bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambitiousness of Sustainable Development Goal (SDG) targets: classification and implications for policy making
Authors: Mustajoki Jyri , Borchardt Steve , Büttner Leonie , Köhler Berit , Lepenies Robert , Lyytimäki Jari , Mille Raoul , Pedersen Anders Branth , Reis Stefan , Richard Didier
Published: October 2022

We analyse how ambitiously the underlying targets for the Sustainable Development Goals (SDGs) of the United Nations Agenda 2030 are set in terms of their semantic formulation and discuss the implications of this for policy making. Our analysis is based on classifying ambitiousness into three types: semantic, relative and absolute ambitiousness; in this paper, we mainly analyse semantic ambitiousness. We establish an evaluation framework that shows clear differences in semantic ambitiousness levels between SDG targets. Awareness of these differences is essential, as semantic ambitiousness also lays the foundation for evaluating other types of ambitiousness of the SDGs in international cross-country comparisons and national policy making processes. We also analyse how progress towards the targets has been reported in the Sustainable Development Report of the SDG Index and in the SDGs Progress Chart of the United Nations. Finally, we discuss possible reasons for the differences in the level of ambitiousness and provide recommendations for operationalising the targets. Our aim is to provide a better understanding of the variability of interpretations that can occur in the evaluation of different SDGs, and to improve the coherence between the goals in developing any future development goal frameworks beyond Agenda 2030.
Discounting Life
Authors: Rajah Jothie
Published: October 2022

Extrajudicial, extraterritorial killings of War on Terror adversaries by the US state have become the new normal. Alongside targeted individuals, unnamed and uncounted others are maimed and killed. Despite the absence of law's conventional sites, processes, and actors, the US state celebrates these killings as the realization of 'justice.' Meanwhile, images, narrative, and affect do the work of law; authorizing and legitimizing the discounting of some lives so that others – implicitly, American nationals – may live. How then, as we live through this unending, globalized war, are we to make sense of law in relation to the valuing of life? Adopting an interdisciplinary approach to law to excavate the workings of necropolitical law, and interrogating the US state's justifications for the project of counterterror, this book's temporal arc, the long War on Terror, illuminates the profound continuities and many guises for racialized, imperial violence informing the contemporary discounting of life.
The Russia-Ukraine War and the Seeds of a New Liberal Plurilateral Order
Authors: Sloss David L. , Dickinson Laura A.
Published: October 2022

Since about 2008, the rise of autocracy and the decline of democracy has threatened the modern liberal international order. To counter the threat of authoritarian international law, the United States should collaborate with liberal democracies from Europe, Asia, Africa, and Latin America to develop new plurilateral institutions and treaties to create a “liberal plurilateral order.” This Essay shows that states are planting the seeds of a future liberal plurilateral order in their response to Russian aggression in Ukraine.
Rank-uniform local law for Wigner matrices
Authors: Cipolloni Giorgio , Erdős László , Schröder Dominik
Published: October 2022

We prove a general local law for Wigner matrices that optimally handles observables of arbitrary rank and thus unifies the well-known averaged and isotropic local laws. As an application, we prove a central limit theorem in quantum unique ergodicity (QUE): that is, we show that the quadratic forms of a general deterministic matrix A on the bulk eigenvectors of a Wigner matrix have approximately Gaussian fluctuation. For the bulk spectrum, we thus generalise our previous result [17] as valid for test matrices A of large rank as well as the result of Benigni and Lopatto [7] as valid for specific small-rank observables.
How can One Health approaches be operationalized in order to enable action to reduce or prevent AMR?
Authors: Keune Hans
Published: October 2022

Antimicrobial resistance (AMR) is a global health threat to humanity, animals, plants and the wider environment. The intrinsic complexity and interconnectivity of human, animal and environmental factors has now been globally acknowledged and warrants a One Health approach. International communities launched guidelines to support the development and implementation of comprehensive national One Health (OH) AMR strategies with a particular concern for threatened antibiotics. Yet, AMR National Action Plans have proven difficult to implement because of social and structural obstacles/barriers, which are well-known as OH challenges (Keune, Payyappallimana, Morand and Rüegg 2022) such as overcoming inter-sectorial and interdisciplinary barriers, taking into account structural societal dynamics, implementing transdisciplinary system’s approaches. To enhance necessary transformative system changes, it is vital to operationalize and contextualize One Health AMR approaches for the design, implementation and evaluation of community-based AMR interventions, tailored to the local circumstances.
An anti-secularist pan-Asianist from Europe: Paul Richard in Japan, 1916–1920
Authors: Krämer Hans Martin
Published: October 2022

The modern Japanese nation-state that was established from 1868 onwards was marked by a strong tendency towards the separation of state and religion: religions were protected as a private matter, but the public sphere was resolutely kept free of them. This was mainly done so that competing religions would not get in the way of state-sanctioned emperor worship. The latter, although imbued with elements from Shinto, was carefully defined as non-religious, so that emperor worship could be prescribed without harm to the constitutionally guaranteed freedom of religion. This secularist approach to policing religions was broadly shared among Japanese elites—but it did not remain unopposed.

From around the turn of the twentieth century, dissatisfaction with the separation of the religious and the secular spheres began to be voiced, especially by pan-Asianist activists, who sought to combine the spiritual unity of Asia with the political liberation of Asian countries from Western colonialism and imperialism. Although Japanese pan-Asianism has conventionally been seen as a purely political movement, one cannot explain it fully without taking into account its spiritual dimension, which up to the 1920s drew its primary inspiration from India. This article will show how pan-Asianist activists in Japan opposed mainstream secularism and discuss what their vision for a unified Asia was. In doing so, it will focus on the Japanese reception of the Frenchman Paul Richard, an important political activist-cum-spiritual seeker who was a central node in the network of Indian and Japanese pan-Asianists in the early twentieth century.
Anti-populist populism: Musical challenges to Trump's America and Erdoğan's Turkey
Authors: Way Lyndon C.S.
Published: October 2022

Populism is a discursive construct that represents popular interests and values by ‘pretend[ing] to speak’ for the people who are constructed separate and opposed to a powerful elite. Yet populism, in its various forms and accents, ‘can adapt flexibly to a variety of substantive ideological values and principles’. This is manifested in ‘the people’ not being a prefixed natural category, but a signifier that acquires meaning through discourses and contexts. This article considers how populism is articulated in hip hop videos that criticise two authoritarian-populist politicians: America's Trump and Turkey's Erdoğan. Using Multimodal Critical Discourse Studies, Eminem's ‘The Storm’ and Ezhel's ‘Yarınımız Yok (We have no tomorrow)’ are analysed to demonstrate how oppositional popular music can articulate its own brands of populism, transcending contexts, yet shaped by them.
Managing uncertainty in decision-making of common congenital cardiac defects
Authors: McMahon Colin J. , Sendžikaitė Skaistė , Jegatheeswaran Anusha , Cheung Yiu-Fai , Majdalany David S. , Hjortdal Vibeke , Redington Andrew N. , Jacobs Jeffrey P. , Asoodar Maryam , Sibbald Matthew , Geva Tal , van Merrienboer Jeroen J.G. , Tretter Justin T.
Published: October 2022

Decision-making in congenital cardiac care, although sometimes appearing simple, may prove challenging due to lack of data, uncertainty about outcomes, underlying heuristics, and potential biases in how we reach decisions. We report on the decision-making complexities and uncertainty in management of five commonly encountered congenital cardiac problems: indications for and timing of treatment of subaortic stenosis, closure or observation of small ventricular septal defects, management of new-onset aortic regurgitation in ventricular septal defect, management of anomalous aortic origin of a coronary artery in an asymptomatic patient, and indications for operating on a single anomalously draining pulmonary vein. The strategy underpinning each lesion and the indications for and against intervention are outlined. Areas of uncertainty are clearly delineated. Even in the presence of “simple” congenital cardiac lesions, uncertainty exists in decision-making. Awareness and acceptance of uncertainty is first required to facilitate efforts at mitigation. Strategies to circumvent uncertainty in these scenarios include greater availability of evidence-based medicine, larger datasets, standardised clinical assessment and management protocols, and potentially the incorporation of artificial intelligence into the decision-making process.
Advancing towards inclusive peace and security: Persons with disabilities and Security Council Resolution 2475
Authors: Ruminowicz Bogna
Published: October 2022

Persons with disabilities are at higher risk of injury or death during an armed conflict, either as specific targets or through inability to protect themselves. Humanitarian responses concentrate on meeting the immediate basic needs of an average population. Yet historically, the situation of persons with disabilities during armed conflict, as well as peacebuilding processes, has been largely absent in the discussion at the Security Council. On 20 June 2019, the United Nations Security Council unanimously passed Resolution 2475. This groundbreaking text marks the first time the Council has dedicated an entire resolution to the situation of persons with disabilities in situations of armed conflict. The resolution has significantly raised the attention and understanding of the situation of persons with disabilities in the context of the armed conflict in the Security Council and beyond. This article details the process that led to Resolution 2475, as well as what has happened since.
Maschinelles Lernen zur Förderung von höheren Kompetenzen
Authors: Giang Christian , Wambsganss Thiemo , Käser Tanja
Published: October 2022

Zusammenfassung: Hintergrund: Die einschneidenden Veränderungen, welche moderne Gesellschaften durch die Digitalisierung erfahren haben, haben es unerlässlich gemacht, heutigen und künftigen Generationen höhere Kompetenzen als Rüstzeug für die neue Lern- und Arbeitswelt mitzugeben. Die Verwendung von digitalen Lernumgebungen zusammen mit maschinellem Lernen kann in diesem Kontext ein leistungsstarkes Werkzeug darstellen. Methoden: In der vorliegenden Übersichtsarbeit werden die Chancen und Herausforderungen von maschinellem Lernen im Bildungswesen anhand ausgewählter Anwendungsbereiche aufgezeigt. Zu jedem Anwendungsbereich wird eine Zusammenfassung der bestehenden Forschung präsentiert und die Anwendung anhand eines konkreten Beispiels aus der jüngsten Forschung veranschaulicht. Ergebnisse: Die Ergebnisse aus der jüngsten Forschung bestätigen, dass maschinelles Lernen ein enormes Potenzial hat, um das Bildungswesen durch personalisierte Lernmöglichkeiten für höhere Kompetenzen zu bereichern. Jedoch ist noch weitere Forschung nötig, um die wirkliche Lernwirksamkeit solcher Ansätze zu validieren.
Stressing the Advantages of Female Leadership Can Place Women at a Disadvantage
Authors: Mousavi Daria , Schulte Anna , Lammers Joris
Published: October 2022

Abstract. An often-heard claim is that women will inevitably take over men’s dominant position in management due to superior female leadership skills. Lammers and Gast (2017) found that such claims paradoxically maintain gender inequality by undermining support for affirmative action. The original article was limited by comparing a single experimental and control text and exclusive reliance on American samples. We report a replication and extension among a German community sample ( N = 300), which tests the effects of five different experimental stimuli, primarily drawn from different German media outlets, against a control stimulus. The data replicate earlier effects and confirm that the media should be careful not to exaggerate claims about female leadership strengths.
Strategic Exploitation by Higher-Status People Incurs Harsher Third-Party Punishment
Authors: Dong Mengchen , van Prooijen Jan-Willem , van Lange Paul A. M.
Published: October 2022

Abstract. It is widely documented that third parties punish norm violations, even at a substantial cost to themselves. However, little is known about how third-party punishment occurs in groups consisting of members who differ in status. Having a higher-status member promotes norm enforcement and group efficiency but also poses threats to collective goods when they strategically exploit people’s trust to maximize self-interest. Two preregistered studies consistently revealed a punitive mechanism contingent on target status and strategic exploitation. Third-party observers generated harsher punishment when high- but not low-status targets transgressed after publicly endorsing cooperation (Study 1) or procedural fairness (Study 2). The findings elucidate third-party punishment as a feasible mechanism to counteract exploitation and maintain social norms in interactions with status asymmetry.
A Cross-Cultural Replication on Humanness Attribution
Authors: Bettinsoli Maria Laura , Formanowicz Magdalena
Published: October 2022

Abstract. Previous research showed that targets achieving (vs. not) a goal were ascribed more humanness. We conceptually replicate previous studies by involving a population of English and Arabic speakers to test cross-cultural replicability of the effect and the contribution of sensorimotor systems in agency representation. Participants ( Ntot = 637) saw animations, where goal achievement and trajectory were manipulated. They evaluated agency, communion, humanness, and attitudes (respect and liking) toward presented targets. Goal achievement versus failure but not movement trajectory increased agency and communion ratings, which in turn affected humanness, respect, and liking (Study 1 and Study 2). Goal manipulation also directly affected humanness ratings (Study 2). Altogether, our findings suggest a superior role of success over trajectory manipulation in perceiving inanimate objects as having humanness.
Together to Welcome, Together to Exclude
Authors: Marinucci Marco , Mazzoni Davide , Aureli Nicolas , De Cristofaro Valeria , Shamloo Soraya E. , Guarino Antonella , Tzankova Ivanova
Published: October 2022

Abstract. This preregistered study examined whether positive and negative intergroup contact with migrants relates to collective action supporting and opposing migrants as well as to interpersonal exclusion toward them via the key processes identified in the Social Identity Model of Collective Action. Structural equation models conducted on cross-sectional data from 506 Italian and English participants showed that positive (negative) contact related to higher (lower) collective inclusion and lower (higher) collective and interpersonal exclusion of migrants via group anger, identification, and efficacy. Considering positive and negative contact, collective action pro and against migrants and interpersonal behaviors simultaneously, this study provided a nuanced picture of the antecedents and processes underlying the advantaged group members’ behaviors toward migrants.
Investigating Drivers of Particulate Matter Pollution Over India and the Implications for Radiative Forcing With GEOS‐Chem‐TOMAS15
Authors: Karambelas Alexandra , Fiore Arlene M. , Westervelt Daniel M. , McNeill V. Faye , Randles Cynthia A. , Venkataraman Chandra , Pierce Jeffrey R. , Bilsback Kelsey R. , Milly George P.
Published: October 2022

Ambient fine particulate matter (PM2.5) concentrations in India frequently exceed 100 μg/m3 during fall and winter pollution episodes. We use the GEOS‐Chem chemical transport model with the TwO‐Moment Aerosol Sectional microphysics scheme with 15 size bins (TOMAS15) to assess PM2.5 composition and impacts on radiation and cloud condensation nuclei (CCN) during pollution episodes as compared to the seasonal (October‐December) average. We conduct high resolution (0.25° × 0.3125°) nested‐domain simulations over India for short‐duration, high‐PM2.5 episodes in the fall of 2015 and 2017. The simulations capture the magnitude and spatial patterns of pollution episodes measured by surface monitors (r2PM2.5 = 0.69) although aerosol optical depth is underestimated. During the episodes, near‐surface organic matter (OM), black carbon (BC), and secondary inorganic aerosol concentrations increase from seasonal averages by up to 36, 7, and 7 μg/m3, respectively. Episodic aerosol increases enhance cooling by lowering the top‐of‐atmosphere clear‐sky direct radiative effect (DRETOA) during the 2015 episode (−6 W/m2), with a smaller impact during the 2017 episode (−1 W/m2). Differences in DRETOA reflect larger increases in scattering aerosols in the column during the 2015 episode (+17 mg/m2) than in 2017 (+13 mg/m2), while absorbing aerosol column enhancements are smaller (+3 mg/m2) in both years. Changes in shortwave radiation at the surface (SWsfc) are spatially similar to DRETOA and mostly negative during both episodes. CCN enhancements (0.2% supersaturation) during these episodes occur across the western Indo‐Gangetic Plain, coincident with higher PM2.5 concentrations. Changes in DRETOA, SWsfc, and CCN during high‐PM2.5 episodes may have implications for crops, the hydrologic cycle, and surface temperature.
High Sensitivity of Compound Drought and Heatwave Events to Global Warming in the Future
Authors: Zhang Qin , She Dunxian , Zhang Liping , Wang Gangsheng , Chen Jie , Hao Zengchao
Published: October 2022

Compound drought and heatwave (CDHW) events have received considerable attention in recent years due to their devastating effects on human society and ecosystem. In this study, we systematically investigated the changes of CDHW events in multi‐spatiotemporal scales for historical period (1951–2014) and four future scenarios (2020–2100) (SSP1‐2.6, SSP2‐4.5, SSP3‐7.0, and SSP5‐8.5) over global land by using Coupled Model Intercomparison Project Phase 6 (CMIP6) models. The responses of the CDHW events to the changes of maximum air temperature and the climatic water balance variable are also examined. The results show that the multi‐model ensembles project a significant increasing trend in CDHW characteristics over almost all global lands under SSP2‐4.5, SSP3‐7.0, and SSP5‐8.5, especially across northern North‐America, Caribbean, Mediterranean and Russian‐Arctic, there is a stronger increasing trend. A significantly increasing CDHW risk will occur across most global land for the medium to long term future without aggressive adaptation and mitigation strategies. The results of path analysis suggest that temperature is the dominant factor influencing CDHW events. Additionally, higher sensitivity of CDHW events to global warming will occur in the future. Particularly, each 1°C global warming increases the duration of the CDHW events by 3 days in the historical period, but by about 10 days in the future period. Overall, this study improves our understanding in the projection of CDHW events and the impacts of climate drivers to the CDHW events under various future scenarios, which could provide supports about the risk assessment, adaptation and mitigation strategies under climate change.
Precipitation Over Southern Africa: Moisture Sources and Isotopic Composition
Authors: Geppert M. , Hartmann K. , Kirchner I. , Pfahl S. , Struck U. , Riedel F.
Published: October 2022

Southern Africa, with its vast arid to semiarid areas, is considered vulnerable to precipitation changes and amplifying weather extremes. However, during the last 100 ka, huge lakes existed in the currently dry central Kalahari. It has been suggested that these lakes could have existed due to altered atmospheric circulation pattern, leading to an increase in precipitation or to changes in the annual precipitation distribution. Past climate changes are recorded in paleo‐archives, yet, for a proper interpretation of paleo‐records, for example, from sedimentological archives or fossils, it is essential to put them in a context with recent observations. This study’s objective is, therefore, to analyze spatially differing annual precipitation distributions at multiple locations in southern Africa with respect to their stable water isotope composition, moisture transport pathways, and sources. Five different precipitation distributions are identified by end‐member modeling and respective rainfall zones are inferred, which differ significantly in their isotopic compositions. By calculating backward trajectories, different moisture source regions are identified for the rainfall zones and linked to typical circulation patterns. Our results furthermore show the importance of the seasonality, the amount effect, and the traveled distance of the moisture for the general isotopic composition over the entire southern Africa. The identified pattern and relationships can be useful in the evaluation of isotope‐enabled climate models for the region and are potentially of major importance for the interpretation of stable water isotope composition in paleo‐records in future research.
Characterization of Southern Ocean Boundary Layer Clouds Using Airborne Radar, Lidar, and In Situ Cloud Data: Results From SOCRATES
Authors: Schima Julian , McFarquhar Greg , Romatschke Ulrike , Vivekanandan Jothiram , D’Alessandro John , Haggerty Julie , Wolff Cory , Schaefer Ethan , Järvinen Emma , Schnaiter Martin
Published: October 2022

Climate and numerical weather prediction models struggle to accurately predict radiative forcing over the Southern Ocean (SO), as the amount of clouds and their phases are poorly represented in such models due to a lack of observations upon which to base parameterizations. To address this, a novel particle identification (PID) scheme, based upon airborne radar and lidar data, was applied to data collected during the Southern Ocean Clouds, Aerosol, Radiation Transport Experimental Study (SOCRATES) to assess the vertical structure of SO boundary layer clouds. A comparison between the PID scheme and in situ phase data from SOCRATES showed relatively good agreement between the two data types. The convectivity of the clouds sampled during SOCRATES was determined using the novel Echo Classification from COnvectivity for Vertically pointing radars product. The PID and in situ data were then used synergistically to identify the following features of cloud vertical structure: (a) Supercooled liquid water was very common (Probability, P ∼ 80%) at cloud top for convective and stratiform clouds; (b) Supercooled large drops with maximum dimensions >95 μm frequently appear within a hundred meters below cloud top, particularly within convective clouds (Max P 35%–45%), but also within stratiform clouds (Max P 20%–30%); (c) Ice production was associated with convective activity, with P ∼ 20% at cloud top, increasing to 50%–70% 200 m below top, compared to P < 30% everywhere in stratiform clouds; (d) Convective clouds were found to be more vertically heterogeneous than stratiform clouds.
Controlled afterglow luminescent particles for photochemical tissue bonding
Authors: Kim Seong-Jong , Choi Minji , Hong Guosong , Hahn Sei Kwang
Published: October 2022

Upconversion materials (UCMs) have been developed to convert tissue-penetrating near-infrared (NIR) light into visible light. However, the low energy conversion efficiency of UCMs has limited their further biophotonic applications. Here, we developed controlled afterglow luminescent particles (ALPs) of ZnS:Ag,Co with strong and persistent green luminescence for photochemical tissue bonding (PTB). The co-doping of Ag+ and Co2+ ions into ZnS:Ag,Co particles with the proper vacancy formation of host ions resulted in high luminescence intensity and long-term afterglow. In addition, the ALPs of ZnS:Ag,Co could be recharged rapidly under short ultraviolet (UV) irradiation, which effectively activated rose bengal (RB) in hyaluronate-RB (HA-RB) conjugates for the crosslinking of dissected collagen layers without additional light irradiation. The remarkable PTB of ZnS:Ag,Co particles with HA-RB conjugates was confirmed by in vitro collagen fibrillogenesis assay, in vivo animal wound closure rate analysis, and in vivo tensile strength evaluation of incised skin tissues. Taken together, we could confirm the feasibility of controlled ALPs for various biophotonic applications.
Fetuin-A is an immunomodulator and a potential therapeutic option in BMP4-dependent heterotopic ossification and associated bone mass loss
Authors: Kan Chen , Yang Jiazhao , Fan Haitao , Dai Yuanjuan , Wang Xingxing , Chen Rui , Liu Jia , Meng Xiangyue , Wang Wei , Li Guiling , Zhou Jiao , Zhang Ya , Zhu Wanbo , Fang Shiyuan , Wei Haiming , Zheng Hong , Wang Siying , Ni Fang
Published: October 2022

Heterotopic ossification (HO) is the abnormal formation of bone in extraskeletal sites. However, the mechanisms linking HO pathogenesis with bone mass dysfunction remain unclear. Here, we showed that mice harboring injury-induced and BMP4-dependent HO exhibit bone mass loss similar to that presented by patients with HO. Moreover, we found that injury-induced hyperinflammatory responses at the injury site triggered HO initiation but did not result in bone mass loss at 1 day post-injury (dpi). In contrast, a suppressive immune response promoted HO propagation and bone mass loss by 7 dpi. Correcting immune dysregulation by PD1/PDL1 blockade dramatically alleviated HO propagation and bone mass loss. We further demonstrated that fetuin-A (FetA), which has been frequently detected in HO lesions but rarely observed in HO-adjacent normal bone, acts as an immunomodulator to promote PD1 expression and M2 macrophage polarization, leading to immunosuppression. Intervention with recombinant FetA inhibited hyperinflammation and prevented HO and associated bone mass loss. Collectively, our findings provide new insights into the osteoimmunological interactions that occur during HO formation and suggest that FetA is an immunosuppressor and a potential therapeutic option for the treatment of HO.
IKCa channels control breast cancer metabolism including AMPK-driven autophagy
Authors: Gross Dominic , Bischof Helmut , Maier Selina , Sporbeck Katharina , Birkenfeld Andreas L. , Malli Roland , Ruth Peter , Proikas-Cezanne Tassula , Lukowski Robert
Published: October 2022

Ca2+-activated K+ channels of intermediate conductance (IK) are frequently overexpressed in breast cancer (BC) cells, while IK channel depletion reduces BC cell proliferation and tumorigenesis. This raises the question, of whether and mechanistically how IK activity interferes with the metabolic activity and energy consumption rates, which are fundamental for rapidly growing cells. Using BC cells obtained from MMTV-PyMT tumor-bearing mice, we show that both, glycolysis and mitochondrial ATP-production are reduced in cells derived from IK-deficient breast tumors. Loss of IK altered the sub-/cellular K+- and Ca2+- homeostasis and mitochondrial membrane potential, ultimately resulting in reduced ATP-production and metabolic activity. Consequently, we find that BC cells lacking IK upregulate AMP-activated protein kinase activity to induce autophagy compensating the glycolytic and mitochondrial energy shortage. Our results emphasize that IK by modulating cellular Ca2+- and K+-dynamics contributes to the remodeling of metabolic pathways in cancer. Thus, targeting IK channel might disturb the metabolic activity of BC cells and reduce malignancy.
Limiting glutamine utilization activates a GCN2/TRAIL-R2/Caspase-8 apoptotic pathway in glutamine-addicted tumor cells
Authors: Yerbes Rosario , Mora-Molina Rocío , Fernández-Farrán F. Javier , Hiraldo Laura , López-Rivas Abelardo , Palacios Carmen
Published: October 2022

Oncogenic transformation leads to changes in glutamine metabolism that make transformed cells highly dependent on glutamine for anabolic growth and survival. Herein, we investigated the cell death mechanism activated in glutamine-addicted tumor cells in response to the limitation of glutamine metabolism. We show that glutamine starvation triggers a FADD and caspase-8-dependent and mitochondria-operated apoptotic program in tumor cells that involves the pro-apoptotic TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), but is independent of its cognate ligand TRAIL. In glutamine-depleted tumor cells, activation of the amino acid-sensing general control nonderepressible-2 kinase (GCN2) is responsible for TRAIL-R2 upregulation, caspase-8 activation, and apoptotic cell death. Interestingly, GCN2-dependent ISR signaling induced by methionine starvation also leads to TRAIL-R2 upregulation and apoptosis. Moreover, pharmacological inhibition of transaminases activates a GCN2 and TRAIL-R2-dependent apoptotic mechanism that is inhibited by non-essential amino acids (NEAA). In addition, metabolic stress upon glutamine deprivation also results in GCN2-independent FLICE-inhibitory protein (FLIP) downregulation facilitating caspase-8 activation and apoptosis. Importantly, downregulation of the long FLIP splice form (FLIPL) and apoptosis upon glutamine deprivation are inhibited in the presence of a membrane-permeable α-ketoglutarate. Collectively, our data support a model in which limiting glutamine utilization in glutamine-addicted tumor cells triggers a previously unknown cell death mechanism regulated by GCN2 that involves the TRAIL-R2-mediated activation of the extrinsic apoptotic pathway.
Liquid biopsy in gastric cancer: predictive and prognostic biomarkers
Authors: Zhang Zihao , Wu Hao , Chong Wei , Shang Liang , Jing Changqing , Li Leping
Published: October 2022

Gastric cancer (GC) is a high-incidence cancer worldwide. Most patients are diagnosed at an advanced stage, by which time they have limited treatment options and poor prognosis. Early diagnosis and precise treatment are important. In the past few years, emerging research has been conducted on the use of non-invasive liquid biopsy, with its advantages of minimal invasiveness and repeated sampling, to monitor tumor occurrence and recurrence in real time and to evaluate prognosis and treatment response. Many studies have demonstrated the potential of liquid biopsy in GC, and the detection of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating free DNA (cfDNA), and exosomes has achieved gratifying results. In this review, we summarize evolving technologies for and information regarding liquid biopsy, the most recently discovered GC liquid biopsy biomarkers, and ongoing clinical trials and discuss the challenges and application prospects of liquid biopsy in GC.
Extracellular vesicles microRNA-592 of melanoma stem cells promotes metastasis through activation of MAPK/ERK signaling pathway by targeting PTPN7 in non-stemness melanoma cells
Authors: Zhang Yuhan , Chen Yan , Shi Lei , Li Jie , Wan Wenjuan , Li Bowen , Liu Doudou , Li Xiaoshuang , Chen Yuting , Xiang Meng , Chen Hao , Zeng Bin , Xing H. Rosie , Wang Jianyu
Published: October 2022

Melanoma, one of the most aggressive malignancies, its high mortality and low survival rates are associated with effective metastatic colonization. Melanoma metastasis hinges on the bidirectional cell-cell communication within the complex metastatic microenvironments (MME). Extracellular vesicles (EVs) are recognized as a new class of molecular mediator in MME programing. Published studies show that melanoma EVs can educate MME stromal cells to acquire the pro-metastatic phenotype to enhance metastatic colonization. Whether EVs can mediate the interactions between heterogenous cancer cells within the MME that alter the course of metastasis has not been investigated at the mechanistic level. In this study, melanoma parental cells (MPCs) and paired derivative cancer stem cell line melanoma stem cells (MSCs) that were derived from melanoma cell line M14 were used. We demonstrate that the EVs-mediated crosstalk between the MSCs and the MPCs is a novel mechanism for melanoma metastasis. We characterized miR-592, a relatively novel microRNA of prognostic potential, in mediation of such intercellular crosstalk. EVs can encapsulate and deliver miR-592 to target MPCs. Upon entering, miR-592 inhibits the expression of its gene target protein tyrosine phosphatase non-receptor type7 (PTPN7), a phosphatase targeting MAPKs. This leads to the relief of the inhibitory effect of PTPN7 on MAPK/ERK signaling and consequently the augmentation of metastatic colonization of MPCs. Thus, via the extracellular vesicle miR-592/PTPN7/MAPK axis, melanoma-CSCs can transfer their metastatic ability to the low-metastatic non-CSC melanoma cells.
Somatic genetic variation in healthy tissue and non-cancer diseases
Authors: Solís-Moruno Manuel , Batlle-Masó Laura , Bonet Núria , Aróstegui Juan I. , Casals Ferran
Published: October 2022

Somatic genetic variants have been studied for several years mostly concerning cancer, where they contribute to its origin and development. It is also clear that the somatic variants load is greater in aged individuals in comparison to younger ones, pointing to a cause/consequence of the senescence process. More recently, researchers have focused on the role of this type of variation in healthy tissue and its dynamics in cell lineages and different organs. In addition, somatic variants have been described to contribute to monogenic diseases, and the number of evidences of their role in complex disorders is also increasing. Thanks to recent advances in next-generation sequencing technologies, this type of genetic variation can be now more easily studied than in the past, although we still face some important limitations. Novel strategies for sampling, sequencing and filtering are being investigated to detect these variants, although validating them with an orthogonal approach will most likely still be needed. In this review, we aim to update our knowledge of somatic variation detection and its relation to healthy tissue and non-cancer diseases.
Emergent helical edge states in a hybridized three-dimensional topological insulator
Authors: Chong Su Kong , Liu Lizhe , Watanabe Kenji , Taniguchi Takashi , Sparks Taylor D. , Liu Feng , Deshpande Vikram V.
Published: October 2022

As the thickness of a three-dimensional (3D) topological insulator (TI) becomes comparable to the penetration depth of surface states, quantum tunneling between surfaces turns their gapless Dirac electronic structure into a gapped spectrum. Whether the surface hybridization gap can host topological edge states is still an open question. Herein, we provide transport evidence of 2D topological states in the quantum tunneling regime of a bulk insulating 3D TI BiSbTeSe2. Different from its trivial insulating phase, this 2D topological state exhibits a finite longitudinal conductance at ~2e2/h when the Fermi level is aligned within the surface gap, indicating an emergent quantum spin Hall (QSH) state. The transition from the QSH to quantum Hall (QH) state in a transverse magnetic field further supports the existence of this distinguished 2D topological phase. In addition, we demonstrate a second route to realize the 2D topological state via surface gap-closing and topological phase transition mechanism mediated by a transverse electric field. The experimental realization of the 2D topological phase in a 3D TI enriches its phase diagram and marks an important step toward functionalized topological quantum devices.
Distinct organization of two cortico-cortical feedback pathways
Authors: Shen Shan , Jiang Xiaolong , Scala Federico , Fu Jiakun , Fahey Paul , Kobak Dmitry , Tan Zhenghuan , Zhou Na , Reimer Jacob , Sinz Fabian , Tolias Andreas S.
Published: October 2022

Neocortical feedback is critical for attention, prediction, and learning. To mechanically understand its function requires deciphering its cell-type wiring. Recent studies revealed that feedback between primary motor to primary somatosensory areas in mice is disinhibitory, targeting vasoactive intestinal peptide-expressing interneurons, in addition to pyramidal cells. It is unknown whether this circuit motif represents a general cortico-cortical feedback organizing principle. Here we show that in contrast to this wiring rule, feedback between higher-order lateromedial visual area to primary visual cortex preferentially activates somatostatin-expressing interneurons. Functionally, both feedback circuits temporally sharpen feed-forward excitation eliciting a transient increase–followed by a prolonged decrease–in pyramidal cell activity under sustained feed-forward input. However, under feed-forward transient input, the primary motor to primary somatosensory cortex feedback facilitates bursting while lateromedial area to primary visual cortex feedback increases time precision. Our findings argue for multiple cortico-cortical feedback motifs implementing different dynamic non-linear operations.
Small molecules targeting the disordered transactivation domain of the androgen receptor induce the formation of collapsed helical states
Authors: Zhu Jiaqi , Salvatella Xavier , Robustelli Paul
Published: October 2022

Intrinsically disordered proteins, which do not adopt well-defined structures under physiological conditions, are implicated in many human diseases. Small molecules that target the disordered transactivation domain of the androgen receptor have entered human trials for the treatment of castration-resistant prostate cancer (CRPC), but no structural or mechanistic rationale exists to explain their inhibition mechanisms or relative potencies. Here, we utilize all-atom molecular dynamics computer simulations to elucidate atomically detailed binding mechanisms of the compounds EPI-002 and EPI-7170 to the androgen receptor. Our simulations reveal that both compounds bind at the interface of two transiently helical regions and induce the formation of partially folded collapsed helical states. We find that EPI-7170 binds androgen receptor more tightly than EPI-002 and we identify a network of intermolecular interactions that drives higher affinity binding. Our results suggest strategies for developing more potent androgen receptor inhibitors and general strategies for disordered protein drug design.
Regulating the scaling relationship for high catalytic kinetics and selectivity of the oxygen reduction reaction
Authors: Zhou Wanlin , Su Hui , Cheng Weiren , Li Yuanli , Jiang Jingjing , Liu Meihuan , Yu Feifan , Wang Wei , Wei Shiqiang , Liu Qinghua
Published: October 2022

The electrochemical oxygen reduction reaction (ORR) is at the heart of modern sustainable energy technologies. However, the linear scaling relationship of this multistep reaction now becomes the bottleneck for accelerating kinetics. Herein, we propose a strategy of using intermetallic-distance-regulated atomic-scale bimetal assembly (ABA) that can catalyse direct O‒O radical breakage without the formation of redundant *OOH intermediates, which could regulate the inherent linear scaling relationship and cause the ORR on ABA to follow a fast-kinetic dual-sites mechanism. Using in situ synchrotron spectroscopy, we directly observe that a self-adjustable N-bridged Pt = N2 = Fe assembly promotes the generation of a key intermediate state (Pt‒O‒O‒Fe) during the ORR process, resulting in high reaction kinetics and selectivity. The well-designed Pt = N2 = Fe ABA catalyst achieves a nearly two orders of magnitude enhanced kinetic current density at the half-wave potential of 0.95 V relative to commercial Pt/C and an almost 99% efficiency of 4-electron pathway selectivity, making it one of the potential ORR catalysts for application to the energy device of zinc‒air cells. This study provides a helpful design principle for developing and optimizing other efficient ORR electrocatalysts.
Speech acoustic indices for differential diagnosis between Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy
Authors: Daoudi Khalid , Das Biswajit , Tykalova Tereza , Klempir Jiri , Rusz Jan
Published: October 2022

While speech disorder represents an early and prominent clinical feature of atypical parkinsonian syndromes such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), little is known about the sensitivity of speech assessment as a potential diagnostic tool. Speech samples were acquired from 215 subjects, including 25 MSA, 20 PSP, 20 Parkinson’s disease participants, and 150 healthy controls. The accurate differential diagnosis of dysarthria subtypes was based on the quantitative acoustic analysis of 26 speech dimensions related to phonation, articulation, prosody, and timing. A semi-supervised weighting-based approach was then applied to find the best feature combinations for separation between PSP and MSA. Dysarthria was perceptible in all PSP and MSA patients and consisted of a combination of hypokinetic, spastic, and ataxic components. Speech features related to respiratory dysfunction, imprecise consonants, monopitch, slow speaking rate, and subharmonics contributed to worse performance in PSP than MSA, whereas phonatory instability, timing abnormalities, and articulatory decay were more distinctive for MSA compared to PSP. The combination of distinct speech patterns via objective acoustic evaluation was able to discriminate between PSP and MSA with very high accuracy of up to 89% as well as between PSP/MSA and PD with up to 87%. Dysarthria severity in MSA/PSP was related to overall disease severity. Speech disorders reflect the differing underlying pathophysiology of tauopathy in PSP and α-synucleinopathy in MSA. Vocal assessment may provide a low-cost alternative screening method to existing subjective clinical assessment and imaging diagnostic approaches.
Seasonal increase of methane emissions linked to warming in Siberian tundra
Authors: Rößger Norman , Sachs Torsten , Wille Christian , Boike Julia , Kutzbach Lars
Published: October 2022

While increasing methane emissions from thawing permafrost are anticipated to be a major climate feedback, no observational evidence for such an increase has previously been documented in the literature. Here we report a trend of increasing methane emissions for the early summer months of June and July at a permafrost site in the Lena River Delta, on the basis of the longest set of eddy covariance methane flux data in the Arctic. Along with a strong air temperature rise of 0.3 ± 0.1 °C yr−1 in June, which corresponds to an earlier warming of 11 d, the methane emissions in June and July have increased by roughly 1.9 ± 0.7% yr−1 since 2004. Although the tundra’s maximum source strength in August has not yet changed, this increase in early summer methane emissions shows that atmospheric warming has begun to considerably affect the methane flux dynamics of permafrost-affected ecosystems in the Arctic.
A living biobank of canine mammary tumor organoids as a comparative model for human breast cancer
Authors: Inglebert Marine , Dettwiler Martina , Hahn Kerstin , Letko Anna , Drogemuller Cord , Doench John , Brown Adam , Memari Yasin , Davies Helen R. , Degasperi Andrea , Nik-Zainal Serena , Rottenberg Sven
Published: October 2022

Mammary tumors in dogs hold great potential as naturally occurring breast cancer models in translational oncology, as they share the same environmental risk factors, key histological features, hormone receptor expression patterns, prognostic factors, and genetic characteristics as their human counterparts. We aimed to develop in vitro tools that allow functional analysis of canine mammary tumors (CMT), as we have a poor understanding of the underlying biology that drives the growth of these heterogeneous tumors. We established the long-term culture of 24 organoid lines from 16 dogs, including organoids derived from normal mammary epithelium or benign lesions. CMT organoids recapitulated key morphological and immunohistological features of the primary tissue from which they were derived, including hormone receptor status. Furthermore, genetic characteristics (driver gene mutations, DNA copy number variations, and single-nucleotide variants) were conserved within tumor-organoid pairs. We show how CMT organoids are a suitable model for in vitro drug assays and can be used to investigate whether specific mutations predict therapy outcomes. Specifically, certain CMT subtypes, such as PIK3CA mutated, estrogen receptor-positive simple carcinomas, can be valuable in setting up a preclinical model highly relevant to human breast cancer research. In addition, we could genetically modify the CMT organoids and use them to perform pooled CRISPR/Cas9 screening, where library representation was accurately maintained. In summary, we present a robust 3D in vitro preclinical model that can be used in translational research, where organoids from normal, benign as well as malignant mammary tissues can be propagated from the same animal to study tumorigenesis.
Galerkin finite element analysis for magnetized radiative-reactive Walters-B nanofluid with motile microorganisms on a Riga plate
Authors: Shahzad Faisal , Jamshed Wasim , Usman  , Ibrahim Rabha W. , Aslam Farheen , Tag El Din El Sayed M. , Khalifa Hamiden Abd El-Wahed , ElSeabee Fayza Abdel Aziz
Published: October 2022

In order to understand the characteristics of bio-convection and moving microorganisms in flows of magnetized Walters-B nano-liquid, we developed a model employing Riga plate with stretchy sheet. The Buongiorno phenomenon is likewise employed to describe nano-liquid motion in the Walters-B fluid. Expending correspondence transformations, the partial differential equation (PDE) control system has been transformed into an ordinary differential equation (ODE) control system. The COMSOL program is used to generate mathematical answers for non-linear equations by employing the Galerkin finite element strategy (G-FEM). Utilizing logical and graphical metrics, temperature, velocity, and microbe analysis are all studied. Various estimates of well-known physical features are taken into account while calculating nanoparticle concentrations. It is demonstrated that this model's computations directly relate the temperature field to the current Biot number and parameter of the Walters-B fluid. The temperature field is increased to increase the approximations of the current Biot number and parameter of the Walters-B fluid.