Competitive blocking of LRP4-sclerostin binding interface strongly promotes bone anabolic functions.

Induction of bone formation by Wnt ligands is inhibited when sclerostin (Scl), an osteocyte-produced antagonist, binds to its receptors, the low-density lipoprotein receptor-related proteins 5 or 6 (LRP5/6). Recently, it was shown that enhanced inhibition is achieved by Scl binding to the co-receptor LRP4. However, it is not clear if the binding of Scl to LRP4 facilitates Scl binding to LRP5/6 or inhibits the Wnt pathway in an LRP5/6-independent manner. Here, using the yeast display system, we demonstrate that Scl exhibits a stronger binding affinity for LRP4 than for LRP6. Moreover, we found stronger Scl binding to LRP6 in the presence of LRP4. We further show that a Scl mutant (SclN93A), which tightly binds LRP4 but not LRP6, does not inhibit the Wnt pathway on its own. We demonstrate that SclN93A competes with Scl for a common binding site on LRP4 and antagonizes Scl inhibition of the Wnt signaling pathway in osteoblasts in vitro. Finally, we demonstrate that 2 weeks of bi-weekly subcutaneous injections of SclN93A fused to the fragment crystallizable (Fc) domain of immunoglobulin (SclN93AFc), which retains the antagonistic activity of the mutant, significantly increases bone formation rate and enhances trabecular volumetric bone fraction, trabecular number, and bone length in developing mice. Our data show that LRP4 serves as an anchor that facilitates Scl-LRP6 binding and that inhibition of the Wnt pathway by Scl depends on its prior binding to LRP4. We further provide evidence that compounds that inhibit Scl-LRP4 interactions offer a potential strategy to promote anabolic bone functions.

Nanonized tetracycline cures deadly diarrheal disease 'shigellosis' in mice, caused by multidrug-resistant Shigella flexneri 2a bacterial infection.

We reported earlier about nano-formulation of tetracycline through its entrapment within calcium-phosphate nano-particle (CPNP) and about killing of pathogenic bacterium Shigella flexnari 2a, resistant to tetracycline (and 9 other antibiotics), by the nanonized antibiotic (Tet-CPNP). Here, we report on therapeutic role of Tet-CPNP against deadly diarrheal disease 'shigellosis' in mice, caused by Shigella infection. Our findings revealed that occurrence of mushy-stool excretion, colon-length shortening, weight-loss and bacterial colonization in gastrointestinal tract of mice due to shigellosis was significantly reduced by Tet-CPNP treatment. Histo- and immuno-logical studies showed that changes in morphology and level of inflammatory cytokines TNF-α, IL-1ß and IFN-γ in intestinal tissue of Shigella-infected mice were reverted to almost normal features by Tet-CPNP treatment. Bulk tetracycline had no anti-shigellosis action. Thus, nanonization of tetracycline rejuvenated the old, cheap, broad-spectrum antibiotic from obsolescence (due to resistance generation), making it highly beneficial for diarrhea-prone developing countries with limited health-care budgets.

Topological Insulator Bi2Se3/Si-Nanowire-Based p-n Junction Diode for High-Performance Near-Infrared Photodetector.

Chemically derived topological insulator Bi2Se3 nanoflake/Si nanowire (SiNWs) heterojunctions were fabricated employing all eco-friendly cost-effective chemical route for the first time. X-ray diffraction studies confirmed proper phase formation of Bi2Se3 nanoflakes. The morphological features of the individual components and time-evolved hybrid structures were studied using field emission scanning electron microscope. High resolution transmission electron microscopic studies were performed to investigate the actual nature of junction whereas elemental distributions at junction, along with overall stoichiometry of the samples were analyzed using energy dispersive X-ray studies. Temperature dependent current-voltage characteristics and variation of barrier height and ideality factor was studied between 50 and 300 K. An increase in barrier height and decrease in the ideality factor were observed with increasing temperature for the sample. The rectification ratio (I+/I-) for SiNWs substrate over pristine Si substrate under dark and near-infrared (NIR) irradiation of 890 nm was found to be 3.63 and 10.44, respectively. Furthermore, opto-electrical characterizations were performed for different light power intensities and highest photo responsivity and detectivity were determined to be 934.1 A/W and 2.30 × 1013 Jones, respectively. Those values are appreciably higher than previous reports for topological insulator based devices. Thus, this work establishes a hybrid system based on topological insulator Bi2Se3 nanoflake and Si nanowire as the newest efficient candidate for advanced optoelectronic materials.

Influence of spherical assembly of copper ferrite nanoparticles on magnetic properties: orientation of magnetic easy axis.

The magnetic properties of copper ferrite (CuFe2O4) nanoparticles prepared via sol-gel auto combustion and facile solvothermal method are studied focusing on the effect of nanoparticle arrangement. Randomly oriented CuFe2O4 nanoparticles (NP) are obtained from the sol-gel auto combustion method, while the solvothermal method allows us to prepare iso-oriented uniform spherical ensembles of CuFe2O4 nanoparticles (NS). X-ray diffractometry (XRD), atomic absorption spectroscopy (AAS), infra-red (IR) spectroscopy, Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), (57)Fe Mössbauer spectroscopy and vibrating sample magnetometer (VSM) are used to investigate the composition, microstructure and magnetic properties of as-prepared ferrite nanoparticles. The field-dependent magnetization measurement for the NS sample at low temperature exhibits a step-like rectangular hysteresis loop (M(R)/M(S) ~ 1), suggesting cubic anisotropy in the system, whereas for the NP sample, typical features of uniaxial anisotropy (M(R)/M(S) ~ 0.5) are observed. The coercive field (HC) for the NS sample shows anomalous temperature dependence, which is correlated with the variation of effective anisotropy (K(E)) of the system. A high-temperature enhancement of H(C) and K(E) for the NS sample coincides with a strong spin-orbit coupling in the sample as evidenced by significant modification of Cu/Fe-O bond distances. The spherical arrangement of nanocrystals at mesoscopic scale provokes a high degree of alignment of the magnetic easy axis along the applied field leading to a step-like rectangular hysteresis loop. A detailed study on the temperature dependence of magnetic anisotropy of the system is carried out, emphasizing the influence of the formation of spherical iso-oriented assemblies.

A cadaveric study of the first dorsal compartment of the wrist and its content tendons: anatomical variations in the Indian population.

de Quervain's disease is a commonly encountered problem; its management is multimodal, and often, there is recurrence which is commonly associated with anatomical variation in the first dorsal compartment of the wrist. Our purpose was to find out the anatomical variation of the first dorsal compartment of the wrist in the general population to assess the anatomical basis of de Quervain's disease and its recurrence. In this cadaveric study, 86 wrists in 46 patients were dissected to search out the first dorsal compartment of the wrist and its content tendons, presence of septa in the compartment, and insertion of the tendons. Supernumerary tendons in the first dorsal compartment were seen in 74.41 % of cases. The most commonly found tendon arrangement was two abductor pollicis longus (APL) and one extensor pollicis brevis (EPB). In all cases, there was a fixed insertion of APL to the base of the first metacarpal. Among other sites, the most common site of insertion of APL is the trapezium, which was 56.14 %. Variations of EPB with respect to number, site of insertion, thickness, and bilaterality were also found. The presence of septations was found in 37.20 % of dissected cadaveric wrists. We had found supernumerary tendons or slips in the first dorsal compartment very commonly. The presence of a septum was less frequently found. So, it may be concluded that there is immense anatomical variation present in the first dorsal compartment of the wrist, supernumerary tendons/tendon slips are commonly found, there is a variation of insertions present in the population, septum/aberrant compartment are also present, and bilateral variations are present in the population. These variations may be responsible for recurrence and unilateral affection in de Quervain's disease.