bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Greek we trust! Παίζοντες μανθάνομεν
Authors: Manolidou Eugenia , Goula Sophia 
Published: September 2023

AbstractThis article presents the method used in Elliniki Agogi, a private small school that teaches the Ancient Greek language as an extra-curricular activity. Over the 29 years of experimenting with educational material, methods, books and exercises, teaching Ancient Greek as a living language seems like the only method that really works for the students. It is immersive, experiential, educational and fun, but most important, it makes students love what they learn; by loving, they keep wanting to come back. By coming back, they repeat. By repeating; they learn. And by learning Greek as a living language, they never forget it. This is our school's aim: to make our students love the language. Experiential learning is highly valued and applied through visits to archaeological sites, and reviving important historical events. But this is only the beginning; playing, drawing, acting, foreign exchanges, educational trips, digital programs, collaborations with foreign institutions and educational organisations come alive in Elliniki Agogi, a small school that was founded 29 years ago in Greece and has joined worldwide efforts in changing the way Greek is taught in order to promote its true, timeless, precious wisdom. In Elliniki Agogi a combination of teaching Greek as a living language and activities that include play and fun, a method as old as time, shows exactly the reason way the words ‘play’ (παιδιά) and ‘education’ (παιδεία) derive from the exact same root word: παῖς (child). Educational material is also provided in order to further enhance and deepen children's knowledge.
In Situ Optimized Substrate Witness Plates: Ground Truth for Key Processes on the Moon and Other Planets
Authors: Saxena Prabal , Morrissey Liam S. , Killen Rosemary M. , McLain Jason L. , Yeo Li Hsia , Curran Natalie M. , Abraham Nithin S. , Graham Heather V. , Tucker Orenthal J. , Sarantos Menelaos , Regberg Aaron B. , Pugel Diane E. , Needham Andrew W. , Hasegawa Mark , Wong Alfred J. 
Published: September 2023

AbstractFuture exploration efforts of the Moon, Mars, and other bodies are poised to focus heavily on persistent and sustainable survey and research efforts, especially given the recent interest in a long‐term sustainable human presence at the Moon. Key to these efforts understands a number of important processes on the lunar surface for both scientific and operational purposes. We discuss the potential value of in situ artificial substrate witness plates, powerful tools that can supplement familiar remote sensing and sample acquisition techniques and provide a sustainable way of monitoring processes in key locations on planetary surfaces while maintaining a low environmental footprint. These tools, which we call Biscuits, can use customized materials as wide ranging as zircon‐based spray coatings to metals potentially useable for surface structures, to target specific processes/questions as part of a small, passive witness plate that can be flexibly placed with respect to location and total time duration. We examine and discuss unique case studies to show how processes such as water presence/transport, presence and contamination of biologically relevant molecules, solar activity related effects, and other processes can be measured using Biscuits. Biscuits can yield key location sensitive, time integrated measurements on these processes to inform scientific understanding of the Moon and enable operational goals in lunar exploration. While we specifically demonstrate this on a simulated traverse and for selected examples, we stress all groups interested in planetary surfaces should consider these adaptable, low footprint, and highly informative tools for future exploration.
Two Decades of Temperature and Specific Humidity Variance Scaling With the Atmospheric Infrared Sounder
Authors: Kahn Brian H. , Fetzer Eric J. , Teixeira Joao , Yue Qing 
Published: September 2023

AbstractA two‐decade climatology of height‐resolved horizontal variance scaling exponents (𝛼) for temperature (T) and specific humidity (q) is described using Aqua Atmospheric Infrared Sounder (AIRS) sounding profiles. The AIRS Team Version 6 (V6), Version 7 (V7), and Community Long‐term Infrared Microwave Combined Atmospheric Product System (CLIMCAPS) retrieval algorithms are compared to European Centre for Medium‐Range Weather Forecasts Reanalysis v5 (ERA5) and Modern‐Era Retrospective analysis for Research and Applications, Version 2 (MERRA‐2) reanalyses. Large‐scale T exponents derived between 600 and 1,200 km (𝛼L) show close agreement between V6, V7, and CLIMCAPS algorithms. However, small‐scale q exponents derived between 150 and 400 km (𝛼S) are in poor agreement, including an unrealistically steep 𝛼S in the planetary boundary layer (PBL) in the V7 and CLIMCAPS algorithms that is caused by a combination of algorithm damping and overconstraint by the first guess fields. ERA5 and MERRA‐2 reanalyses have large values of 𝛼L and 𝛼S for both T and q that indicate reduced small‐scale variability in the reanalysis fields. Differences in 𝛼S between free‐running MERRA‐2 AMIP and MERRA‐2 are negligible, implying that suppressed small‐scale variability in reanalyses is imposed by the background model and not caused by the data assimilation process. AIRS has positively skewed T distributions in the tropical‐free troposphere that is consistent with positively buoyant air parcels in convection, and negative skewness in the PBL that is related to the existence of cold pools, behavior that is mostly absent in ERA5 and MERRA‐2. AIRS provides a global view of scale‐dependent variance and skewness that is useful for subgrid parameterization development and validation of weather and climate prediction models.
Detrital Garnet Geochronology by In Situ U‐Pb and Lu‐Hf Analysis: A Case Study From the European Alps
Authors: Mark Chris , O’Sullivan Gary , Glorie Stijn , Simpson Alexander , Andò Sergio , Barbarano Marta , Stutenbecker Laura , Daly J. Stephen , Gilbert Sarah 
Published: September 2023

AbstractDetrital geochronology employing the widely‐used zircon U‐Pb proxy is biased toward igneous events and metamorphic anatexis; additionally, zircon is highly refractory and frequently polycyclic. Garnet, a rock‐forming and thus commonly occurring mineral, is predominantly metamorphic and much less refractory. Here, we report in situ U‐Pb and Lu‐Hf ages from detrital garnet hosted in ancient and modern sediments of the European Alps. Both geochronometers are biased toward the most recent garnet‐crystallizing metamorphic event in the source area, with fewer inherited ages. This likely reflects efficient removal of inherited garnet during diagenesis and metamorphism, and is in contrast to detrital zircon, apatite, and rutile U‐Pb data, which largely record pre‐Alpine ages. Neither the U‐Pb nor Lu‐Hf system in garnet exhibits a relationship between age recovery and composition. However, the Lu‐Hf system in garnet yields significantly better age recovery than the U‐Pb system. Estimated initial 238U/206Pbc values at the time of crystallization are near unity, suggesting that garnet does not significantly partition U from Pb during crystallization, at least for the generally almandine‐rich garnets analyzed in this study. Hence, Lu‐Hf geochronology of detrital garnet offers an effective method to detect and date the most recent phase of mid‐grade metamorphism in sub‐anatectic source areas, in which detrital zircon U‐Pb analysis may be of less utility.
Baseline levels of miR-223-3p correlate with the effectiveness of electroconvulsive therapy in patients with major depression
Authors: Kaurani Lalit , Besse Matthias , Methfessel Isabel , Methi Aditi , Zhou Jiayin , Pradhan Ranjit , Burkhardt Susanne , Kranaster Laura , Sartorius Alexander , Habel Ute , Grözinger Michael , Fischer Andre , Wiltfang Jens , Zilles-Wegner David 
Published: September 2023

AbstractThere is a strong medical need to develop suitable biomarkers to improve the diagnosis and treatment of depression, particularly in predicting response to certain therapeutic approaches such as electroconvulsive therapy (ECT). MicroRNAs are small non-coding RNAs that have the ability to influence the transcriptome as well as proteostasis at the systems level. Here, we investigate the role of circulating microRNAs in depression and response prediction towards ECT. Of the 64 patients with treatment-resistant major depression (MDD) who received ECT treatment, 62.5% showed a response, defined as a reduction of ≥50% in the MADRS total score from baseline. We performed smallRNA sequencing in blood samples that were taken before the first ECT, after the first and the last ECT. The microRNAome was compared between responders and non-responders. Co-expression network analysis identified three significant microRNA modules with reverse correlation between ECT- responders and non-responders, that were amongst other biological processes linked to inflammation. A candidate microRNA, namely miR-223-3p was down-regulated in ECT responders when compared to non-responders at baseline. In line with data suggesting a role of miR-223-3p in inflammatory processes we observed higher expression levels of proinflammatory factors Il-6, Il-1b, Nlrp3 and Tnf-α in ECT responders at baseline when compared to non-responders. ROC analysis of confirmed the diagnostic power of miR-223-3p demarcating ECT-responders from non-responder subjects (AUC = 0.76, p = 0.0031). Our data suggest that miR-223-3p expression and related cytokine levels could serve as predictors of response to ECT in individuals with treatment-resistant depressive disorders.
Neuronal K+-Cl- cotransporter KCC2 as a promising drug target for epilepsy treatment
Authors: McMoneagle Erin , Zhou Jin , Zhang Shiyao , Huang Weixue , Josiah Sunday Solomon , Ding Ke , Wang Yun , Zhang Jinwei 
Published: September 2023

AbstractEpilepsy is a prevalent neurological disorder characterized by unprovoked seizures. γ-Aminobutyric acid (GABA) serves as the primary fast inhibitory neurotransmitter in the brain, and GABA binding to the GABAAreceptor (GABAAR) regulates Cl-and bicarbonate (HCO3-) influx or efflux through the channel pore, leading to GABAergic inhibition or excitation, respectively. The neuron-specific K+-Cl-cotransporter 2 (KCC2) is essential for maintaining a low intracellular Cl-concentration, ensuring GABAAR-mediated inhibition. Impaired KCC2 function results in GABAergic excitation associated with epileptic activity. Loss-of-function mutations and altered expression of KCC2 lead to elevated [Cl-]iand compromised synaptic inhibition, contributing to epilepsy pathogenesis in human patients. KCC2 antagonism studies demonstrate the necessity of limiting neuronal hyperexcitability within the brain, as reduced KCC2 functioning leads to seizure activity. Strategies focusing on direct (enhancing KCC2 activation) and indirect KCC2 modulation (altering KCC2 phosphorylation and transcription) have proven effective in attenuating seizure severity and exhibiting anti-convulsant properties. These findings highlight KCC2 as a promising therapeutic target for treating epilepsy. Recent advances in understanding KCC2 regulatory mechanisms, particularly via signaling pathways such as WNK, PKC, BDNF, and its receptor TrkB, have led to the discovery of novel small molecules that modulate KCC2. Inhibiting WNK kinase or utilizing newly discovered KCC2 agonists has demonstrated KCC2 activation and seizure attenuation in animal models. This review discusses the role of KCC2 in epilepsy and evaluates its potential as a drug target for epilepsy treatment by exploring various strategies to regulate KCC2 activity.
Identification of novel pathogenic roles of BLZF1/ATF6 in tumorigenesis of gastrointestinal stromal tumor showing Golgi-localized mutant KIT
Authors: Kwon Yujin , Kim Jiyoon , Cho Su-Yeon , Kang Yoon Jin , Lee Jongsoo , Kwon Jaeyoung , Rhee Hyungjin , Bauer Sebastian , Kim Hyung-Sik , Lee Esak , Kim Han Sang , Jung Jae Hung , Kim Hoguen , Kim Won Kyu 
Published: September 2023

AbstractGastrointestinal stromal tumors (GISTs) frequently show KIT mutations, accompanied by overexpression and aberrant localization of mutant KIT (MT-KIT). As previously established by multiple studies, including ours, we confirmed that MT-KIT initiates downstream signaling in the Golgi complex. Basic leucine zipper nuclear factor 1 (BLZF1) was identified as a novel MT-KIT-binding partner that tethers MT-KIT to the Golgi complex. Sustained activation of activated transcription factor 6 (ATF6), which belongs to the unfolded protein response (UPR) family, alleviates endoplasmic reticulum (ER) stress by upregulating chaperone expression, including heat shock protein 90 (HSP90), which assists in MT-KIT folding. BLZF1 knockdown and ATF6 inhibition suppressed both imatinib-sensitive and -resistant GIST in vitro. ATF6 inhibitors further showed potent antitumor effects in GIST xenografts, and the effect was enhanced with ER stress-inducing drugs. ATF6 activation was frequently observed in 67% of patients with GIST (n = 42), and was significantly associated with poorer relapse-free survival (P = 0.033). Overall, GIST bypasses ER quality control (QC) and ER stress-mediated cell death via UPR activation and uses the QC-free Golgi to initiate signaling.
Intranasal delivery of NGF rescues hearing impairment in aged SAMP8 mice
Authors: Castelli Vanessa , d’Angelo Michele , Zazzeroni Francesca , Vecchiotti Davide , Alesse Edoardo , Capece Daria , Brandolini Laura , Cattani Franca , Aramini Andrea , Allegretti Marcello , Cimini Annamaria 
Published: September 2023

AbstractHearing loss impacts the quality of life and affects communication resulting in social isolation and reduced well-being. Despite its impact on society and economy, no therapies for age-related hearing loss are available so far. Loss of mechanosensory hair cells of the cochlea is a common event of hearing loss in humans. Studies performed in birds demonstrating that they can be replaced following the proliferation and transdifferentiation of supporting cells, strongly pointed out on HCs regeneration as the main focus of research aimed at hearing regeneration. Neurotrophins are growth factors involved in neuronal survival, development, differentiation, and plasticity. NGF has been involved in the interplay between auditory receptors and efferent innervation in the cochlea during development. During embryo development, both NGF and its receptors are highly expressed in the inner ears. It has been reported that NGF is implicated in the differentiation of auditory gangliar and hair cells. Thus, it has been proposed that NGF administration can decrease neuronal damage and prevent hearing loss. The main obstacle to the development of hearing impairment therapy is that efficient means of delivery for selected drugs to the cochlea are missing. Herein, in this study NGF was administered by the intranasal route. The first part of the study was focused on a biodistribution study, which showed the effective delivery in the cochlea; while the second part was focused on analyzing the potential therapeutic effect of NGF in senescence-accelerated prone strain 8 mice. Interestingly, intranasal administration of NGF resulted protective in counteracting hearing impairment in SAMP8 mice, ameliorating hearing performances (analyzed by auditory brainstem responses and distortion product otoacoustic emission) and hair cells morphology (analyzed by microscopy analysis). The results obtained were encouraging indicating that the neurotrophin NGF was efficiently delivered to the inner ear and that it was effective in counteracting hearing loss.
Mixed effects of a national protected area network on terrestrial and freshwater biodiversity
Authors: Santangeli Andrea , Weigel Benjamin , Antão Laura H. , Kaarlejärvi Elina , Hällfors Maria , Lehikoinen Aleksi , Lindén Andreas , Salemaa Maija , Tonteri Tiina , Merilä Päivi , Vuorio Kristiina , Ovaskainen Otso , Vanhatalo Jarno , Roslin Tomas , Saastamoinen Marjo 
Published: September 2023

AbstractProtected areas are considered fundamental to counter biodiversity loss. However, evidence for their effectiveness in averting local extinctions remains scarce and taxonomically biased. We employ a robust counterfactual multi-taxon approach to compare occupancy patterns of 638 species, including birds (150), mammals (23), plants (39) and phytoplankton (426) between protected and unprotected sites across four decades in Finland. We find mixed impacts of protected areas, with only a small proportion of species explicitly benefiting from protection—mainly through slower rates of decline inside protected areas. The benefits of protection are enhanced for larger protected areas and are traceable to when the sites were protected, but are mostly unrelated to species conservation status or traits (size, climatic niche and threat status). Our results suggest that the current protected area network can partly contribute to slow down declines in occupancy rates, but alone will not suffice to halt the biodiversity crisis. Efforts aimed at improving coverage, connectivity and management will be key to enhance the effectiveness of protected areas towards bending the curve of biodiversity loss.
Proteogenomics of different urothelial bladder cancer stages reveals distinct molecular features for papillary cancer and carcinoma in situ
Authors: Yao Zhenmei , Xu Ning , Shang Guoguo , Wang Haixing , Tao Hui , Wang Yunzhi , Qin Zhaoyu , Tan Subei , Feng Jinwen , Zhu Jiajun , Ma Fahan , Tian Sha , Zhang Qiao , Qu Yuanyuan , Hou Jun , Guo Jianming , Zhao Jianyuan , Hou Yingyong , Ding Chen 
Published: September 2023

AbstractThe progression of urothelial bladder cancer (UC) is a complicated multi-step process. We perform a comprehensive multi-omics analysis of 448 samples from 190 UC patients, covering the whole spectrum of disease stages and grades. Proteogenomic integration analysis indicates the mutations of HRAS regulated mTOR signaling to form urothelial papilloma rather than papillary urothelial cancer (PUC). DNA damage is a key signaling pathway in the progression of carcinoma in situ (CIS) and related to APOBEC signature. Glucolipid metabolism increase and lower immune cell infiltration are associated with PUC compared to CIS. Proteomic analysis distinguishes the origins of invasive tumors (PUC-derived and CIS-derived), related to distinct clinical prognosis and molecular features. Additionally, loss of RBPMS, associated with CIS-derived tumors, is validated to increase the activity of AP-1 and promote metastasis. This study reveals the characteristics of two distinct branches (PUC and CIS) of UC progression and may eventually benefit clinical practice.
Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles
Authors: Sitarska Ewa , Almeida Silvia Dias , Beckwith Marianne Sandvold , Stopp Julian , Czuchnowski Jakub , Siggel Marc , Roessner Rita , Tschanz Aline , Ejsing Christer , Schwab Yannick , Kosinski Jan , Sixt Michael , Kreshuk Anna , Erzberger Anna , Diz-Muñoz Alba 
Published: September 2023

AbstractTo navigate through diverse tissues, migrating cells must balance persistent self-propelled motion with adaptive behaviors to circumvent obstacles. We identify a curvature-sensing mechanism underlying obstacle evasion in immune-like cells. Specifically, we propose that actin polymerization at the advancing edge of migrating cells is inhibited by the curvature-sensitive BAR domain protein Snx33 in regions with inward plasma membrane curvature. The genetic perturbation of this machinery reduces the cells’ capacity to evade obstructions combined with faster and more persistent cell migration in obstacle-free environments. Our results show how cells can read out their surface topography and utilize actin and plasma membrane biophysics to interpret their environment, allowing them to adaptively decide if they should move ahead or turn away. On the basis of our findings, we propose that the natural diversity of BAR domain proteins may allow cells to tune their curvature sensing machinery to match the shape characteristics in their environment.
Facile hermetic TEM grid preparation for molecular imaging of hydrated biological samples at room temperature
Authors: Kong Lingli , Liu Jianfang , Zhang Meng , Lu Zhuoyang , Xue Han , Ren Amy , Liu Jiankang , Li Jinping , Ling Wai Li , Ren Gang 
Published: September 2023

AbstractAlthough structures of vitrified supramolecular complexes have been determined at near-atomic resolution, elucidating in situ molecular structure in living cells remains a challenge. Here, we report a straightforward liquid cell technique, originally developed for real-time visualization of dynamics at a liquid-gas interface using transmission electron microscopy, to image wet biological samples. Due to the scattering effects from the liquid phase, the micrographs display an amplitude contrast comparable to that observed in negatively stained samples. We succeed in resolving subunits within the protein complex GroEL imaged in a buffer solution at room temperature. Additionally, we capture various stages of virus cell entry, a process for which only sparse structural data exists due to their transient nature. To scrutinize the morphological details further, we used individual particle electron tomography for 3D reconstruction of each virus. These findings showcase this approach potential as an efficient, cost-effective complement to other microscopy technique in addressing biological questions at the molecular level.
De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8
Authors: Roy Anindya , Shi Lei , Chang Ashley , Dong Xianchi , Fernandez Andres , Kraft John C. , Li Jing , Le Viet Q. , Winegar Rebecca Viazzo , Cherf Gerald Maxwell , Slocum Dean , Poulson P. Daniel , Casper Garrett E. , Vallecillo-Zúniga Mary L. , Valdoz Jonard Corpuz , Miranda Marcos C. , Bai Hua , Kipnis Yakov , Olshefsky Audrey , Priya Tanu , Carter Lauren , Ravichandran Rashmi , Chow Cameron M. , Johnson Max R. , Cheng Suna , Smith McKaela , Overed-Sayer Catherine , Finch Donna K. , Lowe David , Bera Asim K. , Matute-Bello Gustavo , Birkland Timothy P. , DiMaio Frank , Raghu Ganesh , Cochran Jennifer R. , Stewart Lance J. , Campbell Melody G. , Van Ry Pam M. , Springer Timothy , Baker David 
Published: September 2023

AbstractThe RGD (Arg-Gly-Asp)-binding integrins αvβ6 and αvβ8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between homologous αvβ6 and αvβ8 and other RGD integrins, stabilize specific conformational states, and have high thermal stability could have considerable therapeutic utility. Existing small molecule and antibody inhibitors do not have all these properties, and hence new approaches are needed. Here we describe a generalized method for computationally designing RGD-containing miniproteins selective for a single RGD integrin heterodimer and conformational state. We design hyperstable, selective αvβ6 and αvβ8 inhibitors that bind with picomolar affinity. CryoEM structures of the designed inhibitor-integrin complexes are very close to the computational design models, and show that the inhibitors stabilize specific conformational states of the αvβ6 and the αvβ8 integrins. In a lung fibrosis mouse model, the αvβ6 inhibitor potently reduced fibrotic burden and improved overall lung mechanics, demonstrating the therapeutic potential of de novo designed integrin binding proteins with high selectivity.