Optimization Study of Bimodal Waveguide Interferometric Biosensors

Clinical diagnosis of diseases dependant on genetics of patients is still limited due to the lack of quick, precise, cheap and reliable technological tools. Such diagnostic tools would allow the design of personalized treatments for each patient according to its genetic profile. Photonic biosensors based on evanescent wave detection can afford such diagnostic tools. Using the evanescent wave detection principle, a new bimodal interferometer sensor has been proposed[1]. This device is comprised of a single mode rib waveguide which abruptly increases its core thickness to guide two transversal modes (TX00 and TX10) propagating until the output of the chip. A sensing area is defined in the bimodal part of the waveguide and, as the fundamental and first order modes have different intensity distribution at the core-cladding interface, the interface pattern is a function of the refractive index in the sensing area. A complete study is made starting from the previous device in order to improve its characteristics. The model used for simulations consisted of a variable thickness core layer (260-380 nm) of Si3N4 with n = 2.0 over a 2 µm SiO2 cladding layer with n = 1.46 and water (n=1.33) in the sensing area over the waveguide core using Film Mode Matching (FMM) Method in Photon Design 5.4[2]

Barriers to School-Based Parent Involvement While Living in Public Housing: A Mother’s Perspective

Parent involvement is associated with child academic outcomes, positive behaviors, and social skills. This qualitative study explored school-based parent involvement barriers experienced by nine low-income mothers. In-depth interviews were used to collect data from mothers participating in a community-based program offered in a large public housing neighborhood. Findings included three main barriers: (a) cultural and language differences in their children’s school, (b) undertones of racism from teachers and parents, and (c) being the primary caregiver or sole provider for their children. Although all parents experience challenges to school involvement, low-income mothers face additional obstacles preventing them from engaging in their children’s schools. This perceived lack of school involvement can lead to feelings of helplessness, shame, and stigma

Advanced Carbon-Based Polymeric Nanocomposites for Forensic Analysis

Nanotechnology is a powerful tool and fast-growing research area in many novel arenas, ranging from biomedicine to engineering and energy storage. Nanotechnology has great potential to make a significant positive contribution in forensic science, which deals with the identification and investigation of crimes, finding relationships between pieces of evidence and perpetrators. Nano-forensics is related to the development of nanosensors for crime investigations and inspection of terrorist activity by analyzing the presence of illicit drugs, explosives, toxic gases, biological agents, and so forth. In this regard, carbon nanomaterials have huge potential for next-generation nanosensors due to their outstanding properties, including strength combined with flexibility, large specific surface area, high electrical conductivity, and little noise. Moreover, their combination with polymers can provide nanocomposites with novel and enhanced performance owed to synergy between the composite components. This review concisely recapitulates up-to-date advances in the development of polymer composites incorporating carbon-based nanomaterials for forensic science. The properties of the different carbon nanomaterials, several methods used to analyze functional polymeric nanocomposites, and their applications in forensic investigation are discussed. Furthermore, present challenges and forthcoming outlooks on the design of new polymer/carbon nanomaterial composites for crime prevention are highlighted

A myosin chaperone, UNC-45A, is a novel regulator of intestinal epithelial barrier integrity and repair

The actomyosin cytoskeleton serves as a key regulator of the integrity and remodeling of epithelial barriers by controlling assembly and functions of intercellular junctions and cell-matrix adhesions. Although biochemical mechanisms that regulate the activity of non-muscle myosin II (NM-II) in epithelial cells have been extensively investigated, little is known about assembly of the contractile myosin structures at the epithelial adhesion sites. UNC-45A is a cytoskeletal chaperone that is essential for proper folding of NM-II heavy chains and myofilament assembly. We found abundant expression of UNC-45A in human intestinal epithelial cell (IEC) lines and in the epithelial layer of the normal human colon. Interestingly, protein level of UNC-45A was decreased in colonic epithelium of patients with ulcerative colitis. CRISPR/Cas9-mediated knock-out of UNC-45A in HT-29cf8 and SK-CO15 IEC disrupted epithelial barrier integrity, impaired assembly of epithelial adherence and tight junctions and attenuated cell migration. Consistently, decreased UNC-45 expression increased permeability of the Drosophila gut in vivo. The mechanisms underlying barrier disruptive and anti-migratory effects of UNC-45A depletion involved disorganization of the actomyosin bundles at epithelial junctions and the migrating cell edge. Loss of UNC-45A also decreased contractile forces at apical junctions and matrix adhesions. Expression of deletion mutants revealed roles for the myosin binding domain of UNC-45A in controlling IEC junctions and motility. Our findings uncover a novel mechanism that regulates integrity and restitution of the intestinal epithelial barrier, which may be impaired during mucosal inflammation.Peer reviewe

Low-cost vertical taper for highly efficient light in-coupling in bimodal nanointerferometric waveguide biosensors

There is still the need for a compact and cost-effective solution for efficient light in-coupling in integrated waveguides employed in photonic biosensors, especially when these waveguides are of submicron dimensions and operate at visible wavelengths. The employment of a vertically stacked taper with a larger input area is proposed to meet this need. The design of the taper is divided into two stages: in the first stage, light is guided downwards by two vertically stacked tapers; in the second stage, an inverted taper directly confines the light inside the waveguide. The design parameters are optimized using commercial software, obtaining a total theoretical light coupling efficiency of 72.25%. The taper is manufactured using SU-8 polymer as the main material, employing standard photolithography techniques at wafer level. After characterization, the results show the practicality of the taper when coupling light from macrometric sources to nanometric waveguides, obtaining an experimental coupling efficiency of 55%. With this vertical taper, a compact, easy-to-couple and cost-effective solution is achieved for waveguide-based biosensors operating at visible wavelengths, opening the way for a truly portable point-of-care biosensor for low-cost and label-free diagnostics

A CO2 optical sensor based on self-assembled metal-organic framework nanoparticles

The development of devices for sensing and monitoring CO levels is crucial for many fields such as food packaging and for human safety indoors. Herein the fabrication of an optical CO sensor by integration of a metal-organic framework (MOF) onto bimodal optical waveguides is reported. This sensor is constructed via self-assembly of a transparent film of zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (size: 32 ± 5 nm) on the waveguides. The nanoZIF-8-based sensor exhibits a broad linear response, with limits of detection of 3130 ppm at room temperature and 774 ppm at 278 K. Furthermore, it is robust, selective, fast and reusable, and can be stored under humid conditions with no loss in performance

Highly sensitive dendrimer-based nanoplasmonic biosensor for drug allergy diagnosis

A label-free biosensing strategy for amoxicillin (AX) allergy diagnosis based on the combination of novel dendrimer-based conjugates and a recently developed nanoplasmonic sensor technology is reported. Gold nanodisks were functionalized with a custom-designed thiol-ending-polyamido-based dendron (d-BAPAD) peripherally decorated with amoxicilloyl (AXO) groups (d-BAPAD-AXO) in order to detect specific IgE generated in patient's serum against this antibiotic during an allergy outbreak. This innovative strategy, which follows a simple one-step immobilization procedure, shows exceptional results in terms of sensitivity and robustness, leading to a highly-reproducible and long-term stable surface which allows achieving extremely low limits of detection. Moreover, the viability of this biosensor approach to analyze human biological samples has been demonstrated by directly analyzing and quantifying specific anti-AX antibodies in patient's serum without any sample pretreatment. An excellent limit of detection (LoD) of 0.6. ng/mL (i.e. 0.25. kU/L) has been achieved in the evaluation of clinical samples evidencing the potential of our nanoplasmonic biosensor as an advanced diagnostic tool to quickly identify allergic patients. The results have been compared and validated with a conventional clinical immunofluorescence assay (ImmunoCAP test), confirming an excellent correlation between both techniques. The combination of a novel compact nanoplasmonic platform and a dendrimer-based strategy provides a highly sensitive label free biosensor approach with over two times better detectability than conventional SPR. Both the biosensor device and the carrier structure hold great potential in clinical diagnosis for biomarker analysis in whole serum samples and other human biological samples

Mitochondrial Na+ controls oxidative phosphorylation and hypoxic redox signalling

All metazoans depend on O2 delivery and consumption by the mitochondrial oxidative phosphorylation (OXPHOS) system to produce energy. A decrease in O2 availability (hypoxia) leads to profound metabolic rewiring. In addition, OXPHOS uses O2 to produce reactive oxygen species (ROS) that can drive cell adaptations through redox signalling, but also trigger cell damage1–4, and both phenomena occur in hypoxia4–8. However, the precise mechanism by which acute hypoxia triggers mitochondrial ROS production is still unknown. Ca2+ is one of the best known examples of an ion acting as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential and collaborating in ion transport10. Here we show that Na+ acts as a second messenger regulating OXPHOS function and ROS production by modulating fluidity of the inner mitochondrial membrane (IMM). We found that a conformational shift in mitochondrial complex I during acute hypoxia11 drives the acidification of the matrix and solubilization of calcium phosphate precipitates. The concomitant increase in matrix free-Ca2+ activates the mitochondrial Na+/Ca2+ exchanger (NCLX), which imports Na+ into the matrix. Na+ interacts with phospholipids reducing IMM fluidity and mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III, generating a redox signal. Inhibition of mitochondrial Na+ import through NCLX is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ import into the mitochondrial matrix controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences in cellular metabolism

Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population

Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10–6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10–10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.Fil: Romero Hidalgo, Sandra. Instituto Nacional de Medicina Genómica; MéxicoFil: Flores Rivera, José. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Rivas Alonso, Verónica. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Barquera, Rodrigo. Max Planck Institute For The Science Of Human History; Alemania. Instituto Nacional de Antropología e Historia; MéxicoFil: Villarreal Molina, María Teresa. Instituto Nacional de Medicina Genómica; MéxicoFil: Antuna Puente, Bárbara. Instituto Nacional de Medicina Genómica; MéxicoFil: Macias Kauffer, Luis Rodrigo. Universidad Nacional Autónoma de México; MéxicoFil: Villalobos Comparán, Marisela. Instituto Nacional de Medicina Genómica; MéxicoFil: Ortiz Maldonado, Jair. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Yu, Neng. American Red Cross; Estados UnidosFil: Lebedeva, Tatiana V.. American Red Cross; Estados UnidosFil: Alosco, Sharon M.. American Red Cross; Estados UnidosFil: García Rodríguez, Juan Daniel. Instituto Nacional de Medicina Genómica; MéxicoFil: González Torres, Carolina. Instituto Nacional de Medicina Genómica; MéxicoFil: Rosas Madrigal, Sandra. Instituto Nacional de Medicina Genómica; MéxicoFil: Ordoñez, Graciela. Neuroimmunología, Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Guerrero Camacho, Jorge Luis. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Treviño Frenk, Irene. American British Cowdray Medical Center; México. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Escamilla Tilch, Monica. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: García Lechuga, Maricela. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Tovar Méndez, Víctor Hugo. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Pacheco Ubaldo, Hanna. Instituto Nacional de Antropología E Historia. Escuela Nacional de Antropología E Historia; MéxicoFil: Acuña Alonzo, Victor. Instituto Nacional de Antropología E Historia. Escuela Nacional de Antropología E Historia; MéxicoFil: Bortolini, María Cátira. Universidade Federal do Rio Grande do Sul; BrasilFil: Gallo, Carla. Universidad Peruana Cayetano Heredia; PerúFil: Bedoya Berrío, Gabriel. Universidad de Antioquia; ColombiaFil: Rothhammer, Francisco. Universidad de Tarapacá; ChileFil: Gonzalez-Jose, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; ArgentinaFil: Ruiz Linares, Andrés. Colegio Universitario de Londres; Reino UnidoFil: Canizales Quinteros, Samuel. Universidad Nacional Autónoma de México; MéxicoFil: Yunis, Edmond. Dana Farber Cancer Institute; Estados UnidosFil: Granados, Julio. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Corona, Teresa. Instituto Nacional de Neurología y Neurocirugía; Méxic