Hydrological response to land use land cover and climate variability, and simulation of sediment export and water yield in the catchment Kotri Sindh Pakistan using Soil and Water Assessment tool model.

The water availability concerns have been increasing due to significant impacts of land use land cover change, and climate variability. In terms of developing countries, it is one of the biggest challenges to overcome and manage sustainability in the present and future. This study aims to evaluate the change in hydrological components and simulation of sediment yield and water yield on the large-scale basin of Kotri barrage with a change in runoff due to a change in land use land cover. This study has been done on the watershed as well as the sub-watershed level to have an accurate estimation and simulation by finding the response of hydrological components toward its natural and human-induced factors using the Soil and Water Assessment tool with high-resolution geospatial-temporal inputs over the Kotri catchment. The sediment and water yield were quantified using 42 years of simulation (1981-2022) on the sub-basin level, projected to land use land cover 1990, 2000, 2010, and 2022. The increase in deforestation, agriculture, and settlement areas resulted increase in sediment load in the catchment. The sub-basins 14, 11, 12, and 13, with a high elevation and slope and with less vegetation showed higher sediment load and water yield than the sub-basins with gentle slope and with high natural vegetation cover. The sub-basins 10, 4, and 1 showed high water yield availability compared to basins 2, 3, 5, 6, 7, 8, 9. This may be the result of vegetation differences. However, contained less sediment load than basins 14, 11, 12, and 13. The main objective was to quantify the significant changes affecting catchment and sub-catchment areas, to have a better understanding of the management plan regarding land use land cover. The simulated data was further projected to prediction using machine algorithms (autoregressive integrated moving average) model for precipitation prediction, and (seasonal autoregressive integrated moving average with exogenous factors) model to predict the sediment yield and water yield in the catchment to 2060.

Seasonality of influenza-like illness and short-term forecasting model in Chongqing from 2010 to 2022.

BACKGROUND: Influenza-like illness (ILI) imposes a significant burden on patients, employers and society. However, there is no analysis and prediction at the hospital level in Chongqing. We aimed to characterize the seasonality of ILI, examine age heterogeneity in visits, and predict ILI peaks and assess whether they affect hospital operations. METHODS: The multiplicative decomposition model was employed to decompose the trend and seasonality of ILI, and the Seasonal Auto-Regressive Integrated Moving Average with exogenous factors (SARIMAX) model was used for the trend and short-term prediction of ILI. We used Grid Search and Akaike information criterion (AIC) to calibrate and verify the optimal hyperparameters, and verified the residuals of the multiplicative decomposition and SARIMAX model, which are both white noise. RESULTS: During the 12-year study period, ILI showed a continuous upward trend, peaking in winter (Dec. - Jan.) and a small spike in May-June in the 2-4-year-old high-risk group for severe disease. The mean length of stay (LOS) in ILI peaked around summer (about Aug.), and the LOS in the 0-1 and ≥ 65 years old severely high-risk group was more irregular than the others. We found some anomalies in the predictive analysis of the test set, which were basically consistent with the dynamic zero-COVID policy at the time. CONCLUSION: The ILI patient visits showed a clear cyclical and seasonal pattern. ILI prevention and control activities can be conducted seasonally on an annual basis, and age heterogeneity should be considered in the health resource planning. Targeted immunization policies are essential to mitigate potential pandemic threats. The SARIMAX model has good short-term forecasting ability and accuracy. It can help explore the epidemiological characteristics of ILI and provide an early warning and decision-making basis for the allocation of medical resources related to ILI visits.

Empirical and simulated investigation of the solid waste reverse supply chain: A complex adaptive system perspective.

Solid waste is increasing rapidly worldwide. In this study, the solid waste (household waste, construction and demolition waste and industrial waste) management systems are treated as reverse supply chain to analyze the critical operational issues based on complex adaptive system theory. At the single-layer, the complexity of the various nodes at a layer arises from rational decision-making and behavioral heterogeneity. The solid waste generation layer is employed as an example to investigate the complexity of node behavioral decisions. Regression analysis results reveal that both endogenous (Attitude, Subjective norm, and Perceived behavioral control) and exogenous factors (Economic incentive, Government supervision, Technical support) positively influence sorting behavior. The effect of Economic incentive (ß=0.327P<0.001) and Attitude (ß=0.249P<0.001) on sorting behavior are the largest. In the multi-layer system, different layers communicate with each other through the material and financial flows and have cross-layer impacts. An agent-based model is developed to investigate the multi-layer feedforward influence mechanism of changes in key layers (e.g., sorting rate, disposal rate) and the material and financial flows adaptive adjustment direction of the solid waste reverse supply chain. High rate of participation and accuracy of source sorting can shorten material flow paths and reduce storage and transportation costs. The increase in disposal rate encourages the transition of solid waste from backfill to resource utilization. This study provides a practice reference for solid waste reverse supply chain and related enterprises managers.

Exploring Endogenous and Exogenous Factors for Successful Artificial Insemination in Sheep: A Global Overview.

Artificial insemination (AI) plays a vital role in animal breeding programs. AI is applied to enhance animal genetics and facilitate the widespread integration of desirable characteristics with a high potential for productivity. However, in sheep, this biotechnology is not commonly practicable due to multi-factorial challenges, resulting in inconsistent outcomes and unpredictable results. Thoughtful selection of semen donors and recipients based on genetic merit deeply impacts ovine AI outcomes. Additionally, endogenous factors such as breed, age, fertility traits, genetic disorders, and cervical anatomy in ewes contribute to ovine AI success. Extensive research has studied exogenous influences on sexual behavior, reproductive health, and hormonal regulation, all impacting ovine AI success. These exogenous factors include techniques like estrus induction, synchronization, semen handling methods (fresh/chilled/frozen), and insemination methods (cervical/laparoscopic), as well as nutritional factors and climatic conditions. This overview of the literature highlights the endogenous and exogenous challenges facing successful ovine AI and proposes strategies and best practices for improvement. This paper will serve as a guide for understanding and optimizing the success of ovine AI.

An overview of floral regulatory genes in annual and perennial plants.

The floral initiation in angiosperms is a complex process influenced by endogenous and exogenous signals. With this approach, we aim to provide a comprehensive review to integrate this complex floral regulatory process and summarize the regulatory genes and their functions in annuals and perennials. Seven primary paths leading to flowering have been discovered in Arabidopsis under several growth condition that include; photoperiod, ambient temperature, vernalization, gibberellins, autonomous, aging and carbohydrates. These pathways involve a series of interlinked signaling pathways that respond to both internal and external signals, such as light, temperature, hormones, and developmental cues, to coordinate the expression of genes that are involved in flower development. Among them, the photoperiodic pathway was the most important and conserved as some of the fundamental loci and mechanisms are shared even by closely related plant species. The activation of floral regulatory genes such as FLC, FT, LFY, and SOC1 that determine floral meristem identity and the transition to the flowering stage result from the merging of these pathways. Recent studies confirmed that alternative splicing, antisense RNA and epigenetic modification play crucial roles by regulating the expression of genes related to blooming. In this review, we documented recent progress in the floral transition time in annuals and perennials, with emphasis on the specific regulatory mechanisms along with the application of various molecular approaches including overexpression studies, RNA interference and Virus-induced flowering. Furthermore, the similarities and differences between annual and perennial flowering will aid significant contributions to the field by elucidating the mechanisms of perennial plant development and floral initiation regulation.

Influence of Exogenous Factors Related to Nutritional and Hydration Strategies and Environmental Conditions on Fatigue in Endurance Sports: A Systematic Review with Meta-Analysis.

The aim of this systematic review with meta-analysis was to examine the influence of exogenous factors related to nutritional and hydration strategies and environmental conditions, as modulators of fatigue, including factors associated with performance fatigability and perceived fatigability, in endurance tests lasting 45 min to 3 h. A search was carried out using four databases: PubMed, Web of Science, SPORTDiscus, and EBSCO. A total of 5103 articles were screened, with 34 included in the meta-analysis. The review was registered with PROSPERO (CRD42022327203) and adhered to the PRISMA guidelines. The study quality was evaluated according to the PEDro score and assessed using Rosenthal's fail-safe N. Carbohydrate (CHO) intake increased the time to exhaustion (p < 0.001) and decreased the heart rate (HR) during the test (p = 0.018). Carbohydrate with protein intake (CHO + PROT) increased lactate during the test (p = 0.039). With respect to hydration, dehydrated individuals showed a higher rate of perceived exertion (RPE) (p = 0.016) and had a higher body mass loss (p = 0.018). In hot conditions, athletes showed significant increases in RPE (p < 0.001), HR (p < 0.001), and skin temperature (p = 0.002), and a decrease in the temperature gradient (p < 0.001) after the test. No differences were found when athletes were subjected to altitude or cold conditions. In conclusion, the results revealed that exogenous factors, such as nutritional and hydration strategies, as well as environmental conditions, affected fatigue in endurance sports, including factors associated with performance fatigability and perceived fatigability.

Alta capacidad: competencias sociales y cyberbullying / High capacity: social competences and cyberbullying

Resumen La Alta Capacidad intelectual (ACI) es una manifestación diferencial de la inteligencia humana, de base neurobiológica, pero que debe expresar su alto potencial a lo largo del desarrollo de la per sona que la posee, mediante la covariación de factores moduladores endógenos (como la competencia social) y exógenos. El objetivo del trabajo es doble: 1) conocer, comparativamente la competencia social de menores con y sin ACI, 2) diferenciar aquellas competencias sociales que podrían ser factores protectores o de riesgo frente al mal uso de las tecnologías digitales. Se administra la Social Skills Improvement System-Rating Scales a una muestra de n = 70 aprendices (n = 35 con ACI, n = 35 con inteligencia promedio) de 11 a 16 años, analizando si existen diferencias estadísticamente significativas en habilidades sociales y en dificultades de conducta. Los resultados muestran diferencias estadísticamente significativas, a favor de los participantes con ACI en habilidades sociales (especialmente en: Responsabilidad, Cooperación y Autocontrol) y mejor ajuste personal, con baja inci dencia de dificultades internalizantes y externalizantes. Se concluye y discute el rol protector de las habilidades sociales para afrontar contextos interactivos complejos como el derivado de la era digital y agresiones como el cyberbullying.

Abstract High Intellectual Ability (HIA) is a differential manifestation of human intelligence with a neurobiologi cal basis but which must express its high potential along the developmental trajectory through the covariation of endogenous (such as social competence) and exogenous modulating factors. The aim of the study is twofold: 1) to know, comparatively, the social competence of children with and without HIA, 2) to differentiate those social competences that could be protective or risk factors against the misuse of digital technologies. The Social Skills Improvement System-Rating Scales were administered to a sample of n = 70 learners (n = 35 with ICA, n = 35 with average intelligence) aged 11 to 16, analysing whether there are statistically significant differences in social skills and behavioural difficulties. Results show statistically significant differences in favour of participants with ICA in social skills (especially in: Responsibility, Co-operation and Self-Control) and better personal adjustment, with low incidence of internalising and externalising difficulties. We conclude and discuss the protective role of social skills in coping with complex interactive contexts such as the digital age and aggressions such as cyberbullying.

Association of exogenous factors with molecular epidemiology of Staphylococcus aureus in human oral cavity.

The frequency of Staphylococcus aureus strains associated with oral cavity microbiota has prodigious consideration. Although S. aureus has been reflected as an ephemeral member of the human oral cavity microbiota, the isolation, identification, and characterization of S. aureus is important. The present study aimed to characterize S. aureus strains from the oral cavity microflora, isolation of S. aureus from the human oral cavity microbiota, and demographic information of the participants to evaluate exogenous factors associated with the presence of S. aureus and their genetic analysis linkage with different factors. The method used in this study is the isolation of oral cavity microbiomes using sheep blood agar and Mannitol salt agar. We performed antibiotic profiling with various antibiotics and genetic analysis utilizing gene-specific primers for specific genes, including nuc, mecA, pvl, agr, and coa. A significant number of S. aureus isolates were found in the oral cavity of humans 18/84 (21.42%), and all 18 strains tested positive for the confirmatory nuc gene. Antibiotic resistance-conferring gene mecA was positive in 10 (55.6%) isolates. It was found that the occurrence of pvl, agr, and coagulase (coa) genes was 9 (50%), 6 (33.33%), and 10 (55.6%), respectively. The genetic analysis reported that significant associations were present between male and mecA gene (P = 0.03) and coa (P = 0.03), smokers with the occurrence of mecA (P = 0.02), agr (P = 0.048) and coa (P = 0.02) genes. Likewise, the association of antibiotic usage was significantly found with mecA (P = 0.02), coa (P = 0.02); however, the individuals who have taken orthodontic treatment recently have a significant association with agr (P = 0.017). The use of mouth rinse was significantly associated with the prevalence of the pvl gene (P = 0.01), and tooth brushing frequency and inflammation of the buccal cavity were also statistically significant in relation to pvl gene prevalence (P = 0.02, 0.00, respectively). Moreover, calories and weight-controlled diet were significantly associated with mecA, agr, and highly significant with coa (P = 0.02, 0.048, 0.000), so all P < 0.05, and no significant association was found between the socioeconomic status of individuals with aforementioned analyzed genes.

[High capacity: social competences and cyberbullying]. / Alta capacidad: competencias sociales y cyberbullying.

High Intellectual Ability (HIA) is a differential manifestation of human intelligence with a neurobiological basis but which must express its high potential along the developmental trajectory through the covariation of endogenous (such as social competence) and exogenous modulating factors. The aim of the study is twofold: 1) to know, comparatively, the social competence of children with and without HIA, 2) to differentiate those social competences that could be protective or risk factors against the misuse of digital technologies. The Social Skills Improvement System-Rating Scales were administered to a sample of n = 70 learners (n = 35 with ICA, n = 35 with average intelligence) aged 11 to 16, analysing whether there are statistically significant differences in social skills and behavioural difficulties. Results show statistically significant differences in favour of participants with ICA in social skills (especially in: Responsibility, Co-operation and Self-Control) and better personal adjustment, with low incidence of internalising and externalising difficulties. We conclude and discuss the protective role of social skills in coping with complex interactive contexts such as the digital age and aggressions such as cyberbullying.

La Alta Capacidad intelectual (ACI) es una manifestación diferencial de la inteligencia humana, de base neurobiológica, pero que debe expresar su alto potencial a lo largo del desarrollo de la persona que la posee, mediante la covariación de factores moduladores endógenos (como la competencia social) y exógenos. El objetivo del trabajo es doble: 1) conocer, comparativamente la competencia social de menores con y sin ACI, 2) diferenciar aquellas competencias sociales que podrían ser factores protectores o de riesgo frente al mal uso de las tecnologías digitales. Se administra la Social Skills Improvement System-Rating Scales a una muestra de n = 70 aprendices (n = 35 con ACI, n = 35 con inteligencia promedio) de 11 a 16 años, analizando si existen diferencias estadísticamente significativas en habilidades sociales y en dificultades de conducta. Los resultados muestran diferencias estadísticamente significativas, a favor de los participantes con ACI en habilidades sociales (especialmente en: Responsabilidad, Cooperación y Autocontrol) y mejor ajuste personal, con baja incidencia de dificultades internalizantes y externalizantes. Se concluye y discute el rol protector de las habilidades sociales para afrontar contextos interactivos complejos como el derivado de la era digital y agresiones como el cyberbullying.

Current perspectives on clinical use of exosomes as novel biomarkers for cancer diagnosis.

Exosomes are a heterogeneous subset of extracellular vesicles (EVs) that biogenesis from endosomes. Besides, exosomes contain a variety of molecular cargoes including proteins, lipids and nucleic acids, which play a key role in the mechanism of exosome formation. Meanwhile, exosomes are involved with physiological and pathological conditions. The molecular profile of exosomes reflects the type and pathophysiological status of the originating cells so could potentially be exploited for diagnostic of cancer. This review aims to describe important molecular cargoes involved in exosome biogenesis. In addition, we highlight exogenous factors, especially autophagy, hypoxia and pharmacology, that regulate the release of exosomes and their corresponding cargoes. Particularly, we also emphasize exosome molecular cargoes as potential biomarkers in liquid biopsy for diagnosis of cancer.

Migraine: interactions between brain's trait and state.

It is well established that migraine is a multifactorial disorder. A deep understanding of migraine should be based upon both the underlying traits and the current states affected by different physiological, psychological, and environmental factors. At this point, there is no framework fully meeting these criteria. Here, we describe a broader view of the migraine disorder defined as a dysfunctional brain state and trait interaction. In this model, we consider events that may enhance or diminish migraine responsivity based on an individual's trait and state. This could provide an expanded view for considering how migraine attacks are sometimes precipitated by "triggers" and sometimes not, how these factors only lead to migraine attacks in migraine patients, or how individuals with an increased risk for migraine do not show any symptoms at all. Summarizing recent studies and evidence that support the concept of migraine as a brain state-trait interaction can also contribute to improving patient care by highlighting the importance of precision medicine and applying measures that are able to capture how different traits and states work together to determine migraine.

A systematic methodology for the robust quantification of energy efficiency at wastewater treatment plants featuring Data Envelopment Analysis.

This article examines the potential benefits of using Data Envelopment Analysis (DEA) for conducting energy-efficiency assessment of wastewater treatment plants (WWTPs). WWTPs are characteristically heterogeneous (in size, technology, climate, function …) which limits the correct application of DEA. This paper proposes and describes the Robust Energy Efficiency DEA (REED) in its various stages, a systematic state-of-the-art methodology aimed at including exogenous variables in nonparametric frontier models and especially designed for WWTP operation. In particular, the methodology systematizes the modelling process by presenting an integrated framework for selecting the correct variables and appropriate models, possibly tackling the effect of exogenous factors. As a result, the application of REED improves the quality of the efficiency estimates and hence the significance of benchmarking. For the reader's convenience, this article is presented as a step-by-step guideline to guide the user in the determination of WWTPs energy efficiency from beginning to end. The application and benefits of the developed methodology are demonstrated by a case study related to the comparison of the energy efficiency of a set of 399 WWTPs operating in different countries and under heterogeneous environmental conditions.

Exogenous factors matter when interpreting the results of an impact evaluation: a case study of rainfall and child health programme intervention in Rwanda.

OBJECTIVE: Public health interventions are often implemented at large scale, and their evaluation seems to be difficult because they are usually multiple and their pathways to effect are complex and subject to modification by contextual factors. We assessed whether controlling for rainfall-related variables altered estimates of the efficacy of a health programme in rural Rwanda and have a quantifiable effect on an intervention evaluation outcomes. METHODS: We conducted a retrospective quasi-experimental study using previously collected cross-sectional data from the 2005 and 2010 Rwanda Demographic and Health Surveys (DHS), 2010 DHS oversampled data, monthly rainfall data collected from meteorological stations over the same period, and modelled output of long-term rainfall averages, soil moisture, and rain water run-off. Difference-in-difference models were used. RESULTS: Rainfall factors confounded the PIH intervention impact evaluation. When we adjusted our estimates of programme effect by controlling for a variety of rainfall variables, several effectiveness estimates changed by 10% or more. The analyses that did not adjust for rainfall-related variables underestimated the intervention effect on the prevalence of ARI by 14.3%, fever by 52.4% and stunting by 10.2%. Conversely, the unadjusted analysis overestimated the intervention's effect on diarrhoea by 56.5% and wasting by 80%. CONCLUSION: Rainfall-related patterns have a quantifiable effect on programme evaluation results and highlighted the importance and complexity of controlling for contextual factors in quasi-experimental design evaluations.

[Progress in exogenous factors affecting the growth and remodeling of condylar process].

Condyle is a critical growth region of the mandible where mandible by endochondral ossification occurs. Condylar cartilage belongs to the secondary cartilage, which is not only affected by genetic factors but also by stress, drug intake, and other local factors. To promote the growth of the mandible, various exogenous and local factors were used to alter the biological environment of the condylar cartilage to stimulate endochondral ossification. This article reviews studies on the influence of exogenous factors on condylar growth and reconstruction. This literature review will provide a reference point for the treatment of patients with mandibular retraction.

Progress in exogenous factors affecting the growth and remodeling of condylar process / 华西口腔医学杂志

Condyle is a critical growth region of the mandible where mandible by endochondral ossification occurs. Condylar cartilage belongs to the secondary cartilage, which is not only affected by genetic factors but also by stress, drug intake, and other local factors. To promote the growth of the mandible, various exogenous and local factors were used to alter the biological environment of the condylar cartilage to stimulate endochondral ossification. This article reviews studies on the influence of exogenous factors on condylar growth and reconstruction. This literature review will provide a reference point for the treatment of patients with mandibular retraction.

Análisis de las pautas de crianza y los tipos de autoridad, y su relación con el surgimiento de conductas criminales: una revisión teórica / Analysis of the childrearing and upbringing guidelines and their relationship with the emergence of criminal conducts: a theoretical review / Análise das diretrizes do criação e dos tipos de autoridade, e sua relação com o surgimento de condutas criminosas: uma revisão teórica

El estudio tuvo como objetivo realizar una revisión teórica acerca de las pautas de crianza, los diferentes tipos de autoridad y la relación de estas con la aparición de conductas criminales en la adultez, para así aportar conocimientos a la comprensión de las posibles causas de la conducta criminal, las cuales han sido un fenómeno ampliamente estudiado. Para ello se realizó una revisión de la literatura de los últimos seis años en las bases de datos Science Direct, Ebsco, Redalyc y Scopus, y se encontró que si bien en el desarrollo de las conductas criminales convergen diversos elementos, los estilos de crianza, autoritarios, negligentes o demasiado permisivos, son uno de los factores explicativos de tipo ambiental más importantes del surgimiento de este tipo de conductas. Al finalizar se discuten las implicaciones de estos resultados en la construcción de programas de intervención y rehabilitación.

The objective of this study was to carry out a theoretical review about childrearing and upbringing, the different types of authority and their relationship with the emergence of criminal conducts in adulthood, in order to contribute some knowledge to the understanding of the possible causes of criminal behavior as a widely studied phenomenon. For this purpose, through a review of the literature produced in the past six years in the Science Direct, Ebsco, Redalyc and Scopus databases, it was found that although diverse elements converge in the development and evolution of criminal conducts, it has to be said that childrearing and upbringing styles either authoritarian or overly permissive are among the main explanatory factors of the environmental type that bear more relevance in the occurrence of this kind of conducts. At the conclusion of the study, the implications of these results in the building of intervention and rehabilitation programs are discussed

O estudo teve como o objetivo realizar uma revisão teórica sobre as diretrizes de criação, os tipos diferentes da autoridade e a relação dessas com a aparência de condutas criminosas na idade adulta, para contribuir o conhecimento à compreensão das causas possíveis da conduta criminal, que foram um fenômeno estudado extensamente. Para isso, uma revisão da literatura dos últimos seis anos foi feita nos bancos de dados Science Direct, Ebsco, Redalyc e Scopus, e encontrou-se que embora no desenvolvimento de condutas criminais os elementos diversos convergissem, os estilos da criação, autoritários, negligentes ou demasiado permissivos, são um dos fatores explicativos do tipo ambiental mais importantes do surgimento deste tipo de condutas. Ao finalizar, as implicações destes resultados são discutidas na construção de programas da intervenção e reabilitação

Descriptive epidemiology and risk factors of primary central nervous system tumors: Current knowledge.

Although comparisons are difficult due to differences in methodologies, the annual incidence rates of central nervous system (CNS) tumors range from 8.5 to 21.4/100,000 population according to cancer registries, with a predominance of neuroepithelial tumors in men and meningiomas in women. An increase in the incidence of CNS tumors has been observed during the past decades in several countries. It has been suggested that this trend could be due to aging of the population, and improvements in diagnostic imaging and healthcare access, but these factors do not explain differences in incidence by gender and histological subtypes. Several etiological hypotheses related to intrinsic (sociodemographic, anthropometric, hormonal, immunological, genetic) and exogenous (ionizing radiation, electromagnetic fields, diet, infections, pesticides, drugs) risk factors have led to analytical epidemiological studies to establish relationships with CNS tumors. The only established environmental risk factor for CNS tumors is ionizing radiation exposure. However, for other risk factors, studies have been inconsistent and inconclusive due to systematic differences in study design and difficulties in accurately measuring exposures. Thus, the etiology of CNS tumors is complex and may involve several genetic and/or environmental factors that may act differently according to histological subtype.

Extracting information from S-curves of language change.

It is well accepted that adoption of innovations are described by S-curves (slow start, accelerating period and slow end). In this paper, we analyse how much information on the dynamics of innovation spreading can be obtained from a quantitative description of S-curves. We focus on the adoption of linguistic innovations for which detailed databases of written texts from the last 200 years allow for an unprecedented statistical precision. Combining data analysis with simulations of simple models (e.g. the Bass dynamics on complex networks), we identify signatures of endogenous and exogenous factors in the S-curves of adoption. We propose a measure to quantify the strength of these factors and three different methods to estimate it from S-curves. We obtain cases in which the exogenous factors are dominant (in the adoption of German orthographic reforms and of one irregular verb) and cases in which endogenous factors are dominant (in the adoption of conventions for romanization of Russian names and in the regularization of most studied verbs). These results show that the shape of S-curve is not universal and contains information on the adoption mechanism.

Neural stem cells differentiated from iPS cells spontaneously regain pluripotency.

Differentiated somatic cells can be reprogrammed into pluripotent stem cells by transduction of exogenous reprogramming factors. After induced pluripotent stem (iPS) cells are established, exogenous genes are silenced. In the pluripotent state, retroviral genes integrated in the host genome are kept inactive through epigenetic transcriptional regulation. In this study, we tried to determine whether exogenous genes remain silenced or are reactivated upon loss of pluripotency or on differentiation using an in vitro system. We induced differentiation of iPS cells into neural stem cells (NSCs) in vitro; the NSCs appeared morphologically indistinguishable from brain-derived NSCs and stained positive for the NSC markers Nestin and Sox2. These iPS cell-derived NSCs (iPS-NSCs) were also capable of differentiating into all three neural subtypes. Interestingly, iPS-NSCs spontaneously formed aggregates on long-term culture and showed reactivation of the Oct4-GFP marker, which was followed by the formation of embryonic stem cell-like colonies. The spontaneously reverted green fluorescent protein (GFP)-positive (iPS-NSC-GFP(+) ) cells expressed high levels of pluripotency markers (Oct4 and Nanog) and formed germline chimeras, indicating that iPS-NSC-GFP(+) cells had the same pluripotency as the original iPS cells. The reactivation of silenced exogenous genes was tightly correlated with the downregulation of DNA methyltransferases (Dnmts) during differentiation of iPS cells. This phenomenon was not observed in doxycycline-inducible iPS cells, where the reactivation of exogenous genes could be induced only by doxycycline treatment. These results indicate that pluripotency can be regained through reactivation of exogenous genes, which is associated with dynamic change of Dnmt levels during differentiation of iPS cells.