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1.
Chemosphere ; 341: 140020, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37690569

ABSTRACT

As the second leading cause of death for cancer among men worldwide, prostate cancer (PCa) prevention and detection remain a critical challenge. One aspect of PCa research is the identification of common environmental agents that may increase the risk of initiation and progression of PCa. Endocrine disrupting chemicals (EDCs) are strong candidates for risk factors, partially because they alter essential pathways for prostate gland development and oncogenesis. Phthalates correspond to a set of commercially used plasticizers that humans are exposed to ubiquitously. Here, we show that maternal exposure to a phthalate mixture interferes with the expression profile of mRNA and proteins in the ventral prostate of offspring and increases the susceptibility to prostate adenocarcinomas in aged animals. The data highlight Ubxn11, Aldoc, Kif5c, Tubb4a, Tubb3, Tubb2, Rab6b and Rab3b as differentially expressed targets in young and adult offspring descendants (PND22 and PND120). These phthalate-induced targets were enriched for pathways such as: dysregulation in post-translational protein modification (PTPM), cell homeostasis, HSP90 chaperone activity, gap junctions, and kinases. In addition, the Kif5c, Tubb3, Tubb2b and Tubb4a targets were enriched for impairment in cell cycle and GTPase activity. Furthermore, these targets showed strong relationships with 12 transcriptional factors (TF), which regulate the phosphorylation of eight protein kinases. The correlation of TF-kinases is associated with alterations in immune system, RAS/ErbB/VEGF/estrogen/HIF-1 signaling pathways, cellular senescence, cell cycle, autophagy, and apoptosis. Downregulation of KIF5C, TUBB3 and RAB6B targets is associated with poor prognosis in patients diagnosed with adenocarcinoma. Collectively, this integrative investigation establishes the post-transcriptional mechanisms in the prostate that are modulated by maternal exposure to phthalate mixture during gestation and lactation.


Subject(s)
Prostatic Neoplasms , Proteome , Animals , Humans , Male , Pregnancy , Rats , Biomarkers , Lactation , Prostatic Neoplasms/chemically induced , Prostatic Neoplasms/genetics , Transcriptome , Female , Maternal Exposure/adverse effects
2.
Front Physiol ; 12: 687654, 2021.
Article in English | MEDLINE | ID: mdl-34295265

ABSTRACT

The increased mass of airway smooth muscle (ASM) in the airways of asthmatic patients may contribute to the pathology of this disease by increasing the capacity for airway narrowing. Evidence for the airway epithelium as a participant in ASM remodeling is accruing. To investigate mechanisms by which airway epithelial cells induce ASM cell (ASMC) proliferation, we have employed a co-culture model to explore markers of ASMC proliferative phenotype. Co-culture with epithelial cells led to incorporation of bromodeoxyuridine into ASMCs, indicating augmented proliferation and an associated increase in mRNA of the pro-proliferative co-transcription factor Elk1. Although the mitogen heparin-binding epidermal growth factor (HB-EGF) was augmented in the co-culture supernatant, the ASMC epidermal growth factor receptor (EGFR), an effector of HB-EGF induced proliferation, did not mediate epithelial-induced proliferation. The co-culture increased the expression of ASMC mRNA for the pro-inflammatory cytokines IL-6 and IL-8 as well as the pro-proliferative microRNA miR-210. The transcriptional repressor Max-binding protein (Mnt), a putative target of miR-210, was transcriptionally repressed in co-cultured ASMCs. Together, these data indicate that the airway epithelium-induced proliferative phenotype of ASMCs is not driven by EGFR signaling, but rather may be dependent on miR210 targeting of tumor suppressor Mnt.

3.
Biomed Mater Eng ; 31(3): 191-201, 2020.
Article in English | MEDLINE | ID: mdl-32568169

ABSTRACT

OBJECTIVE: The main goal of this study was to examine the influence of hydroxyapatite (HAp) macroaggreate concentrations on thermal and mechanical properties of radioactive bone cement and to study the relation of glass transition Tg with its mechanical properties. METHODS: The bone cement as (1-x)PMMA-xHAp binary system was prepared in six [x] distinct concentration parameters of 0.0 up to 0.5. The HAp was synthesized using a solgel procedure following calcination by thermal treatment. The composite was prepared in cold based (non-radioactive) mixing polymethyl methacrylate (PMMA) and HAp. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and mechanical compressive strength (CS) were used to measure the thermal and mechanical properties. RESULTS: The DSC and TGA thermal profiles in function to concentration parameter [x] were presented. The CS lies in a range of 3.71-7.37 MPa and the glass transition temperature Tg = 126.27 °C. There was a direct relationship between the PMMA-HAp thermoplastic properties with mechanical and thermal properties in function of HAp concentrations. CONCLUSION: The specific PMMA-HAp composite, with a concentration ratio of 1:1 and HAp thermal treatment at the Tg, provides a material with a compression strength of 7.37 MPa and a suitable amount of porous similar to a trabecular bone, possible to apply in bone cement implants, regardless of whether they are radioactive or not.


Subject(s)
Biomechanical Phenomena/drug effects , Bone Substitutes/chemistry , Durapatite/pharmacology , Polymethyl Methacrylate/chemistry , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Biocompatible Materials/therapeutic use , Bone Cements/chemical synthesis , Bone Cements/chemistry , Bone Cements/therapeutic use , Bone Substitutes/chemical synthesis , Bone Substitutes/therapeutic use , Compressive Strength/drug effects , Durapatite/chemistry , Humans , Hydroxyapatites/chemistry , Hydroxyapatites/therapeutic use , Materials Testing , Polymethyl Methacrylate/chemical synthesis , Polymethyl Methacrylate/therapeutic use , Porosity/drug effects , Stress, Mechanical , Tensile Strength/drug effects , Thermogravimetry , Vitrification/drug effects
4.
Materials (Basel) ; 13(8)2020 Apr 18.
Article in English | MEDLINE | ID: mdl-32325667

ABSTRACT

Post-extractional implants and immediate loading protocols are becoming much more frequent in everyday clinical practice. Given the existing literature about tapered implants, the objective of this paper was to understand whether implant shape had a direct influence on the results of the insertion torque (IT) and implant stability quotient (ISQ). Seven tapered implant prototypes were developed and distributed into three groups and compared with a control cylindrical implant-VEGA by Klockner Implant System. The implants were inserted into bovine bone type III according to Lekholm and Zarb Classification. The sample size was n = 30 for the three groups. Final IT was measured with a torquemeter, and the ISQ was measured with Penguin Resonance Frequency Analysis (RFA). Modifications done to the Prototype I did not reveal higher values of the ISQ and IT when compared to VEGA. In the second group, when comparing the five prototypes (II-VI) with VEGA, it was seen that the values of the ISQ and IT were not always higher, but there were two values of the ISQ that were statistically significantly higher with the 4.0 mm diameter Prototypes II (76.3 ± 6.1) and IV (78 ± 3.7). Prototype VII was the one with higher and significant values of the ISQ and IT. In both diameters and in both variables, all differences were statistically significant enough to achieve the higher values of primary stability values (IT and ISQ). Given the limitations of this study, it can be concluded that when there is an increase of the diameter of the implant and body taper, there is an increase of the ISQ and IT, showing that the diameter of the implant is an important criteria to obtain higher values of primary stability.

5.
Heredity (Edinb) ; 118(3): 221-228, 2017 03.
Article in English | MEDLINE | ID: mdl-27731328

ABSTRACT

Reproduction and aging evolved to be intimately associated. Experimental selection for early-life reproduction drives the evolution of decreased longevity in Drosophila whereas experimental selection for increased longevity leads to changes in reproduction. Although life history theory offers hypotheses to explain these relationships, the genetic architecture and molecular mechanisms underlying reproduction-longevity associations remain a matter of debate. Here we show that mating triggers accelerated mortality in males and identify hundreds of genes that are modulated upon mating in the fruit fly Drosophila melanogaster. Interrogation of genome-wide gene expression in virgin and recently mated males revealed coherent responses, with biological processes that are upregulated (testis-specific gene expression) or downregulated (metabolism and mitochondria-related functions) upon mating. Furthermore, using a panel of genotypes from the Drosophila Synthetic Population Resource (DSPR) as a source of naturally occurring genetic perturbation, we uncover abundant variation in longevity and reproduction-induced mortality among genotypes. Genotypes displayed more than fourfold variation in longevity and reproduction-induced mortality that can be traced to variation in specific segments of the genome. The data reveal individual variation in sensitivity to reproduction and physiological processes that are enhanced and suppressed upon mating. These results raise the prospect that variation in longevity and age-related traits could be traced to processes that coordinate germline and somatic function.


Subject(s)
Drosophila melanogaster/genetics , Gene Expression , Longevity/genetics , Animals , Down-Regulation , Genotype , Male , Reproduction/genetics , Sexual Behavior, Animal , Testis/physiology , Up-Regulation
6.
J Anim Sci ; 94(10): 4307-4314, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27898865

ABSTRACT

Two experiments were designed to evaluate the effects of monensin, virginiamycin, and flavomycin on growth performance, carcass characteristics, apparent total tract nutrient digestibility, and rumen fermentation of zebu cattle fed a no-roughage finishing diet (whole shelled corn [WSC] based). In Exp. 1, 100 crossbred bulls (; 392 kg [SD 46.8] average initial BW) were blocked by initial BW in a 101-d feedlot trial. Five treatments were evaluated using 4 pens per treatment (5 bulls/pen): monensin at 30 mg/kg DM, virginiamycin at 25 mg/kg DM, monensin at 20 mg/kg DM plus virginiamycin at 25 mg/kg DM, flavomycin at 4.4 mg/kg DM, and monensin at 20 mg/kg DM plus flavomycin at 2.2 mg/kg DM. There were no differences in growth performance (final BW, ADG, DMI, and G:F; ≥ 0.527) and carcass characteristics (HCW, dressing percent, and 12th-rib fat; ≥ 0.235) among treatments. In Exp. 2, 7 ruminally fistulated steers were used in a 7 × 7 Latin square design to evaluate the 5 treatments of Exp. 1 and 2 additional treatments: monensin at 30 mg/kg DM plus virginiamycin at 25 mg/kg DM and monensin at 20 mg/kg DM plus flavomycin at 4.4 mg/kg DM. Experimental periods were 14 d in length (9 d of adaptation and 5 d of measurements). Apparent total tract DM, OM, CP, and NDF digestibilities were similar among treatments ( ≥ 0.224). There was no treatment effect ( ≥ 0.253) in rumen fermentation responses (ruminal pH, rumen ammonia nitrogen, VFA, and number of protozoa). In conclusion, no evidence of benefits to cattle fed a no-roughage WSC-based diet was found to support the use of monensin combined with virginiamycin or flavomycin in the doses tested herein.


Subject(s)
Bambermycins/pharmacology , Cattle , Diet/veterinary , Dietary Fiber , Monensin/pharmacology , Virginiamycin/pharmacology , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Anti-Bacterial Agents/pharmacology , Body Composition/drug effects , Digestion/physiology , Fermentation , Gastrointestinal Tract/drug effects , Male , Protein Synthesis Inhibitors/pharmacology , Proton Ionophores/pharmacology , Rumen/metabolism
7.
J Evol Biol ; 29(8): 1602-16, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27213992

ABSTRACT

Regulatory networks play a central role in the modulation of gene expression, the control of cellular differentiation, and the emergence of complex phenotypes. Regulatory networks could constrain or facilitate evolutionary adaptation in gene expression levels. Here, we model the adaptation of regulatory networks and gene expression levels to a shift in the environment that alters the optimal expression level of a single gene. Our analyses show signatures of natural selection on regulatory networks that both constrain and facilitate rapid evolution of gene expression level towards new optima. The analyses are interpreted from the standpoint of neutral expectations and illustrate the challenge to making inferences about network adaptation. Furthermore, we examine the consequence of variable stabilizing selection across genes on the strength and direction of interactions in regulatory networks and in their subsequent adaptation. We observe that directional selection on a highly constrained gene previously under strong stabilizing selection was more efficient when the gene was embedded within a network of partners under relaxed stabilizing selection pressure. The observation leads to the expectation that evolutionarily resilient regulatory networks will contain optimal ratios of genes whose expression is under weak and strong stabilizing selection. Altogether, our results suggest that the variable strengths of stabilizing selection across genes within regulatory networks might itself contribute to the long-term adaptation of complex phenotypes.


Subject(s)
Gene Regulatory Networks , Selection, Genetic , Adaptation, Physiological , Environment , Models, Genetic , Phenotype
8.
Heredity (Edinb) ; 116(6): 516-22, 2016 06.
Article in English | MEDLINE | ID: mdl-26980343

ABSTRACT

Y chromosomes display population variation within and between species. Co-evolution within populations is expected to produce adaptive interactions between Y chromosomes and the rest of the genome. One consequence is that Y chromosomes from disparate populations could disrupt harmonious interactions between co-evolved genetic elements and result in reduced male fertility, sterility or inviability. Here we address the contribution of 'heterospecific Y chromosomes' to fertility in hybrid males carrying a homozygous region of Drosophila mauritiana introgressed in the Drosophila simulans background. In order to detect Y chromosome-autosome interactions, which may go unnoticed in a single-species background of autosomes, we constructed hybrid genotypes involving three sister species: Drosophila simulans, D. mauritiana, and D. sechellia. These engineered strains varied due to: (i) species origin of the Y chromosome (D. simulans or D. sechellia); (ii) location of the introgressed D. mauritiana segment on the D. simulans third chromosome, and (iii) grandparental genomic background (three genotypes of D. simulans). We find complex interactions between the species origin of the Y chromosome, the identity of the D. mauritiana segment and the grandparental genetic background donating the chromosomes. Unexpectedly, the interaction of the Y chromosome and one segment of D. mauritiana drastically reduced fertility in the presence of Ysim, whereas the fertility is partially rescued by the Y chromosome of D. sechellia when it descends from a specific grandparental genotype. The restoration of fertility occurs in spite of an autosomal and X-linked genome that is mostly of D. simulans origin. These results illustrate the multifactorial basis of genetic interactions involving the Y chromosome. Our study supports the hypothesis that the Y chromosome can contribute significantly to the evolution of reproductive isolation and highlights the conditional manifestation of infertility in specific genotypic combinations.


Subject(s)
Drosophila/genetics , Hybridization, Genetic , Infertility, Male/genetics , Y Chromosome/genetics , Animals , Crosses, Genetic , Female , Genome, Insect , Genotype , Male , Phenotype , Reproduction/genetics , Species Specificity
9.
J Anim Sci ; 94(1): 227-39, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26812329

ABSTRACT

Crossbred steers (British × Continental; = 192; initial BW 391 ± 28 kg) were used to evaluate the effects of feeding ethanol coproducts on feedlot cattle growth performance, apparent nutrient digestibility, and carcass characteristics. Steers were blocked by initial BW and assigned randomly to 1 of 6 dietary treatments within block. Treatments (replicated in 8 pens with 4 steers/pen) included 1) control, steam-flaked corn-based diet (CTL), 2) corn dried distillers grains with solubles (DGS; DRY-C), 3) deoiled corn dried DGS (DRY-CLF), 4) blended 50/50 corn/sorghum dried DGS (DRY-C/S), 5) sorghum dried DGS (DRY-S), and 6) sorghum wet DGS (WET-S). Inclusion of DGS was 25% (DM basis). The DGS diets were isonitrogenous, CTL was formulated for 13.5% CP, and all diets were balanced for ether extract. Final shrunk BW, ADG, and DMI did not differ among CTL and DGS treatments ( ≥ 0.19). Overall G:F did not differ from CTL for DRY-C, DRY-CLF, or WET-S ( ≥ 0.12); however, G:F was 9.6% less for DRY-S compared with CTL ( < 0.01) and tended ( = 0.09) to be less for DRY-C/S than CTL. For grain source, ADG and G:F were less for DRY-S vs. DRY-C ( < 0.05), but blending DRY-C/S tended ( = 0.07) to increase ADG and increased ( = 0.05) carcass-adjusted G:F vs. DRY-S. For WET-S, final BW and ADG were greater ( < 0.05), and G:F tended ( = 0.06) to be greater than for DRY-S. There was no difference in ADG, DMI, or G:F of steers fed DRY-C vs. DRY-CLF ( ≥ 0.35). Apparent DM and OM digestibility did not differ for CTL, DRY-C, DRY-CLF, and WET-S ( ≥ 0.30) but were lower for DRY-C/S and DRY-S ( < 0.05). Nutrient digestibility was lower for DRY-S vs. DRY-C ( < 0.01), but apparent digestibility of OM, DM, NDF, ADF, CP, ether extract, and starch were increased ( < 0.01) for DRY-C/S vs. DRY-S. Although starch digestibility did not differ between DRY-S and WET-S ( 0.18), digestibility of other measured nutrients was greater for WET-S vs. DRY-S ( < 0.01). Ether extract digestibility was greater for DRY-CLF vs. DRY-C ( < 0.05). Carcass weight, dressing percent, and marbling score did not differ between CTL and DGS diets ( ≥ 0.23). For DRY-S, HCW was lower than for DRY-C ( = 0.02); however, compared with DRY-S, HCW tended to be greater for DRY-C/S ( = 0.10) and WET-S ( = 0.07). At a moderately high (25% DM) inclusion, blending C/S or feeding WET-S resulted in cattle growth performance and carcass characteristics similar to those of CTL and corn-based coproducts.


Subject(s)
Animal Feed/analysis , Biofuels , Body Composition/drug effects , Cattle/physiology , Digestion/physiology , Zea mays , Animals , Diet/veterinary , Food Handling/methods , Gastrointestinal Tract/drug effects , Sorghum
10.
J Evol Biol ; 28(10): 1861-71, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26201506

ABSTRACT

Some regions of the genome exhibit sexual asymmetries in inheritance and are thus subjected to sex-biased evolutionary forces. Maternal inheritance of mitochondrial DNA (mtDNA) enables mtDNA mutations harmful to males, but not females, to accumulate. In the face of male-harmful mtDNA mutation accumulation, selection will favour the evolution of compensatory modifiers in the nuclear genome that offset fitness losses to males. The Y chromosome is a candidate to host these modifiers, because it is paternally inherited, known to harbour an abundance of genetic variation for male fertility, and therefore likely to be under strong selection to uphold male viability. Here, we test for intergenomic interactions involving mtDNA and Y chromosomes in male Drosophila melanogaster. Specifically, we examine effects of each of these genomic regions, and their interaction, on locomotive activity, across different environmental contexts--both dietary and social. We found that both the mtDNA haplotype and Y chromosome haplotype affected activity in males assayed in an environment perceived as social. These effects, however, were not evident in males assayed in perceived solitary environments, and neither social nor solitary treatments revealed evidence for intergenomic interactions. Finally, the magnitude and direction of these genetic effects was further contingent on the diet treatment of the males. Thus, genes within the mtDNA and Y chromosome are involved in genotype-by-environment interactions. These interactions might contribute to the maintenance of genetic variation within these asymmetrically inherited gene regions and complicate the dynamics of genetic interactions between the mtDNA and the Y chromosome.


Subject(s)
DNA, Mitochondrial/genetics , Drosophila melanogaster/genetics , Haplotypes , Locomotion , Y Chromosome , Animals , Male
11.
J Endocrinol Invest ; 38(11): 1243-6, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25952298

ABSTRACT

PURPOSE: Telomere dysfunction and telomerase activation underlie cancer transformation. This study aims to investigate the contribution of telomere biology to pituitary tumor behavior. SUBJECTS AND METHODS: Samples from 50 patients with pituitary tumors (11 ACTH-secreting, 18 GH-secreting, and 21 non-secreting tumors) and 7 subjects without pituitary lesions were collected. The expressions of telomerase essential components TERT and TERC and tumor telomere content were measured by quantitative PCR techniques. RESULTS: Telomerase (TERT) expression was detected in 36% of tumors. No correlation was observed between TERT and TERC expression level and tumor size in any tumor type. There was no association between gene expression and clinical findings. Telomere content (T/S ratio) was similar between pituitary adenomas (0.39 ± 0.16) and normal pituitaries (0.47 ± 0.12; p = 0.24) and also was between the different adenoma types: ACTH-secreting (0.43 ± 0.08), GH-secreting (0.31 ± 0.12), and non-secreting (0.42 ± 0.20; p = 0.10) tumors. CONCLUSIONS: The telomere content and expression of telomerase components are comparable between normal pituitary glands and tumor tissues, suggesting that telomere biology does not play an important role in pituitary tumor development.


Subject(s)
Gene Expression/physiology , Pituitary Neoplasms/metabolism , Telomerase/metabolism , Telomere/metabolism , Adult , Humans , Middle Aged , Pituitary Neoplasms/enzymology , RNA/metabolism
12.
Br J Cancer ; 109(11): 2819-28, 2013 Nov 26.
Article in English | MEDLINE | ID: mdl-24201752

ABSTRACT

BACKGROUND: We recently showed that synthetic phosphoethanolamine reduces tumour growth and inhibits lung metastasis in vivo. Here, we investigated its anti-leukaemia effects using acute promyelocytic leukaemia (APL) as a model. METHODS: Cytotoxic effects of Pho-s on leukaemia cells were evaluated by MTT assay. Leukaemic cells obtained from hCG-PML-RARa transgenic mice were transplanted to NOD/SCID mice. After the animals were diagnosed as leukaemic, treatment started with Pho-s using all-trans retinoid acid or daunorubicin as positive control or and saline control. Cell morphology and immunophenotyping were used to detect the undifferentiated blast cells in the spleen, liver and bone marrow. The induction of apoptosis in vitro and in malignant leukaemic clones was evaluated. RESULTS: Synthetic phosphoethanolamine is cytotoxic and induces apoptosis through the mitochondrial pathway in vitro to leukaemia cell lines. In vivo Pho-s exhibits anti-proliferative effects in APL model reducing the number of CD117(+) and Gr-1(+) immature myeloid cells in the BM, spleen and liver. Synthetic phosphoethanolamine impairs the expansion of malignant clones CD34(+)/CD117(+), CD34(+) and Gr-1(+) in the BM. In addition, Pho-s induces apoptosis of immature cells in the spleen and liver, a notable effect. CONCLUSION: Synthetic phosphoethanolamine has anti-leukaemic effects in an APL model by inhibiting malignant clone expansion, suggesting that it is an interesting compound for leukaemia treatment.


Subject(s)
Antineoplastic Agents/pharmacology , Ethanolamines/pharmacology , Leukemia, Promyelocytic, Acute/drug therapy , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/therapeutic use , Cell Proliferation/drug effects , Drug Evaluation, Preclinical , Ethanolamines/chemical synthesis , Ethanolamines/therapeutic use , Humans , Jurkat Cells , K562 Cells , Leukemia, Promyelocytic, Acute/genetics , Leukemia, Promyelocytic, Acute/pathology , Mice , Mice, Inbred NOD , Mice, SCID , Mice, Transgenic , Oncogene Proteins, Fusion/genetics , Tumor Cells, Cultured
13.
Heredity (Edinb) ; 111(1): 8-15, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23591516

ABSTRACT

X-linked sex-ratio distorters that disrupt spermatogenesis can cause a deficiency in functional Y-bearing sperm and a female-biased sex ratio. Y-linked modifiers that restore a normal sex ratio might be abundant and favored when a X-linked distorter is present. Here we investigated natural variation of Y-linked suppressors of sex-ratio in the Winters systems and the ability of these chromosomes to modulate gene expression in Drosophila simulans. Seventy-eight Y chromosomes of worldwide origin were assayed for their resistance to the X-linked sex-ratio distorter gene Dox. Y chromosome diversity caused males to sire ∼63% to ∼98% female progeny. Genome-wide gene expression analysis revealed hundreds of genes differentially expressed between isogenic males with sensitive (high sex ratio) and resistant (low sex ratio) Y chromosomes from the same population. Although the expression of about 75% of all testis-specific genes remained unchanged across Y chromosomes, a subset of post-meiotic genes was upregulated by resistant Y chromosomes. Conversely, a set of accessory gland-specific genes and mitochondrial genes were downregulated in males with resistant Y chromosomes. The D. simulans Y chromosome also modulated gene expression in XXY females in which the Y-linked protein-coding genes are not transcribed. The data suggest that the Y chromosome might exert its regulatory functions through epigenetic mechanisms that do not require the expression of protein-coding genes. The gene network that modulates sex ratio distortion by the Y chromosome is poorly understood, other than that it might include interactions with mitochondria and enriched for genes expressed in post-meiotic stages of spermatogenesis.


Subject(s)
Chromosomes, Insect/genetics , Down-Regulation , Drosophila Proteins/genetics , Drosophila/genetics , Gene Expression Regulation , Y Chromosome/genetics , Animals , Chromosomes, Insect/metabolism , Drosophila/metabolism , Drosophila Proteins/metabolism , Female , Male , Organ Specificity , Sex Ratio , Testis/metabolism , Y Chromosome/metabolism
14.
Leukemia ; 26(3): 451-60, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21869839

ABSTRACT

The vitamin E derivative (+)α-tocopheryl succinate (α-TOS) exerts pro-apoptotic effects in a wide range of tumors and is well tolerated by normal tissues. Previous studies point to a mitochondrial involvement in the action mechanism; however, the early steps have not been fully elucidated. In a model of acute promyelocytic leukemia (APL) derived from hCG-PML-RARα transgenic mice, we demonstrated that α-TOS is as effective as arsenic trioxide or all-trans retinoic acid, the current gold standards of therapy. We also demonstrated that α-TOS induces an early dissipation of the mitochondrial membrane potential in APL cells and studies with isolated mitochondria revealed that this action may result from the inhibition of mitochondrial respiratory chain complex I. Moreover, α-TOS promoted accumulation of reactive oxygen species hours before mitochondrial cytochrome c release and caspases activation. Therefore, an in vivo antileukemic action and a novel mitochondrial target were revealed for α-TOS, as well as mitochondrial respiratory complex I was highlighted as potential target for anticancer therapy.


Subject(s)
Arsenicals/therapeutic use , Electron Transport Complex I/antagonists & inhibitors , Leukemia, Promyelocytic, Acute/drug therapy , Mitochondria/drug effects , Oxides/therapeutic use , Tretinoin/therapeutic use , alpha-Tocopherol/pharmacology , alpha-Tocopherol/therapeutic use , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Apoptosis/drug effects , Arsenic Trioxide , Caspases/metabolism , Cell Line, Tumor , Cytochromes c/metabolism , Disease Models, Animal , Electron Transport Complex II/antagonists & inhibitors , Humans , Leukemia, Promyelocytic, Acute/mortality , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Transgenic , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Oncogene Proteins, Fusion/metabolism , Protein Stability/drug effects , Rats , Reactive Oxygen Species/metabolism , Transplantation, Isogeneic
15.
Eur Arch Paediatr Dent ; 11(4): 192-5, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20840830

ABSTRACT

AIM: This was to investigate the prevalence of sleep bruxism in Brazilian schoolchildren. METHODS: A cross-sectional study was carried out examining 652 randomly selected children aged from 7 to 10 years of age from both public and private schools in Belo Horizonte, Brazil. Sleep bruxism among children was reported by parents by means of a pretested questionnaire based on the criteria of the American Academy of Sleep Disorders. The Social Vulnerability Index from Municipal database was used to determine social classification of families. A chi-square test was used with a significance level of 5%. RESULTS: Sleep bruxism was present in 230 children, showing a prevalence of 35.3%. Among the 652 children, 340 (52.0%) were girls and 312 (48.0%) were boys, predominatly of 8-year-olds (84.2%). Sleep bruxism was present in 56.5% of the girls and 43.5% of the boys. The majority of the families were of a low social vulnerability (54.2%), whereas another 45.8% were of a high social vulnerability. More than half of the children without sleep bruxism (55.2%) were of low socio-economic background. CONCLUSIONS: The high prevalence of 35.3% demonstrates the need for further research on this issue.


Subject(s)
Sleep Bruxism/epidemiology , Brazil/epidemiology , Child , Cross-Sectional Studies , Female , Humans , Male , Marital Status/statistics & numerical data , Population Surveillance , Prevalence , Self Report , Social Class , Surveys and Questionnaires , Vulnerable Populations/statistics & numerical data
17.
Head Neck ; 28(12): 1115-21, 2006 Dec.
Article in English | MEDLINE | ID: mdl-16823873

ABSTRACT

BACKGROUND: The University of Washington Quality of Life (UW-QOL) questionnaire is an English-language survey instrument used worldwide to assess the quality of life of patients with head and neck cancer. To be used in other cultures, such instruments require careful translation and psychometric validation in other languages. METHODS: The translation and cultural adaptation of the questionnaire were performed following accepted international guidelines. The psychometric validation was performed on a consecutive series of patients with at least 1 year of disease-free survival after treatment for squamous cell carcinoma of the upper aerodigestive tract, recruited from October 2004 to January 2005 from a tertiary cancer center hospital. Eligible subjects were invited to complete the Portuguese version of the UW-QOL questionnaire during routine clinical consultation and complete it again within 15 days. They also completed a validated Portuguese version of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and a questionnaire to evaluate anxiety and depression symptoms (Hospital Anxiety and Depression Scale [HADS]). RESULTS: A Portuguese version of the questionnaire was developed in iterative fashion. In the psychometric validation process, a total of 109 patients were analyzed. Reliability was excellent, including both internal consistency (Cronbach's alpha [alpha] of 0.744) and test retest reliability (intraclass correlation coefficient [ICC] of 0.882). Construct validity was supported by statistically significant relationships between the SF-36 and HAD questionnaires and the translated UW-QOL questionnaire. CONCLUSIONS: The Brazilian-Portuguese version of the UW-QOL questionnaire appears to be culturally appropriate and psychometrically valid. This version is a valuable tool to evaluate accurately the quality of life of Brazilian patients with head and neck cancer.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Quality of Life , Surveys and Questionnaires , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/therapy , Female , Head and Neck Neoplasms/therapy , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Psychometrics , Reproducibility of Results
18.
Braz J Biol ; 65(3): 395-406, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16341417

ABSTRACT

This work is based on a survey of small mammals carried out in the Chapada dos Veadeiros National Park, a natural reserve located in the mountains of the Planalto Central Goiano in the Cerrado of Central Brazil. The 227 specimens collected represented six marsupial and 13 rodent species. Taxonomic, karyologic, and ecologic considerations are present and discussed in the present work. Our data reflected the faunal heterogeneity with respect to both elevation and vegetation because only eight of the 19 species were collected at both high and low elevations. The composition of the small mammal fauna of the park is influenced by predominance of forest formations at low elevations and cerrado with rupestrian areas at high elevations. Presence of endemic species and one undescribed demonstrated that the cerrado has an endemic fauna and a little known diversity of small mammals.


Subject(s)
Marsupialia/classification , Rodentia/classification , Altitude , Animals , Biodiversity , Brazil , Female , Karyotyping , Male , Marsupialia/anatomy & histology , Marsupialia/genetics , Population Density , Rodentia/anatomy & histology , Rodentia/genetics , Trees
19.
Braz. j. biol ; 65(3): 395-406, Aug. 2005.
Article in English | LILACS | ID: lil-418141

ABSTRACT

Este trabalho é baseado em um levantamento sobre pequenos mamíferos realizado no Parque Nacional da Chapada dos Veadeiros, localizado nas montanhas do Planalto Central Goiano, no Cerrado do Brasil Central. Foram coletadas 227 espécimes, representando 6 espécies de marsupiais e 13 de roedores. Considerações taxonômicas, cariológicas e ecológicas são apresentadas e discutidas. Nossos dados refletem a heterogeneidade da fauna em relação à altitude e à vegetação do Cerrado, sendo apenas 8 das 19 espécies coletadas comuns às altitudes elevadas e baixas. A composição da fauna de pequenos mamíferos do parque está influenciada pela predominância de formações florestais nas altitudes baixas e de cerrado rupestre nas altitudes elevadas. A presença de espécies endêmicas e uma ainda não descrita demonstram que o Cerrado apresenta uma fauna endêmica associada, sendo pouco entendida a diversidade de seus pequenos mamíferos.


Subject(s)
Animals , Male , Female , Pregnancy , Marsupialia/classification , Rodentia/classification , Altitude , Biodiversity , Brazil , Karyotyping , Marsupialia/anatomy & histology , Marsupialia/genetics , Population Density , Rodentia/anatomy & histology , Rodentia/genetics , Trees
20.
J Evol Biol ; 18(4): 838-46, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16033555

ABSTRACT

The thermal range for viability is quite variable among Drosophila species and it has long been known that these variations are correlated with geographic distribution: temperate species are on average more cold tolerant but more heat sensitive than tropical species. At both ends of their viability range, sterile males have been observed in all species investigated so far. This symmetrical phenomenon restricts the temperature limits within which permanent cultures can be kept in the laboratory. Thermal heat sterility thresholds are very variable across species from 23 degrees C in heat sensitive species up to 31 degrees C in heat tolerant species. In Drosophila melanogaster, genetic variations are observed among geographic populations. Tropical populations are more tolerant to heat induced sterility and recover more rapidly than temperate ones. A genetic analysis revealed that about 50% of the difference observed between natural populations was due to the Y chromosome. Natural populations have not reached a selection limit, however: thermal tolerance was still increased by keeping strains at a high temperature, close to the sterility threshold. On the low temperature side, a symmetrical reverse phenomenon seems to exist: temperate populations are more tolerant to cold than tropical ones. Compared to Mammals, drosophilids exhibit two major differences: first, male sterility occurs not only at high temperature, but also at a low temperature; second, sterility thresholds are not evolutionarily constrained, but highly variable. Altogether, significant and sometimes major genetic variations have been observed between species, between geographic races of the same species, and even between strains kept in the laboratory under different thermal regimes. In each case, it is easily argued that the observed variations correspond to adaptations to climatic conditions, and that male sterility is a significant component of fitness and a target of natural selection.


Subject(s)
Adaptation, Physiological/physiology , Drosophila melanogaster/physiology , Infertility, Male/physiopathology , Temperature , Y Chromosome/genetics , Adaptation, Physiological/genetics , Animals , Male , Species Specificity
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