bluuebunny/crossref_metadata_2025 huggingface dataset:
TAREA 18
Authors: Carrasco Gómez Flor
Published: June 2024

El cine es una diversión que hay que tomar muy en serio. Un fin que puede, incluso, ser tomado como medio. Los educadores así lo han comprendido desde hace años, y los profesores de Derecho no iban a ser menos. Al cine nada de lo humano le es ajeno, y por eso quienes se dedican a la docencia en el ámbito jurídico son conscientes de que, si se puede gozar con el cine —esa bella arte—, también se puede trabajar con él en el aula. Es necesario, claro está, estar dispuesto a ello, poseer una cultura cinematográfica apropiada y diseñar adecuadamente esta estrategia pedagógica, como se hace con cualquier táctica formativa para que resulte eficaz. Es esencial seleccionar correctamente aquellas películas o escenas que puedan ser útiles en un determinado momento para trabajar en clase, teniendo claro qué se pretende del alumnado con dicho trabajo, además de ilustrar el tratamiento de la cuestión académica que sea. El presente libro es fruto del trabajo desarrollado por un grupo de docentes, principalmente profesores de asignaturas jurídicas de la Universidad de Málaga, miembros de un Proyecto de Innovación Educativa titulado «La inserción del cine en la docencia de asignaturas jurídicas: la relevancia de la lengua inglesa» (PIE19-016), coordinado por el Profesor de Derecho Civil Antonio J. Quesada Sánchez. En él se recopilan una serie de fichas de trabajo que describen experiencias individuales puestas en práctica por los docentes con sus respectivos grupos de alumnos, todas conectadas con el cine.
TAREA 24
Authors: Benítez Llamazares Nuria
Published: June 2024

El cine es una diversión que hay que tomar muy en serio. Un fin que puede, incluso, ser tomado como medio. Los educadores así lo han comprendido desde hace años, y los profesores de Derecho no iban a ser menos. Al cine nada de lo humano le es ajeno, y por eso quienes se dedican a la docencia en el ámbito jurídico son conscientes de que, si se puede gozar con el cine —esa bella arte—, también se puede trabajar con él en el aula. Es necesario, claro está, estar dispuesto a ello, poseer una cultura cinematográfica apropiada y diseñar adecuadamente esta estrategia pedagógica, como se hace con cualquier táctica formativa para que resulte eficaz. Es esencial seleccionar correctamente aquellas películas o escenas que puedan ser útiles en un determinado momento para trabajar en clase, teniendo claro qué se pretende del alumnado con dicho trabajo, además de ilustrar el tratamiento de la cuestión académica que sea. El presente libro es fruto del trabajo desarrollado por un grupo de docentes, principalmente profesores de asignaturas jurídicas de la Universidad de Málaga, miembros de un Proyecto de Innovación Educativa titulado «La inserción del cine en la docencia de asignaturas jurídicas: la relevancia de la lengua inglesa» (PIE19-016), coordinado por el Profesor de Derecho Civil Antonio J. Quesada Sánchez. En él se recopilan una serie de fichas de trabajo que describen experiencias individuales puestas en práctica por los docentes con sus respectivos grupos de alumnos, todas conectadas con el cine.
TAREA 9
Authors: Gálvez Criado Antonio
Published: June 2024

El cine es una diversión que hay que tomar muy en serio. Un fin que puede, incluso, ser tomado como medio. Los educadores así lo han comprendido desde hace años, y los profesores de Derecho no iban a ser menos. Al cine nada de lo humano le es ajeno, y por eso quienes se dedican a la docencia en el ámbito jurídico son conscientes de que, si se puede gozar con el cine —esa bella arte—, también se puede trabajar con él en el aula. Es necesario, claro está, estar dispuesto a ello, poseer una cultura cinematográfica apropiada y diseñar adecuadamente esta estrategia pedagógica, como se hace con cualquier táctica formativa para que resulte eficaz. Es esencial seleccionar correctamente aquellas películas o escenas que puedan ser útiles en un determinado momento para trabajar en clase, teniendo claro qué se pretende del alumnado con dicho trabajo, además de ilustrar el tratamiento de la cuestión académica que sea. El presente libro es fruto del trabajo desarrollado por un grupo de docentes, principalmente profesores de asignaturas jurídicas de la Universidad de Málaga, miembros de un Proyecto de Innovación Educativa titulado «La inserción del cine en la docencia de asignaturas jurídicas: la relevancia de la lengua inglesa» (PIE19-016), coordinado por el Profesor de Derecho Civil Antonio J. Quesada Sánchez. En él se recopilan una serie de fichas de trabajo que describen experiencias individuales puestas en práctica por los docentes con sus respectivos grupos de alumnos, todas conectadas con el cine.
พื้นที่ทางการเมืองของกลุ่มชาติพันธุ์ในการเลือกตั้งระดับชาติ
Authors: ลีปรีชา ประสิทธิ์
Published: June 2024

การเมืองในการเลือกตั้งระดับชาติเป็นเรื่องของอำนาจและผลประโยชน์ การแข่งขันกันเพื่อให้ได้รับการเลือกตั้งจึงเต็มไปด้วยกลยุทธ์ที่หลากหลายของนักการเมืองและพรรคการเมือง เพื่อเอาชนะคู่แข่ง ตามมาด้วยเป้าหมายการเป็นรัฐบาลบริหารประเทศซึ่งมีตำแหน่ง อำนาจและผลประโยชน์มากมาย จึงเป็นการยากสำหรับคนรากหญ้าที่เป็นกลุ่มชายขอบในการก้าวเข้าสู่เวทีการเมืองระดับชาติ กระนั้นก็ตาม การเลือกตั้งระดับชาติเมื่อปี 2562 และปี 2566 เริ่มเห็นบทบาทของนักการเมืองชาติพันธุ์มากขึ้น บทความนี้จึงนำเสนอพัฒนาการและบทบาทของคนชาติพันธุ์ในการทำการเมืองระดับชาติ ผู้เขียนพบว่ากลุ่มชาติพันธุ์ที่เป็นคนชายขอบสามารถสร้างพื้นที่ทางการเมืองในการเลือกตั้งระดับชาติด้วยการลงรับการเลือกตั้งทั้งในระบบเขตและระบบบัญชีรายชื่อของพรรคการเมืองต่าง ๆ แต่กระบวนการเข้าสู่พรรคการเมืองและแข่งขันเพื่อให้ได้รับการเลือกตั้งนั้นมิได้ราบรื่นเสมอไป การทำการเมืองนำมาซึ่งการแยกย้ายกันไปอยู่คนละพรรคและแข่งขันกันเอง กระนั้นก็ตาม กระแสความนิยมในพรรคก้าวไกลทำให้ได้ สส. ชาติพันธุ์เข้าไปมีพื้นที่ทางการเมืองในสภานิติบัญญัติแห่งชาติ เนื้อหาในบทความนี้รวบรวมจากการติดตามความเคลื่อนไหวในการทำการเมืองของคนชาติพันธุ์ผ่านสื่อสังคมออนไลน์ การสังเกตการณ์ และการสัมภาษณ์อย่างเป็นทางการและไม่เป็นทางการ ทั้งก่อน ระหว่างและหลังการเลือกตั้งทั้งสองครั้ง โดยใช้แนวคิดพื้นที่ทางการเมืองเป็นกรอบในการวิเคราะห์
Penerapan AAA Security Dalam Aplikasi BNI Mobile Banking
Authors: Saputri Dita Ayu Eka , Ernawati Ida Ayu , Rabbaanii Nimas Adjeng Nutfa , Satriani Adibah Dewi
Published: June 2024

Information system security is crucial in the digital era. The application of AAA (Authentication, Authorization, and Accounting) has become a broad approach to protecting data in information systems. This study aims to analyze the application of AAA in improving information system security in BNI Mobile Banking. This research method includes literature and experimental studies which are used as a research approach. The results of the study show that BNI Mobile Banking is sufficient to apply AAA significantly to improve the security of its information system.
Social actor representation in mining discourse in the Philippines: A critical discourse analysis
Authors: Diamante Jennifier
Published: June 2024

This paper addresses the need to investigate media’s representation of mining issues in the Philippines, an unexplored linguistic field within Critical Discourse Analysis (CDA). It focuses on referential strategies used in naming the social actors (SAs) involved in mining issues from 2012 to 2017 by three national broadsheets. A sample of 224 news reports was analyzed at the sentence level, and was validated by software and two inter-coders. The study found that SAs were commonly named by their unique identities mainly through nomination and categorization strategies. The valuing of the “elites” in the mining discourse is also traceable in the prominent use of nomination strategies, particularly formalization and honorification. While these strategies reflect the conventional linguistic features of the news genre which reinforces specificity, formality, and brevity, it is evident that they were seldom used to refer to the mine workers, disenfranchising them in the process. The tendency of the media to influence public perception through its construction of societal issues demands readers to be skeptical of what they read and to be aware of the machination which underlies the process of discourse production.
Essential elements in Etlingera elatior (Jack) R. M. Sm. and Etlingera philippinensis (Ridl.) R. M. Sm.
Authors: Barbosa Gina , Alinapon Cresilda , Gultiano Analyn
Published: June 2024

Despite the advancements contributed to botanical research, scientific attention on many Zingiberaceae plants in spite of their numerous health-promoting applications is still few. Existing reports mostly focus on the common species of Zingiberaceae specifically on the rhizomes, with less emphasis on Philippine endemic gingers such as Etlingera philippinensis (Ridl.) R. M. Sm. In this study, the concentration of essential elements (Fe, Cu, Zn, Ni) in Etlingera elatior (Jack) R. M. Sm. and E. philippinensis leaves and rhizomes were determined using atomic absorption spectroscopy. Among the essential elements, Cu was found highest in E. elatior leaves and E. philippinensis rhizomes. However, the identified levels of Fe, Cu, Zn, and Ni for these two zingiberaceaes indicate that all are below the permissible limit set by World Health Organization (WHO) for plants. Thus, this study ventures in the exploration of the baseline information on the essential element content of the less studied Philippine endemic E. philippinensis.
Status of coral reefs, butterflyfishes, and benthic macro-invertebrates in Araceli and Dumaran, Palawan, Philippines
Authors: Climaco Russell , Aludia Geofrey , Mecha Niño Jess Mar , Cornel Anton Rey , Acebuque Ace Niño Andrew , Rodriguez Jomil , Miguel Jona , Menardo Ian , Dolorosa Roger
Published: June 2024

As a major fishing ground in Palawan, the reefs in the municipal waters of Araceli and Dumaran are continuously facing anthropogenic and climate-related threats. Hence, to provide information about the reef conditions, surveys were undertaken in three sites of each municipality as the basis for management. Data collection used the C30 method where a 75 m x 25 m sampling area was established at the upper reef slope (2-5 m deep) of each site. Substrates were photo-documented at predetermined random positions and the photos were processed using Coral Point Count with excel extension software (CPCe) to determine the percent substrate categories. Identification and counting of butterflyfishes and benthic macro-invertebrates were also undertaken. The hard-coral cover (HCC) ranged between 27.10 and 53.88% (fair to very good) for Araceli and 22.66 and 48.62% (fair to good) for Dumaran. The number of species and density of butterflyfishes largely varied across reefs. The benthic macro-invertebrates only included the blue Linckia starfish and giant clams. The current reef condition calls for urgent management actions.
Økobevisst fotografi
Authors: Stien Hanne Hammer , Fjellestad Marthe Tolnes
Published: June 2024

Current practices of eco-conscious photography, informed by the ongoing climate crisis and post-humanist theory, share characteristics such as collectivity, co-creation, and pro- cess orientation. By way of examples from the UK and the Nordic region, we investigate how these aspects are made (in)visible within the framework of photographic institu- tions: artist-led organizations, photographic festivals, exhibitions, and museums. We ask what implications can, or even should, eco-conscious photography have for the ways researchers, curators and institutions think about and engage with photography, both as an image and a practice.
Når eksplosioner er kunst
Authors: Kloster Poulsen Steffen
Published: June 2024

This article argues for an expanded effort to search for, and actively utilize, concepts and methods from the sociolinguistic periphery of the otherwise anglocentric academic lit- erature on photography in order to achieve a more level playing field between vernacular concepts and purportedly universal ones. Taking the history of public debate on photo- graphy in Japan as a departure point, this article aims to map out a new area of explora- tion for photographic research in the academic field of art history. Japan has been home to a vivid public and intellectual debate on photography since the birth of photography and, although its output of photographers and photobooks has been globally acclaimed and exported to museums and galleries internationally, especially in the past thirty years, lit- tle emphasis in academic research and elsewhere has been put on Japanese photographic critique, theory and debate outside the archipelago. As an example of unexplored theory, this article analyzes two published lectures by Japanese photographer Hatakeyama Naoya in which he reflects on photography's value as art, its place in the art world and the processes by which photographers become labelled as artists. Using a metaphor from analogue photography, he deems photographers “latent artists” who by a development process can become artists. Following Hatakeyama’s line of thought, this article argues furthermore that the metaphor can be extended to photographs themselves.
Performing aspects of V. Gavrilin’s “Russian Notebook”: dramaturgy, theatricalization, peasant song, folklore genres
Authors: Shkirtil' Lyudmila Vyacheslavovna , Serov Yuri Eduardovich
Published: June 2024

The article is devoted to one of the most important Russian chamber vocal cycles of the second half of the twentieth century – “Russian Notebook” by V. Gavrilin. Its appearance in 1965 made a strong impression on both the musical community and listeners. Everything about her was unusual, fresh, sincere. The stylistic unity of the “Russian Notebook” is due to its reliance on folk sources – literary texts and musical material. Gavrilin interpreted folk music in a deeply personal way, refracted it through the prism of a powerful spiritual and moral concept, outlined new directions for its research and comprehension, and proposed multi-valued interpretations and unexpected syntheses. “Russian Notebook” became the most important component of the significant artistic movement “new folk wave” that appeared in Russian music at the turn of the 1960s. Its brightest representatives were the “sixties” composers R. Shchedrin, E. Denisov, B. Tishchenko, S. Slonimsky. The main conclusion of the study is the idea that V. Gavrilin’s “Russian Notebook” is a genuine encyclopedia of folk genres. The composer penetrates deeply into the folk song tradition, organically refracts folklore, passes it through his amazing artistic world, thereby making the folklore language accessible to the general public. The author of the article focuses on the performing aspects of V. Gavrilin’s cycle, on the variety of interpretive possibilities coming from the diversity of folk (primarily peasant) song. The vocalist and accompanist-pianist need to seriously study the folk traditions before taking on the “Russian Notebook”. The intense dramaturgy of the cycle and the theatricalization of vocal music should also be the focus of the performers’ attention. V. Gavrilin’s composition opens up new interpretive paths and possibilities, new vocal techniques, and creates a multi-tasking performing world.
Coal power: Class, fetishism, memory, and disjuncture in Romania’s Jiu Valley and Appalachian West Virginia
Authors: Kideckel David A.
Published: June 2024

This essay compares the social disjuncture of coal’s decline in Romania's Jiu Valley and southern West Virginia/Appalachia. In both regions coal is fetishized, concentrating belief and creating a paradigm of meaning. But when fetishes lose power, social dislocation results. Coal's decline is often thought to produce common conditions in former coal regions. However, we suggest four factors shape regional variation: 1) political economy of class and industrial control; 2) state power over mining; 3) extent and diversity of non-governmental organizations related to the industrial control system; and 4) gender activism, emerging from political economy. We examine social conditions, coal memory, and nostalgia related to the above. In the Jiu Valley, there is a weakening of organization, coal nostalgia, as well as decline in coal-related disjuncture with existing conflict now largely a province of regional elites. In West Virginia, however, a weak state, active organizational environment, and women's activism produce conflict between coal supporters and detractors. These circumstances also influence the regions’ futures. Jiu Valley people are protected by state intervention, but this weakens class identity and the intensity of change efforts. In Appalachia the tensioned organizational environment perpetuates conflict but creates an intensity toward the future.
Economic nationalisms in a world on fire
Authors: Kingsolver Ann , Mathur Chandana , Onto Gustavo
Published: June 2024

In the recent context of a global pandemic, wars, and climate-related crises amplified by capitalism’s structural violence, a wave of economic nationalist regimes have come into power with anti-globalist stances exemplified by the United Kingdom’s withdrawal from the European Union and Trump, Putin, and Bolsonaro’s defiance of transnational treaties. What do economic nationalist policies share transnationally, and how are they distinct in terms of their political articulation and the lived experiences of those most affected by them? The ways in which economic nationalist arguments are used, often in combination with populist and white supremacist tactics, to violently restrict cultural and national citizenship, close borders, silence minority voices, oppress workers, and reject oversight of environmental destruction and human rights violations are discussed in this issue by authors working in the United States, India, Brazil, Guatemala, Italy, the Kurdish region, Turkey, and the United Kingdom. Ethnographic exploration of the plurality of economic nationalisms makes it possible to compare state-specific political strategies while noting parallels in the ways in which economic nationalist rhetoric emphasizes the protection of those imagined as belonging to the enisled economic nation while ironically relying profoundly on global constellations of labor and resource extraction and circulation.
Studying frictions: Activists, journalists and Bedouin around a “ghost-village” in Israel
Authors: Koensler Alexander
Published: June 2024

In the Israeli Negev desert, home demolition of unauthorized Arab-Bedouin villages is a contested issue, enacting multiple and contradictory realities. The tents and shacks of el-Shams, for instance, have been demolished almost ten times in one year by the Israeli police, but each time they have been reconstructed with the help of human rights activists. Surprisingly and in contrast to nearly all circulating discourses, nobody ever lived in the demolished buildings – what at one level becomes a humanitarian catastrophe, at another becomes a “ghost village”. Drawing on recent reflections on global ethnography, this article seeks to follow “zones of friction” and connections among people, money, discourses, and emotions that developed around this specific case: relations that range from solidarity activities to the discursive practices of journalists and dislocated officials of international organizations. On a more abstract level, the emerging contradictions between these levels reveal the implications of an uncritically reproduced idea of “local community”. I argue that by following such connections, we gain important insights how transnational power relations are shaping multiple realities around a political conflict.
The use of smartphones and the quest for a future among West African men in reception centers in Italy
Authors: Santanera Giovanna
Published: June 2024

In this article, I will analyse the creative use of smartphone by West African men living in reception centers in Torino, in Italy. As the usurpation of time has become an integral part of the European border regime, I place migrants’ media practices in relation to their claims for temporal justices. Drawing on ethnographic data, I argue that the use of smartphones – and especially the making and sharing of images – represents a practice of future making, which is linked to the dimension of hope and desire more than that of nostalgia. After having considered the mobile phone as an instrument for “killing time” during the slow daily routine of the reception centers, I will go on to analyse how the skillfully crafting of one’s own virtual image helps to carry out migratory projects and to obtain a residence permit. Finally, I will turn my attention to the materiality of the smartphone. As an “object of desire,” it is part of a chain of gifts and counter-gifts capable of unlocking new scenarios through the creation of relationships. I conclude that the smartphone can be seen as a weapon in the battle over time which is proper of contemporary migration politics and governance.
Pierre Bourdieu on capitals, the state and forced resettlement
Authors: Smart Alan
Published: June 2024

Pierre Bourdieu distinguished two main ways to teach sociology, by either teaching the principles and formal procedures, or by revealing examples of these formal procedures at work, and preferred to harness both together. This essay attempts to adopt this approach to consider three of his books recently translated to English, using my own research on forms of capital, the state and resettlement to engage with his arguments. I suggest that the utilization of Bourdieu’s powerful ideas are limited in areas like social capital and resettlement research by some inconsistencies and lack of definitional clarity.
A chronic signaling TGFb zebrafish reporter identifies immune response in melanoma
Authors: Noonan Haley R , Thornock Alexandra M , Barbano Julia , Xifaras Michael E , Baron Chloe S , Yang Song , Koczirka Katherine , McConnell Alicia M , Zon Leonard I
Published: June 2024

Developmental signaling pathways associated with growth factors such as TGFb are commonly dysregulated in melanoma. Here we identified a human TGFb enhancer specifically activated in melanoma cells treated with TGFB1 ligand. We generated stable transgenic zebrafish with this TGFb Induced Enhancer driving green fluorescent protein (TIE:EGFP). TIE:EGFP was not expressed in normal melanocytes or early melanomas but was expressed in spatially distinct regions of advanced melanomas. Single-cell RNA-sequencing revealed that TIE:EGFP+ melanoma cells down-regulated interferon response while up-regulating a novel set of chronic TGFb target genes. ChIP-sequencing demonstrated that AP-1 factor binding is required for activation of chronic TGFb response. Overexpression of SATB2, a chromatin remodeler associated with tumor spreading, showed activation of TGFb signaling in early melanomas. Confocal imaging and flow cytometric analysis showed that macrophages localize to TIE:EGFP+ regions and preferentially phagocytose TIE:EGFP+ melanoma cells compared to TIE:EGFP- melanoma cells. This work identifies a TGFb induced immune response and demonstrates the need for the development of chronic TGFb biomarkers to predict patient response to TGFb inhibitors.
Distance and grid-like codes support the navigation of abstract social space in the human brain
Authors: Liang Zilu , Wu Simeng , Wu Jie , Wang Wen-Xu , Qin Shaozheng , Liu Chao
Published: June 2024

People form impressions about others during daily social encounters and infer personality traits from others' behaviors. Such trait inference is thought to rely on two universal dimensions: competence and warmth. These two dimensions can be used to construct a ‘social cognitive map’ organizing massive information obtained from social encounters efficiently. Originating from spatial cognition, the neural codes supporting the representation and navigation of spatial cognitive maps have been widely studied. Recent studies suggest similar neural mechanism subserves the map-like architecture in social cognition as well. Here we investigated how spatial codes operate beyond the physical environment and support the representation and navigation of social cognitive map. We designed a social value space defined by two dimensions of competence and warmth. Behaviorally, participants were able to navigate to a learned location from random starting locations in this abstract social space. At the neural level, we identified the representation of distance in the precuneus, fusiform gyrus, and middle occipital gyrus. We also found partial evidence of grid-like representation patterns in the medial prefrontal cortex and entorhinal cortex. Moreover, the intensity of grid-like response scaled with the performance of navigating in social space and social avoidance trait scores. Our findings suggest a neurocognitive mechanism by which social information can be organized into a structured representation, namely cognitive map and its relevance to social well-being.
Bacteria Are a Major Determinant of Orsay Virus Transmission and Infection in Caenorhabditis elegans
Authors: Vassallo Brian G. , Scheidel Noémie , Fischer Sylvia E. J. , Kim Dennis H.
Published: June 2024

The microbiota is a key determinant of the physiology and immunity of animal hosts. The factors governing the transmissibility of viruses between susceptible hosts are incompletely understood. Bacteria serve as food for
Caenorhabditis elegans
and represent an integral part of the natural environment of
C. elegans.
We determined the effects of bacteria isolated with
C. elegans
from its natural environment on the transmission of Orsay virus in
C. elegans
using quantitative virus transmission and host susceptibility assays. We observed that
Ochrobactrum
species promoted Orsay virus transmission, whereas
Pseudomonas lurida
MYb11 attenuated virus transmission relative to the standard laboratory bacterial food
Escherichia coli
OP50. We found that pathogenic
Pseudomonas aeruginosa
strains PA01 and PA14 further attenuated virus transmission. We determined that the amount of Orsay virus required to infect 50% of a
C. elegans
population on
P. lurida
MYb11 compared with
Ochrobactrum vermis
MYb71 was dramatically increased, over three orders of magnitude. Host susceptibility was attenuated even further in presence of
P. aeruginosa
PA14. Genetic analysis of the determinants of
P. aeruginosa
required for attenuation of
C. elegans
susceptibility to Orsay virus infection revealed a role for regulators of quorum sensing. Our data suggest that distinct constituents of the
C. elegans
microbiota and potential pathogens can have widely divergent effects on Orsay virus transmission, such that associated bacteria can effectively determine host susceptibility versus resistance to viral infection. Our study provides quantitative evidence for a critical role for tripartite host-virus-bacteria interactions in determining the transmissibility of viruses among susceptible hosts.
Identification and characterization of intermediate states in mammalian neural crest cell epithelial to mesenchymal transition and delamination
Authors: Zhao Ruonan , Moore Emma L , Gogol Madelaine M , Unruh Jay R , Yu Zulin , Scott Allison R , Wang Yan , Rajendran Naresh K , Trainor Paul A
Published: June 2024

Epithelial to mesenchymal transition (EMT) is a cellular process that converts epithelial cells to mesenchymal cells with migratory potential in developmental and pathological processes. Although originally considered a binary event, EMT in cancer progression involves intermediate states between a fully epithelial and a fully mesenchymal phenotype, which are characterized by distinct combinations of epithelial and mesenchymal markers. This phenomenon has been termed epithelial to mesenchymal plasticity (EMP), however, the intermediate states remain poorly described and it’s unclear whether they exist during developmental EMT. Neural crest cells (NCC) are an embryonic progenitor cell population that gives rise to numerous cell types and tissues in vertebrates, and their formation and delamination is a classic example of developmental EMT. However, whether intermediate states also exist during NCC EMT and delamination remains unknown. Through single-cell RNA sequencing of mouse embryos, we identified intermediate NCC states based on their transcriptional signature and then spatially defined their locations in situ in the dorsolateral neuroepithelium. Our results illustrate the importance of cell cycle regulation and functional role for the intermediate stage marker Dlc1 in facilitating mammalian cranial NCC delamination and may provide new insights into mechanisms regulating pathological EMP.
TMC7 deficiency causes acrosome biogenesis defects and male infertility in mice
Authors: Wang Jing , Yin Yingying , Yang Lei , Qin Junchao , Wang Zixiang , Qiu Chunhong , Gao Yuan , Lu Gang , Gao Fei , Chen Zi-jiang , Zhang Xiyu , Liu Hongbin , Liu Zhaojian
Published: June 2024

Transmembrane channel-like (TMC) proteins are a highly conserved ion channel family consisting of eight members (TMC1–TMC8) in mammals. TMC1/2 are components of the mechanotransduction channel in hair cells, and mutations of TMC1/2 cause deafness in humans and mice. However, the physiological roles of other TMC proteins remain largely unknown. Here, we show that
Tmc7
is specifically expressed in the testis and that it is required for acrosome biogenesis during spermatogenesis.
Tmc7
−/−
mice exhibited abnormal sperm head, disorganized mitochondrial sheaths, and reduced number of elongating spermatids, similar to human oligo-astheno-teratozoospermia. We further demonstrate that TMC7 is colocalized with GM130 at the cis-Golgi region in round spermatids. TMC7 deficiency leads to aberrant Golgi morphology and impaired fusion of Golgi-derived vesicles to the developing acrosome. Moreover, upon loss of TMC7 intracellular ion homeostasis is impaired and ROS levels are increased, which in turn causes Golgi and endoplasmic reticulum (ER) stress. Taken together, these results suggest that TMC7 is required to maintain pH and ion homeostasis, which is needed for acrosome biogenesis. Our findings unveil a novel role for TMC7 in acrosome biogenesis during spermiogenesis.
Reversing protonation of weakly basic drugs greatly enhances intracellular diffusion and decreases lysosomal sequestration
Authors: Dey Debabrata , Marciano Shir , Poryval Anna , Groborz Ondřej , Wohlrabova Lucie , Slanina Tomás , Schreiber Gideon
Published: June 2024

For drugs to be active they have to reach their targets. Within cells this requires crossing the cell membrane, and then free diffusion, distribution, and availability. Here, we explored the in-cell diffusion rates and distribution of a series of small molecular fluorescent drugs, in comparison to proteins, by microscopy and fluorescence recovery after photobleaching (FRAP). While all proteins diffused freely, we found a strong correlation between pKa and the intracellular diffusion and distribution of small molecule drugs. Weakly basic, small-molecule drugs displayed lower fractional recovery after photobleaching and 10- to-20-fold slower diffusion rates in cells than in aqueous solutions. As, more than half of pharmaceutical drugs are weakly basic, they, are protonated in the cell cytoplasm. Protonation, facilitates the formation of membrane impermeable ionic form of the weak base small molecules. This results in ion trapping, further reducing diffusion rates of weakly basic small molecule drugs under macromolecular crowding conditions where other nonspecific interactions become more relevant and dominant. Our imaging studies showed that acidic organelles, particularly the lysosome, captured these molecules. Surprisingly, blocking lysosomal import only slightly increased diffusion rates and fractional recovery. Conversely, blocking protonation by N-acetylated analogues, greatly enhanced their diffusion and fractional recovery after FRAP. Based on these results, N-acetylation of small molecule drugs may improve the intracellular availability and distribution of weakly basic, small molecule drugs within cells.
Reversing protonation of weakly basic drugs greatly enhances intracellular diffusion and decreases lysosomal sequestration
Authors: Dey Debabrata , Marciano Shir , Poryvai Anna , Groborz Ondřej , Wohlrábová Lucie , Slanina Tomás , Schreiber Gideon
Published: June 2024

For drugs to be active they have to reach their targets. Within cells this requires free diffusion, distribution, and availability. Here, we explored the intracellular diffusion rates and distribution of a series of small molecular fluorescent drugs, in comparison to proteins, by microscopy and fluorescence recovery after photobleaching (FRAP). While all proteins diffused freely, we found a strong correlation between p
K
a
and the intracellular diffusion and distribution of small molecule drugs. Weakly basic, small-molecule drugs displayed lower fractional recovery after photobleaching and 10-to-20-fold slower diffusion rates in cells than in aqueous solutions. As, more than half of pharmaceutical drugs are weakly basic, they, are protonated at pH 7.4, resulting in their sequestration in the cell cytoplasm. Protonation, facilitates the formation of membrane impermeable ionic form of the weak base small molecules. This results in ion trapping, further reducing diffusion rates of weakly basic small molecule drugs under macromolecular crowding conditions where other nonspecific interactions become more relevant and dominant. Our imaging studies showed that acidic organelles, particularly the lysosome, captured these molecules. Surprisingly, blocking lysosomal import only slightly increased diffusion rates and fractional recovery. Conversely, blocking protonation by
N-
acetylated analogues, greatly enhanced their diffusion and fractional recovery after FRAP. Based on these results,
N
-acetylation of small molecule drugs may improve the intracellular availability and distribution of weakly basic, small molecule drugs.
Upregulated expression of ubiquitin ligase TRIM21 promotes PKM2 nuclear translocation and astrocyte activation in experimental autoimmune encephalomyelitis
Authors: Yang Luting , Hu Chunqing , Chen Xiaowen , Zhang Jie , Feng Zhe , Xiao Yanxin , He Weitai , Cui Tingting , Zhang Xin , Yang Yang , Zhang Yaling , Yan Yaping
Published: June 2024

Reactive astrocytes play critical roles in the occurrence of various neurological diseases such as multiple sclerosis. Activation of astrocytes is often accompanied by a glycolysis-dominant metabolic switch. However, the role and molecular mechanism of metabolic reprogramming in activation of astrocytes have not been clarified. Here, we found that PKM2, a rate-limiting enzyme of glycolysis, displayed nuclear translocation in astrocytes of EAE (experimental autoimmune encephalomyelitis) mice, an animal model of multiple sclerosis. Prevention of PKM2 nuclear import by DASA-58 significantly reduced the activation of mice primary astrocytes, which was observed by decreased proliferation, glycolysis and secretion of inflammatory cytokines. Most importantly, we identified the ubiquitination-mediated regulation of PKM2 nuclear import by ubiquitin ligase TRIM21. TRIM21 interacted with PKM2, promoted its nuclear translocation and stimulated its nuclear activity to phosphorylate STAT3, NF-κB and interact with c-myc. Further single-cell RNA sequencing and immunofluorescence staining demonstrated that TRIM21 expression was upregulated in astrocytes of EAE. TRIM21 overexpressing in mice primary astrocytes enhanced PKM2-dependent glycolysis and proliferation, which could be reversed by DASA-58. Moreover, intracerebroventricular injection of a lentiviral vector to knockdown TRIM21 in astrocytes or intraperitoneal injection of TEPP-46, which inhibit the nuclear translocation of PKM2, effectively decreased disease severity, CNS inflammation and demyelination in EAE. Collectively, our study provides novel insights into the pathological function of nuclear glycolytic enzyme PKM2 and ubiquitination-mediated regulatory mechanism that are involved in astrocyte activation. Targeting this axis may be a potential therapeutic strategy for the treatment of astrocyte-involved neurological disease.
Formation of multinucleated osteoclasts depends on an oxidized species of cell surface-associated La protein
Authors: Leikina Evgenia , Whitlock Jarred M , Melikov Kamran , Zhang Wendy , Bachmann Michael P , Chernomordik Leonid
Published: June 2024

The bone-resorbing activity of osteoclasts plays a critical role in the life-long remodeling of our bones that is perturbed in many bone loss diseases. Multinucleated osteoclasts are formed by the fusion of precursor cells, and larger cells – generated by an increased number of cell fusion events – have higher resorptive activity. We find that osteoclast fusion and bone resorption are promoted by reactive oxygen species (ROS) signaling and by an unconventional low molecular weight species of La protein, located at the osteoclast surface. Here, we develop the hypothesis that La’s unique regulatory role in osteoclast multinucleation and function is controlled by an ROS switch in La trafficking. Using antibodies that recognize reduced or oxidized species of La, we find that differentiating osteoclasts enrich an oxidized species of La at the cell surface, which is distinct from the reduced La species conventionally localized within cell nuclei. ROS signaling triggers the shift from reduced to oxidized La species, its dephosphorylation and delivery to the surface of osteoclasts, where La promotes multinucleation and resorptive activity. Moreover, intracellular ROS signaling in differentiating osteoclasts oxidizes critical cysteine residues in the C-terminal half of La, producing this unconventional La species that promotes osteoclast fusion. Our findings suggest that redox signaling induces changes in the location and function of La and may represent a promising target for novel skeletal therapies.
Formation of multinucleated osteoclasts depends on an oxidized species of cell surface associated La protein
Authors: Leikina Evgenia , Whitlock Jarred M. , Melikov Kamran , Zhang Wendy , Bachmann Michael P. , Chernomordik Leonid V.
Published: June 2024

The bone-resorbing activity of osteoclasts plays a critical role in the life-long remodeling of our bones that is perturbed in many bone loss diseases. Multinucleated osteoclasts are formed by the fusion of precursor cells, and larger cells - generated by an increased number of cell fusion events - have higher resorptive activity. We find that osteoclast fusion and bone-resorption are promoted by reactive oxygen species (ROS) signaling and by an unconventional low molecular weight species of La protein, located at the osteoclast surface. Here, we develop the hypothesis that La’s unique regulatory role in osteoclast multinucleation and function is controlled by a ROS switch in La trafficking. Using antibodies that recognize reduced or oxidized species of La, we find that differentiating osteoclasts enrich an oxidized species of La at the cell surface, which is distinct from the reduced La species conventionally localized within cell nuclei. ROS signaling triggers the shift from reduced to oxidized La species, its dephosphorylation and delivery to the surface of osteoclasts, where La promotes multinucleation and resorptive activity. Moreover, intracellular ROS signaling in differentiating osteoclasts oxidizes critical cysteine residues in the C-terminal half of La, producing this unconventional La species that promotes osteoclast fusion. Our findings suggest that redox signaling induces changes in the location and function of La and may represent a promising target for novel skeletal therapies.
Srs2 binding to PCNA and its sumoylation contribute to RPA antagonism during the DNA damage response
Authors: Fan Jiayi , Dhingra Nalini , Yang Tammy , Yang Vicki , Zhao Xiaolan
Published: June 2024

Activation of the DNA damage checkpoint upon genotoxin treatment induces a multitude of cellular changes, such as cell cycle arrest or delay, to cope with genome stress. After prolonged genotoxin treatment, the checkpoint can be downregulated to allow cell cycle and growth resumption. In yeast, downregulation of the DNA damage checkpoint requires the Srs2 DNA helicase, which removes the ssDNA binding complex RPA and the associated Mec1 checkpoint kinase from DNA, thus dampening Mec1-mediated checkpoint. However, it is unclear whether the ‘anti-checkpoint’ role of Srs2 is temporally and spatially regulated to both allow timely checkpoint termination and to prevent superfluous RPA removal. Here we address this question by examining regulatory elements of Srs2, such as its phosphorylation, sumoylation, and protein-interaction sites. Our genetic analyses and checkpoint level assessment suggest that the RPA countering role of Srs2 is promoted by Srs2 binding to PCNA, which recruits Srs2 to a subset of ssDNA regions. RPA antagonism is further fostered by Srs2 sumoylation, which we found depends on the Srs2-PCNA interaction. Srs2 sumoylation is additionally reliant on Mec1 and peaks after Mec1 activity reaches maximal levels. Based on these data, we propose a two- step model of checkpoint downregulation wherein Srs2 recruitment to PCNA proximal ssDNA- RPA filaments and subsequent sumoylation stimulated upon Mec1 hyperactivation facilitate checkpoint recovery. This model suggests that Srs2 removal of RPA is minimized at ssDNA regions with no proximal PCNA to permit RPA-mediated DNA protection at these sites.
Srs2 binding to PCNA and its sumoylation contribute to RPA antagonism during the DNA damage response
Authors: Fan Jiayi , Dhingra Nalini , Yang Tammy , Yang Vicki , Zhao Xiaolan
Published: June 2024

Activation of the DNA damage checkpoint upon genotoxin treatment induces a multitude of cellular changes, such as cell cycle arrest, to cope with genome stress. After prolonged genotoxin treatment, the checkpoint can be downregulated to allow cell cycle and growth resumption. In yeast, downregulation of the DNA damage checkpoint requires the Srs2 DNA helicase, which removes the ssDNA binding complex RPA and the associated Mec1 checkpoint kinase from DNA, thus dampening Mec1 activation. However, it is unclear whether the ‘anti-checkpoint’ role of Srs2 is temporally and spatially regulated to both allow timely checkpoint termination and to prevent superfluous RPA removal. Here we address this question by examining regulatory elements of Srs2, including its phosphorylation, sumoylation, and protein-interaction sites. Our genetic analyses and checkpoint level assessment suggest that the RPA countering role of Srs2 is promoted by Srs2 binding to PCNA, which is known to recruit Srs2 to subsets of ssDNA regions. RPA antagonism is further fostered by Srs2 sumoylation, which we found depends on the Srs2-PCNA interaction. Srs2 sumoylation is additionally reliant on Mec1 and peaks after Mec1 activity reaches maximal levels. Collectively, our data provide evidence for a two-step model wherein checkpoint downregulation is facilitated by PCNA-mediated Srs2 recruitment to ssDNA-RPA filaments and the subsequent Srs2 sumoylation stimulated upon Mec1 hyperactivation. We propose that this mechanism allows Mec1 hyperactivation to trigger checkpoint recovery.
SLC35G1 is a highly chloride-sensitive transporter responsible for the basolateral membrane transport in intestinal citrate absorption
Authors: Mimura Yoshihisa , Yasujima Tomoya , Inoue Katsuhisa , Akino Shogo , Namba Chitaka , Kusuhara Hiroyuki , Sekiguchi Yutaro , Ohta Kinya , Yamashiro Takahiro , Yuasa Hiroaki
Published: June 2024

The intestinal absorption of essential nutrients, especially those not readily biosynthesized, is a critical physiological process for maintaining homeostasis. Numerous studies have indicated that intestinal absorption is mediated by various membrane transporters. Citrate, a crucial bioactive compound produced as an intermediate in the Krebs cycle, is absorbed in the small intestine through carrier-mediated systems because of its high hydrophilicity. While the luminal absorption of citrate is mediated by Na+-dicarboxylate cotransporter 1 (NaDC1/SLC13A2), the mechanism governing the release of the transported citrate into the bloodstream remains unknown. Here, we explored the transporters responsible for intestinal citrate absorption at the basolateral membrane, focusing on highly expressed orphan transporters in the small intestine as candidates. Consequently, SLC35G1, originally identified as a partner of stromal interaction molecule 1, a cell surface transmembrane glycoprotein, was found to play a role in the intestinal absorption of citrate at the basolateral membrane. Furthermore, our results revealed that SLC35G1-mediated citrate transport was diminished by chloride ions at physiologically relevant extracellular concentrations. This suggests that SLC35G1, to our best knowledge, is the first transporter identified to be extremely sensitive to chloride ions among those functioning on the basolateral membrane of intestinal epithelial cells. This study provides valuable insights into the intestinal absorption of citrate and significantly contributes to elucidating the poorly understood molecular basis of the intestinal absorption system.
Campaigning in a Quagmire
Authors: Friedman Jeffrey A.
Published: June 2024

This chapter tackles the politics of image-making that shaped the life cycle of the Vietnam War. It examines the case studies of the 1964, 1968, and 1972 presidential campaigns where no presidential nominees attempted to win public support by making proposals for handling the war that voters supported on their merits. The chapter details how Lyndon Johnson, and his election opponent Republican senator Barry Goldwater, recommended escalating the Vietnam War to shape their personal images. Meanwhile, throughout the 1968 presidential campaign, Richard Nixon promised to deliver peace with honor in Vietnam but he never explained how he would do so. The chapter cites that the politics of image-making enable open-ended military interventions and influence electoral strategy in a manner that conventional notions of democratic politics do not capture.
Image-Making in an Age of Endless Wars
Authors: Friedman Jeffrey A.
Published: June 2024

This chapter looks into how the politics of image-making shaped US military interventions in the post-Cold War era. It focuses on the politics of military intervention in Bosnia and Iraq by Bill Clinton alongside Barack Obama's military intervention in Afghanistan and Libya. Both presidents present a common pattern wherein elected officials made choices designed to cultivate or maintain impressions of leadership strength, even when that required steering US foreign policy in a direction that was more hawkish than what voters wanted. Moreover, history provides further indication of the extensive relationship between public opinion and US foreign policy. The chapter mentions that Obama's tenure as commander in chief also demonstrates the difficulty of bringing structural change to US foreign policy.
When Networks Don’t Work
Authors: Edelman Marc
Published: June 2024

This chapter evaluates the roots of competing conservative and progressive visions of “civil society.” It discusses the inadequacy of Gramsci's concept of “organic intellectuals” for the study of agrarian movements, and examines the demise and subsequent reemergence of transnational peasant organization networks in Central America. The chapter notes the problems of “fictitious,” “shell,” or “paper organizations” and gatekeeper groups that vet movements seeking to affiliate with transnational networks, as well as the occasionally problematical representation claims of the peasant organizations. It constitutes an experiment in self-criticism and a corrective to the overly optimistic interpretation in the previous chapter, which was written in a moment when transnational peasant politics in Central America was ascendant, before processes of organizational decomposition and massive out-migration made the project of regional solidarity ever more challenging. However, as the chapter also points out, even as some networks collapsed, others emerged to confront elite-dominated regional integration plans.