Many ways to make darker flies: Intra- and interspecific variation in Drosophila body pigmentation components.

Body pigmentation is an evolutionarily diversified and ecologically relevant trait with substantial variation within and between species, and important roles in animal survival and reproduction. Insect pigmentation, in particular, provides some of the most compelling examples of adaptive evolution, including its ecological significance and genetic bases. Pigmentation includes multiple aspects of color and color pattern that may vary more or less independently, and can be under different selective pressures. We decompose Drosophila thorax and abdominal pigmentation, a valuable eco-evo-devo model, into distinct measurable traits related to color and color pattern. We investigate intra- and interspecific variation for those traits and assess its different sources. For each body part, we measured overall darkness, as well as four other pigmentation properties distinguishing between background color and color of the darker pattern elements that decorate each body part. By focusing on two standard D. melanogaster laboratory populations, we show that pigmentation components vary and covary in distinct manners depending on sex, genetic background, and temperature during development. Studying three natural populations of D. melanogaster along a latitudinal cline and five other Drosophila species, we then show that evolution of lighter or darker bodies can be achieved by changing distinct component traits. Our results paint a much more complex picture of body pigmentation variation than previous studies could uncover, including patterns of sexual dimorphism, thermal plasticity, and interspecific diversity. These findings underscore the value of detailed quantitative phenotyping and analysis of different sources of variation for a better understanding of phenotypic variation and diversification, and the ecological pressures and genetic mechanisms underlying them.

Additive and non-additive effects of day and night temperatures on thermally plastic traits in a model for adaptive seasonal plasticity.

Developmental plasticity can match organismal phenotypes to ecological conditions, helping populations to deal with the environmental heterogeneity of alternating seasons. In contrast to natural situations, experimental studies of plasticity often use environmental conditions that are held constant during development. To explore potential interactions between day and night temperatures, we tested effects of circadian temperature fluctuations on thermally plastic traits in a seasonally plastic butterfly, Bicyclus anynana. Comparing phenotypes for four treatments corresponding to a full-factorial analysis of cooler and warmer temperatures, we found evidence of significant interaction effects between day and night temperatures. We then focused on comparing phenotypes between individuals reared under two types of temperature fluctuations (warmer days with cooler nights, and cooler days with warmer nights) and individuals reared under a constant temperature of the same daily mean. We found evidence of additive-like effects (for body size), and different types of dominance-like effects, with one particular period of the light cycle (for development time) or one particular extreme temperature (for eyespot size) having a larger impact on phenotype. Differences between thermally plastic traits, which together underlie alternative seasonal strategies for survival and reproduction, revealed their independent responses to temperature. This study underscores the value of studying how organisms integrate complex environmental information toward a complete understanding of natural phenotypic variation and of the impact of environmental change thereon.

Hypoalbuminemia: a price worth paying for improved dialytic removal of middle-molecular-weight uremic toxins?

Hemodiafiltration (HDF) increases the removal of middle-molecular-weight uremic toxins and may improve outcomes in patients with end-stage kidney disease (ESKD), but it requires complex equipment and comes with risks associated with infusion of large volumes of substitution solution. New high-flux hemodialysis membranes with improved diffusive permeability profiles do not have these limitations and offer an attractive alternative to HDF. However, both strategies are associated with increased albumin loss into the dialysate, raising concerns about the potential for decreased serum albumin concentrations that have been associated with poor outcomes in ESKD. Many factors can contribute to hypoalbuminemia in ESKD, including protein energy wasting, inflammation, volume expansion, renal loss and loss into the dialysate; of these factors, loss into the dialysate is not necessarily the most important. Furthermore, recent studies suggest that mild hypoalbuminemia per se is not an independent predictor of increased mortality in dialysis patients, but in combination with inflammation it is a poor prognostic sign. Thus, whether hypoalbuminemia predisposes to increased morbidity and mortality may depend on the presence or absence of inflammation. In this review we summarize recent findings on the role of dialysate losses in hypoalbuminemia and the importance of concomitant inflammation on outcomes in patients with ESKD. Based on these findings, we discuss whether hypoalbuminemia may be a price worth paying for increased dialytic removal of middle-molecular-weight uremic toxins.

Thrombotic microangiopathy associated with Mycoplasma pneumoniae infection.

Thrombotic microangiopathy (TMA) comprises a process of sequential endothelial damage, microvascular thrombosis, consumptive thrombocytopenia and microangiopathic haemolytic anaemia that can affect several organs, including the kidney. A 36-year-old woman was presented with a petechial rash 3 weeks after an upper respiratory tract infection. Laboratory results showed normocytic normochromic anaemia, thrombocytopenia and evidence of TMA with decreased haptoglobin, elevated serum lactate dehydrogenase and a peripheral blood smear with numerous schistocytes. Treatment included daily plasmapheresis and prednisolone, with favourable clinical evolution. Antibodies anti-ADAMTS13 were positive, establishing the diagnosis of acquired thrombotic thrombocytopenic purpura. There was also serological evidence of a recent infection by Mycoplasma pneumoniae, and therefore the preceding respiratory tract infection by this agent was the most likely trigger for the disease. Due to the high mortality rate and poor outcomes, the prompt diagnostic and treatment are crucial in this rare disease. The identification of triggers related to this pathology can allow new therapeutic targets or preventive strategies.

The higher mortality associated with low serum albumin is dependent on systemic inflammation in end-stage kidney disease.

BACKGROUND: The correlation of low serum albumin with mortality in patients with chronic kidney disease (CKD) is partly linked to its association with systemic inflammation. However, it is not clear to what extent albumin's correlation with mortality depends on concomitant systemic inflammation. Here we addressed this question in patients with CKD stage 5. METHODS: Serum albumin (S-Alb), systemic inflammation (high-sensitive C-reactive protein, hsCRP), cardiovascular disease (CVD) and nutritional status (subjective global assessment, SGA) were assessed at baseline in 822 patients: 523 incident dialysis patients, 212 prevalent hemodialysis (HD) and 87 prevalent peritoneal dialysis (PD) patients. Patients were divided into four groups according to hsCRP and S-Alb in each cohort: Group 1 -normal S-Alb and normal hsCRP (reference); Group 2 -low S-Alb and normal hsCRP; Group 3-normal S-Alb and high hsCRP; Group 4-low S-Alb and high hsCRP. Survival over 60 months was analyzed. RESULTS: In Cox analysis, Group 4 had an increased mortality risk (adjusted Hazard ratio (95% confidence interval): 1.62 (1.06-2.47); p = 0.02) whereas the augmented mortality risks for Groups 2 and 3 in univariate analyses were not significant after adjustments for age, gender, blood pressure, diabetes mellitus, smoking, SGA, renal function and renal replacement technique. CONCLUSIONS: Whereas mortality risk was increased in CKD stage 5 patients with low S-Alb and high CRP, it was not increased in patients with low S-Alb and normal CRP. Our observation suggests that inflammatory status should be taken into account when using S-albumin for risk assessment in CKD stage 5 patients.

Radical-mediated step-growth: Preparation of hybrid polymer monolithic columns with fine control of nanostructural and chromatographic characteristics.

The currently most successful type of porous polymer monoliths utilized in chromatography is prepared by free-radical cross-linking (co)polymerization in porogenic solvents and a single-step molding process. Though such types of materials are well-recognized in the scientific community, they suffer from their multi-scale heterogeneity originating from the nanoscale through to their microscale and ultimately limited performance on their macroscale. This is in particular true when estimating their performance under equilibrium (i.e. isocratic) elution conditions for retained compounds. In this contribution, we study a new concept in the preparation of porous monolithic hybrid materials based on polyhedral oligomeric vinylsilsesquioxanes which undergo radical mediated step-growth cross-linking with thiol-linkers. Fundamental characterization of this new entry of materials is performed via a variety of characterization approaches including infrared and Raman spectroscopies, thermogravimetric analysis, gel fraction, dry-state surface area analysis, and visualization of the capillary-scale porous structure by scanning electron microscopy. This characterization identifies that a rational choice of experimental conditions in monolith preparation leads to destined and desirable materials' properties, in particular with experimentally accessible near-ideal nanoscale network structures. With the obtained structural informations at hand, we finally evidence the monoliths' tailored chromatographic performance by isocratic elution experiments of structurally similar small molecules under reversed-phase type of chromatographic conditions. This validates the fundamental origin for an improved performance of these types of monolithic materials under solvated conditions that has its foundation established in the creation of near-ideal nanoscale networks of material. This identified ideality is manifested in an enhanced and almost retention-insensitive performance in liquid chromatographic separations of small molecules across wide ranges of retention factors over at least two orders of magnitude and wide ranges of mobile phase compositions. Such experimental observation is explained by a more homogeneous energetic distribution of partition and adsorption sites. A reference analysis of normalized plate height data at varied retention was performed and set in context with data of state-of-the-art silica- and polymer-based monoliths. This analysis clearly identifies the present materials to display performance behavior clearly located in the domain of derivatized silica-based monoliths.

P,O-Phosphinophenolate zinc(II) species: synthesis, structure and use in the ring-opening polymerization (ROP) of lactide, ε-caprolactone and trimethylene carbonate.

The P,O-type phosphinophenol proligands (1·H, 2-PPh2-4-Me-6-Me-C6H2OH; 2·H, 2-PPh2-4-Me-6-(t)Bu-C6H2OH) readily react with one equiv. of ZnEt2 to afford in high yields the corresponding Zn(II)-ethyl dimers of the type [(κ(2)-P,O)Zn-Et]2 (3 and 4) with two µ-OPh bridging oxygens connecting the two Zn(II) centers, as determined by X-ray diffraction (XRD) studies in the case of 3. Based on diffusion-ordered NMR spectroscopy (DOSY), both species 3 and 4 retain their dimeric structures in solution. The alcoholysis reaction of Zn(II) alkyls 3 and 4 with BnOH led to the high yield formation of the corresponding Zn(II) benzyloxide species [(κ(2)-P,O)Zn-OBn]2 (5 and 6), isolated in a pure form as colorless solids. The centrosymmetric and dimeric nature of Zn(II) alkoxides 5 and 6 in solution was deduced from DOSY NMR experiments and multinuclear NMR data. Though the heteroleptic species 5 is stable in solution, its analogue 6 is instable in CH2Cl2 solution at room temperature to slowly decompose to the corresponding homoleptic species 8via the transient formation of (κ(2)-P,O)2Zn2(µ-OBn)(µ­κ(1):κ(1)-P,O) (6'). Crystallization of compound 6 led to crystals of 6', as established by XRD analysis. The reaction of ZnEt2 with two equiv. of 1·H and 2·H allowed access to the corresponding homoleptic species of the type [Zn(P,O)2] (7 and 8). All gathered data are consistent with compound 7 being a dinuclear species in the solid state and in solution. Data for species 8, which bears a sterically demanding P,O-ligand, are consistent with a mononuclear species in solution. The Zn(II) alkoxide species 5 and the [Zn(P,O)2]-type compounds 7 and 8 were evaluated as initiators of the ring-opening polymerization (ROP) of lactide (LA), ε-caprolactone (ε-CL) and trimethylene carbonate (TMC). Species 5 is a well-behaved ROP initiator for the homo-, co- and ter-polymerization of all three monomers with the production of narrow disperse materials under living and immortal conditions. Though species 7 and 8 are ROP inactive on their own, they readily polymerize LA in the presence of a nucleophile such as BnOH to produce narrow disperse PLA, presumably via an activated-monomer ROP mechanism.

Evaluation of solubility and partition properties of ampicillin-based ionic liquids.

In order to overcome the problems associated with low water solubility, and consequently low bioavailability of active pharmaceutical ingredients (APIs), herein we explore a modular ionic liquid synthetic strategy for improved APIs. Ionic liquids containing L-ampicillin as active pharmaceutical ingredient anion were prepared using the methodology developed in our previous work, using organic cations selected from substituted ammonium, phosphonium, pyridinium and methylimidazolium salts, with the intent of enhancing the solubility and bioavailability of L-ampicillin forms. In order to evaluate important properties of the synthesized API-ILs, the water solubility at 25 °C and 37 °C (body temperature) as well as octanol-water partition coefficients (Kow's) and HDPC micelles partition at 25 °C were measured. Critical micelle concentrations (CMC's) in water at 25 °C and 37 °C of the pharmaceutical ionic liquids bearing cations with surfactant properties were also determined from ionic conductivity measurements.

Synthesis, characterization, and liposome partition of a novel tetracycline derivative using the ionic liquids framework.

Recently, efforts have been put on the development of new drug formulations using ionic liquid framework. In this work, two different species of abroad-spectrum polyketide antibiotic, tetracycline, are studied in terms of some important properties for antibiotics such as solubility in water and hydrophilic-hydrophobic balance. Tetracycline was used as cation, whereas docusate, a biocompatible anion, which enables the tailoring of the hydrophilicity of salts, was chosen as the anion. The developed innovative ion pair, tetracycline docusate, was characterized in terms of its thermal stability, water solubility, octanol-water, and liposome-water partition coefficients, using UV-vis spectrophotometry because of the absorbance of tetracycline around 270 nm. Egg yolk phosphatidylcholine liposomes were used as cell membrane models, and the interactions of both tetracycline hydrochloride and tetracycline docusate with the liposomes were quantified by determination of the partition coefficient using derivative spectrophotometry. A theoretical model based on simple partition drugs between two different media was used to determine the partition coefficient in liposomes.

Conceptual design of large surface area porous polymeric hybrid media based on polyhedral oligomeric silsesquioxane precursors: preparation, tailoring of porous properties, and internal surface functionalization.

We report on the preparation of hybrid, organic-inorganic porous materials derived from polyhedral oligomeric vinylsilsesquioxanes (vinylPOSS) via a single-step molding process. The monolithic, large surface area materials are studied with a particular focus on morphology and porous properties. Radical vinyl polymerization of the nanometer-sized POSS building blocks is therefore utilized via a thermally initiated route and in porogenic diluents such as tetrahydrofuran and polyethylene glycols of varying composition. Careful choice of these porogenic solvents and proper choice of initiator concentration lead to highly porous monolithic building entities which show a rigid, 3D-adhered, porous structure, macroscopically adapting the shape of a given mold. The described materials reflect Brunauer-Emmett-Teller (BET) surface areas of 700 m2/g or more and maximum tunable mesopore volumes of up to 2 cm3/g. Experimental investigations demonstrate the option to tailor nanoporosity and macroporosity in the single-step free-radical polymerization process. While studies on the influence of the used porogenic solvents reveal tuneability of pore sizes due to the unique pore formation process, tailored existence of residual vinyl groups allows facile postpolymerization modification of the highly porous, large surface area hybrid materials exploited via thiol-ene "click" chemistry. Our developed, simply realizable preparation process explores a new route to derive porous organic-inorganic hybrid adsorbents for a wide variety of applications such as extraction, separation science, and catalysis.

The role of ion fluxes in polarized cell growth and morphogenesis: the pollen tube as an experimental paradigm.

In order to cope with reproduction in a dry environment without any sort of motility, plants have developed a very specialized and unique sexual system. Of special notice, the two sperm cells that will perform the double fertilization typical of higher plants are carried by one of the fastest growing cells in nature, the pollen tube. This tube develops from the vegetative cell of the pollen grain upon germination on the female tissues. While it cannot be considered as a canonical excitable cell, pollen tubes depend for most of their fundamental functional features on a close regulation of ion dynamics, namely in terms of polarization of extracellular fluxes and formation of standing cytosolic free ion gradients, namely of calcium (Ca(2+)) and protons (H(+)). In turn, these imply that plasma membrane transporters are polarized, or polarly regulated, and that internal signaling cascades transduce this spatial information into the basic features of growth and morphogenesis needed for pollen tubes to target correctly the ovules and discharge the sperm cells. Because of the singularity of this organization, and the ease with which pollen tubes can be experimentally handled, recent years have witnessed an accumulation of data at many levels, from basic biophysical and cell biology characterization, to gene assignment and transcriptomic description of pollen development. In this review we aim to organize this information in terms of the basic biophysical features of membrane function and integrate it into conceptual testable hypotheses on how the dynamics of ion regulation may underlie fundamental properties of cell development.

Modeling segmental patterning in Drosophila: Maternal and gap genes.

We propose a new mathematical model describing the establishment of maternal and gap proteins segmental patterning along the antero-posterior axis of the Drosophila early embryo. This model is based on experimental data and, without recurring to pre-defined activation thresholds, predicts qualitatively and quantitatively the expression patterns of the maternal and gap proteins, as well as the expression patterns of proteins resulting from mRNA ectopic expression and from some loss-of-function mutations. We conclude that the gap genes segmental patterning and consequent spatial organization of the embryo is determined by three main factors: (1) the initial positioning of the maternal bicoid and torso mRNA inside the egg, and subsequent diffusion of the corresponding proteins; (2) the structure of the genetic regulatory network; (3) the role of conservation laws in the establishment of steady and non-uniform spatial distributions of non-diffusing proteins.

A simple framework to describe the regulation of gene expression in prokaryotes.

Based on the bimolecular mass action law and the derived mass conservation laws, we propose a mathematical framework in order to describe the regulation of gene expression in prokaryotes. It is shown that the derived models have all the qualitative properties of the activation and inhibition regulatory mechanisms observed in experiments. The basic construction considers genes as templates for protein production, where regulation processes result from activators or repressors connecting to DNA binding sites. All the parameters in the models have a straightforward biological meaning. After describing the general properties of the basic mechanisms of positive and negative gene regulation, we apply this framework to the self-regulation of the trp operon and to the genetic switch involved in the regulation of the lac operon. One of the consequences of this approach is the existence of conserved quantities depending on the initial conditions that tune bifurcations of fixed points. This leads naturally to a simple explanation of threshold effects as observed in some experiments.