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Despite the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway being frequently altered in T-ALL/LBL, no specific therapy has been approved for T-ALL/LBL patients with constitutive signalling by JAK/STAT, so there is an urgent need to identify pathway members that may be potential therapeutic targets. In the present study, we searched for JAK/STAT pathway members potentially modulated through aberrant methylation and identified SOCS3 hypermethylation as a recurrent event in T-ALL/LBL. Additionally, we explored the implications of SOCS3 deregulation in T-ALL/LBL and demonstrated that SOCS3 counteracts the constitutive activation of the JAK/STAT pathway through different molecular mechanisms. Therefore, SOCS3 emerges as a potential therapeutic target in T-ALL/LBL, Comunidad de Madrid, Grant/Award Number: B2017/BMD-3778; LINFOMAS-CM; Fundación Científica Asociación Española Contra el Cáncer, Grant/Award Number: PROYE18054PIRI; Fundación Ramón Areces, Grant/Award Number: CIVP19S7917; Instituto de Investigación Sanitaria Fundación Jiménez Díaz; Ministerio de Ciencia, Innovación y Universidades, Grant/ Award Number: RTI2018- 093330-B-I00 and MCIU/FEDER; Ministerio de Economía y Competitividad, Grant/Award Number: SAF2015-70561-R and MINECO/FEDER

10 pages, 5 figures, 1 table, supplementary information https://doi.org/10.1039/D2AY02019J, Analogues of palytoxin (PLTX), one of the most potent marine biotoxins, are produced by some species of the marine dinoflagellates of the genus Ostreopsis. The proliferation of these species in different coastal zones represents a potential threat of seafood poisoning in humans because the produced toxins can be transferred through marine food webs. Thus, the determination of the concentration of PLTX analogues (ovatoxins—OVTXs, ostreocins—OSTs and isobaric PLTX) in different matrices (seawater, marine fauna, etc.) is necessary to protect human health. This study is addressed to overcome some of the challenges that the chemical complexity of these molecules poses to their quantification by ultra-high-performance liquid chromatography high-resolution mass spectrometry-based techniques (UHPLC-HRMS). In particular, the mass spectra of the palytoxin analogues show the presence of a large number of ions (including mono- and multiply charged ions) whose nature, relative abundances and behavior can lead to quantitation errors if the correct ions are not selected. In this work, the variability of the PLTX and OVTX profiles under different instrument conditions, including the use of diverse electrospray generation sources and different quantitation methods, is studied. Moreover, the extraction protocol in seawater containing Ostreopsis sp. ovata cells is also evaluated. The use of a heated electrospray operating at 350 °C and a quantitative method including ions from different multiply charged species provides a more robust and reliable method for overcoming the problems due to the variability in the toxin's mass spectrum profile. A single MeOH : H2O (80 : 20, v/v) extraction is proposed as the best and reliable procedure. The overall method proposed was applied to quantify OVTXs (-a to -g) and iso-PLTX along the 2019 Ostreopsis cf. ovata bloom. The cells contained a total toxin concentration of up to 20.39 pg per cell, The authors thank the different financing agencies that supported the study. N. I. M.-P. was granted the fellowship FISDUR2020-00254 (AGAUR, Government of Catalonia). Financial support: MICIU (Spain, project PGC2018-095013-B-I00), AGAUR (Generalitat de Catalunya, project 2017SGR-310) and the Water Research Institute (IdRA, University of Barcelona). Support was provided also by the CoCliME project, an ERA4CS network (ERA-NET) initiated by JPI Climate and co-financed by FORMAS (SE) and the European Union (Grant no. 690462), ERC-2019-CoG-863934-GlycoSpec (European Research Council Consolidator Grant), With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)

The signaling molecule stimulator of IFN genes (STING) was identified as a crucial regulator of the DNA-sensing cyclic GMP-AMP synthase (cGAS)-STING pathway, and this signaling pathway regulates inflammation and energy homeostasis under conditions of obesity, kidney fibrosis, and AKI. However, the role of STING in causing CKD, including diabetic kidney disease (DKD) and Alport syndrome, is unknown.To investigate whether STING activation contributes to the development and progression of glomerular diseases such as DKD and Alport syndrome, immortalized human and murine podocytes were differentiated for 14 days and treated with a STING-specific agonist. We used diabeticThe activation of the STING pathway acts as a mediator of disease progression in DKD and Alport syndrome. Targeting STING may offer a therapeutic option to treat glomerular diseases of metabolic and nonmetabolic origin or prevent their development, progression, or both.

Resumen El sistema jurídico de los Estados se construye sobre la base de los usos y costumbres de la población; no obstante, en el sistema jurídico peruano se impone la tradición greco-romana, que conduce a la clandestinidad al derecho de costumbre. El objetivo de esta investigación es evidenciar la naturaleza de la formación académica del derecho en las universidades públicas y privadas del Perú mediante el análisis de los currículos de estudios. Se utilizó como método la revisión documental de información disponible en la página web de la Superintendencia Nacional de Educación Superior Universitaria - SUNEDU. De acuerdo con los resultados, en el Perú, de las Facultades que forman profesionales en derecho 29.8% corresponde a universidades públicas y 70.2% a privadas. De ellas, 70.24% establecen que la materia de Derecho romano y Derecho anglosajón son de carácter obligatorio, mientras que 71.4% no consideran cursos referidos al pluralismo jurídico o derecho consuetudinario. Por lo tanto, la formación profesional en derecho y por ende, la administración de justicia no va acorde con el contexto. En los últimos años se han desencadenado graves crisis y conflictos sociales con trasfondos de inequidades culturales. Por lo cual se debe considerar el derecho consuetudinario andino como materia relevante en la formación universitaria peruana de los futuros abogados que impartirán justicia en una población que se autoidentifica como indígena. Abstract The legal system of the states is built on the basis of the uses and customs of the population; however, in the Peruvian legal system, the Greco-Roman tradition is imposed, leading to the clandestinity of customary law. The objective of this research is to demonstrate the academic formation of law in public and private universities in Peru through the analysis of the curricula. The method used was the documentary review available on the website of the National Superintendence of University Higher Education - SUNEDU. According to the results, in Peru, 29.8% of the faculties that train law professionals correspond to public universities and 70.2% to private universities. Of these, 70.24% state that Roman law and common law are mandatory subjects, while 71.4% do not consider courses on legal pluralism or common law. Therefore, the professional training in law and therefore, the administration of justice is not in accordance with the context, due to the fact that in recent years serious crises and social conflicts have been unleashed with backgrounds of cultural inequalities. Therefore, Andean customary law should be considered as a relevant subject in the Peruvian university education of future lawyers, who will impart justice in a population that self-identifies as indigenous.

Background Psychological stress and increased permeability are implicated as contributing factors in the initiation and worsening of gastrointestinal diseases. A link between stress and intestinal permeability has been shown in animal models as well as in human small intestine, but stress effects on the human colorectal mucosal barrier has not been reported. Objective To investigate the potential effects of acute psychological stress on colorectal mucosal barrier function and to explore stress-induced molecular events in the rectal mucosa under healthy conditions. Methods Endoscopic biopsies were taken from the rectosigmoid region of healthy volunteers, who had been subjected to dichotomous listening stress and after a control session, respectively. Paracellular and transcellular permeability were assessed in modified Ussing chambers. RNA expression (microarray technology confirmed by quantitative real-time polymerase chain reaction) and biological pathway analysis were used to investigate the local mucosal response to acute stress. Results Dichotomous listening stress induced a subjective and objective stress response, and significantly increased paracellular but not transcellular permeability. We also identified a stress-induced reduction in RNA expression of genes related to immune cell activation and maturation (CR2, CD20, TCLA1, BANK1, CD22, FDCSP), signaling molecules of homing of immune cells to the gut (chemokines: CCL21, CXCL13, and CCL19, and receptors: CCR7, CXCR5), and innate immunity (DUOX2). Eight of the 10 top down-regulated genes are directly involved in B cell activation, signaling and migration. The systemic stress response correlated positively with paracellular permeability and negatively with DUOX2 expression. Conclusion Dichotomous listening stress increases paracellular permeability and modulates immune cell activity in the rectal mucosa. Further studies are warranted to identify the primary mechanisms of stress-mediated reduction of mucosal defensive activity and barrier dysfunction, and their potential implications for gastrointestinal disorders. Funding Agencies|Fondo de Investigacion Sanitaria and CIBERehd, Instituto de Salud Carlos III, Subdireccion General de Investigacion Sanitaria, Ministerio de Economia y Competitividad [PI17/0190, PI19/01643]; Futurum, Region Jonkoping County [12406, 1460]; Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas [CB06/04/0021]; Vetenskapsradet [2014-02537, 2017-02475]; Forskningsradet i Sydostra Sverige [37841]

Frataxin is a kinetic activator of the mitochondrial supercomplex for iron-sulfur cluster assembly. Low frataxin expression or a decrease in its functionality results in Friedreich's Ataxia (FRDA). With the aim of creating new molecular tools to study this metabolic pathway, and ultimately, to explore new therapeutic strategies, we have investigated the possibility of obtaining small proteins exhibiting a high affinity for frataxin. In this study, we applied the ribosome display approach, using human frataxin as the target. We focused on Affi_224, one of the proteins that we were able to select after five rounds of selection. We have studied the interaction between both proteins and discussed some applications of this specific molecular tutor, concerning the modulation of the supercomplex activity. Affi_224 and frataxin showed a K

Genotype networks are sets of genotypes connected by small mutational changes that share the same phenotype. They facilitate evolutionary innovation by enabling the exploration of different neighborhoods in genotype space. Genotype networks, first suggested by theoretical models, have been empirically confirmed for proteins and RNAs. Comparative studies also support their existence for gene regulatory networks (GRNs), but direct experimental evidence is lacking. Here, we report the construction of three interconnected genotype networks of synthetic GRNs producing three distinct phenotypes in Escherichia coli. Our synthetic GRNs contain three nodes regulating each other by CRISPR interference and governing the expression of fluorescent reporters. The genotype networks, composed of over twenty different synthetic GRNs, provide robustness in face of mutations while enabling transitions to innovative phenotypes. Through realistic mathematical modeling, we quantify robustness and evolvability for the complete genotype-phenotype map and link these features mechanistically to GRN motifs. Our work thereby exemplifies how GRN evolution along genotype networks might be driving evolutionary innovation., Nature Communications, 14 (1), ISSN:2041-1723

SARS-CoV-2 was identified as the pathogenic agent causing the COVID-19 pandemic. Among the proteins codified by this virus, the Spike is one of the most external and exposed. A fragment of the Spike protein, named the Receptor Binding Protein (RBD) interacts with the ACE2 receptors of human cells, allowing the entrance of the viruses. RBD has been proposed as an interesting protein for the development of diagnosis tools, treatment and prevention of the disease. In this work, a method for recombinant RBD production using Pichia pastoris as a cell factory in a Stirred Tank Bioreactor (SRTB) up to 7 L was developed. Using a basal saline medium with glycerol, methanol and compressed air in a four stages procedure, around 500 mg/L of raw yRBD (RBD produced by yeasts) and 206 mg/L of purified (>95%) RBD were obtained. Thereby, the proposed method represents a feasible, simple, scalable and cheap procedure for the obtention of RBD for diagnosis kits and vaccines formulation

Background Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them. Methods We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date. Results IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety. Conclusions These findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders.

PurposeThis paper proposes a maturity model to indicate the operational excellence (OE) implementation status of businesses in emerging countries, considering its importance in Industry 4.0.Design/methodology/approachThe study involves four steps. First, undertake a study of the literature to identify the variables to consider in the maturity model; second, identify how to organize the variables found in the first step; third, structure a questionnaire to define the maturity model; and lastly, validate the variables found in the literature and the maturity levels.FindingsA total of 23 variables were validated through interviews with general managers, operation managers and experts within organizations. Interviews were carried out in 49 companies from different sectors. Five maturity levels were defined in this study: basic level, beginner level, training level, innovative level and champion level.Originality/valueMany businesses are implementing OE as a practice to remain competitive in their industries, targeting economic, environmental and social sustainability. However, OE implementation in companies from developing or emerging countries is far below the average level of that in developed companies due to cultural, political or economic constraints. To the best of the authors’ knowledge, there is no model that indicates the status of OE implementation in companies from emerging countries or the different levels to implement OE. This study fills the mentioned gap.

Microbes are fascinating molecular machines which can be equipped with synthetic genetic programs that allow them to produce therapeutic molecules targeted on demand upon disease sensing. Cutibacterium acnes engraftment capacity and living habitat close to important pharmacological targets makes it an attractive chassis to create skin living therapeutics. Here, we report the engineering of this bacterium, the most abundant commensal of the human skin, to produce and secrete the therapeutic molecule neutrophil gelatinase-associated lipocalin thereby modulating sebum production.

Endoglin is a membrane glycoprotein that acts as a coreceptor for transforming growth factor-β. We and others have previously suggested a function of endoglin as a tumor suppressor in epithelial cancer. Here, we study the expression of endoglin during chemical mouse skin carcinogenesis. We find that shedding of membrane endoglin, allowing the secretion of a soluble endoglin form, is a late event associated with progression from squamous to spindle cell carcinomas. Knockdown of endoglin in transformed keratinocytes activates the Smad2/3 signaling pathway resulting in cell growth arrest, delayed tumor latencies, and a squamous to spindle phenotypic conversion. Forced expression of the long endoglin isoform in spindle carcinoma cells blocks transforming growth factor-β1 stimulation of Smad2/3 signaling and prevents tumor formation. In contrast, expression of the short endoglin isoform has no effect on spindle cell growth in vitro or in vivo. Our results show that endoglin behaves as a suppressor of malignancy during the late stages of carcinogenesis. Therefore, disruption of membrane endoglin emerges as a crucial event for progression to spindle cell carcinomas. [Cancer Res 2007;67(21):10268–77]

Supplementary Figure 3 from A Role for Endoglin as a Suppressor of Malignancy during Mouse Skin Carcinogenesis

Supplementary Table 1 from A Role for Endoglin as a Suppressor of Malignancy during Mouse Skin Carcinogenesis

Supplementary Figure 2 from A Role for Endoglin as a Suppressor of Malignancy during Mouse Skin Carcinogenesis

Supplementary Figure Legends 1-3 from A Role for Stroma-Derived Annexin A1 as Mediator in the Control of Genetic Susceptibility to T-Cell Lymphoblastic Malignancies through Prostaglandin E2 Secretion

Supplementary Table 1 from A Role for Stroma-Derived Annexin A1 as Mediator in the Control of Genetic Susceptibility to T-Cell Lymphoblastic Malignancies through Prostaglandin E2 Secretion

Supplementary Figure 3 from A Role for Stroma-Derived Annexin A1 as Mediator in the Control of Genetic Susceptibility to T-Cell Lymphoblastic Malignancies through Prostaglandin E2 Secretion

Supplementary Figure 2 from A Role for Stroma-Derived Annexin A1 as Mediator in the Control of Genetic Susceptibility to T-Cell Lymphoblastic Malignancies through Prostaglandin E2 Secretion

Supplementary Figure 1 from A Role for Stroma-Derived Annexin A1 as Mediator in the Control of Genetic Susceptibility to T-Cell Lymphoblastic Malignancies through Prostaglandin E2 Secretion

The Fas/FasL system mediates induced apoptosis of immature thymocytes and peripheral T lymphocytes, but little is known about its implication in genetic susceptibility to T-cell malignancies. In this article, we report that the expression of FasL increases early in all mice after γ-radiation treatments, maintaining such high levels for a long time in mice that resisted tumor induction. However, its expression is practically absent in T-cell lymphoblastic lymphomas. Interestingly, there exist significant differences in the level of expression between two mice strains exhibiting extremely distinct susceptibilities that can be attributed to promoter functional polymorphisms. In addition, several functional nucleotide changes in the coding sequences of both Fas and FasL genes significantly affect their biological activity. These results lead us to propose that germ-line functional polymorphisms affecting either the levels of expression or the biological activity of both Fas and FasL genes could be contributing to the genetic risk to develop T-cell lymphoblastic lymphomas and support the use of radiotherapy as an adequate procedure to choose in the treatment of T-cell malignancies. [Cancer Res 2007;67(11):5107–16]

Supplementary Table 3 from A Role for Endoglin as a Suppressor of Malignancy during Mouse Skin Carcinogenesis

Cancer susceptibility is essentially attributable to multiple low-penetrance genes. Using interspecific consomic and congenic mice between the tumor-resistant SEG/Pas and the tumor-sensitive C57BL/6J strains, a region on chromosome 19 involved in the genetic resistance to γ-irradiation–induced T-cell lymphomas (Tlyr1) has been identified. Through the development of nonoverlapping subcongenic strains, it has been further shown that Anxa1 may be a candidate resistance gene on the basis of its differential expression in thymus stroma cells after γ-radiation exposure. In addition, thymus stroma cells of thymic lymphomas exhibited a significant reduction in the expression levels of Anxa1. Interestingly, the activity of Anxa1 relies on prostaglandin E2 (PGE2) induction that brings about apoptosis in thymocytes. In fact, in vitro transfection experiments revealed that PGE2 production was enhanced when HEK 293 cells were transfected with full-length cDNAs of Anxa1, with PGE2 production in the cells transfected with the allele of the resistant strain (Anxa1Tyr) being higher than that in cells transfected with the allele of the susceptible strain (Anxa1Phe). Furthermore, the presence of this compound in the medium induced apoptosis of immature CD4+CD8+CD3low cells in a dose-dependent manner. These results improve our knowledge of the molecular mechanisms triggering T-cell lymphoblastic lymphoma development while highlighting the relevance of the stroma in controlling genetic susceptibility and the use of PGE2 as a new therapeutic approach in T-cell hematologic malignancies. [Cancer Res 2009;69(6):2577–87]

Supplementary Table 2 from A Role for Endoglin as a Suppressor of Malignancy during Mouse Skin Carcinogenesis

Supplementary Table 4 from A Role for Endoglin as a Suppressor of Malignancy during Mouse Skin Carcinogenesis

Supplementary Figure 1 from A Role for the Fas/FasL System in Modulating Genetic Susceptibility to T-Cell Lymphoblastic Lymphomas

Supplementary Table 1 from A Role for the Fas/FasL System in Modulating Genetic Susceptibility to T-Cell Lymphoblastic Lymphomas

La educación es uno de los sectores más afectados por la pandemia, lo que ha generado la necesidad de analizar el tema desde diversas perspectivas, incluyendo la de los usuarios. Por lo tanto, este artículo aborda dicha problemática desde la perspectiva de los estudiantes universitarios, con el objetivo de comprender el proceso de adaptación a la educación virtual e identificar las dificultades y experiencias resilientes que han enfrentado. La metodología utilizada fue cuantitativa, descriptiva y prospectiva de cohorte transversal. Se llevó a cabo en una universidad pública de Perú con una muestra de 190 estudiantes de Antropología, a quienes se les aplicó un cuestionario en línea mediante la plataforma de encuestas QuestionPro. Los resultados del estudio revelan que el 81.05 % de los estudiantes consideran la educación presencial tradicional como muy importante, mientras que el 40.53 % califica como buena la educación virtual recibida. En cuanto a las dificultades logísticas de los estudiantes, el 69.47 % manifestó haber recibido sus clases virtuales a través de un teléfono celular, el 57.37 % indica haber compartido su espacio de estudio con un familiar directo en su hogar, mientras que el 72.11 % y el 37.89 % simultáneamente apoyaron en actividades económicas de sus padres. En cuanto a la percepción de satisfacción en el uso de herramientas por parte de los docentes, entre el 55.84 % y el 61.04 % de los estudiantes consideran que el desempeño docente es bueno o aceptable. En conclusión, la mayoría de los estudiantes universitarios opina que la educación presencial tradicional es muy importante y califica como buena la educación virtual, aunque existen limitaciones logísticas y de conectividad que han afectado el proceso de aprendizaje. Estos resultados resaltan la importancia de seguir investigando y mejorando las prácticas educativas en el contexto de pandemia.

PurposeGreen Lean tools are aligned with the Circular Economy strategy as they aim at reducing waste, however, they miss the creation of value through waste. Therefore, this paper investigates whether the current implementation of the Green Lean strategy promotes the introduction of the Circular philosophy to achieve sustainable management production processes. It analyses how the resources were managed by implementing the different strategies and tools presented in Green Lean case studies under the lens of Circular Economy and highlights future research paths on the Circular Lean integration.Design/methodology/approachAn analysis of the implementation of Green Lean case studies, selected through a Systematic Literature Review, from the manufacturing sector is conducted.FindingsThe majority of Green Lean implementations were aimed at minimizing waste, which is aligned with the narrowing strategy of Circular Economy and only a few cases studies aimed at closing the production cycles. Even though the main results indicate that being eco-efficient is a good starting point to move towards sustainability, from a Circular Economy point of view, this approach could remain limited. Therefore, the current contribution of Green Lean to the implementation of circular practices is limited. It can be concluded that introducing the circular philosophy in the Green Lean methodology can be achieved through redirecting Green Lean from waste reduction towards a value creation focus.Originality/valueThe originality of this paper is that it provides a critical review of the literature on the topic of Green Lean integration and Circular Economy.

The iron-binding motif EexxED from the frataxin family was grafted on the surface of E. coli thioredoxin. The variant showed native-conformational features and was enzimatically functional in the context of the new protein structure.

In the modern era, information technology-based solution providers are encountering a growing request for satisfying the versatile requirements of their customers in terms of software applications. To this end, specific approaches have been designed to streamline the way of accomplishing software projects in an efficient manner, i.e., agile-oriented frameworks. Even though previous studies have highlighted variations of such a framework, the literature has not addressed the adaptations required in response to the gradual maturity of a wide-ranging case study dealing with software applications. Following a case study-oriented methodology, this paper focuses on elaborating a set of workable maneuvers to mature the Scrum framework when applied to portfolio management. Particularly, we highlight how Scrum should be adapted from its basic setting to a vision and goal-oriented configuration or Scrumban under certain conditions. As a maturing practice, we propose a heuristic scoring technique to determine the sprint length of subprojects with different characteristics in the context of a portfolio. The study also introduces a multi-level refinement structure to enhance the monitoring of the teams' performance under the proposed mature framework. The results obtained display a considerable spike in the realization rate of release planning in light of the actual performance.

Franco Javier Santos se adentra en los obstáculos a los que nos enfrentamos dentro del proceso educativo, así como a la incultura musical de un porcentaje del alumnado.

In this work, we have designed and generated a Fe(III)-binding protein with thiol oxidoreductase activity. The consensus iron-binding motif EExxED from the frataxin protein family was grafted on a model peptide and on the surface of thioredoxin (TRX) from

Imaging technology is constantly improving and enabling accurate, deterministic simulations of transport properties through the pore space of the imaged rock sample. Meanwhile, data-driven machine learning has emerged as an alternate tool for modeling transport properties that, once trained, use a fraction of the computational resources that traditional simulations require. However, machine learning models often fail to strictly enforce the physical constraints of the system, leading to solutions that are less accurate than that of traditional solvers. Here we propose a novel hybrid workflow that combines machine learning and conventional simulation methods. The workflow begins with a three-dimensional, binary image of a sample. A trained convolutional neural network extracts spatial relationships between the porous medium geometry and the electrostatic potential field and predicts the electrical properties through a new medium. Instead of assuming a linear potential gradient, this prediction is used as the initial condition of a validated finite difference solver. The implementation of this workflow can improve the simulation run time by an order of magnitude for small images. The success of the proposed workflow heavily depends on the accuracy of model prediction. We previously developed successful methods for prediction of the velocity field (and permeability) of a Newtonian fluid in a porous medium in the laminar regime. Here, we extend the method to predict the electrical potential field. We explore one strategy of improving a model's ability to generalize to unseen samples by supplying geometric characterizations of the pore space. We find that models trained with these features individually do not result in an improvement over the baseline model trained with only the binary image. However, they do provide the model with relational information that can be incorporated into future models. Analysis of electrical properties is one of the most common methods of delineating hydrocarbon saturation in reservoir rock. The proposed workflow helps accelerate the calculation of the electric potential field and can lead to estimating hydrocarbon saturation in real time. We also expect that this workflow is easily generalized to many other transport problems in porous media.

Bacteria use type II secretion systems (T2SS) to secrete to their surface folded proteins that confer diverse functions, from nutrient acquisition to virulence. In the Klebsiella species, T2SS-mediated secretion of pullulanase (PulA) requires assembly of a dynamic filament called pseudopilus. The inner membrane assembly platform (AP) complex is essential for PulA secretion and pseudopilus assembly. The AP components PulL and PulM form an inner membrane complex interacting through their C-terminal globular domains and transmembrane segments. Here we investigated the roles of periplasmic helices and cytoplasmic domains of PulL and PulM in their assembly. We found that PulL and PulM variants lacking periplasmic helices were defective for interactions in the bacterial two-hybrid (BACTH) assay. Their function in PulA secretion and assembly of PulG subunits into pseudopilus filaments were strongly reduced. In addition, deleting the cytoplasmic peptide of PulM in variant PulMΔN nearly abolished interaction with PulG in the BACTH assay, without affecting the interaction with PulL. Nevertheless, PulL was degraded in the presence of the PulMΔN variant, suggesting that PulM N-terminal peptide interacts with PulL in the cytoplasm and plays a stabilizing role. We discuss the implication of these results for the mechanism of T2S and type IV pilus assembly.

Genotype networks are sets of genotypes connected by small mutational changes that share the same phenotype. They facilitate evolutionary innovation by enabling the exploration of different neighborhoods in genotype space. Genotype networks, first suggested by theoretical models, have been empirically confirmed for proteins and RNAs. Comparative studies also support their existence for gene regulatory networks (GRNs), but direct experimental evidence is lacking. Here, we report the construction of three interconnected genotype networks of synthetic GRNs producing three distinct gene expression phenotypes in Escherichia coli. These genotype networks, composed of over twenty different synthetic GRNs, provide robustness in face of mutations while enabling transitions to innovative phenotypes. Through realistic mathematical modeling, we quantify robustness and evolvability for the complete genotype-phenotype map and link these features mechanistically to GRN motifs. Our work thereby exemplifies how GRN evolution along genotype networks might be driving evolutionary innovation.

Reseña: Cruz Romeo, María, Pilar Salomón, María & Tabanera, Nuria (eds.): Católicos, Reaccionarios y Nacionalistas. Política e identidad nacional en Europa y América Latina Contemporáneas. Granada, Comares Historia, 2021, 242 pp., ISBN: 978-84-1369-141-1.

La interculturalidad como praxis cotidiana es todavía una agenda pendiente. Si bien hay avances muy significativos en la valoración de la diversidad cultural existente, la implementación de políticas de educación intercultural bilingüe y, el tímido reconocimiento del bagaje de conocimientos que poseen los pueblos andino-amazónicos. No obstante, persisten aún brechas muy profundas a seguir forjando. El año del bicentenario del Perú tiene implicancias hacia una revisión de la historia, de los aciertos y desaciertos en una sociedad tan compleja, tan diversa y tan desigual. En un contexto donde se ha practicado un diálogo de espaldas, superponiendo los intereses propios, sin cargo de conciencia de los efectos que ocasionan en los otros aún invisibilizados, cuyo abordaje significa ineludiblemente, desentrañar puntos neurálgicos de las sociedades con ascendencia prehispánica que fueron sistemáticamente acalladas.

¿Tienen las remesas de los trabajadores efecto multiplicador robusto sobre la economía familiar y nacional? Cuando este tipo de ingreso es destinado a consumo y no a inversión o ahorro, por ejemplo, su influencia sobre la economía es limitada. Para especialistas como Bámaca-López (2017) las remesas deberían ser menos utilizadas en la satisfacción de necesidades básicas y más en inversiones productivas.

Purpose This research has the following specific objectives: provide an overview of the literature addressing operational excellence (OE) and OE in emerging countries; propose an integrative framework of OE attributes; and propose future research directions for the OE literature. Design/methodology/approach To remain competitive in industry, many organizations are implementing OE initiatives. However, achieving OE in emerging markets has been a pressing challenge due to the scarce knowledge on how it works. Through a systematic review of the literature, this study aims to contribute to a deeper understanding of the concept of OE in emerging countries through the triple bottom line. Findings This study has found nine attributes of OE based on the three pillars of sustainability or triple bottom line (economic, environmental and social). Four of them were the most cited and served to build the proposed framework. The analysis concludes that most of the studies related to OE in emerging countries have been carried out in Asia. Finally, based on the results obtained from the literature review, six points of future research are proposed based on three research directions: OE in emerging countries, active participation by employees and culture generation and finally, research methods. Originality/value The gap that is filled in this study is that some authors have studied the application of OE in emerging countries, specifically on the Asian continent. In those cases, the literature is either oriented to describing OE from different perspectives or to its application in different companies, some of which are emerging countries. However, to the best of the authors’ knowledge, there is no study that describes the specific and complete aspects that make up a model of OE and which can show how this model can be applied in emerging countries.

Over the last few decades, environmental changes have occurred in the Cantabrian Mountains (Northwest Spain) as a result of economic, social and climatic transformations. The depopulation in the rural environment with the transformation of traditional land uses, the closure of coal mining operations, and the increase in temperatures have modified the geometry of channels, water flow, and sediment connectivity of mountain rivers.The runoff and the sediment load are modified, and the reservoirs located downstream collect all these changes thanks to the gauging stations for water flow, up and down the reservoir and the sediment sequences inside the reservoir. Studies have been carried out in natural cuts of several reservoirs during their dry season with the aim of knowing in detail the effects of each environmental change. The studied variables are accumulation rhythms, exceptional events, granulometry, and some chemical patterns. Data have already been published in the Pisuerga River basin (Palencia) from the analysis of the sediments retained in the La Requejada Reservoir (Pisabarro et al., 2019) but are not still published in Tuerto River basin in the Villameca Reservoir (León) and in Ibias River in the Grandas de Salime Reservoir (Lugo-Asturias).In the first one, it was found a clear tendency to reduce the grain size since 80’s, when the land use change from crops and grasslands towards rewilding were increased. This process was aid with a decrease of runoff close to 20% between 60’s to 2010’s. In the other two reservoirs, the Villameca and the Grandas de Salime, there are interesting sediment outcrops too, in the last one affected by mining activity. Samples of sediment have been taken which also show the tendency to a smaller grain-size particle in the sediments’ upper levels. In the Villameca Reservoir at consequence of a clear reduction of the extreme events in the last decades.Significant differences in sediment thickness have been observed between northern and southern slopes of the Cantabrian Mountains partly due to the marked asymmetry slopes, proper of this mountain range. In the first (the Grandas de Salime) up to 5.5 m has been found form since 1953 (2021), but in the La Requejada and Villameca reservoirs (in the Southern slope) only 1-2 m since 1940 (2016) and 1947 (2021). During the next dry season of the reservoirs, the research will be extended to other reservoirs with the main goal of extending this analysis and understanding the Global Change implications in the connectivity and the fluvial dynamics. Pisabarro, A., Pellitero, R., Serrano, E., Lopez-Moreno, J.I. (2019) Impacts of land abandonment and climate variability on runoff generation and sediment transport in the Pisuerga headwaters (Cantabrian Mountains, Spain), Geografiska Annaler: Series A, Physical Geography, 101:3, 211-224, DOI: 10.1080/04353676.2019.1591042

The Schmidt-hammer has been used in Geomorphology for the last decades. The effectiveness of the method has been proven by several authors, but some limitations also exists. In this work, this procedure has been tested in glacial and periglacial landforms in five different massifs in the province of León (northwestern Spain): Vizcodillo, Arcos del Agua, Muxivén, San Isidro and Peña Pieta. Tested landforms include moraines, rock glaciers, polished outcrops, talus slopes, blockfields and a debris avalanche. Quartzite has been widely used for this purpose, but granodiorite, shales and sandstones have also been tested. Results show that Schmidt-hammer data generally agree with geomorphological reconstructions. They also show strong correlation with cosmic-ray exposure ages where they exist. Rebound values are high, ranging from ≈70-72 in the oldest landforms (last glacial stage) to ≈77-80 in the most recent ones, with small differences within massifs.In Vizcodillo, four glacial stages have been clearly differentiated since the last local glacial maximum. In Arcos del Agua, periglacial deposits show two different stages of rock glaciers generation and a progressively younger age for different talus slopes related to deglaciation. At both sites, the blockfields are younger than rock glaciers. In Muxivén, Schmidt-hammer data agree with the cosmic-ray exposure dating results, indicating that most of the postglacial deposits were generated due to rapid deglaciation during the Bølling-Allerød period. In San Isidro, the results show two possible stages for rock glaciers. In Peña Prieta, different glacial and periglacial deposits were tested, but poor results were obtained.Relevant differences have been observed depending on the lithology. The mean coefficient of variation in the rebound values of the boulders was 3.1% in Arcos del Agua (quartzite), 3.5% in Vizcodillo (quartzite), 3.8% in Muxivén (quartzite), 4.7% in San Isidro (quartzite sandstones), but 9.9% in Peña Prieta (granodiorite). The differences between boulders of the same landform were also clearly greater in Peña Prieta than in the other massifs, with the quarzitic areas showing the most robust results. Although it has been used in previous works with good results, in this study granodiorite presented a significant dispersion in the rebound values of the boulders, due to the fact that its internal composition is coarse-grained and presents grains with different resistance. Shales could not be correctly tested because they offered great dispersion in the data. The results addressed the importance of selecting suitable and comparable areas on boulder surfaces for Schmidt-hammer impacts, with resistant and homogeneous lithology showing better results. Conversely, areas with high lithological heterogeneity or coarse-grained boulders may not to be suitable for the Schmidt-hammer method. Further surface exposure dating is needed to establish a calibration curve in this area.

espanolLas complicaciones del embarazo y el parto son una de las principales causas de muerte y discapacidad entre las mujeres en edad reproductiva (15 a 44 anos) de los paises menos desarrollados. Ademas, estan estrechamente asociadas a la mortalidad fetal y a condiciones precarias de salud y crecimiento para los ninos. En la mayor parte de las gestaciones de riesgo, el momento mas adecuado para iniciar el control del bienestar fetal se situa en torno a las 32-34 semanas. No obstante, en situaciones de riesgo muy elevado materno fetal -preeclampsia precoz, retraso del crecimiento intraute1ino precoz se puede iniciar en la semana 26-24. El monitoreo electronico fetal anteparto consiste en la valoracion de los latidos cardiacos fetales a traves de un registro continuo de los latidos cardiacos fetales, a traves de un monitor, quien se encarga de graficar la frecuencia cardiaca fetal por un tiempo no menor a 20 minutos, en el queda plasmado todas las caracteristicas, que nos permite cuantificar los elementos de la frecuencia cardiaca fetal, que a la interpretacion nos dara un diagnostico. La metodologia de la investigacion es una revision bibliografica, apoyada en medios electronicos, como fuente primaria de la obtencion de la informacion. Son muchos los factores de riesgo a la que puede estar sometida una mujer embarazada, desde factores geneticos hasta factores de salud pre existentes como obesidad, diabetes, hiperten-sion, entre otras; que pueden convertir un embarazo en alto riesgo, y es asi, ya que el nacimiento del feto, puede estar comprometido, dependiendo de riesgo que presente la mujer embarazada. Sin embargo, a pesar de estos riesgos, hay herramientas que pueden ayudar de una manera temprana y a tiempo a sobrellevar un embarazo de alto riesgo para que este pueda llegar a termino, como es la valoracion fetal anteparto por medio del monitoreo, que mide los valores de los latidos cardiacos fetales a traves de un registro continuo y disminuir complicaciones tales como: convulsiones neonatales, paralisis cerebral o muerte fetal ante e intraparto, mientras disminuye la necesidad de intervenciones obstetricas innecesarias (parto vaginal instrumentado o cesarea). EnglishComplications of pregnancy and childbirth are one of the leading causes of death and disability among women of repro-ductive age (15-44 years) in less developed countries. In addition, they are closely associated with fetal mortality and poor health and growth conditions for children. In most high-risk pregnancies, the best time to start monitoring fetal well-being is around 32-34 weeks. However, in situations of very high maternal-fetal risk - early pre-eclampsia, early intrauterine growth retardation, can begin at week 26-24. Antepartum electronic fetal monitoring consists of evaluating the fetal heartbeat through a continuous recording of the fetal heartbeat, through a monitor, which is in charge of graphing the fetal heart rate for a time not less than 20 minutes, In it, all the characteristics are captured, which allows us to quantify the elements of the fetal heart rate, which will give us a diagnosis upon interpretation. The research methodology is a bibliographic review, supported by electronic media, as the primary source for obtaining information. There are many risk factors that a pregnant woman may be subjected to, from genetic factors to pre-existing health factors such as obesity, diabetes, hypertension, among others; that can turn a pregnancy into high risk, and this is the case, since the birth of the fetus may be compro-mised, depending on the risk presented by the pregnant woman. However, despite these risks, there are tools that can help early and in time to cope with a high-risk pregnancy so that it can reach term, such as antepartum fetal evaluation through monitoring, which measures the values fetal heartbeat through continuous recording and reduce complications such as: neonatal seizures, cerebral palsy or fetal death before and intrapartum, while reducing the need for unnecessary obstetric interventions (instrumented vaginal delivery or cesarean section).

Here, a new gas chromatography-atmospheric pressure photoionization-high-resolution mass spectrometry (GC-APPI-HRMS) method combined with selective pressurized liquid extraction (sPLE) has been developed for the selective determination of Dechlorane Plus (DP) and its related compounds in gull egg samples used as a bioindicator of contamination. To the best of our knowledge, this is the first time these compounds have been analyzed by GC-MS using atmospheric pressure photoionization (APPI). Negative ion dopant-assisted APPI using vapors of diethyl ether and a source temperature of 250 °C provided high ionization efficiencies and mass spectra characterized by intense in-source fragment ions as well as the presence of molecular ion and characteristic cluster ions containing oxygen atoms in their chemical structure. This made it possible to improve the selectivity in the determination of these compounds compared to that obtained with traditional GC-MS ion sources. Under optimized conditions, the sPLE GC-APPI-HRMS (Orbitrap) method provided high recoveries (> 91%), good precisions (RSD%, This work received financial support from the Spanish Ministry of Science, Innovation and Universities under the project PGC2018-095013-B-I00 and PID2019-105732GB-C21, as well as the Generalitat of Catalonia under the project 2017-SGR-310 and the Spanish Autonomous Organism of National Parks under the project 2012/768. Juan F. Ayala-Cabrera received PhD fellowship from the Spanish Ministry of Education, Culture and Sports (FPU14/05539).