Large-scale evaluation of candidate genes identifies associations between VEGF polymorphisms and bladder cancer risk

Common genetic variation could alter the risk for developing bladder cancer. We conducted a large-scale evaluation of single nucleotide polymorphisms (SNPs) in candidate genes for cancer to identify common variants that influence bladder cancer risk. An Illumina GoldenGate assay was used to genotype 1,433 SNPs within or near 386 genes in 1,086 cases and 1,033 controls in Spain. The most significant finding was in the 5′ UTR of VEGF (rs25648, p for likelihood ratio test, 2 degrees of freedom = 1 × 10⁻⁵). To further investigate the region, we analyzed 29 additional SNPs in VEGF, selected to saturate the promoter and 5′ UTR and to tag common genetic variation in this gene. Three additional SNPs in the promoter region (rs833052, rs1109324, and rs1547651) were associated with increased risk for bladder cancer: odds ratio (95% confidence interval): 2.52 (1.06–5.97), 2.74 (1.26–5.98), and 3.02 (1.36–6.63), respectively; and a polymorphism in intron 2 (rs3024994) was associated with reduced risk: 0.65 (0.46–0.91). Two of the promoter SNPs and the intron 2 SNP showed linkage disequilibrium with rs25648. Haplotype analyses revealed three blocks of linkage disequilibrium with significant associations for two blocks including the promoter and 5′ UTR (global p = 0.02 and 0.009, respectively). These findings are biologically plausible since VEGF is critical in angiogenesis, which is important for tumor growth, its elevated expression in bladder tumors correlates with tumor progression, and specific 5′ UTR haplotypes have been shown to influence promoter activity. Associations between bladder cancer risk and other genes in this report were not robust based on false discovery rate calculations. In conclusion, this large-scale evaluation of candidate cancer genes has identified common genetic variants in the regulatory regions of VEGF that could be associated with bladder cancer risk.     

犬齿窝与人类中面部骨骼的演化

犬齿窝是包括现代人类在内的许多人族成员面部骨骼的重要性状,但在分类学上的意义仍存在争议。有学者认为该性状是一个发生于基础面形的近祖性状,除了一些例外,在灭绝和现生的大猿及人属中都存在。另有学者认为,犬齿窝是仅存在于智人及其直系祖先的衍生性状,在发育上与颧齿槽突嵴有关。这种关系并非总是成立,在智人中存在着明显的差异：弧型颧齿槽突嵴和直斜型颧齿槽突嵴与犬齿窝有时共存,有时不共存。我们由此推测,犬齿窝的发生和形态与上颌窦的前部发育有关,颧齿槽突嵴的形态与鼻窦的侧面发育有关。在人类演化的过程中,犬齿窝经历了不同的变形,比如上颌沟(如南方古猿非洲种、傍人粗壮种)、上颌小窝(如傍人粗壮种)、上颌沟(如匠人)或犬齿窝缺如(如傍人埃塞俄比亚种、傍人鲍氏种、肯尼亚扁脸人、人属鲁道夫种)。犬齿窝消失的原因各类群并不相同,如中新世和早更新世人属以及中更新世人属(如人属海德堡种/人属罗得西亚种、人属尼安德特种)。人属罗得西亚种具有弱化的犬齿窝,不具备演化为智人的可能,因此被排除在智人的演化支之外。     

Disturbance calls of five migratory Characiformes species and advertisement choruses in Amazon spawning sites

Species-specific disturbance calls of five commercially-important characiform species are described, the Curimatidae commonly called branquinhas: Potamorhina latior, Potamorhina altamazonica and Psectrogaster amazonica; Prochilodontidae: jaraquí Semaprochilodus insignis and curimatã Prochilodus nigricans. All species have a two-chambered swimbladder and the sonic mechanism, present exclusively in males, utilises hypertrophied red muscles between ribs that adhere to the anterior chamber. The number of muscles is unusually plastic across species and varies from 1 to 4 pairs suggesting considerable evolution in an otherwise conservative system. Advertisement calls are produced in river confluences in the Madeira Basin during the high-water mating season (January–February). Disturbance calls and sampling allowed recognition of underwater advertisement choruses from P. latior, S. insignis and P. nigricans. The advertisement calls of the first two species have largely similar characteristics and they mate in partially overlapping areas in the Guaporé River. However, P. latior sounds have a lower dominant frequency and it prefers to call from river confluences whereas S. insignis shoals occur mostly in the main river channel adjacent to the confluence. These results help identify and differentiate underwater sounds and evaluate breeding areas during the courtship of commercially important characids likely to be affected by two hydroelectric dams.     

Evaluating the genetic structure of wild and commercial red cusk-eel (Genypterus chilensis) populations through the development of novel microsatellite markers from a reference transcriptome

Molecular Biology Reports - The red cusk-eel (Genypterus chilensis) is a native Chilean species with a high-value market, with the potential to diversify Chilean aquaculture. The objective of this...     

Consistency of females’ stridulatory behaviour during inter‐sexual interactions in spiders

In a sexual context, it is expected that females base their choice of mate on the behaviours that males perform during courtship, as such behaviours are associated with the male's mate quality. Stridulation is one form of female communication in arthropods, for example, spiders. In spiders, stridulation during sexual interactions is relatively common in some groups but mainly restricted to males. In the pholcid spider Holocnemus pluchei (Pholcidae), both sexes have stridulatory organs. The aims of the present work were to: (a) determine possible differences in the frequency of occurrence of stridulation between females during inter‐sexual interactions, (b) establish female consistency in stridulation along repeated interactions and (c) analyse if female stridulation is associated with certain male behaviours during pre‐copulatory courtship and with male size. Female H. pluchei showed highly repeatable differences in their frequency of stridulation across consecutive encounters with males (ICC = 0.64). However, only a modest level of repeatability was detected in total time females spent stridulating across trials (ICC = 0.19). Females’ mean stridulatory behaviour did not change across ten consecutive trials spread across 20 days, and their behaviour was apparently unaffected by male persistence of copulatory attempted and/or size. These results imply that the frequency of female stridulatory behaviour is a trait that is highly characteristic of each individual. Finally, our work opens the door to determine whether behavioural consistency manifests in other ecological contexts and their functional implications.     

Adrenomedullin Is a Diagnostic and Prognostic Biomarker for Acute Intracerebral Hemorrhage

Hemorrhagic stroke remains an important health challenge. Adrenomedullin (AM) is a vasoactive peptide with an important role in cardiovascular diseases, including stroke. Serum AM and nitrate–nitrite and S-nitroso compounds (NOx) levels were measured and compared between healthy volunteers (n = 50) and acute hemorrhagic stroke patients (n = 64). Blood samples were taken at admission (d0), 24 h later (d1), and after 7 days or at the time of hospital discharge (d7). Neurological severity (NIHSS) and functional prognosis (mRankin) were measured as clinical outcomes. AM levels were higher in stroke patients at all times when compared with healthy controls (p < 0.0001). A receiving operating characteristic curve analysis identified that AM levels at admission > 69.0 pg/mL had a great value as a diagnostic biomarker (area under the curve = 0.89, sensitivity = 80.0%, specificity = 100%). Furthermore, patients with a favorable outcome (NIHSS ≤ 3; mRankin ≤ 2) experienced an increase in AM levels from d0 to d1, and a decrease from d1 to d7, whereas patients with unfavorable outcome had no significant changes over time. NOx levels were lower in patients at d0 (p = 0.04) and d1 (p < 0.001) than in healthy controls. In conclusion, AM levels may constitute a new diagnostic and prognostic biomarker for this disease, and identify AM as a positive mediator for hemorrhagic stroke resolution.     

Toxic action of etoposide on mouse peritoneal macrophages and its modulation by interleukin 3

In the present work, we have studied the toxic action of etoposide on mouse peritoneal macrophages. First, we have determined the induction of DNA fragmentation by this antitumour compound. To study the possible influence of interleukin 3 on the effects of etoposide on mouse macrophages, we studied intracellular protein phosphorylation induced by interleukin 3. After incubation of the cells in the presence of interleukin 3, increased phosphorylation levels of proteins of estimated molecular weights of around 29,000, 34,000, 50,000 and 61,000 daltons were observed. We have also investigated a possible influence of interleukin 3 on DNA degradation induced by etoposide. The changes of Bax levels induced by etoposide that we have observed seemed to be modulated by this cytokine. From these results, a possible role of interleukin 3 can be suggested in the attenuation of some toxic effects produced by etoposide in mouse peritoneal macrophages. Thus, a therapeutic application of interleukin 3 on antitumour treatments in cells from the mononuclear phagocytic system might be proposed.     

Kinetic and thermodynamic characterization of the RNA-cleaving 8-17 deoxyribozyme

The 8-17 deoxyribozyme is a small DNA catalyst of significant applicative interest. We have analyzed the kinetic features of a well behaved 8-17 construct and determined the influence of several reaction conditions on such features, providing a basis for further exploration of the deoxyribozyme mechanism. The 8-17 bound its substrate with a rate constant ~10-fold lower than those typical for the annealing of short complementary oligonucleotides. The observed free energy of substrate binding indicates that an energetic penalty near to +7 kcal/mol is attributable to the deoxyribozyme core. Substrate cleavage required divalent metal ion cofactors, and the dependence of activity on the concentration of Mg²⁺, Ca²⁺ or Mn²⁺ suggests the occurrence of a single, low-specificity binding site for activating ions. The efficiency of activation correlated with the Lewis acidity of the ion cofactor, compatible with a metal-assisted deprotonation of the reactive 2′-hydroxyl group. However, alternative roles of the metal ions cannot be excluded, because those ions that are stronger Lewis acids are also capable of forming stronger interactions with ligands such as the phosphate oxygens. The apparent enthalpy of activation for the 8-17 reaction was close to the values observed for hydroxide-catalyzed and hammerhead ribozyme-catalyzed RNA cleavage.