Ribeirão Preto Medical School University of São Paulo (UNESP) Experimental Research Unit (UNIPEX) Botucatu Medical School São Paulo State University (UNESP)

The inbred high drinking in the dark (iHDID1 and iHDID2) strains are two replicate lines bred from the parent HS/Npt (HS) line for achieving binge levels of blood ethanol concentration (&ge, 80 mg/dL BEC) in a four-hour period. In this work, we sought to evaluate differences in baseline and ethanol-induced c-Fos activation between the HS, iHDID1, and iHDID2 genetic lines in brain regions known to process the aversive properties of ethanol. Methods: Male and female HS, iHDID1, and iHDID2 mice underwent an IP saline 2 3 g/kg ethanol injection. Brain sections were then stained for c-Fos expression in the basolateral/central amygdala (BLA/CeA), bed nucleus of the stria terminals (BNST), A2, locus coeruleus (LC), parabrachial nucleus (PBN), lateral/medial habenula (LHb/MHb), paraventricular nucleus of the thalamus (PVT), periaqueductal gray (PAG), Edinger&ndash, Westphal nuclei (EW), and rostromedial tegmental nucleus (RMTg). Results: The iHDID1 and iHDID2 lines showed similar and distinct patterns of regional c-Fos, however, in no region did the two both significantly differ from the HS line together. Conclusions: These data lend further support to altered baseline or ethanol-induced activation in brain regions associated with processing the aversive properties of ethanol in the iHDID1 and iHDID2 genetic lines.

Paragangliomas are neuroendocrine tumors of the autonomic nervous system that are variably clinically functional and have a potential for metastasis. Up to 40% occur in the setting of a hereditary syndrome, most commonly due to germline mutations in succinate dehydrogenase (SDHx) genes. Immunohistochemically, paragangliomas are characteristically GATA3-positive and cytokeratin-negative, with loss of SDHB expression in most hereditary cases. In contrast, the rare paragangliomas arising in the cauda equina (CEP) or filum terminale region have been shown to be hormonally silent, clinically indolent, and have variable keratin expression, suggesting these tumors may represent a separate pathologic entity. We retrospectively evaluated seventeen CEPs from eleven male and six female patients with a median age of 38 years (range 21–82), none with a family history of neuroendocrine neoplasia. Six of the seventeen tumors demonstrated prominent gangliocytic or ganglioneuromatous differentiation. By immunohistochemistry, none of the CEPs showed GATA3 positivity or loss of SDHB staining; all seventeen CEPs were cytokeratin positive. Genome-wide DNA methylation profiling was performed on twelve of the tumors and compared with publicly available genome-wide DNA methylation data. Clustering analysis showed that CEPs form a distinct epigenetic group, separate from paragangliomas of extraspinal sites, pheochromocytomas, and other neuroendocrine neoplasms. Copy number analysis revealed diploid genomes in the vast majority of CEPs, whereas extraspinal paragangliomas were mostly aneuploid with recurrent trisomy 1q and monosomies of 1p, 3, and 11, none of which were present in the cohort of CEP. Together, these findings indicate that CEPs likely represent a distinct entity. Future genomic studies are needed to further elucidate the molecular pathogenesis of these tumors.

Male mating plugs have been used in many species to prevent female re-mating and sperm competition. One of the most extreme examples of a mating plug is the sphragis, which is a large, complex and externalized plug found only in butterflies. This structure is found in many species in the genus Acraea (Nymphalidae) and provides an opportunity for investigation of the effects of the sphragis on the morphology of the genitalia, which is poorly understood. This study aims to understand morphological interspecific variation in the genitalia of Acraea butterflies. Using specimens from museum collections, abdomen dissections were conducted on 19 species of Acraea: 9 sphragis bearing and 10 non-sphragis bearing species. Genitalia imaging was performed for easier comparison and analysis and measurements of genitalia structures was done using ImageJ software. Some distinguishing morphological features in the females were found. The most obvious difference is the larger and more externalized copulatory opening in sphragis bearing species, with varying degrees of external projections. Females of the sphragis bearing species also tend to have a shorter ductus (the structure that connects the copulatory opening with the sperm storage organ) than those without the sphragis. These differences may be due to a sexually antagonistic coevolution between the males and females, where the females evolve larger and more difficult to plug copulatory openings and the males attempt to prevent re-mating with the sphragis.

Many bacteria and archaea possess a cell surface layer – S-layer – made of a 2D protein array that covers the entire cell. As the outermost component of the cell envelope, S-layers play crucial roles in many aspects of cell physiology. Importantly, many clinically relevant bacterial pathogens possess a distinct S-layer that forms an initial interface with the host, making it a potential target for development of species-specific antimicrobials. Targeted therapeutics are particularly important for antibiotic resistant pathogens such as Clostridioides difficile, the most frequent cause of hospital acquired diarrhea, which relies on disruption of normal microbiota through antibiotic usage. Despite the ubiquity of S-layers, only partial structural information from a very limited number of species is available and their function and organization remains poorly understood. Here we report the first complete atomic level structure and in situ assembly model of an S-layer from a bacterial pathogen and reveal its role in disease severity. SlpA, the main C. difficile S-layer protein, assembles through tiling of triangular prisms abutting the cell wall, interlocked by distinct ridges facing the environment. This forms a tightly packed array, unlike the more porous S-layer models previously described. We report that removing one of the SlpA ridge features dramatically reduces disease severity, despite being dispensable for overall SlpA structure and S-layer assembly. Remarkably, the effect on disease severity is independent of toxin production and bacterial colonization within the mouse model of disease. Our work combines X-ray and electron crystallography to reveal a novel S-layer organization in atomic detail, highlighting the need for multiple technical approaches to obtain structural information on these paracrystalline arrays. These data also establish a direct link between specific structural elements of S-layer and virulence for the first time, in a crucial paradigm shift in our understanding of C. difficile disease, currently largely attributed to the action of potent toxins. This work highlights the crucial role of S-layers in pathogenicity and the importance of detailed structural information for providing new therapeutic avenues, targeting the S-layer. Understanding the interplay between S-layer and other virulence factors will further enhance our ability to tackle pathogens carrying an S-layer. We anticipate that this work provides a solid basis for development of new, C. difficile-specific therapeutics, targeting SlpA structure and S-layer assembly to reduce the healthcare burden of these infections.

The present contribution investigates the biocatalytic performance of the lipase obtained from the latex of the native plant known as Araujia sericifera (ASL) in the hydrolysis followed by the esterification of released free fatty acids and transesterification of glycerides of sunflower waste cooking oil WCO. A specific enzymatic activity of 719.05 μmol mg−1 h−1 (60 % conversion of triglycerides towards free fatty acids) was obtained in the hydrolysis of WCO with 0.05 % of biocatalyst (typically, 10.0 g WCO and 5.0 mg of enzyme) and 50 % w/w of water added in 30 min of reaction at 25 °C in homogeneous type of reaction system. The lipase has the capacity to catalyze the hydrolysis of the triglycerides mainly towards monoglycerides and diglycerides in a lesser extent. The released FFAs and the remaining glycerides reacted in tandem by addition of short chain alcohols immediately after the hydrolysis (without addition of more enzyme to the reaction media). Above 90 % conversion of the FFAs was obtained with methanol, ethanol, n-propanol and n-butanol at contents as low as 1:0.2 oil: alcohol molar ratio at 25 °C. The transesterification of the remaining monoglycerides (about 20 %) was also observed although no further reaction of the triglycerides was detected even under a great excess of alcohol. Fil: Mateos, Paula Stefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Ciencias Aplicadas; Argentina Fil: Navas, Marisa Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Ciencias Aplicadas; Argentina Fil: Morcelle del Valle, Susana Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación de Proteínas Vegetales; Argentina Fil: Ruscitti, Claudia Beatriz. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Matemáticas; Argentina Fil: Matkovic, Silvana Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Ciencias Aplicadas; Argentina Fil: Briand, Laura Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Ciencias Aplicadas; Argentina

Neuroendocrine neoplasms (NENs) are clinically diverse and incompletely characterized cancers that are challenging to classify. MicroRNAs (miRNAs) are small regulatory RNAs that can be used to classify cancers. Recently, a morphology-based classification framework for evaluating NENs from different anatomical sites was proposed by experts, with the requirement of improved molecular data integration. Here, we compiled 378 miRNA expression profiles to examine NEN classification through comprehensive miRNA profiling and data mining. Following data preprocessing, our final study cohort included 221 NEN and 114 non-NEN samples, representing 15 NEN pathological types and 5 site-matched non-NEN control groups. Unsupervised hierarchical clustering of miRNA expression profiles clearly separated NENs from non-NENs. Comparative analyses showed that miR-375 and miR-7 expression is substantially higher in NEN cases than non-NEN controls. Correlation analyses showed that NENs from diverse anatomical sites have convergent miRNA expression programs, likely reflecting morphological and functional similarities. Using machine learning approaches, we identified 17 miRNAs to discriminate 15 NEN pathological types and subsequently constructed a multilayer classifier, correctly identifying 217 (98%) of 221 samples and overturning one histological diagnosis. Through our research, we have identified common and type-specific miRNA tissue markers and constructed an accurate miRNA-based classifier, advancing our understanding of NEN diversity.

Lung neuroendocrine neoplasms (NENs) can be challenging to classify due to subtle histologic differences between pathological types. MicroRNAs (miRNAs) are small RNA molecules that are valuable markers in many neoplastic diseases. To evaluate miRNAs as classificatory markers for lung NENs, we generated comprehensive miRNA expression profiles from 14 typical carcinoid (TC), 15 atypical carcinoid (AC), 11 small cell lung carcinoma (SCLC), and 15 large cell neuroendocrine carcinoma (LCNEC) samples, through barcoded small RNA sequencing. Following sequence annotation and data preprocessing, we randomly assigned these profiles to discovery and validation sets. Through high expression analyses, we found that miR-21 and -375 are abundant in all lung NENs, and that miR-21/miR-375 expression ratios are significantly lower in carcinoids (TC and AC) than in neuroendocrine carcinomas (NECs, SCLC and LCNEC). Subsequently, we ranked and selected miRNAs for use in miRNA-based classification, to discriminate carcinoids from NECs. Using miR-18a and -155 expression, our classifier discriminated these groups in discovery and validation sets, with 93% and 100% accuracy. We also identified miR-17, -103, and -127, and miR-301a, -106b, and -25, as candidate markers for discriminating TC from AC, and SCLC from LCNEC, respectively. However, these promising findings require external validation due to sample size.

The almond cake is a protein-rich residue generated by the mechanical expression of the almond oil. The effects of the aqueous (AEP) and enzyme-assisted aqueous extraction processes (EAEP) on the biological properties of the almond cake protein were evaluated. Total phenolic content (TPC), antioxidant capacity, inhibitory effects against crucial enzymes related to metabolic syndrome, antimicrobial potential, and in vitro protein digestibility profile were assessed. EAEP provided the best results for antioxidant capacity by both ORAC (397.2 µmol TE per g) and ABTS (650.5 µmol TE per g) methods and also showed a high (~ 98%) potential for α-glucosidase inhibition. The AEP resulted in protein extracts with the highest lipase inhibition (~ 70%) in a dose-dependent way. Enzymatic kinetic analyses revealed that EAEP generated uncompetitive inhibitors against α-glucosidase, while EAEP, AEP, and HEX-AEP (used as control) generated the same kind of inhibitors against lipase. No protein extract was effective against any of the bacteria strains tested at antimicrobial assays. An in silico theoretical hydrolysis of amandin subunits corroborated with the results found for antioxidant capacity, enzyme inhibitory experiments, and antimicrobial activity. Digestibility results indicated that the digestive proteases used were efficient in hydrolyzing almond proteins, regardless of the extraction applied and that HEX-AEP presented the highest digestibility (85%). In summary, EAEP and AEP skim proteins have the potential to be used as a nutraceutical ingredient. The biological properties observed in these extracts could help mitigate the development of metabolic syndrome where EAEP and AEP skim proteins could be potentially used as a prophylactic therapy for diabetes and obesity, respectively.

Made available in DSpace on 2020-12-10T20:02:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-06-03 Brazilian National Science Fund (Conselho Nacional de Desenvolvimento Cientifico and Tecnologico) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) BackgroundMost of our understanding on the social behavior and genomics of bees and other social insects is centered on the Western honey bee, Apis mellifera. The genus Apis, however, is a highly derived branch comprising less than a dozen species, four of which genomically characterized. In contrast, for the equally highly eusocial, yet taxonomically and biologically more diverse Meliponini, a full genome sequence was so far available for a single Melipona species only. We present here the genome sequence of Frieseomelitta varia, a stingless bee that has, as a peculiarity, a completely sterile worker caste.ResultsThe assembly of 243,974,526 high quality Illumina reads resulted in a predicted assembled genome size of 275Mb composed of 2173 scaffolds. A BUSCO analysis for the 10,526 predicted genes showed that these represent 96.6% of the expected hymenopteran orthologs. We also predicted 169,371 repetitive genomic components, 2083 putative transposable elements, and 1946 genes for non-coding RNAs, largely long non-coding RNAs. The mitochondrial genome comprises 15,144bp, encoding 13 proteins, 22 tRNAs and 2 rRNAs. We observed considerable rearrangement in the mitochondrial gene order compared to other bees. For an in-depth analysis of genes related to social biology, we manually checked the annotations for 533 automatically predicted gene models, including 127 genes related to reproductive processes, 104 to development, and 174 immunity-related genes. We also performed specific searches for genes containing transcription factor domains and genes related to neurogenesis and chemosensory communication.ConclusionsThe total genome size for F. varia is similar to the sequenced genomes of other bees. Using specific prediction methods, we identified a large number of repetitive genome components and long non-coding RNAs, which could provide the molecular basis for gene regulatory plasticity, including worker reproduction. The remarkable reshuffling in gene order in the mitochondrial genome suggests that stingless bees may be a hotspot for mtDNA evolution. Hence, while being just the second stingless bee genome sequenced, we expect that subsequent targeting of a selected set of species from this diverse clade of highly eusocial bees will reveal relevant evolutionary signals and trends related to eusociality in these important pollinators. Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, Ribeirao Preto, SP, Brazil Univ Fed Alfenas, Inst Ciencias Biomed, Dept Biol Celular & Desenvolvimento, Alfenas, MG, Brazil Univ Fed Vales Jequitinhonha & Mucuri, Fac Ciencias Biol & Saude, Dept Ciencias Biol, Diamantina, MG, Brazil Univ Fed Sao Carlos, Ctr Ciencias Biol & Saude, Dept Genet & Evolucao, Sao Carlos, SP, Brazil Univ Tecnol Fed Parana, Cornelio Procopio, PR, Brazil Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil Univ, Estadual Paulista Julio de Mesquita Filho, Fac Ciencias Agr & Vet, Dept Tecnol, Jaboticabal, SP, Brazil Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Biol, Ribeirao Preto, SP, Brazil Univ, Estadual Paulista Julio de Mesquita Filho, Fac Ciencias Agr & Vet, Dept Tecnol, Jaboticabal, SP, Brazil Brazilian National Science Fund (Conselho Nacional de Desenvolvimento Cientifico and Tecnologico): 454103/2014-0 FAPESP: 2015/06657-0 CAPES: 001

To initiate replication on a double-stranded DNA de novo, all organisms require primase, an RNA polymerase making short RNA primers which are then extended by DNA polymerases. Here, we show that primase can use metabolic cofactors as initiating substrates, instead of its canonical substrate ATP. DnaG primase of Escherichia coli initiates synthesis of RNA with NADH (the reduced form of nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide) in vitro. These cofactors consist of an ADP core covalently bound to extra moieties. The ADP component of these metabolites base-pairs with the DNA template and provides a 3′-OH group for RNA extension. The additional cofactors moieties apparently contact the ‘basic ridge’ domain of DnaG, but not the DNA template base at the –1 position. ppGpp, the starvation response regulator, strongly inhibits the initiation with cofactors, hypothetically due to competition for overlapping binding sites. Efficient RNA primer processing is a prerequisite for Okazaki fragments maturation, and we find that the efficiency of primer processing by DNA polymerase I in vitro is specifically affected by the cofactors on its 5′-end. Together these results indicate that utilization of cofactors as substrates by primase may influence regulation of replication initiation and Okazaki fragments processing.

Brain cancers are the leading cause of cancer-related deaths in children. Biological changes in these tumors likely include epigenetic deregulation during embryonal development of the nervous system. Histone acetylation is one of the most widely investigated epigenetic processes, and histone deacetylase inhibitors (HDACis) are increasingly important candidate treatments in many cancer types. Here, we review advances in our understanding of how HDACis display antitumor effects in experimental models of specific pediatric brain tumor types, i.e., medulloblastoma (MB), ependymoma (EPN), pediatric high-grade gliomas (HGGs), and rhabdoid and atypical teratoid/rhabdoid tumors (ATRTs). We also discuss clinical perspectives for the use of HDACis in the treatment of pediatric brain tumors.

Temporal variation in demographic rates has been observed in various fish populations and environmental influences are likely to be a key factor. Here we show how it can be important to combine state-space models for environmental covariates and demographic rates when evaluating effects of the former on the latter. In an application to Georges Bank Atlantic cod (Gadus morhua), we show how estimates of the environmental covariate can be aliased with unknown temporal variation in growth rates and that stronger and opposite effects of the environment can incorrectly be found when the autocorrelation in the growth rate is not separately modeled. The perception of effects on maturity also depends on whether an appropriate distribution is considered for the maturity observations. Bottom temperature did not improve prediction of maturity parameters, but temporal variation driven by other sources did. Both bottom temperature and temporal variation improved performance of growth models. Finally, we found growth and maturity estimation to be important contributors to uncertainty of spawning biomass and biological reference points when incorporated into a state-space assessment model.

Background Nonoperative management of proximal humeral fractures (PHFs) is the most common treatment, but its functional outcome may improve with early mobilization. In frail osteoporotic patients, quick recovery of prefracture independency is mandatory. This study assessed fracture displacement in PHFs managed with conservative treatment after early mobilization and a home-based self-exercise program. Methods We retrospectively analyzed the radiologic displacement of fracture fragments of PHFs treated conservatively with early mobilization and a home-based self-exercise program. Results Included were 99 patients with 26 one-part, 32 two-part, 32 three-part, and 9 four-part PHFs managed conservatively, followed by early mobilization and a home-based self-exercise program. In the x-ray examinations, the head displaced from varus into valgus 55° ± 23° to 42° ± 22°, in the normal range of anatomic values. The medial hinge displaced from medial to the diaphysis (+1 ± 6 mm) to lateral to the head (−0.6 ± 6 mm). The greater tuberosity displaced cranially from −1 ± 7 mm to 2 ± 5 mm. The Constant score at the 1-year follow-up was 79.69 ± 16.3. Discussion and conclusions The home-based self-exercise program for conservative treatment of PHFs displaces the head-diaphysis angle and the medial hinge toward anatomic reduction, but there is a risk of greater tuberosity cranial displacement. Functional results are fairly good, allowing frail patients to keep on with their independency and life style. Because a large number of patients might need further physiotherapy, the quality of the home-based self-exercises should be supervised.

Made available in DSpace on 2019-10-06T15:59:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-10-01 Background/Aims: The objective of our study was to evaluate the effects of zinc supplementation on cardiac remodeling following acute myocardial infarction in rats. Methods: Animals were subdivided into 4 groups and observed for 3 months: 1) Sham Control; 2) Sham Zinc: Sham animals receiving zinc supplementation; 3) Infarction Control; 4) Infarction Zinc. After the followup period, we studied hypertrophy and ventricular geometry, functional alterations in vivo and in vitro, changes related to collagen, oxidative stress, and inflammation, assessed by echocardiogram, isolated heart study, western blot, flow cytometer, morphometry, and spectrophotometry. Results: Infarction induced a significant worsening of the functional variables. On the other hand, zinc attenuated both systolic and diastolic cardiac dysfunction induced by infarction. Considering the infarct size, there was no difference between the groups. Catalase and superoxide dismutase decreased in infarcted animals, and zinc increased its activity. We found higher expression of collagens I and III in infarcted animals, but there was no effect of zinc supplementation. Likewise, infarcted animals had higher levels of IL-10, but without zinc interference. Nrf-2 values were not different among the groups. Infarction increased the amount of Treg cells in the spleen as well as the amount of total lymphocytes. Zinc increased the amount of CD4+ in infarcted animals, but we did not observe effects in relation to Treg cells. Conclusion: zinc attenuates cardiac remodeling after infarction in rats; this effect is associated with modulation of antioxidant enzymes, but without the involvement of collagens I and III, Nrf-2, IL-10, and Treg cells. São Paulo State University (Unesp) Botucatu Medical School Internal Medicine Department São Paulo State University (Unesp) Institute of Biosciences of Botucatu Chemistry and Biochemistry Department São Paulo State University (Unesp) Institute of Biosciences of Botucatu Microbiology and Immunology Department Flow Citometry Laboratory Amaral Carvalho Fundation São Paulo State University (Unesp) Botucatu Medical School Internal Medicine Department São Paulo State University (Unesp) Institute of Biosciences of Botucatu Chemistry and Biochemistry Department São Paulo State University (Unesp) Institute of Biosciences of Botucatu Microbiology and Immunology Department

Background: Elevated body mass index (BMI) is associated with increased risk of estrogen receptor-positive postmenopausal breast cancer. Mechanistically, most individuals with elevated BMI have breast white adipose tissue inflammation (WATi) which confers increased breast cancer risk, particularly in those with existing benign breast disease. Individuals with WATi have elevated in-breast expression of aromatase and several systemic changes that increase breast cancer risk, including hyperinsulinemia and higher levels of C-reactive protein. However, women with normal BMI but high levels of body fat are also likely to harbor WATi and are at increased risk of postmenopausal breast cancer. The accuracy of BMI for assessing adiposity and predicting obesity-related disorders, including cancer, varies across race and ethnicity. Whether the association between BMI and WATi varies by race is unknown. Here we aimed to characterize relationships among breast WATi and clinicopathologic features in a racially diverse cohort undergoing mastectomy for breast cancer treatment. Methods: Non-tumorous breast tissue and fasting blood were collected from women undergoing mastectomy for breast cancer treatment or prevention at a single center serving a racially diverse patient population. Breast WATi was detected by the presence of crown-like structures in the breast (CLS-B), which are composed of a dead/dying adipocyte surrounded by CD68+ macrophages. Clinicopathologic data were abstracted from electronic medical records. Associations among categorical variables were examined using Fisher's exact test. Relationships between continuous variables were examined using the Spearman correlation. Results: As of May 18, 2018 62 patients have been accrued; median age 55 (range 32 to 84). Self-reported race distribution was: 36 (58%) Asian, 5 African American (8%), 20 (32%) Caucasian, and 1 (2%) unknown. Breast tissue has been analyzed for WATi in 60 cases thus far. Clinicopathologic features stratified by the presence or absence of breast WATi are presented in. Breast WAT inflammation was associated with obesity (P=0.02) and a trend to association was observed with dyslipidemia (P VariableBreast WATi Absent (n=25)Breast WATi Present (n=35)Age, years Median (range)51 (32 to 71)59 (36 to 80)BMI, kg/m2 Median (range)22.5 (18.1 to 35.3)28.0 (19.2 to 38.9)BMI Category Underweight1 (4%)0 (0%)Normal16 (64%)10 (29%)Overweight5 (20%)18 (51%)Obese3 (12%)7 (20%)Race, n (%) Asian15 (60%)19 (54%)African American2 (8%)3 (9%)Caucasian8 (32%)12 (34%)Unknown0 (0%)1 (3%)Menopausal Status, n (%) Pre10 (40%)12 (34%)Post15 (60%)23 (66%)Hypertension, n (%)7 (28%)16 (46%)Diabetes mellitus, n (%)0 (0%)5 (14%)Dyslipidemia, n (%)1 (4%)11 (31%) Conclusions: Breast adipose inflammation is associated with elevated BMI and possibly metabolic syndrome disorders in a racially diverse population. These findings are consistent with observations from predominantly Caucasian cohorts. Race-specific characteristics will also be examined. Study accrual is ongoing and updated results will be presented. Citation Format: Iyengar NM, Siegel B, Malik M, Giri DD, Tsai J, Hughes M, Adam A, Williams S, Zhou XK, Rodgers W, Ginter P, Patel A, Yong F, Cherian A, August P, Dannenberg AJ. Obesity, adipose inflammation, and race in patients with early stage breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-07-05.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune inflammatory disease with genomic and non-genomic contributions to risk. We hypothesize that epigenetic factors are a significant contributor to SLE risk and may be informative for identifying pathogenic mechanisms and therapeutic targets. To test this hypothesis while controlling for genetic background, we performed an epigenome-wide analysis of DNA methylation in genomic DNA from whole blood in three pairs of female monozygotic (MZ) twins of European ancestry, discordant for SLE. Results were replicated on the same array in four cell types from a set of four Danish female MZ twin pairs discordant for SLE. Genes implicated by the epigenetic analyses were then evaluated in 10 independent SLE gene expression datasets from the Gene Expression Omnibus (GEO). There were 59 differentially methylated loci between unaffected and affected MZ twins in whole blood, including 11 novel loci. All but two of these loci were hypomethylated in the SLE twins relative to the unaffected twins. The genes harboring these hypomethylated loci exhibited increased expression in multiple independent datasets of SLE patients. This pattern was largely consistent regardless of disease activity, cell type, or renal tissue type. The genes proximal to CpGs exhibiting differential methylation (DM) in the SLE-discordant MZ twins and exhibiting differential expression (DE) in independent SLE GEO cohorts (DM-DE genes) clustered into two pathways: the nucleic acid-sensing pathway and the type I interferon pathway. The DM-DE genes were also informatically queried for potential gene–drug interactions, yielding a list of 41 drugs including a known SLE therapy. The DM-DE genes delineate two important biologic pathways that are not only reflective of the heterogeneity of SLE but may also correlate with distinct IFN responses that depend on the source, type, and location of nucleic acid molecules and the activated receptors in individual patients. Cell- and tissue-specific analyses will be critical to the understanding of genetic factors dysregulating the nucleic acid-sensing and IFN pathways and whether these factors could be appropriate targets for therapeutic intervention.

Background GM2-gangliosidosis is a fatal neurodegenerative lysosomal storage disease (LSD) caused by deficiency of either β-hexosaminidase A (Hex-A) and β-hexosaminidase B (Hex-B) together, or the GM2 activator protein. Clinical signs can be variable and are not pathognomonic for the specific, causal deficiency. Objectives To characterize the phenotype and genotype of GM2-gangliosidosis disease in an affected dog. Animals One affected Shiba Inu and a clinically healthy dog. Methods Clinical and neurologic evaluation, brain magnetic resonance imaging (MRI), assays of lysosomal enzyme activities, and sequencing of all coding regions of HEXA, HEXB, and GM2A genes. Results A 14-month-old, female Shiba Inu presented with clinical signs resembling GM2-gangliosidosis in humans and GM1-gangliosidosis in the Shiba Inu. Magnetic resonance imaging (MRI) of the dog's brain indicated neurodegenerative disease, and evaluation of cerebrospinal fluid (CSF) identified storage granules in leukocytes. Lysosomal enzyme assays of plasma and leukocytes showed deficiencies of Hex-A and Hex-B activities in both tissues. Genetic analysis identified a homozygous, 3-base pair deletion in the HEXB gene (c.618-620delCCT). Conclusions and Clinical Importance Clinical, biochemical, and molecular features are characterized in a Shiba Inu with GM2-gangliosidosis. The deletion of 3 adjacent base pairs in HEXB predicts the loss of a leucine residue at amino acid position 207 (p.Leu207del) supporting the hypothesis that GM2-gangliosidosis seen in this dog is the Sandhoff type. Because GM1-gangliosidosis also exists in this breed with almost identical clinical signs, genetic testing for both GM1- and GM2-gangliosidosis should be considered to make a definitive diagnosis.

The study of geographic variation of social mating systems can shed new light on our understanding of how ecological variables shape extant mating associations.We report data on the social mating system, parental care and life history traits of a temperate population of southern Sedge Wrens (Cistothorus platensis platensis) in South America. We compared our results with published records of two temperate populations of northern Sedge Wren (Cistothorus platensis stellaris) in North America. The southern temperate population had a lower social polygyny rate, greater male contribution to feeding nestlings and smaller clutch sizes than northern temperate populations. A similar pattern of low rates of social polygyny and smaller clutch sizes in the south versus moderate rates of social polygyny and bigger clutch sizes in the north has been reported for the House Wren (Troglodytes aedon). This suggests that different selective forces may be operating in northern and southern wren populations. Future work in additional study populations is essential to establishing the generality of our results. Fil: Llambias, Paulo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; Argentina Fil: Garrido Coria, Paula Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; Argentina Fil: Jefferies, María Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; Argentina Fil: Fernández, Gustavo J.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Made available in DSpace on 2018-12-11T17:12:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-08-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The objective of this study was to evaluate the influence of tomato or lycopene supplementation on cardiac remodeling after myocardial infarction (MI). Male Wistar rats were assigned to four groups: the sham group (animals that underwent simulated surgery) that received a standard chow (S; n=18), the infarcted group that received a standard chow (MI; n=13), the infarcted group supplemented with lycopene (1 mg of lycopene/kg body weight/day) (MIL; n=16) and the infarcted group supplemented with tomato (MIT; n=16). After 3 months, morphological, functional and biochemical analyses were performed. The groups MIL and MIT showed decreased interstitial fibrosis induced by infarction. Tomato supplementation attenuated the hypertrophy induced by MI. In addition, tomato and lycopene improved diastolic dysfunction evaluated by echocardiographic and isolated heart studies, respectively. The MI group showed higher levels of cardiac TNF-α compared to the MIL and MIT groups. Decreased nuclear factor E2-related factor 2 was measured in the MIL group. Lipid hydroperoxide levels were higher in the infarcted groups; however, the MIT group had a lower concentration than did the MI group [S=223±20.8, MI=298±19.5, MIL=277±26.6, MIT=261±28.8 (nmol/g); n=8; P