Silk fibroin microparticles as carriers for delivery of human recombinant bone morphogenetic protein-2 : in vitro and in vivo bioactivity

The in vitro and in vivo efficiency of fibroin microparticles as a delivery carrier for bone morphogenetic protein-2 (BMP-2) was evaluated. BMP-2 was encapsulated in silk fibroin particles that were produced by a simple and very mild processing method. The dose-response of BMP-2-loaded fibroin particles was examined in C2C12 cells, after 5 days of culture. The BMP-2 retained most of its activity as observed by the increase in alkaline phosphatase activity, which was much higher when BMP-2 was encapsulated into the particles rather than just surface-adsorbed. After 2 weeks of culture, increased mineralization was observed with BMP-2-loaded particles in comparison to soluble added growth factor. No significant cytotoxicity was detected. When implanted in a rat ectopic model, bone formation was observed by in vivo micro-computed tomography after 2 and 4 weeks postimplantation, with particles loaded with 5 or 12.5 microg BMP-2. An increase in bone density was observed over time. Histology revealed further evidence of ectopic bone formation, observed by strong alizarin red staining and osteocalcin immunostaining. Our findings show that fibroin microparticles may present an interesting option for future clinical applications in the bone tissue engineering field, and therefore, further studies have been planned.The authors acknowledge Anna Hofmann and Anna Khadem for additional help with some experiments, and Karin Brenner for animal maintenance. This work was supported by Fundacao para a Ciencia e Tecnologia (Ph.D. grant SFRH/BD/17049/2004), project ElastM (POCI/CTM/57177/2004 funded by FEDER and the Fundacao para a Ciencia e Tecnologia), Marie Curie Alea Jacta EST short-term grant (MEST-CT-2004-8104), and European STREP Project HIP-POCRATES (NMP3-CT-2003-505758). This work was carried out under the scope of the European NoE EXPERTISSUES (NMP3-CT-2004-500283)

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10−12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10−14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10−103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10−49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10−93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10−23 and OR = 3.39, P = 5.2 × 10−82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20–37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Complete Ventricular Asystole in a Patient with Altered Mental Status

Patients who present with recurrent syncope are at risk for having underlying conduction disease, which may worsen if not promptly recognized and treated. We describe a patient who initially presented to a Mexican clinic with recurrent syncope and an electrocardiogram that showed complete heart block. After being transferred to our emergency department, he deteriorated into complete ventricular asystole with preserved atrial function and required placement of a transvenous cardiac pacemaker. [West J Emerg Med. 2014;15(2):149-151.

Complete Ventricular Asystole in a Patient with Altered Mental Status

Patients who present with recurrent syncope are at risk for having underlying conduction disease, which may worsen if not promptly recognized and treated. We describe a patient who initially presented to a Mexican clinic with recurrent syncope and an electrocardiogram that showed complete heart block. After being transferred to our emergency department, he deteriorated into complete ventricular asystole with preserved atrial function and required placement of a transvenous cardiac pacemaker

Complete Ventricular Asystole in a Patient with Altered Mental Status

Patients who present with recurrent syncope are at risk for having underlying conduction disease, which may worsen if not promptly recognized and treated. We describe a patient who initially presented to a Mexican clinic with recurrent syncope and an electrocardiogram that showed complete heart block. After being transferred to our emergency department, he deteriorated into complete ventricular asystole with preserved atrial function and required placement of a transvenous cardiac pacemaker. [West J Emerg Med. 2014;15(2):149-151.

Remote Sensing Requirements Development: A Simulation-Based Approach

Earth science research and application requirements for multispectral data have often been driven by currently available remote sensing technology. Few parametric studies exist that specify data required for certain applications. Consequently, data requirements are often defined based on the best data available or on what has worked successfully in the past. Since properties such as spatial resolution, swath width, spectral bands, signal-to-noise ratio (SNR), data quantization and band-to-band registration drive sensor platform and spacecraft system architecture and cost, analysis of these criteria is important to optimize system design objectively. Remote sensing data requirements are also linked to calibration and characterization methods. Parameters such as spatial resolution, radiometric accuracy and geopositional accuracy affect the complexity and cost of calibration methods. However, few studies have quantified the true accuracies required for specific problems. As calibration methods and standards are proposed, it is important that they be tied to well-known data requirements. The Application Research Toolbox (ART) developed at the John C. Stennis Space Center provides a simulation-based method for multispectral data requirements development. The ART produces simulated datasets from hyperspectral data through band synthesis. Parameters such as spectral band shape and width, SNR, data quantization, spatial resolution and band-to-band registration can be varied to create many different simulated data products. Simulated data utility can then be assessed for different applications so that requirements can be better understood

An Approach to Application Validation of Multispectral Sensors Using AVIRIS

High-resolution multispectral data are becoming widely available for commercial and scientific use. For specific applications, such as agriculture studies, there is a need to quantify the performance of such systems. In many cases, parameters such as GSD and SNR can be optimized. Data sets with varying GSD's for the Landsat ETM+ bands were produced to evaluate the effects of GSD on various algorithms and transformations, such as NDVI, principal component analysis, unsupervised classification, and mixture analysis. By showing that AVIRIS data can be used to simulate spaceborne and airborne multispectral platforms over a wide range of GSD, this research can be used to assist in band selection and spatial resolution specifications for new sensors and in optimization of acquisition strategies for existing multispectral systems