A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment.

Aging involves the deterioration of organismal function, leading to the emergence of multiple pathologies. Environmental stimuli, including lifestyle, can influence the trajectory of this process and may be used as tools in the pursuit of healthy aging. To evaluate the role of epigenetic mechanisms in this context, we have generated bulk tissue and single cell multi-omic maps of the male mouse dorsal hippocampus in young and old animals exposed to environmental stimulation in the form of enriched environments. We present a molecular atlas of the aging process, highlighting two distinct axes, related to inflammation and to the dysregulation of mRNA metabolism, at the functional RNA and protein level. Additionally, we report the alteration of heterochromatin domains, including the loss of bivalent chromatin and the uncovering of a heterochromatin-switch phenomenon whereby constitutive heterochromatin loss is partially mitigated through gains in facultative heterochromatin. Notably, we observed the multi-omic reversal of a great number of aging-associated alterations in the context of environmental enrichment, which was particularly linked to glial and oligodendrocyte pathways. In conclusion, our work describes the epigenomic landscape of environmental stimulation in the context of aging and reveals how lifestyle intervention can lead to the multi-layered reversal of aging-associated decline.

Preventing bisphosphonate induced osteonecrosis of the jaw with a polyguanidine conjugate (GuaDex): A promising new approach.

Osteonecrosis of the jaw (ONJ) is a relatively rare side effect after prolonged use of bisphosphonates, which are drugs used to treat bone resorption in osteoporosis and certain cancers. This study introduces a novel ONJ model in rats by combining exposure to bisphosphonates, oral surgery, and bacterial inoculation. Potential ONJ preventive effects of polyguanidine (GuaDex) or antibiotics were evaluated. The study consisted of twenty-four male Wistar rats were divided into four groups. Groups 1 to 3 were given weekly doses of i.v. Zoledronic acid (ZA), four weeks before and two weeks after an osteotomy procedure on their left mandibular first molar. Group 4 was a negative control. Streptococcus gordonii bacteria were introduced into the osteotomy pulp chamber and via the food for seven days. On day eight, the rats were given different treatments. Group 1 was given a GuaDex injection into the osteotomy socket, Group 2 was given an intramuscular (i.m.) injection of clindamycin, Group 3 (positive control) was given an i.m. injection of saline, and Group 4 was given an i.m. injection of saline. Blood samples were taken two weeks after the osteotomy procedure, after which the rats were euthanized. Bone healing, bone mineral density, histology, and blood status were analyzed. The results showed that Group 1 (GuaDex) had no ONJ, extensive ongoing bone regeneration, active healing activity, vascularization, and no presence of bacteria. Group 2 (clindamycin) showed early stages of ONJ, avascular areas, and bacteria. Group 3 showed stages of ONJ, inflammatory infiltrates, defective healing, and bacterial presence, and Group 4 had normal healing activity and no bacterial presence. Conclusion: ZA treatment and bacterial inoculation after tooth extraction inhibited bone remodeling/healing and induced ONJ characteristic lesions in the rats. Only GuaDex apparently prevented ONJ development, stimulated bone remodeling, and provided an antimicrobial effect.

A contribution to lipid digestion of Odobenidae family: Computational analysis of gastric and pancreatic lipases from walrus (Odobenus rosmarus divergens).

Triacylglycerols (TAGs) are a primary energy source for marine mammals during lipid digestion. Walruses (Odobenus rosmarus divergens) consume prey with a high content of long-chain polyunsaturated fatty acids; however, their digestive physiology and lipid digestion remain poorly studied. The present study aims to model and characterize the gastric (PWGL) and pancreatic (PWPL) lipases of Pacific walruses using an in-silico approach. The confident 3D models of PWGL and PWPL were obtained via homology modeling and protein threading and displayed the structural features of lipases. Molecular docking analysis demonstrated substrate selectivity for long-chain TAG (Trieicosapentaenoin; TC20:5n-3) in PWGL and short-chain TAG (Trioctanoin; TC8:0) in PWPL. Molecular dynamics simulations demonstrate that PWGL bound to tridocosahexaenoin (TC22:6n-3), the protein is considerably stable at all three salinity conditions, but fluctuations are observed in the regions associated with catalytic sites and the lid, indicating the potential hydrolysis of the substrate. This is the first study to report on the digestion of TAGs in walruses, including modeling and lipases characterization and proposing a digestive tract for pinnipeds.

Judo for older adults: the coaches' knowledge and needs of education.

This study aimed to explore the views of judo coaches on their perceived knowledge (PK) and needs for education (NE) for training older practitioners. In total, 470 international (Europe = 48%, Americas = 22%, Africa = 23%, Asia = 5% and Oceania = 2%) judo coaches (IJF: level 1 = 55,3%, level 2 = 33%; judo black belt: 3,4 ± 1,7 dan; F = 15%; university education: 68% >BA) responded an online survey encompassing demographic information and 35 items relevant to training older adults (Aging process; Safety and First Aid; Organization & Environment; Physiology and Fitness; Psychology & Mental Health; Teaching & Training) to be rated on a 7-point Likert scale for PK and NE. Non parametric statistics (p > 0.05) was applied to ascertain differences and relationships between PK and NE, respectively. A bivariate go-zone plot was used to highlight items with the lowest PK and the highest NE mean values. The coaches reported high PK (4.5 ± 0.3 pt) and NE (4.7 ± 0.1 pt) values, with significant higher PK values emerging for high education levels and judo experience. In considering their unique needs and special role, the judo coaches presented valuable insights to develop a sustainable educational curriculum tailored to train older judo practitioners.

Integrative single-cell chromatin and transcriptome analysis of human plasma cell differentiation.

ABSTRACT: Plasma cells (PCs) are highly specialized cells representing the end stage of B-cell differentiation. We have shown that PC differentiation can be reproduced in vitro using elaborate culture systems. The molecular changes occurring during PC differentiation are recapitulated in this in vitro differentiation model. However, a major challenge exists to decipher the spatiotemporal epigenetic and transcriptional programs that drive the early stages of PC differentiation. We combined single cell (sc) RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high throughput sequencing (scATAC-seq) to decipher the trajectories involved in PC differentiation. ScRNA-seq experiments revealed a strong heterogeneity of the preplasmablastic and plasmablastic stages. Among genes that were commonly identified using scATAC-seq and scRNA-seq, we identified several transcription factors with significant stage specific potential importance in PC differentiation. Interestingly, differentially accessible peaks characterizing the preplasmablastic stage were enriched in motifs of BATF3, FOS and BATF, belonging to activating protein 1 (AP-1) transcription factor family that may represent key transcriptional nodes involved in PC differentiation. Integration of transcriptomic and epigenetic data at the single cell level revealed that a population of preplasmablasts had already undergone epigenetic remodeling related to PC profile together with unfolded protein response activation and are committed to differentiate in PC. These results and the supporting data generated with our in vitro PC differentiation model provide a unique resource for the identification of molecular circuits that are crucial for early and mature PC maturation and biological functions. These data thus provide critical insights into epigenetic- and transcription-mediated reprogramming events that sustain PC differentiation.

Modeling and experimental analysis of CO2 methanation reaction using Ni/CeO2 monolithic catalyst.

In this study, the effect of the cell density of monolithic catalysts was investigated and further mathematically modeled on cordierite supports used in CO2 methanation. Commercial cordierite monoliths with 200, 400, and 500 cpsi cell densities were coated by immersion into an ethanolic suspension of Ni/CeO2 active phase. SEM-EDS analysis confirmed that, owing to the low porosity of cordierite (surface area < 1 m2 g-1), the Ni/CeO2 diffusion into the walls was limited, especially in the case of low and intermediate cell density monoliths; thus, active phase was predominantly loaded onto the channels' external surface. Nevertheless, despite the larger exposed surface area in the monolith with high cell density, which would allow for better distribution and accessibility of Ni/CeO2, its higher macro-pore volume resulted in some introduction of the active phase into the walls. As a result, the catalytic evaluation showed that it was more influenced by increments in volumetric flow rates. The low cell density monolith displayed diffusional control at flow rates below 500 mL min-1. In contrast, intermediate and high cell density monoliths presented this behavior up to 300 mL min-1. These findings suggest that the interaction reactants-catalyst is considerably more affected by a forced non-uniform flow when increasing the injection rate. This condition reduced the transport of reactants and products within the catalyst channels and, in turn, increased the minimum temperature required for the reaction. Moreover, a slight diminution of selectivity to CH4 was observed and ascribed to the possible formation of hot spots that activate the reverse water-gas shift reaction. Finally, a mathematical model based on fundamental momentum and mass transfer equations coupled with the kinetics of CO2 methanation was successfully derived and solved to analyze the fluid dynamics of the monolithic support. The results showed a radial profile with maximum fluid velocity located at the center of the channel. A reactive zone close to the inlet was obtained, and maximum methane production (4.5 mol m-3) throughout the monolith was attained at 350 °C. Then, linear streamlines of the chemical species were developed along the channel.

Ophthalmologic Findings in a Premature Infant leading to a Zika Diagnosis during the COVID-19 Pandemic: A Case Report.

We report on the first case of congenital Zika syndrome to be identified during the COVID-19 pandemic in Puerto Rico. The Zika virus (ZIKV) infection was first seen in Puerto Rico in December 2015. It is a flavivirus with vertical transmission, spreading from infected mothers to their fetuses and having a broad spectrum of clinical manifestations, of which microcephaly is the most worrisome. In Puerto Rico, routine ZIKV screening during pregnancy was implemented in October 2016. However, this practice has become less frequent over time. Nevertheless, the transmission of ZIKV continues, so it is important to ensure routine ZIKV screening in endemic regions, such as Puerto Rico.

Neural evidence for referential understanding of object words in dogs.

Using words to refer to objects in the environment is a core feature of the human language faculty. Referential understanding assumes the formation of mental representations of these words.1,2 Such understanding of object words has not yet been demonstrated as a general capacity in any non-human species,3 despite multiple behavior-based case reports.4,5,6,7,8,9,10 In human event-related potential (ERP) studies, object word knowledge is typically tested using the semantic violation paradigm, where words are presented either with their referent (match) or another object (mismatch).11,12 Such mismatch elicits an N400 effect, a well-established neural correlate of semantic processing.12,13 Reports of preverbal infant N400 evoked by semantic violations14 assert the use of this paradigm to probe mental representations of object words in nonverbal populations. Here, measuring dogs' (Canis familiaris) ERPs to objects primed with matching or mismatching object words, we found a mismatch effect at a frontal electrode, with a latency (206-606 ms) comparable to the human N400. A greater difference for words that dogs knew better, according to owner reports, further supported a semantic interpretation of this effect. Semantic expectations emerged irrespective of vocabulary size, demonstrating the prevalence of referential understanding in dogs. These results provide the first neural evidence for object word knowledge in a non-human animal. VIDEO ABSTRACT.

Synergistic photocatalysis of a hydrochar/CeO2 composite for dye degradation under visible light.

The synthesis and characterization of a hydrochar/CeO2 composite along with its evaluation in methylene blue degradation under visible light are presented. The methodology consisted of a single-pass hydrothermal method, having as synthesis conditions 9 h of reaction time, 210 °C, autogenous pressure, and a biomass/CeO2 ratio of 100:1. The composite characterization revealed good dispersion of CeO2 in the carbonaceous matrix and significant synergy in the composite activation using visible irradiation. The photodegradation experiments showed an efficiency of 98% for white LED light, 91% for UV light, 96% for solar irradiation, and 85% for blue LED light using as conditions pH 7.0, 50 mg of composite, 50 mL of solution, 10 mg/L of dye initial concentration, and 120 min of contact time. Meanwhile, the reusability experiments evidenced a reuse capacity of up to five times with a constant photodegradation efficiency (99%); moreover, it was determined that the presence of electrolytes at pH below 7.0 during degradation negatively affected methylene blue degradation. Finally, the results of this work demonstrate that the hydrochar/CeO2 composite can be synthesized by a green method and used for the efficient treatment of water contaminated with methylene blue.

Production of activated carbon from agave residues and its synergistic application in a hybrid adsorption-AOPs system for effective removal of sulfamethazine from aqueous solutions.

Tequila production in Mexico generates large quantities of agave bagasse (AB), a waste that could be used more efficiently. AB has a high cellulose, hemicellulose, and lignin content, which allows its use as a precursor for synthesizing carbonaceous materials. In the present work, the synthesis of activated carbon impregnated with Fe2+ (AG-Fe-II) and Fe3+ (AG-Fe-III) was carried out and evaluated in a hybrid adsorption-AOP (advanced oxidation process) methodology for sulfamethazine removal (SMT). The materials were characterized before and after the process to determine their morphological, textural, and physicochemical properties. Subsequently, the effect of the main operational variables (pH, initial SMT concentration, mass, and activator dosage) on the hybrid adsorption-degradation process was studied. The Fenton-like reaction was selected as the AOP for the degradation step, and potassium persulfate (K2S2O8) was used as an activating agent. The main iron crystallographic phases in AG-Fe-II were FeS, with a uniform distribution of iron particles over the material's surface. The main crystallographic phase for AG-Fe-III was Fe3O4. The hybrid process achieved 61% and 78% removal efficiency using AG-Fe-II and AG-Fe-III samples, respectively. The pH and initial SMT concentration were the most critical factors for removing SMT from an aqueous phase. Finally, the material was successfully tested in repeated adsorption-degradation cycles.

Easier comparison of bets in evaluation does not reduce classical preference reversals: Evidence against a context-dependent explanation.

In preference reversals, subjects express different rankings over a set of alternatives depending on how preferences are elicited. In classical reversal tasks, for instance, subjects often select a safe bet over a risky one when given a choice between the two in a pair, but then assign a higher monetary evaluation to the risky bet. Motivated by a rich literature on context-dependent preferences, we conjecture that comparisons across bets in a pair can influence both Choice and Evaluation. Yet deciders are less likely to mentally compare the bets in the latter case, as bets are typically evaluated in isolation. This asymmetry between Choice and Evaluation is, we surmise, one cause of the reversals. If we further assume that memory decay affects mental comparisons in Evaluation, the account predicts order and timing effects on the reversal probability. We run several treatments designed to facilitate or hinder the retrieval from memory of the alternative bet during evaluation of a bet. However, the reversal rate does not vary across treatments in the predicted direction, and we find no systematic order or timing effects. We conclude that reversals are not influenced by the ease with which subjects recall the alternative bet during the evaluations, which suggests in turn that a relatively smaller frequency of comparisons across bets during the (typically isolated) evaluations is not a significant cause of reversals.

Efficient removal of triclosan from water through activated carbon adsorption and photodegradation processes.

This study investigated the application of adsorption with activated carbons (ACs) and photodegradation to reduce the concentration of triclosan (TCS) in aqueous solutions. Concerning adsorption, ACs (Darco, Norit, and F400) were characterised and batch experiments were performed to elucidate the effect of pH on equilibrium. The results showed that at pH = 7, the maximum adsorption capacity of TCS onto the ACs was 18.5 mg g-1 for Darco, 16.0 mg g-1 for Norit, and 15.5 mg g-1 for F400. The diffusional kinetic model allowed an adequate interpretation of the experimental data. The effective diffusivity varied and increased with the amount of TCS adsorbed, from 1.06 to 1.68 × 10-8 cm2 s-1. In the case of photodegradation, it was possible to ensure that the triclosan molecule was sensitive to UV light of 254 nm because the removal was over 80 % using UV light. The removal of TCS increased in the presence of sulfate radicals. It was possible to identify 2,4-dichlorophenol as one of the photolytic degradation products of triclosan, which does not represent an environmental hazard at low concentrations of triclosan in water. These results confirm that the use of AC Darco, Norit, and F400 and that photodegradation processes with UV light and persulfate radicals are effective in removing TCS from water, reaching concentration levels that do not constitute a risk to human health or environmental hazard. Both methods effectively eliminate pollutants with relatively easy techniques to implement.

Long chain capsaicin analogues synthetized by CALB-CLEAs show cytotoxicity on glioblastoma cell lines.

Glioblastoma is one of the most lethal tumors, displaying striking cellular heterogeneity and drug resistance. The prognosis of patients suffering from glioblastoma after 5 years is only 5%. In the present work, capsaicin analogues bearing modifications on the acyl chain with long-chain fatty acids showed promising anti-tumoral activity by its cytotoxicity on U-87 and U-138 glioblastoma multiforme cells. The capsaicin analogues were enzymatically synthetized with cross-linked enzyme aggregates of lipase B from Candida antarctica (CALB). The catalytic performance of recombinant CALB-CLEAs was compared to their immobilized form on a hydrophobic support. After 72 h of reaction, the synthesis of capsaicin analogues from linoleic acid, docosahexaenoic acid, and punicic acid achieved a maximum conversion of 69.7, 8.3 and 30.3% with CALB-CLEAs, respectively. Similar values were obtained with commercial CALB, with conversion yields of 58.3, 24.2 and 22% for capsaicin analogues from linoleic acid, DHA and punicic acid, respectively. Olvanil and dohevanil had a significant cytotoxic effect on both U-87 and U-138 glioblastoma cells. Irrespective of the immobilization form, CALB is an efficient biocatalyst for the synthesis of anti-tumoral capsaicin derivatives. KEY POINTS: • This is the first report concerning the enzymatic synthesis of capsaicin analogues from docosahexaenoic acid and punicic acid with CALB-CLEAs. • The viability U-87 and U-138 glioblastoma cells was significantly affected after incubation with olvanil and dohevanil. • Capsaicin analogues from fatty acids obtained by CALB-CLEAs are promising candidates for therapeutic use as cytotoxic agents in glioblastoma cancer cells.

The Spectrum of Global Electron Content: A New Potential Indicator of Space Weather Activity.

The time evolution of the total number of free electrons in the Earth's ionosphere, i.e., the Global Electron Content (GEC), during more than two solar cycles is analyzed in this work. The GEC time series has been extracted from the Global Ionospheric Maps (GIMs) of Vertical Total Electron Content (VTEC) estimated by UPC-IonSAT with TOMION-v1 software from global GPS measurements since the end of 1996. A dual-layer voxel-based tomographic model solved with a forward Kalman scalar filter, from dual-frequency carrier GPS data only, provides the so-called UQRG GIM after VTEC kriging interpolation, with a resolution of 15 min in time, 5° in longitude and 2.5° in latitude. UQRG is one of the best behaving GIMs in the International GNSS Service (IGS).In this context, the potential application of the GEC spectrum evolution as a potential space weather index is discussed and demonstrated.

Application of artificial intelligence for the optimization of advanced oxidation processes to improve the water quality polluted with pharmaceutical compounds.

Sulfamethoxazole and metronidazole are emerging pollutants commonly found in surface water and wastewater. These compounds have a significant environmental impact, being necessary in the design of technologies for their removal. Recently, the advanced oxidation process has been proven successful in the elimination of this kind of compounds. In this sense, the present work discusses the application of UV/H2O2 and ozonation for the degradation of both molecules in single and binary systems. Experimental kinetic data from O3 and UV/H2O2 process were adequately described by a first and second kinetic model, respectively. From the ANOVA analysis, it was determined that the most statistically significant variables were the initial concentration of the drugs (0.03 mmol L-1) and the pH = 8 for UV/H2O2 system, and only the pH (optimal value of 6) was significant for degradation with O3. Results showed that both molecules were eliminated with high degradation efficiencies (88-94% for UV/H2O2 and 79-98% for O3) in short reaction times (around 30-90 min). The modeling was performed using a quadratic regression model through response surface methodology representing adequately 90 % of the experimental data. On the other hand, an artificial neural network was used to evaluate a non-linear multi-variable system, a 98% of fit between the model and experimental data was obtained. The identification of degradation byproducts was performed by high-performance liquid chromatography coupled to a time mass detector. After each process, at least four to five stable byproducts were found in the treated water, reducing the mineralization percentage to 20% for both molecules.

New trends in modelling of breakthrough curves to remove pollutants using adsorption on advanced monoliths geometries.

This work proposes a rigorous mathematical model capable of reproducing the adsorption process in dynamic regime on advanced monoliths geometries. For this, four bed geometries with axisymmetric distribution of channels and similar solid mass were proposed. In each geometry a different distribution of channels was suggested, maintaining constant the bed dimensions of 15 cm high and 5 cm radius. The mathematical modeling includes mass and momentum transfer phenomena, and it was solved with the COMSOL Multiphysics software using mass transfer parameters published in the literature. The overall performance of the column was evaluated in terms of breakthrough (CA/CA0 = 0.1) and saturation times (CA/CA0 = 0.9). The mass and velocity distributions obtained from the proposed model show good physical consistency with what is expected in real systems. In addition, the model proved to be easy to solve given the short convergence times required (2-4 h). Modifications were made to the bed geometry to achieve a better use of the adsorbent material which reached up to 80%. The proposed bed geometries allow obtaining different mixing distributions, in such a way that inside the bed a thinning of the boundary layer is caused, thus reducing diffusive effects at the adsorbent solid-fluid interface, given dissipation rates of about 323 × 10-11 m2/s3. The bed geometry composed of intersecting rings deployed the best performance in terms of usage of the material adsorbent, and acceptable hydrodynamical behavior inside the channels (maximum fluid velocity = 35.4 × 10-5 m/s and drop pressure = 0.19 Pa). Based on these results, it was found that it is possible to reduce diffusional effects and delimit the mass transfer zone inside the monoliths, thus increasing the efficiency of adsorbent fixed beds.

Development of a rapid assay for ß-etherase activity using a novel chromogenic substrate.

Biocatalytic processes play a crucial role in the valorization of lignin; therefore, methods enabling the monitoring of enzymes such as ß-etherases, capable of breaking ß-O-4 aryl-ether bonds, are of significant biotechnological interest. A novel method for quantifying ß-etherase activity was developed based on the ß-ester bond formation between a chromophore and acetovainillone. The chromogenic substrate ß-(ρ-nitrophenoxy)-α-acetovanillone (PNPAV), was chemically synthesized. Kintetic monitoring of ρ-nitrophenolate release at 410 nm over 10 min, using recombinant LigF from Sphingobium sp SYK-6, LigF-AB and LigE-AB from Althererytrobacter sp B11, yielded enzimatic activities of 404. 3 mU/mg, 72 mU/mg, and 50 mU/mg, respectively. This method is applicable in a pH range of 7.0-9.0, with a sensitivity of up to 50 ng of enzyme, exhibiting no interference with lipolytic, glycolytic, proteolytic, and oxidoreductase enzymes.

Digestive glycosidases from cannonball jellyfish (Stomolophus sp. 2): identification and temporal-spatial variability.

Jellyfish are economically important organisms in diverse countries, carnivorous organisms that consume various prey (crustaceans, mollusks, bivalves, etc.) and dissolved carbohydrates in marine waters. This study was focused on detecting and quantifying the activity of digestive glycosidases from the cannonball jellyfish (Stomolophus sp. 2) to understand carbohydrate digestion and its temporal-spatial variation. Twenty-three jellyfish gastric pouches were collected in 2015 and 2016 in the Gulf of California in three localities (Las Guásimas, Hermosillo, and Caborca). Nine samples were in intra-localities from Las Guásimas. Chitinase (Ch), ß-glucosidase (ß-glu), and ß-N-acetylhexosaminidase (ß-NAHA) were detected in the gastric pouches. However, cellulase, exoglucanase, α-amylase, polygalacturonase, xylanase, and κ-carrageenase were undetected. Detected enzymes showed halotolerant glycolytic activity (i = 0-4 M NaCl), optimal pH, and temperature at 5.0 and 30-50 °C, respectively. At least five ß-glucosidase and two ß-N-acetylhexosaminidase were detected using zymograms; however, the number of proteins with chitinase activity is not precise. The annual variation of cannonball jellyfish digestive glycosidases from Las Guásimas between 2015-2016 does not show significant differences despite the difference in phytoplankton measured as chlorophyll α (1.9 and 3.4 mg/m3, respectively). In the inter-localities, the glycosidase activity was statistically different in all localities, except for ß-N-acetylhexosaminidase activity between Caborca and Hermosillo (3,009.08 ± 87.95 and 3,101.81 ± 281.11 mU/g of the gastric pouch, respectively), with chlorophyll α concentrations of 2.6, 3.4 mg/m3, respectively. For intra-localities, the glycosidase activity did not show significant differences, with a mean chlorophyll α of 1.3 ± 0.1 mg/m3. These results suggest that digestive glycosidases from Stomolophus sp. 2 can hydrolyze several carbohydrates that may belong to their prey or carbohydrates dissolved in marine waters, with salinity over ≥ 0.6 M NaCl and diverse temperature (4-80 °C) conditions. Also, chlorophyll α is related to glycosidase activity in both seasons and inter-localities, except for chitinase activity in an intra-locality (Las Guásimas).

The thyroid hormone enhances mouse embryonic fibroblasts reprogramming to pluripotent stem cells: role of the nuclear receptor corepressor 1.

Introduction: Pluripotent stem cells can be generated from somatic cells by the Yamanaka factors Oct4, Sox2, Klf4 and c-Myc. Methods: Mouse embryonic fibroblasts (MEFs) were transduced with the Yamanaka factors and generation of induced pluripotent stem cells (iPSCs) was assessed by formation of alkaline phosphatase positive colonies, pluripotency gene expression and embryod bodies formation. Results: The thyroid hormone triiodothyronine (T3) enhances MEFs reprogramming. T3-induced iPSCs resemble embryonic stem cells in terms of the expression profile and DNA methylation pattern of pluripotency genes, and of their potential for embryod body formation and differentiation into the three major germ layers. T3 induces reprogramming even though it increases expression of the cyclin kinase inhibitors p21 and p27, which are known to oppose acquisition of pluripotency. The actions of T3 on reprogramming are mainly mediated by the thyroid hormone receptor beta and T3 can enhance iPSC generation in the absence of c-Myc. The hormone cannot replace Oct4 on reprogramming, but in the presence of T3 is possible to obtain iPSCs, although with low efficiency, without exogenous Klf4. Furthermore, depletion of the corepressor NCoR (or Nuclear Receptor Corepressor 1) reduces MEFs reprogramming in the absence of the hormone and strongly decreases iPSC generation by T3 and also by 9cis-retinoic acid, a well-known inducer of reprogramming. NCoR depletion also markedly antagonizes induction of pluripotency gene expression by both ligands. Conclusions: Inclusion of T3 on reprogramming strategies has a potential use in enhancing the generation of functional iPSCs for studies of cell plasticity, disease and regenerative medicine.

Photon-counting detector CT allows significant reduction in radiation dose while maintaining image quality and noise on non-contrast chest CT.

Purpose: To investigate if clinical non-contrast chest CT studies obtained with PCD CT using much lower radiation exposure can achieve the same image quality as with the currently established EID protocol. Materials/methods: A total of seventy-one patients were identified who had a non-contrast chest computed tomography (CT) done on PCD CT and EID CT scanners within a 4-month interval. Five fellowship trained chest radiologists, blinded to the scanner details were asked to review the cases side-by-side and record their preference for images from either the photon-counting-detector (PCD) CT or the energy-integrating detector (EID) CT scanner. Results: The median CTDIvol for PCD-CT system was 4.710 mGy and EID system was 7.80 mGy (p < 0.001). The median DLP with the PCD-CT was 182.0 mGy.cm and EID system was 262.60 mGy.cm (p < 0.001). The contrast to noise ratio (CNR) was superior on the PCD-CT system 59.2 compared to the EID-CT 53.3; (p < 0.001). Kappa-statistic showed that there was poor agreement between the readers over the image quality from the PCD and EID scanners (κ = 0.19; 95 % CI: 0.12 - 0.27; p < 0.001). Chi-square analysis revealed that 3 out of 5 readers showed a significant preference for images from the PCDCT (p ≤ 0.012). There was no significant difference in the preferences of two readers between EID-CT and PCD-CT images. Conclusion: The first clinical PCD-CT system allows a significant reduction in radiation exposure while maintaining image quality and image noise using a standardized non-contrast chest CT protocol.