Description and characterization of the melanic morphotype of Rhodnius nasutus Stål, 1859 (Hemiptera: Reduviidae: Triatominae)

IntroductionFor the first time we provide the description of the melanic (dark) morphotype of Rhodnius nasutus and determine the pattern of genetic inheritance for this characteristic.MethodsDark morph R. nasutus specimens were crossbred with standard (typically patterned) R. nasutus.ResultsWe present the first occurrence of the melanic morphotype in the genus Rhodnius. The crossbreeding results demonstrate that the inheritance pattern of this characteristic follows Mendel's simple laws of segregation and an independent assortment of alleles.ConclusionsPhenotypic variation of R. nasutus reinforces the heterogeneity found in the Triatominae. Descriptions of new species in this subfamily require rigorous validation criteria.

History of insecticide resistance of Triatominae vectors

AbstractIn the last 15 years, different types of Triatominae resistance to different insecticides have been reported; thus, resistance may be more widespread than known, requiring better characterization and delimitation, which was the aim of this review. This review was structured on a literature search of all articles from 1970 to 2015 in the PubMed database that contained the keywords Insecticide resistance and Triatominae . Out of 295 articles screened by title, 33 texts were selected for detailed analysis. Insecticide resistance of Triatomines is a complex phenomenon that has been primarily reported in Argentina and Bolivia, and is caused by different factors (associated or isolated). Insecticide resistance of Triatominae is a characteristic inherited in an autosomal and semi-dominant manner, and is polygenic, being present in both domestic and sylvatic populations. The toxicological profile observed in eggs cannot be transposed to different stages of evolution. Different toxicological profiles exist at macro- and microgeographical levels. The insecticide phenotype has both reproductive and developmental costs. Different physiological mechanisms are involved in resistance. Studies of Triatomine resistance to insecticides highlight three deficiencies in interpreting the obtained results: I) the vast diversity of methodologies, despite the existence of a single guiding protocol; II) the lack of information on the actual impact of resistance ratios in the field; and III) the concept of the susceptibility reference lineage. Research on the biological and behavioral characteristics of each Triatominae species that has evolved resistance is required in relation to the environmental conditions of each region.

Noonan syndrome: a clinical and genetic study of 31 patients

Noonan syndrome is a multiple congenital anomaly syndrome, inherited in an autosomal dominant pattern. We studied 31 patients (18 males and 13 females) affected by this disorder regarding their clinical and genetic characteristics. The most frequent clinical findings were short stature (71%); craniofacial dysmorphisms, especially hypertelorism, ptosis, downslanting of the palpebral fissures; short or webbed neck (87%); cardiac anomalies (65%), and fetal pads in fingers and toes (70%). After studying the probands' first-degree relatives, we made the diagnosis of Noonan syndrome in more than one family member in three families. Therefore, the majority of our cases were sporadic.

Cerebral vasculopathy in children with sickle cell disease A study of genetic modulators of the disease

Sickle cell disease (SCD) is a genetic disorder with recessive transmission, caused by the mutation HBB:c.20A>T. It originates hemoglobin S that forms polymers inside the erythrocyte, upon deoxygenation, deforming it and ultimately leading to premature hemolysis. The disease presents with high heterogeneity of clinical manifestations, the most devastating of which, ischemic stroke, occurs in 11% of patients until 20 years of age. In this study, we tried to identify genetic modifiers of risk and episodes of stroke by studying 66 children with SCD, grouped according to the degree of cerebral vasculopathy (Stroke, Risk and Control). Association studies were performed between the three phenotypic groups and hematological and biochemical parameters of patients, as well as with 23 polymorphic regions in genes related to vascular cell adhesion (VCAM-1, THBS-1 and CD36), vascular tonus (NOS3 and ET-1) and inflammation (TNF-α and HMOX-1). Relevant data was collected from patient’s medical records. Known genetic modulators of SCD (beta-globin cluster haplotype and HBA and BCL11A genotypes) and putative genetic modifiers of cerebral vasculopathy were characterized. Differences in their distribution among groups were assessed. VCAM-1 rs1409419 allele C and NOS3 rs207044 allele C were associated to stroke events, while VCAM-1 rs1409419 allele T was found to be protective. Alleles 4a and 4b of NOS3 27 bp VNTR appeared to be respectively associated to stroke risk and protection. HMOX-1 longer STRs seemed to predispose to stroke. Higher hemoglobin F levels were found in Control group, as a result of Senegal haplotype or of BCL11A rs11886868 allele T, and higher lactate dehydrogenase levels, marker of hemolysis, were found in Risk group. Molecular mechanisms underlying the modifier functions of the relevant genetic variants are discussed.

Colorectal cancer screening

Colorectal cancer (CRC) is the third most common cancer in the world, and mortality has remained the same for the past 50 years, despite advances in diagnosis and treatment. Because significant numbers of patients present with advanced or incurable stages, patients with pre-malignant lesions (adenomatous polyps) that occur as result of genetic inheritance or age should be screened, and patients with long-standing inflammatory bowel disease should undergo surveillance. There are different risk groups for CRC, as well as different screening strategies. It remains to be determined which screening protocol is the most cost-effective for each risk catagory. The objective of screening is to reduce morbidity and mortality in a target population. The purpose of this review is to analyze the results of the published CRC screening studies, with regard to the measured reduction of morbidity and mortality, due to CRC in the studied populations, following various screening procedures. The main screening techniques, used in combination or alone, include fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy. Evidence from the published literature on screening methods for specific risk groups is scanty and frequently does not arise from controlled studies. Nevertheless, data from these studies, combined with recent advances in molecular genetics, certainly lead the way to greater efficacy and lower cost of CRC screening.

Oral manifestations of Albright hereditary Osteodystrophy: a case report

Albright hereditary osteodystrophy is a hereditary metabolic disorder of dominant autosomal etiology that is commonly characterized by short stature, round face, small metacarpus and metatarsus, mental retardation, osteoporosis, subcutaneous calcification, variable hypocalcemia, and hyperphosphatemia. In this study, we report a clinical case of a 17-year-old woman with Albright hereditary osteodystrophy, and we discuss her clinical, radiographic, and laboratory test characteristics together with the oral manifestations, and we correlate them with the characteristics found in the literature. We also discuss the odontological management of treatment of related periodontal disease and planning for corrections of related malocclusions.

Quantitative Centromere Epigenetics

A PhD is like a box of chocolates, …… and in this thesis I will present what I got. My work has been focused on a cellular structure that is essential for accurate genome inheritance: the centromere. Centromeres are chromosomal domains that do not rely on the presence of any specific DNA sequence. Rather, they are determined by the presence of a histone variant called CENP-A. Stable transmission of CENP-A containing chromatin is accomplished through 1) an unusually high level of protein stability, 2) selfdirected recruitment of nascent CENP-A near existing molecules, and 3) strict cell cycle regulation of assembly. Together, these features lead to a self-sustaining loop that allows for epigenetic maintenance of centromeres.(...)

Aging and Alzheimer's disease: Searching for novel molecular cues

Tese de Doutoramento em Ciências da Saúde

A sucessão em sede de reversão do processo de execução fiscal

Dissertação de mestrado em Direito Tributário e Fiscal

Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-d pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach to treatment.

Dos efeitos da Procriação Medicamente Assistida no Direito Sucessório

Dissertação de mestrado em Direito das Crianças, Família e Sucessões

Association of Peripheral Arterial and Cardiovascular Diseases in Familial Hypercholesterolemia

Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c). Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD). Objective: This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD), such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. Methods: The diagnosis of PAD was established by ankle-brachial index (ABI) values ≤ 0.90. This study assessed 202 patients (35% of men) with heterozygous FH (90.6% with LDL receptor mutations), mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. Results: The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049). Conclusion: Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients.

A ação dos gens gametofíticos com referência especial ao milho

1) The first part deals with the different processes which may complicate Mendelian segregation and which may be classified into three groups, according to BRIEGER (1937b) : a) Instability of genes, b) Abnormal segregation due to distur- bances during the meiotic divisions, c) obscured segregation, after a perfectly normal meiosis, caused by elimination or during the gonophase (gametophyte in higher plants), or during zygophase (sporophyte). Without entering into detail, it is emphasized that all the above mentioned complications in the segregation of some genes may be caused by the action of other genes. Thus in maize, the instability of the Al factor is observed only when the gene dt is presente in the homozygous conditions (RHOADES 1938). In another case, still under observation in Piracicaba, an instability is observed in Mirabilis with regard to two pairs of alleles both controlling flower color. Several cases are known, especially in corn, where recessive genes, when homozigous, affect the course of meiosis, causing asynapsis (asyndesis) (BEADLE AND MC CLINTOCK 1928, BEADLE 1930), sticky chromosomes (BEADLE 1932), supermunmerary divisions (BEADLE 1931). The most extreme case of an obscured segregatiou is represented by the action of the S factors in self stetrile plants. An additional proof of EAST AND MANGELSDORF (1925) genetic formula of self sterility has been contributed by the studies on Jinked factors in Nicotina (BRIEGER AND MANGELSDORF (1926) and Antirrhinum (BRIEGER 1930, 1935), In cases of a incomplete competition and selection between pollen tubes, studies of linked indicator-genes are indispensable in the genetic analysis, since it is impossible to analyse the factors for gametophyte competition by direct aproach. 2) The flower structure of corn is explained, and stated that the particularites of floral biology make maize an excellent object for the study of gametophyte factors. Since only one pollen tube per ovule may accomplish fertilization, the competition is always extremely strong, as compared with other species possessing multi-ovulate ovaries. The lenght of the silk permitts the study of pollen tube competitions over a varying distance. Finally the genetic analysis of grains characters (endosperm and aleoron) simpliflen the experimental work considerably, by allowing the accumulation of large numbers for statistical treatment. 3) The four methods for analyzing the naturing of pollen tube competition are discussed, following BRIEGER (1930). Of these the first three are: a) polinization with a small number of pollen grains, b) polinization at different times and c) cut- ting the style after the faster tubes have passe dand before the slower tubes have reached the point where the stigma will be cut. d) The fourth method, alteration of the distatice over which competition takes place, has been applied largely in corn. The basic conceptions underlying this process, are illustrated in Fig. 3. While BRINK (1925) and MANGELSDORF (1929) applied pollen at different levels on the silks, the remaining authors (JONES, 1922, MANGELSDORF 1929, BRIEGER, at al. 1938) have used a different process. The pollen was applied as usual, after removing the main part of the silks, but the ears were divided transversally into halves or quarters before counting. The experiments showed generally an increase in the intensity of competition when there was increase of the distance over which they had to travel. Only MANGELSDORF found an interesting exception. When the distance became extreme, the initially slower tubes seemed to become finally the faster ones. 4) Methods of genetic and statistical analysis are discussed, following chiefly BRIEGER (1937a and 1937b). A formula is given to determine the intensity of ellimination in three point experiments. 5) The few facts are cited which give some indication about the physiological mechanism of gametophyte competition. They are four in number a) the growth rate depends-only on the action of gametophyte factors; b) there is an interaction between the conductive tissue of the stigma or style and the pollen tubes, mainly in self-sterile plants; c) after self-pollination necrosis starts in the tissue of the stigma, in some orchids after F. MÜLLER (1867); d) in pollon mixtures there is an inhibitory interaction between two types of pollen and the female tissue; Gossypium according to BALLS (1911), KEARNEY 1923, 1928, KEARNEY AND HARRISON (1924). A more complete discussion is found in BRIEGER 1930). 6) A list of the gametophyte factors so far localized in corn is given. CHROMOSOME IV Ga 1 : MANGELSDORF AND JONES (1925), EMERSON 1934). Ga 4 : BRIEGER (1945b). Sp 1 : MANGELSDORF (1931), SINGLETON AND MANGELSDORF (1940), BRIEGER (1945a). CHROMOSOME V Ga 2 : BRIEGER (1937a). CHROMOSOME VI BRIEGER, TIDBURY AND TSENG (1938) found indications of a gametophyte factor altering the segregation of yellow endosperm y1. CHROMOSOME IX Ga 3 : BRIEGER, TIDBURY AND TSENG (1938). While the competition in these six cases is essentially determined by one pair of factors, the degree of elimination may be variable, as shown for Ga2 (BRIEGER, 1937), for Ga4 (BRIEGER 1945a) and for Spl (SINGLETON AND MANGELSDORF 1940, BRIEGER 1945b). The action of a gametophyte factor altering the segregation of waxy (perhaps Ga3) is increased by the presence of the sul factor which thus acts as a modifier (BRINCK AND BURNHAM 1927). A polyfactorial case of gametophyte competition has been found by JONES (1922) and analysed by DEMEREC (1929) in rice pop corn which rejects the pollen tubes of other types of corn. Preference for selfing or for brothers-sister mating and partial elimination of other pollen tubes has been described by BRIEGER (1936). 7) HARLAND'S (1943) very ingenious idea is discussed to use pollen tube factors in applied genetics in order to build up an obstacle to natural crossing as a consequence of the rapid pollen tube growth after selfing. Unfortunately, HARLAND could not obtain the experimental proof of the praticability of his idea, during his experiments on selection for minor modifiers for pollen tube grouth in cotton. In maize it should be possible to employ gametophyte factors to build up lines with preference for crossing, though the method should hardly be of any practical advantage.

Comportamento dos cromossômios na meiose de Euryophthalmus rufipennis Laporte (Hemiptera Pyrrhocoridae)

In this paper an account is given of the principal facts observer in the meiosis of Euryophthalmus rufipennis Laporte which afford some evidence in favour of the view held by the present writer in earlier publications regarding the existence of two terminal kinetochores in Hem ip ter an chromosomes as well as the transverse division of the chromosomes. Spermatogonial mitosis - From the beginning of prophase until metaphase nothing worthy of special reference was observed. At anaphase, on the contrary, the behavior of the chromosomes deserves our best attention. Indeed, the chromoso- mes, as soon as they begin to move, they show both ends pronouncedly turned toward the poles to which they are connected by chromosomal fibres. So a premature and remarkable bending of the chromosomes not yet found in any other species of Hemiptera and even of Homoptera points strongly to terminally localized kinetochores. The explanation proposed by HUGHES-SCHRADER and RIS for Nautococcus and by RIS for Tamalia, whose chromosomes first become bent late in anaphase do not apply to chromosomes which initiate anaphase movement already turned toward the corresponding pole. In the other hand, the variety of positions assumed by the anaphase chromosomes of Euryophthalmus with regard to one another speaks conclusively against the idea of diffuse spindle attachments. First meiotic division - Corresponding to the beginning of the story of the primary spermatocytes cells are found with the nucleus entirelly filled with leptonema threads. Nuclei with thin and thick threads have been considered as being in the zygotente phase. At the pachytene stage the bivalents are formed by two parallel strands clearly separated by a narrow space. The preceding phases differ in nothing from the corresponding orthodox ones, pairing being undoubtedly of the parasynaptic type. Formation of tetrads - When the nuclei coming from the diffuse stage can be again understood the chromosomes reappear as thick threads formed by two filaments intimately united except for a short median segment. Becoming progressively shorter and thicker the bivalents sometimes unite their extremities forming ring-shaped figures. Generally, however, this does not happen and the bivalents give origin to more or less condensed characteristic Hemipteran tetrads, bent at the weak median region. The lateral duplicity of the tetrads is evident. At metaphase the tetrads are still bent and are connected with both poles by their ends. The ring-shaped diakinesis tetrads open themselves out before metaphase, showing in this way that were not chiasmata that held their ends together. Anaphase proceeds as expected. If we consider the median region of the tetrads as being terminalized chiasmata, then the chromosomes are provided with a single terminal kinetochore. But this it not the case. A critical analysis of the story of the bivalents before and after the diffuse stage points to the conclusion that they are continuous throughout their whole length. Thence the chromosomes are considered as having a kinetochore at each end. Orientation - There are some evidences that Hemipteran chromosomes are connected by chiasmata. If this is true, the orientation of the tetrads may be understood in the following manner: Chiasmata being hindered to scape by the terminal kinetochores accumulate at the ends of the tetrads, where condensation begins. Repulsion at the centric ends being prevented by chiasmata the tetrads orient themselves as if they were provided with a single kinetochore at each extremity, taking a position parallelly to the spindle axis. Anaphase separation - Anaphase separation is consequently due to a transverse division of the chromosomes. Telophase and secund meiotic division - At telophase the kinetochore repeli one another following the moving apart of the centosomes, the chiasmata slip toward the acentric extremities and the chromosomes rotate in order to arrange themselves parallelly to the axis of the new spindle. Separation is therefore throughout the pairing plane. Origin of the dicentricity of the chromosomes - Dicentricity of the chromosomes is ascribed to the division of the kinetochore of the chromosomes reaching the poles followed by separation and distension of the chromatids which remain fused at the acentric ends giving thus origin to terminally dicentric iso-chromosomes. Thence, the transverse division of the chromosomes, that is, a division through a plane perpendicular to the plane of pairing, actually corresponds to a longitudinal division realized in the preceding generation. Inactive and active kinetochores - Chromosomes carrying inactive kinetochore is not capable of orientation and active anaphasic movements. The heterochromosome of Diactor bilineatus in the division of the secondary spermatocytes is justly in this case, standing without fibrilar connection with the poles anywhere in the cell, while the autosomes are moving regularly. The heterochromosome of Euryophthalmus, on the contrary, having its kinetochores perfectly active ,is correctly oriented in the plane of the equator together with the autosomes and shows terminal chromosomal connection with both poles. Being attracted with equal strength by two opposite poles it cannot decide to the one way or the other remaining motionless in the equator until some secondary causes (as for instances a slight functional difference between the kinetochores) intervene to break the state of equilibrium. When Yiothing interferes to aide the heterochromosome in choosing its way it distends itself between the autosomal plates forming a fusiform bridge which sometimes finishes by being broken. Ordinarily, however, the bulky part of the heterochromosome passes to one pole. Spindle fibers and kinetic activity of chromosomal fragments - The kinetochore is considered as the unique part of the chromosome capable of being influenced by other kinetochore or by the poles. Under such influence the kinetochore would be stimulated or activited and would elaborate a sort of impulse which would run toward the ends. In this respect the chromosome may be compared to a neüròn, the cell being represented by the kinetochore and the axon by the body of the chromosome. Due to the action of the kinetochore the entire chromosome becomes also activated for performing its kinetic function. Nothing is known at present about the nature of this activation. We can however assume that some active chemical substance like those produced by the neuron and transferred to the effector passes from the kinetochore to the body of the chromosome runing down to the ends. And, like an axon which continues to transmit an impulse after the stimulating agent has suspended its action, so may the chromosome show some residual kinetic activity even after having lost its kinetochore. This is another explanation for the kinetic behavior of acentric chromosomal fragmehs. In the orthodox monocentric chromosomes the kinetic activity is greater at the kinetochore, that is, at the place of origin of the active substance than at any other place. In chromosomes provided with a kinetochore at each end the entire body may become active enough to produce chromosomal fibers. This is probably due to a more or less uniform distribution and concentration of the active substance coming simultaneously from both extremities of the chromosome.