Transfer of Dorsoventral and Terminal Information from the Ovary to the Embryo by a Common Group of Eggshell Proteins in .

The eggshell is an extracellular matrix that confers protection to the egg and also plays a role in transferring positional information from the ovary to pattern the embryo. Among the constituents of the eggshell, Nasrat, Polehole, and Closca form a group of proteins related by sequence, secreted by the oocyte, and mutually required for their incorporation into the eggshell. Besides their role in eggshell integrity, Nasrat, Polehole, and Closca are also required for embryonic terminal patterning by anchoring or stabilizing Torso-like at the eggshell.

Modulation of Human Peripheral Blood Mononuclear Cell Signaling by Medicinal Cannabinoids.

Medical marijuana is increasingly prescribed as an analgesic for a growing number of indications, amongst which terminal cancer and multiple sclerosis. However, the mechanistic aspects and properties of cannabis remain remarkably poorly characterized. In this study we aimed to investigate the immune-cell modulatory properties of medical cannabis.

Synovial fluid adipokines are associated with clinical severity in knee osteoarthritis: a cross-sectional study in female patients with joint effusion.

Background: Adipokines are related to knee osteoarthritis, but their exact role is not well known. The aim of this study was to evaluate the association between adipokines in synovial fluid and clinical severity in patients with knee osteoarthritis with joint effusion.

Methods: Cross-sectional study with systematic inclusion of female patients with symptomatic primary knee osteoarthritis with ultrasound-confirmed joint effusion.

Long-Term Estrogen Receptor Beta Agonist Treatment Modifies the Hippocampal Transcriptome in Middle-Aged Ovariectomized Rats.

Estradiol (E2) robustly activates transcription of a broad array of genes in the hippocampal formation of middle-aged ovariectomized rats via estrogen receptors (ERα, ERβ, and G protein-coupled ER). Selective ERβ agonists also influence hippocampal functions, although their downstream molecular targets and mechanisms are not known. In this study, we explored the effects of long-term treatment with ERβ agonist diarylpropionitrile (DPN, 0.

Heteromeric amino acid transporters. In search of the molecular bases of transport cycle mechanisms.

Heteromeric amino acid transporters (HATs) are relevant targets for structural studies. On the one hand, HATs are involved in inherited and acquired human pathologies. On the other hand, these molecules are the only known examples of solute transporters composed of two subunits (heavy and light) linked by a disulfide bridge.

Reversible Size Modulation of Aqueous Microgels via Orthogonal or Combined Application of Thermo- and Phototriggers.

Aqueous microgels that respond orthogonally to external temperature and light stimuli and to a combination of both stimuli were developed. N-Vinylcaprolactam (VCL) was copolymerized with small feed amounts (<5 mol %) of 4-[(4-methacryloyloxy)phenylazo] benzenesulfonic acid (ABSA) and cross-linked with N,N'-methylenebis(acrylamide) (BIS) to synthesize monodisperse and colloidally stable P(VCL-BIS-ABSA) microgels. The volume phase transition information on the microgels under both orthogonal and combined application of temperature and light stimuli was investigated in situ by dynamic light scattering (DLS) instrument.

Arl2- and Msps-dependent microtubule growth governs asymmetric division.

Asymmetric division of neural stem cells is a fundamental strategy to balance their self-renewal and differentiation. It is long thought that microtubules are not essential for cell polarity in asymmetrically dividing Drosophila melanogaster neuroblasts (NBs; neural stem cells). Here, we show that Drosophila ADP ribosylation factor like-2 (Arl2) and Msps, a known microtubule-binding protein, control cell polarity and spindle orientation of NBs.

Novel cystine transporter in renal proximal tubule identified as a missing partner of cystinuria-related plasma membrane protein rBAT/SLC3A1.

Heterodimeric amino acid transporters play crucial roles in epithelial transport, as well as in cellular nutrition. Among them, the heterodimer of a membrane protein b(0,+)AT/SLC7A9 and its auxiliary subunit rBAT/SLC3A1 is responsible for cystine reabsorption in renal proximal tubules. The mutations in either subunit cause cystinuria, an inherited amino aciduria with impaired renal reabsorption of cystine and dibasic amino acids.

Synthesis and Biological Evaluation of a Teixobactin Analogue.

The first synthesis and biological activity of a teixobactin analogue is reported. Substitution of the unusual L-allo-enduracididine residue by the naturally occurring L-arginine was achieved, and the analogue gave an activity trend similar to that of teixobactin (against Gram-postive bacteria) and meropenem, which was approved by the FDA in 1996. The synthetic route used allows for the synthesis of the natural product as well as the development of a program of medicinal chemistry.

Epithelial IL-1R2 acts as a homeostatic regulator during remission of ulcerative colitis.

Ulcerative colitis (UC) is a chronic intestinal inflammatory disease that may undergo periods of activity followed by remission. We aimed to identify the endogenous regulatory mechanisms that may promote disease remission. Transcriptional and protein analysis of the intestinal mucosa revealed that the IL-1 decoy receptor, interleukin-1 receptor type 2 (IL1R2), was upregulated in remission compared with active UC and controls.

A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation.

We previously described diaryl trifluorothiazoline compound 1a (hereafter referred to as fluorizoline) as a first-in-class small molecule that induces p53-independent apoptosis in a wide range of tumor cell lines. Fluorizoline directly binds to prohibitin 1 and 2 (PHBs), two proteins involved in the regulation of several cellular processes, including apoptosis. Here we demonstrate that fluorizoline-induced apoptosis is mediated by PHBs, as cells depleted of these proteins are highly resistant to fluorizoline treatment.

2-Methyltetrahydrofuran and cyclopentyl methyl ether for green solid-phase peptide synthesis.

2-MeTHF and CPME were evaluated as greener alternatives for the most employed solvents in peptide synthesis. The ability of these solvents to dissolve amino acid derivatives and a range of coupling reagents were evaluated as well as the swelling of polystyrene and polyethylene glycol resins. In addition, racemization and coupling efficiencies were also determined.

Methods, setup and safe handling for anhydrous hydrogen fluoride cleavage in Boc solid-phase peptide synthesis.

Solid-phase peptide synthesis (SPPS) using tert-butyloxycarbonyl (Boc)/benzyl (Bzl) chemistry is an indispensable technique in many laboratories around the globe, and it provides peptides to the pharmaceutical industry and to thousands of scientists working in basic research. The Boc/Bzl strategy has several advantages, including reliability in the synthesis of long and difficult polypeptides, alternative orthogonality regarding protecting groups and ease of producing C-terminal thioesters for native chemical ligation applications. In this process, anhydrous hydrogen fluoride (HF) is used to remove the side chain protecting groups of the assembled peptide and to release the peptide from the resin, a process typically described as 'HF cleavage'.

Production and physicochemical assessment of new stevia amino acid sweeteners from the natural stevioside.

New stevia amino acid sweeteners, stevia glycine ethyl ester (ST-GL) and stevia l-alanine methyl ester (ST-GL), were synthesised and characterised by IR, NMR ((1)H NMR and (13)C NMR) and elemental analysis. The purity of the new sweeteners was determined by HPLC and their sensory properties were evaluated relative to sucrose in an aqueous system. Furthermore, the stevia derivatives (ST-GL and ST-AL) were evaluated for their acute toxicity, melting point, solubility and heat stability.

Linear versus branched poly-lysine/arginine as polarity enhancer tags.

The design and synthesis of Lys- and Arg-containing peptides as solubilizing tags were studied to evaluate their influence on polarity. The relevance of spatial arrangement of polar groups, in α- or ε-amino positions, was confirmed by chromatographic analysis of a rational PolyLys-based synthesized structure. The most promising of the solubilizing tags here analyzed was conjugated to a commercial water-insoluble drug (indomethacin) as proof of concept.

Direct measurement of the dielectric polarization properties of DNA.

The electric polarizability of DNA, represented by the dielectric constant, is a key intrinsic property that modulates DNA interaction with effector proteins. Surprisingly, it has so far remained unknown owing to the lack of experimental tools able to access it. Here, we experimentally resolved it by detecting the ultraweak polarization forces of DNA inside single T7 bacteriophages particles using electrostatic force microscopy.

BOP-OXy, BOP-OBt, and BOP-OAt: novel organophosphinic coupling reagents useful for solution and solid-phase peptide synthesis.

Stand-alone coupling reagents derived from bis(2-oxo-3-oxazolidinyl)phosphorodiamidic chloride show efficient performance in solution and SPPS. In particular, the Oxyma Pure (Luxembourg Biotech., Tel Aviv, Israel) derivative shows the additional advantage of being highly soluble in DMF and even fairly soluble in CH3 CN, which can extend its use for the synthesis of complex peptides.

Rescuing biological activity from synthetic phakellistatin 19.

Phakellistatins is one of the families of Pro-rich cyclic peptides whose synthetic counterparts have revealed cytotoxicities that differ greatly from those displayed by their corresponding natural ones. This is also the case of the last member isolated from this family, phakellistatin19, an octacyclopeptide containing three Pro moieties and a high percentage of apolar residues. Exhaustive NMR studies on the synthetic and natural phakellistatin 19 have been performed in order to find a plausible explanation for this intriguing behavior.

Orthogonal chemistry for the synthesis of thiocoraline-triostin hybrids. Exploring their structure-activity relationship.

The natural compounds triostin and thiocoraline are potent antitumor agents that act as DNA bisintercalators. From a pharmaceutical point of view, these compounds are highly attractive although they present a low pharmacokinetic profile, in part due to their low solubility. Synthetically, they represent a tour de force because no robust strategies have been developed to access a broad range of these bicyclic (depsi)peptides in a straightforward manner.

Toward an atomistic description of the urea-denatured state of proteins.

We present here the characterization of the structural, dynamics, and energetics of properties of the urea-denatured state of ubiquitin, a small prototypical soluble protein. By combining state-of-the-art molecular dynamics simulations with NMR and small-angle X-ray scattering data, we were able to: (i) define the unfolded state ensemble, (ii) understand the energetics stabilizing unfolded structures in urea, (iii) describe the dedifferential nature of the interactions of the fully unfolded proteins with urea and water, and (iv) characterize the early stages of protein refolding when chemically denatured proteins are transferred to native conditions. The results presented herein are unique in providing a complete picture of the chemically unfolded state of proteins and contribute to deciphering the mechanisms that stabilize the native state of proteins, as well as those that maintain them unfolded in the presence of urea.

Design of peptide-membrane interactions to modulate single-file water transport through modified gramicidin channels.

Water permeability through single-file channels is affected by intrinsic factors such as their size and polarity and by external determinants like their lipid environment in the membrane. Previous computational studies revealed that the obstruction of the channel by lipid headgroups can be long-lived, in the range of nanoseconds, and that pore-length-matching membrane mimetics could speed up water permeability. To test the hypothesis of lipid-channel interactions modulating channel permeability, we designed different gramicidin A derivatives with attached acyl chains.

MKP-1: a critical phosphatase in the biology of macrophages controlling the switch between proliferation and activation.

Macrophages play a central role in the immune response. These cells either proliferate in response to, for example, growth factors or become activated in response to, for example, LPS and develop functional activities. Experiments carried out in mice showed that macrophage proliferation requires a short period of ERK phosphorylation, while an extended period is required for macrophage activation.