Comparative Analysis of CRISPR-Cas Systems in Pseudomonas Genomes.

Pseudomonas is a bacterial genus with some saprophytic species from land and others associated with opportunistic infections in humans and animals. Factors such as pathogenicity or metabolic aspects have been related to CRISPR-Cas, and in silico studies into it have focused more on the clinical and non-environmental setting. This work aimed to perform an in silico analysis of the CRISPR-Cas systems present in Pseudomonas genomes. It analyzed 275 complete genomic sequences of Pseudomonas taken from the NCBI database. CRISPR loci were obtained from CRISPRdb. The genes associated with CRISPR (cas) and CAS proteins, and the origin and diversity of spacer sequences, were identified and compared by BLAST. The presence of self-targeting sequences, PAMs, and the conservation of DRs were visualized using WebLogo 3.6. The CRISPR-like RNA secondary structure prediction was analyzed using RNAFold and MFold. CRISPR structures were identified in 19.6% of Pseudomonas species. In all, 113 typical CRISPR arrays with 18 putative cas were found, as were 2050 spacers, of which 52% showed homology to bacteriophages, 26% to chromosomes, and 22% to plasmids. No potential self-targeting was detected within the CRISPR array. All the found DRs can form thermodynamically stable secondary RNA structures. The comparison of the CRISPR/Cas system can help understand the environmental adaptability of each evolutionary lineage of clinically and environmentally relevant species, providing data support for bacterial typing, traceability, analysis, and exploration of unconventional CRISPR.

Macromolecular crowding impact on anti-CRISPR AcrIIC3/NmeCas9 complex: Insights from scaled particle theory, molecular dynamics, and elastic networks models.

The coupling of Cas9 and its inhibitor AcrIIC3, both from the bacterium Neisseria meningitidis (Nme), form a homodimer of the (NmeCas9/AcrIIC3)2 type. This coupling was studied to assess the impact of their interaction with the crowders in the following environments: (1) homogeneous crowded, (2) heterogeneous, and (3) microheterogeneous cytoplasmic. For this, statistical thermodynamic models based on the scaled particle theory (SPT) were used, considering the attractive and repulsive protein-crowders contributions and the stability of the formation of spherocylindrical homodimers and the effects of changes in the size of spherical dimers were estimated. Studies based on models of dynamics, elastic networks, and statistical potentials to the formation of complexes NmeCas9/AcrIIC3 using PEG as the crowding agent support the predictions from SPT. Macromolecular crowding stabilizes the formation of the dimers, being more significant when the attractive protein-crowder interactions are weaker and the crowders are smaller. The coupling is favored towards the formation of spherical and compact dimers due to crowding addition (excluded-volume effects) and the thermodynamic stability of the dimers is markedly dependent on the size of the crowders. These results support the experimental mechanistic proposal of inhibition of NmeCas9 mediated by AcrIIC3.

Current state and future perspectives for palliative care in Latin America with a special focus on Peru.

The evolution of palliative care in Latin America has been slow compared with other parts of the world, especially developed countries. Current data show inequality in the development of palliative care in the region and those differences are also evident within countries between urban and rural populations. Peru is situated in the low-ranking group in terms of palliative care services in Latin America. The main reasons are a lack of education and funding and misconceptions about palliative care. Limited access to the use of opioids and regulatory barriers are also common features. The development of more palliative care units in Peru, as well as in other Latin American countries, is needed to ensure access to adequate and timely treatment for patients receiving palliative care.

Glycosaminoglycans: What Remains To Be Deciphered?

Glycosaminoglycans (GAGs) are complex polysaccharides exhibiting a vast structural diversity and fulfilling various functions mediated by thousands of interactions in the extracellular matrix, at the cell surface, and within the cells where they have been detected in the nucleus. It is known that the chemical groups attached to GAGs and GAG conformations comprise "glycocodes" that are not yet fully deciphered. The molecular context also matters for GAG structures and functions, and the influence of the structure and functions of the proteoglycan core proteins on sulfated GAGs and vice versa warrants further investigation. The lack of dedicated bioinformatic tools for mining GAG data sets contributes to a partial characterization of the structural and functional landscape and interactions of GAGs. These pending issues will benefit from the development of new approaches reviewed here, namely (i) the synthesis of GAG oligosaccharides to build large and diverse GAG libraries, (ii) GAG analysis and sequencing by mass spectrometry (e.g., ion mobility-mass spectrometry), gas-phase infrared spectroscopy, recognition tunnelling nanopores, and molecular modeling to identify bioactive GAG sequences, biophysical methods to investigate binding interfaces, and to expand our knowledge and understanding of glycocodes governing GAG molecular recognition, and (iii) artificial intelligence for in-depth investigation of GAGomic data sets and their integration with proteomics.

Stochastic Nature and Intramolecular Coupling in Optical Response Profiles: Critical Analysis through Semiclassical Models.

We have studied the nonlinear absorptive and dispersive responses considering a molecular system consisting of two-levels, where aspects of the vibrational internal structure and intramolecular coupling are inserted, in addition to the considerations of interaction with the thermal reservoir. The Born-Oppenheimer electronic energy curve for this molecular model consists of two-intercrossing harmonic oscillator potentials with minima displaced in energy and nuclear coordinate. The results obtained show how these optical responses are sensitive to explicit considerations of both intramolecular coupling and the presence of the solvent through their stochastic interaction. Our study shows that the permanent dipoles of the system and the transition dipoles induced by electromagnetic field effects represent critical quantities for the analysis. The solvent action in our model is treated through the natural Bohr frequency shift to a time-dependent function, with explicit manifestations in its comparison as if the upper state were broadened. Significant variations in the nonlinear optical properties for cases of perturbative and saturative treatments, relaxation times, and optical propagation, mainly due to changes in the probe and pump intensities, are studied. Our studies relating the intramolecular effects with those generated by the presence of the solvent and its stochastic interaction with the solute of study, have allowed not only to analyze the influence of these in the profile of the optical responses, but they could also provide some insights into the analysis and characterization of molecular systems through nonlinear optical properties.

Intrinsic Dynamics of the ClpXP Proteolytic Machine Using Elastic Network Models.

ClpXP complex is an ATP-dependent mitochondrial matrix protease that binds, unfolds, translocates, and subsequently degrades specific protein substrates. Its mechanisms of operation are still being debated, and several have been proposed, including the sequential translocation of two residues (SC/2R), six residues (SC/6R), and even long-pass probabilistic models. Therefore, it has been suggested to employ biophysical-computational approaches that can determine the kinetics and thermodynamics of the translocation. In this sense, and based on the apparent inconsistency between structural and functional studies, we propose to apply biophysical approaches based on elastic network models (ENM) to study the intrinsic dynamics of the theoretically most probable hydrolysis mechanism. The proposed models ENM suggest that the ClpP region is decisive for the stabilization of the ClpXP complex, contributing to the flexibility of the residues adjacent to the pore, favoring the increase in pore size and, therefore, with the energy of interaction of its residues with a larger portion of the substrate. It is predicted that the complex may undergo a stable configurational change once assembled and that the deformability of the system once assembled is oriented, to increase the rigidity of the domains of each region (ClpP and ClpX) and to gain flexibility of the pore. Our predictions could suggest under the conditions of this study the mechanism of the interaction of the system, of which the substrate passes through the unfolding of the pore in parallel with a folding of the bottleneck. The variations in the distance calculated by molecular dynamics could allow the passage of a substrate with a size equivalent to ∼3 residues. The theoretical behavior of the pore and the stability and energy of binding to the substrate based on ENM models suggest that in this system, there are thermodynamic, structural, and configurational conditions that allow a possible translocation mechanism that is not strictly sequential.

BBX24 Interacts with JAZ3 to Promote Growth by Reducing DELLA Activity in Shade Avoidance.

Shade avoidance syndrome (SAS) is a strategy of major adaptive significance and typically includes elongation of the stem and petiole, leaf hyponasty, reduced branching and phototropic orientation of the plant shoot toward canopy gaps. Both cryptochrome 1 and phytochrome B (phyB) are the major photoreceptors that sense the reduction in the blue light fluence rate and the low red:far-red ratio, respectively, and both light signals are associated with plant density and the resource reallocation when SAS responses are triggered. The B-box (BBX)-containing zinc finger transcription factor BBX24 has been implicated in the SAS as a regulator of DELLA activity, but this interaction does not explain all the observed BBX24-dependent regulation in shade light. Here, through a combination of transcriptional meta-analysis and large-scale identification of BBX24-interacting transcription factors, we found that JAZ3, a jasmonic acid signaling component, is a direct target of BBX24. Furthermore, we demonstrated that joint loss of BBX24 and JAZ3 function causes insensitivity to DELLA accumulation, and the defective shade-induced elongation in this mutant is rescued by loss of DELLA or phyB function. Therefore, we propose that JAZ3 is part of the regulatory network that controls the plant growth in response to shade, through a mechanism in which BBX24 and JAZ3 jointly regulate DELLA activity. Our results provide new insights into the participation of BBX24 and JA signaling in the hypocotyl shade avoidance response in Arabidopsis.

ElectroPredictor: An Application to Predict Mayr's Electrophilicity E through Implementation of an Ensemble Model Based on Machine Learning Algorithms.

Electrophilicity (E) is one of the most important parameters to understand the reactivity of an organic molecule. Although the theoretical electrophilicity index (ω) has been associated with E in a small homologous series, the use of w to predict E in a structurally heterogeneous set of compounds is not a trivial task. In this study, a robust ensemble model is created using Mayr's database of reactivity parameters. A combination of topological and quantum mechanical descriptors and different machine learning algorithms are employed for the model's development. The predictability of the model is assessed using different statistical parameters, and its validation is examined, including a training/test partition, an applicability domain, and a y-scrambling test. The global ensemble model presents a Q5-fold2 of 0.909 and a Qext2 of 0.912, demonstrating an excellent predictability performance of E values and showing that w is not a good descriptor for the prediction of E, especially for the case of neutral compounds. ElectroPredictor, a noncommercial Python application (https://github.com/mmoreno1/ElectroPredictor), is developed to predict E. QM9, a well-known large dataset containing 133885 neutral molecules, is used to perform a virtual screening (94.0% coverage). Finally, the 10 most electrophilic molecules are analyzed as possible new Mayr's electrophiles, which have not yet been experimentally tested. This study confirms the necessity to build an ensemble model using nonlinear machine learning algorithms, topographic descriptors, and separating molecules into charged and neutral compounds to predict E with precision.

In vitro wearing away of orthodontic brackets and wires in different conditions: A review.

Introduction: The release of metallic ions from orthodontic brackets and wires typically depends on their quality (chemical composition) and the medium to which they are exposed, e.g., acidic, alkaline, substances with a high fluoride concentration, etc. This review examines corrosion and wear of orthodontic brackets, wires, and arches exposed to different media, including: beverages (juices), mouthwashes and artificial saliva among others, and the possible health effects resulting from the release of metallic ions under various conditions. Objective: This review aims to determine the exposure conditions that cause the most wear on orthodontic devices, as well as the possible health effects that can be caused by the release of metallic ions under various conditions. Sources: A search was carried out in the Scopus database, for articles related to oral media that can corrode brackets and wires. The initial research resulted in 8,127 documents, after applying inclusion and exclusion criteria, 76 articles remained. Conclusion: Stainless steel, which is commonly used in orthodontic devices, is the material that suffers the most wear. It was also found that acidic pH, alcohols, fluorides, and chlorides worsen orthodontic material corrosion. Further, nickel released from brackets and wires can cause allergic reactions and gingival overgrowth into patients.

Searching glycolate oxidase inhibitors based on QSAR, molecular docking, and molecular dynamic simulation approaches.

Primary hyperoxaluria type 1 (PHT1) treatment is mainly focused on inhibiting the enzyme glycolate oxidase, which plays a pivotal role in the production of glyoxylate, which undergoes oxidation to produce oxalate. When the renal secretion capacity exceeds, calcium oxalate forms stones that accumulate in the kidneys. In this respect, detailed QSAR analysis, molecular docking, and dynamics simulations of a series of inhibitors containing glycolic, glyoxylic, and salicylic acid groups have been performed employing different regression machine learning techniques. Three robust models with less than 9 descriptors-based on a tenfold cross (Q2 CV) and external (Q2 EXT) validation-were found i.e., MLR1 (Q2 CV = 0.893, Q2 EXT = 0.897), RF1 (Q2 CV = 0.889, Q2 EXT = 0.907), and IBK1 (Q2 CV = 0.891, Q2 EXT = 0.907). An ensemble model was built by averaging the predicted pIC50 of the three models, obtaining a Q2 EXT = 0.933. Physicochemical properties such as charge, electronegativity, hardness, softness, van der Waals volume, and polarizability were considered as attributes to build the models. To get more insight into the potential biological activity of the compouds studied herein, docking and dynamic analysis were carried out, finding the hydrophobic and polar residues show important interactions with the ligands. A screening of the DrugBank database V.5.1.7 was performed, leading to the proposal of seven commercial drugs within the applicability domain of the models, that can be suggested as possible PHT1 treatment.

Interaction of the new inhibitor paxlovid (PF-07321332) and ivermectin with the monomer of the main protease SARS-CoV-2: A volumetric study based on molecular dynamics, elastic networks, classical thermodynamics and SPT.

The COVID-19 pandemic has accelerated the study of drugs, most notably ivermectin and more recently Paxlovid (PF-07321332) which is in phase III clinical trials with experimental data showing covalent binding to the viral protease Mpro. Theoretical developments of catalytic site-directed docking support thermodynamically feasible non-covalent binding to Mpro. Here we show that Paxlovid binds non-covalently at regions other than the catalytic sites with energies stronger than reported and at the same binding site as the ivermectin B1a homologue, all through theoretical methodologies, including blind docking. We volumetrically characterize the non-covalent interaction of the ivermectin homologues (avermectins B1a and B1b) and Paxlovid with the mMpro monomer, through molecular dynamics and scaled particle theory (SPT). Using the fluctuation-dissipation theorem (FDT), we estimated the electric dipole moment fluctuations at the surface of each of complex involved in this study, with similar trends to that observed in the interaction volume. Using fluctuations of the intrinsic volume and the number of flexible fragments of proteins using anisotropic and Gaussian elastic networks (ANM+GNM) suggests the complexes with ivermectin are more dynamic and flexible than the unbound monomer. In contrast, the binding of Paxlovid to mMpro shows that the mMpro-PF complex is the least structurally dynamic of all the species measured in this investigation. The results support a differential molecular mechanism of the ivermectin and PF homologues in the mMpro monomer. Finally, the results showed that Paxlovid despite beingbound in different sites through covalent or non-covalent forms behaves similarly in terms of its structural flexibility and volumetric behaviour.

In Silico Searching for Alternative Lead Compounds to Treat Type 2 Diabetes through a QSAR and Molecular Dynamics Study.

Free fatty acid receptor 1 (FFA1) stimulates insulin secretion in pancreatic ß-cells. An advantage of therapies that target FFA1 is their reduced risk of hypoglycemia relative to common type 2 diabetes treatments. In this work, quantitative structure-activity relationship (QSAR) approach was used to construct models to identify possible FFA1 agonists by applying four different machine-learning algorithms. The best model (M2) meets the Tropsha's test requirements and has the statistics parameters R2 = 0.843, Q2CV = 0.785, and Q2ext = 0.855. Also, coverage of 100% of the test set based on the applicability domain analysis was obtained. Furthermore, a deep analysis based on the ADME predictions, molecular docking, and molecular dynamics simulations was performed. The lipophilicity and the residue interactions were used as relevant criteria for selecting a candidate from the screening of the DiaNat and DrugBank databases. Finally, the FDA-approved drugs bilastine, bromfenac, and fenofibric acid are suggested as potential and lead FFA1 agonists.

QSAR Studies, Molecular Docking, Molecular Dynamics, Synthesis, and Biological Evaluation of Novel Quinolinone-Based Thiosemicarbazones against Mycobacterium tuberculosis.

In this study, a series of novel quinolinone-based thiosemicarbazones were designed in silico and their activities tested in vitro against Mycobacterium tuberculosis (M. tuberculosis). Quantitative structure-activity relationship (QSAR) studies were performed using quinolinone and thiosemicarbazide as pharmacophoric nuclei; the best model showed statistical parameters of R2 = 0.83; F = 47.96; s = 0.31, and was validated by several different methods. The van der Waals volume, electron density, and electronegativity model results suggested a pivotal role in antituberculosis (anti-TB) activity. Subsequently, from this model a new series of quinolinone-thiosemicarbazone 11a-e was designed and docked against two tuberculosis protein targets: enoyl-acyl carrier protein reductase (InhA) and decaprenylphosphoryl-ß-D-ribose-2'-oxidase (DprE1). Molecular dynamics simulation over 200 ns showed a binding energy of -71.3 to -12.7 Kcal/mol, suggesting likely inhibition. In vitro antimycobacterial activity of quinolinone-thiosemicarbazone for 11a-e was evaluated against M. bovis, M. tuberculosis H37Rv, and six different strains of drug-resistant M. tuberculosis. All compounds exhibited good to excellent activity against all the families of M. tuberculosis. Several of the here synthesized compounds were more effective than the standard drugs (isoniazid, oxafloxacin), 11d and 11e being the most active products. The results suggest that these compounds may contribute as lead compounds in the research of new potential antimycobacterial agents.

Sobrevida de un paciente adulto mayor con cáncer de pulmón, tratado con quimioterapia de primera línea

RESUMEN Introducción: El cáncer de pulmón está afectando cada vez más a la población de adultos mayores, a medida que la expectativa de vida aumenta. Sin embargo, es difícil establecer la eficacia de la quimioterapia y el pronóstico de estos pacientes es grave. Objetivo: Presentar un caso de paciente adulto mayor con cáncer de pulmón avanzado de células no pequeñas, con una prolongada sobrevida que recibió solamente quimioterapia de primera línea. Caso clínico: Paciente no fumador, de 71 años, diagnosticado con cáncer de pulmón de células no pequeñas avanzado, del subtipo adenocarcinoma, con compromiso pleural. Inició tratamiento con carboplatino 5 AUC y gemcitabina 1,1 g. En el noveno ciclo, se encontró reducción de los nódulos pulmonares, pero también metástasis en el nivel D6-D7. Inició la segunda línea de tratamiento con carboplatino 5,4 AUC, paclitaxel 200 mg y ácido zolendrónico en dosis de 4,0 mg. Debido a eventos adversos, el tratamiento fue cambiado a vinorelbina 2,5 g y ácido zolendrónico 4,0 mg. Tras dos ciclos, el paciente fallece, alcanzando 21 meses de sobrevida global, solo con quimioterapia. Conclusión: El tratamiento del paciente adulto mayor con cáncer de pulmón es complejo. En el presente esquema de quimioterapia, el paciente pudo alcanzar 21 meses de sobrevida global, a pesar de que no fue caracterizado molecularmente.

ABSTRACT Introduction: Lung cancer is taking an increasing toll on the older population as life expectancy increases. However, the efficacy of chemotherapy is difficult to establish and the prognosis of these patients is severe. Objective: Report a case of an older adult patient with advanced non-small cell lung cancer with prolonged survival who received only first-line chemotherapy. Case report: A 71-year-old non-smoker patient diagnosed with advanced non-small cell lung cancer, adenocarcinoma subtype, with pleural involvement. He started treatment with carboplatin 5 AUC and gemcitabine 1,1 g. In the ninth cycle, reduction of pulmonary nodules was found, but he also had metastases at the D6-D7 level. He started the second line of treatment with carboplatin 5,4 AUC, paclitaxel 200 mg and zolendronic acid at a dose of 4,0 mg. Due to adverse events, the treatment was changed to vinorelbine 2,5 g and zolendronic acid 4.0 mg. After two cycles, the patient died, reaching 21 months of overall survival, only with chemotherapy. Conclusion: The treatment of the older adult patient with lung cancer is challenging. In the present chemotherapy treatment, the patient was able to achieve 21 months of overall survival, despite the fact that he was not molecularly characterized.

Effect of the Nucleophile's Nature on Chloroacetanilide Herbicides Cleavage Reaction Mechanism. A DFT Study.

In this study, the degradation mechanism of chloroacetanilide herbicides in the presence of four different nucleophiles, namely: Br-, I-, HS-, and S2O3-2, was theoretically evaluated using the dispersion-corrected hybrid functional wB97XD and the DGDZVP as a basis set. The comparison of computed activation energies with experimental data shows an excellent correlation (R2 = 0.98 for alachlor and 0.97 for propachlor). The results suggest that the best nucleophiles are those where a sulfur atom performs the nucleophilic attack, whereas the other species are less reactive. Furthermore, it was observed that the different R groups of chloroacetanilide herbicides have a negligible effect on the activation energy of the process. Further insights into the mechanism show that geometrical changes and electronic rearrangements contribute 60% and 40% of the activation energy, respectively. A deeper analysis of the reaction coordinate was conducted, employing the evolution chemical potential, hardness, and electrophilicity index, as well as the electronic flux. The charge analysis shows that the electron density of chlorine increases as the nucleophilic attack occurs. Finally, NBO analysis indicates that the nucleophilic substitution in chloroacetanilides is an asynchronous process with a late transition state for all models except for the case of the iodide attack, which occurs through an early transition state in the reaction.

Predicting the Adsorption of Amoxicillin and Ibuprofen on Chitosan and Graphene Oxide Materials: A Density Functional Theory Study.

The occurrence, persistence, and accumulation of antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) represent a new environmental problem due to their harmful effects on human and aquatic life. A suitable absorbent for a particular type of pollutant does not necessarily absorb other types of compounds, so knowing the compatibility between a particular pollutant and a potential absorbent before experimentation seems to be fundamental. In this work, the molecular interactions between some pharmaceuticals (amoxicillin, ibuprofen, and tetracycline derivatives) with two potential absorbers, chitosan and graphene oxide models (pyrene, GO-1, and coronene, GO-2), were studied using the ωB97X-D/6-311G(2d,p) level of theory. The energetic interaction order found was amoxicillin/chitosan > amoxicillin/GO-1 > amoxicillin/GO-2 > ibuprofen/chitosan > ibuprofen/GO-2 > ibuprofen/GO-1, the negative sign for the interaction energy in all complex formations confirms good compatibility, while the size of Eint between 24-34 kcal/mol indicates physisorption processes. Moreover, the free energies of complex formation were negative, confirming the spontaneity of the processes. The larger interaction of amoxicillin Gos, compared to ibuprofen Gos, is consistent with previously reported experimental results, demonstrating the exceptional predictability of these methods. The second-order perturbation theory analysis shows that the amoxicillin complexes are mainly driven by hydrogen bonds, while van der Waals interactions with chitosan and hydrophobic interactions with graphene oxides are modelled for the ibuprofen complexes. Energy decomposition analysis (EDA) shows that electrostatic energy is a major contributor to the stabilization energy in all cases. The results obtained in this work promote the use of graphene oxides and chitosan as potential adsorbents for the removal of these emerging pollutants from water.

First report in pre-Columbian mummies from Bolivia of Enterobius vermicularis infection and capillariid eggs: A contribution to Paleoparasitology studies.

OBJECTIVE: This study was designed to search for ancient parasites in abdominal content and coprolites from Bolivian mummies. MATERIALS: Twelve mummified individuals from the Andean highlands, housed at the National Museum of Archaeology (MUNARQ) in La Paz, Bolivia. METHODS: Microscopic analysis of rehydrated samples (coprolites and abdominal content), following Lutz's spontaneous sedimentation technique. RESULTS: Eggs of Enterobius vermicularis were identified in coprolites from one mummy, and capillariid eggs in the organic abdominal content from another individual. CONCLUSIONS: This is the first evidence of ancient intestinal parasites in Bolivian mummies. SIGNIFICANCE: This pioneering study focused on the search of ancient intestinal parasites in human remains of the Bolivian Andes and contributes to greater knowledge of paleoparasitology in South America. LIMITATIONS: All mummies in the MUNARQ belonged to the Andean Bolivian highlands (post-Tiwanaku era or Late Intermediate Period), although the exact provenance of the material and the associated contexts are not well recorded. SUGGESTIONS FOR FURTHER RESEARCH: Considering the great number of well-known archaeological sites and other unexplored sites in Bolivia, in addition to large collections in museums, further paleopathological and paleoparasitological molecular studies in mummies and skeletons are called for.

Use of omics analytical methods in the study of genetically modified maize varieties tested in 90 days feeding trials.

Genetically modified (GM) maize and their non-modified counterparts were compared using MON810 varieties, the only GMO event cultivated in Europe. The differences in grain samples were analysed by omics profiles, including transcriptomics, proteomics and metabolomics. Other cultivated maize varieties were analysed as a reference for the variability that will exist between cultivated varieties. The observed differences between modified and non-modified maize varieties do not exceed typical differences between non-modified varieties. The use of these advanced analytical approaches to analyse novel plant materials as compared to the results from animal feeding trials with whole foods is assessed. No indications were observed for changes in the GM varieties that warrant further investigations. Furthermore, it was shown that such indications will be obtained if maize samples of inferior quality are analysed similarly. Omics data provide detailed analytical information of the plant material, which facilitates a risk assessment procedure of new (GM) plant varieties.

New structural insights into the role of TROVE2 complexes in the on-set and pathogenesis of systemic lupus erythematosus determined by a combination of QCM-D and DPI.

The mechanism of self-recognition of the autoantigen TROVE2, a common biomarker in autoimmune diseases, has been studied with a quartz crystal microbalance with dissipation monitoring (QCM-D) and dual polarization interferometry (DPI). The complementarity and remarkable analytical features of both techniques has allowed new insights into the onset of systemic lupus erythematosus (SLE) to be achieved at the molecular level. The in vitro study for SLE patients and healthy subjects suggests that anti-TROVE2 autoantibodies may undergo an antibody bipolar bridging. An epitope-paratope-specific binding initially occurs to activate a hidden Fc receptor in the TROVE2 tertiary structure. This bipolar mechanism may contribute to the pathogenic accumulation of anti-TROVE2 autoantibody immune complex in autoimmune disease. Furthermore, the specific calcium-dependent protein-protein bridges point out at how the TRIM21/TROVE2 association might occur, suggesting that the TROVE2 protein could stimulate the intracellular immune signaling via the TRIM21 PRY-SPRY domain. These findings may help to better understand the origins of the specificity and affinity of TROVE2 interactions, which might play a key role in the SLE pathogenesis. This manuscript gives one of the first practical applications of two novel functions (-df/dD and Δh/molec) for the analysis of the data provided by QCM-D and DPI. In addition, it is the first time that QCM-D has been used for mapping hidden Fc receptors as well as linear epitopes in a protein tertiary structure. Graphical abstract ᅟ.

Applicability of demirjian and chaillet's methods in estimating dental age in children from the state of Zulia, Venezuela / Aplicabilidad de los métodos de demirjian y chaillet en la estimación de la edad dental de niños del estado Zulia, Venezuela

ABSTRACT. Introduction: dental age (DA) is used in clinical disciplines to assess whether an individual is advanced or delayed in his or her dental development, or to determine the age of living or deceased subjects with no valid identification documents; it is also useful in forensic practice. Objective: to study the applicability of the methods of Demirjian et al (revised, 1976) and Chaillet et al in estimating DA in a sample of Venezuelan children and adolescents. Methods: a descriptive, retrospective field study in 516 panoramic X-rays of patients of both sexes with chronological ages ranging from 6 to 18 years. Dental development was assessed in the seven lower left teeth using the maturation stages proposed in the method of Demirjian et al, while DA calculation was carried out according to the reference tables provided by each method. Descriptive statistics were obtained, as well as mean differences between chronological age (CA) and DA estimated by a Student's test. Results: there was age overestimation with Demirjian's method up to the age of 15 years, as well as age underestimation with Chaillet's method. Considering the total sample, both methods underestimated age (Demirjian 0.20 ± 1.46; Chaillet 0.34 ± 1.39), and the difference between CA and DA was significant (Demirjian p = 0.0002; Chaillet p = 0.000). Conclusions: both methods can be used in the sample studied, considering that DA should be assessed in conjunction with other indicators of maturation to evaluate the development of an individual.

RESUMEN Introducción: la edad dental (ED) es empleada en disciplinas clínicas para evaluar si el individuo se encuentra avanzado o atrasado en su desarrollo dentario, o bien para asignar la edad de sujetos vivos o fallecidos sin documentos válidos de identificación, y es de utilidad en la práctica forense. Objetivo: estudiar la aplicabilidad de los métodos de Demirjian et al revisado (1976) y Chaillet et al en la estimación de la ED en una muestra de niños y adolescentes venezolanos. Métodos: se realizó un estudio descriptivo, retrospectivo y de campo; para ello se analizaron 516 radiografías panorámicas de pacientes de ambos sexos con edades cronológicas entre 6 y 18 años. El desarrollo dental fue evaluado en los siete dientes inferiores izquierdos mediante los estadios de maduración propuestos en el método de Demirjian et al, mientras que el cálculo de la ED fue realizado de acuerdo a las tablas de referencia proporcionadas por cada método. Se obtuvieron estadísticas descriptivas, así como diferencias de media entre la edad cronológica (EC) y la ED estimada mediante un test de Student. Resultados: se observó sobreestimación de la edad por el método de Demirjian hasta los 15 años de edad, así como subestimación de la edad con el método de Chaillet. Considerando el total de la muestra, ambos métodos subestimaron la edad (Demirjian 0,20 ± 1,46; Chaillet 0,34 ± 1,39), y la diferencia entre EC y ED fue significativa (Demirjian p = 0,0002; Chaillet p = 0,000). Conclusiones: ambos métodos pueden ser empleados en la muestra estudiada, teniendo en cuenta que la ED debe ser valorada en conjunto con otros indicadores de maduración para la evaluación del desarrollo del individuo.