201 research outputs found
Polymorphisms in the hypoxia-inducible factor 1 alpha gene in Mexican patients with preeclampsia: A case-control study
<p>Abstract</p> <p>Background</p> <p>Although the etiology of preeclampsia is still unclear, recent work suggests that changes in circulating angiogenic factors play a key role in its pathogenesis. In the trophoblast of women with preeclampsia, hypoxia-inducible factor 1 alpha (HIF-1α) is over-expressed, and induces the expression of non-angiogenic factors and inhibitors of trophoblast differentiation. This observation prompted the study of HIF-1α and its relation to preeclampsia. It has been described that the C1772T (P582S) and G1790A (A588T) polymorphisms of the <it>HIF1A </it>gene have significantly greater transcriptional activity, correlated with an increased expression of their proteins, than the wild-type sequence. In this work, we studied whether either or both <it>HIF1A </it>variants contribute to preeclampsia susceptibility.</p> <p>Results</p> <p>Genomic DNA was isolated from 150 preeclamptic and 105 healthy pregnant women. Exon 12 of the <it>HIF1A </it>gene was amplified by PCR, and the genotypes of <it>HIF1A </it>were determined by DNA sequencing.</p> <p>In preeclamptic women and controls, the frequencies of the T allele for C1772T were 4.3 vs. 4.8%, and the frequencies of the A allele for G1790A were 0.0 vs. 0.5%, respectively. No significant differences were found between groups.</p> <p>Conclusion</p> <p>The frequency of the C1772T and G1790A polymorphisms of the <it>HIF1A </it>gene is very low, and neither polymorphism is associated with the development of preeclampsia in the Mexican population.</p
Hypoxia-inducible factor-1α gene polymorphisms and cancer risk: a meta-analysis
<p>Abstract</p> <p>Background</p> <p>The results from the published studies on the association between <it>hypoxia-inducible factor -1α </it>(HIF-1α) polymorphisms and cancer risk are conflicting. In this meta-analysis, we aimed to investigate the association between <it>HIF-1α </it>1772 C/T and 1790 G/A polymorphisms and cancer.</p> <p>Methods</p> <p>The meta-analysis for 1772 C/T polymorphism included 4131 cancer cases and 5387 controls, and for 1790 G/A polymorphism included 2058 cancer cases and 3026 controls. Allelic and genotypic comparisons between cases and controls were evaluated. Subgroup analyses by cancer types, ethnicity, and gender were also performed. We included prostate cancer in male subgroup, and female specific cancers in female subgroup.</p> <p>Results</p> <p>For the 1772 C/T polymorphism, the analysis showed that the T allele and genotype TT were significantly associated with higher cancer risk: odds ratio (OR) = 1.29 [95% confidence interval (CI, 1.01, 1.65)], P = 0.04, P<sub>heterogeneity </sub>< 0.00001, and OR = 2.18 [95% CI (1.32, 3.62)], P = 0.003, P<sub>heterogeneity </sub>= 0.02, respectively. The effect of the genotype TT on cancer especially exists in Caucasians and female subjects: OR = 2.40 [95% CI (1.26, 4.59)], P = 0.008, P<sub>heterogeneity </sub>= 0.02, and OR = 3.60 [95% CI (1.17, 11.11)], P = 0.03, P<sub>heterogeneity </sub>= 0.02, respectively. For the 1790 G/A polymorphism, the pooled ORs for allelic frequency comparison and dominant model comparison suggested a significant association of 1790 G/A polymorphism with a decreased breast cancer risk: OR = 0.28 [95% CI (0.08, 0.90)], P = 0.03, P<sub>heterogeneity </sub>= 0.45, and OR = 0.29 [95% CI (0.09, 0.97)], P = 0.04, P<sub>heterogeneity </sub>= 0.41, respectively. The frequency of the <it>HIF-1α </it>1790 A allele was very low and only two studies were included in the breast cancer subgroup.</p> <p>Conclusions</p> <p>Our meta-analysis suggests that the <it>HIF-1α </it>1772 C/T polymorphism is significantly associated with higher cancer risk, and 1790 G/A polymorphism is significantly associated with decreased breast cancer risk. The effect of the 1772 C/T polymorphism on cancer especially exists in Caucasians and female subjects. Only female specific cancers were included in female subgroup, which indicates that the 1772 C/T polymorphism is significantly associated with an increased risk for female specific cancers. The association between the 1790 G/A polymorphism and lower breast cancer risk could be due to chance.</p
Beneficial effect of the oxygen free radical scavenger amifostine (WR-2721) on spinal cord ischemia/reperfusion injury in rabbits
<p>Abstract</p> <p>Background</p> <p>Paraplegia is the most devastating complication of thoracic or thoraco-abdominal aortic surgery. During these operations, an ischemia-reperfusion process is inevitable and the produced radical oxygen species cause severe oxidative stress for the spinal cord. In this study we examined the influence of Amifostine, a triphosphate free oxygen scavenger, on oxidative stress of spinal cord ischemia-reperfusion in rabbits.</p> <p>Methods</p> <p>Eighteen male, New Zealand white rabbits were anesthetized and spinal cord ischemia was induced by temporary occlusion of the descending thoracic aorta by a coronary artery balloon catheter, advanced through the femoral artery. The animals were randomly divided in 3 groups. Group I functioned as control. In group II the descending aorta was occluded for 30 minutes and then reperfused for 75 min. In group III, 500 mg Amifostine was infused into the distal aorta during the second half-time of ischemia period. At the end of reperfusion all animals were sacrificed and spinal cord specimens were examined for superoxide radicals by an ultra sensitive fluorescent assay.</p> <p>Results</p> <p>Superoxide radical levels ranged, in group I between 1.52 and 1.76 (1.64 ± 0.10), in group II between 1.96 and 2.50 (2.10 ± 0.23), and in group III (amifostine) between 1.21 and 1.60 (1.40 ± 0.19) (p = 0.00), showing a decrease of 43% in the Group of Amifostine. A lipid peroxidation marker measurement ranged, in group I between 0.278 and 0.305 (0.296 ± 0.013), in group II between 0.427 and 0.497 (0.463 ± 0.025), and in group III (amifostine) between 0.343 and 0.357 (0.350 ± 0.007) (p < 0.00), showing a decrease of 38% after Amifostine administration.</p> <p>Conclusion</p> <p>By direct and indirect methods of measuring the oxidative stress of spinal cord after ischemia/reperfusion, it is suggested that intra-aortic Amifostine infusion during spinal cord ischemia phase, significantly attenuated the spinal cord oxidative injury in rabbits.</p
A meta-analysis of hypoxia inducible factor 1-alpha (HIF1A) gene polymorphisms: association with cancers
Effects of Salt Stress on Three Ecologically Distinct Plantago Species
Comparative studies on the responses to salt stress of taxonomically related taxa should
help to elucidate relevant mechanisms of stress tolerance in plants. We have applied this
strategy to three Plantago species adapted to different natural habitats, P. crassifolia and P.
coronopus both halophytes and P. major, considered as salt-sensitive since it is never
found in natural saline habitats. Growth inhibition measurements in controlled salt treatments
indicated, however, that P. major is quite resistant to salt stress, although less than
its halophytic congeners. The contents of monovalent ions and specific osmolytes were
determined in plant leaves after four-week salt treatments. Salt-treated plants of the three
taxa accumulated Na+ and Cl- in response to increasing external NaCl concentrations, to a
lesser extent in P. major than in the halophytes; the latter species also showed higher ion
contents in the non-stressed plants. In the halophytes, K+ concentration decreased at moderate
salinity levels, to increase again under high salt conditions, whereas in P. major K+
contents were reduced only above 400 mM NaCl. Sorbitol contents augmented in all plants,
roughly in parallel with increasing salinity, but the relative increments and the absolute values
reached did not differ much in the three taxa. On the contrary, a strong (relative) accumulation
of proline in response to high salt concentrations (600 800 mM NaCl) was
observed in the halophytes, but not in P. major. These results indicate that the responses to
salt stress triggered specifically in the halophytes, and therefore the most relevant for tolerance
in the genus Plantago are: a higher efficiency in the transport of toxic ions to the
leaves, the capacity to use inorganic ions as osmotica, even under low salinity conditions,
and the activation, in response to very high salt concentrations, of proline accumulation and
K+ transport to the leaves of the plants.MAH was a recipient of an Erasmus Mundus pre-doctoral scholarship financed by the European Commission (Welcome Consortium). AP acknowledges the Erasmus mobility programme for funding her stay in Valencia to carry out her Master Thesis.Al Hassan, M.; Pacurar, AM.; López Gresa, MP.; Donat Torres, MDP.; Llinares Palacios, JV.; Boscaiu Neagu, MT.; Vicente Meana, Ó. (2016). Effects of Salt Stress on Three Ecologically Distinct Plantago Species. PLoS ONE. 11(8):1-21. doi:10.1371/journal.pone.0160236S12111
SIMS: A Hybrid Method for Rapid Conformational Analysis
Proteins are at the root of many biological functions, often performing complex tasks as the result of large changes in their
structure. Describing the exact details of these conformational changes, however, remains a central challenge for
computational biology due the enormous computational requirements of the problem. This has engendered the
development of a rich variety of useful methods designed to answer specific questions at different levels of spatial,
temporal, and energetic resolution. These methods fall largely into two classes: physically accurate, but computationally
demanding methods and fast, approximate methods. We introduce here a new hybrid modeling tool, the Structured
Intuitive Move Selector (SIMS), designed to bridge the divide between these two classes, while allowing the benefits of both
to be seamlessly integrated into a single framework. This is achieved by applying a modern motion planning algorithm,
borrowed from the field of robotics, in tandem with a well-established protein modeling library. SIMS can combine precise
energy calculations with approximate or specialized conformational sampling routines to produce rapid, yet accurate,
analysis of the large-scale conformational variability of protein systems. Several key advancements are shown, including the
abstract use of generically defined moves (conformational sampling methods) and an expansive probabilistic
conformational exploration. We present three example problems that SIMS is applied to and demonstrate a rapid solution
for each. These include the automatic determination of ムムactiveメメ residues for the hinge-based system Cyanovirin-N,
exploring conformational changes involving long-range coordinated motion between non-sequential residues in Ribose-
Binding Protein, and the rapid discovery of a transient conformational state of Maltose-Binding Protein, previously only
determined by Molecular Dynamics. For all cases we provide energetic validations using well-established energy fields,
demonstrating this framework as a fast and accurate tool for the analysis of a wide range of protein flexibility problems
Hypericum sp.: essential oil composition and biological activities
Phytochemical composition of Hypericum
genus has been investigated for many years. In the recent past, studies on the essential oils (EO) of this genus have been progressing and many of them have reported interesting biological activities. Variations in the EO composition of Hypericum species influenced
by seasonal variation, geographic distribution, phenological cycle and type of the organ in which EO are produced and/or accumulated have also been reported. Although many reviews attributed to the characterization
as well as biological activities of H. perforatum
crude extracts have been published, no review has been published on the EO composition and biological activities of Hypericum species until recently (Crockett
in Nat Prod Commun 5(9):1493–1506, 2010;
Bertoli et al. in Global Sci Books 5:29–47, 2011). In this article, we summarize and update information regarding the composition and biological activities of Hypericum species EO. Based on experimental work carried out in our laboratory we also mention possible biotechnology approaches envisaging EO improvement of some species of the genus.Fundação para a Ciência e a Tecnologia (FCT) - project PTDC/AGR AAM/70418/2006, SFRH/BD/
13283/2003
Rapid Sampling of Molecular Motions with Prior Information Constraints
Proteins are active, flexible machines that perform a range of different
functions. Innovative experimental approaches may now provide limited partial
information about conformational changes along motion pathways of proteins.
There is therefore a need for computational approaches that can efficiently
incorporate prior information into motion prediction schemes. In this paper, we
present PathRover, a general setup designed for the integration
of prior information into the motion planning algorithm of rapidly exploring
random trees (RRT). Each suggested motion pathway comprises a sequence of
low-energy clash-free conformations that satisfy an arbitrary number of prior
information constraints. These constraints can be derived from experimental data
or from expert intuition about the motion. The incorporation of prior
information is very straightforward and significantly narrows down the vast
search in the typically high-dimensional conformational space, leading to
dramatic reduction in running time. To allow the use of state-of-the-art energy
functions and conformational sampling, we have integrated this framework into
Rosetta, an accurate protocol for diverse types of structural modeling. The
suggested framework can serve as an effective complementary tool for molecular
dynamics, Normal Mode Analysis, and other prevalent techniques for predicting
motion in proteins. We applied our framework to three different model systems.
We show that a limited set of experimentally motivated constraints may
effectively bias the simulations toward diverse predicates in an outright
fashion, from distance constraints to enforcement of loop closure. In
particular, our analysis sheds light on mechanisms of protein domain swapping
and on the role of different residues in the motion
Current trends in cannulation and neuroprotection during surgery of the aortic arch in Europe†‡
OBJECTIVES To conduct a survey across European cardiac centres to evaluate the methods used for cerebral protection during aortic surgery involving the aortic arch. METHODS All European centres were contacted and surgeons were requested to fill out a short, comprehensive questionnaire on an internet-based platform. One-third of more than 400 contacted centres completed the survey correctly. RESULTS The most preferred site for arterial cannulation is the subclavian-axillary, both in acute and chronic presentation. The femoral artery is still frequently used in the acute condition, while the ascending aorta is a frequent second choice in the case of chronic presentation. Bilateral antegrade brain perfusion is chosen by the majority of centres (2/3 of cases), while retrograde perfusion or circulatory arrest is very seldom used and almost exclusively in acute clinical presentation. The same pumping system of the cardio pulmonary bypass is most of the time used for selective cerebral perfusion, and the perfusate temperature is usually maintained between 22 and 26°C. One-third of the centres use lower temperatures. Perfusate flow and pressure are fairly consistent among centres in the range of 10-15 ml/kg and 60 mmHg, respectively. In 60% of cases, barbiturates are added for cerebral protection, while visceral perfusion still receives little attention. Regarding cerebral monitoring, there is a general tendency to use near-infrared spectroscopy associated with bilateral radial pressure measurement. CONCLUSIONS These data represent a snapshot of the strategies used for cerebral protection during major aortic surgery in current practice, and may serve as a reference for standardization and refinement of different approache
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