Association of alpha1a-adrenergic receptor polymorphism and blood pressure phenotypes in the Brazilian population

Background: The alpha1A-adrenergic receptor (alpha(1A)-AR) regulates the cardiac and peripheral vascular system through sympathetic activation. Due to its important role in the regulation of vascular tone and blood pressure, we aimed to investigate the association between the Arg347Cys polymorphism in the alpha(1A)-AR gene and blood pressure phenotypes, in a large sample of Brazilians from an urban population. Methods: A total of 1568 individuals were randomly selected from the general population of the Vitoria City metropolitan area. Genetic analysis of the Arg347Cys polymorphism was conducted by polymerase chain reaction/restriction fragment length polymorphism. We have compared cardiovascular risk variables and genotypes using ANOVA, and Chi-square test for univariate comparisons and logistic regression for multivariate comparisons. Results: Association analysis indicated a significant difference between genotype groups with respect to diastolic blood pressure (p = 0.04), but not systolic blood pressure (p = 0.12). In addition, presence of the Cys/Cys genotype was marginally associated with hypertension in our population (p = 0.06). Significant interaction effects were observed between the studied genetic variant, age and physical activity. Presence of the Cys/Cys genotype was associated with hypertension only in individuals with regular physical activity (odds ratio = 1.86; p = 0.03) or younger than 45 years (odds ratio = 1.27; p = 0.04). Conclusion: Physical activity and age may potentially play a role by disclosing the effects of the Cys allele on blood pressure. According to our data it is possible that the Arg347Cys polymorphism can be used as a biomarker to disease risk in a selected group of individuals.

Testing Evolutionary and Dispersion Scenarios for the Settlement of the New World

Background: Discussion surrounding the settlement of the New World has recently gained momentum with advances in molecular biology, archaeology and bioanthropology. Recent evidence from these diverse fields is found to support different colonization scenarios. The currently available genetic evidence suggests a ""single migration'' model, in which both early and later Native American groups derive from one expansion event into the continent. In contrast, the pronounced anatomical differences between early and late Native American populations have led others to propose more complex scenarios, involving separate colonization events of the New World and a distinct origin for these groups. Methodology/Principal Findings: Using large samples of Early American crania, we: 1) calculated the rate of morphological differentiation between Early and Late American samples under three different time divergence assumptions, and compared our findings to the predicted morphological differentiation under neutral conditions in each case; and 2) further tested three dispersal scenarios for the colonization of the New World by comparing the morphological distances among early and late Amerindians, East Asians, Australo-Melanesians and early modern humans from Asia to geographical distances associated with each dispersion model. Results indicate that the assumption of a last shared common ancestor outside the continent better explains the observed morphological differences between early and late American groups. This result is corroborated by our finding that a model comprising two Asian waves of migration coming through Bering into the Americas fits the cranial anatomical evidence best, especially when the effects of diversifying selection to climate are taken into account. Conclusions: We conclude that the morphological diversity documented through time in the New World is best accounted for by a model postulating two waves of human expansion into the continent originating in East Asia and entering through Beringia.

Genome structure of a Saccharomyces cerevisiae strain widely used in bioethanol production

Bioethanol is a biofuel produced mainly from the fermentation of carbohydrates derived from agricultural feedstocks by the yeast Saccharomyces cerevisiae. One of the most widely adopted strains is PE-2, a heterothallic diploid naturally adapted to the sugar cane fermentation process used in Brazil. Here we report the molecular genetic analysis of a PE-2 derived diploid (JAY270), and the complete genome sequence of a haploid derivative (JAY291). The JAY270 genome is highly heterozygous (similar to 2 SNPs/kb) and has several structural polymorphisms between homologous chromosomes. These chromosomal rearrangements are confined to the peripheral regions of the chromosomes, with breakpoints within repetitive DNA sequences. Despite its complex karyotype, this diploid, when sporulated, had a high frequency of viable spores. Hybrid diploids formed by outcrossing with the laboratory strain S288c also displayed good spore viability. Thus, the rearrangements that exist near the ends of chromosomes do not impair meiosis, as they do not span regions that contain essential genes. This observation is consistent with a model in which the peripheral regions of chromosomes represent plastic domains of the genome that are free to recombine ectopically and experiment with alternative structures. We also explored features of the JAY270 and JAY291 genomes that help explain their high adaptation to industrial environments, exhibiting desirable phenotypes such as high ethanol and cell mass production and high temperature and oxidative stress tolerance. The genomic manipulation of such strains could enable the creation of a new generation of industrial organisms, ideally suited for use as delivery vehicles for future bioenergy technologies.

Penile anthropometry in systemic lupus erythematosus patients

The aim of this study was to evaluate penile anthropometry in systemic lupus erythematosus (SLE) patients compared with healthy controls and the possible relevant pubertal, clinical, hormonal and treatment factors that could influence penile dimensions. Twenty-five consecutive SLE patients were assessed by urological examination, sexual function, testicular ultrasound, hormones, sperm analysis, genetic analysis, clinical features and treatment. The control group included 25 age-matched healthy males. SLE patients had a lower median penis length and circumference [8 (7.5-10) vs. 10 (8-13) cm, p = 0.0001; 8 (7-10) vs. 10 (7-11) cm, p = 0.001; respectively], lower median testicular volume by right and left Prader [15 (10-25) vs. 20 (12-25) ml, p = 0.003; 15 (10-25) vs. 20 (12-25) ml, p = 0.006; respectively], higher median of follicle-stimulating hormone [5.8 (2.1-25) vs. 3.3 (1.9-9) IU/l, p = 0.002] and lower morning total testosterone levels (28% vs. 0%, p = 0.009) compared with controls. In spite of that, erectile dysfunction was not observed in patients or controls. Analyses of lupus patients revealed that the median penis circumference was lower in patients with disease onset before first ejaculation compared with those with disease onset after first ejaculation [7.8 (7-10) vs. 9.0 (7.5-10) cm, p = 0.026]. No differences were observed in the median penile anthropometry regarding sexual dysfunction (p = 0.610), lower morning total testosterone levels (p = 0.662), oligo/azoospermia (p = 0.705), SLE Disease Activity Index >= 4 (p = 0.562), Systemic Lupus International Collaborating Clinics/ACR Damage Index >= 1 (p = 0.478), prednisone cumulative dose (p = 0.789) and intravenous cyclophosphamide therapy (p = 0.754). Klinefelters syndrome (46XY/47XXY) was diagnosed in one (4%) SLE patient with decreased penile size whereas Y-chromosomal microdeletions was absent in all of them. In conclusion, we have identified reduced penile dimensions in SLE patients with no deleterious effect in erectile function. Disease onset before first ejaculation seems to affect penis development in pre-pubertal lupus. Lupus (2011) 20, 512-518.

A new FOXL2 gene mutation in a woman with premature ovarian failure and sporadic blepharophimosis-ptosis-epicanthus inversus syndrome

Objective: To describe a new FOXL2 gene mutation in a woman with sporadic blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and hypergonadotropic hypogonadism. Design: Case report. Setting: University medical center. Patient(s): A 28-year-old woman. Intervention(s): Clinical evaluation, hormone assays, gene mutation research. Main Outcome Measure(s): FOXL2 gene mutation. Result(s): The patient with hypergonadotropic hypogonadism was diagnosed with BPES due to a new FOXL2 gene mutation. Conclusion(s): Blepharophimosis-ptosis-epicanthus inversus syndrome is a rare disorder associated with premature ovarian failure (POF). The syndrome is an autosomal dominant trait that causes eyelid malformations and POF in affected women. Mutations in FOXL2 gene, located in chromosome 3, are related to the development of BPES with POF (BPES type I) or without POF (BPES type II). This report demonstrates a previously undescribed de novo mutation in the FOXL2 gene-a thymidine deletion, c. 627delT (g. 864delT)-in a woman with a sporadic case of BPES and POF. This mutation leads to truncated protein production that is related to a BPES type I phenotype. This report shows the importance of family history and genetic analysis in the evaluation of patients with POF and corroborates the relationship between mutations on the FOXL2 gene and ovarian insufficiency. (Fertil Steril (R) 2010; 93: 1006.e3-e6. (C) 2010 by American Society for Reproductive Medicine.)

IRF8 Mutations and Human Dendritic-Cell Immunodeficiency

BACKGROUND The genetic analysis of human primary immunodeficiencies has defined the contribution of specific cell populations and molecular pathways in the host defense against infection. Disseminated infection caused by bacille Calmette-Guerin (BCG) vaccines is an early manifestation of primary immunodeficiencies, such as severe combined immunodeficiency. In many affected persons, the cause of disseminated BCG disease is unexplained. METHODS We evaluated an infant presenting with features of severe immunodeficiency, including early-onset disseminated BCG disease, who required hematopoietic stem-cell transplantation. We also studied two otherwise healthy subjects with a history of disseminated but curable BCG disease in childhood. We characterized the monocyte and dendritic-cell compartments in these three subjects and sequenced candidate genes in which mutations could plausibly confer susceptibility to BCG disease. RESULTS We detected two distinct disease-causing mutations affecting interferon regulatory factor 8 (IRF8). Both K108E and T80A mutations impair IRF8 transcriptional activity by disrupting the interaction between IRF8 and DNA. The K108E variant was associated with an autosomal recessive severe immunodeficiency with a complete lack of circulating monocytes and dendritic cells. The T80A variant was associated with an autosomal dominant, milder immunodeficiency and a selective depletion of CD11c+CD1c+ circulating dendritic cells. CONCLUSIONS These findings define a class of human primary immunodeficiencies that affect the differentiation of mononuclear phagocytes. They also show that human IRF8 is critical for the development of monocytes and dendritic cells and for antimycobacterial immunity. (Funded by the Medical Research Council and others.)

APOE polymorphism is associated with lipid profile, but not with arterial stiffness in the general population

Background: Cardiovascular diseases (CVD) are the main cause of death and disability in developed countries. In most cases, the progress of CVD is influenced by environmental factors and multifactorial inheritance. The purpose of this study was to investigate the association between APOE genotypes, cardiovascular risk factors, and a noninvasive measure of arterial stiffness in the Brazilian population. Methods: A total of 1493 urban Brazilian individuals were randomly selected from the general population of the Vitoria City Metropolitan area. Genetic analysis of the APOE polymorphism was conducted by PCR-RFLP and pulse wave velocity analyzed with a noninvasive automatic device. Results: Age, gender, body mass index, triglycerides, creatinine, uric acid, blood glucose, blood pressure phenotypes were no different between epsilon 2, epsilon 3 and epsilon 4 alleles. The epsilon 4 allele was associated with higher total-cholesterol (p < 0.001), LDL-C (p < 0.001), total-cholesterol/HDL-C ratio (p < 0.001), LDL/HDL-C ratio (p < 0.001), lower HDL-C values (p < 0.001) and higher risk to obesity (OR = 1.358, 95% CI = 1.019-1.811) and hyperuricemia (OR = 1.748, 95% CI = 1.170-2.611). Nevertheless, pulse wave velocity (p = 0.66) measures were no different between genotypes. The significant association between APOE genotypes and lipid levels persisted after a 5-year follow-up interval, but no interaction between time and genotype was observed for lipids longitudinal behavior. Conclusion: The epsilon 4 allele of the APOE gene is associated with a worse lipid profile in the Brazilian urban population. In our relatively young sample, the observed effect of APOE genotype on lipid levels was not translated into significant effects in arterial wall stiffness.

The ubiquitin-proteasome system in Strongyloididae. Biochemical evidence for developmentally regulated proteolysis in Strongyloides venezuelensis

Nematode parasites from the genus Strongyloides spp. are important pathogens of the intestinal mucosa of animals and humans. Their complex life cycles involve alternating developmental adaptations between larvae stages and the adult parthenogenetic female. Here, we report, primarily through homology-based searching, the existence of the major components of the ubiquitin-proteasome system in this genus, using the available EST data from S. ratti, S. stercoralis, and Parastrongyloides trichosuri. In this study, S. venezuelensis was used as our model organism for detection of proteasome activity and ubiquitinated substrates in cytosolic preparations from the L3 larvae and the adult female. Marked differences in proteasome capabilities were found when these two stages were compared. A preference for degradation of chymotryptic synthetic peptides was found in both stages with the adult exhibiting a higher rate of hydrolysis compared to the larvae. Due to the high evolutionary conservation of proteasome alpha subunits, an anti-human proteasome antibody was able to recognize proteasome subunits in these preparations by Western blotting, supporting the proposal that the activity of the ubiqutin-proteasome system is developmentally regulated in this nematode.

3q27 Aberrations in a Childhood Ovary Teratoma With Associated Malignant Germ Cell Component

Cytogenetic Studies of childhood ovary tumors have been poorly described. in the present article, the cytogenetic findings of an ovarian teratoma with malignant germ cell (yolk-sac) component occurring in an 8-year-old female are detailed. GTG-banding showed a karyotype of 46,XX, t(3;20)(q27;q13.3) [4]/46,XX, del3q27 [3]/46,XX [30]. Previous Studies have demonstrated common sites of loss of heterozygosity at 3q27-q28 region in different types of cancer, suggesting the presence of tumor Suppressor genes within this region. Pediatr Blood Cancer 2009;52:398-401. (C) 2008 Wiley-Liss, Inc.

An INDEL polymorphism at the X-STR GATA172D05 flanking region

A new polymorphic INDEL was detected at the X-STR GATA172D05 flanking region, which corresponds to an 18-bp deletion, 141 bp upstream the TAGA repeat motif. This INDEL was found to be polymorphic in different population samples from Native Americans, Africans, and Europeans as well as in an admixed population from the Amazonia (Bel,m). Gene diversities varied between 37.5% in Native Americans and 49.9% in Africans. Comparison between human and chimpanzee sequences showed that the ancestral state corresponds to the presence of two copies of 18 bp, detected in both species; and the mutated allele has lost one of these two copies. The simultaneous analysis of the short tandem repeat (STR) and INDEL variation showed an association between the INDEL ancestral allele with the shorter STR alleles. High diversities were found in all population groups when combining the information provided by the INDEL and STR variation. Gene diversities varied between 76.7% in Native Americans and 80.6% in both Portugal and Bel,m.

Allelic status of 1p and 19q in oligodendrogliomas and glioblastomas: multiplex ligation-dependent probe amplification versus loss of heterozygosity

Identification of the 1p/19q allelic status in gliomas, primarily those with a major oligodendroglial component, has become an excellent molecular complement to tumor histology in order to identify those cases sensitive to chemotherapy. In addition to loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), or comparative genomic hybridization (CGH), multiplex ligation-dependent probe amplification (MLPA) has been shown to be an alternative methodology to identify deletions of those chromosome arms. We used MLPA to explore the 1p and 19q glioblastomas, and a series of 76 gliomas: 41 tumors with a major oligodendroglial component, 34 glioblastomas, and one low-grade astrocytoma. We compared the MLPA findings of the oligodendroglial cases with those previously obtained using LOH in the same samples. Thirty-eight of 41 oligodendrogliomas displayed identical findings by both LOH and MLPA, and losses at either 1p and/or 19q were identified in 12 of 35 (34%) astrocytic tumors. These findings agree with data previously reported comparing MLPA versus FISH or CGH in gliomas and suggest that MLPA can be used in the identification 1p/19q allelic deletions on these brain neoplams. (c) 2009 Elsevier Inc. All rights reserved. reserved.

Transferability and characterization of nine microsatellite markers for the tropical tree species Tabebuia roseo-alba

Microsatellite loci that were previously developed in the tropical tree Tabebuia aurea were used for the genetic analysis of Tabebuia roseo-alba populations. Nine of 10 simple sequence repeat markers were amplified, and the polymorphism was assessed in 58 individuals sampled from two stands in southeastern Brazil. All loci were polymorphic with Mendelian inheritance. The allele numbers were high, ranging from 5 to 13 in population I and 3 to 7 in population II, with means of 8.9 and 5.5, respectively. We conclude that these markers can be efficiently used for parentage and gene-flow studies.

Drosophila melanogaster lipins are tissue-regulated and developmentally regulated and present specific subcellular distributions

Lipins constitute a novel family of Mg2+-dependent phosphatidate phosphatases that catalyze the dephosphorylation of phosphatidic acid to yield diacylglycerol, an important intermediate in lipid metabolism and cell signaling. Whereas a single lipin is detected in less complex organisms, in mammals there are distinct lipin isoforms and paralogs that are differentially expressed among tissues. Compatible with organism tissue complexity, we show that the single Drosophila Lpin1 ortholog (CG8709, here named DmLpin) expresses at least three isoforms (DmLpinA, DmLpinK and DmLpinJ) in a temporal and spatially regulated manner. The highest levels of lipin in the fat body, where DmLpinA and DmLpinK are expressed, correlate with the highest levels of triacylglycerol (TAG) measured in this tissue. DmLpinK is the most abundant isoform in the central nervous system, where TAG levels are significantly lower than in the fat body. In the testis, where TAG levels are even lower, DmLpinJ is the predominant isoform. Together, these data suggest that DmLpinA might be the isoform that is mainly involved in TAG production, and that DmLpinK and DmLpinJ could perform other cellular functions. In addition, we demonstrate by immunofluorescence that lipins are most strongly labeled in the perinuclear region of the fat body and ventral ganglion cells. In visceral muscles of the larval midgut and adult testis, lipins present a sarcomeric distribution. In the ovary chamber, the lipin signal is concentrated in the internal rim of the ring canal. These specific subcellular localizations of the Drosophila lipins provide the basis for future investigations on putative novel cellular functions of this protein family.

A Combined Regenerative Approach for the Treatment of Aggressive Periodontitis: Long-term Follow-up of a Familial Case

This article reports the longitudinal follow-up of a familial case of aggressive periodontitis treated by a combined regenerative approach that consisted of root conditioning, bone grafting, and membrane positioning. Treatment resulted in attachment level gain, reduction of probing depth, absence of bleeding on probing, and complete bone filling of the defect. The short-term results obtained after surgery were maintained after 6 years, suggesting that the combined regenerative approach is able to completely arrest the disease with long-term stability. (Int J Periodontics Restorative Dent 2009; 29: 69-79.)

PODOCARPUS SP.PL. REFUGIA IN BRAZIL`S ATLANTIC FOREST: ANALYSING THE PAST TO IMPROVE FUTURE PROTECTION

The Atlantic rainforest has the second highest biodiversity in Brazil. It has been shrinking rapidly in area as a result of intensive deforestation, and only 7% of the original cover now remains, as isolated patches or in ecological reserves. In order to obtain new information on the distribution of the Atlantic rainforest during the Quaternary, we examined herbarium data to locate relevant populations and extracted DNA from fresh leaves from 26 populations. The present-day distribution of endemic Podocarpus populations shows that they are widely dispersed across eastern Brazil, and that the expansion of Podocarpus recorded in single Amazonian pollen records may have originated from either western or eastern populations. Genetic analysis enabled us to determine the boundaries of their regional expansion: northern and central populations of P. sellowii appeared between 5 degrees and 15 degrees S some 16,000 years ago; populations of P lambertii or sellowii have appeared between 15 degrees and 23 degrees S at different times since the last glaciation at least; and P lambertii appeared between 23 degrees and 30 degrees S during the recent expansion of Araucaria forests. The combination of botanical, pollen, and molecular analyses proved to be a rapid means of inferring distribution boundaries for sparse populations and their regional evolution within tropical ecosystems. Today the rainforest refugia we identified have become hotspots that are crucial to the survival of the Atlantic forest under unfavourable climatic conditions and, as such, offer the only possible opportunity for this type of forest to expand in the event of future climate change.