425 research outputs found
A Biometric Model for Mineralization of Type-I Collagen Fibrils
The bone and dentin mainly consist of type-I collagen fibrils mineralized by hydroxyapatite (HAP) nanocrystals. In vitro biomimetic models based on self-assembled collagen fibrils have been widely used in studying the mineralization mechanism of type-I collagen. In this chapter, the protocol we used to build a biomimetic model for the mechanistic study of type-I collagen mineralization is described. Type-I collagen extracted from rat tail tendon or horse tendon is self-assembled into fibrils and mineralized by HAP in vitro. The mineralization process is monitored by cryoTEM in combination with two-dimensional (2D) and three-dimensional (3D) stochastic optical reconstruction microscopy (STORM), which enables in situ and high-resolution visualization of the process
Controlling Internal Pore Sizes in Bicontinuous Polymeric Nanospheres
Complex polymeric nanospheres were formed in water from comb-like amphiphilic block copolymers. Their internal morphology was determined by three-dimensional cryo-electron tomographic analysis. Varying the polymer molecular weight (MW) and the hydrophilic block weight content allowed for fine control over the internal structure. Construction of a partial phase diagram allowed us to determine the criteria for the formation of bicontinuous polymer nanosphere (BPN), namely for copolymers with MW of up to 17?kDa and hydrophilic weight fractions of ?0.25; and varying the organic solvent to water ratio used in their preparation allowed for control over nanosphere diameters from 70 to 460?nm. Significantly, altering the block copolymer hydrophilicâhydrophobic balance enabled control of the internal pore diameter of the BPNs from 10 to 19?nm
MOCCASIN: converting MATLAB ODE models to SBML
MATLAB is popular in biological research for creating and simulating models that use ordinary differential equations (ODEs). However, sharing or using these models outside of MATLAB is often problematic. A community standard such as Systems Biology Markup Language (SBML) can serve as a neutral exchange format, but translating models from MATLAB to SBML can be challengingâespecially for legacy models not written with translation in mind. We developed MOCCASIN (Model ODE Converter for Creating Automated SBML INteroperability) to help. MOCCASIN can convert ODE-based MATLAB models of biochemical reaction networks into the SBML format
A classical view on nonclassical nucleation
Understanding and controlling nucleation is important for many crystallization applications. Calcium carbonate (CaCO_{3}) is often used as a model system to investigate nucleation mechanisms. Despite its great importance in geology, biology, and many industrial applications, CaCO_{3} nucleation is still a topic of intense discussion, with new pathways for its growth from ions in solution proposed in recent years. These new pathways include the so-called nonclassical nucleation mechanism via the assembly of thermodynamically stable prenucleation clusters, as well as the formation of a dense liquid precursor phase via liquidâliquid phase separation. Here, we present results from a combined experimental and computational investigation on the precipitation of CaCO_{3} in dilute aqueous solutions. We propose that a dense liquid phase (containing 4â7 H_{2}O per CaCO_{3} unit) forms in supersaturated solutions through the association of ions and ion pairs without significant participation of larger ion clusters. This liquid acts as the precursor for the formation of solid CaCO_{3} in the form of vaterite, which grows via a net transfer of ions from solution according to z Ca^{2+} + zCO_{3}^{2â} â z CaCO_{3}. The results show that all steps in this process can be explained according to classical concepts of crystal nucleation and growth, and that long-standing physical concepts of nucleation can describe multistep, multiphase growth mechanisms
Telomere length associations with cognition depend on Alzheimer's disease biomarkers
Introduction
While telomere shortening, a marker of cellular aging, may impact the progression of ageârelated neurodegenerative diseases, its association with cognition is unclear, particularly in the context of Alzheimer's disease (AD) pathology.
Methods
Telomere, cognitive, and CSF data from 482 participants in the AD Neuroimaging Initiative (148 cognitively normal, 283 mild cognitive impairment, 51 AD) was leveraged to assess telomere length associations with cognition (measured by memory and executive function) and interactions with CSF amyloidâÎČ, tau, and APOEâΔ4. Secondary analyses assessed brain volume and thickness outcomes.
Results
Longer telomeres at baseline were associated with faster executive function decline. AmyloidâÎČ and tau interacted with telomere length on cognition, with longer telomeres related to faster decline among biomarkerâpositive individuals.
Discussion
Telomere associations with cognition shift with AD progression, with longer telomeres related to worse outcomes as pathology increases, highlighting the need for further investigation of telomere length along the AD neuropathological cascade
Readthrough of nonsense mutations in Rett syndrome: evaluation of novel aminoglycosides and generation of a new mouse model
Thirty-five percent of patients with Rett syndrome carry nonsense mutations in the MECP2 gene. We have recently shown in transfected HeLa cells that readthrough of nonsense mutations in the MECP2 gene can be achieved by treatment with gentamicin and geneticin. This study was performed to test if readthrough can also be achieved in cells endogenously expressing mutant MeCP2 and to evaluate potentially more effective readthrough compounds. A mouse model was generated carrying the R168X mutation in the MECP2 gene. Transfected HeLa cells expressing mutated MeCP2 fusion proteins and mouse ear fibroblasts isolated from the new mouse model were treated with gentamicin and the novel aminoglycosides NB30, NB54, and NB84. The localization of the readthrough product was tested by immunofluorescence. Readthrough of the R168X mutation in mouse ear fibroblasts using gentamicin was detected but at lower level than in HeLa cells. As expected, the readthrough product, full-length Mecp2 protein, was located in the nucleus. NB54 and NB84 induced readthrough more effectively than gentamicin, while NB30 was less effective. Readthrough of nonsense mutations can be achieved not only in transfected HeLa cells but also in fibroblasts of the newly generated Mecp2R168X mouse model. NB54 and NB84 were more effective than gentamicin and are therefore promising candidates for readthrough therapy in Rett syndrome patients
Glucose-6-phosphate dehydrogenase deficiency with recurrent infections: case report
OBJECTIVE: To report a case of rare neutrophil functional disorder with clinical and laboratory findings similar to those of chronic granulomatous disease. METHODS: Patient with extremely reduced level of glucose-6-phosphate dehydrogenase and recurrent infections that improved after continuous use of cotrimoxazole. The patient presented leukocytes with defective respiratory burst, similar to what occurs in chronic granulomatous disease. COMMENTS: The diagnosis of glucose-6-phosphate dehydrogenase deficiency in neutrophils should be considered in any patient with hemolytic anemia whose level of G6PD is extremely low or in any patient that presents recurrent infections as differential diagnosis of chronic granulomatous disease.OBJETIVO: relatar a ocorrĂȘncia de uma deficiĂȘncia funcional de neutrĂłfilos rara, com quadro clĂnico e laboratorial semelhante ao da doença granulomatosa crĂŽnica. MĂTODOS: relato de caso de paciente com deficiĂȘncia acentuada da glicose-6-fosfato desidrogenase e infecçÔes de repetição. Realizada pesquisa bibliogrĂĄfica utilizando as bases de dados Medline e Lilacs, abrangendo o perĂodo de 1972 a 2000. RESULTADOS: paciente com nĂvel da glicose-6-fosfato desidrogenase extremamente reduzido e quadro de infeçÔes graves com melhora clĂnica apĂłs uso de cotrimoxazol contĂnuo. Os leucĂłcitos do paciente apresentam defeito no metabolismo oxidativo, similar ao da doença granulomatosa crĂŽnica. CONCLUSĂES: o diagnĂłstico da deficiĂȘncia da glicose-6-fosfato desidrogenase em neutrĂłfilos deve ser considerado em qualquer paciente com anemia hemolĂtica nĂŁo esferocĂtica congĂȘnita no qual o nĂvel da glicose-6-fosfato desidrogenase esteja anormalmente baixo ou apresente infeçÔes de repetição. Ă diagnĂłstico diferencial da doença granulomatosa crĂŽnica.Univ. Federal de SĂŁo Paulo Depto. de Pediatria Disc. de Alergia, Imunologia ClĂnicaUniv. Federal do Rio de Janeiro Fac. de Medicina Depto. de Medicina PreventivaUNICAMP Faculdade de CiĂȘncias MĂ©dicas Depto. de PediatriaUniv. de SĂŁo Paulo Fac. de MedicinaUNIFESP-EPM Depto. de PediatriaUSP Instituto de CiĂȘncias BiomĂ©dicas Depto. de ImunologiaUFRJ Fac. Med. Depto. de Medicina PreventivaUFRJ Fac. de Medicina Depto. de PediatriaUNIFESP, EPM, Depto. de PediatriaSciEL
Ultrastructure of the Interlamellar Membranes of the Nacre of the Bivalve Pteria hirundo, Determined by Immunolabelling
The current model for the ultrastructure of the interlamellar membranes of molluscan nacre imply that they consist of a core of aligned chitin fibers surrounded on both sides by acidic proteins. This model was based on observations taken on previously demineralized shells, where the original structure had disappeared. Despite other earlier claims, no direct observations exist in which the different components can be unequivocally discriminated. We have applied different labeling protocols on non-demineralized nacreous shells of the bivalve Pteria. With this method, we have revealed the disposition and nature of the different fibers of the interlamellar membranes that can be observed on the surface of the nacreous shell of the bivalve Pteria hirundo by high resolution scanning electron microscopy (SEM). The minor chitin component consists of very thin fibers with a high aspect ratio and which are seemingly disoriented. Each fiber has a protein coat, which probably forms a complex with the chitin. The chitin-protein-complex fibers are embedded in an additional proteinaceous matrix. This is the first time in which the sizes, positions and distribution of the chitin fibers have been observed in situ.AJOM was financed by a PhD Grant of the FPI program from the Spanish Ministerio de Ciencia e InnovaciĂłn; TCB's PhD Grant belonged to the FPU Program of the same Ministry. AJOM and AGC were supported by Projects CGL2010-20748-C02-01 and CGL2013-48247-P of the mentioned Ministry, and RNM6433 of the ConsejerĂa de EconomĂa, InnovaciĂłn y Ciencia of the Junta de AndalucĂa. The European COST Action TD0903 contributed via two Short Term Scientific Missions to AJOM in FM's lab in Dijon
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