The role of halogen substituents and substrate pKa in defining the substrate specificity of 2,6-dichlorohydroquinone 1,2-dioxygenase (PcpA).

2,6-Dichlorohydroquinone 1,2-dioxygenase (PcpA) is a non-heme Fe(II) enzyme that is specific for ortho-dihalohydroquinones. Here we deconvolute the role of halogen polarizability vs. substrate pKa in defining this specificity, and show how substrate binding compares to the structurally homologous catechol extradiol dioxygenases. The substrates 2,6-dichloro- and 2,6-dibromohydroquinone (polarizable halogens, pKa1 = 7.3), 2,6-difluorohydroquinone (nonpolarizable halogens, pKa1 = 7.5), and 2-chloro-6-methylhydroquinone (polarizable halogen, pKa1 = 9.0) were examined through spectrophotometric titrations and steady-state kinetics. The results show that binding of the substrates to the enzyme decreased [Formula: see text] by about 0.5, except for 2,6-difluorohydroquinone, which showed no change. Additionally, the Kd values of 2,6-dichloro- and 2,6-dibromohydroquinone are about equal to their respective [Formula: see text]. For comparison, with catechol 2,3-dioxygenase (XylE), the substrates 4-methyl- and 3-bromocatechol are bound to the enzyme exclusively in the monoanion form over a wide pH range, indicating a [Formula: see text] of at least - 2.9 and - 1.2, respectively. The steady-state kinetic studies showed that 2,6-difluorohydroquinone is a poor substrate, with [Formula: see text] approximately 40-fold lower and [Formula: see text] 20-fold higher than 2,6-dichlorohydroquinone, despite its similar pKa1. Likewise, the pH dependence of [Formula: see text] for 2-chloro-6-methylhydroquinone is nearly identical to that of 2,6-dichlorohydroquinone, despite its very different pKa1. These results show that (1) it is clearly the halogen polarizability and not the lower substrate pKa that determines the substrate specificity of PcpA, and (2) that PcpA, unlike the catechol extradiol dioxygenases, lacks an active site base that assists with substrate deprotonation, highlighting a key functional difference in what are otherwise similar active sites that defines their different reactivity.

Non-redundant roles for the human mRNA decapping cofactor paralogs DCP1a and DCP1b.

Eukaryotic gene expression is regulated at the transcriptional and post-transcriptional levels, with disruption of regulation contributing significantly to human diseases. The 5' m7G mRNA cap is a central node in post-transcriptional regulation, participating in both mRNA stabilization and translation efficiency. In mammals, DCP1a and DCP1b are paralogous cofactor proteins of the mRNA cap hydrolase DCP2. As lower eukaryotes have a single DCP1 cofactor, the functional advantages gained by this evolutionary divergence remain unclear. We report the first functional dissection of DCP1a and DCP1b, demonstrating that they are non-redundant cofactors of DCP2 with unique roles in decapping complex integrity and specificity. DCP1a is essential for decapping complex assembly and interactions between the decapping complex and mRNA cap-binding proteins. DCP1b is essential for decapping complex interactions with protein degradation and translational machinery. DCP1a and DCP1b impact the turnover of distinct mRNAs. The observation that different ontological groups of mRNA molecules are regulated by DCP1a and DCP1b, along with their non-redundant roles in decapping complex integrity, provides the first evidence that these paralogs have qualitatively distinct functions.

Shear-induced orientation of gyroid PS-b-P4VP(PDP) supramolecules.

The phase behavior of block copolymer based supramolecular complexes polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) and amphiphilic pentadecylphenol (PDP) molecules resembles the phase behavior of conventional block copolymers. Several PS-b-P4VP(PDP) complexes are found to self-assemble into gyroid nanostructures. Typically, the grains are randomly oriented with a maximal size of several micrometers. Here, the orientation of a gyroid PS-b-P4VP(PDP) complex upon shearing is reported. It is found that the (111) gyroid lattice direction orients parallel to the shear direction after only several seconds of large amplitude oscillatory shearing. Oriented gyroid complexes can be used as templates for the preparation of metal nanofoams with improved ordering with potentially superior properties.

Reproductive and Obstetric Outcomes after Fertility-Sparing Treatments for Cervical Cancer: Current Approach and Future Directions.

Cervical cancer is one of the leading causes of cancer-related death in women of reproductive age. The established fertility-sparing approaches for the management of early-stage cervical cancer for women who plan pregnancy are associated with a decline in fecundity and an increased risk of pregnancy complications. This article aims to offer an overview of fertility-sparing approaches and the management of potential subfertility and pregnancy complications after these treatments. An extensive search for the available data about infertility and cervical cancer, fertility-sparing techniques in patients with cervical cancer, fertility treatment, obstetrical complications, and pregnancy outcomes in cervical cancer patients was completed. Fertility-preserving procedures such as loop electrosurgical excision procedure (LEEP), cold-knife conization, and trachelectomy in women diagnosed with cervical cancer can be considered as safe and effective treatments that preserve reproductive potential. Current fertility-preserving procedures, based on the balance of the oncological characteristics of patients as well as their desire for reproduction, allow one to obtain acceptable reproductive and obstetric outcomes in women treated for cervical cancer. Nevertheless, careful monitoring of pregnancies obtained after fertility-preserving procedures is recommended, since this cohort of patients should be considered at higher risk compared with a healthy population.

Nanoporous network channels from self-assembled triblock copolymer supramolecules.

Supramolecular complexes of a poly(tert-butoxystyrene)-block-polystyrene-block-poly(4-vinylpyridine) triblock copolymers and less than stoichiometric amounts of pentadecylphenol (PDP) are shown to self-assemble into a core-shell gyroid morphology with the core channels formed by the hydrogen-bonded P4VP(PDP)complexes. After structure formation, PDP was removed using a simple washing procedure, resulting in well-ordered nanoporous films that were used as templates for nickel plating.

[Arterial hypertension and salt intake]. / Arterijska hipertenzija i kuhinjska sol.

More than 25% of adult population worldwide and according to the EHUH study 37% of the adult population of Croatia have hypertension. In the last decades, a dramatic increase has been recorded in the prevalence of hypertension, and it is predicted that this trend will lead to an even higher prevalence in the near future. This could primarily be explained by strong influence of environmental factors. Many epidemiological and interventional studies have proved that high salt intake is one of the most important risk factors. High salt intake increases total peripheral vascular resistance, induces oxidative stress and inflammation, thus accelerating the atherosclerotic process. Independently of the effects on blood pressure, salt intake promotes left ventricular hypertrophy and microalbuminuria and increases the risk of stroke. Interventional studies have shown that salt intake reduction is associated with lower blood pressure and lower cardiovascular morbidity and mortality. Reducing salt intake in daily meals should be the main measure in primary prevention of cardiovascular and renal diseases, and it should be repeatedly emphasized not only to hypertensive patients, but also to the population at large.

Clinical and ultrasonographic parameters in assessment of labor induction success in nulliparous women.

Purpose: Evaluation of simplified Bishop score and ultrasound cervicometry in the assessment of labor induction success in nulliparous women.Methods: Prospective cohort study included 146 nulliparous women with singleton pregnancy and indications for labor induction. Prior to labor induction, cervicometry and Bishop score were determined. Upon delivery, patients were classified as those delivered vaginally and by cesarean section (CS) after unsuccessful labor induction.Results: Bishop score >5 was found in 47.95% of vaginally delivered women and 12.33% of patients delivered by CS (p < .01). Cervicometry had appropriate findings in 34.2% of vaginally delivered women and 75.3% of those delivered by CS (p < .01). Bishop score (>5 versus ≤5) had lower sensitivity (52.05%) and specificity (12.33%) than cervicometry (good versus unfavorable findings) (sensitivity 65.75%, specificity 75.34%) for prediction of labor induction success. If Bishop score was ≤5, cervicometry had 50.0% sensitivity and 78.13% specificity, while if Bishop score was >5, 82.86% sensitivity and 55.56% specificity. Obtained model for predicting labor induction outcome in nulliparous women based on their clinical and ultrasonographical characteristics identified the Bishop score as the most important predictor.Conclusions: Study confirmed the usefulness of simplified Bishop score and ultrasound cervicometry in the assessment of labor induction success in nulliparous women.

Human external ophthalmomyiasis caused by Lucilia sericata Meigen (Diptera: Calliphoridae)--a green bottle fly.

Ophthalmomyiasis externa is the result of infestation of the conjunctiva by the larval form or maggots of flies from the order Diptera. If not recognized and managed appropriately, it can be complicated by the potentially fatal condition ophthalmomyiasis interna. Ophthalmomyiasis externa is mainly caused by the sheep bot fly (Oestrus ovis). We present the first case, to our knowledge, of ophthalmomyiasis externa in an elderly woman from Belgrade caused by Lucilia sericata Meigen--a green bottle fly.

Gyroid nickel nanostructures from diblock copolymer supramolecules.

Nanoporous metal foams possess a unique combination of properties - they are catalytically active, thermally and electrically conductive, and furthermore, have high porosity, high surface-to-volume and strength-to-weight ratio. Unfortunately, common approaches for preparation of metallic nanostructures render materials with highly disordered architecture, which might have an adverse effect on their mechanical properties. Block copolymers have the ability to self-assemble into ordered nanostructures and can be applied as templates for the preparation of well-ordered metal nanofoams. Here we describe the application of a block copolymer-based supramolecular complex - polystyrene-block-poly(4-vinylpyridine)(pentadecylphenol) PS-b-P4VP(PDP) - as a precursor for well-ordered nickel nanofoam. The supramolecular complexes exhibit a phase behavior similar to conventional block copolymers and can self-assemble into the bicontinuous gyroid morphology with two PS networks placed in a P4VP(PDP) matrix. PDP can be dissolved in ethanol leading to the formation of a porous structure that can be backfilled with metal. Using electroless plating technique, nickel can be inserted into the template's channels. Finally, the remaining polymer can be removed via pyrolysis from the polymer/inorganic nanohybrid resulting in nanoporous nickel foam with inverse gyroid morphology.

Hierarchical self-assembly of two-length-scale multiblock copolymers.

The self-assembly in diblock copolymer-based supramolecules, obtained by hydrogen bonding short side chains to one of the blocks, as well as in two-length-scale linear terpolymers results in hierarchical structure formation. The orientation of the different domains, e.g. layers in the case of a lamellar-in-lamellar structure, is determined by the molecular architecture, graft-like versus linear, and the relative magnitude of the interactions involved. In both cases parallel and perpendicular arrangements have been observed. The comb-shaped supramolecules approach is ideally suited for the preparation of nanoporous structures. A bicontinuous morphology with the supramolecular comb block forming the channels was finally achieved by extending the original approach to suitable triblock copolymer-based supramolecules.

Supramolecular route to well-ordered metal nanofoams.

Metal nanofoams with a porosity above 50% v/v have recently attracted great interest in materials science due to their interesting properties. We demonstrate a new straightforward route to prepare such nanofoams using diblock copolymer-based PS-block-P4VP(PDP) supramolecules that self-assemble into a bicontinuous gyroid morphology, consisting of PS network channels in a P4VP(PDP) matrix. After dissolving the PDP, the P4VP collapses onto the PS struts and a free-standing bicontinuous gyroid template of 50-100 µm thickness and interconnected, uniformly sized pores is formed. The hydrophilic P4VP corona facilitates the penetration of water-based plating reagents into the porous template and enables a successful metal deposition. After plating, the polymer is simply degraded by heating, resulting in a well-ordered inverse gyroid nickel foam. Essential to this approach is the removal of only one part of the matrix (i.e., PDP). Therefore, the template accounts for 50% v/v or more. The porosity characteristics (amount, size of pores) can be tuned by selecting the appropriate copolymer and by adjusting the amount of PDP.