Exploring the Combined Action of Adding Pertuzumab to Branded Trastuzumab versus Trastuzumab Biosimilars for Treating HER2+ Breast Cancer.

The binding activity of various trastuzumab biosimilars versus the branded trastuzumab towards the glycosylated extracellular domain of the human epidermal growth factor receptor 2 (HER2) target in the presence of pertuzumab was investigated. We employed size exclusion chromatography with tetra-detection methodology to simultaneously determine absolute molecular weight, concentration, molecular size, and intrinsic viscosity. All trastuzumab molecules in solution exhibit analogous behavior in their binary action towards HER2 regardless of the order of addition of trastuzumab/pertuzumab. This analogous behavior of all trastuzumab molecules, including biosimilars, highlights the robustness and consistency of their binding activity towards HER2. Furthermore, the addition of HER2 to a mixture of trastuzumab and pertuzumab leads to increased formation of high-order HER2 complexes, up to concentrations of one order of magnitude higher than in the case of sequential addition. The observed increase suggests a potential synergistic effect between these antibodies, which could enhance their therapeutic efficacy in HER2-positive cancers. These findings underscore the importance of understanding the complex interplay between therapeutic antibodies and their target antigens, providing valuable insights for the development of more effective treatment strategies.

Assessing the Impact of the 2020 Council of State and Territorial Epidemiologists Case Definition for Pertussis on Reported Pertussis Cases.

BACKGROUND: In 2020, the Council of State and Territorial Epidemiologists (CSTE) pertussis case definition was modified; the main change was classifying PCR-positive cases as confirmed, regardless of cough duration. Pertussis data reported through Enhanced Pertussis Surveillance (EPS) in seven sites and the National Notifiable Diseases Surveillance System (NNDSS) were used to evaluate the impact of the new case definition. METHODS: We compared the number of EPS cases with cough onset in 2020 to the number that would have been reported based on the prior (2014) CSTE case definition. To assess the impact of the change nationally, the proportion of EPS cases newly reportable under the 2020 CSTE case definition was applied to 2020 NNDSS data to estimate how many additional cases were captured nationally. RESULTS: Among 442 confirmed and probable cases reported to EPS states in 2020, 42 (9.5%) were newly reportable according to the 2020 case definition. Applying this proportion to the 6,124 confirmed and probable cases reported nationally in 2020, we estimated that the new definition added 582 cases. Had the case definition not changed, reported cases in 2020 would have decreased by 70% from 2019; the observed decrease was 67%. CONCLUSIONS: Despite a substantial decrease in reported pertussis cases in the setting of COVID-19, our data show that the 2020 pertussis case definition change resulted in additional case reporting compared with the previous case definition, providing greater opportunities for public health interventions such as prophylaxis of close contacts.

The DEAD-box ATPase Dbp10/DDX54 initiates peptidyl transferase center formation during 60S ribosome biogenesis.

DEAD-box ATPases play crucial roles in guiding rRNA restructuring events during the biogenesis of large (60S) ribosomal subunits, but their precise molecular functions are currently unknown. In this study, we present cryo-EM reconstructions of nucleolar pre-60S intermediates that reveal an unexpected, alternate secondary structure within the nascent peptidyl-transferase-center (PTC). Our analysis of three sequential nucleolar pre-60S intermediates reveals that the DEAD-box ATPase Dbp10/DDX54 remodels this alternate base pairing and enables the formation of the rRNA junction that anchors the mature form of the universally conserved PTC A-loop. Post-catalysis, Dbp10 captures rRNA helix H61, initiating the concerted exchange of biogenesis factors during late nucleolar 60S maturation. Our findings show that Dbp10 activity is essential for the formation of the ribosome active site and reveal how this function is integrated with subsequent assembly steps to drive the biogenesis of the large ribosomal subunit.

Phenotypic and genotypic characterizations of bacteria isolated from the respiratory microbiota of healthy turkeys with potential for probiotic composition.

Desirable characteristics of Staphylococcus sp., Streptococcus sp., Bacillus sp., Klebsiella sp., Escherichia coli, and Pseudomonas pseudoalcaligenes isolated from the trachea of healthy turkeys were evaluated as probiotic candidates in the search for new alternatives to solve antimicrobial resistance issues in poultry. In current study phenotypic and genotypic capacity to produce bacteriocin-like substances, efficacy to inhibit the growth of avian pathogens, susceptibility to antimicrobials of bacteria isolated from the respiratory microbiota of healthy turkeys, and the presence of virulence-associated genes (VAGs) predictors of Avian Pathogenic Escherichia coli (APEC) were evaluated. Nine E. coli and one Klebsiella sp. strains produced bacteriocin-like substances, and all harbored the cvaA gene. Some strains also showed antagonistic activity against APEC. Multidrug-resistant profile was found in 54% of the strains. Six strains of bacteriocin-like substances producing E. coli also harbored 3-5 VAGs. The study showed that two bacterial genuses (Klebsiella sp. and E. coli) present desirable probiotic characteristics. Our results identified strains with potential for poultry's respiratory probiotic.

Un desafío terapéutico: la heterorresistencia en Mycobacterium tuberculosis / An emerging problem: heteroresistance in Mycobacterium tuberculosis

Resumen Se considera infección mixta por Mycobacterium tuberculosis (Mtb) a la coexistencia en forma simul tánea y en un mismo paciente de 2 cepas diferentes de Mtb o 2 variantes distintas de la misma cepa. Cuando una de las variantes selecciona mutaciones de resistencia, se denomina heterorresistencia (HTR) monoclonal; en caso de que sean 2 cepas diferentes, una sensible y una resistente (o cepas con diferentes patrones de resistencia), se denomina HTR policlo nal. Se presentan 3 pacientes, HIV/sida, todos con reiterados problemas de adherencia al tratamiento, en los cuales a través de la secuenciación genómica completa de Mtb se diagnosticó HTR monoclonal con coexistencia de 2 variantes de la misma cepa aisladas de muestras de pulmón y ganglios linfáticos, con diferentes perfiles de resistencia en cada uno de los casos. Es importante pensar en la posibilidad de HTR, principalmente en pacientes con múltiples intentos terapéuticos previos y altas poblaciones bacilares, como en el sida avanzado, dado que esta situación compromete potencialmente los resultados del tratamiento al coexistir cepas o variantes de ce pas sensibles y resistentes.

Abstract Mixed infection by Mycobacterium tuberculosis (Mtb) consists in the simultaneous coexistence in the same patient of two different strains of Mtb or 2 different variants of the same strain. When one of the variants selects for resistance mutations, it is called monoclonal heteroresistance (HTR); if there are 2 different strains, one sensitive and one resistant (or with different resis tance patterns), it is called polyclonal HTR. Three cases of HIV/AIDS patients are presented, all with repeated treatment adherence problems, in whom monoclonal HTR was diagnosed through Mtb complete genomic sequentiation with the coexistence of two variants of the same strain isolated from samples from lung and lymph nodes, with different resistance profiles in each case. It is important to consider the possibility of HTR, especially in patients with multiple previous therapeu tic attempts and high bacillary populations, such as in advanced AIDS, since this situation potentially com promises treatment results by coexisting sensitive and resistant variants of a strain (or strains).

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

The DEAD-box ATPase Dbp10/DDX54 initiates peptidyl transferase center formation during 60S ribosome biogenesis.

DEAD-box ATPases play crucial roles in guiding rRNA restructuring events during the biogenesis of large (60S) ribosomal subunits, but their precise molecular functions are currently unknown. In this study, we present cryo-EM reconstructions of nucleolar pre-60S intermediates that reveal an unexpected, alternate secondary structure within the nascent peptidyl-transferase-center (PTC). Our analysis of three sequential nucleolar pre-60S intermediates reveals that the DEAD-box ATPase Dbp10/DDX54 remodels this alternate base pairing and enables the formation of the rRNA junction that anchors the mature form of the universally conserved PTC A-loop. Post-catalysis, Dbp10 captures rRNA helix H61, initiating the concerted exchange of biogenesis factors during late nucleolar 60S maturation. Our findings show that Dbp10 activity is essential for the formation of the ribosome active site and reveal how this function is integrated with subsequent assembly steps to drive the biogenesis of the large ribosomal subunit.

[An emerging problem: heteroresistance in Mycobacterium tuberculosis]. / Un desafío terapéutico: la heterorresistencia en Mycobacterium tuberculosis.

Mixed infection by Mycobacterium tuberculosis (Mtb) consists in the simultaneous coexistence in the same patient of two different strains of Mtb or 2 different variants of the same strain. When one of the variants selects for resistance mutations, it is called monoclonal heteroresistance (HTR); if there are 2 different strains, one sensitive and one resistant (or with different resistance patterns), it is called polyclonal HTR. Three cases of HIV/AIDS patients are presented, all with repeated treatment adherence problems, in whom monoclonal HTR was diagnosed through Mtb complete genomic sequentiation with the coexistence of two variants of the same strain isolated from samples from lung and lymph nodes, with different resistance profiles in each case. It is important to consider the possibility of HTR, especially in patients with multiple previous therapeutic attempts and high bacillary populations, such as in advanced AIDS, since this situation potentially compromises treatment results by coexisting sensitive and resistant variants of a strain (or strains).

Se considera infección mixta por Mycobacterium tuberculosis (Mtb) a la coexistencia en forma simultánea y en un mismo paciente de 2 cepas diferentes de Mtb o 2 variantes distintas de la misma cepa. Cuando una de las variantes selecciona mutaciones de resistencia, se denomina heterorresistencia (HTR) monoclonal; en caso de que sean 2 cepas diferentes, una sensible y una resistente (o cepas con diferentes patrones de resistencia), se denomina HTR policlonal. Se presentan 3 pacientes, HIV/sida, todos con reiterados problemas de adherencia al tratamiento, en los cuales a través de la secuenciación genómica completa de Mtb se diagnosticó HTR monoclonal con coexistencia de 2 variantes de la misma cepa aisladas de muestras de pulmón y ganglios linfáticos, con diferentes perfiles de resistencia en cada uno de los casos. Es importante pensar en la posibilidad de HTR, principalmente en pacientes con múltiples intentos terapéuticos previos y altas poblaciones bacilares, como en el sida avanzado, dado que esta situación compromete potencialmente los resultados del tratamiento al coexistir cepas o variantes de cepas sensibles y resistentes.

Binding Affinity of Trastuzumab and Pertuzumab Monoclonal Antibodies to Extracellular HER2 Domain.

The binding affinity of trastuzumab and pertuzumab to HER2 has been studied using both experimental and in silico methods. The experiments were conducted using the antibodies in their complete IgG form, as used in clinical therapy, and the extracellular domain of the HER2 protein in solution. This approach provides a precise, reproducible, and reliable view of the interaction between them in physicochemical conditions similar to those found in the tumoral environment. Dynamic light scattering and size exclusion chromatography coupled with tetra detection were utilized to characterize the protein complexes, measure their concentrations, and calculate the equilibrium-free binding energy, ΔGbind. In addition, PRODIGY, a QSAR-like model with excellent predictive ability, was employed to obtain in silico ΔGbind estimations. The results obtained indicate that pertuzumab exhibits a slightly higher binding affinity to HER2 than trastuzumab. The difference in binding affinity was explained based on the contribution of the different interfacial contact (IC) descriptors to the ΔGbind value estimated by the PRODIGY model. Furthermore, experiments revealed that the pertuzumab IgG antibody binds preferentially to two HER2 proteins, one per Fab fragment, while trastuzumab mainly forms a monovalent complex. This finding was interpreted based on a geometrical model that identified steric crowding in the trastuzumab-HER2 complex as compared with the pertuzumab-HER2 complex.

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study Protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5,000 richly-phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

Mucuna pruriens cannot develop phytoremediation of tebuthiuron in agricultural soil with vinasse: a morphometrical and ecotoxicological analysis.

Pesticides offer stakeholders cost-effective solutions to control weeds. Nevertheless, such active compounds can manifest as severe environmental pollutants when escaping from agroecosystems into surrounding natural ecosystems, driving the need to remediate them. We, hence, analyzed whether Mucuna pruriens can develop a potential phytoremediator for treating tebuthiuron (TBT) in soil with vinasse. We exposed M. pruriens to microenvironments containing tebuthiuron at 0.5, 1, 1.5, and 2 (standard dose) L ha-1 and vinasse at 75, 150 (industrial recommendation), and 300 m3·ha-1. Experimental units without organic compounds represented controls. We assessed M. pruriens for morphometrical features, such as plant height and stem diameter and shoot/root dry mass, over approximately 60 days. We obtained evidence for M. pruriens not effectively removing tebuthiuron from the terrestrial medium. Such a pesticide developed phytotoxicity, significantly limiting its germination and growth. The higher the dose, the more negatively the tebuthiuron impacted the plant. In addition, introducing vinasse into the system, irrespective of volume, intensified the damage to photosynthetic and non-photosynthetic structures. Equally important, its antagonist action further decreased the production and accumulation of biomass. As M. pruriens could not effectively extract tebuthiuron from the soil, it could allow neither Crotalaria juncea nor Lactuca sativa to grow on synthetic media containing residual pesticide. An atypical performance of such testing (tebuthiuron-sensitive) organisms over independent ecotoxicological bioassays validated inefficient phytoremediation. Hence, M. pruriens could not offer a functional remediative option to treat environmental pollution by tebuthiuron in agroecosystems where vinasse occurs, such as sugarcane-producing areas. Although M. pruriens considered a tebuthiuron phytoremediator as cited in the literature, satisfactory results did not occur in our research due to high concentrations of vinasse in the soil. Therefore, this information requires more specific studies about the influence of high concentrations of organic matter on M. pruriens productivity and phytoremediation performance.

High post-exposure prophylaxis (PEP) uptake among household contacts of pertussis patients enrolled in a PEP effectiveness evaluation - United States, 2015-2017.

BACKGROUND: Post-exposure prophylaxis (PEP) for pertussis is recommended for household contacts of pertussis cases in the United States within 21 days of exposure, but data on PEP effectiveness for prevention of secondary cases in the setting of widespread pertussis vaccination are limited. We implemented a multi-state evaluation of azithromycin PEP use and effectiveness among household contacts. METHODS: Culture- or PCR-confirmed pertussis cases were identified through surveillance. Household contacts were interviewed within 7 days of case report and again 14-21 days later. Interviewers collected information on exposure, demographics, vaccine history, prior pertussis diagnosis, underlying conditions, PEP receipt, pertussis symptoms, and pertussis testing. A subset of household contacts provided nasopharyngeal and blood specimens during interviews. RESULTS: Of 299 household contacts who completed both interviews, 12 (4%) reported not receiving PEP. There was no evidence of higher prevalence of cough or pertussis symptoms among contacts who did not receive PEP. Of 168 household contacts who provided at least one nasopharyngeal specimen, four (2.4%) were culture or PCR positive for B. pertussis; three of these received PEP prior to their positive test result. Of 156 contacts with serologic results, 14 (9%) had blood specimens that were positive for IgG anti-pertussis toxin (PT) antibodies; all had received PEP. CONCLUSIONS: Very high PEP uptake was observed among household contacts of pertussis patients. Although the number of contacts who did not receive PEP was small, there was no difference in prevalence of pertussis symptoms or positive laboratory results among these contacts compared with those who did receive PEP.

rRNA methylation by Spb1 regulates the GTPase activity of Nog2 during 60S ribosomal subunit assembly.

Biogenesis of the large ribosomal (60S) subunit involves the assembly of three rRNAs and 46 proteins, a process requiring approximately 70 ribosome biogenesis factors (RBFs) that bind and release the pre-60S at specific steps along the assembly pathway. The methyltransferase Spb1 and the K-loop GTPase Nog2 are essential RBFs that engage the rRNA A-loop during sequential steps in 60S maturation. Spb1 methylates the A-loop nucleotide G2922 and a catalytically deficient mutant strain (spb1D52A) has a severe 60S biogenesis defect. However, the assembly function of this modification is currently unknown. Here, we present cryo-EM reconstructions that reveal that unmethylated G2922 leads to the premature activation of Nog2 GTPase activity and capture a Nog2-GDP-AlF4- transition state structure that implicates the direct involvement of unmodified G2922 in Nog2 GTPase activation. Genetic suppressors and in vivo imaging indicate that premature GTP hydrolysis prevents the efficient binding of Nog2 to early nucleoplasmic 60S intermediates. We propose that G2922 methylation levels regulate Nog2 recruitment to the pre-60S near the nucleolar/nucleoplasmic phase boundary, forming a kinetic checkpoint to regulate 60S production. Our approach and findings provide a template to study the GTPase cycles and regulatory factor interactions of the other K-loop GTPases involved in ribosome assembly.

First report on quality and purity assessment of sweet almond oil in Brazilian body oils by gas chromatography and mass spectrometry.

Sweet almond oil is a raw material with high-added value used in different products. Then, the aim of this study is to evaluate the quality and purity of 10 body oils based on sweet almond oils currently available in the Brazilian market. Fatty acid composition and triacylglycerol (TAG) profile were determined by gas chromatography with flame ionization detector (GC-FID) and atmospheric solids analysis probe mass spectrometry (ASAP-MS), respectively. The authenticity of samples was assessed using an analytical curve equation. Soybean oil was chosen as the adulterant because it is the cheapest vegetable oil commercialized in Brazil. Hierarchical clustering analysis (HCA) in conjunction with ASAP-MS classified product samples according to the type of vegetable oil (soybean and sweet almond oils). The addition of soybean oil (8.79% to 99.70%) was confirmed in samples. However, only two samples stated in their label the presence of soybean oil as an ingredient. These findings highlight the need for better oversight by regulatory bodies to ensure that consumers acquire high quality and authentic products based on equally high quality and purity of sweet almond oils.

Impact of the final agitation system in the irrigant diffusion inside the root canal: A micro-CT analysis.

This study evaluated, through micro-computed tomography (micro-CT), the volume of irrigant diffusion by different techniques of final agitation. Sixty mesiobuccal canals were scanned in a micro-CT and standardised according to the volume. They were instrumented with the MTwo 40/04 system and using the Terebrix 35 contrast solution as irrigant, were divided into six groups (n = 10): Conventional irrigation with syringe and needle (CI), EndoActivator (EA), EasyClean (EC), RinsEndo (RE), Utrasonic agitation (UI) and XP-Clean (XP). A second micro-CT scan was performed and the total irrigant volume and in the final 3 mm apical were determined. The data were analysed using the Anova, Kruskal-Wallis and Dunn tests (p < 0.05). UI and XP showed a higher percentage of total diffusion than CI, EA and RS groups (p < 0.05). In apical diffusion, there was no significant difference between groups (p > 0.05). The final agitation system increases the diffusion of irrigating agents inside the root canal.

Influencia del modelo social, actividad físico-deportiva y salud en alumnos de secundaria

Introducción: La inactividad física en adolescentes es uno de los problemas actuales que ha cobrado relevancia, debido a que investigaciones proyectan hábitos de vida no saludables en la adultez. Es por ello, que instancias públicas y privadas buscan romper con esta mala práctica. Esto estimula a investigar sobre los actores que interactúan de forma continua con los adolescentes, de tal manera que los motive a entrar a un entorno que promueva la realización de actividades físicas. Objetivo: Evaluar la influencia de los modelos sociales que influyen en la realización de actividades físicas y en la salud de los estudiantes del nivel secundario en República Dominicana. Métodos: El estudio fue realizado en base a un enfoque cuantitativo descriptivo de corte transversal mediante encuesta, empleando el muestreo no probabilístico por conveniencia, debido a la disponibilidad mostrada por la población objeto de estudio al llenado del instrumento. La población estuvo integrada por 777 estudiantes, quienes brindaron las informaciones relativas al índice de actividad física y modelos sociales que influyen a su práctica. En la investigación se utilizó Cuestionario Internacional sobre el Estilo de Vida del Alumnado. Resultados: Los datos alcanzados muestran altos niveles de sedentarismo sobrepasando el 83 % en ambos sexos, con mayor presencia en las mujeres. En lo concerniente a los modelos sociales que tributan a la práctica de actividad física, se reafirman los padres y las amistades como los más influyentes. Conclusiones: Existen altos niveles de sedentarismo chicos y chicas adolescentes contrastado con la influencia positiva que reciben de padres y amigos para la realización de actividad física, lo cual puede ser utilizado con el objetivo de crear proyectos que incentiven la práctica de actividad físico-deportiva y contribuyan a la prevención de las enfermedades no transmisibles.

Introduction : Physical inactivity in adolescents is one of the current problems that has gained relevance, due to the fact that research projects unhealthy lifestyle habits in adulthood in this age group. For this reason, public and private instances seek to break this bad practice. The aforementioned, stimulates research on the actors that interact continuously with adolescents, in such a way that motivates them to enter an environment that promotes physical activities. Objective: To evaluate the impact of social models that influence the performance of physical activities and the health of secondary school students in the Dominican Republic. Methods: The present study was carried out based on a cross-sectional, descriptive quantitative approach by means of a survey, using non-probabilistic sampling by convenience, due to the availability shown by the population under study when filling out the instrument. The population consisted of 777 students, who provided information on the rate of physical activity and social models that influence its practice. The International Student Lifestyle Questionnaire was used in the research. Results: The data obtained show high levels of sedentary lifestyles, exceeding 83% in both sexes, with a greater presence in women. Regarding the social models that contribute to the practice of physical activity, parents and friends are reaffirmed as the most influential. Conclusions: There are high levels of sedentary adolescent boys and girls contrasted with the positive influence they receive from parents and friends for the practice of physical activity, which can be used with the aim of creating projects that encourage the practice of physical-sports activities and contribute to the prevention of non-communicable diseases.

Sequence-specific remodeling of a topologically complex RNP substrate by Spb4.

DEAD-box ATPases are ubiquitous enzymes essential in all aspects of RNA biology. However, the limited in vitro catalytic activities described for these enzymes are at odds with their complex cellular roles, most notably in driving large-scale RNA remodeling steps during the assembly of ribonucleoproteins (RNPs). We describe cryo-EM structures of 60S ribosomal biogenesis intermediates that reveal how context-specific RNA unwinding by the DEAD-box ATPase Spb4 results in extensive, sequence-specific remodeling of rRNA secondary structure. Multiple cis and trans interactions stabilize Spb4 in a post-catalytic, high-energy intermediate that drives the organization of the three-way junction at the base of rRNA domain IV. This mechanism explains how limited strand separation by DEAD-box ATPases is leveraged to provide non-equilibrium directionality and ensure efficient and accurate RNP assembly.

Comparative Performance of the Resilience Inventory (IRES) and Resilience Scale-14 (RS-14) Spanish Versions Among Postpartum Adolescent Mothers.

We sought to evaluate the psychometric properties of two resilience scales; the Resilience Inventory (IRES) and the 14-item Resilience Scale (RS-14) among Peruvian postpartum adolescent mothers. This cross-sectional study included 785 adolescent mothers who delivered at a maternity hospital in Lima, Peru. The Spanish versions of IRES and RS-14 were used to evaluate the properties of the measures. We examined reliability using Cronbach's alpha. We used exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to assess the construct validity and factor structures of the two scales. Both scales had good internal consistency (Cronbach's alpha > 0.7). Correlation between IRES and RS-14 scores was fair (r = 0.53). The EFA results of both scales yielded a three-factor structure. EFA including all items from IRES and RS-14 yielded a six-factor structure. CFA results corroborated the original seven-factor structure for IRES and yielded measures indicating a good level of goodness of fit (comparative fit index of 0.93) and accuracy (root mean square error of approximation of 0.07). Overall, Spanish language versions of both the IRES and the RS-14 are reliable and valid scales for assessing resilience among Peruvian postpartum adolescent mothers. Additional research is needed to integrate culturally-specific traits into resilience measures.

Histone deacetylases modulate resistance to the therapy in lung cancer.

The acetylation status of histones located in both oncogenes and tumor suppressor genes modulate cancer hallmarks. In lung cancer, changes in the acetylation status are associated with increased cell proliferation, tumor growth, migration, invasion, and metastasis. Histone deacetylases (HDACs) are a group of enzymes that take part in the elimination of acetyl groups from histones. Thus, HDACs regulate the acetylation status of histones. Although several therapies are available to treat lung cancer, many of these fail because of the development of tumor resistance. One mechanism of tumor resistance is the aberrant expression of HDACs. Specific anti-cancer therapies modulate HDACs expression, resulting in chromatin remodeling and epigenetic modification of the expression of a variety of genes. Thus, HDACs are promising therapeutic targets to improve the response to anti-cancer treatments. Besides, natural compounds such as phytochemicals have potent antioxidant and chemopreventive activities. Some of these compounds modulate the deregulated activity of HDACs (e.g. curcumin, apigenin, EGCG, resveratrol, and quercetin). These phytochemicals have been shown to inhibit some of the cancer hallmarks through HDAC modulation. The present review discusses the epigenetic mechanisms by which HDACs contribute to carcinogenesis and resistance of lung cancer cells to anticancer therapies.

Agro-residual biomass and disposable protective face mask: a merger for converting waste to plastic-fiber fuel via an integrative carbonization-pelletization framework.

Incineration and landfilling offer possibilities for addressing high-rate management of COVID-waste streams. However, they can be costly and environmentally unsustainable. In addition, they do not allow to convert them to fuels and chemicals as waste-to-energy and waste-to-product technologies. Therefore, we analyzed whether integrating hydrothermal carbonization (HTC) and pelletization can allow converting the surgical face mask (SFM) and biomass to composite plastic-fiber fuel (CPFF). We blended the plastic material and corncob, peanut shell, or sugarcane bagasse at the proportion of 50:50 (%, dry mass basis) for HTC. We performed the thermal pretreatment of blends in an autoclaving reactor at 180 °C and 1.5 MPa. Then we pelletized the hydrochars in a presser machine at 200 MPa and 125 °C. By analyzing the evidence from our study, we recognized the viability of combining the SFM and agricultural residues for CPFF from comparable technical features of our products to standards for premium-grade wood pellets. For instance, the elemental composition of their low-meltable ash was not stoichiometrically sufficient to severely produce slagging and fouling in the equipment for thermal conversion. Although they contained synthetic polymers in their structures, such as polyethylene from filter layers and nylon from the earloop, they emitted CO and NOx below the critical limits of 200 and 500 mg m-3, respectively, for occupational safety. Therefore, we extended the knowledge on waste-to-energy pathways to transform SFM into high-quality hybrid fuel by carbonization and pelletization. Our framework can provide stakeholders opportunities to address plastic and biogenic waste in the context of a circular economy. Supplementary Information: The online version contains supplementary material available at 10.1007/s13399-022-03285-4.