bluuebunny/crossref_metadata_2025 huggingface dataset:
Gestures in Slow Motion: On Making Use of Video Art in Phenomenology
Authors: Bejinariu Alexandru
Published: January 2024

This article deals with the relevance of video art and filmic techniques for the phenomenological method by thematizing how slow-motion scenes can be used in the analysis of gestures. Drawing on Edmund Husserl's theory of image consciousness, I argue that while, for the empirical researcher, slow motion is a non-analogizing moment that helps the researcher observe the positional image subject, for the phenomenologist, it depicts a different, neutralized image subject that serves as an initial example. This approach leads to further insights revealing a specific form of disappointment of our passively constituted patterns of anticipation concerning the pace of gestural interaction.
An Overview of Israel's ‘Judicial Overhaul’: Small Parts of a Big Populist Picture
Authors: Navot Suzie
Published: January 2024

In the comparative constitutional field relating to backsliding democracies, it is difficult to find an example of a single constitutional event that undermines the basic principles of democracy. Democracies die in a slow and gradual process. Each of the laws passed is not in itself fatal for democracy but when the measures are examined together, cumulatively, the whole is greater than the sum of its parts. It is the big picture, the whole series of legal moves, that brings about a fundamental change in the state's regime until it is no longer a liberal democracy. In these situations of gradual erosion there is no single law that can reveal the magnitude of the change inherent in it. To understand the risk, it is therefore necessary to refer to its overall institutional context. The proposed reform in Israel may result in serious harm to the principle of separation of powers. Moreover, given the importance of imposing limits on governmental power as a tool for protecting human rights and the ‘rules of the game’ in democratic regimes, the reform would seriously harm the protection afforded to these rights and principles, and constitute a clear and present danger to Israel's liberal democracy.
Kinematic calibration and feedforward control of a heavy-load manipulator using parameters optimization by an ant colony algorithm
Authors: Wang Xinpei , Xie Lingbo , Jiang Mian , He Kuanfang , Chen Yong
Published: January 2024

Most of the currently available three-degree-of-freedom manipulators are light load and cannot achieve full continuous rotation; given this, we designed a heavy-load manipulator that achieves unrestricted and continuous rotation. Due to manufacturing and assembly errors, parameter deviations between the real manipulator and its underlying theoretical model were unavoidable. Because of the lack of high-precision, high-frequency, and real-time closed-loop detection methods, we proposed a type of kinematics calibration of parameterized ant colony optimization and feedforward control methods. This was done to achieve high-precision motion control. First, an error model combining structural parameters and joint output angles was established, and the global sensitivity of each error source was analyzed to distinguish both primary and secondary sources. Based on the measured data of a laser tracker, the ant colony optimization was then used to identify six error sources. This resulted in both link length and joint driving errors of the designed manipulator. As it is a type of systematic error, the rounding error of the theoretical trajectory was carefully analyzed, and feedforward control methods with different coefficients were designed to further improve positioning accuracy based on the kinematic calibration. Experimental results showed that the proposed kinematic calibration and feedforward control methods achieved relatively precise motion control for the designed manipulator.
Rural–urban variation in COVID-19 vaccination uptake in Aotearoa New Zealand: Examining the national roll-out
Authors: Liepins Talis , Davie Gabrielle , Miller Rory , Whitehead Jesse , De Graaf Brandon , Clay Lynne , Crengle Sue , Nixon Garry
Published: January 2024

This study aimed to understand rural–urban differences in the uptake of COVID-19 vaccinations during the peak period of the national vaccination roll-out in Aotearoa New Zealand (NZ). Using a linked national dataset of health service users aged 12+ years and COVID-19 immunization records, age-standardized rates of vaccination uptake were calculated at fortnightly intervals, between June and December 2021, by rurality, ethnicity, and region. Rate ratios were calculated for each rurality category with the most urban areas (U1) used as the reference. Overall, rural vaccination rates lagged behind urban rates, despite early rapid rural uptake. By December 2021, a rural–urban gradient developed, with age-standardized coverage for R3 areas (most rural) at 77%, R2 81%, R1 83%, U2 85%, and U1 (most urban) 89%. Age-based assessments illustrate the rural–urban vaccination uptake gap was widest for those aged 12–44 years, with older people (65+) having broadly consistent levels of uptake regardless of rurality. Variations from national trends are observable by ethnicity. Early in the roll-out, Indigenous Māori residing in R3 areas had a higher uptake than Māori in U1, and Pacific peoples in R1 had a higher uptake than those in U1. The extent of differences in rural–urban vaccine uptake also varied by region.
Comparative study of intracytoplasmic sperm injection using the traditional holding and the oocyte-holding pipette without aspiration
Authors: Vergara Francisco , Fernández Javier , Pedrosa Concepción , Muñoz María , Jerez Elvira , Varón Mireia , Moyano Carmen , Yoldi Alberto , Ponce Jordi
Published: January 2024

Despite the high level of standardization of the intracytoplasmic sperm injection (ICSI) technique, there are some aspects that deserve special attention and should still be improved. The major drawback of the technique is its invasiveness, as during cytoplasmic aspiration different structures of the oocyte may be lost or damaged. This is partly because the microtools used in ICSI were not specially designed for assisted reproduction but for other medical–biological disciplines. In view of the above caveats, the aim of the study was to compare the results of ICSI with the traditional oocyte-holding pipette and the oocyte-holding pipette without aspiration (PiWA). In total, 155 patients and 1037 oocytes were included in the study. In each ICSI cycle, half of the oocytes were microinjected using a traditional holding pipette and the other half using a PiWA. In result, the PiWA technique produced a significant increase in the fertilization rate: 88.12% (95%CI: 84.62–90.92%); holding pipette: 73.33% (95%CI: 68.72–77.49%). Also, it produced a significant decrease in the embryo degeneration rate compared with the traditional holding pipette [PiWA: 2.07% (95%CI: 1.11–3.8%); holding pipette: 4.51% (95%CI: 3.06–6.59%)]. Pregnancy rate depended on the holding technique used, both in single embryo transfers (n = 59; χ2 = 4.608; P-value = 0.032) and double embryo transfers (n = 156; χ2 = 4.344; P-value = 0.037); with PiWA presenting a significantly higher pregnancy rate than the traditional holding technique. Based on current evidence and the present results, improvements should focus on decreasing the invasiveness of the microinjection itself by minimizing or avoiding aspiration and cytoplasmic disorganization, as is successfully achieved with PiWA.
Association of European Paediatric and Congenital Cardiology practical recommendations for surveillance and prevention of cardiac disease in childhood cancer survivors: the importance of physical activity and lifestyle changes From the Association of European Paediatric and Congenital Cardiology Working Group Sports Cardiology, Physical Activity and Prevention, Working Group Adult Congenital Heart Disease, Working Group Imaging and Working Group Heart Failure
Authors: Kesting Sabine , Giordano Ugo , Weil Jochen , McMahon Colin J. , Albert Dimpna C. , Berger Claire , Budts Werner , Fritsch Peter , Hidvégi Erzsébet V. , Oberhoffer-Fritz Renate , Milano Giuseppe M. , Wacker-Gußmann Annette , Herceg-Čavrak Vesna
Published: January 2024

Background:

Childhood cancer survivors are at increased risk of developing cardiovascular diseases, presenting as the main causes of morbidity and mortality within this group. Besides the usual primary and secondary prevention in combination with screening during follow-up, the modifiable lifestyle factors of physical activity, nutrition, and body weight have not yet gained enough attention regarding potential cardiovascular risk reduction.

Objective:

These practical recommendations aim to provide summarised information and practical implications to paediatricians and health professionals treating childhood cancer survivors to reduce the risk of cardiovascular late effects.

Methods:

The content derives from either published guidelines or expert opinions from Association of European Paediatric and Congenital Cardiology working groups and is in accordance with current state-of-the-art.

Results:

All usual methods of prevention and screening regarding the risk, monitoring, and treatment of occurring cardiovascular diseases are summarised. Additionally, modifiable lifestyle factors are explained, and clear practical implications are named.

Conclusion:

Modifiable lifestyle factors should definitely be considered as a cost-effective and complementary approach to already implemented follow-up care programs in cardio-oncology, which can be actively addressed by the survivors themselves. However, treating physicians are strongly encouraged to support survivors to develop and maintain a healthy lifestyle, including physical activity as one of the major influencing factors. This article summarises relevant background information and provides specific practical recommendations on how to advise survivors to increase their level of physical activity.
Assessing association of household diet diversity with mother’s time use on productive and reproductive activities: a case for gender sensitive social safety nets
Authors: Chaturvedi Surabhi , Swaminathan Sumathi , Makkar Sanchit , John Anjaly Teresa , Thomas Tinku
Published: January 2024

Objective:

In South Asia, while women make substantial economic contributions through their participation in agricultural sector, these contributions are undercounted as most of their work is underpaid or unpaid. This paper examines how mothers allocate their time to productive and reproductive activities and its association with a household’s ability to achieve high household diet diversity score.

Design:

The analysis uses data on household consumption and expenditure including food during the kharif (June to October) season (seeds are sown) and a modular time-use survey.

Setting:

Two districts of rural Bihar, India.

Participants:

Mothers with children less than 5 years of age and supported by the head of the household from 2026 households.

Results:

The estimates indicate that the high household diet diversity (High HDDS ≥ 10) is associated with greater time spent in reproductive activities by all women (OR = 1·12, 95 % CI: 1·06, 1·18). However, with increasing time spent in productive activities by the women the odds of achieving ‘High HDDS’ reduced (OR = 0·83, 95 % CI: 0·77, 0·89) in adjusted logistic regression analysis.

Conclusion:

The findings highlight propensity to achieve ‘High HDDS’ in Bihar increased with mothers allocating time towards reproductive activities, while it had an opposing effect with mothers allocating time on productive activities. Our study highlights that the policies that encourage women’s participation in agriculture or livestock should acknowledge the unpaid nature of some of the productive activities and design programs to improve economic agency of women to actuate the true potential of agriculture-nutrition pathways.
Modeling and management of cyber risk: a cross-disciplinary review
Authors: He Rong , Jin Zhuo , Li Johnny Siu-Hang
Published: January 2024

This paper provides a review of cyber risk research accomplished in different disciplines, with a primary goal to aid researchers in the field of insurance and actuarial science in identifying potential research gaps as well as leveraging useful models and techniques that have been considered in the literature. We highlight the recent advancements in cyber risk prediction, modeling, management, and insurance achieved in different domains including computer engineering, actuarial science, and business studies. The surveyed works are classified according to their respective modeling approaches, allowing readers to more easily compare the technical aspects of the surveyed works and spot out research gaps based on the research tools of their liking. We conclude this paper with a summary of possible research directions that are identified from the review.
Changing Climate Threatens Irrigation Benefits of Maize Gross Primary Productivity in China
Authors: Liao Dehai , Niu Jun , Ciais Philippe , Du Taisheng , Zhang Baozhong , Kang Shaozhong
Published: January 2024

Intensive irrigation has been proven to profoundly impact climate through the surface energy budget. However, the impacts of irrigation and climate interactions on gross primary productivity (GPP) in maize cultivated areas remain uncertain. Here we quantified the irrigation effects on maize GPP (∆GPP) across China by combining a land surface model and a light‐use efficiency model and using satellite‐based irrigation water use. We show that irrigation significantly contributed to an increase in maize GPP by an average of 430 gC · m−2 · yr−1, equivalent to 28% of the irrigated maize GPP in China. These benefits (∆GPP) were attributed to irrigation effects (water supply, surface cooling) and climate interactions based on a machine learning framework (eXtreme Gradient Boosting model‐SHapley Additive exPlanations). Irrigation water supply and surface cooling explained 54% ± 19% and 23% ± 20% of ∆GPP respectively, the rest being due to strong climate interactions with irrigation through water and energy balance. Assuming business‐as‐usual irrigation levels, changing climate both increases and decreases ΔGPP over different regions, driven primarily by temperature changes. The irrigation benefits in those areas under heat stress are greatly threatened due to changing climate. The roles of climate change on ∆GPP are reversed from beneficial to detrimental in the North China Plain, dominated by different warming levels of future scenarios. Our analysis provides new insights into assessing irrigation potential with the climate interactions and future irrigation priority regions.
Hamiltonian Monte Carlo to Characterize Induced Earthquakes: Application to a ML 3.4 Event in the Groningen Gas Field and the Role of Prior
Authors: Masfara La Ode Marzujriban , Weemstra Cornelis
Published: January 2024

The Hamiltonian Monte Carlo algorithm is known to be highly efficient when sampling high‐dimensional model spaces due to Hamilton's equations guiding the sampling process. For weakly non‐linear problems, linearizing the forward problem enhances this efficiency. This study integrates this linearization with geological prior knowledge for optimal results. We test this approach to estimate the source parameters of a 3.4 magnitude induced event that originated in the Groningen gas field in 2019. The source parameters are the event's centroid (three components), its moment tensor (six components), and its origin time. In terms of prior knowledge, we tested two sets of centroid priors. The first set exploits the known fault geometry of the Groningen gas field, whereas the second set is generated by placing initial centroid priors on a uniform horizontal grid at a depth of 3 km (the approximate depth of the gas reservoir). As for the forward problem linearization, we use an approach in which the linearization is run iteratively in tandem with updates of the centroid prior. We demonstrate that, in the absence of a sufficiently accurate initial centroid prior, the linearization of the forward model necessitates multiple initial centroid priors. Eventually, both prior sets yield similar posteriors. Most importantly, however, they agree with the geological knowledge of the area: the posterior peaks for model vectors containing a centroid near a major fault and a moment tensor that corresponds to normal faulting along a plane with a strike almost aligning with that of the major fault.
Comment on “Five Decades of Observed Daily Precipitation Reveal Longer and More Variable Drought Events Across Much of the Western United States”
Authors: Paciorek C. J. , Wehner M. F.
Published: January 2024

Changes in precipitation patterns with climate change could have important impacts on human and natural systems. Zhang et al. (2021, https://doi.org/10.1029/2020gl092293) report trends in daily precipitation patterns over the last five decades in the western United States, focusing on meteorological drought. They report that dry intervals (calculated at the annual or seasonal level) have increased across much of the southwestern U.S., with statistical assessment suggesting the results are statistically robust. However, Zhang et al. (2021, https://doi.org/10.1029/2020gl092293) preprocess their annual (or seasonal) averages to compute 5‐year moving window averages before using established statistical techniques for trend analysis that assume independence about some fixed trend. Here we show that the moving window preprocessing violates that independence assumption and inflates the statistical significance of their trend estimates. This raises questions about the robustness of their results. We conclude by discussing the difficulty of adjusting for spatial structure when assessing time trends in a regional context.
EBSD Analysis of Iron‐Nickel Metal in L Type Ordinary Chondrites: 1. The Microstructural Shock Signatures
Authors: Luo Yexin , Chen Hongyi , Beard Sky , Zeng Xiaojia , Hu Sen , Du Zhimao , Jin Lei , Liu Jiahui , Li Shaolin , Zhang Xiaoping
Published: January 2024

The diverse microstructures of Fe‐Ni metal in 10 L groups ordinary chondrites that experienced progressive shock alteration were investigated using the electron backscattered diffraction technique. Through a combination of metallography and a silicate‐based shock classification scheme, we established the shock metamorphic features of metal phases corresponding to particular impact stages. In weakly shocked chondrites (S1–S2), the interlaced Neumann bands occur in polycrystalline kamacite, resulting from multiple small impact events on its parent body, and the internal crystallographic orientation difference of each kamacite monocrystal exceeds 5°. In moderately shocked samples (S2–S4), partial austenitization of metal occurs, accompanied by the emergence of net plessite. In strongly shocked samples (S4–S6), the metal has undergone complete austenitization and transformed into a homogenous fcc phase. In subsequent different cooling processes, polycrystalline kamacite with consistent internal crystallographic orientation, martensite, pearlitic plessite, duplex plessite, and acicular plessite form and finally appear in L group chondrites. This study demonstrates the significant utility of the microstructure of metal phases as a valuable tool for both the shock classification of L chondrites and the determination of shock metamorphism stages in iron meteorites.
Patterns of Alluviation in Mixed Bedrock‐Alluvial Channels: 1. Numerical Model
Authors: Cho Jongseok , Nelson Peter A.
Published: January 2024

Mixed bedrock‐alluvial rivers can exhibit partial alluvial cover, which plays an important role in controlling bedrock erosion rates and landscape evolution. However, numerical morphodynamic models are generally unable to predict quasi‐steady persistent patches of depositional alluvial features under conditions where the sediment supply is less than the sediment transport capacity of the channel. Hence, we present a new two‐dimensional depth‐averaged morphodynamic model that can be applied to both fully alluvial and mixed bedrock‐alluvial channels, and we use the model to gain insight into the mechanisms responsible for the development of sediment patches and patterns of bedrock alluviation. The model computes hydrodynamics, sediment transport, and bed evolution using a roughness partitioning that accounts for differential roughness of sediment and bedrock, roughness due to sediment transport, and form drag. The model successfully replicates observations of bar development and migration from a fully alluvial flume experiment, and it models persistent sediment patches observed in a mixed bedrock‐alluvial flume experiment. Numerical experiments in which the form drag, sediment transport roughness, and bedform stress correction were neglected did not successfully reproduce the observed persistent sediment cover in the mixed bedrock‐alluvial case, suggesting that accounting for these different roughness components is critical to successfully model sediment dynamics in bedrock channels.
Vitamin D ameliorates age-induced nonalcoholic fatty liver disease by increasing the mitochondrial contact site and cristae organizing system (MICOS) 60 level
Authors: Kim Gyu Hee , Jeong Hyeon-Ju , Lee Yoo Jeong , Park Hyeon Young , Koo Soo Kyung , Lim Joo Hyun
Published: January 2024

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease. Despite intensive research, considerable information on NAFLD development remains elusive. In this study, we examined the effects of vitamin D on age-induced NAFLD, especially in connection with mitochondrial abnormalities. We observed the prevention of NAFLD in 22-month-old C57BL/6 mice fed a vitamin D3-supplemented (20,000 IU/kg) diet compared with mice fed a control (1000 IU/kg) diet. We evaluated whether vitamin D3 supplementation enhanced mitochondrial functions. We found that the level of mitochondrial contact site and cristae organizing system (MICOS) 60 (Mic60) level was reduced in aged mice, and this reduction was specifically restored by vitamin D3. In addition, depletion of Immt, the human gene encoding the Mic60 protein, induced changes in gene expression patterns that led to fat accumulation in both HepG2 and primary hepatocytes, and these alterations were effectively prevented by vitamin D3. In addition, silencing of the vitamin D receptor (VDR) decreased the Mic60 levels, which were recovered by vitamin D treatment. To assess whether VDR directly regulates Mic60 levels, we performed chromatin immunoprecipitation and reporter gene analysis. We discovered that VDR directly binds to the Immt 5’ promoter region spanning positions −3157 to −2323 and thereby upregulates Mic60. Our study provides the first demonstration that a reduction in Mic60 levels due to aging may be one of the mechanisms underlying the development of aging-associated NAFLD. In addition, vitamin D3 could positively regulate Mic60 expression, and this may be one of the important mechanisms by which vitamin D could ameliorate age-induced NAFLD.
Significance of chitinase-3-like protein 1 in the pathogenesis of inflammatory diseases and cancer
Authors: Yu Ji Eun , Yeo In Jun , Han Sang-Bae , Yun Jaesuk , Kim Bongcheol , Yong Yoon Ji , Lim Young-soo , Kim Tae Hun , Son Dong Ju , Hong Jin Tae
Published: January 2024

Chitinase-3-like protein 1 (CHI3L1) is a secreted glycoprotein that mediates inflammation, macrophage polarization, apoptosis, and carcinogenesis. The expression of CHI3L1 is strongly upregulated by various inflammatory and immunological diseases, including several cancers, Alzheimer’s disease, and atherosclerosis. Several studies have shown that CHI3L1 can be considered as a marker of disease diagnosis, prognosis, disease activity, and severity. In addition, the proinflammatory action of CHI3L1 may be mediated via responses to various proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and interferon-γ. Therefore, CHI3L1 may contribute to a vast array of inflammatory diseases. However, its pathophysiological and pharmacological roles in the development of inflammatory diseases remain unclear. In this article, we review recent findings regarding the roles of CHI3L1 in the development of inflammatory diseases and suggest therapeutic approaches that target CHI3L1.
Multifaceted roles of CCAR family proteins in the DNA damage response and cancer
Authors: Lugano D. , Barrett L. , Westerheide S. D. , Kee Y.
Published: January 2024

The cell cycle apoptosis regulator (CCAR) family of proteins consists of two proteins, CCAR1 and CCAR2, that play a variety of roles in cellular physiology and pathology. These multidomain proteins are able to perform multiple interactions and functions, playing roles in processes such as stress responses, metabolism, and the DNA damage response. The evolutionary conservation of CCAR family proteins allows their study in model organisms such as Caenorhabditis elegans, where a role for CCAR in aging was revealed. This review particularly highlights the multifaceted roles of CCAR family proteins and their implications in the DNA damage response and in cancer biology.
Association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Egyptian children and adolescents
Authors: Boraey Naglaa F. , Bebars Marwa A. , Wahba Ali A. , Abd El Lateef Hanan M. , Attia Mohamed Atif , Elsayed Ahmed H. , Rashed Khalid A. , Sorour Ehab I. , Ahmed Mohamed F. , Abd-Elrehim Ghada A. B. , Soliman Attia A. , Shehab Mohamed M. M. , Elhindawy Eman M. , Ibraheem Ahmed A. A. , Shehata Hassan , Yousif Yousif M. , Hashem Mustafa I. A. , Ahmed Amani A. , Emam Ahmed A. , Gameil Dalia M. , Abdelhady Eman M. , Abdelkhalek Khalil , Morsi Walaa E. M. A. , Selim Dalia M. , Razek Suzan A. , Ashraf Bassem , Saleh Ahmed S. E. , Eltrawy Heba H. , Alanwar Mohamed I. , Fouad Rania A. , Omar Walaa E. , Nabil Rehab M. , Abdelhamed Mohamed R. , Ibrahim Mona Yousri , Malek Mai M. , Afify Mona R. , Alharbi Mohanned T. , Nagshabandi Mohammed K. , Tarabulsi Muyassar K. , Qashqary Mohammed Esmail , Almoraie Laila M. , Salem Hanan F. , Rashad Manal M. , El-Gaaly Sonya A. A. , El- Deeb Nahawand A. , Abdallah Amany M. , Fakhreldin Ahmed R. , Hassouba Mohamed , Massoud Yasmine M. , Attaya Mona S. M. , Haridi Mohammed K.
Published: January 2024

Background

Given the sparse data on the renin-angiotensin system (RAS) and its biological effector molecules ACE1 and ACE2 in pediatric COVID-19 cases, we investigated whether the ACE1 insertion/deletion (I/D) polymorphism could be a genetic marker for susceptibility to COVID-19 in Egyptian children and adolescents.

Methods

This was a case-control study included four hundred sixty patients diagnosed with COVID-19, and 460 well-matched healthy control children and adolescents. The I/D polymorphism (rs1799752) in the ACE1 gene was genotyped by polymerase chain reaction (PCR), meanwhile the ACE serum concentrations were assessed by ELISA.

Results

The ACE1 D/D genotype and Deletion allele were significantly more represented in patients with COVID-19 compared to the control group (55% vs. 28%; OR = 2.4; [95% CI: 1.46–3.95]; for the DD genotype; P = 0.002) and (68% vs. 52.5%; OR: 1.93; [95% CI: 1.49–2.5] for the D allele; P = 0.032). The presence of ACE1 D/D genotype was an independent risk factor for severe COVID-19 among studied patients (adjusted OR: 2.6; [95% CI: 1.6–9.7]; P < 0.001.

Conclusions

The ACE1 insertion/deletion polymorphism may confer susceptibility to SARS-CoV-2 infection in Egyptian children and adolescents.

Impact

Recent studies suggested a crucial role of renin-angiotensin system and its biological effector molecules ACE1 and ACE2 in the pathogenesis and progression of COVID-19.

To our knowledge, ours is the first study to investigate the association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Caucasian children and adolescents.

The presence of the ACE1 D/D genotype or ACE1 Deletion allele may confer susceptibility to SARS-CoV-2 infection and being associated with higher ACE serum levels; may constitute independent risk factors for severe COVID-19.

The ACE1 I/D genotyping help design further clinical trials reconsidering RAS-pathway antagonists to achieve more efficient targeted therapies.
LncRNA ZNF674-AS1 drives cell growth and inhibits cisplatin-induced pyroptosis via up-regulating CA9 in neuroblastoma
Authors: Zhao Kunming , Wang Xinyi , Jin Yaqiong , Zhu Xiaoxiao , Zhou Tao , Yu Yongbo , Ji Xiaoying , Chang Yan , Luo Jiao , Ni Xin , Guo Yongli , Yu Dianke
Published: January 2024

Neuroblastoma (NB) is a challenging pediatric extracranial solid tumor characterized by a poor prognosis and resistance to chemotherapy. Identifying targets to enhance chemotherapy sensitivity in NB is of utmost importance. Increasing evidence implicates long noncoding RNAs (lncRNAs) play important roles in cancer, but their functional roles remain largely unexplored. Here, we analyzed our RNA sequencing data and identified the upregulated lncRNA ZNF674-AS1 in chemotherapy non-responsive NB patients. Elevated ZNF674-AS1 expression is associated with poor prognosis and high-risk NB. Importantly, targeting ZNF674-AS1 expression in NB cells suppressed tumor growth in vivo. Further functional studies have revealed that ZNF674-AS1 constrains cisplatin sensitivity by suppressing pyroptosis and promoting cell proliferation. Moreover, ZNF674-AS1 primarily relies on CA9 to fulfill its functions on cisplatin resistance. High CA9 levels were associated with high-risk NB and predicted poor patient outcomes. Mechanistically, ZNF674-AS1 directly interacted with the RNA binding protein IGF2BP3 to enhance the stability of CA9 mRNA by binding with CA9 transcript, leading to elevated CA9 expression. As a novel regulator of CA9, IGF2BP3 positively upregulated CA9 expression. Together, these results expand our understanding of the cancer-associated function of lncRNAs, highlighting the ZNF674-AS1/IGF2BP3/CA9 axis as a constituting regulatory mode in NB tumor growth and cisplatin resistance. These insights reveal the pivotal role of ZNF674-AS1 inhibition in recovering cisplatin sensitivity, thus providing potential therapeutic targets for NB treatment.
Targeting KCa3.1 channels to overcome erlotinib resistance in non-small cell lung cancer cells
Authors: Todesca Luca Matteo , Gerke Matthias , Bulk Emma Etmar , Bachmann Magdalena , Rudersdorf Alisa , Antonuzzo Lorenzo , Pillozzi Serena , Düfer Martina , Szabo Ildiko , Schwab Albrecht
Published: January 2024

Almost all non-small cell lung cancer (NSCLC) patients initially responding to EGFR tyrosine kinase inhibitors (TKIs) develop acquired resistance. Since KCa3.1 channels, expressed in mitochondria and plasma membrane, regulate similar behavioral traits of NSCLC cells as EGFR, we hypothesized that their blockade contributes to overcoming EGFR-TKI resistance. Meta-analysis of microarray data revealed that KCa3.1 channel expression in erlotinib-resistant NSCLC cells correlates with that of genes of integrin and apoptosis pathways. Using erlotinib-sensitive and –resistant NSCLC cells we monitored the role of mitochondrial KCa3.1 channels in integrin signaling by studying cell-matrix adhesion with single-cell force spectroscopy. Apoptosis was quantified with fluorescence-based assays. The function of mitochondrial KCa3.1 channels in these processes was assessed by measuring the mitochondrial membrane potential and by quantifying ROS production. Functional assays were supplemented by biochemical analyses. We show that KCa3.1 channel inhibition with senicapoc in erlotinib-resistant NSCLC cells increases cell adhesion by increasing β1-integrin expression, that in turn depends on mitochondrial ROS release. Increased adhesion impairs migration of NSCLC cells in a 3D matrix. At the same time, the senicapoc-dependent ROS production induces cytochrome C release and triggers apoptosis of erlotinib-resistant NSCLC cells. Thus, KCa3.1 channel blockade overcomes EGFR-TKI resistance by inhibiting NSCLC motility and inducing apoptosis.
Modulation of tumor microenvironment by targeting histone acetylation in bladder cancer
Authors: Nunes Sandra P. , Morales Lucia , Rubio Carolina , Munera-Maravilla Ester , Lodewijk Iris , Suárez-Cabrera Cristian , Martínez Victor G. , Pérez-Escavy Mercedes , Pérez-Crespo Miriam , Alonso Sánchez Miguel , Montesinos Esther , San José-Enériz Edurne , Agirre Xabier , Prósper Felipe , Pineda-Lucena Antonio , Henrique Rui , Dueñas Marta , Correia Margareta P. , Jerónimo Carmen , Paramio Jesús M.
Published: January 2024

Alterations in the epigenetic machinery in both tumor and immune cells contribute to bladder cancer (BC) development, constituting a promising target as an alternative therapeutic option. Here, we have explored the effects of a novel histone deacetylase (HDAC) inhibitor CM-1758, alone or in combination with immune checkpoint inhibitors (ICI) in BC. We determined the antitumor effects of CM-1758 in various BC cell lines together with the induction of broad transcriptional changes, with focus on the epigenetic regulation of PD-L1. Using an immunocompetent syngeneic mouse model of metastatic BC, we studied the effects of CM-1758 alone or in combination with anti-PD-L1 not only on tumor cells, but also in the tumor microenvironment. In vitro, we found that CM-1758 has cytotoxic and cytostatic effects either by inducing apoptosis or cell cycle arrest in BC cells at low micromolar levels. PD-L1 is epigenetically regulated by histone acetylation marks and is induced after treatment with CM-1758. We also observed that treatment with CM-1758 led to an important delay in tumor growth and a higher CD8 + T cell tumor infiltration. Moreover, anti-PD-L1 alone or in combination with CM-1758 reprogramed macrophage differentiation towards a M1-like polarization state and increased of pro-inflammatory cytokines systemically, yielding potential further antitumor effects. Our results suggest the possibility of combining HDAC inhibitors with immunotherapies for the management of advanced metastatic BC.
Combining stochastic resetting with Metadynamics to speed-up molecular dynamics simulations
Authors: Blumer Ofir , Reuveni Shlomi , Hirshberg Barak
Published: January 2024

Metadynamics is a powerful method to accelerate molecular dynamics simulations, but its efficiency critically depends on the identification of collective variables that capture the slow modes of the process. Unfortunately, collective variables are usually not known a priori and finding them can be very challenging. We recently presented a collective variables-free approach to enhanced sampling using stochastic resetting. Here, we combine the two methods, showing that it can lead to greater acceleration than either of them separately. We also demonstrate that resetting Metadynamics simulations performed with suboptimal collective variables can lead to speedups comparable with those obtained with optimal collective variables. Therefore, applying stochastic resetting can be an alternative to the challenging task of improving suboptimal collective variables, at almost no additional computational cost. Finally, we propose a method to extract unbiased mean first-passage times from Metadynamics simulations with resetting, resulting in an improved tradeoff between speedup and accuracy. This work enables combining stochastic resetting with other enhanced sampling methods to accelerate a broad range of molecular simulations.
The low-density lipoprotein receptor promotes infection of multiple encephalitic alphaviruses
Authors: Ma Hongming , Adams Lucas J. , Raju Saravanan , Sariol Alan , Kafai Natasha M. , Janova Hana , Klimstra William B. , Fremont Daved H. , Diamond Michael S.
Published: January 2024

Members of the low-density lipoprotein receptor (LDLR) family, including LDLRAD3, VLDLR, and ApoER2, were recently described as entry factors for different alphaviruses. However, based on studies with gene edited cells and knockout mice, blockade or abrogation of these receptors does not fully inhibit alphavirus infection, indicating the existence of additional uncharacterized entry factors. Here, we perform a CRISPR-Cas9 genome-wide loss-of-function screen in mouse neuronal cells with a chimeric alphavirus expressing the Eastern equine encephalitis virus (EEEV) structural proteins and identify LDLR as a candidate receptor. Expression of LDLR on the surface of neuronal or non-neuronal cells facilitates binding and infection of EEEV, Western equine encephalitis virus, and Semliki Forest virus. Domain mapping and binding studies reveal a low-affinity interaction with LA domain 3 (LA3) that can be enhanced by concatenation of LA3 repeats. Soluble decoy proteins with multiple LA3 repeats inhibit EEEV infection in cell culture and in mice. Our results establish LDLR as a low-affinity receptor for multiple alphaviruses and highlight a possible path for developing inhibitors that could mitigate infection and disease.
A link between repeating and non-repeating fast radio bursts through their energy distributions
Authors: Kirsten F. , Ould-Boukattine O. S. , Herrmann W. , Gawroński M. P. , Hessels J. W. T. , Lu W. , Snelders M. P. , Chawla P. , Yang J. , Blaauw R. , Nimmo K. , Puchalska W. , Wolak P. , van Ruiten R.
Published: January 2024

Fast radio bursts (FRBs) are extremely energetic, millisecond-duration radio flashes that reach Earth from extragalactic distances. Broadly speaking, FRBs can be classified as repeating or (apparently) non-repeating. It is still unclear, however, whether the two types share a common physical origin and differ only in their activity rate. Here we report on an observing campaign that targeted one hyperactive repeating source, FRB 20201124A, for more than 2,000 h using four 25–32 m class radio telescopes. We detected 46 high-energy bursts, many more than one would expect given previous observations of lower-energy bursts using larger radio telescopes. We find a high-energy burst distribution that resembles that of the non-repeating FRB population, suggesting that apparently non-repeating FRB sources may simply be the rarest bursts from repeating sources. Also, we discuss how FRB 20201124A contributes strongly to the all-sky FRB rate and how similar sources would be observable even at very high redshift.
African savanna raptors show evidence of widespread population collapse and a growing dependence on protected areas
Authors: Shaw Phil , Ogada Darcy , Dunn Leah , Buij Ralph , Amar Arjun , Garbett Rebecca , Herremans Marc , Virani Munir Z. , Kendall Corinne J. , Croes Barbara M. , Odino Martin , Kapila Shiv , Wairasho Peter , Rutz Christian , Botha André , Gallo-Orsi Umberto , Murn Campbell , Maude Glyn , Thomsett Simon
Published: January 2024

The conversion of natural habitats to farmland is a major cause of biodiversity loss and poses the greatest extinction risk to birds worldwide. Tropical raptors are of particular concern, being relatively slow-breeding apex predators and scavengers, whose disappearance can trigger extensive cascading effects. Many of Africa’s raptors are at considerable risk from habitat conversion, prey-base depletion and persecution, driven principally by human population expansion. Here we describe multiregional trends among 42 African raptor species, 88% of which have declined over a ca. 20–40-yr period, with 69% exceeding the International Union for Conservation of Nature criteria classifying species at risk of extinction. Large raptors had experienced significantly steeper declines than smaller species, and this disparity was more pronounced on unprotected land. Declines were greater in West Africa than elsewhere, and more than twice as severe outside of protected areas (PAs) than within. Worryingly, species suffering the steepest declines had become significantly more dependent on PAs, demonstrating the importance of expanding conservation areas to cover 30% of land by 2030—a key target agreed at the UN Convention on Biological Diversity COP15. Our findings also highlight the significance of a recent African-led proposal to strengthen PA management—initiatives considered fundamental to safeguarding global biodiversity, ecosystem functioning and climate resilience.
Recent gene selection and drug resistance underscore clinical adaptation across Candida species
Authors: Schikora-Tamarit Miquel Àngel , Gabaldón Toni
Published: January 2024

Understanding how microbial pathogens adapt to treatments, humans and clinical environments is key to infer mechanisms of virulence, transmission and drug resistance. This may help improve therapies and diagnostics for infections with a poor prognosis, such as those caused by fungal pathogens, including Candida. Here we analysed genomic variants across approximately 2,000 isolates from six Candida species (C. glabrata, C. auris, C. albicans, C. tropicalis, C. parapsilosis and C. orthopsilosis) and identified genes under recent selection, suggesting a highly complex clinical adaptation. These involve species-specific and convergently affected adaptive mechanisms, such as adhesion. Using convergence-based genome-wide association studies we identified known drivers of drug resistance alongside potentially novel players. Finally, our analyses reveal an important role of structural variants and suggest an unexpected involvement of (para)sexual recombination in the spread of resistance. Our results provide insights on how opportunistic pathogens adapt to human-related environments and unearth candidate genes that deserve future attention.
Antagonistic interactions between phage and host factors control arbitrium lysis–lysogeny decision
Authors: Zamora-Caballero Sara , Chmielowska Cora , Quiles-Puchalt Nuria , Brady Aisling , Gallego del Sol Francisca , Mancheño-Bonillo Javier , Felipe-Ruíz Alonso , Meijer Wilfried J. J. , Penadés José R. , Marina Alberto
Published: January 2024

Phages can use a small-molecule communication arbitrium system to coordinate lysis–lysogeny decisions, but the underlying mechanism remains unknown. Here we determined that the arbitrium system in Bacillus subtilis phage phi3T modulates the bacterial toxin–antitoxin system MazE–MazF to regulate the phage life cycle. We show that phi3T expresses AimX and YosL, which bind to and inactivate MazF. AimX also inhibits the function of phi3T_93, a protein that promotes lysogeny by binding to MazE and releasing MazF. Overall, these mutually exclusive interactions promote the lytic cycle of the phage. After several rounds of infection, the phage-encoded AimP peptide accumulates intracellularly and inactivates the phage antiterminator AimR, a process that eliminates aimX expression from the aimP promoter. Therefore, when AimP increases, MazF activity promotes reversion back to lysogeny, since AimX is absent. Altogether, our study reveals the evolutionary strategy used by arbitrium to control lysis–lysogeny by domesticating and fine-tuning a phage-defence mechanism.
A Dataset of Amphibian Species in U.S. National Parks
Authors: LaFrance Benjamin J. , Ray Andrew M. , Fisher Robert N. , Grant Evan H. Campbell , Shafer Charles , Beamer David A. , Spear Stephen F. , Pierson Todd W. , Davenport Jon M. , Niemiller Matthew L. , Pyron R. Alexander , Glorioso Brad M. , Barichivich William J. , Halstead Brian J. , Roberts Kory G. , Hossack Blake R.
Published: January 2024

National parks and other protected areas are important for preserving landscapes and biodiversity worldwide. An essential component of the mission of the United States (U.S.) National Park Service (NPS) requires understanding and maintaining accurate inventories of species on protected lands. We describe a new, national-scale synthesis of amphibian species occurrence in the NPS system. Many park units have a list of amphibian species observed within their borders compiled from various sources and available publicly through the NPSpecies platform. However, many of the observations in NPSpecies remain unverified and the lists are often outdated. We updated the amphibian dataset for each park unit by collating old and new park-level records and had them verified by regional experts. The new dataset contains occurrence records for 292 of the 424 NPS units and includes updated taxonomy, international and state conservation rankings, hyperlinks to a supporting reference for each record, specific notes, and related fields which can be used to better understand and manage amphibian biodiversity within a single park or group of parks.
Multi-frequency steady-state visual evoked potential dataset
Authors: Mu Jing , Liu Shuo , Burkitt Anthony N. , Grayden David B.
Published: January 2024

The Steady-State Visual Evoked Potential (SSVEP) is a widely used modality in Brain-Computer Interfaces (BCIs). Existing research has demonstrated the capabilities of SSVEP that use single frequencies for each target in various applications with relatively small numbers of commands required in the BCI. Multi-frequency SSVEP has been developed to extend the capability of single-frequency SSVEP to tasks that involve large numbers of commands. However, the development on multi-frequency SSVEP methodologies is falling behind compared to the number of studies with single-frequency SSVEP. This dataset was constructed to promote research in multi-frequency SSVEP by making SSVEP signals collected with different frequency stimulation settings publicly available. In this dataset, SSVEPs were collected from 35 participants using single-, dual-, and tri-frequency stimulation and with three different multi-frequency stimulation variants.
Genome assembly and population genomic data of a pulmonate snail Ellobium chinense
Authors: Kwak Haena , Lee Damin , Kim Yukyung , Park Joohee , Yeum Heeseung , Kim Donghee , Dong Yun-Wei , Nakano Tomoyuki , Jeong Choongwon , Park Joong-Ki
Published: January 2024

Ellobium chinense is an airbreathing, pulmonate gastropod species that inhabits saltmarshes in estuaries of the northwestern Pacific. Due to a rapid population decline and their unique ecological niche in estuarine ecosystems, this species has attracted special attention regarding their conservation and the genomic basis of adaptation to frequently changing environments. Here we report a draft genome assembly of E. chinense with a total size of 949.470 Mb and a scaffold N50 of 1.465 Mb. Comparative genomic analysis revealed that the GO terms enriched among four gastropod species are related to signal transduction involved in maintaining electrochemical gradients across the cell membrane. Population genomic analysis using the MSMC model for 14 re-sequenced individuals revealed a drastic decline in Korean and Japanese populations during the last glacial period, while the southern Chinese population retained a much larger effective population size (Ne). These contrasting demographic changes might be attributed to multiple environmental factors during the glacial–interglacial cycles. This study provides valuable genomic resources for understanding adaptation and historical demographic responses to climate change.