Extracellular vesicles of stromal origin target and support hematopoietic stem and progenitor cells.

Extracellular vesicles (EVs) have been recently reported as crucial mediators in cell-to-cell communication in development and disease. In this study, we investigate whether mesenchymal stromal cells that constitute a supportive microenvironment for hematopoietic stem and progenitor cells (HSPCs) released EVs that could affect the gene expression and function of HSPCs. By taking advantage of two fetal liver-derived stromal lines with widely differing abilities to maintain HSPCs ex vivo, we demonstrate that stromal EVs play a critical role in the regulation of HSPCs.

Epithelial chemokine CXCL14 synergizes with CXCL12 allosteric modulation of CXCR4.

The chemokine receptor, CXC chemokine receptor 4 (CXCR4), is selective for CXC chemokine ligand 12 (CXCL12), is broadly expressed in blood and tissue cells, and is essential during embryogenesis and hematopoiesis. CXCL14 is a homeostatic chemokine with unknown receptor selectivity and preferential expression in peripheral tissues. Here, we demonstrate that CXCL14 synergized with CXCL12 in the induction of chemokine responses in primary human lymphoid cells and cell lines that express CXCR4.

Current Care and Investigational Therapies in Achondroplasia.

Purpose Of Review: The goal of this review is to evaluate the management options for achondroplasia, the most common non-lethal skeletal dysplasia. This disease is characterized by short stature and a variety of complications, some of which can be quite severe.

Recent Findings: Despite several attempts to standardize care, there is still no widely accepted consensus.

Splicing repression allows the gradual emergence of new Alu-exons in primate evolution.

Alu elements are retrotransposons that frequently form new exons during primate evolution. Here, we assess the interplay of splicing repression by hnRNPC and nonsense-mediated mRNA decay (NMD) in the quality control and evolution of new Alu-exons. We identify 3100 new Alu-exons and show that NMD more efficiently recognises transcripts with Alu-exons compared to other exons with premature termination codons.

Evolutionary clues in lncRNAs.

The diversity of long non-coding RNAs (lncRNAs) in the human transcriptome is in stark contrast to the sparse exploration of their functions concomitant with their conservation and evolution. The pervasive transcription of the largely non-coding human genome makes the evolutionary age and conservation patterns of lncRNAs to a topic of interest. Yet it is a fairly unexplored field and not that easy to determine as for protein-coding genes.

Streptococcus pyogenes strains in Sao Paulo, Brazil: molecular characterization as a basis for StreptInCor coverage capacity analysis.

Background: Several human diseases are caused by Streptococcus pyogenes, ranging from common infections to autoimmunity. Characterization of the most prevalent strains worldwide is a useful tool for evaluating the coverage capacity of vaccines under development. In this study, a collection of S.

Drosophila melanogaster mitochondrial Hsp22: a role in resistance to oxidative stress, aging and the mitochondrial unfolding protein response.

Aging is characterized by the accumulation of dysfunctional mitochondria. Since these organelles are involved in many important cellular processes, different mechanisms exist to maintain their integrity. Among them is the mitochondrial unfolding protein response, which triggers the expression of a set of proteins aimed at re-establishing mitochondrial homeostasis.

Neuronal morphology generates high-frequency firing resonance.

The attenuation of neuronal voltage responses to high-frequency current inputs by the membrane capacitance is believed to limit single-cell bandwidth. However, neuronal populations subject to stochastic fluctuations can follow inputs beyond this limit. We investigated this apparent paradox theoretically and experimentally using Purkinje cells in the cerebellum, a motor structure that benefits from rapid information transfer.

Monoclonal antibody-targeted, temperature-sensitive liposomes: in vivo tumor chemotherapeutics in combination with mild hyperthermia.

The development of actively targeted, responsive delivery vectors holds great promise for cancer therapy. Here, we investigated whether enhanced therapeutic activity of temperature sensitive liposomes (TSL) could be obtained by mild hyperthermia-triggered release of the chemotherapeutic drug doxorubicin (DOX) after hCTMO1 monoclonal antibody (anti-MUC-1) binding and uptake into cancer cells. We showed that traditional TSL (TTSL) liposome systems maintained their physicochemical and thermal properties after conjugation to hCTMO1 full IgG.

Importance of the polarity of the glycosaminoglycan chain on the interaction with FGF-1.

Heparin-like saccharides play an essential role in binding to the fibroblast growth factor (FGF)-1 and to their membrane receptors fibroblast growth factor receptor forming a ternary complex that is responsible of the internalization of the signal, via the dimerization of the intracellular regions of the receptor. In this study, we report the binding affinities between five synthetic hexasaccharides with human FGF-1 obtained by surface plasmon resonance experiments, and compare with the induced mitogenic activity previously obtained. These five oligosaccharides differ in sulfation pattern and in sequence.

DNA-binding proteins in plant mitochondria: implications for transcription.

The structural complexity of plant mitochondrial genomes correlates with the variety of single-strand DNA-binding proteins found in plant mitochondria. Most of these are plant-specific and have roles in homologous recombination and genome maintenance. Mitochondrial nucleoids thus differ fundamentally between plants and yeast or animals, where the principal nucleoid protein is a DNA-packaging protein that binds double-stranded DNA.

Stress responses of the industrial workhorse Bacillus licheniformis to osmotic challenges.

The Gram-positive endospore-forming bacterium Bacillus licheniformis can be found widely in nature and it is exploited in industrial processes for the manufacturing of antibiotics, specialty chemicals, and enzymes. Both in its varied natural habitats and in industrial settings, B. licheniformis cells will be exposed to increases in the external osmolarity, conditions that trigger water efflux, impair turgor, cause the cessation of growth, and negatively affect the productivity of cell factories in biotechnological processes.

Cancer becomes wasteful: emerging roles of exosomes(†) in cell-fate determination.

Extracellular vesicles (EVs), including exosomes, have been widely recognized for their role in intercellular communication of the immune response system. In the past few years, significance has been given to exosomes in the induction and modulation of cell-fate-inducing signalling pathways, such as the Hedgehog (Hh), Wnts, Notch, transforming growth factor (TGF-β), epidermal growth factor (EGF) and fibroblast growth factor (FGF) pathways, placing them in the wider context of development and also of cancer. These protein families induce signalling cascades responsible for tissue specification, homeostasis and maintenance.

A circadian clock transcription model for the personalization of cancer chronotherapy.

Circadian timing of anticancer medications has improved treatment tolerability and efficacy several fold, yet with intersubject variability. Using three C57BL/6-based mouse strains of both sexes, we identified three chronotoxicity classes with distinct circadian toxicity patterns of irinotecan, a topoisomerase I inhibitor active against colorectal cancer. Liver and colon circadian 24-hour expression patterns of clock genes Rev-erbα and Bmal1 best discriminated these chronotoxicity classes, among 27 transcriptional 24-hour time series, according to sparse linear discriminant analysis.

Virus-human cell interactomes.

Using global approaches and high-throughput technologies in virology brings a new vision of the infections physiology and allows the identification of cellular factors, mandatory for viral life cycle, that could be targeted by original therapeutic agents. It opens perspectives for the treatment of viral infections by acting on cellular pathways that the virus must use for its own replication. Combining these new molecules with classical antiviral drugs and immunomodulators diversifies and enlarges the antiviral arsenal and contributes to fight drug resistance.

Kinetics of phyllosemiquinone oxidation in the Photosystem I reaction centre of Acaryochloris marina.

Light-induced electron transfer reactions in the chlorophyll a/d-binding Photosystem I reaction centre of Acaryochloris marina were investigated in whole cells by pump-probe optical spectroscopy with a temporal resolution of ~5ns at room temperature. It is shown that phyllosemiquinone, the secondary electron transfer acceptor anion, is oxidised with bi-phasic kinetics characterised by lifetimes of 88±6ns and 345±10ns. These lifetimes, particularly the former, are significantly slower than those reported for chlorophyll a-binding Photosystem I, which typically range in the 5-30ns and 200-300ns intervals.

Synaptic stability and plasticity in a floating world.

A fundamental feature of membranes is the lateral diffusion of lipids and proteins. Control of lateral diffusion provides a mechanism for regulating the structure and function of synapses. Single-particle tracking (SPT) has emerged as a powerful way to directly visualize these movements.

Molecular aspects of cyclophilins mediating therapeutic actions of their ligands.

Cyclosporine A (CsA) is an immunosuppressive cyclic peptide that binds with a high affinity to 18 kDa human cyclophilin-A (hCyPA). CsA and its several natural derivatives have some pharmacological potential in treatment of diverse immune disorders. More than 20 paralogues of CyPA are expressed in the human body while expression levels and functions of numerous ORFs encoding cyclophilin-like sequences remain unknown.

Overcoming merohedral twinning in crystals of bacteriorhodopsin grown in lipidic mesophase.

Twinning is one of the most common crystal-growth defects in protein crystallography. There are neither efficient rational approaches for the growth of nontwinned protein crystals nor are there examples of systematic studies of the dependence of the twinning-ratio distribution on crystallization conditions. The description of the twinning phenomenon has been covered even less for membrane-protein crystals and is non-existent for crystals grown using lipidic phases (in meso).

Toward a unified representation of protein structural dynamics in solution.

An atomic resolution description of protein flexibility is essential for understanding the role that structural dynamics play in biological processes. Despite the unique dependence of nuclear magnetic resonance (NMR) to motional averaging on different time scales, NMR-based protein structure determination often ignores the presence of dynamics, representing rapidly exchanging conformational equilibria in terms of a single static structure. In this study, we use the rich dynamic information encoded in experimental NMR parameters to develop a molecular and statistical mechanical characterization of the conformational behavior of proteins in solution.

On transversal hydrophobicity of some proteins and their modules.

Hydrophobicity of proteins encoded in the genomes of diverse organisms was quantified using two novel concepts: (A) amino acid (AA) bulkiness-dependent hydrophobicity profiles and (B) spatial context of hydrophobicity distribution in AA triads. Both concepts were introduced into an algorithm that was used for extracting protein clusters from diverse genomic databases whose sequence attributes were similar to those in the multiple sequence alignment (MSA) of a given family of proteins. The sequences of the G protein-coupled receptors (GPCRs) encoded in different genomes were used as templates for testing the above concepts.

Protein conformational flexibility from structure-free analysis of NMR dipolar couplings: quantitative and absolute determination of backbone motion in ubiquitin.

A robust procedure for the determination of protein-backbone motions on time scales of pico- to milliseconds directly from residual dipolar couplings has been developed that requires no additional scaling relative to external references. The results for ubiquitin (blue in graph: experimental N-HN order parameters) correspond closely to the amplitude, nature, and distribution of motion found in a 400 ns molecular-dynamics trajectory of ubiquitin (red).

Inhibition of chaperone-dependent bacterial ribosome biogenesis.

In Escherichia coli, the molecular chaperone HSP70 (DnaK) is necessary for 30S and 50S ribosomal subunit assembly at temperatures above 37 degrees C. Inhibitors of DnaK should therefore hinder ribosome biogenesis, in addition to all of the other DnaK-dependent cellular functions. An easily testable phenotype of DnaK is described here based on alpha-complementation of beta-galactosidase.

[Human resistance to African trypanosoma infections].

African trypanosomes (prototype: Trypanosoma brucei) are protozoan flagellates that infect a wide range of different mammals. In humans, these parasites have to counteract innate immunity because human serum possesses efficient trypanolytic activity. Resistance to this activity has arisen in two T.