Paraproteinaemic keratopathy simulating a crystalline keratopathy.

BACKGROUND: Paraproteinemic keratopathy is a rare disorder characterized by the bilateral accumulation of polychromatic deposits diffusely in all corneal layers together or not with diffuse or patchy pseudo lipid deposits. We present an atypical case of paraproteinemic keratopathy which lead to an initial misdiagnosis of infectious crystalline keratopathy. CASE PRESENTATION: a 69-year-old woman with an asymptomatic keratopathy detected during a cataract intervention. Slit-lamp examination revealed several hyper refringent subepithelial foci with fern-shaped branches, resembling crystalline keratopathy, in her left eye. Anterior segment optical coherence tomography revealed exclusively subepithelial hyperreflective lesions limited to the anterior stroma. The progressive bilateralization and progression of the condition prompted us to include other entities with crystalline corneal deposits in our differential diagnosis. Hematological analysis showed a high number of free Kappa light chains. Despite the typical clinical appearance of crystalline keratopathy, the atypical evolution and test results led us to consider that monoclonal gammopathy could be the cause of this entity. CONCLUSIONS: Paraproteinemic keratopathy may present in its early stages as a unilateral subepithelial crystalline keratopathy. Thus, it must always be taken into account in the differential diagnosis of any crystalline keratopathy, particularly when there are no predisposing factors for an infectious crystalline keratopathy. Early recognition of this rare entity is important to address the associated potentially serious systemic disease.

An Evaluation of the Radioactive Content of Ashes Obtained from the Use of Fuels from Recycled Materials by Co-Processing in the Cement Industry.

The co-processing of different wastes as fuels in the manufacture of cement clinker not only meets the objectives of a circular economy but also contributes to the reduction in CO2 emissions in the manufacture of Portland cement. However, waste used as alternative fuels, such as sludge or organic-rich residues, may contain naturally occurring radionuclides that can be concentrated during the combustion process. In this study, the presence of natural radionuclides (radioactive series of uranium, thorium, and 40K) and anthropogenic radionuclides (137Cs) in these wastes has been investigated by gamma spectrometry. Possible relationships between the radioactive content and the obtained chemical composition, determined by X-ray fluorescence, have also been studied by applying a principal component analysis (PCA). The results showed that the wastes with the highest radioactive content were sewage sludge with activity concentrations of 238U and 210Pb of 321 ± 38 Bq kg-1 and 110 ± 14 Bq kg-1, respectively. A correlation between radioactive content and Fe2O3 concentration was also observed. The annual effective dose rates to workers for the ashes estimated from the ash content ranged from 0.0033 mSv to 0.092 mSv and therefore do not pose a risk to workers as they are lower than the 1 mSv per year limit for the general public (DIRECTIVE 2013/59/EURATOM).

A viral protein targets mitochondria and chloroplasts by subverting general import pathways and specific receptors.

IMPORTANCE: Many plant proteins and some proteins from plant pathogens are dually targeted to chloroplasts and mitochondria, and are supposed to be transported along the general pathways for organellar protein import, but this issue has not been explored yet. Moreover, organellar translocon receptors exist as families of several members whose functional specialization in different cargos is supposed but not thoroughly studied. This article provides novel insights into such topics showing for the first time that an exogenous protein, the melon necrotic spot virus coat protein, exploits the common Toc/Tom import systems to enter both mitochondria and chloroplasts while identifying the involved specific receptors.

Unbalanced redox status network as an early pathological event in congenital cataracts.

The lens proteome undergoes dramatic composition changes during development and maturation. A defective developmental process leads to congenital cataracts that account for about 30% of cases of childhood blindness. Gene mutations are associated with approximately 50% of early-onset forms of lens opacity, with the remainder being of unknown etiology. To gain a better understanding of cataractogenesis, we utilized a transgenic mouse model expressing a mutant ubiquitin protein in the lens (K6W-Ub) that recapitulates most of the early pathological changes seen in human congenital cataracts. We performed mass spectrometry-based tandem-mass-tag quantitative proteomics in E15, P1, and P30 control or K6W-Ub lenses. Our analysis identified targets that are required for early normal differentiation steps and altered in cataractous lenses, particularly metabolic pathways involving glutathione and amino acids. Computational molecular phenotyping revealed that glutathione and taurine were spatially altered in the K6W-Ub cataractous lens. High-performance liquid chromatography revealed that both taurine and the ratio of reduced glutathione to oxidized glutathione, two indicators of redox status, were differentially compromised in lens biology. In sum, our research documents that dynamic proteome changes in a mouse model of congenital cataracts impact redox biology in lens. Our findings shed light on the molecular mechanisms associated with congenital cataracts and point out that unbalanced redox status due to reduced levels of taurine and glutathione, metabolites already linked to age-related cataract, could be a major underlying mechanism behind lens opacities that appear early in life.

New Approach to Determine the Activity Concentration Index in Cements, Fly Ashes, and Slags on the Basis of Their Chemical Composition.

The manufacture of Portland cement entails high energy and environmental costs, and various solutions have been implemented in recent years to mitigate this negative impact. These solutions include improvements in the manufacture of cement clinker or the use of supplementary cementitious materials (SCMs), such as fly ash (FA) or slag as a replacement for a portion of the clinker in cement. The incorporation of these SCMs in cement may increase its radiological content as they are naturally occurring radioactive materials (NORMs). The Activity Concentration Index (ACI) is a screening tool established in the European EURATOM Directive 2013/59 to determine the radiation protection suitability of a final construction material. The ACI is determined by the activity concentrations of 226Ra, 232Th and 40K, usually determined by gamma spectrometry. The methodology of gamma spectrometry is accurate and appropriate, but this technique is not available in all laboratories. For this reason, and taking into account that there is a relationship between the chemical and radiological composition of these building materials, a new approach is proposed to determine the radiological content of these materials from a chemical analysis such as X-ray fluorescence (XRF). In this paper, principal component analysis (PCA) is used to establish the relationships between the chemical composition and radiological content of cements, FAs, and slags of different natures. Through PCA it was possible to group the cements based on two variables: CaO content and Fe2O3-Al2O3-TiO2 content. A lower correlation was observed for the FAs and slags, as the sample scores were centered around the origin of the coordinates and showed greater dispersion than the cements. The clusters obtained in the HJ-Biplots allowed the determination, using multiple regression, of models relating the activity concentration of 226Ra, 232Th (212Pb), and 40K to the oxide percentages obtained for the three matrices studied. The models were validated using five cements, one FA and one slag with relative percentage deviations (RSD(%)) equal to or less than 30% for 89% of the activity concentrations and 100% of the ACI determined.

Effects of dietary supplementation with purple garlic powder and oregano essential oil on intestinal health in post-weaning piglets from commercial farms.

This work studied the effects of the inclusion of Purple Garlic Powder (PGP) and Oregano Essential Oil (OEO) in the feed, at different doses and combinations, on intestinal health and the growth performance of 140 and 3000 piglets, respectively, weaned at 21 days of age. Seven dietary treatments were used: a negative control group (basal diet), a positive control group with ZnO (3000 mg/Kg of feed), two groups with OEO at 0.4% and 1.2% respectively, two groups with PGP at 0.4% and 2% respectively and one group with OEO at 1.2% combined with PGP at 2%. Only the positive control group received ZnO in the diet. Each group of piglets received the treatment for seven weeks, from weaning, and were later sacrificed to obtain jejunum and ileum samples for counting of goblet cells, intraepithelial lymphocytes, and IgA-producing cells. The growth performance were measured at the beginning and at the end of the seven weeks. In jejunum and ileum, the number of goblet cells increased in the groups with ZnO, PGP 2%, OEO 1.2% and PGP 2% + OEO 1.2%, presenting significant differences with the rest of the groups. The results obtained for the intraepithelial lymphocyte count were in line with those obtained for the count of goblet cells. Regarding IgA-producing cells, the groups that showed significantly favourable results in the jejunum and ileum were OEO 1.2%, PGP 2% and their combination, but the groups that showed the most similar means to ZnO were the OEO 0.4% and the PGP 0.4%. Regarding the growth performance, PGP 2%, OEO 1.2% and their combination had similar results to ZnO. The intestinal health of piglets could be improved, without harming the growth performance, by means of the supplementation of PGP 2%, OEO 1.2% and PGP 2% + OEO 1.2% offering a natural alternative to the use of ZnO.

Molecular characterization, targeting and expression analysis of chloroplast and mitochondrion protein import components in Nicotiana benthamiana.

Improved bioinformatics tools for annotating gene function are becoming increasingly available, but such information must be considered theoretical until further experimental evidence proves it. In the work reported here, the genes for the main components of the translocons of the outer membrane of chloroplasts (Toc) and mitochondria (Tom), including preprotein receptors and protein-conducting channels of N. benthamiana, were identified. Sequence identity searches and phylogenetic relationships with functionally annotated sequences such as those of A. thaliana revealed that N. benthamiana orthologs mainly exist as recently duplicated loci. Only a Toc34 ortholog was found (NbToc34), while Toc159 receptor family was composed of four orthologs but somewhat different from those of A. thaliana. Except for NbToc90, the rest (NbToc120, NbToc159A and NbToc159B) had a molecular weight of about 150 kDa and an acidic domain similar in length. Only two orthologs of the Tom20 receptors, NbTom20-1 and NbTom20-2, were found. The number of the Toc and Tom receptor isoforms in N. benthamiana was comparable to that previously reported in tomato and what we found in BLAST searches in other species in the genera Nicotiana and Solanum. After cloning, the subcellular localization of N. benthamiana orthologs was studied, resulting to be identical to that of A. thaliana receptors. Phenotype analysis after silencing together with relative expression analysis in roots, stems and leaves revealed that, except for the Toc and Tom channel-forming components (NbToc75 and NbTom40) and NbToc34, functional redundancy could be observed either among Toc159 or mitochondrial receptors. Finally, heterodimer formation between NbToc34 and the NbToc159 family receptors was confirmed by two alternative techniques indicating that different Toc complexes could be assembled. Additional work needs to be addressed to know if this results in a functional specialization of each Toc complex.

Radiological Characteristics of Carbonated Portland Cement Mortars Made with GGBFS.

The objective of this study is to assess whether the carbonation process can modify the physicochemical characteristics of the natural radionuclides of the three natural radioactive series, together with 40K. Three mortar specimens with different percentages of ground granulated blast-furnace slag (GGBFS), cured under water for 1, 3, 7, 14, or 28 days, were subjected to a natural carbonation process. Activity concentrations for the solid and ground mortars were determined by gamma spectrometry and by radiochemical separation of isotopic uranium. The novelty of this paper relies principally on the study we have carried out, for the first time, of the radiological characteristics of carbonated Portland cement mortars. It was found that the chemical properties of the 3 mortar specimens were not affected by the carbonation process, with particular attention placed on uranium (238U, 235U, and 234U), the activity concentrations of which were equivalent to the 226Ra results and ranged from 5.5 ± 1.6 Bq kg-1 to 21.4 ± 1.2 Bq kg-1 for the 238U. The average activity concentrations for the 3 types of mortars were lower than 20.1 Bq kg-1, 14.5 Bq kg-1, and 120.2 Bq kg-1 for the 226Ra, 232Th (212Pb), and 40K, respectively. Annual effective dose rates were equivalent to the natural background of 0.024 mSv. In addition, it was observed that the variation rate for the 222Rn emanation was due primarily to the Portland cement hydration and not due to the pore size redistribution as a consequence of the carbonation process. This research will provide new insights into the potential radiological risk from carbonated cement-based materials. Moreover, the assessment that is presented in this study will convey valuable information for future research that will explore the activity concentration of building materials containing NORM materials.

Oligodendroglia Generated From Adult Rat Adipose Tissue by Direct Cell Conversion.

Obtaining oligodendroglial cells from dispensable tissues would be of great interest for autologous or immunocompatible cell replacement therapy in demyelinating diseases, as well as for studying myelin-related pathologies or testing therapeutic approaches in culture. We evaluated the feasibility of generating oligodendrocyte precursor cells (OPCs) from adult rat adipose tissue by expressing genes encoding transcription factors involved in oligodendroglial development. Adipose-derived mesenchymal cells were lentivirally transduced with tetracycline-inducible Sox10, Olig2, Zfp536, and/or Nkx6.1 transgenes. Immunostaining with the OPC-specific O4 monoclonal antibody was used to mark oligodendroglial induction. O4- and myelin-associated glycoprotein (MAG)-positive cells emerged after 3 weeks when using the Sox10 + Olig2 + Zfp536 combination, followed in the ensuing weeks by GFAP-, O1 antigen-, p75NTR (low-affinity NGF receptor)-, and myelin proteins-positive cells. The O4+ cell population progressively expanded, eventually constituting more than 70% of cells in culture by 5 months. Sox10 transgene expression was essential for generating O4+ cells but was insufficient for inducing a full oligodendroglial phenotype. Converted cells required continuous transgene expression to maintain their glial phenotype. Some vestigial characteristics of mesenchymal cells were maintained after conversion. Growth factor withdrawal and triiodothyronine (T3) supplementation generated mature oligodendroglial phenotypes, while FBS supplementation produced GFAP+- and p75NTR+-rich cultures. Converted cells also showed functional characteristics of neural-derived OPCs, such as the expression of AMPA, NMDA, kainate, and dopaminergic receptors, as well as similar metabolic responses to differentiation-inducing drugs. When co-cultured with rat dorsal root ganglion neurons, the converted cells differentiated and ensheathed multiple axons. We propose that functional oligodendroglia can be efficiently generated from adult rat mesenchymal cells by direct phenotypic conversion.

Effect of Female Sex Hormones on the Immune Response against Chlamydia abortus and on Protection Conferred by an Inactivated Experimental Vaccine in a Mouse Model.

Mice are valuable models extensively used to test vaccine candidates against Chlamydia abortus and to clarify immunopathological mechanisms of the bacteria. As this pathogen has the ability to reactivate during pregnancy, it is important to deepen the knowledge and understanding of some of the effects of female hormones on immunity and vaccination. This study is aimed at describing the role of sex hormones in the pathology of OEA during chlamydial clearance using ovariectomised mice and also gaining an understanding of how 17ß-oestradiol or progesterone may impact the effectiveness of vaccination. Animals were treated with sex hormones and infected with C. abortus, and the kinetics of infection and immune response were analysed by means of bacterial isolation, histopathology, and immunohistochemistry. In a second phase of the study, protection conferred by an experimental vaccine after hormone treatment was assessed. Oestradiol showed a stimulatory effect on the immune response during infection, with a more efficient recruitment of macrophages and T-cells at the infection site. Furthermore, after vaccination, oestradiol-treated animals showed a stronger protection against infection, indicating that this hormone has a positive effect, stimulating a specific memory response to the pathogen.

Hybrid Cements: Mechanical Properties, Microstructure and Radiological Behavior.

The use of more eco-efficient cements in concretes is one of the keys to ensuring construction industry sustainability. Such eco-efficient binders often contain large but variable proportions of industrial waste or by-products in their composition, many of which may be naturally occurring radioactive materials (NORMs). This study explored the application of a new gamma spectrometric method for measuring radionuclide activity in hybrid alkali-activated cements from solid 5 cm cubic specimens rather than powder samples. The research involved assessing the effect of significant variables such as the nature of the alkaline activator, reaction time and curing conditions to relate the microstructures identified to the radiological behavior observed. The findings showed that varying the inputs generated pastes with similar reaction products (C-S-H, C-A-S-H and (N,C)-A-S-H) but different microstructures. The new gamma spectrometric method for measuring radioactivity in solid 5 cm cubic specimens in alkaline pastes was found to be valid. The variables involved in hybrid cement activation were shown to have no impact on specimen radioactive content. The powder samples, however, emanated 222Rn (a descendent of 226Ra), possibly due to the deformation taking place in fly ash structure during alkaline activation. Further research would be required to explain that finding.

Microstructural, Mechanical and Radiological Characterization of Mortars Made with Granite Sand.

The study reported the effect of granite sand on strength and microstructural developments in mortars prepare from OPC with a high coal fly ash (FA) content or from hybrid alkaline cements. The radiological behaviour of the resulting mortars was compared to materials prepared with siliceous sand (with particles sizes of <2 mm) and the relationship between such radiological findings and mortar microstructure and strength was explored. A new method for determining natural radionuclides and their activity concentration Index (ACI) on cement mortars (specifically to solid 5-cm cubic specimens) was applied and validated. The microstructural changes associated in mortars have no effect on mortar radiological content measurements. The mortars with granite sand exhibited very high ACI > 0.96, which would ultimately limit their use. A conclusion of interest is that where information is at hand on the starting materials (OPC, FA, sand, admixtures), their proportions in the mortar and the mixing liquid content (water or alkaline activators) their radiological content is accurately predicted. The inference is that a mortar's radiological content and ACI can be known prior to mixing, providing a criterion for determining its viability. That in turn lowers environmental risks and the health hazards for people in contact with such materials.

Europe-Wide Atmospheric Radionuclide Dispersion by Unprecedented Wildfires in the Chernobyl Exclusion Zone, April 2020.

From early April 2020, wildfires raged in the highly contaminated areas around the Chernobyl nuclear power plant (CNPP), Ukraine. For about 4 weeks, the fires spread around and into the Chernobyl exclusion zone (CEZ) and came within a few kilometers of both the CNPP and radioactive waste storage facilities. Wildfires occurred on several occasions throughout the month of April. They were extinguished, but weather conditions and the spread of fires by airborne embers and smoldering fires led to new fires starting at different locations of the CEZ. The forest fires were only completely under control at the beginning of May, thanks to the tireless and incessant work of the firefighters and a period of sustained precipitation. In total, 0.7-1.2 TBq 137Cs were released into the atmosphere. Smoke plumes partly spread south and west and contributed to the detection of airborne 137Cs over the Ukrainian territory and as far away as Western Europe. The increase in airborne 137Cs ranged from several hundred µBq·m-3 in northern Ukraine to trace levels of a few µBq·m-3 or even within the usual background level in other European countries. Dispersion modeling determined the plume arrival time and was helpful in the assessment of the possible increase in airborne 137Cs concentrations in Europe. Detections of airborne 90Sr (emission estimate 345-612 GBq) and Pu (up to 75 GBq, mostly 241Pu) were reported from the CEZ. Americium-241 represented only 1.4% of the total source term corresponding to the studied anthropogenic radionuclides but would have contributed up to 80% of the inhalation dose.

Might exogenous circular RNAs act as protein-coding transcripts in plants?

Circular RNAs (circRNAs) are regulatory molecules involved in the modulation of gene expression. Although originally assumed as non-coding RNAs, recent studies have evidenced that animal circRNAs can act as translatable transcripts. The study of plant-circRNAs is incipient, and no autonomous coding plant-circRNA has been described yet. Viroids are the smallest plant-pathogenic circRNAs known to date. Since their discovery 50 years ago, viroids have been considered valuable systems for the study of the structure-function relationships in RNA, essentially because they have not been shown to have coding capacity. We used two pathogenic circRNAs (Hop stunt viroid and Eggplant latent viroid) as experimental tools to explore the coding potential of plant-circRNAs. Our work supports that the analysed viroids contain putative ORFs able to encode peptides carrying subcellular localization signals coincident with the corresponding replication-specific organelle. Bioassays in well-established hosts revealed that mutations in these ORFs diminish their biological efficiency. Interestingly, circular forms of HSVd and ELVd were found to co-sediment with polysomes, revealing their physical interaction with the translational machinery of the plant cell. Based on this evidence we hypothesize about the possibility that plant circRNAs in general, and viroids in particular, can act, under certain cellular conditions, as non-canonical translatable transcripts.

Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice.

Disrupted homeostasis of the microtubule binding protein tau is a shared feature of a set of neurodegenerative disorders known as tauopathies. Acetylation of soluble tau is an early pathological event in neurodegeneration. In this work, we find that a large fraction of neuronal tau is degraded by chaperone-mediated autophagy (CMA) whereas, upon acetylation, tau is preferentially degraded by macroautophagy and endosomal microautophagy. Rerouting of acetylated tau to these other autophagic pathways originates, in part, from the inhibitory effect that acetylated tau exerts on CMA and results in its extracellular release. In fact, experimental blockage of CMA enhances cell-to-cell propagation of pathogenic tau in a mouse model of tauopathy. Furthermore, analysis of lysosomes isolated from brains of patients with tauopathies demonstrates similar molecular mechanisms leading to CMA dysfunction. This study reveals that CMA failure in tauopathy brains alters tau homeostasis and could contribute to aggravate disease progression.

New Approach for the Determination of Radiological Parameters on Hardened Cement Pastes with Coal Fly Ash.

Supplementary cementitious materials (SCMs) in industrial waste and by-products are routinely used to mitigate the adverse environmental effects of, and lower the energy consumption associated with, ordinary Portland cement (OPC) manufacture. Many such SCMs, such as type F coal fly ash (FA), are naturally occurring radioactive materials (NORMs). 226Ra, 232Th and 40K radionuclide activity concentration, information needed to determine what is known as the gamma-ray activity concentration index (ACI), is normally collected from ground cement samples. The present study aims to validate a new method for calculating the ACI from measurements made on unground 5 cm cubic specimens. Mechanical, mineralogical and radiological characterisation of 28-day OPC + FA pastes (bearing up to 30 wt % FA) were characterised to determine their mechanical, mineralogical and radiological properties. The activity concentrations found for 226Ra, 212Pb, 232Th and 40K in hardened, intact 5 cm cubic specimens were also statistically equal to the theoretically calculated values and to the same materials when ground to a powder. These findings consequently validated the new method. The possibility of determining the activity concentrations needed to establish the ACI for cement-based materials on unground samples introduces a new field of radiological research on actual cement, mortar and concrete materials.

Autophagy and Glycative Stress: A Bittersweet Relationship in Neurodegeneration.

Autophagy is a fine-tuned proteolytic pathway that moves dysfunctional/aged cellular components into the lysosomal compartment for degradation. Over the last 3 decades, global research has provided evidence for the protective role of autophagy in different brain cell components. Autophagic capacities decline with age, which contributes to the accumulation of obsolete/damaged organelles and proteins and, ultimately, leads to cellular aging in brain tissues. It is thus well-accepted that autophagy plays an essential role in brain homeostasis, and malfunction of this catabolic system is associated with major neurodegenerative disorders. Autophagy function can be modulated by different types of stress, including glycative stress. Glycative stress is defined as a cellular status with abnormal and accelerated accumulation of advanced glycation end products (AGEs). It occurs in hyperglycemic states, both through the consumption of high-sugar diets or under metabolic conditions such as diabetes. In recent years, glycative stress has gained attention for its adverse impact on brain pathology. This is because glycative stress stimulates insoluble, proteinaceous aggregation that is linked to the malfunction of different neuropathological proteins. Despite the emergence of new literature suggesting that autophagy plays a major role in fighting glycation-derived damage by removing cytosolic AGEs, excessive glycative stress might also negatively impact autophagic function. In this mini-review, we provide insight on the status of present knowledge regarding the role of autophagy in brain physiology and pathophysiology, with an emphasis on the cytoprotective role of autophagic function to ameliorate the adverse effects of glycation-derived damage in neurons, glia, and neuron-glia interactions.

Regeneration of lingual musculature in rats using myoblasts over porcine bladder acellular matrix.

OBJECTIVES: To use tissue engineering muscle repair (TEMR) for regenerating the lingual musculature of hemiglossectomized rats using neonatal myoblasts (NM) on porcine acellular urinary bladder matrix (AUBM). MATERIAL AND METHODS: The study used 80 male rats. A volumetric muscle loss (VML) injury was created on the left side of the tongue. The rats were randomized into four groups: Group 1 (AUBM + myoblasts); Group 2 (AUBM); Group 3 (myoblasts); and Group 4 (control). NM were obtained from neonatal rats. The animals were weighed on day 0 and just before euthanasia. Five rats in each group were euthanized at days 2, 14, 28, and 42; the tongues were prepared for morphometric analysis, postoperative left hemitongue weight, and immunohistochemical analysis (desmin, CD-31, and anti-neurofilament). RESULTS: The weight gain from greatest to least was as follows: AUBM + myoblasts > myoblasts > AUBM > control. The tongue dorsum occupied by VML, and difference in mg between control side and intervened side from least to great was as follows: AUBM + myoblasts < myoblasts < AUBM < control. The order from highest to lowest antibody positivity was as follows: AUBM + myoblasts > myoblasts > AUBM > control. CONCLUSION: The use of porcine AUBM and NM for the regeneration of lingual musculature was found to be an effective TEMR treatment for repairing tongue VML injury.

Extracellular vesicles as potential tools for regenerative therapy.

Small extracellular vesicles released by fibroblasts from young human donors diminish lipid peroxidation in senescent cells and in different old mice organs due to their enrichment in Glutathione-S-transferase Mu lipid antioxidant activity.