bluuebunny/crossref_metadata_2025 huggingface dataset:
Προσβάσιμη λεξικογραφία
Authors: Γαρούφος Απόστολος
Published: February 2025

Στόχο της διδακτορικής διατριβής αποτελεί η δημιουργία ενός ειδικού ηλεκτρονικού λεξικού προσβάσιμου για μαθητές/μαθήτριες της πρωτοβάθμιας και δευτεροβάθμιας εκπαίδευσης με οπτικές αναπηρίες με τρόπο διαφανή μέσω της συστηματικής καταγραφής των βημάτων εκπόνησης σε λεξικογραφικό πρωτόκολλο. Το ηλεκτρονικό λεξικό περιλαμβάνει 3.830 λήμματα τα οποία καλύπτουν ένα εκτενές εύρος λεξιλογίου, το οποίο έχει αντληθεί από τα σχολικά βοηθήματα των αντίστοιχων μαθημάτων της πρωτοβάθμιας και δευτεροβάθμιας εκπαίδευσης. Επίσης, το συγκεκριμένο λεξικό, διαθέτει νέα τεχνολογία, όπου θα βοηθάει τους μαθητές/μαθήτριες να μπορούν να αυτο-εξυπηρετηθούν ως προς την κατάκτηση της γνώσης, βελτιώνοντας έτσι δεξιότητες και στρατηγικές μάθησης, μέσω της χρήσης των έξι πλήκτρων. Στην ουσία, ο/η χρήστης του λεξικού με προβλήματα όρασης, έχει πλέον τη δυνατότητα ορισμού συντομεύσεων, μετατρέποντας το συμβατικό πληκτρολόγιο σε βασικό πληκτρολόγιο Braille. Επομένως, μπορεί να αναζητεί πολύ πιο εύκολα οποιαδήποτε καταχώριση στο λεξικό χρησιμοποιώντας μόνο έξι κουμπιά στο πληκτρολόγιο, όπως θα έκανε με μια γραφομηχανή Braille. Συνεπώς, ο χρήστης δεν υποχρεούται να μαθαίνει και να χρησιμοποιείτο πληκτρολόγιο QWERTY. Παρέχεται, επίσης, τόσο ηχητική ανάγνωση της αναζητούμενης καταχώρισης όσο και ηχητική αποφώνηση. Πρωταρχικό κίνητρο για την ανάπτυξη της εφαρμογής αυτής και για την εκπόνηση της παρούσας διατριβής αποτέλεσε η κοινωνική διάσταση του θέματος και η διασφάλιση της ανεμπόδιστης πρόσβασης των ατόμων με αναπηρίες στην εκπαίδευση. Επομένως, απώτερος στόχος είναι η προσβασιμότητα και οι ίσες εκπαιδευτικές δυνατότητες όλων των μαθητών και μαθητριών στη γλωσσική διδασκαλία, δημιουργώντας όλες εκείνες τις απαραίτητες συνθήκες κατά την εκπαιδευτική διαδικασία. Η συμβολή της εργασίας έγκειται στη δημιουργία ενός νέου προσβάσιμου εκπαιδευτικού πόρου για την κοινότητα των ατόμων με οπτική αναπηρία και η συστηματική καταγραφή της πορείας εκπόνησης σε λεξικογραφικό πρωτόκολλο διαθέσιμο σε όλους.
How to Prepare Future Primary School Teachers to Participate in Pedagogical Achievement Competitions
Authors: Lebedeva N. , Pradun I.
Published: February 2025

In the article, the authors share their experience of teaching the subject “Pedagogical Mastery of Primary School Teachers” at a university, developing the topic: “The Role of Professional Pedagogical Competitions in the Formation of Pedagogical Mastery of Future Primary School Teachers”. Examples of assignments and methodological developments are offered that can be useful to teachers in the process of forming and developing pedagogical mastery through the possible participation of students – future primary school teachers – in professional pedagogical competitions.
Development of children's creative independence in visual activity
Authors: Ershova Dar'ya
Published: February 2025

The development of creative independence is the most important prerequisite for personal self-determination and self-realization of the child. This article examines the concept of creative independence, and for the first time formulates its definition in relation to children's visual activities. The characteristic features of creative independence in the context of primary school age are investigated on the basis of a humanistic and personality-oriented approach. The conclusion is drawn that creative independence finds its embodiment in the author's artistic images based on the processing of individual impressions of the surrounding reality and expressing a child's worldview. The role of experimental activity and artistic reflection is emphasized. The result of the study is a description of the pedagogical conditions for the development of creative independence in primary school, based on motivational, cognitive and activity structural components.
Artificial Intelligence Tools in Environmental Education: Facilitating Creative Learning about Complex Interaction in Nature
Authors: Sachyani Dana , Gal Adiv
Published: February 2025

This article aims to answer the research question: How do 5th grade students experience the use of artificial intelligence (AI) tools to create a comic strip describing the survival struggle between the Myna and the Lesser Kestrel? This study utilized a case-study approach to examine the advantages and challenges experienced by 5th grade students using AI tools to create a comic strip about the Lesser Kestrel's survival struggle. Data were collected through qualitative methods, including student reflections, drawings, and analyses of the comic strips they created. Additionally, a questionnaire was used to assess students' attitudes towards the four components of 21st century skills: Creativity, critical thinking, collaboration, and communication. The study indicates that the development of 21st century skills among students requires a collaborative effort involving both parents and teachers. It is not sufficient to rely solely on technological tools; there must be intermediary processes and support from teachers, who are obliged to adjust their teaching methods. Additionally, a teaching approach that supports the creation of a future citizen with a humanistic outlook and awareness of the complexity of life, is essential. This approach develops students' environmental citizenship, which is also an important 21st century skill. This involves integrating ethical, inclusive, and holistic perspectives to address complex problems, such as the survival struggle between the Lesser Kestrel and Myna.
eIF5A downregulated by mechanical overloading delays chondrocyte senescence and osteoarthritis by regulating the CREBBP-mediated Notch pathway
Authors: Huang Jialuo , Zheng Jianrong , Yin Jianbin , Lin Rengui , Wu Junfeng , Xu Hao-Ran , Zhu Jinjian , Zhang Haiyan , Wang Guiqing , Cai Daozhang
Published: February 2025

Aims

To examine how eukaryotic translation initiation factor 5A (eIF5A) regulates osteoarthritis (OA) during mechanical overload and the specific mechanism.

Methods

Histological experiments used human bone samples and C57BL/6J mice knee samples. All cell experiments were performed using mice primary chondrocytes. Messenger RNA (mRNA) sequencing was performed on chondrocytes treated with 20% cyclic tensile strain for 24 hours. Western blot (WB) and quantitative polymerase chain reaction were employed to detect relevant indicators of cartilage function in chondrocytes. We created the destabilization of the medial meniscus (DMM) model and the mechanical overload-induced OA model and injected with overexpressing eIF5A adenovirus (eIF5A-ADV). Cartilage degeneration was evaluated using Safranin O/Fast Green staining. Relative protein levels were ascertained by immunohistochemistry (IHC) and immunofluorescence (IF) staining.

Results

After OA initiation, eIF5A caused an upregulation of type II collagen (COL2) and a downregulation of matrix metalloproteinase 13 (MMP13), P16, and P21, which postponed the aggravation of OA. Further sequencing and experimental findings revealed that eIF5A knockdown accelerated the progression of OA by boosting the expression of histone acetyltransferase cyclic-adenosine monophosphate response element binding protein (CREB)-binding protein (CREBBP) to mediate activation of the Notch pathway.

Conclusion

Our findings identified a crucial functional mechanism for the onset of OA, and suggest that intra-articular eIF5A injections might be a useful therapeutic strategy for OA treatment.

Cite this article: Bone Joint Res 2025;14(2):124–135.
Application of Lenstra–Lenstra–Lovasz on Elliptic Curve Cryptosystem Using IOT Sensor Nodes
Authors: Khan Md Sameeruddin , Chen Thomas M. , Sathiyanarayanan Mithileysh , Mujeerulla Mohammed , Raja S. Pravinth
Published: February 2025

The Internet of Things (IoT) model is presented in this paper with multi-layer security based on the Lenstra-Lenstra-Lovasz (LLL) algorithm. End nodes for the Internet of Things include inexpensive gadgets like the Raspberry Pi and Arduino boards. It is not practical to run rigorous algorithms on them, as opposed to computer systems. Therefore, a cryptography procedure is required that could function on this IOT equipment. Bitcoins and Ethereum are examples of cryptocurrency and Ripple employs techniques such as elliptic curve digital signature, Elliptic-Curve Diffie-Hellman (ECDH), and algorithm to sign any cryptocurrency on SECP256k1 elliptic curves transactions. By using Lenstra-Lenstra-Lovasz on a real-world Bitcoin blockchain and applying it to multiple dimensions, such as nonce leakage and weak nonces across several elliptic curves with different bit sizes on a Raspberry Pi, we can demonstrate the security of elliptic curve cryptosystems. Public key encryption techniques are seriously threatened by the development of quantum computing. Therefore, employing lattice encryption with Nth Degree Truncated Polynomial Ring Units (NTRU-NTH) on the Bitcoin blockchain will increase the resistance of Bitcoin blocks to quantum computing assaults. The execution time taken on SECP256k1 is 131.7 Milli seconds comparatively faster than NIST-224P and NIST-384P.
Viajes forzados y otras tensiones del adentro y el afuera: Agripina Samper de Ancízar e Inés Ancízar Samper, dos mujeres liberales del fin de siglo XIX
Authors: Alzate Carolina
Published: February 2025

Abstract: This paper examines the exile resulting from the preeminence of the ultraconservative political movement led in Colombia by Rafael Núñez (1825–1894) known as the Regeneración, in a selection of poems, letters, and diaries written by two Colombian women authors at the end of the nineteenth century: Agripina Samper de Ancízar and her daughter, Inés Ancízar Samper. In its apparently domestic theme, Agripina's poetry, specifically the pieces dedicated to her late husband and absent children published in periodicals, constitute clear and stark incursions into the political scene of the moment. Inés's intimate writing provides access to unexpected spaces of experience: the discussion of politics within the domestic space of the living room, the streets, and even her home—not entirely hers—, and the loss of her homeland. For both women, the lack of place within the nation precedes exile and invites readers to approach home and writing as ever-elusive spaces.
El destierro de Adolfo León-Gómez: Necroescritura y modernización en Agua de Dios
Authors: Martínez-Pinzón Felipe
Published: February 2025

Abstract: This text reconstructs Colombian poet Adolfo León-Gómez's (1856–1927) banishment, writings, and first experiences in the leprosarium of Agua de Dios (Colombia), placing it in the broader context of a necro-literature emerging from the horrors of the War of the Thousand Days (1899–1902). By paying close attention to the ways in which the press narrated his banishment to this colony and the ways in which León-Gómez narrated it in La Ciudad del Dolor: Ecos de enterrados vivos y del presidio de inocentes (1923), this essay analyzes the political tools given to the macabre and the necrological. First, it argues that León-Gómez practiced a "necropoetics" (Davison) to show how inhabitants of the leprosarium were "buried alive" in so much as they were, because of their condition, deprived of their political rights and, thus, turned into ex-citizens. Secondly, it reflects on the links between modernization, popular music, and poetry to show how musical adaptations and recordings of León-Gómez poetry about Agua de Dios created a pathway to (re)connecting the world of the living (the 'healthy') with the world of the dead (the infirmed) as a reflection on speed and empathy in times of rural modernization in Colombia.
Cómo estar ausente en todas partes: Los viajes de José Ingenieros
Authors: De La Torre Ana María Pozo
Published: February 2025

Abstract: José Ingenieros (1877–1925), the Argentine psychiatrist born in Italy, was part of the "cultural coalition of the new liberal state" (Ludmer 35). However, because of his migrant status, he faced a nationalistic elite that did not fully accept him. In 1905, Ingenieros traveled to Europe to participate in the International Congress of Psychology. By analyzing his crónicas de viaje and his correspondence, this essay explores his use of simulation to market himself and rub shoulders with Enrico Ferri and Cesare Lombroso. On this travel, two perspectives come together: the European that sees him as Argentine, and the Argentine that sees him as a migrant. Ingenieros's writing plays with these two perspectives, and in a paradoxical way, embodies the idea that one must be a foreigner to truly be successful in Argentina. This trip is compared to his second: in 1911, Ingenieros closed his doctor's office, self-exiled, and wrote El hombre mediocre (1913), in which he defined the destiny of men of genius as "being absent everywhere" (305). By reading his correspondence and El hombre mediocre , this essay analyzes Ingenieros as the Italian migrant who travels to Europe not simply to return to his lost homeland, but as a Latin American who has been shaped by disappointment. In this second trip, Ingenieros represents, also paradoxically, that being a Latin American means living in the periphery and inhabiting failure.
Extractive Care, Economic Violence, and Horizons of Grievability in Canción sin nombre (2019)
Authors: Renker Tess
Published: February 2025

Abstract: The present essay considers Peruvian filmmaker Melina León's Canción sin nom bre (2019), which traces the story of an Indigenous migrant woman whose infant is stolen at a maternity clinic. While the film takes place in 1988 and makes frequent, explicit references to Peru's Internal Armed Conflict (~1980–2000)—thus designating it a Conflict film —Peru's civil war is overshadowed by the racialized economic violence and extractive care suffered by the protagonist. This essay considers the friction produced by the film's discrepancies in plot and framing, arguing that it suggests new interpretive frameworks for conceptualizing Peru's Internal Armed Conflict. Concretely, it proposes that the film presents economic violence as violence , forcing a retheorization of the Conflict's past and current consequences for migrant, racialized, and otherwise marginalized populations, with a particular emphasis on the impact of (neo)liberal economic models. Finally, and using Judith Butler's notion of grievability as a point of departure, it argues that the film presents a model for making non-physical, economic violences grievable violences and for expanding what I call Peru's horizons of grievability to include the lives and experiences of those who, according to capitalist logics, do not matter.
Pornographic Economies: Metaphoricity in Alan Pauls's Historia del dinero
Authors: Morales José Luis Suárez
Published: February 2025

Abstract: This article analyzes the metaphorical play between money, gender, pornography, and literary representation in Alan Pauls's 2013 novel Historia del dinero . This novel accurately depicts the economic instability of Argentina since the 1970s when the military dictatorship imposed neoliberalism and upended state-guided economies. The ways in which neoliberal economic relations are structured by gender relations and sexual difference are also explored. In this regard, this analysis will argue that the use of pornographic tropes in Historia del dinero , while being deployed to look critically at the place of money in Argentinian society, also sheds light on the limits of metaphoric language. By dialoguing with Verónica Gago, Paul Preciado, and Jacques Derrida, this piece problematizes the interplay between economic and gendered languages that allow readers to understand these social phenomena. By using Derrida's notion of metaphoricity as the ground zero of language, it is shown that metaphors do not represent the external world accurately but rather transfer one concept across linguistic realms to create meaning. In the case of Historia del dinero , pornographic excess points to a moment in which metaphoric relations collapse, thus showing that metaphors are, despite their structural failure, the only way through which language signifies.
Who Killed the Southern Cotton Textile Industry?
Authors: Hughes Joseph “Chip”
Published: February 2025

Abstract: Life in southern cotton textile mill villages during the late nineteenth and early twentieth centuries was shaped by the dynamics of industrialization, economic exploitation, and a distinct social structure. Living conditions in these villages were rudimentary, and the work environment was often hazardous. Machinery in the mills lacked proper safety measures, and accidents were common. Noise, dust, and unhealthy working conditions took a toll on workers’ physical well-being. The challenges faced by these workers, both in their working conditions and their struggle for rights, played a crucial role in the evolution of the broader labor movement in the United States. Organizing campaigns in the late 1970s hold enduring significance in American labor history, as they exemplify the struggles faced by workers in their quest for fair wages, safe working conditions, and the right to organize.
What Is It Worth?
Authors: O’Bryan Libby
Published: February 2025

Abstract: An installation titled What is it Worth? was created as part of the 2015 Made in WNC exhibition for the Center for Craft. The installation examined the process, product, and value of textile manufacturing. Its creators produced thirty blankets and documented, choreographed, and filmed each stage of production—design, weaving, cutting, sewing, finishing, and fulfillment. Viewers were asked to define the meaning of this project and assess its relative worth. To illuminate the costs and labor involved in producing these blankets, the audience was asked to evaluate the data, respond to a survey, and “crowd price” the blankets. The organizers collected 142 responses over a four-week installation. Averaged results included business managers pricing the blanket at $344.76, and consumers on average willing to pay $283.80. The author feels the real worth of empowered employees creating meaningful products is the effects they have on a community’s culture.
“Blinging just like us”: Beading and Legacy in New Orleans
Authors: Pleasant Marwan , Chanin Natalie , Terenzio Olivia Ware
Published: February 2025

Abstract: This interview with fashion designer and Mardi Gras Indian Marwan Pleasant, conducted by Natalie Chanin and Olivia Terenzio of Project Threadways, describes Pleasant’s experience with textiles. Pleasant grew up masking as a Mardi Gras Indian in the Golden Eagles tribe in New Orleans, Louisiana. He learned to bead and embroider from his grandfather, Big Chief Monk Boudreaux, creating elaborate suits for Mardi Gras each year. He has used those skills to create his own successful fashion brand, Marlence. In the conversation, Pleasant discussed his family tradition of beading and sewing, the role and perception of Mardi Gras Indians in his New Orleans community, and the incredible amount of creativity, work, and detail that goes into a suit. His skills allowed him to launch a career as a fashion designer and educator, and he sold one hundred embellished hats to fund six months in Paris to learn more techniques.
Penelope Rich as Interlocutor in Richard Barnfield's The Affectionate Shepheard
Authors: Grayson Spencer
Published: February 2025

Abstract: This article argues that Richard Barnfield's The Affectionate Shepheard configures its dedicatee, Penelope Rich, as what I call an "interlocutor": a collaborative reader who transforms the text's interpretive value and facilitates a wider readership. I identify resonances in diction between the collection's dedication and main text that interpolate Rich into the collection's diegesis. Within the diegesis, Rich both guides the collection into elite literary circles and reframes its lover/beloved relationship as a mutually constitutive collaboration between text and reader. Reading for interlocutors reveals increased female textual agency in nonauthorial positions, which expands possible methodologies for work in feminist bibliography.
Different Worlds: Otherness and Double Consciousness in the Essays and Memoirs of Charles Simic
Authors: Janjatović Violeta , Popin Aleksandra
Published: February 2025

Abstract: Charles Simic, the Serbian-American poet laureate (15th Poet Laureate Consultant in Poetry to the Library of Congress in Washington, D.C., 2007) and essayist, extensively explored themes of otherness and double consciousness in his literary oeuvre. After he left Yugoslavia with his mother at the age of 15, Simic's upbringing and acute awareness of his Yugoslav heritage imbued his work with a distinctive identity characterized by a profound sense of doubleness and otherness, characteristic of the works of immigrant authors. To illustrate this double identity, we have examined primary sources which include Simic's prose works, The Monster Loves His Labyrinth, A Fly in the Soup , and Orphan Factory . This paper will draw upon the scholarship of Gloria Anzaldúa, Stuart Hall, Susan Stanford Friedman, and Werner Sollors, whose diverse perspectives and conceptual frameworks offer valuable insights into hybrid identities, cultural belonging, and the complexities of immigrant experiences as portrayed in Simic's works. Simic's essays, among other things, grappled with the complexities of his Yugoslav heritage amidst the socio-political transformations of the wars in the 1990s on the territory of the former SFRY, juxtaposed with his evolving American identity. By incorporating Anzaldúa's concept of borderlands and Hall's examination of cultural identity, this study sheds light on Simic's exploration of hybrid identities and the inherent tension between belonging and alienation. Additionally, Friedman's delineation of hybrid identities and Sollor's theory of multiethnic literature offer nuanced perspectives on Simic's exploration of dual belonging. This paper illuminates how Simic's prose navigated the intricate intersections of identity, culture, and language within the framework of I – we – they constructs, thereby providing fresh insights into the complexities of immigrant experiences and the formation of hybrid identities.
Global and national actions to prevent trade in substandard and adulterated medicines
Authors: Wilder Richard , Halabi Sam , Gostin Lawrence O.
Published: February 2025

Recent mass-poisoning events caused by substandard medicines placed in global markets raise the question as to what more can be done to stop it. Efforts have been underway for years at the World Health Organization and other multilateral fora, such as the National Academies of Medicine in the U.S. While these efforts have led to improvements, several gaps remain which, unless addressed, will allow this problem in international trade to continue. Some countries have failed to implement the standards set by the WHO by not fully empowering national regulatory agencies to lead national efforts. Further, some countries do not fully exercise their responsibility under WHO standards to confirm that the information in documents accompanying internationally traded medicines is complete, accurate, and current. It is time to revisit international standards in this area to determine the causes of these problems and to address them.
A person-centered approach to cognitive performance analysis in primary school children: Comparisons through self-organizing maps
Authors: Montalt-García Sergio , Estevan Isaac , Villarrasa-Sapiña Israel , García-Massó Xavier
Published: February 2025

The objective of this study was to identify distinct student profiles based on physical, psychological, and social characteristics, and examine their impact on cognitive performance. A total of 194 children participated in this cross-sectional design study (mean age = 10.61 years, SD = 0.45; 48.96% girls). The study included participants from diverse racial backgrounds. Using Self-Organizing Maps, an unsupervised neural network clustering technique, six distinct profiles were identified. These profiles revealed significant effects in daily physical activity, self-reported physical, social, and psychological factors, and physical performance. Profiles characterized by higher physical activity levels and positive social and psychological factors were associated with better cognitive performance, in contrast to profiles with lower levels in these domains. These findings suggest that students’ cognitive outcomes may be linked to their physical, psychological, and social characteristics, which interact to shape cognitive functioning. The recognition of the diversity of student profiles in specific educational settings may facilitate the design of more targeted programs that address individual needs and strengths, thereby enhancing their development in these domains within similar educational contexts.
Organizer and axes formation as a self-organizing process.
Authors: Meinhardt H
Published: February 2025

It is a widely held view that axis formation is based essentially on pre-localized determinants. However, the robustness of early development, the pattern regulation observed after experimental interferences and the existence of systems that don't require maternal determinants suggest that self-regulating pattern forming systems are also involved. A model is proposed that allows axes formation by a chain of reactions based on local self-enhancement and long-range inhibition. Their appropriate linkage ensures that the intermediary patterns emerge in the correct sequence and have the correct spatial relation to each other. Specifically, the model comprises the following events: the generation of a pole by a pattern-forming process, the formation of a second organizer eccentric to the pole (e.g. the Nieuwkoop center), the ecto-meso-endo subdivision, the generation of the Spemann-Mangold organizer with its anterior-posterior subdivision under the influence of the Nieuwkoop center, the conversion of the Spemann-Mangold organizer (a hot spot) into the notochord (a hot stripe), and the marking of the left side of the organism by a patterning reaction influenced by the midline. The pattern forming reactions do not depend on but can make use of maternally pre-localized determinants or asymmetries. Comparison with known genes and molecules reveals that many of the expected ingredients are present. Computer simulations show that the model accounts for many regulatory features reported in the literature. The computer simulations are available in an animated form at.
A study of Xlim1 function in the Spemann-Mangold organizer.
Authors: Kodjabachian L , Karavanov A A , Hikasa H , Hukriede N A , Aoki T , Taira M , Dawid I B
Published: February 2025

The Spemann-Mangold organizer is required in amphibian embryos to coordinate cell fate specification, differentiation of dorsal cell types and morphogenetic movements at early stages of development. A great number of genes are specifically expressed within the organizer, most of them encoding secreted proteins and transcription factors. The challenge is now to uncover genetic cascades and networks of interactions between these genes, in order to understand how the organizer functions. The task is immense and requires loss-of-function approaches to test the requirement for a given factor in a specific process. For transcription factors, it is possible to generate inhibitory molecules by fusing the DNA binding region to a repressor or activator domain, which should in principle antagonize the activity of the endogenous protein at the level of the DNA targets. We used this strategy to design activated and inhibitory forms of the LIM homeodomain transcription factor Lim1, which is encoded by an organizer gene involved in head development, as revealed by analyses of knockout mice. We found that Lim1 is a transcriptional activator, and can trigger dorso-anterior development upon ventral expression of hyperactive forms, in which Ldb1 is fused to Lim1. Using inhibitory Lim1 fusion proteins, we found that Lim1, or genes closely related to it, is required for head formation as well as for notochord development. Co-expression experiments revealed that Lim1 is required downstream of the early organizer factor Siamois, first, to establish the genetic program of the organizer and second, to mediate the action of organizer agents that are responsible for blocking ventralizing activities in the gastrula.
Fox (forkhead) genes are involved in the dorso-ventral patterning of the Xenopus mesoderm.
Authors: El-Hodiri H , Bhatia-Dey N , Kenyon K , Ault K , Dirksen M , Jamrich M
Published: February 2025

Fox (forkhead/winged helix) genes encode a family of transcription factors that are involved in embryonic pattern formation, regulation of tissue specific gene expression and tumorigenesis. Several of them are transcribed during Xenopus embryogenesis and are important for the patterning of ectoderm, mesoderm and endoderm. We have isolated three forkhead genes that are activated during gastrulation and play an important role in the dorso-ventral patterning of the mesoderm. XFKH1 (FoxA4b), the first vertebrate forkhead gene to be implicated in embryonic pattern formation, is expressed in the Spemann-Mangold organizer region and later in the embryonic notochord. XFKH7, the Xenopus orthologue of the murine Mfh1(Foxc2), is expressed in the presomitic mesoderm, but not in the notochord or lateral plate mesoderm. Finally, XFD-13'(FoxF1b)1 is expressed in the lateral plate mesoderm, but not in the notochord or presomitic mesoderm. Expression pattern and functional experiments indicate that these three forkhead genes are involved in the dorso-ventral patterning of the mesoderm.
Nodal signaling and the zebrafish organizer.
Authors: Schier A F , Talbot W S
Published: February 2025

Systematic genetic screens in zebrafish have led to the discovery of mutations that affect organizer function and development. The molecular isolation and phenotypic analysis of the affected genes have revealed that TGF-beta signals of the Nodal family play a key role in organizer formation. The activity of the Nodal signals Cyclops and Squint is regulated extracellularly by the EGF-CFC cofactor One-eyed Pinhead and by antagonists belonging to the Lefty family of TGF-beta molecules. In the absence of Nodal signaling, the fate of cells in the organizer is transformed from dorsal mesoderm to neural ectoderm. Differential Nodal signaling also patterns the organizer along the anterior-posterior axis, with high levels required for anterior cell fates and lower levels for posterior fates. In addition, Nodal signaling cooperates with the homeodomain transcription factor Bozozok in organizer formation and neural patterning. The combination of genetic, molecular and embryological approaches in zebrafish has thus provided a framework to understand the mechanisms underlying organizer development.
Role of the anterior visceral endoderm in restricting posterior signals in the mouse embryo.
Authors: Perea-Gomez A , Rhinn M , Ang S L
Published: February 2025

Recent genetic and embryological experiments have demonstrated that head formation in the mouse embryo is dependent on signals provided by two organising centers during gastrulation, the anterior visceral endoderm (AVE) and the anterior primitive streak (also called the Early Gastrula Organiser, EGO). However the molecular nature of the signals triggering anterior neural formation from the epiblast is not clearly understood. The analysis of mouse mutants has allowed the identification of some of the molecular players involved in the process of head formation. In this review, we describe different mutant embryos in which impairment of visceral endoderm function leads to similar defects in antero-posterior axis specification. These phenotypes are consistent with a role of the AVE in protecting anterior embryonic regions from signals that promote posterior development. We propose that a genetic cascade in the AVE, involving HNF3beta, Lim1, Otx2, Smad2 and ActRIB, leads to the production of secreted TGFbeta antagonists that protect the anterior epiblast region from Nodal signalling.
Contribution of the Belgian school of embryology to the concept of neural induction by the organizer.
Authors: Alexandre H
Published: February 2025

Albert BRACHET, founder of the Brussels School of embryology, conducted delicate experiments in which he selectively destroyed zones of the grey crescent with heated needles. This allowed him to observe, in 1923, that the median region of the grey crescent of the blastula is a area of spontaneous differentiation and that this "primary self-differentiation centre" organizes the axial organs in anurans. It is thus fair to say that A. BRACHET contributed significantly to the emergence of the organizer concept. Albert DALCQ and Jean PASTEELS, successors of A. BRACHET, trying to solve the problem of the organizer's determination, proposed their famous quantitative theory of embryonic development resulting in the concept of morphogenetic potential, which increases with the CV concentration, a combination of a cortical constituent C and a vegetal substance V. Jean BRACHET, the younger son of A. BRACHET and one of the founding father of molecular biology and embryology, was soon convinced that the organizer owes its inducing power to a chemical substance. Being the first to suggest the role of RNA in protein synthesis, he first imagined that RNA could be the active substance in induction but became convinced afterwards that the inducer must have a proteic nature. His interest in the molecular aspects of induction stimulated research that was to make chemical embryology molecular.
Consequences of the Spemann-Mangold organizer concept for embryological research in Russia: personal impressions.
Authors: Mikhailov A T , Gorgolyuk N A
Published: February 2025

The impact of the organizer concept on Russian experimental embryology is shortly reviewed. Attempts to study embryonic induction in Russia may be grouped into embryological and biochemical approaches. This paper provides a framework for, and overvalue of, the contributions of Russian biologists to the problem of embryonic induction. Two model systems--lens and neural inductions--are of special significance to modern developmental biologists. Moreover, the study of eye lens induction actually gave rise to research on developmental mechanics in Russia. This was one of the reasons why we limited this article to these two model systems. After retrospective consideration of the results of the search for possible lens-inducing factor candidates, the discussion turns towards some of the examples of neural-inducing agents detected in embryonic tissues and the new questions raised by the progress that has been made in the analysis of the Spemann-Mangold organizer.
Endocrine function and regulation of the fetal and neonatal testis.
Authors: Huhtaniemi I
Published: February 2025

An interesting sex difference prevails in the early development of endocrine functions in the ovary and testis. The testis actively produces androgens already in utero whereas the physiologically important steroid hormone production of the ovary does not start until puberty. Likewise, the different components of the hypothalamic-pituitary-gonadal axis seem to mature earlier in the male. The hormonal regulation of the fetal testes differs in many respects from that of the adult, and these differences make it possible for the fetal testes to function in the intrauterine endocrine milieu. The purpose of this review is to summarize our findings on the development, special functional characteristics and physiological role of the fetal and neonatal pituitary-gonadal axis.
Development of progestin-specific response in the chicken oviduct.
Authors: Tuohimaa P , Joensuu T , Isola J , Keinanen R , Kunnas T , Niemela A , Pekki A , Wallen M , Ylikomi T , Kulomaa M
Published: February 2025

Avidin is a host acute defense protein induced by progestins and by inflammation caused by injurious factors such as microbes, viruses, toxic factors or tissue trauma. In the reproductive tract of egg-laying vertebrates avidin has evolved into a progestin-dependent secretory protein involved in anti-microbial action through its biotin avidity. For "progestin-dependent avidin" production, cellular differentiation by estrogen is necessary. In contrast, the expression of "progestin-independent or inflammation-induced avidin" does not require differentiation. Many cell types such as macrophages, heterophils and fibroblasts can produce avidin after non-specific cellular injuries. The wide distribution of avidin in avian, reptilian and amphibian species could be explained on the basis of its vital functions such as antimicrobial or antifungal, metabolic and immunomodulatory actions. The ontogeny of the progestin-dependent avidin synthesis is a complex event involving oviductal differentiation by steroid hormones leading to a specific gene expression. The first phase in oviductal differentiation by estrogens is characterized by a new chromatin organization and by an infiltration of progesterone receptor (PR)-containing mesenchymal cells into the subepithelial mucosa leading to epithelial cell differentiation ("mesenchymal and epithelial cell interaction"). The second phase in the differentiation of progestin-induced response is dependent on the presence of PR in the secretory cells. Two kinds of PR expression occur in the oviduct. The first is a "constitutive PR" and is found in the epithelial, submucosal and peritoneal cells of the immature chick oviduct without steroid treatment, and the second is an "inducible PR" found especially in the mucosal mesenchymal and smooth muscle cells. Avidin production requires PR in the target cells, but not all PR-containing cells can produce avidin. Therefore, in addition to PR, other transcription factors are needed to define the target cell specificity of the response to progestins. Earlier biochemical studies suggested that cytosolic and/or nuclear unoccupied PR was complexed as an 8 S form with the heat shock protein 90 (hsp90). Our immunohistochemical results, however, indicate that PR in vivo is not bound to hsp90, which is located entirely in the cytoplasm, whereas PR is an entirely nuclear protein in both ligand-occupied and unoccupied forms. Therefore, we assume that PR is a monomeric (4S) or homodimeric (5S) (chromatin?) protein associated to DNA. Ligand binding to PR appears to lead to a conformational change, dimer formation, tighter binding to PRE (progesterone responsive element) and to transcription factors, phosphorylation and proteolysis of PR as well as a chromatin change.(ABSTRACT TRUNCATED AT 400 WORDS)
Sex steroid sensitivity of developing bursa of Fabricius.
Authors: Ylikomi T , Tuohimaa P
Published: February 2025

Sex steroid sensitivity of the bursa of Fabricius (BF) was studied from the early embryonic time until its regression. Expression of progesterone receptor (PR) served as a dual marker: first, as a marker for progesterone sensitivity and second, as a marker for estrogen action, since it is an estrogen-induced protein. The progesterone binding molecule in the bursa was characterized by different chromatography methods and by steroid binding studies. We showed that it fulfils the criteria of a progesterone receptor by binding, structural and immunological properties. With immunohistochemistry and with the combined techniques of immunohistochemistry and autoradiography we demonstrated two cell types which express the PR: smooth muscle cells surrounding the BF and stromal cells located under the bursal epithelium and between the lymphoid follicles. The epithelium and the cells inside the lymphoid follicles were negative. Using immunoelectron microscopy the PR-expressing stromal cells were shown to be fibroblasts. The cloacal mesenchyme, from which the BF develops, was shown to be sensitive to exogenous estrogen very early during the embryonic time. The mesenchyme around and inside the developing BF reached estrogen sensitivity a few days later. The estrogen-sensitive mesenchymal cells were first seen surrounding the bursal primordium and later in the center of the plicae. During a natural sexual maturation without exogenous estradiol an expression of the PR was detected much later, at the age of 10-12 weeks after hatching. This expression correlates with the onset of the bursal regression and with the increase of the sex steroid levels in the blood. In the oviduct stroma PR was undetectable before the onset of sexual maturation. In the oviduct stroma PR becomes detectable a few weeks earlier than in the bursa.
Organ transplantations: from basic research to clinical applications. A personal odyssey.
Authors: Hayry P
Published: February 2025

This article is a summary of the impact on contemporary medicine of organ and tissue transplantation. The article describes how, via trial and error, and beginning from basic research, the results of organ transplantation have steadily increased as has the number of organs that can be transplanted. Currently, the short-term results of most organ transplants, with the notable exception of the pancreas and the lung, are close to perfect; very few organs are lost any longer due to acute rejection. There is, however, little information on long-term results using the current modalities of immunosuppression, particularly on the effect of chronic rejection on late graft survival.
Regulation and function of the terminal gap gene huckebein in the Drosophila blastoderm.
Authors: Bronner G , Jackle H
Published: February 2025

Pattern formation in Drosophila involves a cascade of maternal and zygotic factors which are spatially restricted in the blastoderm embryo. Here we show that the Drosophila gene huckebein (hkb), a member of the gap gene class of segmentation genes, is not only required for suppression of segmentation in the terminal regions of the embryo but also to spatially restrict germ layer formation at the beginning of gastrulation. hkb encodes a Sp1/egr-like zinc finger protein, likely to be a transcription factor. Its absence in hkb mutants causes the ectodermal and mesodermal primordia to expand at the expense of endoderm anlagen, which are completely absent in null alleles of hkb. Conversely, ectopic expression of hkb inhibits the formation of the major gastrulation fold which gives rise to the mesoderm and prevents normal segmentation in the ectoderm of the trunk region.
Localization of a high molecular weight form of DNA topoisomerase I in amphibian oocytes.
Authors: Gebauer D , Mais C , Zinger K , Hock R , Lieb B , Scheer U
Published: February 2025

Xenopus oocytes express a 165 kDa variant of DNA topoisomerase I (topo I) as opposed to the canonical 110 kDa form of somatic cells (Richard and Bogenhagen, Dev. Biol. 146: 4-11, 1991). By immunofluorescence microscopy using variant-specific antibodies we show that this high molecular weight form is associated with lampbrush chromosome loops and the inner regions of the amplified nucleoli. Inhibition of topo I-activity by either Camptothecin-treatment or microinjection of neutralizing antibodies resulted in loop retraction and the condensation of chromosomes and amplified nucleoli. These data indicate that the oocyte-specific 165 kDa form of topo I is involved in transcriptional processes mediated by RNA polymerase I and II and is therefore functionally equivalent to the somatic cell 110 kDa counterpart.
Retinoic acid receptors and nuclear orphan receptors in the development of Xenopus laevis.
Authors: Dreyer C , Ellinger-Ziegelbauer H
Published: February 2025

Nuclear hormone receptors are ligand-activated transcription factors that regulate the expression of target genes by binding to hormone responsive elements (HRE) in their 5' upstream region. Retinoids which are known for their teratogenicity and which have a potential role in the specification of the anteroposterior axis of vertebrate embryos regulate transcription via a hormone-like mechanism by activating nuclear retinoic acid receptors, designated RAR and RXR. Of the several isoforms of RAR found in embryos of Xenopus laevis, xRAR gamma 2 appears to be the most abundant. During the early retinoic acid-sensitive period of development, the total amount of xRAR gamma 2 transcript and protein is increased and a highly specific pattern of expression emerges. During neurulation, the receptor is predominantly found in the dorsal posterior region, in the head endomesoderm, and in the rostral hindbrain. The dependence of this pattern on mesoderm induction and on neural induction is discussed. Contrasting with the elaborate pattern of xRAR gamma 2, the FTZ-F1-related nuclear orphan receptors (xFF1rA/B) are ubiquitous nuclear proteins in Xenopus embryos, as are the peroxisome proliferator-activated receptors xPPAR alpha and beta. PPARs are activated by polyunsaturated fatty acids and regulate the synthesis of enzymes involved in lipid metabolism. Later in development, the isoforms xPPAR alpha, beta, and gamma attain different tissue specificities.
Nucleoskeleton and nucleo-cytoplasmic transport in oocytes and early development of Xenopus laevis.
Authors: Rudt F , Firmbach-Kraft I , Petersen M , Pieler T , Stick R
Published: February 2025

We use amphibian oocytes and eggs as favorite biological systems to study various cell biological phenomena. We have analyzed the role of the zinc finger protein TFIIIA and ribosomal protein L5 in nucleo-cytoplasmic transfer of 5S ribosomal RNA and report on the structural requirements of the 5S RNA for the interaction with TFIIIA. Furthermore, we have used the oocyte/egg system to analyze the kinetics of the posttranslational isoprenylation of oocyte nuclear lamin B3 and its fate during egg maturation. We demonstrate, that isoprenylation of newly synthesized lamins takes place in the oocyte cytoplasm before uptake into the nucleus and show, that the isoprene modifications alone are not sufficient to maintain stable association of lamins with nuclear envelope derived membranes in eggs. Finally, initial results of the identification of cis-acting sequence elements, involved in translational repression of lamin mRNAs in oocytes, are reported.
Mesoderm migration in the Xenopus gastrula.
Authors: Winklbauer R , Nagel M , Selchow A , Wacker S
Published: February 2025

During Xenopus gastrulation, the mesoderm involutes at the blastopore lip and moves on the inner surface of the BCR toward the animal pole of the embryo. Active cell migration is involved in this mesoderm translocation. In vitro, mesoderm cells migrate non-persistently and intermittently by extending and retracting multiple lamellipodia, which pull the cell body in their direction. Lamellipodia formation is induced by FN. FN fibrils are present on the BCR as part of the in vivo substrate of mesoderm migration. Mesoderm cells can attach to the BCR independently of FN, but interaction with FN is required for lamellipodia extension and cell migration on the BCR. In contrast to preinvolution mesoderm, involuted migrating mesoderm always stays on the surface of the BCR cell layer: migrating mesoderm cells do not mix with BCR cells, and a stable interface between tissues is maintained. A corresponding change in cell sorting behavior occurs during mesoderm involution. In Xenopus, the mesoderm moves as a multilayered coherent cell mass held together by cadherin-mediated cell adhesion. Aggregate formation changes mesoderm cell behavior, rendering it more continuous, persistent and directional, i.e. more efficient. The mesoderm possesses an intrinsic tissue polarity which biases the direction of its movement. In addition, the fibrillar FN matrix of the BCR contains guidance cues which also direct the mesoderm toward the animal pole. Haptotaxis is most likely not involved in this substrate-dependent guidance of the mesoderm, but intact FN fibrils seem to be required. A polarity of the BCR cell layer which underlies this anisotropy of the BCR matrix develops under the influence of the marginal zone in the late blastula. Although in other amphibian species, gastrulation depends critically on mesoderm cell migration, in Xenopus, convergent extension of the axial mesoderm seems to provide the main driving force for gastrulation.