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Cell cycle checkpoint abrogation, especially the inhibition of Chk1 in combination with DNA-damaging treatments, has been proposed as a promising way of sensitizing cancer cells. However, less is known about the possibility to selectively affect tumor cells when they are treated with agents that block DNA synthesis in combination with replication checkpoint inhibitors. Here, we present clear insights in the different responses of tumor and non-transformed cells to the inhibition of DNA replication with hydroxyurea in combination with checkpoint abrogation via inhibition of Ataxia telangiectasia–mutated– (ATM) and Rad3-related/ATM (ATR/ATM) and Chk1 kinases. Interestingly, we find that non-transformed cell lines activate ATR/ATM- and Chk1-independent pathways in response to replication inhibition to prevent mitotic entry with unreplicated DNA. In contrast, tumor cell lines such as HCT116 and HeLa cells rely entirely on Chk1 activity for a proper response to replication inhibitors. Our results show that p38 is activated in response to hydroxyurea treatment and collaborates with Chk1 to prevent mitotic entry in non-transformed cell lines by maintaining cyclin B1/Cdk1 complexes inactive. Furthermore, DNA replication arrest down-regulates cyclin B1 promoter activity in non-transformed cells, but not in tumor cells in a Chk1- and p38-independent way. Thus, our data show that non-transformed cells present a more robust DNA replication checkpoint response compared with tumor cells that involves activation of the p38 pathway. We show that some of these responses to replication block can be lost in tumor cells, causing a defective checkpoint and providing a rationale for tumor-selective effects of combined therapies. [Cancer Res 2007;67(24):11648–56]

Supplementary Figure 3 from Different S/M Checkpoint Responses of Tumor and Non–Tumor Cell Lines to DNA Replication Inhibition

Seismic tube waves, produced by flexure of the well boundary, pressure changes in the fluid in the well, and deformation of the material immediately surrounding the well, are particularly sensitive to variations in the state of the well. We evaluate a direct approach for generating and observing tube waves as a means of detecting well damage. While we find that it can be difficult to reliably excite observable tube waves without a very strong surface source, time-frequency techniques can be employed to increase the detectability of tube wave reflections. New technologies, particularly distributed acoustic sensing, hold great promise for evaluating well integrity by monitoring tube waves, temperature changes, and seismic noise due to well deformation and fluid leakage.

Early life social interactions in gregarious mammals provide an important source of stimulation required for the development of species-typical behaviors. In the present study, complete deprivation of maternal and littermate contact through artificial rearing was used to examine the role of early social stimulation on copulatory behavior and the ejaculate in adult rats. We found that artificially reared naïve male rats were sexually motivated; nevertheless, they did not acquire the level of sexual experience that typically occurs during copulatory training. Disrupted expression of sexual experience of artificially reared rats was demonstrated by an inconsistent pattern of ejaculatory behavior across training tests. Artificial tactile stimulation applied during isolation prevented this disruption and rats achieved ejaculation in most copulatory tests. Despite the irregularity of ejaculatory behavior in isolated rats, their sperm count and seminal plug were similar to control maternally reared (sexually experienced) and artificially-reared rats that received tactile stimulation. These results suggest that tactile sensory information provided by the mother and/or littermates to the offspring is crucial for the development of copulatory behavior. The absence of social and/or tactile stimulation during early life compromises the ability of male rats to gain sexual experience in adulthood.

A palladium-catalyzed asymmeric conjugate addition of aryl boronic acids to medium-sized cycloalkenones followed by intramolecular aldol trapping is reported.

The Minamata Convention on Mercury (Article 4) prohibits the manufacture, import, or export of skin-lightening products containing mercury concentrations aboveThe objective of this study was to increase our understanding of worldwide human mercury exposure from skin-lightening products.A systematic search of peer-reviewed scientific literature was performed for relevant articles in four databases (PubMed, Web of Science Core Collection, Scopus, and TOXLINE). The search strategy, eligibility criteria, and data-extraction methods were establishedThis review was based on data contained in 41 peer-reviewed scientific papers from 22 countries worldwide published between 2000 and 2022. In total, we captured mercury concentration values from 787 skin-lightening product samples [overall pooled central median mercury level wasThis review suggests that mercury widely exists as an active ingredient in many skin-lightening products worldwide and that users are at risk of variable and often high exposures. These synthesized findings identify data gaps and help increase our understanding of the health risks associated with the use of these products. https://doi.org/10.1289/EHP10808.

Verónica Rodríguez wants to acknowledge that the edition of this Special Issue and the co-writing of this Introduction was supported by the research group “CBTBarcelona (Contemporary British Theatre Barcelona)” (https://www.ub.edu/cbtbarcelona/), led by Mireia Aragay. Isabel Guerrero wants to acknowledge that the edition of this Special Issue and the co-writing of this Introduction was supported by the research projects “Shakespeare en el siglo XX” and “Poéticas de lo real en el teatro del siglo XXI” (Proyectos Talento Joven UNED), led respectively by Clara Calvo and Isabel Guerrero. David Rodríguez-Solás is thankful to the Biblioteca de la Fundación Juan March for their support while co-writing this Introduction.

The TecNM campus Lerdo is developing a Web Based System for the Management of the Residence Procedures (SIGEPRORE), in order to adhere to the ISO 9001:2015, which this institution of higher education currently operates under, for which it is necessary to automate the current professional residency quality management system. SIGEPRORE is an institutional software package designed to support all those involved in the professional residency procedure. It has a new and improved web design, which allows the integration of new modules, functionalities, and technological tools for increased user optimization. Participants in this project are students from the engineering degree in computer systems of the ITSL and professors’ part of the academic body in consolidation "Software engineering applied to solutions". The agile methodology used as a guideline to develop the project was the SCRUM. The impact of the project is of great relevance as it is intended to establish a web system which will contain all the operating policies of the professional residence and quality management system.

The object of this research was the comparative analysis of the students assisted by the Institutional Tutoring Program (PIT) of the Tecnologico Nacional de Mexico and who are enrolled in different academic engineering studies. The research was done in three technological institutes in the Comarca Lagunera. A comparative study with t-test was carried out between the administrative and IT study areas, with a confidence level of 97%. Among the findings, it is worth noting that the tutored students of administrative careers are more sociable than their peers in the IT area, but these students have more confidence in their tutor to talk about their personal problems; students who use institutional support services perceive that their participation in the tutorial program improves their grades, they ask their tutor for help and are more willing to listen to his advice and recommendations. Regarding the type of family, students who live in families with both parents are more daring than those who come from another family type.

As a consequence of industrial mining activity, high volumes of tailings are scattered around Mexico. Frequently, tailings contain heavy metals (HM) which entail threats against all organisms. The aim of this research was to identify plants and root fungal endophytes in polymetallic polluted tailings with the potential to be used in strategies of bioremediation. Four deposits of mine wastes, situated in a semi-arid region near urban and semi-urban populations, and agricultural areas, were studied. The physical and chemical characteristics of substrates, accumulation of HM in plant tissues, root colonization between arbuscular mycorrizal (AMF) and dark septate endophyte (DSE) fungi, and the identification of DSE fungi isolated from the roots of two plant species were studied. Substrates from all four sites exhibited extreme conditions: high levels in sand; low water retention; poor levels in available phosphorus and nitrogen content; and potentially toxic levels of lead (Pb), cadmium (Cd), and zinc (Zn). The native plants Lupinus campestris, Tagetes lunulata, and Cerdia congestiflora, as well as the exotic Cortaderia selloana and Asphodelus fistulosus, demonstrated a relevant potential role in the phytostabilization and/or phytoextraction of Pb, Cd, and Zn, according to the accumulation of metal in roots and translocation to shoots. Roots of eleven analyzed plant species were differentially co-colonized between AMF and DSE fungi; the presence of arbuscules and microsclerotia suggested an active physiological interaction. Fourteen DSE fungi were isolated from the inner area of roots of T. lunulata and Pennisetum villosum; molecular identification revealed the predominance of Alternaria and other Pleosporales. The use of native DSE fungi could reinforce the establishment of plants for biological reclamation of mine waste in semi-arid climate. Efforts are needed in order to accelerate a vegetation practice of mine wastes under study, which can reduce, in turn, their potential ecotoxicological impact on organisms, human populations, and agricultural areas.

Pre-harvest sprouting (PHS) is a common threat to cereal crops in which the grain maturation phase takes place under rainy, moist conditions. Susceptibility to PHS is higher in sorghum genotypes displaying low levels of seed dormancy before harvest maturity. Other attributes such as glume or panicle morphology may also affect susceptibility to PHS. Breeding for resistance to PHS in grain sorghum requires the identification of grain physiological and morphological attributes affecting this trait, and a protocol for phenotyping and rating genotypes according to their susceptibility to PHS. In this work, we tested germination under laboratory conditions using detached grains and intact panicles for a panel of 20 sorghum genotypes including 11 parental lines, 6 hybrids and 3 reference inbred lines with contrasting PHS response. Records for natural sprouting in the field for these genotypes were also included in the analysis. Multivariate analyses of germination data allowed separation of genotypes into two major categories (resistant and susceptible to PHS). Laboratory germination data correlated significantly with PHS in the field. In most genotypes, the glumes had a significant, inhibitory effect on germination. The low levels of grain dormancy were observed among high tannin backgrounds, and vice versa, indicating that a pigmented testa alone does not provide resistance to PHS. Altogether, the phenotyping protocol allowed the classification of sorghum genotypes according to their susceptibility to PHS and the identification of different attributes useful for breeding for PHS resistance in this crop.

BackgroundThe Minamata Convention on Mercury (Article 4) prohibits the manufacture, import or export of skin-lightening products containing mercury concentrations above 1 μg/g. However, there is a lack of knowledge surrounding the global prevalence of mercury-added skin-lightening products.ObjectiveThe objective of this study was to increase our understanding of worldwide human mercury exposure and associated health risks from the use of skin-lightening products.MethodsA systematic search of peer-reviewed scientific literature was performed in four databases (PubMed, Web of Science Core Collection, Scopus, and Toxline). The initial search in July of 2018 identified 1,711 unique scientific articles, of which 34 were ultimately deemed eligible for inclusion after iterative screens at the title, abstract, and whole text levels. A second search was performed in November of 2020 using the same methods, of which another 7 scientific articles were included. All papers were organized according to four data groups 1) “Mercury in products”, 2) “Usage of products”, 3) “Human biomarkers of exposure”; and 4) “Health impacts”, prior to data extraction and synthesis.ResultsThis review was based on data contained within 41 peer-reviewed scientific papers from 22 countries worldwide published between 2000 and 2020. In total, we captured mercury concentration values from 787 skin-lightening product samples (overall pooled central median mercury level was 0.49 μg/g, IQR: 0.02 – 5.9) and 1,042 human biomarker measurements from 863 individuals. We also synthesized usage information from 3,898 individuals, and self-reported health impacts associated with using mercury-added products from 832 individuals.DiscussionThis review suggests that mercury widely exists as an active ingredient in many skin-lightening products worldwide, and that users are at risk of variable, and often high exposures. These synthesized findings help increase our understanding of the health risks associated with the use of these products.

Since the adoption of European Union Council Directive 92/43 on the conservation of natural habitats and wild fauna and flora, some opposition has arisen among owners and managers of land affected by the directive. Some studies have indicated that some of this opposition has found expression in subsequent arson fires in these areas. This article analyses the occurrence of arson fires in the SACs (Special Areas of Conservation) included in the European ecological network, Natura 2000, in Galicia (Spain), more specifically in the montes vecinales en mano común (MVMCs), which are privately owned collective lands. We tested whether the declaration of SACs had a statistical impact on the forest fire regime in the period 1999–2014. The analyses focused on the sub-periods of 1999–2004 and 2005–2014, i.e., before and after the approval of the list of sites of community importance in the study area in December 2004. The results obtained show that, after the declaration of protection, there was a statistically significant increase in the area burnt by fire in these areas, mainly on private estates. We also found that the percentage of arson fires after 2004 was higher in SACs than in other territorial units. We found that the percentage of arson fires was reduced less in SACs than in other territorial units. Furthermore, we found that the area burnt per fire after 2004 in SACs was almost double that in the MVMC-SACs (12.04 ha versus 6.64 ha), so it can be concluded that the conservationist policies of the Natura 2000 network in Galicia have not had a positive effect on the forest fire regime.

El presente artículo de investigación da cuenta de los avances del proyecto de investigación A-PIDC-246: “Producción, visibilidad y vinculación del conocimiento resultante de proyectos de investigación en la Universidad Nacional de la Matanza Decenio 1994-2003”, radicado en el Departamento de Humanidades y Ciencias Sociales de la misma universidad, y que forma parte del Programa: “Gestión y Vinculación del Conocimiento en Ciencia y Tecnología en la Universidad Nacional de la Matanza”. Los resultados parciales alcanzados en el proyecto, -focalizados en la producción académica derivada de proyectos del Programa de Incentivos a docentes-investigadores de la Secretaría de Políticas Universitarias acreditados en el Departamento de Ciencias Económicas de la UNLaM durante los años1994 a 1999-ha permitido establecer una estimación de la productividad alcanzada a partir del relevamiento del cuerpo documental compuesto por cincuenta informes finales de investigación analizados en cuanto a los registros de producción científico-académica y vinculación con organismos diversos en ellos detectados. Sumado a esto último se ha establecido también la constitución por género de los integrantes de los proyectos de investigación y la visibilidad estimada de las producciones detectadas. Fil: Ezeiza Pohl, Carlos Enrique. Universidad Nacional de La Matanza; Argentina. Fil: Galardo, Verónica Elisa. Universidad Nacional de La Matanza; Argentina. Fil: Rodríguez, Verónica. Universidad Nacional de La Matanza; Argentina. Fil: Goncalves, Alejando José. Universidad Nacional de La Matanza; Argentina. Fil: Bertuné Fatgalá, Mirta Natalia. Universidad Nacional de La Matanza; Argentina. Fil: Fontan, Silvia Graciela. Universidad Nacional de La Matanza; Argentina. Fil: Ferrero, Eduardo Daniel. Universidad Nacional de La Matanza; Argentina. Fil: Castillo, Alicia Susana. Universidad Nacional de La Matanza; Argentina. Fil: Juárez, Marcelo Adrián. Universidad Nacional de La Matanza; Argentina. Fil: Lazarte, María Belén. Universidad Nacional de La Matanza; Argentina. Fil: Gómez, Gabriela Ángela. Universidad Nacional de La Matanza; Argentina. Fil: Madrid, Laura Cristina. Universidad Nacional de La Matanza; Argentina. Fil: Bosco, Gabriel Osvaldo. Universidad Nacional de La Matanza; Argentina. Fil: Ezeiza Pohl, Ana Carolina. Universidad Nacional de La Matanza; Argentina. Fil: Iribarne, Alba Ester. Universidad Nacional de La Matanza; Argentina. Fil: Artola, Analía Yael. Universidad Nacional de La Matanza; Argentina. Fil: Saracino, Sandra Patricia. Universidad Nacional de La Matanza; Argentina. Fil: Brunetti, Juan. Universidad Nacional de La Matanza; Argentina. Fil: Field, Marcela. Universidad Nacional de La Matanza; Argentina. Fil: Ormart, Elizabeth. Universidad Nacional de La Matanza; Argentina. Fil: De Luca, Jorge Misael. Universidad Nacional de La Matanza; Argentina. Fil: Martínez, Miranda. Universidad Nacional de La Matanza; Argentina. Fil: Moreno, Julieta. Universidad Nacional de La Matanza; Argentina. Fil: Pistarchi, Natalia. Universidad Nacional de La Matanza; Argentina. Fil: Olthoff, Belén. Universidad Nacional de La Matanza; Argentina.

Glycoproteins and glycopeptides are an interesting focus of research, because of their potential use as therapeutic agents, since they are related to carbohydrate-carbohydrate, carbohydrate-protein, and carbohydrate-lipid interactions, which are commonly involved in biological processes. It has been established that natural glycoconjugates could be an important source of templates for the design and development of molecules with therapeutic applications. However, isolating large quantities of glycoconjugates from biological sources with the required purity is extremely complex, because these molecules are found in heterogeneous environments and in very low concentrations. As an alternative to solving this problem, the chemical synthesis of glycoconjugates has been developed. In this context, several methods for the synthesis of glycopeptides in solution and/or solid-phase have been reported. In most of these methods, glycosylated amino acid derivatives are used as building blocks for both solution and solid-phase synthesis. The synthetic viability of glycoconjugates is a critical parameter for allowing their use as drugs to mitigate the impact of microbial resistance and/or cancer. However, the chemical synthesis of glycoconjugates is a challenge, because these molecules possess multiple reaction sites and have a very specific stereochemistry. Therefore, it is necessary to design and implement synthetic routes, which may involve various protection schemes but can be stereoselective, environmentally friendly, and high-yielding. This review focuses on glycopeptide synthesis by recapitulating the progress made over the last 15 years.

El desarrollo sexual del adolescente está implicado por procesos físicos, aceptación de la imagen corporal, descubrimiento de las necesidades sexuales, desarrollo de la personalidad, aprendizaje de las relaciones interpersonales y establecimiento de un sistema propio de valores sexuales. Por ello es importante estudiar la percepción de la primera relación sexual, correspondiendo a la elaboración o expresión de un juicio a partir de la experiencia, donde influyen creencias, normas sociales, sistemas de poder y significados previos que regulan el comportamiento. El tipo de investigación es descriptivo, de diseño transversal, donde las variables principales corresponden a la percepción de la primera relación sexual en adolescentes, y las variables asociadas son: V1–dimensión cognitiva, V2–dimensión afectiva y V3–dimensión conductual. Estas fueron analizadas de acuerdo a las siguientes categorías: a) comienzo de la vida sexual b) embarazo y métodos anticonceptivos, c) infecciones de transmisión sexual y d) redes sociales. Para ello se llevaron a cabo entrevistas semiestructuradas a cinco adolescentes del estado de Hidalgo, que tuvieron su primera relación sexual, analizando el contenido intrínseco de manera vertical y horizontal. En esta investigación se identifica el comportamiento de la primera relación sexual, así como la influencia de las redes sociales. Los adolescentes se encuentran en constante cambio en sus roles y estereotipos en torno a su sexualidad y prácticas sexuales, aunque tienen información no hay percepción de riesgo, ni conductas preventivas.

Este artículo pretende exponer algunas nociones conceptuales y jurisprudenciales alrededor de una realidad jurídica vigente. Esto es, la indebida interferencia de la justicia constitucional –a través de la acción de protección–, en el arbitraje. Para dicho propósito, se abordarán temas relacionados a la naturaleza de las decisiones arbitrales y de las garantías jurisdiccionales.

Objective: Vocal fold paralysis is an uncommon problem in children. Clinical presentation covers a wide range of signs and symptoms. Our objective is to evaluate de efficacy and security of the Endoscopic Arytenoid Abduction Lateropexy (EAAL) in pediatric patients with vocal cord paralysis and to present the results. Material and method: From January 2011 to September 2018 10 patients with vocal fold paralysis underwent examination and treatment. The mean age at treatment was 4.87 years old (2-16). The parameters considered at the pre-/postsurgical time for the clinical assessment of each patient were as follows: the presence or absence of stridor and respiratory distress, the existence or nonexistence of previous tracheostomy, voice alterations, and feeding aspiration events. The mean follow-up was 49.5 months (5-104). Results: EAAL were realized successfully in 10 patients. There were no complications associated with the surgical procedure. In terms of sequelae, we noted 2 cases of minimal liquid-feeding difficulties that were alleviated within three weeks of the surgery with the help of phoniatrics reeducation, and 5 cases of mild dysphonia. In 4 cases tracheostomy was avoided, in 4 cases patients with prior tracheostomy were successfully decannulated following EAAL. Conclusions: EAAL may be selected as a first-line technique in management of vocal cord paralysis, since it is minimally invasive, easy to perform, and produces satisfactory results.

We assess the performance of the joint inversion of receiver functions (RF) and surface-wave dispersion in the characterization of the sedimentary package comprising the Parnaíba basin. This procedure is routinely utilized in passive-source crustal studies to retrieve S-wave velocity variations with depth, and has seldom been used with higher-frequency datasets to investigate fine sedimentary structure. The Parnaíba basin is a Paleozoic cratonic basin composed of five supersequences, accumulating ∼3.5 km of sedimentary rocks interbedded by Late Cretaceous diabase sills. The dataset used for this research was acquired between 2015 and 2017 through deployment of 10 short-period and one broadband seismic stations distributed along an approximately 100-kilometer-long linear array in the center of the basin. The deployment was carried out under the Parnaíba Basin Analysis Project, a multi-institutional and multidisciplinary effort funded by BP Energy do Brasil. High-frequency RFs (f