Design and fabrication of 3D-printed anatomically shaped lumbar cage for intervertebra disc (IVD) degeneration treatment

Spinal fusion is the gold standard surgical procedure for degenerative spinal conditions when conservative therapies have been unsuccessful in rehabilitation of patients. Novel strategies are required to improve biocompatibility and osseointegration of traditionally used materials for lumbar cages. Furthermore, new design and technologies are needed to bridge the gap due to the shortage of optimal implant sizes to fill the intervertebral disc defect. Within this context, additive manufacturing technology presents an excellent opportunity to fabricate ergonomic shape medical implants. The goal of this study is to design and manufacture a 3D-printed lumbar cage for lumbar interbody fusion. Optimisations of the proposed implant design and its printing parameters were achieved via in silico analysis. The final construct was characterised via scanning electron microscopy, contact angle, x-ray micro computed tomography (μCT), atomic force microscopy, and compressive test. Preliminary in vitro cell culture tests such as morphological assessment and metabolic activities were performed to access biocompatibility of 3D-printed constructs. Results of in silico analysis provided a useful platform to test preliminary cage design and to find an optimal value of filling density for 3D printing process. Surface characterisation confirmed a uniform coating of nHAp with nanoscale topography. Mechanical evaluation showed mechanical properties of final cage design similar to that of trabecular bone. Preliminary cell culture results showed promising results in terms of cell growth and activity confirming biocompatibility of constructs. Thus for the first time, design optimisation based on computational and experimental analysis combined with the 3D-printing technique for intervertebral fusion cage has been reported in a single study. 3D-printing is a promising technique for medical applications and this study paves the way for future development of customised implants in spinal surgical applications

History of discovery of the patagonian lizards

Knowledge of the history is necessary to understand why things are today as they are. Argentinean and Chilean Patagonia have a very interesting story about the native fauna and its discovery. The main character of this story is an adventurer spirit wanting to increase knowledge by traveling to the “end of the world”, ignoring barriers only to search and see what is beyond. Many well-known naturalists have visited this land eager and willing to find new species never seen before, while others have made some amazing contributions while never setting one foot on Patagonian soil. In this chapter, we intend to summarize how Patagonian herpetofauna was discovered, described and studied over time. In addition, we want to mention important scientists, whose work led the way for the future researchers to come.Fil: Williams, Jorge Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología de Vertebrados. Sección Herpetología; ArgentinaFil: Kass, Camila Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología de Vertebrados. Sección Herpetología; ArgentinaFil: Avila, Luciano Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentin

Constraints on a second planet in the WASP-3 system

There have been previous hints that the transiting planet WASP-3 b is accompanied by a second planet in a nearby orbit, based on small deviations from strict periodicity of the observed transits. Here we present 17 precise radial velocity measurements and 32 transit light curves that were acquired between 2009 and 2011. These data were used to refine the parameters of the host star and transiting planet. This has resulted in reduced uncertainties for the radii and masses of the star and planet. The radial-velocity data and the transit times show no evidence for an additional planet in the system. Therefore, we have determined the upper limit on the mass of any hypothetical second planet, as a function of its orbital period.Comment: Accepted for publication in The Astronomical Journa

The binary near-Earth asteroid (175706) 1996 FG3 - An observational constraint on its orbital evolution

Using our photometric observations taken between 1996 and 2013 and other published data, we derived properties of the binary near-Earth asteroid (175706) 1996 FG3 including new measurements constraining evolution of the mutual orbit with potential consequences for the entire binary asteroid population. We also refined previously determined values of parameters of both components, making 1996 FG3 one of the most well understood binary asteroid systems. We determined the orbital vector with a substantially greater accuracy than before and we also placed constraints on a stability of the orbit. Specifically, the ecliptic longitude and latitude of the orbital pole are 266{\deg} and -83{\deg}, respectively, with the mean radius of the uncertainty area of 4{\deg}, and the orbital period is 16.1508 +/- 0.0002 h (all quoted uncertainties correspond to 3sigma). We looked for a quadratic drift of the mean anomaly of the satellite and obtained a value of 0.04 +/- 0.20 deg/yr^2, i.e., consistent with zero. The drift is substantially lower than predicted by the pure binary YORP (BYORP) theory of McMahon and Scheeres (McMahon, J., Scheeres, D. [2010]. Icarus 209, 494-509) and it is consistent with the theory of an equilibrium between BYORP and tidal torques for synchronous binary asteroids as proposed by Jacobson and Scheeres (Jacobson, S.A., Scheeres, D. [2011]. ApJ Letters, 736, L19). Based on the assumption of equilibrium, we derived a ratio of the quality factor and tidal Love number of Q/k = 2.4 x 10^5 uncertain by a factor of five. We also derived a product of the rigidity and quality factor of mu Q = 1.3 x 10^7 Pa using the theory that assumes an elastic response of the asteroid material to the tidal forces. This very low value indicates that the primary of 1996 FG3 is a 'rubble pile', and it also calls for a re-thinking of the tidal energy dissipation in close asteroid binary systems.Comment: Many changes based on referees comment

Derivation of some translation-invariant Lindblad equations for a quantum Brownian particle

We study the dynamics of a Brownian quantum particle hopping on an infinite lattice with a spin degree of freedom. This particle is coupled to free boson gases via a translation-invariant Hamiltonian which is linear in the creation and annihilation operators of the bosons. We derive the time evolution of the reduced density matrix of the particle in the van Hove limit in which we also rescale the hopping rate. This corresponds to a situation in which both the system-bath interactions and the hopping between neighboring sites are small and they are effective on the same time scale. The reduced evolution is given by a translation-invariant Lindblad master equation which is derived explicitly.Comment: 28 pages, 4 figures, minor revisio

Legionella pneumophila macrophage infectivity potentiator protein appendage domains modulate protein dynamics and inhibitor binding

Macrophage infectivity potentiator (MIP) proteins are widespread in human pathogens including Legionella pneumophila, the causative agent of Legionnaires' disease and protozoans such as Trypanosoma cruzi. All MIP proteins contain a FKBP (FK506 binding protein)-like prolyl-cis/trans-isomerase domain that hence presents an attractive drug target. Some MIPs such as the Legionella pneumophila protein (LpMIP) have additional appendage domains of mostly unknown function. In full-length, homodimeric LpMIP, the N-terminal dimerization domain is linked to the FKBP-like domain via a long, free-standing stalk helix. Combining X-ray crystallography, NMR and EPR spectroscopy and SAXS, we elucidated the importance of the stalk helix for protein dynamics and inhibitor binding to the FKBP-like domain and bidirectional crosstalk between the different protein regions. The first comparison of a microbial MIP and a human FKBP in complex with the same synthetic inhibitor was made possible by high-resolution structures of LpMIP with a [4.3.1]-aza-bicyclic sulfonamide and provides a basis for designing pathogen-selective inhibitors. Through stereospecific methylation, the affinity of inhibitors to L. pneumophila and T. cruzi MIP was greatly improved. The resulting X-ray inhibitor-complex structures of LpMIP and TcMIP at 1.49 and 1.34 Å, respectively, provide a starting point for developing potent inhibitors against MIPs from multiple pathogenic microorganisms.</p

PGC-1 alpha induced mitochondrial biogenesis in stromal cells underpins mitochondrial transfer to melanoma

INTRODUCTION: Progress in the knowledge of metabolic interactions between cancer and its microenvironment is ongoing and may lead to novel therapeutic approaches. Until recently, melanoma was considered a glycolytic tumour due to mutations in mitochondrial-DNA, however, these malignant cells can regain OXPHOS capacity via the transfer of mitochondrial-DNA, a process that supports their proliferation in-vitro and in-vivo. Here we study how melanoma cells acquire mitochondria and how this process is facilitated from the tumour microenvironment. METHODS: Primary melanoma cells, and MSCs derived from patients were obtained. Genes’ expression and DNA quantification was analysed using Real-time PCR. MSC migration, melanoma proliferation and tumour volume, in a xenograft subcutaneous mouse model, were monitored through bioluminescent live animal imaging. RESULTS: Human melanoma cells attract bone marrow-derived stromal cells (MSCs) to the primary tumour site where they stimulate mitochondrial biogenesis in the MSCs through upregulation of PGC1a. Mitochondria are transferred to the melanoma cells via direct contact with the MSCs. Moreover, inhibition of MSC-derived PGC1a was able to prevent mitochondrial transfer and improve NSG melanoma mouse tumour burden. CONCLUSION: MSC mitochondrial biogenesis stimulated by melanoma cells is prerequisite for mitochondrial transfer and subsequent tumour growth, where targeting this pathway may provide an effective novel therapeutic approach in melanoma

Siglec-7 Mediates Immunomodulation by Colorectal Cancer-Associated Fusobacterium nucleatum ssp. animalis

Fusobacterium nucleatum is involved in the development of colorectal cancer (CRC) through innate immune cell modulation. However, the receptors of the interaction between F. nucleatum ssp. and immune cells remain largely undetermined. Here, we showed that F. nucleatum ssp. animalis interacts with Siglecs (sialic acid–binding immunoglobulin-like lectins) expressed on innate immune cells with highest binding to Siglec-7. Binding to Siglec-7 was also observed using F. nucleatum-derived outer membrane vesicles (OMVs) and lipopolysaccharide (LPS). F. nucleatum and its derived OMVs or LPS induced a pro-inflammatory profile in human monocyte-derived dendritic cells (moDCs) and a tumour associated profile in human monocyte-derived macrophages (moMϕs). Siglec-7 silencing in moDCs or CRISPR-cas9 Siglec-7-depletion of U-937 macrophage cells altered F. nucleatum induced cytokine but not marker expression. The molecular interaction between Siglec-7 and the LPS O-antigen purified from F. nucleatum ssp. animalis was further characterised by saturation transfer difference (STD) NMR spectroscopy, revealing novel ligands for Siglec-7. Together, these data support a new role for Siglec-7 in mediating immune modulation by F. nucleatum strains and their OMVs through recognition of LPS on the bacterial cell surface. This opens a new dimension in our understanding of how F. nucleatum promotes CRC progression through the generation of a pro-inflammatory environment and provides a molecular lead for the development of novel cancer therapeutic approaches targeting F. nucleatum-Siglec-7 interaction