Muraymycins,novel peptidoglycan biosynthesis inhibitors: semisynthesis and SAR of their derivatives

Sixteen muraymycin derivatives 2-17 were synthesized based on selective reactions of the primary and secondary amino groups of muraymycin C1 (1) with isocyanates and aldehydes. Disubstituted derivatives 3-9 demonstrated no activity against either MraY or MurG at 相似文献   

Fgf8-related secondary organizers exert different polarizing planar instructions along the mouse anterior neural tube

Early brain patterning depends on proper arrangement of positional information. This information is given by gradients of secreted signaling molecules (morphogens) detected by individual cells within the responding tissue, leading to specific fate decisions. Here we report that the morphogen FGF8 exerts initially a differential signal activity along the E9.5 mouse neural tube. We demonstrate that this polarizing activity codes by RAS-regulated ERK1/2 signaling and depends on the topographical location of the secondary organizers: the isthmic organizer (IsO) and the anterior neural ridge (anr) but not on zona limitans intrathalamica (zli). Our results suggest that Sprouty2, a negative modulator of RAS/ERK pathway, is important for regulating Fgf8 morphogenetic signal activity by controlling Fgf8-induced signaling pathways and positional information during early brain development.     

Precise Spatial and Temporal Control of Oxygen within In Vitro Brain Slices via Microfluidic Gas Channels

The acute brain slice preparation is an excellent model for studying the details of how neurons and neuronal tissue respond to a variety of different physiological conditions. But open slice chambers ideal for electrophysiological and imaging access have not allowed the precise spatiotemporal control of oxygen in a way that might realistically model stroke conditions. To address this problem, we have developed a microfluidic add-on to a commercially available perfusion chamber that diffuses oxygen throughout a thin membrane and directly to the brain slice. A microchannel enables rapid and efficient control of oxygen and can be modified to allow different regions of the slice to experience different oxygen conditions. Using this novel device, we show that we can obtain a stable and homogeneous oxygen environment throughout the brain slice and rapidly alter the oxygen tension in a hippocampal slice. We also show that we can impose different oxygen tensions on different regions of the slice preparation and measure two independent responses, which is not easily obtainable with current techniques.     

From Desert to Rainforest: Phenotypic Variation in Functionally Important Traits of Bushy-Tailed Woodrats (Neotoma cinerea) Across Two Climatic Extremes

Changes in body size inversely related to ambient temperatures have been described in woodrats (Neotoma) over time scales ranging from decades to millennia. However, climate-mediated variation in other traits has not been evaluated, and the effects of precipitation have been overlooked. We assessed variation in skull morphology among bushy-tailed woodrats (Neotoma cinerea) over two sampling transects spanning coastal rainforest and interior desert environments to determine whether skull morphology varied with climate. We also tested whether previously described size-temperature relationships could be generalized to our study populations. In both transects, linear measurements of functionally significant traits differed between coastal and interior populations. Geometric morphometric analyses of shape confirmed some of those differences and revealed additional patterns of skull variation. Variation in some linear measurements, including body size, was predicted by climate. However, body and skull size, as well as measurements of skull components, displayed varying responses. Although longitudinal patterns of body size variation supported Bergmann’s rule, skull size variation was only weakly associated with climate. The strongest phenotypic responses to climate were those of auditory, dental, and palatal skull traits. Altogether, our findings suggest that geographic variation in temperature and precipitation mediated selective heterogeneity and plasticity in skull traits associated with food processing and sensory organs in N. cinerea. This was consistent with our expectation of resource-dependent phenotypic variation among populations in environments with highly contrasting climatic regimes.     

Matrix‐assisted peptide synthesis on nanoparticles

We report a new method for multistep peptide synthesis on polymeric nanoparticles of differing sizes. Polymeric nanoparticles were functionalized via their temporary embedment into a magnetic inorganic matrix that allows multistep peptide synthesis. The matrix is removed at the end of the process for obtaining nanoparticles functionalized with peptides. The matrix‐assisted synthesis on nanoparticles was proved by generating various biologically relevant peptides. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.     

Design,synthesis, and evaluation of gadolinium cationic lipids as tools for biodistribution studies of gene delivery complexes

Gadolinium-chelating cationic lipids have been synthesized to obtain lipoplexes with MRI contrast properties. These compounds were designed to follow the biodistribution of synthetic DNA for gene delivery by nuclear magnetic resonance imaging. The lipid MCO-I-68 was synthesized, and chelate complexes with gadolinium were formed and characterized in terms of physicochemical and DNA binding properties. The transfection activity of MCO-I-68-Gd/DNA complexes was assayed in vitro on NIH 3T3. Different formulations of the product were tested. When up to 5% of the gadolinium lipid complexes were co-formulated with the cationic lipid RPR120535 used as a reference, the transfection levels were maintained as compared to RPR120535 alone. To date, only a liposomal formulation of a gadolinium-cationic lipid chelate without DNA had been observed using magnetic resonance imaging. In vivo intratumoral administration of MCO-I-68-Gd/DNA lipoplexes to tumor model led to an important increase of the NMR signal. It was demonstrated that the new complexes also acted as transfection carriers when they were formulated from liposomes.     

Role of hydrophobic interactions in collagen fibril formation: Effect of alkylureas in vitro

Alkylureas inhibit the rate of in vitro fibril formation at 10 mm range of concentrations. There is a direct correlation between the extent of inhibition and the length of the alkyl chain (degree of hydrophobicity). When the alkylureas are added during the lag phase, the extent of inhibition depends on the time, after the onset of polymerization, in which the alkylurea is added. The effect of alkylureas is reversible since after dialysis the rate of fibril formation is normal. In conditions in which the lag phase is very short or not observable, the rate of fibril formation is not affected by the alkylureas. Ethylurea inhibits the rate of fibril formation but the extent of polymerization appears to be unaffected. In the presence of alkylurea there is an increase in the activation energy. It is concluded that hydrophobic interactions are significantly involved in the stabilization of intermediates formed during the lag phase.     

Microwave assisted preparation of C1-C11 oxygen-bridged pregnanes

1,11-Epoxysteroids may be obtained by an intramolecular remote functionalization using Suarez reagent (diacetoxyiodobenzene/I₂) and irradiation with visible light. We have found that photolysis with visible light may be advantageously replaced by microwave irradiation to prepare 1,11-oxygen bridges resulting in higher yields and shorter reaction times especially in the case of sensitive substrates. Both methodologies were compared on a set of representative 11-α-hydroxypregnanes (3, 8, 10 and 11).     

Erection of Ibirhynchus gen. nov. (Acanthocephala: Polymorphidae), based on molecular and morphological data

The genus Southwellina is composed of 3 described species, i.e., S. hispida (the type species), S. dimorpha, and S. macracanthus. All 3 are endoparasites of fish-eating birds that have worldwide distributions. Morphologically, the genus is characterized by possessing a short and compact trunk, 2 fields of spines in the anterior region of the trunk (in at least 1 sex), a short cylindrical proboscis (sometimes with a swollen region armed with numerous longitudinal rows of hooks), a double-walled proboscis receptacle, and 4 tubular cement glands in males. In the current study, specimens identified as S. dimorpha were collected from Eudocimus albus (white ibis), the type host from the Gulf of Mexico. Sequences of 2 nuclear genes (small subunit [SSU] and long subunit [LSU] ribosomal DNA) and 1 mitochondrial gene (cytochrome c oxidase subunit 1 [cox 1]) of S. dimorpha and S. hispida were obtained and used to reconstruct the phylogenetic relationships of both species with respect to published sequences of 11 species representing 6 genera of Polymorphidae. Maximum parsimony (MP) and maximum likelihood (ML) analyses of the concatenated data set (SSU + LSU + cox 1) were identical in depicting Southwellina as paraphyletic, indicating that the genus should be revised. The MP and ML trees identified S. hispida as a sister to Polymorphus brevis, whereas S. dimorpha was a sister to Hexaglandula corynosoma. Morphologically, S. dimorpha is distinct from H. corynosoma, which is characterized by a short trunk with 1 field of spines in the anterior part of the trunk in both genders, and males with 6 tubular cement glands. The genetic divergence estimated from a concatenated data set between 2 isolates of S. hispida and S. dimorpha ranged from 10.7 to 11.0%. This range of genetic divergence is similar to that found among other genera of Polymorphidae, which extends from 6.0 to 12.0%. Southwellina dimorpha differs from S. hispida in the shape of the proboscis and the presence of 1 field of spines (S. dimorpha) versus 2 fields (S. hispida) on the anterior region of the trunk in females. Based on the phylogenetic position of S. dimorpha within Polymorphidae, coupled with levels of genetic divergence and, more importantly, the morphological and ecological (host specificity) differences, we propose the erection of a new genus to accommodate S. dimorpha.