Identification of aneuploidy-tolerating mutations.

Aneuploidy causes a proliferative disadvantage in all normal cells analyzed to date, yet this condition is associated with a disease characterized by unabated proliferative potential, cancer. The mechanisms that allow cancer cells to tolerate the adverse effects of aneuploidy are not known. To probe this question, we identified aneuploid yeast strains with improved proliferative abilities. Their molecular characterization revealed strain-specific genetic alterations as well as mutations shared between different aneuploid strains. Among the latter, a loss-of-function mutation in the gene encoding the deubiquitinating enzyme Ubp6 improves growth rates in four different aneuploid yeast strains by attenuating the changes in intracellular protein composition caused by aneuploidy. Our results demonstrate the existence of aneuploidy-tolerating mutations that improve the fitness of multiple different aneuploidies and highlight the importance of ubiquitin-proteasomal degradation in suppressing the adverse effects of aneuploidy.

Retromer dysfunction in amyotrophic lateral sclerosis.

Retromer is a heteropentameric complex that plays a specialized role in endosomal protein sorting and trafficking. Here, we report a reduction in the retromer proteins-vacuolar protein sorting 35 (VPS35), VPS26A, and VPS29-in patients with amyotrophic lateral sclerosis (ALS) and in the ALS model provided by transgenic (Tg) mice expressing the mutant superoxide dismutase-1 G93A. These changes are accompanied by a reduction of levels of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluA1, a proxy of retromer function, in spinal cords from Tg SOD1G93A mice. Correction of the retromer deficit by a viral vector expressing VPS35 exacerbates the paralytic phenotype in Tg SOD1G93A mice. Conversely, lowering Vps35 levels in Tg SOD1G93A mice ameliorates the disease phenotype. In light of these findings, we propose that mild alterations in retromer inversely modulate neurodegeneration propensity in ALS.

Maintaining the permanence principle of death during normothermic regional perfusion in controlled donation after the circulatory determination of death: Results of a prospective clinical study.

One concern about the use of normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is that the brain may be perfused. We aimed to demonstrate that certain technical maneuvers preclude such brain perfusion. A nonrandomized trial was performed on cDCD donors. In abdominal normothermic regional perfusion (A-NRP), the thoracic aorta was blocked with an intra-aortic occlusion balloon. In thoracoabdominal normothermic regional perfusion (TA-NRP), the arch vessels were clamped and the cephalad ends vented to the atmosphere. The mean intracranial arterial blood pressure (ICBP) was invasively measured at the circle of Willis. Ten cDCD donors subject to A-NRP or TA-NRP were included. Mean ICBP and mean blood pressure at the thoracic and the abdominal aorta during the circulatory arrest were 17 (standard deviation [SD], 3), 17 (SD, 3), and 18 (SD, 4) mmHg, respectively. When A-NRP started, pressure at the abdominal aorta increased to 50 (SD, 13) mmHg, while the ICBP remained unchanged. When TA-NRP was initiated, thoracic aorta pressure increased to 71 (SD, 18) mmHg, but the ICBP remained unmodified. Recorded values of ICBP during NRP were 10 mmHg. In conclusion, appropriate technical measures applied during NRP preclude perfusion of the brain in cDCD. This study might help to expand NRP and increase the number of organs available for transplantation.

Alternative splicing regulation of membrane trafficking genes during myogenesis.

Alternative splicing transitions occur during organ development, and, in numerous diseases, splicing programs revert to fetal isoform expression. We previously found that extensive splicing changes occur during postnatal mouse heart development in genes encoding proteins involved in vesicle-mediated trafficking. However, the regulatory mechanisms of this splicing-trafficking network are unknown. Here, we found that membrane trafficking genes are alternatively spliced in a tissue-specific manner, with striated muscles exhibiting the highest levels of alternative exon inclusion. Treatment of differentiated muscle cells with chromatin-modifying drugs altered exon inclusion in muscle cells. Examination of several RNA-binding proteins revealed that the poly-pyrimidine tract binding protein 1 (PTBP1) and quaking regulate splicing of trafficking genes during myogenesis, and that removal of PTBP1 motifs prevented PTBP1 from binding its RNA target. These findings enhance our understanding of developmental splicing regulation of membrane trafficking proteins which might have implications for muscle disease pathogenesis.

Consequences of gaining an extra chromosome.

Mistakes in chromosome segregation leading to aneuploidy are the primary cause of miscarriages in humans. Excluding sex chromosomes, viable aneuploidies in humans include trisomies of chromosomes 21, 18, or 13, which cause Down, Edwards, or Patau syndromes, respectively. While individuals with trisomy 18 or 13 die soon after birth, people with Down syndrome live to adulthood but have intellectual disabilities and are prone to multiple diseases. At the cellular level, mistakes in the segregation of a single chromosome leading to a cell losing a chromosome are lethal. In contrast, the cell that gains a chromosome can survive. Several studies support the hypothesis that gaining an extra copy of a chromosome causes gene-specific phenotypes and phenotypes independent of the identity of the genes encoded within that chromosome. The latter, referred to as aneuploidy-associated phenotypes, are the focus of this review. Among the conserved aneuploidy-associated phenotypes observed in yeast and human cells are lower viability, increased gene expression, increased protein synthesis and turnover, abnormal nuclear morphology, and altered metabolism. Notably, abnormal nuclear morphology of aneuploid cells is associated with increased metabolic demand for de novo synthesis of sphingolipids. These findings reveal important insights into the possible pathological role of aneuploidy in Down syndrome. Despite the adverse effects on cell physiology, aneuploidy is a hallmark of cancer cells. Understanding how aneuploidy affects cell physiology can reveal insights into the selective pressure that aneuploid cancer cells must overcome to support unlimited proliferation.

Consequences of aneuploidy in human fibroblasts with trisomy 21.

An extra copy of chromosome 21 causes Down syndrome, the most common genetic disease in humans. The mechanisms contributing to aneuploidy-related pathologies in this syndrome, independent of the identity of the triplicated genes, are not well defined. To characterize aneuploidy-driven phenotypes in trisomy 21 cells, we performed global transcriptome, proteome, and phenotypic analyses of primary human fibroblasts from individuals with Patau (trisomy 13), Edwards (trisomy 18), or Down syndromes. On average, mRNA and protein levels were increased by 1.5-fold in all trisomies, with a subset of proteins enriched for subunits of macromolecular complexes showing signs of posttranscriptional regulation. These results support the lack of evidence for widespread dosage compensation or dysregulation of chromosomal domains in human autosomes. Furthermore, we show that several aneuploidy-associated phenotypes are present in trisomy 21 cells, including lower viability and increased dependency on serine-driven lipid synthesis. Our studies establish a critical role of aneuploidy, independent of triplicated gene identity, in driving cellular defects associated with trisomy 21.

Environmental prospective of valorizing corn processing effluent to produce ferulic acid grafted chitosan polymer.

The food industry requires new production models that include more environmentally friendly waste management practices, considering that the environmental loads of solid waste and wastewater associated with this sector cause damage to the receiving ecosystems. The approach considered in this study focuses on the design and environmental assessment of an enzymatic process for the valorization of ferulic acid present in the effluent of a corn tortilla plant. The ferulic acid can be immobilized on chitosan so that the ferulic acid grafted chitosan can be used as a bioactive film with enhanced antioxidant properties with potential applications in the biotechnology sector. Its real projection approach requires the evaluation of its environmental and economic performance, trying to identify its benefits and potential in the value chain, using the Techno-Economic Analysis (TEA) as a phase for the conceptual design of the process and the Life Cycle Assessment (LCA) methodology for the environmental evaluation. It should be noted that the TEA indicators are promising, since the values of the financial indicators obtained are representative of the economic profitability, which makes the ferulic acid valorization a viable process. In terms of the environmental impact of the process, the buffer dose and the chitosan production process are identified as the main critical points. This double benefit in environmental and economic terms shows that the valorization of ferulic acid for chitosan functionalization is a promising alternative to improve the sustainability performance of corn processing.

Kidney transplantation reduces the risk of chronic limb threatening ischemia and amputation among patients with end-stage renal disease on hemodialysis.

OBJECTIVE: This study aimed to analyze the risk of chronic limb threatening ischemia (CLTI) or amputation among patients with end-stage renal disease (ESRD) entering a hemodialysis (HD) program and to evaluate the protective effect associated with kidney transplantation (KT). DESIGN, MATERIAL AND METHODS: Retrospective cohort of all consecutive ESRD patients entering into a HD program at our institution between 2000 and 2010. Collected variables included baseline characteristics (pre-entry in hemodialysis), time on HD program, KT and the composite outcome of chronic limb threatening ischemia or need for any amputation (CLTI/AMP). Patients with previous symptomatic peripheral arterial disease or amputation were excluded. RESULTS: The study group included 336 patients (mean age 63 years, 66% male). The mean follow up was 6.7 years with an average time on HD of 4.2 years. Ninety two patients (27.4 %) underwent transplantation. CLTI free survival rates were 90.3 % and 82.6 % at 5 and 10 years, respectively. The episodes of CLT involved 28 revascularization procedures (17 endovascular and 11 open surgeries), 18 minor amputations and 20 major amputations. KT was associated with a protective effect over the development of CLTI (HR: 0.065; CI 95% 0.02-0.21) after adjustment for confounding factors. The long-term survival of non-transplanted patients was 45 % and 15 % at 5 and 10 years, respectively and the long-term survival in transplanted patients was 89% and 80% at 5 and 10 years, respectively; but decreased to 47 % at 1 year and 18.2 % at 5 years once CLTI occurred. CONCLUSION: Patients on HD program show a notorious risk of chronic limb threatening ischemia or amputation over time. Once this complication occurs, patient's survival is markedly reduced. Transplantation confers an independent protective effect over the development of chronic limb threatening ischemia or amputation.

Population genetic structure and morphological diversity of Cruzia tentaculata (Nematoda: Ascaridida), a parasite of marsupials (Didelphinae), along the Atlantic Forest on the eastern coast of South America.

Cruzia tentaculata is a helminth parasite of marsupials and has a wide geographic distribution from Mexico to Argentina. The aim of this study was to analyse the genetic population structure of this nematode along the Atlantic Forest biome. Cruzia tentaculata specimens were recovered from Didelphis aurita, Didelphis albiventris and Philander quica in 9 localities. Morphological and morphometric data were investigated for phenotypic diversity among localities and hosts using multivariate discriminant analysis of principal components. Phylogenetic relationships of C. tentaculata were determined using maximum likelihood and Bayesian inference. The population structure was analysed by fixation indices, molecular variance analysis, Tajima's D and Fu's Fs neutrality tests, Mantel tests and Bayesian clustering analysis. A higher significant morphometric difference for males was observed between localities. In the haplogroup networks, 2 groups were recovered, separating locations from the north and from the south/southeast. The morphometric variation in C. tentaculata between different localities was compatible with this north and southeast/south pattern, suggesting adaptation to different ecological conditions. Population genetic analyses suggested a pattern of evolutionary processes driven by Pleistocene glacial refugia in the northeast and southeast of the Atlantic Forest based on the distribution of genetic diversity.

Maternal hair cortisol concentrations across pregnancy and the early postpartum period in a Puerto Rican sample.

OBJECTIVE: Hair cortisol is a noninvasive, long-term biomarker of human stress. Strengths and weaknesses of this biomarker as a proxy measure of perinatal stress are not yet well understood. Hair cortisol data were collected from pregnant women in Puerto Rico to investigate maternal cortisol level variance across pregnancy. METHODS: In 2017, we recruited 86 pregnant women planning to birth at a large urban hospital. We aimed to collect four hair samples from each participant, one in each trimester and one in the postpartum period. RESULTS: Median cortisol in the first trimester (n = 82) was 5.7 picograms/milligram (pg/mg) (range: 1.0-62.4). In the second, third, and postpartum periods, the medians were 6.8 pg/mg (1.0-69.5), (n = 46), 20.1 pg/mg (5.6-89.0), (n = 30), and 14.1 pg/mg (1.7-39.8), (n = 9), respectively. These medians disguise a 10-fold and 50-fold variability for two participants. Our sample sizes declined sharply when Hurricane Maria caused major disruptions in services and participants' lives. CONCLUSION: Maternal hair cortisol concentrations were lower in the first and second trimester than the third trimester and early postpartum period. We also observed a wide range of variation in cortisol levels throughout pregnancy and in the postpartum period.

De novo headache in ischemic stroke patients treated with thrombectomy: a prospective study.

BACKGROUND AND AIM: Headache attributed to intracranial endovascular procedures is described in the ICHD-3. Our aim was to study the frequency and characteristics of headache specifically related to thrombectomy in patients with ischemic stroke. METHODS: Prospective evaluation of clinical features of headache after thrombectomy using an ad hoc questionnaire. RESULTS: One hundred seventeen patients were included (52.1% females). Most had an anterior circulation artery occlusion (91.5%). 93 (79.5%) received general anaesthesia. 111 (94.9%) required stent retriever, 21 (24.4%) angioplasty and 19 (16.2%) aspiration thrombectomy. 31 (26.5%; 95% CI 18.8-35.5%) had headache related to thrombectomy, and it was associated with a history of primary headache (p = 0.004). No differences about sex, initial NIHSS score, or the type or complexity of the procedure were observed. Headache was usually moderate and oppressive, ipsilateral to the artery occlusion and usually lasted less than 48 hours. CONCLUSIONS: Almost one-third of patients with ischemic stroke who undergo endovascular thrombectomy experience headache in the first 24 hours, occurring more frequently in patients who had a previous history of headaches regardless of the procedure complexity.

Safety and efficacy of the INC bioprosthetic heart valve in humans.

INTRODUCTION: Heart valve bioprostheses are the gold standard for aortic valve surgical replacement in selected patients. OBJECTIVE: To evaluate the safety and efficacy of the National Institute of Cardiology (INC) bioprosthetic heart valve in humans. METHODS: Single-center study that included 341 patients who underwent single surgical aortic valve replacement with INC heart valve. RESULTS: 318 implants were performed de novo (93%) and 23 as redo surgery (7%); STS scores were 1.4 and 1.8%, and follow-up was for 42 and 46 months, respectively. There were no differences in clinical complications or pacemaker implantation rate. Both groups maintained a normal LVEF. Overall improvement in functional class was observed, with worsening only in two patients of the de novo group. INC prosthesis dysfunction requiring surgical reintervention was observed in eight patients (4.65%) of the de novo group vs. one patient in the redo group. CONCLUSIONS: The INC heart valve is efficacious and safe, and is associated with a low rate of complications and functional class improvement during long-term follow-up. Prospective, comparative studies of this valve are required.

INTRODUCCIÓN: Las bioprótesis de válvulas cardiacas son el estándar de oro para el reemplazo quirúrgico de la válvula aórtica en pacientes seleccionados. OBJETIVO: Evaluar la seguridad y eficacia de la válvula cardiaca bioprotésica del Instituto Nacional de Cardiología (INC) en humanos. MÉTODOS: Estudio unicéntrico que incluyó 341 pacientes que se sometieron a reemplazo valvular quirúrgico único de válvula aórtica con válvula INC. RESULTADOS: Se realizaron 318 implantes de novo (93 %) y 23 como segunda cirugía (7 %); las puntuaciones STS fueron de 1.4 y 1.8 % y el seguimiento de 42 y 46 meses, respectivamente. No existieron diferencias en las complicaciones ni en la tasa de implantación de marcapasos. Ambos grupos mantuvieron una FEVI normal. Se observó mejoría global en la clase funcional con empeoramiento solo en dos pacientes del grupo de novo. La disfunción de la prótesis INC que ameritó reintervención quirúrgica se observó en ocho pacientes (4.65 %) del grupo de novo versus un paciente (7.69 %) con segunda cirugía. CONCLUSIONES: La válvula cardiaca INC es eficaz y segura, se asocia a baja tasa de complicaciones y mejoría de la clase funcional durante el seguimiento a largo plazo. Se necesitan estudios prospectivos comparativos de esta válvula.

New data on eggshell structure of capillariid species: a SEM perspective.

Capillariidae is a group of nematode parasites of vertebrates with a complex taxonomy. The structure of the eggshell, which was indicated as the most important characteristic for identification of genus or species through eggs, is very diverse among genera. The visualization and characterization of eggshell by light microscopy (LM) are a challenging task since different planes of the egg surface are needed. Nevertheless, categories of eggshell ornamentation were proposed by LM: smooth, punctuated, reticulated type I, and reticulated type II. The present study aimed to characterize the eggshell structure of Capillariidae species, parasites of mammals and avians, deposited in a helminthological collection using scanning electron microscopy (SEM). Institutional Biological Collections are taxonomic repositories of specimens described and strictly identified at the species level by systematics specialists. SEM eggshell images were obtained from 12 species belonging to 5 genera (Aonchotheca, Baruscapillaria, Capillaria, Echinocoleus, Eucoleus) and compared to their respective LM images. Eggshell patterns observed using SEM were associated categories of eggshell ornamentation previously proposed by LM images. The SEM data indicate that eggshell categories are not in agreement with capillariid genera or sites of infection. However, the study provides previously unknown SEM eggshell information from curated species, which contributes with a specific and supplementary taxonomic feature at the species level of Capillariidae.

Sarcoplasmic reticulum Ca2+ ATPases genes differential expression in breast cancer cells.

INTRODUCTION: Sarcoplasmic reticulum Ca2+ ATPases (SERCA) enzymes are essential for intracellular Ca2+ homeostasis. SERCA genes (ATP2A1-3) encode for different functional isoforms of the protein, whose expression or function is altered in several types of cancer, such as gastric and oral, as well as colon, breast, lung, thyroid, liver, and prostate cancer, among others. However, the role played by SERCA pumps in carcinogenesis is unknown. METHODS: Techniques such as real-time polymerase chain reaction, optical microscopy, proliferation and cell death assays, as well as bioinformatic analyses were used. OBJECTIVES: To evaluate the expression levels of the ATP2A2 and ATP2A3 genes in cell lines representative of different subtypes of breast cancer. RESULTS: The results show that the MDA-MB-231 cell line expresses lower mRNA levels for the ATP2A3 gene in comparison with MCF-7 cells. The use of the phytoestrogen resveratrol induces ATP2A3 expression, decreases proliferation, and induces apoptosis in both cell types. CONCLUSIONS: SERCA expression might function as a tool to differentiate breast cancer subtypes, which have different treatment requirements.

INTRODUCCIÓN: Las enzimas SERCA son esenciales para la homeostasis intracelular de Ca2+. Los genes SERCA (ATP2A1-3) codifican para distintas isoformas funcionales de la proteína, cuya expresión o función se encuentra alterada en diversos tipos de cáncer, como el gástrico y el oral, así como de colon, mama, pulmón, tiroides, hígado y próstata, entre otros. Sin embargo, se desconoce el papel de las bombas SERCA en la carcinogénesis. MÉTODOS: Se utilizaron estudios como reacción en cadena de la polimerasa en tiempo real, microscopia óptica, ensayos de proliferación y muerte celular, así como análisis bioinformáticos. OBJETIVOS: Evaluar los niveles de expresión de los genes ATP2A2 y ATP2A3 en líneas celulares que representan diferentes subtipos de cáncer de mama. RESULTADOS: La línea celular MDA-MB-231 expresa niveles más bajos del ARNm para el gen ATP2A3, en comparación con las células MCF-7. El uso del fitoestrógeno resveratrol induce la expresión de ATP2A3, disminuye la proliferación e induce apoptosis en ambos tipos de células. CONCLUSIONES: La expresión de SERCA puede funcionar como una herramienta para diferenciar los subtipos de cáncer de mama, los cuales tienen distintas necesidades de tratamiento.

Structural basis for the modulation of plant cytosolic triosephosphate isomerase activity by mimicry of redox-based modifications.

Reactive oxidative species (ROS) and S-glutathionylation modulate the activity of plant cytosolic triosephosphate isomerases (cTPI). Arabidopsis thaliana cTPI (AtcTPI) is subject of redox regulation at two reactive cysteines that function as thiol switches. Here we investigate the role of these residues, AtcTPI-Cys13 and At-Cys218, by substituting them with aspartic acid that mimics the irreversible oxidation of cysteine to sulfinic acid and with amino acids that mimic thiol conjugation. Crystallographic studies show that mimicking AtcTPI-Cys13 oxidation promotes the formation of inactive monomers by reposition residue Phe75 of the neighboring subunit, into a conformation that destabilizes the dimer interface. Mutations in residue AtcTPI-Cys218 to Asp, Lys, or Tyr generate TPI variants with a decreased enzymatic activity by creating structural modifications in two loops (loop 7 and loop 6) whose integrity is necessary to assemble the active site. In contrast with mutations in residue AtcTPI-Cys13, mutations in AtcTPI-Cys218 do not alter the dimeric nature of AtcTPI. Therefore, modifications of residues AtcTPI-Cys13 and AtcTPI-Cys218 modulate AtcTPI activity by inducing the formation of inactive monomers and by altering the active site of the dimeric enzyme, respectively. The identity of residue AtcTPI-Cys218 is conserved in the majority of plant cytosolic TPIs, this conservation and its solvent-exposed localization make it the most probable target for TPI regulation upon oxidative damage by reactive oxygen species. Our data reveal the structural mechanisms by which S-glutathionylation protects AtcTPI from irreversible chemical modifications and re-routes carbon metabolism to the pentose phosphate pathway to decrease oxidative stress.

Whipworm Infection Promotes Bacterial Invasion, Intestinal Microbiota Imbalance, and Cellular Immunomodulation.

Infections with Trichuris trichiura are among the most common causes of intestinal parasitism in children worldwide, and the diagnosis is based on microscopic egg identification in the chronic phase of the infection. During parasitism, the adult worm of the trichurid nematode maintains its anterior region inserted in the intestinal mucosa, which causes serious damage and which may open access for gut microorganisms through the intestinal tissue. The immune-regulatory processes taking place during the evolution of the chronic infection are still not completely understood. By use of the Swiss Webster outbred mouse model, mice were infected with 200 eggs, and tolerance to the establishment of a chronic Trichuris muris infection was induced by the administration of a short pulse of dexamethasone during nematode early larval development. The infected mice presented weight loss, anemia, an imbalance of the microbiota, and intense immunological cell infiltration in the large intestine. It was found that mice have a mixed Th1/Th2/Th17 response, with differences being found among the different anatomical locations. After 45 days of infection, the parasitism induced changes in the microbiota composition and bacterial invasion of the large intestine epithelium. In addition, we describe that the excretory-secretory products from the nematode have anti-inflammatory effects on mouse macrophages cultured in vitro, suggesting that T. muris may modulate the immune response at the site of insertion of the worm inside mouse tissue. The data presented in this study suggest that the host immune state at 45 days postinfection with T. muris during the chronic phase of infection is the result of factors derived from the worm as well as alterations to the microbiota and bacterial invasion. Taken together, these results provide new information about the parasite-host-microbiota relationship and open new treatment possibilities.

A simple spectroscopic method to determine dimethoate in water samples by complex formation.

A simple and rapid method for the determination of dimethoate in water was developed based on the monitoring of the complex formation between bis 5-phenyldipyrrinate of nickel (II) and the herbicide dimethoate. The method showed a short response time (10 s), high selectivity (very low interference from other sulfate and salts), high sensitivity (limit of detection (LOD) 0.45 µM, limit of quantitation (LOQ) of 1.39 µM), and a Kd of 2.4 µM. Stoichiometry experiments showed that complex formation occurred with a 1:1 relation. The method was applied to different environmental water samples such as lagoon, stream, urban, and groundwater samples. The results indicated that independently from the water source, the method exhibited high precision (0.25-2.47% variation coefficient) and accuracy (84.42-115.68% recovery). In addition, the method was also tested using an effluent from a wastewater treatment plant from Mexico; however, the results indicated that the presence of organic matter had a pronounced effect on the detection.

Epigenetic regulation of the human ATP2A3 gene promoter in gastric and colon cancer cell lines.

The knowledge about the role of calcium-regulated pathways in cancer cell growth and differentiation could be useful for the development of new therapeutic approaches to diminish its mortality. The ATP2A genes encode for SERCA pumps, which modulate cytosolic Ca2+ concentration, regulating various cellular processes including cell growth. ATP2A3 gene transcriptional down-regulation has been reported in gastric and colon cancer, but there is still a lack of understanding about the epigenetic processes regulating its transcription. In this work, we report that butyrate, trichostatin A, and 5-azacytidine treatments increase SERCA3 expression, increased apoptosis, and decreased cell viability of the KATO-III gastric carcinoma cell line. We analyzed the methylation profile of the ATP2A3 gene promoter CpG island, finding clones with methylated status through -280 to -135 promoter region, harboring Sp1 and AP-2 binding sites, which could have a role in transcriptional repression. Post-translational modifications of histones show a major role in the ATP2A3 transcriptional regulation, and our results show histones marks linked to transcriptional repression associated with the -262 to -135 region, this repressive context changed to transcriptional permissive through SERCA3 re-expressing conditions. These results suggest that the nucleotide sequence from -280 to -135 position is an ATP2A3 epigenetic regulatory CpG region in KATO-III cells. Analyses of online-databases show a decreased SERCA3 expression in gastric and colon tumors, as well as overall survival results, showed that high SERCA3 expression could serve as a favorable prognostic marker for colon and gastric cancer patients.

Long-term ethanol intake causes morphological changes in Schistosoma mansoni adult worms in mice.

Schistosoma mansoni adult worms are extensively challenged by reactive oxygen species from intrinsic sources. However, the effects of extrinsic sources such as ethanol have not been looked at in schistosomes. We examined adult worms recovered from ethanol-consuming mice by light (LM), confocal (CM) and scanning electron microscopy (SEM) to address this question. Schistosomiasis-infected mice were orally gavaged with 18% (v/v) ethanol from 35 to 63 days post-infection, when they were euthanized. CM examination revealed reduced germ cells density (-36%, p = 0.0001) and sperm density (-58%, p = 0.0001) in testicular lobes, and immature cells in seminal vesicle compared to unexposed control worms. Female worms showed reduced density of vitellin glands (-71%, p = 0.0001), maturation of oocytes (-7%, p = 0.0071) and reduced spermatozoa density (-23%, p = 0.0002) within the seminal receptacle. SEM revealed remarkable damages in male's tegument, including tubercles flattening, tegumental peeling and erosive lesions. Given that lipids are present in reproductive system and tegument, our results suggest that phenotypic changes are due to ethanol-induced lipid peroxidation. To the best of our knowledge, this is the first report revealing the biological action of ethanol intake on adult schistosomes in vivo.

Aliphatic Diacidic Long-Chain C16 Polyesters from 10,16-Dihydroxyhexadecanoic Acid Obtained from Tomato Residual Wastes.

10,16-dihydroxyhexadecanoic acid obtained from agroresidual tomato waste, was oxidized to produce 7-oxohexadecanedioic acid in good yield (>70%) and purified without oxidation side products in one step. Polycondensation with 1,8-octanediol, yielded the polyester (poly(ω-carboxyl PA-co-OD)) with Mw = 2155.15 and Mn = 1637.27. The best enzymatic reaction conditions to get the polyester were using lipase CAL-B (%-by-wt relative to monomer) in toluene as a solvent for 1 h at 60 °C. The poly(ω-carboxyl PA-co-OD) was characterized by 1H- and 13C-NMR, mass spectrometry (MALDI-TOF) and the polyester film formed with a Langmuir-Blodgett Trough was analyzed by means of spectroscopic ellipsometry and atomic force microscopy.