bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying sources of bias when testing three available algorithms for quantifying white matter lesions: BIANCA, LPA and LGA
Authors: Miller Tatiana , Bittner Nora , Moebus Susanne , Caspers Svenja
Published: August 2024

Brain magnetic resonance imaging frequently reveals white matter lesions (WMLs) in older adults. They are often associated with cognitive impairment and risk of dementia. Given the continuous search for the optimal segmentation algorithm, we broke down this question by exploring whether the output of algorithms frequently used might be biased by the presence of different influencing factors. We studied the impact of age, sex, blood glucose levels, diabetes, systolic blood pressure and hypertension on automatic WML segmentation algorithms. We evaluated three widely used algorithms (BIANCA, LPA and LGA) using the population-based 1000BRAINS cohort (N = 1166, aged 18–87, 523 females, 643 males). We analysed two main aspects. Firstly, we examined whether training data (TD) characteristics influenced WML estimations, assessing the impact of relevant factors in the TD. Secondly, algorithm’s output and performance within selected subgroups defined by these factors were assessed. Results revealed that BIANCA’s WML estimations are influenced by the characteristics present in the TD. LPA and LGA consistently provided lower WML estimations compared to BIANCA’s output when tested on participants under 67 years of age without risk cardiovascular factors. Notably, LPA and LGA showed reduced accuracy for these participants. However, LPA and LGA showed better performance for older participants presenting cardiovascular risk factors. Results suggest that incorporating comprehensive cohort factors like diverse age, sex and participants with and without hypertension in the TD could enhance WML-based analyses and mitigate potential sources of bias. LPA and LGA are a fast and valid option for older participants with cardiovascular risk factors.
Long-term Aftershock Properties of the Catastrophic 6 February 2023 Kahramanmaraş (Türkiye) Earthquake Sequence
Authors: Tan Onur
Published: August 2024

Nine hours apart, two catastrophic earthquakes (Mw 7.8 and 7.6) occurred on 6 February 2023, in eastern Türkiye. The mainshocks destroyed several cities and villages in 11 provinces, including Kahramanmaraş, Hatay, Adıyaman, Malatya, Adana and Gaziantep. Over about 50,000 aftershocks were detected in the nine months. Because the resolution of hypocentral locations in the Turkish national earthquake catalogs is limited, about 31,000 events are relocated using the double-difference method in this study. The aftershock distribution and its relation to energy release on the faults and Coulomb stress change areas are investigated. The improved hypocenters give a clearer image to understand the activity on the faults. The event distribution indicates that the rupture of the first mainshock in Pazarcık (Mw 7.8) propagates unilaterally on the northernmost segment of the Dead Sea Fault Zone and then transfers to the East Anatolian Fault Zone at the Maraş Triple Junction. The bilaterally extending rupture causes dense aftershock activity on the fault zone from Samandağ to Pütürge. The second mainshock in Elbistan (Mw 7.6) was triggered because of the positive Coulomb stress change on the Çardak fault, which generates dense clusters at both ends of the fault. It is observed that a high number of aftershocks occur on the low slip patches, and the high-energy release areas have low activity because of the stress equilibrium on the fault surfaces.
Classification and Novelty Detection of Tampered ICs Using ResCav
Authors: Nechiyil Aditya , McCue Jamin J. , Lee Robert , Chapman Gregg
Published: August 2024

This paper investigates the capabilities of the resonant cavity system (ResCav) for detecting tampered integrated circuits (ICs) within supply chains. Prior research showcased ResCav’s ability to discern minor circuit variations, this study focuses on enhancing supervised classification results and introduces a one-class support vector machine (SVM) approach with a modified radial basis function kernel for novelty detection. Through finer hyperparameter tuning, the system achieves improved classification accuracy, demonstrating its potential to identify nuanced alterations with even higher precision and recall rates. Additionally, the application of a one-class SVM enables the detection of tampered ICs without reliance on labeled datasets, expanding utility in scenarios where access is limited to golden ICs. These advancements in ResCav’s capabilities signify progress in failure prevention methodologies, offering an efficient and non-destructive solution crucial for safeguarding against counterfeit and non-conforming components infiltrating critical supply chains.
On the Cut Locus of Submanifolds of a Finsler Manifold
Authors: Bhowmick Aritra , Prasad Sachchidanand
Published: August 2024

In this article, we investigate the cut locus of closed (not necessarily compact) submanifolds in a forward complete Finsler manifold. We explore the deformation and characterization of the cut locus, extending the results of Basu and Prasad (Algebr Geom Topol 23(9):4185–4233, 2023). Given a submanifold N, we consider an N-geodesic loop as an N-geodesic starting and ending in N, possibly at different points. This class of geodesics were studied by Omori (J Differ Geom 2:233–252, 1968). We obtain a generalization of Klingenberg’s lemma for closed geodesics (Klingenberg in: Ann Math 2(69):654–666, 1959). for N-geodesic loops in the reversible Finsler setting.
Enigmatic fragment possibly marks the first pterosaur record from the Lower Toarcian of Grimmen, NE Germany
Authors: Schade Marco , Ansorge Jörg
Published: August 2024

Pterosaurs are a well-known component of many Mesozoic fossil ecosystems worldwide. To date, marine and terrestrial faunal elements such as cephalopods, fish, marine reptiles, dinosaurs and insects have been discovered in the Lower Jurassic clay pit near Grimmen (Western Pomerania). A new fragmentary bone is thoroughly described herein and interpreted to represent the first evidence for the presence of pterosaurs in this locality.
Bio-economic analysis of irrigation schedules considering shallow groundwater: lessons from South Africa
Authors: Hadebe Ruth , Grové Bennie , Matthews Nicolette , Barnard Johan
Published: August 2024

Due to the pressure on South Africa’s irrigated agriculture to improve efficiency and optimal water use, irrigators must consider alternative water sources, such as root-accessible shallow groundwater tables, to supply the crop evapotranspiration requirement. Devising irrigation scheduling strategies that will optimize conjunctive water use is difficult because the contribution of shallow groundwater tables is not directly observed and is a function of irrigation management decisions; as a result, very few irrigators use these strategies. This paper aims to evaluate the profitability of using shallow groundwater tables as a source of irrigation water to satisfy crop evapotranspiration requirements. A bio-economic simulation model consisting of the soil–water–atmosphere–plant model and an economic accounting module was developed to calculate the profitability of conjunctive irrigation practices under different states of nature. The bio-economic simulation model was linked to a differential evolutionary algorithm to optimize the irrigation scheduling decisions. The results showed that irrigators could substantially increase profitability and water use efficiency if they consider the shallow groundwater table in their irrigation decision. About 51% of crop evapotranspiration could originate from shallow groundwater tables, reducing the irrigation requirements substantially without impacting crop yields. Sequential adaptive irrigation decision-making does not improve the bio-economic indicators much since using the shallow groundwater table mitigates the risk of undersupplying water. Therefore, conjunctive water use strategies using shallow groundwater tables economically benefit irrigators. However, a complex interplay exists between irrigation adjustments, crop yields and economic performance in different states, emphasizing the careful consideration of context-specific factors in irrigation management decisions.
Topical metronidazole after haemorrhoidectomy to reduce postoperative pain: a systematic review
Authors: Eberspacher Chiara , Mascagni Domenico , Pontone Stefano , Arcieri Francesco Leone , Arcieri Stefano
Published: August 2024

Excisional haemorrhoidectomy is the gold standard for operating haemorrhoids, but it is accompanied by a significant problem: postoperative pain. Several strategies have been adopted to minimize this condition. Oral metronidazole has been proven to reduce postoperative pain but with some complications. This systematic review was conducted to investigate the effects and general efficacy of topical metronidazole administration and to evaluate its potential superiority over the oral formula. A systematic review of the literature was carried out. Randomized controlled trials published until September 2023 on PubMed, Central, and Web of Science were considered. The primary outcome considered was postoperative pain, which was evaluated using visual analogue scores. The secondary outcomes were analgesic use, return to work, and complications. Six randomized controlled trials were included, with a total of 536 patients. Topical metronidazole was compared with placebo in two studies, with oral formula in three studies, and with placebo and oral administration in one study. Topical metronidazole was found to be effective for treating postoperative pain when compared to a placebo but had no significant advantage over the oral formula. No complications were reported in the studies. Topical and oral metronidazole are effective solutions for postoperative pain after excisional haemorrhoidectomy. No superiority was demonstrated based on the route of administration, and complications were marginal for both formulas. Further studies are required to determine the best metronidazole solution.
Structure, electrical, and optical properties of Co0.7-xZnxNi0.3Fe2O4 (0.3 ≥ x ≥ 0.7) nano-ferrite by sol–gel auto-combustion technique
Authors: El-Sayed O. , Ghozza M. H. , Hamid R. K. Abd.El.
Published: August 2024

Zn2+ doped Ni0.3ZnxCo0.7-xFe2O4 (0.3 ≥ x ≥ 0.7) spinel nanoparticles were synthesized via Sol–gel-auto combustion methods using EDTA and citric acid as fuel. XRD, Raman spectroscopy, FE-SEM, and EDX demonstrated that samples possessed a well-crystalline cubic spinel structure. Both crystallite size and the lattice parameter values increased due to the smaller ionic radius of Co2+-ions compared to the Zn2+ ionic radius. The crystallite size average values ranged from 24–50 nm while lattice parameters were between 8.3877 Å and 8.4268 Å. The surface morphological variation and the elements supplied were analyzed using FE-SEM and EDX, displaying spherical-shaped nanoparticles and all constituent elements. Based on the results of the optical properties, raising Zn2+ caused the refractive index and the reflectance to rise. The dielectric constant and dielectric loss of Ni0.3ZnxCo0.7-xFe2O4 reduced substantially with increasing frequency. Moreover, the increase in Zn2+ concentration causes the decrease in dielectric constant due to Fe3+-ion migration from the hopping procedure, which decreases the hopping process (Fe2+ and Fe3+-ions) according to Koop's theory (Maxwell–Wagner polarization). The maximum dielectric constant, reported at x = 0.7 (no Co2+-ions), may be related to the generation of Fe2+-ions occupying octahedral sites. This leads to an increase in Fe2+ and Fe3+ electron exchange, polarization, and conductivity enhancement. These results revealed that Ni0.3Zn0.7xFe2O4 has a high capacitance and loss, making it promising option for electronic equipment such as computer memory cards, microwave absorbers and capacitors.
Navigating the Urgency: A Narrative Review on the Critical Demand for Robust Outcome Measures in Post-Intensive Care Syndrome (PICS)
Authors: Goel Tanya , Arunmozhi R.
Published: August 2024

Background

Post intensive care syndrome (PICS) is a new emerging condition affecting more than 80% of the population discharged from Intensive care unit (ICU). It affects the individual with a myriad of symptoms degrading the individual’s quality of life (QoL). Most critical method to prevent this is early diagnosis through a reliable measure taking into account the multidimensional nature of PICS. Thus, this study aims to find out is there a need of a comprehensive assessment scale for PICS covering all the domains.

Methods

Data was searched on databases incorporating PubMed, Cochrane Library, Google Scholar and EBSCO, Psyc INFO, Web of Science, Scopus, Science Direct, Medline, CINAHL. 18,756 articles were retrieved. It was narrowed down to 20 articles which were finally reviewed. The review summarizing all the reasons why a comprehensive outcome measure is needed for PICS including all the aspects of the syndrome. Furthermore, the review delineates the potential advantages that a novel assessment tool could provide, enriching our comprehension and handling of the intricate ramifications of PICS.

Results

The review highlights several key findings that underscore the necessity of a thorough outcome measure for assessing PICS: (i) the multifaceted nature of symptoms; (ii) challenges related to underdiagnosis and misdiagnosis; (iii) inconsistencies in assessment measures; (iv) insufficient attention to social aspects; (v) confounding factors related to comorbidities; (vi) the diverse array of assessment measures presently employed. All this is currently contributing to a confusing assessment of PICS leading to increased population affected with multitude of symptoms experienced after ICU discharge.

Conclusion

The existing assessment instruments for PICS exhibit wide variability in complexity, difficult comparison and evidence integration, thereby complicating therapeutic decisions. The lack of a universally accepted measurement standard increases the challenge of diagnosing and preventing PICS. Additionally, some tools may inaccurately represent PICS characteristics, leading to inconsistent reporting. Thus, there is an urgent demand for a comprehensive, multidimensional tool to provide a valid diagnosis.
Soil contamination with microplastics (MPs) from treated wastewater and sewage sludge: risks and sustainable mitigation strategies
Authors: Hechmi Sarra , Bhat Mansoor Ahmad , Kallel Amjad , Khiari Oumaima , Louati Zeineb , Khelil Mohamed Naceur , Zoghlami Rahma Inès , Cherni Yasmine , Melki Samira , Trabelsi Ismail , Jedidi Naceur
Published: August 2024

This review explores the hidden hazards associated with the reuse of treated wastewater and sewage sludge in agriculture while proposing mitigation strategies. It examines the origins and pathways of microplastics (MPs) in wastewater treatment plants and how these pollutants infiltrate agricultural ecosystems. The review assesses the effectiveness of MP removal from wastewater and its fate in soil after reuse, highlighting contamination dynamics and the need for proactive measures. Introducing soil remediation methods is crucial for addressing this issue. Alarming evidence of MPs in human blood, testis, semen, and placenta underscores the urgency for solutions, revealing significant threats to human health, particularly reproductive health. The review advocates for sustainable agricultural practices and effective soil remediation strategies to mitigate MP contamination, promoting environmental preservation, food safety, and human health protection.

Graphical Abstract
Assessing Skills of Everyday Technical Problem Solving
Authors: Schrickel Marcus , Stemmann Jennifer , Goldhammer Frank , Hahnel Carolin
Published: August 2024

Abstract: With the ongoing digitalization of home automation and appliances, users often face situations in which they lack the information required to reach an intended goal when using an unfamiliar device. To solve such technical problems, users need to acquire and apply operational knowledge in a self-regulated way. Our study assesses skills in technical problem solving (TPS) and provides the first empirical validation of a score interpretation of a developed TPS test. The examined hypotheses concern the internal structure of the TPS test and the association of the item solution rate with device characteristics (complexity and intransparency) and person-by-device characteristics (the extent of system exploration, use of operating manuals, and device-specific prior knowledge). An ad hoc adult sample ( n = 213) processed nine computer-simulated TPS units, each including a knowledge acquisition and knowledge application phase per device. As expected, the internal structure of the TPS test was one-dimensional. Intransparency, but not complexity, affected the item solution rate. Completeness of system exploration, use of operating manuals, and device-specific prior knowledge independently showed positive effects on item solution rates. Along with an evaluation of the developed TPS test, we discuss the role of the salience of device features for knowledge acquisition.
Role of Strong Sea Surface Temperature Diurnal Variation in Triggering the Summer Monsoon Onset Over the Bay of Bengal in a Climate Model
Authors: Song Yajuan , Yang Xiaodan , Bao Ying , Qiao Fangli , Song Zhenya
Published: August 2024

The earliest Asian summer monsoon onset (SMO) occurs in the Bay of Bengal (BoB), heralding the coming of the rainy season. In late April or early May, the strong sea surface temperature (SST) diurnal variation accompanied by ocean surface warming triggers the SMO. However, this observed diurnal cycle intensity cannot be reasonably simulated by state‐of‐the‐art climate models, resulting in a spurious delayed SMO. To address this issue, the SST diurnal cycle parameterized by a diagnostic sublayer scheme was incorporated into a climate model named FIO‐ESM v2.0. The large diurnal amplitude of SST contributes to surface warming and changes atmospheric circulation. Consequently, the high‐pressure anomaly at high levels and an inverted trough at low levels promote more convective activity, triggering an earlier SMO. Our findings improve the ability of climate models in simulating the evolution of the Asian monsoon system.
A Data‐Driven Approach to Assess the Impact of Climate Change on a Tropical Mangrove in India
Authors: Deb Burman Pramit Kumar , Das Pulakesh
Published: August 2024

As a potential carbon sink, mangroves play an important role in climate mitigation. India houses several major global mangrove patches, which remain vulnerable to climate change. The ecosystem‐atmosphere CO2 exchange is most accurately measured by the eddy covariance method, whereas satellites provide the biophysical parameters for a wider area. In the present study, the Sentinel‐2 satellite data is used to map the land cover types in the Pichavaram mangrove forest and identify two major dominant species (Rhizophora spp. and Avicennia marina), which indicated more than 95% classification accuracy. We used 2 years (2017 and 2018) of in situ gross primary productivity (GPP) and leaf area index (LAI) measurements and rectified the Moderate Resolution Imaging Spectroradiometer (MODIS) GPP and LAI products from 2010 to 2018. The modified MODIS GPP and LAI products were used to develop machine learning models, that is, Random Forest (RF) and Extreme Gradient Boosting (XGBoost) to study the climate influence on mangrove productivity. The RF model (R2 = 0.85 and root mean square error (RMSE) = 0.2) outperformed the XGBoost model (R2 = 0.75 and RMSE = 0.26) and was used to project the impact of climate change on the mangrove GPP for two extreme climate change scenarios, namely SSP1‐1.26 and SSP5‐8.5. The GPP increases and decreases in future during wet and dry periods, respectively. Overall, the projected GPP indicated a reduction of 3.73%–20.3% from 2050 to 2060 and of 4.82%–28.15% from 2090 to 2100, compared to its current average (from 2010 to 2018).
Deciphering Subduction Polarity During Ancient Arc‐Continent Collisions
Authors: Yan Zhiyong , Chen Lin , Zuza Andrew V. , Xiang Xiao , Xie Renxian , Ai Sanxi
Published: August 2024

The closure of an ancient ocean basin via oceanic arc‐continent collision has two subduction styles with opposite polarities, which may proceed via subduction polarity reversal (SPR) or a subduction zone jump (SZJ). Interpreting the geometry or kinematic evolution of ancient collisional zones, especially the original subduction polarity, can be challenging. Here we used 2D thermo‐mechanical modeling to investigate the dynamic evolution process of SPR versus SZJ. Our modeling predicts different structural, topographic, magmatic, and basin histories for SPR and SZJ, which can be compared against, and help interpret, the geologic record past sites of oceanic closure during collisional orogens. Our results match geologic observations of past collisions in Kamchatka, eastern Russia, and the Banda Arc, eastern Indonesia, and thus our results can help effectively decode the evolutionary history of past arc‐continent collisions.
A meta-analysis of genome-wide studies of resilience in the German population
Authors: Herrera-Rivero Marisol , Garvert Linda , Horn Katrin , Löbner Margrit , Weitzel Elena Caroline , Stoll Monika , Lichtner Peter , Teismann Henning , Teumer Alexander , Van der Auwera Sandra , Völzke Henry , Völker Uwe , Andlauer Till F. M. , Meinert Susanne , Heilmann-Heimbach Stefanie , Forstner Andreas J. , Streit Fabian , Witt Stephanie H. , Kircher Tilo , Dannlowski Udo , Scholz Markus , Riedel-Heller Steffi G. , Grabe Hans J. , Baune Bernhard T. , Berger Klaus
Published: August 2024

Resilience is the capacity to adapt to stressful life events. As such, this trait is associated with physical and mental functions and conditions. Here, we aimed to identify the genetic factors contributing to shape resilience. We performed variant- and gene-based meta-analyses of genome-wide association studies from six German cohorts (N = 15822) using the 11-item version of the Resilience Scale (RS-11) as outcome measure. Variant- and gene-level results were combined to explore the biological context using network analysis. In addition, we conducted tests of correlation between RS-11 and the polygenic scores (PGSs) for 12 personality and mental health traits in one of these cohorts (PROCAM-2, N = 3879). The variant-based analysis found no signals associated with resilience at the genome-wide level (p < 5 × 10−8), but suggested five genomic loci (p < 1 × 10−5). The gene-based analysis identified three genes (ROBO1, CIB3 and LYPD4) associated with resilience at genome-wide level (p < 2.48 × 10−6) and 32 potential candidates (p < 1 × 10−4). Network analysis revealed enrichment of biological pathways related to neuronal proliferation and differentiation, synaptic organization, immune responses and vascular homeostasis. We also found significant correlations (FDR < 0.05) between RS-11 and the PGSs for neuroticism and general happiness. Overall, our observations suggest low heritability of resilience. Large, international efforts will be required to uncover the genetic factors that contribute to shape trait resilience. Nevertheless, as the largest investigation of the genetics of resilience in general population to date, our study already offers valuable insights into the biology potentially underlying resilience and resilience’s relationship with other personality traits and mental health.
Potential of GSPT1 as a novel target for glioblastoma therapy
Authors: Sasayama Takashi , Hamada Takeshi , Tanaka Kazuhiro , Nagashima Hiroaki , Yamanishi Shunsuke , Ueyama Takehiko
Published: August 2024

Glioblastoma is the most common malignant brain tumor in adults, the survival rate of which has not significantly improved over the past three decades. Therefore, there is an urgent need to develop novel treatment modalities. We previously reported that G1 to S phase transition 1 (GSPT1) depletion induces delayed cell cycle in primary astrocytes. Herein, we examined the potential of GSPT1 as a novel target for glioblastoma therapy. CC-885, a cereblon modulator that degrades GSPT1 by bridging GSPT1 to the CRL4 E3 ubiquitin ligase complex, was administered to nude mice with transplanted brain tumors of U87 glioblastoma cells. The survival period was significantly longer in CC-885 treated mice than in control mice. Furthermore, we generated GSPT1-knockout (KO) U87 cells and GSPT1-KO U87 cells with stable overexpression of FLAG-tagged GSPT1 (Rescued GSPT1-KO). Mice with transplanted GSPT1-KO U87 cells and Rescued GSPT1-KO U87 cells showed significantly longer and similar survival periods, respectively, as those with wild-type (WT) U87 cells. GSPT1-KO U87 cells showed enhanced apoptosis, detected by cleaved PARP1, compared to WT U87 cells. Brain tumors with transplantation of GSPT1-KO U87 cells also showed enhanced apoptosis compared to those with transplantation of WT and Rescued GSPT1-KO U87 cells. GSPT1 expression was confirmed in patients with glioblastoma. However, the clinical study using 87 glioblastoma samples showed that GSPT1 mRNA levels were not associated with overall survival. Taken together, we propose that GSPT1 is an essential protein for glioblastoma growth, but not its malignant characteristics, and that GSPT1 is a potential target for developing glioblastoma therapeutics.
Fatty links between multisystem proteinopathy and small VCP-interacting protein
Authors: Ramzan Firyal , Kumar Ashish , Abrar Fatima , Gray Rachel A. V. , Campbell Zurie E. , Liao Lucia Meng Qi , Dang Anthony , Akanni Oluwadurotimi , Guyn Colm , Martin Dale D. O.
Published: August 2024

Multisystem proteinopathy (MSP) is a rare, dominantly inherited disorder that includes a cluster of diseases, including frontotemporal dementia, inclusion body myopathy, and Paget’s disease of bone. MSP is caused by mutations in the gene encoding valosin-containing protein (VCP). Patients with the same mutation, even within the same family, can present with a different combination of any or all of the above diseases, along with amyotrophic lateral sclerosis (ALS). The pleiotropic effects may be linked to the greater than 50 VCP co-factors that direct VCP’s many roles in the cell. Small VCP-interacting protein (SVIP) is a small protein that directs VCP to autophagosomes and lysosomes. We found that SVIP directs VCP localization to lysosomes in an acylation-dependent manner. We demonstrate that SVIP is myristoylated at Glycine 2 and palmitoylated at Cysteines 4 and 7. Acylation of SVIP is required to mediate cell death in the presence of the MSP-associated VCP variant (R155H-VCP), whereas blocking SVIP myristoylation prevents cytotoxicity. Therefore, SVIP acylation may present a novel target in MSP.
Mass spectrometry imaging of SOD1 protein-metal complexes in SOD1G93A transgenic mice implicates demetalation with pathology
Authors: Hale Oliver J. , Wells Tyler R. , Mead Richard J. , Cooper Helen J.
Published: August 2024

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons in the central nervous system (CNS). Mutations in the metalloenzyme SOD1 are associated with inherited forms of ALS and cause a toxic gain of function thought to be mediated by dimer destabilization and misfolding. SOD1 binds two Cu and two Zn ions in its homodimeric form. We have applied native ambient mass spectrometry imaging to visualize the spatial distributions of intact metal-bound SOD1G93A complexes in SOD1G93A transgenic mouse spinal cord and brain sections and evaluated them against disease pathology. The molecular specificity of our approach reveals that metal-deficient SOD1G93A species are abundant in CNS structures correlating with ALS pathology whereas fully metalated SOD1G93A species are homogenously distributed. Monomer abundance did not correlate with pathology. We also show that the dimer-destabilizing post-translational modification, glutathionylation, has limited influence on the spatial distribution of SOD1 dimers.
Human tumor suppressor protein Pdcd4 binds at the mRNA entry channel in the 40S small ribosomal subunit
Authors: Brito Querido Jailson , Sokabe Masaaki , Díaz-López Irene , Gordiyenko Yuliya , Zuber Philipp , Du Yifei , Albacete-Albacete Lucas , Ramakrishnan V. , Fraser Christopher S.
Published: August 2024

Translation is regulated mainly in the initiation step, and its dysregulation is implicated in many human diseases. Several proteins have been found to regulate translational initiation, including Pdcd4 (programmed cell death gene 4). Pdcd4 is a tumor suppressor protein that prevents cell growth, invasion, and metastasis. It is downregulated in most tumor cells, while global translation in the cell is upregulated. To understand the mechanisms underlying translational control by Pdcd4, we used single-particle cryo-electron microscopy to determine the structure of human Pdcd4 bound to 40S small ribosomal subunit, including Pdcd4-40S and Pdcd4-40S-eIF4A-eIF3-eIF1 complexes. The structures reveal the binding site of Pdcd4 at the mRNA entry site in the 40S, where the C-terminal domain (CTD) interacts with eIF4A at the mRNA entry site, while the N-terminal domain (NTD) is inserted into the mRNA channel and decoding site. The structures, together with quantitative binding and in vitro translation assays, shed light on the critical role of the NTD for the recruitment of Pdcd4 to the ribosomal complex and suggest a model whereby Pdcd4 blocks the eIF4F-independent role of eIF4A during recruitment and scanning of the 5′ UTR of mRNA.
Two-dimensional single-crystalline mesoporous high-entropy oxide nanoplates for efficient electrochemical biomass upgrading
Authors: Wang Yanzhi , He Hangjuan , Lv Hao , Jia Fengrui , Liu Ben
Published: August 2024

Mesoporous single crystals have received more attention than ever in catalysis-related applications due to their unique structural functions. Despite great efforts, their progress in engineering crystallinity and composition has been remarkably slower than expected. In this manuscript, a template-free strategy is developed to prepare two-dimensional high-entropy oxide (HEO) nanoplates with single-crystallinity and penetrated mesoporosity, which further ensures precise control over high-entropy compositions and crystalline phases. Single-crystalline mesoporous HEOs (SC-MHEOs) disclose high electrocatalytic performance in 5-hydroxymethylfurfural oxidation reaction (HMFOR) for efficient biomass upgrading, with remarkable HMF conversion of 99.3% and superior 2,5-furandicarboxylic acid (FDCA) selectivity of 97.7%. Moreover, with nitrate reduction as coupling cathode reaction, SC-MHEO realizes concurrent electrosynthesis of value-added FDCA and ammonia in the two-electrode cell. Our study provides a powerful paradigm for producing a library of novel mesoporous single crystals for important catalysis-related applications, especially in the two-electrode cell.
Seed longevity is controlled by metacaspases
Authors: Liu Chen , Hatzianestis Ioannis H. , Pfirrmann Thorsten , Reza Salim H. , Minina Elena A. , Moazzami Ali , Stael Simon , Gutierrez–Beltran Emilio , Pitsili Eugenia , Dörmann Peter , D’Andrea Sabine , Gevaert Kris , Romero–Campero Francisco , Ding Pingtao , Nowack Moritz K. , Van Breusegem Frank , Jones Jonathan D. G. , Bozhkov Peter V. , Moschou Panagiotis N.
Published: August 2024

To survive extreme desiccation, seeds enter a period of quiescence that can last millennia. Seed quiescence involves the accumulation of protective storage proteins and lipids through unknown adjustments in protein homeostasis (proteostasis). Here, we show that mutation of all six type–II metacaspase (MCA–II) proteases in Arabidopsis thaliana disturbs proteostasis in seeds. MCA–II mutant seeds fail to restrict the AAA ATPase CELL DIVISION CYCLE 48 (CDC48) at the endoplasmic reticulum to discard misfolded proteins, compromising seed storability. Endoplasmic reticulum (ER) localization of CDC48 relies on the MCA–IIs-dependent cleavage of PUX10 (ubiquitination regulatory X domain–containing 10), the adaptor protein responsible for titrating CDC48 to lipid droplets. PUX10 cleavage enables the shuttling of CDC48 between lipid droplets and the ER, providing an important regulatory mechanism sustaining spatiotemporal proteolysis, lipid droplet dynamics, and protein homeostasis. In turn, the removal of the PUX10 adaptor in MCA–II mutant seeds partially restores proteostasis, CDC48 localization, and lipid droplet dynamics prolonging seed lifespan. Taken together, we uncover a proteolytic module conferring seed longevity.
Histone-methyltransferase KMT2D deficiency impairs the Fanconi anemia/BRCA pathway upon glycolytic inhibition in squamous cell carcinoma
Authors: Liu Wei , Cao Hongchao , Wang Jing , Elmusrati Areeg , Han Bing , Chen Wei , Zhou Ping , Li Xiyao , Keysar Stephen , Jimeno Antonio , Wang Cun-Yu
Published: August 2024

Histone lysine methyltransferase 2D (KMT2D) is the most frequently mutated epigenetic modifier in head and neck squamous cell carcinoma (HNSCC). However, the role of KMT2D in HNSCC tumorigenesis and whether its mutations confer any therapeutic vulnerabilities remain unknown. Here we show that KMT2D deficiency promotes HNSCC growth through increasing glycolysis. Additionally, KMT2D loss decreases the expression of Fanconi Anemia (FA)/BRCA pathway genes under glycolytic inhibition. Mechanistically, glycolytic inhibition facilitates the occupancy of KMT2D to the promoter/enhancer regions of FA genes. KMT2D loss reprograms the epigenomic landscapes of FA genes by transiting their promoter/enhancer states from active to inactive under glycolytic inhibition. Therefore, combining the glycolysis inhibitor 2-DG with DNA crosslinking agents or poly (ADP-ribose) polymerase (PARP) inhibitors preferentially inhibits tumor growth of KMT2D-deficient mouse HNSCC and patient-derived xenografts (PDXs) harboring KMT2D-inactivating mutations. These findings provide an epigenomic basis for developing targeted therapies for HNSCC patients with KMT2D-inactivating mutations.
High-entropy superparaelectrics with locally diverse ferroic distortion for high-capacitive energy storage
Authors: Duan Jianhong , Wei Kun , Du Qianbiao , Ma Linzhao , Yu Huifen , Qi He , Tan Yangchun , Zhong Gaokuo , Li Hao
Published: August 2024

Superparaelectrics are considered promising candidate materials for achieving superior energy storage capabilities. However, due to the complicated local structural design, simultaneously achieving high recoverable energy density (Wrec) and energy storage efficiency (η) under high electric fields remains a challenge in bulk superparaelectrics. Here, we propose utilizing entropy engineering to disrupt long-range ferroic orders into local polymorphic distortion disorder with multiple BO6 tilt types and diverse heterogeneous polarization configurations. This strategy reduces the switching barriers, thereby facilitating the emergence of superparaelectric behaviors with ideal polarization forms. Furthermore, it enables high polarization response, negligible remnant polarization, delayed polarization saturation, and enhanced breakdown electric fields (Eb) in high-entropy superparaelectrics. Consequently, an extraordinary Wrec of 15.48 J cm–3 and an ultrahigh η of 90.02% are achieved at a high Eb of 710 kV cm–1, surpassing the comprehensive energy storage performance of previously reported bulk superparaelectrics. This work demonstrates that entropy engineering is a viable strategy for designing high-performance superparaelectrics.
Spermidine is essential for fasting-mediated autophagy and longevity
Authors: Hofer Sebastian J. , Daskalaki Ioanna , Bergmann Martina , Friščić Jasna , Zimmermann Andreas , Mueller Melanie I. , Abdellatif Mahmoud , Nicastro Raffaele , Masser Sarah , Durand Sylvère , Nartey Alexander , Waltenstorfer Mara , Enzenhofer Sarah , Faimann Isabella , Gschiel Verena , Bajaj Thomas , Niemeyer Christine , Gkikas Ilias , Pein Lukas , Cerrato Giulia , Pan Hui , Liang YongTian , Tadic Jelena , Jerkovic Andrea , Aprahamian Fanny , Robbins Christine E. , Nirmalathasan Nitharsshini , Habisch Hansjörg , Annerer Elisabeth , Dethloff Frederik , Stumpe Michael , Grundler Franziska , Wilhelmi de Toledo Françoise , Heinz Daniel E. , Koppold Daniela A. , Rajput Khokhar Anika , Michalsen Andreas , Tripolt Norbert J. , Sourij Harald , Pieber Thomas R. , de Cabo Rafael , McCormick Mark A. , Magnes Christoph , Kepp Oliver , Dengjel Joern , Sigrist Stephan J. , Gassen Nils C. , Sedej Simon , Madl Tobias , De Virgilio Claudio , Stelzl Ulrich , Hoffmann Markus H. , Eisenberg Tobias , Tavernarakis Nektarios , Kroemer Guido , Madeo Frank
Published: August 2024

Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders. Here, we asked whether the cellular and physiological consequences of caloric restriction and fasting depend on polyamine metabolism. We report that spermidine levels increased upon distinct regimens of fasting or caloric restriction in yeast, flies, mice and human volunteers. Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, nematodes and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan- and healthspan-extending effects, as well as the cardioprotective and anti-arthritic consequences of fasting. Mechanistically, spermidine mediated these effects via autophagy induction and hypusination of the translation regulator eIF5A. In summary, the polyamine–hypusination axis emerges as a phylogenetically conserved metabolic control hub for fasting-mediated autophagy enhancement and longevity.
Century-long timelines of herbarium genomes predict plant stomatal response to climate change
Authors: Lang Patricia L. M. , Erberich Joel M. , Lopez Lua , Weiß Clemens L. , Amador Gabriel , Fung Hannah F. , Latorre Sergio M. , Lasky Jesse R. , Burbano Hernán A. , Expósito-Alonso Moisés , Bergmann Dominique C.
Published: August 2024

Dissecting plant responses to the environment is key to understanding whether and how plants adapt to anthropogenic climate change. Stomata, plants’ pores for gas exchange, are expected to decrease in density following increased CO2 concentrations, a trend already observed in multiple plant species. However, it is unclear whether such responses are based on genetic changes and evolutionary adaptation. Here we make use of extensive knowledge of 43 genes in the stomatal development pathway and newly generated genome information of 191 Arabidopsis thaliana historical herbarium specimens collected over 193 years to directly link genetic variation with climate change. While we find that the essential transcription factors SPCH, MUTE and FAMA, central to stomatal development, are under strong evolutionary constraints, several regulators of stomatal development show signs of local adaptation in contemporary samples from different geographic regions. We then develop a functional score based on known effects of gene knock-out on stomatal development that recovers a classic pattern of stomatal density decrease over the past centuries, suggesting a genetic component contributing to this change. This approach combining historical genomics with functional experimental knowledge could allow further investigations of how different, even in historical samples unmeasurable, cellular plant phenotypes may have already responded to climate change through adaptive evolution.
Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populations
Authors: Argentieri M. Austin , Xiao Sihao , Bennett Derrick , Winchester Laura , Nevado-Holgado Alejo J. , Ghose Upamanyu , Albukhari Ashwag , Yao Pang , Mazidi Mohsen , Lv Jun , Millwood Iona , Fry Hannah , Rodosthenous Rodosthenis S. , Partanen Jukka , Zheng Zhili , Kurki Mitja , Daly Mark J. , Palotie Aarno , Adams Cassandra J. , Li Liming , Clarke Robert , Amin Najaf , Chen Zhengming , van Duijn Cornelia M.
Published: August 2024

Circulating plasma proteins play key roles in human health and can potentially be used to measure biological age, allowing risk prediction for age-related diseases, multimorbidity and mortality. Here we developed a proteomic age clock in the UK Biobank (n = 45,441) using a proteomic platform comprising 2,897 plasma proteins and explored its utility to predict major disease morbidity and mortality in diverse populations. We identified 204 proteins that accurately predict chronological age (Pearson r = 0.94) and found that proteomic aging was associated with the incidence of 18 major chronic diseases (including diseases of the heart, liver, kidney and lung, diabetes, neurodegeneration and cancer), as well as with multimorbidity and all-cause mortality risk. Proteomic aging was also associated with age-related measures of biological, physical and cognitive function, including telomere length, frailty index and reaction time. Proteins contributing most substantially to the proteomic age clock are involved in numerous biological functions, including extracellular matrix interactions, immune response and inflammation, hormone regulation and reproduction, neuronal structure and function and development and differentiation. In a validation study involving biobanks in China (n = 3,977) and Finland (n = 1,990), the proteomic age clock showed similar age prediction accuracy (Pearson r = 0.92 and r = 0.94, respectively) compared to its performance in the UK Biobank. Our results demonstrate that proteomic aging involves proteins spanning multiple functional categories and can be used to predict age-related functional status, multimorbidity and mortality risk across geographically and genetically diverse populations.
Detection and tracking of barchan dunes using artificial intelligence
Authors: Cúñez Esteban A. , Franklin Erick M.
Published: August 2024

Barchans are crescent-shape dunes ubiquitous on Earth and other celestial bodies, which are organized in barchan fields where they interact with each other. Over the last decades, satellite images have been largely employed to detect barchans on Earth and on the surface of Mars, with AI (Artificial Intelligence) becoming an important tool for monitoring those bedforms. However, automatic detection reported in previous works is limited to isolated dunes and does not identify successfully groups of interacting barchans. In this paper, we inquire into the automatic detection and tracking of barchans by carrying out experiments and exploring the acquired images using AI. After training a neural network with images from controlled experiments where complex interactions took place between dunes, we did the same for satellite images from Earth and Mars. We show, for the first time, that a neural network trained properly can identify and track barchans interacting with each other in different environments, using different image types (contrasts, colors, points of view, resolutions, etc.), with confidence scores (accuracy) above 70%. Our results represent a step further for automatically monitoring barchans, with important applications for human activities on Earth, Mars and other celestial bodies.
Study of microstructure and corrosion behavior of nano-Al2O3 coating layers on TiO2 substrate via polymeric method and microwave combustion
Authors: El-Hamid H. K. Abd , Gaber A. A. , Ngida Rehab E. A. , Sadek H. E. H. , Khattab R. M. , Mandour Howida S.
Published: August 2024

The study describes the successful development of a TiO2 ceramic substrate with a protective nano-Al2O3 coating using two different coating techniques: microwave combustion and polymeric methods. The coated ceramics demonstrate enhanced corrosion resistance compared to the uncoated substrate. The optimal TiO2 substrate was prepared by firing it at 1000 °C. This was done to give the desired physical properties of the TiO2 substrate for the coating procedures. Nano-Al2O3 powder was coated onto the surface of the TiO2 substrates. The TiO2 substrates with the Al2O3 coating were then calcined (heat-treated) at 800 and 1000 °C. The structures, morphology, phase composition, apparent porosity, bulk density, and compressive strength of the substrate and coated substrate were characterized. Upon firing at 1000 °C, it was discovered that the two phases of TiO2—rutile and anatase—combine in the substrate. Once the substrate has been coated with nano Al2O3 at 1000 °C, the anatase is transferred into rutile. When compared to the substrate, the coated substrate resulted in a decrease in porosity and an increase in strength. The efficiency of the ceramic metal nanoparticles Al2O3 as a good coating material to protect the TiO2 substrates against the effect of the corrosive medium 0.5 M solution of H2SO4 was measured by two methods: potentio-dynamic polarization (PDP) and the electrochemical impedance spectroscopy (EIS). The results indicated that the corrosion rate was decreased after the substrate coated with alumina from (67.71 to 16.30 C.R. mm/year) and the percentage of the inhibition efficiency recorded a high value reaching (78.56%). The surface morphology and composition after electrochemical measurements are investigated using SEM and EDX analysis. After conducting the corrosion tests and all the characterization, the results indicated that the coated TiO2 substrate prepared by the polymeric method at 800 °C displayed the best physical, mechanical, and corrosion-resistant behavior.
Deep learning enables accurate soft tissue tendon deformation estimation in vivo via ultrasound imaging
Authors: Huff Reece D. , Houghton Frederick , Earl Conner C. , Ghajar-Rahimi Elnaz , Dogra Ishan , Yu Denny , Harris-Adamson Carisa , Goergen Craig J. , O’Connell Grace D.
Published: August 2024

Image-based deformation estimation is an important tool used in a variety of engineering problems, including crack propagation, fracture, and fatigue failure. These tools have been important in biomechanics research where measuring in vitro and in vivo tissue deformations are important for evaluating tissue health and disease progression. However, accurately measuring tissue deformation in vivo is particularly challenging due to limited image signal-to-noise ratio. Therefore, we created a novel deep-learning approach for measuring deformation from a sequence of images collected in vivo called . Utilizing a training dataset that incorporates image artifacts, was designed to maximize performance in challenging, in vivo settings. Artificially generated image sequences of human flexor tendons undergoing known deformations were used to compare benchmark against two conventional image-based strain measurement techniques. outperformed the traditional techniques by nearly 90%. High-frequency ultrasound imaging was then used to acquire images of the flexor tendons engaged during contraction. Only was able to track tissue deformations under the in vivo test conditions. Findings revealed strong correlations between tendon deformation and applied forces, highlighting the potential for to be a valuable tool for assessing rehabilitation strategies or disease progression. Additionally, by using real-world data to train our model, was able to generalize and reveal important relationships between the effort exerted by the participant and tendon mechanics. Overall, demonstrated the effectiveness of using deep learning for image-based strain analysis in vivo.