Iron overload in a murine model of hereditary hemochromatosis is associated with accelerated progression of osteoarthritis under mechanical stress.

OBJECTIVE: Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. DESIGN: OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. RESULTS: Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. CONCLUSIONS: HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA.

Hot carriers from intra- and interband transitions in gold-silver alloy nanoparticles.

Hot electrons and holes generated from the decay of localised surface plasmons in metallic nanoparticles can be harnessed for applications in solar energy conversion and sensing. In this paper, we study the generation of hot carriers in large spherical gold-silver alloy nanoparticles using a recently developed atomistic modelling approach that combines a solution of Maxwell's equations with large-scale tight-binding simulations. We find that hot-carrier properties depend sensitively on the alloy composition. Specifically, nanoparticles with a large gold fraction produce hot carriers under visible light illumination while nanoparticles with a large silver fraction require higher photon energies to produce hot carriers. Moreover, most hot carriers in nanoparticles with a large gold fraction originate from interband transitions which give rise to energetic holes and 'cold' electrons near the Fermi level. Increasing the silver fraction enhances the generation rate of hot carriers from intraband transitions which produce energetic electrons and 'cold' holes. These findings demonstrate that alloy composition is a powerful tuning parameter for the design of nanoparticles for applications in solar energy conversion and sensing that require precise control of hot-carrier properties.

Effect of crystal facets in plasmonic catalysis.

While the role of crystal facets is well known in traditional heterogeneous catalysis, this effect has not yet been thoroughly studied in plasmon-assisted catalysis, where attention has primarily focused on plasmon-derived mechanisms. Here, we investigate plasmon-assisted electrocatalytic CO2 reduction using different shapes of plasmonic Au nanoparticles - nanocube (NC), rhombic dodecahedron (RD), and octahedron (OC) - exposing {100}, {110}, and {111} facets, respectively. Upon plasmon excitation, Au OCs doubled CO Faradaic efficiency (FECO) and tripled CO partial current density (jCO) compared to a dark condition, with NCs also improving under illumination. In contrast, Au RDs maintained consistent performance irrespective of light exposure, suggesting minimal influence of light on the reaction. Temperature experiments ruled out heat as the main factor to explain such differences. Atomistic simulations and electromagnetic modeling revealed higher hot carrier abundance and electric field enhancement on Au OCs and NCs than RDs. These effects now dominate the reaction landscape over the crystal facets, thus shifting the reaction sites when comparing dark and plasmon-activated processes. Plasmon-assisted H2 evolution reaction experiments also support these findings. The dominance of low-coordinated sites over facets in plasmonic catalysis suggests key insights for designing efficient photocatalysts for energy conversion and carbon neutralization.

Atomistic Theory of Hot-Carrier Relaxation in Large Plasmonic Nanoparticles.

Recently, there has been significant interest in harnessing hot-carriers generated from the decay of localized surface plasmons in metallic nanoparticles for applications in photocatalysis, photovoltaics, and sensing. In this work, we develop an atomistic method that makes it possible to predict the population of hot-carriers under continuous wave illumination for large nanoparticles of relevance to experimental studies. For this, we solve the equation of motion of the density matrix, taking into account both the excitation of hot-carriers and subsequent relaxation effects. We present results for spherical Au and Ag nanoparticles with up to 250,000 atoms. We find that the population of highly energetic carriers depends on both the material and the nanoparticle size. We also study the increase in the electronic temperature upon illumination and find that Ag nanoparticles exhibit a much larger temperature increase than Au nanoparticles. Finally, we investigate the effect of using different models for the relaxation matrix but find that the qualitative features of the hot-carrier population are robust. These insights can be harnessed for the design of improved hot-carrier devices.

Ultraviolet radiation and handling medium osmolarity affect chimaerism success in zebrafish.

The effects of a predefined ultraviolet radiation dose (0.529 mW/cm2 for 30s) together with two different micromanipulation medium osmolarities (30 mOsm/kg vs 300 mOsm/kg) were tested on embryo survival at different developmental stages and on the somatic (skin) and germ-line chimaerism rates. Somatic (13%, 6/47 adults) and germ-line chimaerism (50% pigmented F1 larvae) were detected only in the UV-treated recipient embryos micromanipulated in a 300 mOsm/kg medium. From the results obtained, we concluded that the conditions cited above were the most suitable to improve somatic and germ-line chimaerism rates in zebrafish.

Micromanipulation medium osmolarity compromises zebrafish (Danio rerio) embryo and cell survival in chimaerism experiments.

In zebrafish chimaerism experiments, the cell injection can involve intra-embryonic cell lyses by osmolar effects. Moreover, the donor cells can be injured during manipulation due to osmolar changes into the transplant pipette. Therefore, the present study aimed to assess the effects of manipulation medium osmolarity on embryonic survival and donor cell viability.In Experiment I, 0.1 microl to 0.15 microl approximately of an isosmolar solution (300 mOsm) was injected into recipient embryos, which were kept at 300 (E1) or 30 mOsm (E2). Survival at day 1 was significantly higher in the E2 group than in E1 (E1: 68% vs E2: 81%, p < 0.05), but after 5 days embryo survival in the E1 group was slightly higher. In Experiment II, donor cells from zebrafish embryos were exposed (or not) to a possible osmolarity change (inner pipette medium: 300 mOsm vs external medium: 30 or 300 mOsm) using two different micropipette outer diameters, 40-50 and 60-70 microm. Cell mechanical damage was detected in the 40-50 microm pipette (p < 0.05), but not by the handling medium osmolarity. Results recommend the use of a 300 mOsm manipulation medium and bore-sized pipettes adjusted as closely as possible to the donor cell size.

Definition of three somatic adult cell nuclear transplant methods in zebrafish (Danio rerio): before, during and after egg activation by sperm fertilization.

Zebrafish somatic nuclear transplant has only been attempted using preactivated eggs. In this work, three methods to carry out the nuclear transplant using adult cells before, during and after the egg activation/fertilization were developed in zebrafish with the aim to be used in reprogramming studies. The donor nucleus from somatic adult cells was inserted: (method A) in the central region of the egg and subsequently fertilized; (method B) in the incipient animal pole at the same time that the egg was fertilized; and (method C) in the completely defined animal pole after fertilization. Larval and adult specimens were obtained using the three methods. Technical aspects related to temperature conditions, media required, egg activation/fertilization, post-ovulatory time of the transplant, egg aging, place of the donor nucleus injection in each methodology are presented. In conclusion, the technical approach developed in this work can be used in reprogramming studies.

Ultraviolet radiation dose to be applied in recipient zebrafish embryos for germ-line chimaerism is strain dependent.

Germ-line chimaerism is a powerful technique that has proved to be useful to produce viable gametes when transplanted blastomeres colonize the germinal ridges in recipient embryos and obtaining offspring from such transplanted cells. In fish, ionizing radiations were commonly used for embryo penalization to cancelling the cell participation of recipient embryos in development and in gamete production. The ultraviolet (UV) radiation when compared with other radiation types is cheaper, easier and no special installations are required for its use. So, the aim of this work was to establish the optimal UV radiation dose to be applied in zebrafish embryos at mid-blastula transition stage of development, in order to use them as penalized recipient embryos in futures chimaerism assays. A UV germicide lamp was used as radiation source (0.529 mW/cm(2)). Four exposure levels and three exposure times of UV radiation were tested. The survival rates obtained with the non-dechorionated embryos without lid group suggested that it could be the optimal exposure level to achieve the objective proposed. With the obtained results, we concluded that this UV radiation dose for 60 and 30 s are optimal parameters to penalize recipient wild and gold strain zebrafish embryos, respectively in chimaerism assays, but without involving their survival and apparently normal development.

A Fluorescence Sensing Method with Reduced DNA Typing and Low-Cost Instrumentation for Detection of Sample Tampering Cases in Urinalysis.

This work presents a method to unequivocally detect urine sample tampering in cases where integrity of the sample needs to be verified prior to urinalysis. The technique involves the detection of distinct patterns of a triplex short tandem repeats system in DNA extracted from human urine. The analysis is realized with single-dye fluorescence detection and using a regular smartphone camera. The experimental results had demonstrated the efficacy of the analytical approach to obtaining distinct profiles of amplicons in urine from different sample providers. Reproducibility tests with fresh and stored urine have revealed a maximum variation in the profiles within an interval of 5 to 9%. Cases of urine sample tampering via mixture were simulated in the study, and the experiments have identified patterns of mixed genotypes from dual mixtures of urine samples. Moreover, sample adulteration by mixing a non-human fluid with urine in a volume ratio over 25% can be detected. The low cost of the approach is accompanied by the compatibility of the technique to use with different DNA sample preparation protocols and PCR instrumentation. Furthermore, the possibility of realizing the method in an integrated microchip system open great perspectives to conducting sample integrity tests at the site of urine sample reception and/or at resource-limited settings.

KITE: high-performance accurate modelling of electronic structure and response functions of large molecules, disordered crystals and heterostructures.

We present KITE, a general purpose open-source tight-binding software for accurate real-space simulations of electronic structure and quantum transport properties of large-scale molecular and condensed systems with tens of billions of atomic orbitals (N ∼ 1010). KITE's core is written in C++, with a versatile Python-based interface, and is fully optimized for shared memory multi-node CPU architectures, thus scalable, efficient and fast. At the core of KITE is a seamless spectral expansion of lattice Green's functions, which enables large-scale calculations of generic target functions with uniform convergence and fine control over energy resolution. Several functionalities are demonstrated, ranging from simulations of local density of states and photo-emission spectroscopy of disordered materials to large-scale computations of optical conductivity tensors and real-space wave-packet propagation in the presence of magneto-static fields and spin-orbit coupling. On-the-fly calculations of real-space Green's functions are carried out with an efficient domain decomposition technique, allowing KITE to achieve nearly ideal linear scaling in its multi-threading performance. Crystalline defects and disorder, including vacancies, adsorbates and charged impurity centres, can be easily set up with KITE's intuitive interface, paving the way to user-friendly large-scale quantum simulations of equilibrium and non-equilibrium properties of molecules, disordered crystals and heterostructures subject to a variety of perturbations and external conditions.

Can vitrified zebrafish blastomeres be used to obtain germ-line chimaeras?

Blastomere cryopreservation plays an important role in maintaining the genetic diversity for valuable fish species. Recently, an original procedure for blastomere vitrification in zebrafish (Danio rerio) was developed in our lab. In the present work, blastomeres from the wild strain embryos, previously vitrified-thawed by this procedure, were injected into embryos from the gold strain in order to assess their ability to colonise the germ-line of recipient embryos. The blastomere survival rate at thawing (higher than 90 percent) as well as the whole number of recovered blastomeres per donor embryo (around 20 percent), were in the ranges previously reported for this vitrification technique. Despite this, only 2 adult chimaeric specimens were finally obtained from a total of 47 injected embryos. Signals of chimaerism were not detected at any stage of development of the chimaeric embryos (somatic chimaerism) or in adulthood (somatic and germ-line chimaerism). In relation to this, difficulties during blastomere insertion are thought to be responsible for the poor results obtained, their aspects being discussed in detail in this work. More improvements to overcome such technical difficulties are needed and, until then, blastomere vitrification may only be of interest for germplasm cryobanking.

Structural analysis of two different stent configurations.

Two different stent configurations (i.e. the well known Palmaz-Schatz (PS) and a new stent configuration) are mechanically investigated. A finite element model was used to study the two geometries under combining loads and a computational fluid dynamic model based on fluid structure interaction was developed investigating the plaque and the artery wall reactions in a stented arterial segment. These models determine the stress and displacement fields of the two stents under internal pressure conditions. Results suggested that stent designs cause alterations in vascular anatomy that adversely affect arterial stress distributions within the wall, which have impact in the vessel responses such as the restenosis. The hemodynamic analysis shows the use of new stent geometry suggests better biofluid mechanical response such as the deformation and the progressive amount of plaque growth.

Behaviour of two typical stents towards a new stent evolution.

This study explores the analysis of a new stent geometry from two typical stents used to treat the coronary artery disease. Two different finite element methods are applied with different boundary conditions to investigate the stenosis region. Computational fluid dynamics (CFD) models including fluid-structure interaction are used to assess the haemodynamic impact of two types of coronary stents implantation: (1) type 1-based on a strut-link stent geometry and (2) type 2-a continuous helical stent. Using data from a recent clinical stenosis, flow disturbances and consequent shear stress alterations introduced by the stent treatment are investigated. A relationship between stenosis and the induced flow fields for the two types of stent designs is analysed as well as the correlation between haemodynamics and vessel wall biomechanical factors during the initiation and development of stenosis formation in the coronary artery. Both stents exhibit a good performance in reducing the obstruction artery. However, stent type 1 presents higher radial deformation than the type 2. This deformation can be seen as a limitation with a long-term clinical impact.

Identification of DVT diseases using numerical simulations.

This research provides useful insights for better diagnosis and understanding the vein blockage induced by a deep venous thrombosis and the occurrence of reverse flow in human veins, allowing a proper detection of serious diseases related to deep venous insufficiency. An arbitrary Lagrangian-Eulerian formulation is used in a coupled model (i.e. fluid and structure equations solved together), considering two domains, specifically the blood flow and the flexible structures (i.e. vein and valves). Computational fluid dynamics mathematical model based on finite element method, with special elements and boundary characterization, is addressed to find the best solution. This research presents a novel model to study the interaction between non-Newtonian laminar fluid flows, the blood, within nonlinear structures, the vein walls. Simulation results are validated using in vivo echo-Doppler measurements.

[Frequency of digestive symptoms in Brazilian patients with Diabetes Mellitus]. / Freqüência de sintomas digestivos em pacientes brasileiros com Diabetes Mellitus.

PURPOSE: To determine the frequencies of digestive symptoms in an unselected sample of Brazilian diabetics, in comparison to those verified in the general population. METHODS: The frequencies of 13 digestive symptoms were determined in 153 type 1 and type 2 diabetics and in 50 apparently healthy controls, utilizing a structured, standardized questionnaire. RESULTS: The percentage of diabetics with at least one symptom was significantly higher than in controls (70% vs 36%, p = 0.01). Higher frequencies of upper digestive symptoms, such as postprandial epigastric fullness (30% vs 35%), heartburn (30% vs 34%), as well as constipation (17% vs 12%) were observed in both groups. Nevertheless, only the prevalence of dysphagia (13% vs 2%) was significantly increased (p = 0.02) in diabetics. CONCLUSION: These findings indicate that gastrointestinal symptoms are common in diabetics, but this seems also to be the case in the general population, with the exception of dysphagia. The frequencies of symptoms observed in Brazil were similar to those reported in studies from the North Hemisphere, a finding that does not support the hypothesis that external factors may influence the prevalence of gastrointestinal symptoms in diabetics.

WFS1 and non-syndromic low-frequency sensorineural hearing loss: a novel mutation in a Portuguese case.

Low-frequency sensorineural hearing loss (LFSNHL) is an unusual type of HL in which frequencies at 2,000 Hz and below are predominantly affected. Most of the families with LFSNHL carry missense mutations in WFS1 gene, coding for wolframin. A Portuguese patient aged 49, reporting HL since her third decade of life, and also referring tinnitus, was shown to display bilateral moderate LFSNHL after audiological evaluation. Molecular analysis led to the identification of a novel mutation, c.511G>A (p.Asp171Asn), found in heterozygosity in the exon 5 of the WFS1 gene, and changing the aspartic acid at position 171 to an asparagine, in the extracellular N-terminus domain of the wolframin protein. This novel mutation wasn't present either in 200 control chromosomes analyzed or in the hearing proband's half-brother, and it had not been reported in 1000 Genomes, Exome Variant Server, HGMD or dbSNP databases. No mutations were found in GJB2 and GJB6 genes. Multi-alignment of 27 wolframin sequences from mammalian species, against the human wolframin sequence in ConSurf, indicated a conservation score corresponding to 7 in a 1-9 color scale where 9 is conserved and 1 is variable. In addition, the mutation p.Asp171Asn was predicted to be damaging and possibly damaging by SIFT and Polyphen-2, respectively. The auditory phenotype of this patient could thus be due to the novel mutation p.Asp171Asn. Further functional characterization might enable to elucidate in which way the change in the residue 171, as other changes introduced by LFSNHL-associated mutations previously described, leads to this type of HL.

Life at the top: rank and stress in wild male baboons.

In social hierarchies, dominant individuals experience reproductive and health benefits, but the costs of social dominance remain a topic of debate. Prevailing hypotheses predict that higher-ranking males experience higher testosterone and glucocorticoid (stress hormone) levels than lower-ranking males when hierarchies are unstable but not otherwise. In this long-term study of rank-related stress in a natural population of savannah baboons (Papio cynocephalus), high-ranking males had higher testosterone and lower glucocorticoid levels than other males, regardless of hierarchy stability. The singular exception was for the highest-ranking (alpha) males, who exhibited both high testosterone and high glucocorticoid levels. In particular, alpha males exhibited much higher stress hormone levels than second-ranking (beta) males, suggesting that being at the very top may be more costly than previously thought.