Rapid and Sequential Dual Oxime Ligation Enables De Novo Formation of Functional Synthetic Membranes from Water-Soluble Precursors.

Cell membranes define the boundaries of life and primarily consist of phospholipids. Living organisms assemble phospholipids by enzymatically coupling two hydrophobic tails to a soluble polar head group. Previous studies have taken advantage of micellar assembly to couple single-chain precursors, forming non-canonical phospholipids. However, biomimetic nonenzymatic coupling of two alkyl tails to a polar head-group remains challenging, likely due to the sluggish reaction kinetics of the initial coupling step. Here we demonstrate rapid de novo formation of biomimetic liposomes in water using dual oxime bond formation between two alkyl chains and a phosphocholine head group. Membranes can be generated from non-amphiphilic, water-soluble precursors at physiological conditions using micromolar concentrations of precursors. We demonstrate that functional membrane proteins can be reconstituted into synthetic oxime liposomes from bacterial extracts in the absence of detergent-like molecules.

Parallel Versus Antiparallel ß-Sheet Structure in Cyclic Peptide Hybrids Containing γ- or δ-Cyclic Amino Acids.

Cyclic peptides with disc-shaped structures have emerged as potent building blocks for the preparation of new biomaterials in fields ranging from biological to material science. In this work, we analyze in depth the self-assembling properties of a new type of cyclic peptides based on the alternation of α-residues and cyclic δ-amino acids (α,δ-CPs). To examine the preferred stacking properties adopted by cyclic peptides bearing this type of amino acids, we carried out a synergistic in vitro/in silico approximation by using simple dimeric models and then extended to nanotubes. Although these new cyclic peptides (α,δ-CPs) can interact either in a parallel or antiparallel fashion, our results confirm that although the parallel ß-sheet is more stable, it can be switched to the antiparallel stacking by choosing residues that can establish favorable cross-strand interactions. Moreover, the subsequent comparison by using the same methodology but applied to α,γ-CPs models, up to the moment assumed as antiparallel-like d,l-α-CPs, led to unforeseen conclusions that put into question preliminary conjectures about these systems. Surprisingly, they tend to adopt a parallel ß-sheet directed by the skeleton interactions. These results imply a change of paradigm with respect to cyclic peptide designs that should be considered for dimers and nanotubes.

New self-assembling peptide nanotubes of large diameter using δ-amino acids.

Here we show that 4-aminocyclohexanecarboxylic acid is a rigid stretcher building block for the preparation of cyclic peptides that self-assemble to form peptide nanotubes with large diameter and hydrophobic pores. The hydrophobic properties of the resulting nanotubes provided by the two methylene groups per δ-residue allow the encapsulation of C60 moieties forming a new type of bionanopeapod structure.

Regeneración del colapso vestibular en el sector anterior del maxilar con membrana de PTFE, aloinjerto e injerto de tejido conectivo. Colocación de un implante en situación ideal. Presentación de un caso clínico / Regeneration of vestibular collapse on the anterior maxillary segment with PTFE membrane, allograft and connective tissue graft. Placing an implant on the ideal position. A case report

Tras una extracción dental se produce un proceso fisiológico de reabsorción ósea, que origina una pérdida de volumen en los maxilares, y que de producirse a nivel de la tabla ósea vestibular se conoce con el término de colapso vestibular. Para evitar o reducir el nivel de reabsorción se llevan a cabo técnicas de preservación alveolar. En determinadas situaciones la pérdida de volumen es previa a la exodoncia, y va acompañada de pérdida de inserción de tejidos blandos. En estos casos se pueden utilizar membranas sintéticas no reabsorbibles de politetrafluoroetileno (PTFE), que aíslan el alveolo del epitelio y el medio externo. Se presenta el caso de un varón de 48 años que muestra una recesión gingival severa con fenestración apical en el diente 11. Tras la extracción se rellena el alveolo con aloinjerto desmineralizado Mineross y membrana de PTFE. A los 5 meses, y con la mejoría de volumen óseo obtenido se procede a la colocación de un implante en la posición tridimensional ideal en el maxilar, y de un injerto de tejido conectivo subepitelial para optimizar el volumen de tejido blando (AU)

After a tooth extraction a physiological process of bone resorption occurs, resulting in a loss of volume in the maxillary, and because it occurs at the level of the buccal bone plate is known by the term vestibular collapse. To avoid or reduce the level of absorption, techniques of alveolar preservation are carried out. In certain situations the volume loss is prior to extraction, and it is accompanied by insertion loss of soft tissue. In these cases you can use non absorbable synthetic polytetrafluoroethylene (PTFE) membranes, which isolate the socket of the epithelium and the external environment. For a 48 year old male showing severe gingival recession with apical fenestration on tooth 11. After dental extraction the socket is filled with demineralized allograft Mineross and PTFE membrane. 5 months later, and with improvement of bone volume obtained, following process is the placement of an implant in an ideal three-dimensional position in the maxillary, and a subepithelial connective tissue graft to optimize the volume of soft tissue (AU)

Adipocyte and leptin accumulation in tumor-induced thymic involution.

Cell-mediated immunity is an important defense mechanism against pathogens and developing tumor cells. The thymus is the main lymphoid organ involved in the formation of the cell-mediated immune response by the maturation and differentiation of lymphocytes that travel from the bone marrow, through the lymphatic ducts, to become T lymphocytes. Thymic involution has been associated with aging; however, other factors such as obesity, viral infection and tumor development have been shown to increase the rate of shrinkage of this organ. The heavy infiltration of adipocyte fat cells has been reported in the involuted thymuses of aged mice. In the present study, the possible accumulation of such cells in the thymus during tumorigenesis was examined by immunohistochemistry. A significant number of adipocytes around and infiltrating the thymuses of tumor-bearing mice was observed. Leptin is a pro-inflammatory adipocytokine that enhances thymopoiesis and modulates T cell immune responses. The levels of leptin and adiponectin, another adipocytokine that has anti-inflammatory properties, were examined by western blot analysis. While no changes were observed in the amounts of adiponectin present in the thymuses of the normal and tumor-bearing mice, significantly higher levels of leptin were detected in the thymocytes of the tumor-bearing mice. This correlated with an increase in the expression of certain cytokines, such as interleukin (IL)-2, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF). The co-culture of thymocytes isolated from normal mice with ex vivo isolated adipocytes from tumor-bearing mice yielded similar results. Our findings suggest that the infiltration and accumulation of adipocytes in the thymuses of tumor-bearing mice play an important role in their altered morphology and functions.

A novel Toxoplasma gondii nuclear factor TgNF3 is a dynamic chromatin-associated component, modulator of nucleolar architecture and parasite virulence.

In Toxoplasma gondii, cis-acting elements present in promoter sequences of genes that are stage-specifically regulated have been described. However, the nuclear factors that bind to these cis-acting elements and regulate promoter activities have not been identified. In the present study, we performed affinity purification, followed by proteomic analysis, to identify nuclear factors that bind to a stage-specific promoter in T. gondii. This led to the identification of several nuclear factors in T. gondii including a novel factor, designated herein as TgNF3. The N-terminal domain of TgNF3 shares similarities with the N-terminus of yeast nuclear FK506-binding protein (FKBP), known as a histone chaperone regulating gene silencing. Using anti-TgNF3 antibodies, HA-FLAG and YFP-tagged TgNF3, we show that TgNF3 is predominantly a parasite nucleolar, chromatin-associated protein that binds specifically to T. gondii gene promoters in vivo. Genome-wide analysis using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identified promoter occupancies by TgNF3. In addition, TgNF3 has a direct role in transcriptional control of genes involved in parasite metabolism, transcription and translation. The ectopic expression of TgNF3 in the tachyzoites revealed dynamic changes in the size of the nucleolus, leading to a severe attenuation of virulence in vivo. We demonstrate that TgNF3 physically interacts with H3, H4 and H2A/H2B assembled into bona fide core and nucleosome-associated histones. Furthermore, TgNF3 interacts specifically to histones in the context of stage-specific gene silencing of a promoter that lacks active epigenetic acetylated histone marks. In contrast to virulent tachyzoites, which express the majority of TgNF3 in the nucleolus, the protein is exclusively located in the cytoplasm of the avirulent bradyzoites. We propose a model where TgNF3 acts essentially to coordinate nucleolus and nuclear functions by modulating nucleosome activities during the intracellular proliferation of the virulent tachyzoites of T. gondii.

Urban solid waste collection system using mathematical modelling and tools of geographic information systems.

A poorly designed urban solid waste collection system has an enormous impact on labour, operational and transport costs, and on society in general due to road contamination and negative effects on public health and the environment. This study proposes a methodology for designing an urban solid waste collection system. This methodology uses combinatorial optimisation and integer programing, and GIS tools to minimise collection time, and operational and transport costs while enhancing the current solid waste collection system. This methodology establishes feasible collection routes, determines an adequate vehicle fleet size and presents a comparative cost and sensitivity analysis of the results. The implementation of this methodology in a study case of a zone in Santiago yields significant cost savings in the total collection system.