bluuebunny/crossref_metadata_2025 huggingface dataset:
The Theology of the Book of Samuel
Authors: Goldingay John
Published: May 2024

The Old Testament book of Samuel is an intriguing narrative that offers an account of the origin of the monarchy in Israel. It also deals at length with the fascinating stories of Saul and David. In this volume, John Goldingay works through the book, exploring the main theological ideas as they emerge in the narratives about Samuel, Saul, and David, as well as in the stories of characters such as Hannah, Michal, Bathsheba, and Tamar. Goldingay brings out the key ideas about God and God's involvement in the lives of people, and their involvement with him through prayer and worship. He also delves into the mystery and complexity of human persons and their roles in events. Goldingay's study traces how God pursues his purpose for Israel and, ultimately, for the world in these narratives. It shows how this pursuit is interwoven with the realities of family, monarchy, war, love, ambition, loss, failure, and politics.
Signal characteristics of surface seismic explosive sources near the West Antarctic Ice Sheet divide
Authors: Karplus Marianne S. , Nakata Nori , Kaip Galen M. , Harder Steven H. , Gonzalez Lucia F. , Booth Adam D. , Smith Emma C. , Veitch Stephen A. , Walter Jacob I. , Christoffersen Poul
Published: May 2024

Seismic imaging in 3-D holds great potential for improving our understanding of ice sheet structure and dynamics. Conducting 3-D imaging in remote areas is simplified by using lightweight and logistically straightforward sources. We report results from controlled seismic source tests carried out near the West Antarctic Ice Sheet Divide investigating the characteristics of two types of surface seismic sources, Poulter shots and detonating cord, for use in both 2-D and 3-D seismic surveys on glaciers. Both source types produced strong basal P-wave and S-wave reflections and multiples recorded in three components. The Poulter shots had a higher amplitude for low frequencies (<10 Hz) and comparable amplitude at high frequencies (>50 Hz) relative to the detonating cord. Amplitudes, frequencies, speed of source set-up, and cost all suggested Poulter shots to be the preferred surface source compared to detonating cord for future 2-D and 3-D seismic surveys on glaciers.
Pre-operative intratympanic gentamicin in patients undergoing retrosigmoid resection of large vestibular schwannomas: a pilot study
Authors: Potdar Tejal , Slim M. Afiq M. , Kontorinis Georgios
Published: May 2024

Purpose

To assess the effects of intratympanic gentamicin on the recovery of patients with large vestibular schwannomas undergoing retrosigmoid resection.

Methods

We conducted a prospective case-control pilot study over 24 months, including 13 patients with large vestibular schwannomas (25–41 mm intracranial diameter); seven patients received intratympanic gentamicin pre-operatively, while six did not. Outcome measures were duration of stay (main), age, gender, vestibular schwannoma size, body mass index and financial costs.

Results

Age had the highest association with longer inpatient stay. The non-gentamicin patients had longer hospital stays, were older, had lower body mass indices and larger vestibular schwannomas. A trend towards shorter stay was seen in patients receiving gentamicin with tumours less than 35 mm in size, but not in patients with larger tumours. Costs were lower for the gentamicin group.

Conclusion

Although not statistically significant, there was a positive trend in patients with vestibular schwannomas greater than 35 mm in size; thus, intratympanic gentamicin as prehabilitation could be considered.
Westward Excursion of Pc1/EMIC Waves and Their Source Protons: Paradoxical Observations From Ground and Space
Authors: Yin Ze‐Fan , Zhou Xu‐Zhi , Hu Ze‐Jun , Yue Chao , Zong Qiu‐Gang , Liu Zhi‐Yang , Liu Jian‐Jun , Shiokawa Kazuo , Oyama Shin‐ichiro , Baishev Dmitry
Published: May 2024

Pc1 geomagnetic pulsations within the frequency range of 0.2–5 Hz, the ground signatures of electromagnetic ion cyclotron (EMIC) waves, are usually observed to progress westward. A plausible explanation is that their westward‐excursion speed is defined by the drift velocity of the source particles in the geomagnetic dipole field. In this study, this relationship is examined through conjugate observations from ground‐based and spaceborne instruments. The ground‐based observations, including Pc1 pulsations and auroral emissions, consistently demonstrate a westward‐excursion speed of ∼4–5 MLT per hour, which agrees with the time delay between EMIC wave observations at two equatorial spacecraft. Observations of the wave source particles, however, indicate an inconsistency between the slow westward excursion speed and the high energy of the wave source protons. This apparent inconsistency is reconciled by the trapping motion of energetic particles within magnetic dips, which is supported by the simultaneous flux enhancements of protons across a broad energy range between ∼50 and ∼100 keV. These results improve our understanding of the westward excursion of Pc1 pulsations, and also underscore the need for caution when directly linking their westward‐excursion speed to the energies of the source particles.
Cracking Soils Could Accelerate Climate Change
Authors: Cutts Elise
Published: May 2024

Climate change is expected to lead to more frequent and intense drought, which in turn causes soil to crack, releasing more carbon dioxide and further warming the planet.
Optical probing of ultrafast laser-induced solid-to-overdense-plasma transitions
Authors: Azamoum Yasmina , Becker Georg Alexander , Keppler Sebastian , Duchateau Guillaume , Skupin Stefan , Grech Mickael , Catoire Fabrice , Hell Sebastian , Tamer Issa , Hornung Marco , Hellwing Marco , Kessler Alexander , Schorcht Franck , Kaluza Malte Christoph
Published: May 2024

Understanding the solid target dynamics resulting from the interaction with an ultrashort laser pulse is a challenging fundamental multi-physics problem involving atomic and solid-state physics, plasma physics, and laser physics. Knowledge of the initial interplay of the underlying processes is essential to many applications ranging from low-power laser regimes like laser-induced ablation to high-power laser regimes like laser-driven ion acceleration. Accessing the properties of the so-called pre-plasma formed as the laser pulse’s rising edge ionizes the target is complicated from the theoretical and experimental point of view, and many aspects of this laser-induced transition from solid to overdense plasma over picosecond timescales are still open questions. On the one hand, laser-driven ion acceleration requires precise control of the pre-plasma because the efficiency of the acceleration process crucially depends on the target properties at the arrival of the relativistic intensity peak of the pulse. On the other hand, efficient laser ablation requires, for example, preventing the so-called “plasma shielding”. By capturing the dynamics of the initial stage of the interaction, we report on a detailed visualization of the pre-plasma formation and evolution. Nanometer-thin diamond-like carbon foils are shown to transition from solid to plasma during the laser rising edge with intensities < 1016 W/cm². Single-shot near-infrared probe transmission measurements evidence sub-picosecond dynamics of an expanding plasma with densities above 1023 cm−3 (about 100 times the critical plasma density). The complementarity of a solid-state interaction model and kinetic plasma description provides deep insight into the interplay of initial ionization, collisions, and expansion.
Macrophage-derived ectosomal miR-350-3p promotes osteoarthritis progression through downregulating chondrocyte H3K36 methyltransferase NSD1
Authors: Lin Rengui , Yin Jianbin , Huang Jialuo , Zou Liping , Liu Liangliang , Tang Wen , Zhang Hongbo , Yang Lingfeng , Zhang Yu , Li Guangming , Wang Guiqing , Cai Daozhang , Zhang Haiyan , Liu Yanli , Shao Yan
Published: May 2024

Mechanical overloading can promote cartilage senescence and osteoarthritis (OA) development, but its impact on synovial macrophages and the interaction between macrophages and chondrocytes remain unknown. Here, we found that macrophages exhibited M1 polarization under mechanical overloading and secreted ectosomes that induced cartilage degradation and senescence. By performing miRNA sequencing on ectosomes, we identified highly expressed miR-350-3p as a key factor mediating the homeostatic imbalance of chondrocytes caused by M1-polarized macrophages, this result being confirmed by altering the miR-350-3p level in chondrocytes with mimics and inhibitor. In experimental OA mice, miR-350-3p was increased in synovium and cartilage, while intra-articular injection of antagomir-350-3p inhibited the increase of miR-350-3p and alleviated cartilage degeneration and senescence. Further studies showed that macrophage-derived ectosomal miR-350-3p promoted OA progression by inhibiting nuclear receptor binding SET domain protein 1(NSD1) in chondrocytes and regulating histone H3 lysine 36(H3K36) methylation. This study demonstrated that the targeting of macrophage-derived ectosomal miRNAs was a potential therapeutic method for mechanical overload-induced OA.
Spontaneous persistent activity and inactivity in vivo reveals differential cortico-entorhinal functional connectivity
Authors: Choudhary Krishna , Berberich Sven , Hahn Thomas T. G. , McFarland James M. , Mehta Mayank R.
Published: May 2024

Understanding the functional connectivity between brain regions and its emergent dynamics is a central challenge. Here we present a theory-experiment hybrid approach involving iteration between a minimal computational model and in vivo electrophysiological measurements. Our model not only predicted spontaneous persistent activity (SPA) during Up-Down-State oscillations, but also inactivity (SPI), which has never been reported. These were confirmed in vivo in the membrane potential of neurons, especially from layer 3 of the medial and lateral entorhinal cortices. The data was then used to constrain two free parameters, yielding a unique, experimentally determined model for each neuron. Analytic and computational analysis of the model generated a dozen quantitative predictions about network dynamics, which were all confirmed in vivo to high accuracy. Our technique predicted functional connectivity; e. g. the recurrent excitation is stronger in the medial than lateral entorhinal cortex. This too was confirmed with connectomics data. This technique uncovers how differential cortico-entorhinal dialogue generates SPA and SPI, which could form an energetically efficient working-memory substrate and influence the consolidation of memories during sleep. More broadly, our procedure can reveal the functional connectivity of large networks and a theory of their emergent dynamics.
A wireless controlled robotic insect with ultrafast untethered running speeds
Authors: Liu Zhiwei , Zhan Wencheng , Liu Xinyi , Zhu Yangsheng , Qi Mingjing , Leng Jiaming , Wei Lizhao , Han Shousheng , Wu Xiaoming , Yan Xiaojun
Published: May 2024

Running speed degradation of insect-scale (less than 5 cm) legged microrobots after carrying payloads has become a bottleneck for microrobots to achieve high untethered locomotion performance. In this work, we present a 2-cm legged microrobot (BHMbot, BeiHang Microrobot) with ultrafast untethered running speeds, which is facilitated by the complementary combination of bouncing length and bouncing frequency in the microrobot’s running gait. The untethered BHMbot (2-cm-long, 1760 mg) can achieve a running speed of 17.5 BL s−1and a turning centripetal acceleration of 65.4 BL s−2at a Cost of Transport of 303.7 and a power consumption of 1.77 W. By controlling its two front legs independently, the BHMbot demonstrates various locomotion trajectories including circles, rectangles, letters and irregular paths across obstacles through a wireless control module. Such advancements enable the BHMbot to carry out application attempts including sound signal detection, locomotion inside a turbofan engine and transportation via a quadrotor.
Structural basis and synergism of ATP and Na+ activation in bacterial K+ uptake system KtrAB
Authors: Chiang Wesley Tien , Chang Yao-Kai , Hui Wei-Han , Chang Shu-Wei , Liao Chen-Yi , Chang Yi-Chuan , Chen Chun-Jung , Wang Wei-Chen , Lai Chien-Chen , Wang Chun-Hsiung , Luo Siou-Ying , Huang Ya-Ping , Chou Shan-Ho , Horng Tzyy-Leng , Hou Ming-Hon , Muench Stephen P. , Chen Ren-Shiang , Tsai Ming-Daw , Hu Nien-Jen
Published: May 2024

The K+ uptake system KtrAB is essential for bacterial survival in low K+ environments. The activity of KtrAB is regulated by nucleotides and Na+. Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na+ activates KtrAB and the Na+ binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na+, as supported by X-ray crystallography and ICP-MS. Thermostability assays and functional studies demonstrated that Na+ binding stabilizes the ATP-bound BsKtrAB complex and enhances its K+ flux activity. Comparing ATP- and ADP-BsKtrAB structures suggests that BsKtrB Arg417 and Phe91 serve as a channel gate. The synergism of ATP and Na+ in activating BsKtrAB is likely applicable to Na+-activated K+ channels in central nervous system.
Converting inorganic sulfur into degradable thermoplastics and adhesives by copolymerization with cyclic disulfides
Authors: Deng Yuanxin , Huang Zhengtie , Feringa Ben L. , Tian He , Zhang Qi , Qu Da-Hui
Published: May 2024

Converting elementary sulfur into sulfur-rich polymers provides a sustainable strategy to replace fossil-fuel-based plastics. However, the low ring strain of eight-membered rings, i.e., S8 monomers, compromises their ring-opening polymerization (ROP) due to lack of an enthalpic driving force and as a consequence, poly(sulfur) is inherently unstable. Here we report that copolymerization with cyclic disulfides, e.g., 1,2-dithiolanes, can enable a simple and energy-saving way to convert elementary sulfur into sulfur-rich thermoplastics. The key strategy is to combine two types of ROP—both mediated by disulfide bond exchange—to tackle the thermodynamic instability of poly(sulfur). Meanwhile, the readily modifiable sidechain of the cyclic disulfides provides chemical space to engineer the mechanical properties and dynamic functions over a large range, e.g., self-repairing ability and degradability. Thus, this simple and robust system is expected to be a starting point for the organic transformation of inorganic sulfur toward sulfur-rich functional and green plastics.
Repression of developmental transcription factor networks triggers aging-associated gene expression in human glial progenitor cells
Authors: Mariani John N. , Mansky Benjamin , Madsen Pernille M. , Salinas Dennis , Kesmen Deniz , Huynh Nguyen P. T. , Kuypers Nicholas J. , Kesel Erin R. , Bates Janna , Payne Casey , Chandler-Militello Devin , Benraiss Abdellatif , Goldman Steven A.
Published: May 2024

Human glial progenitor cells (hGPCs) exhibit diminished expansion competence with age, as well as after recurrent demyelination. Using RNA-sequencing to compare the gene expression of fetal and adult hGPCs, we identify age-related changes in transcription consistent with the repression of genes enabling mitotic expansion, concurrent with the onset of aging-associated transcriptional programs. Adult hGPCs develop a repressive transcription factor network centered on MYC, and regulated by ZNF274, MAX, IKZF3, and E2F6. Individual over-expression of these factors in iPSC-derived hGPCs lead to a loss of proliferative gene expression and an induction of mitotic senescence, replicating the transcriptional changes incurred during glial aging. miRNA profiling identifies the appearance of an adult-selective miRNA signature, imposing further constraints on the expansion competence of aged GPCs. hGPC aging is thus associated with acquisition of a MYC-repressive environment, suggesting that suppression of these repressors of glial expansion may permit the rejuvenation of aged hGPCs.
Controlling chaos using edge computing hardware
Authors: Kent Robert M. , Barbosa Wendson A. S. , Gauthier Daniel J.
Published: May 2024

Machine learning provides a data-driven approach for creating a digital twin of a system – a digital model used to predict the system behavior. Having an accurate digital twin can drive many applications, such as controlling autonomous systems. Often, the size, weight, and power consumption of the digital twin or related controller must be minimized, ideally realized on embedded computing hardware that can operate without a cloud-computing connection. Here, we show that a nonlinear controller based on next-generation reservoir computing can tackle a difficult control problem: controlling a chaotic system to an arbitrary time-dependent state. The model is accurate, yet it is small enough to be evaluated on a field-programmable gate array typically found in embedded devices. Furthermore, the model only requires 25.0 $$\pm 7.0$$
±
7.0
nJ per evaluation, well below other algorithms, even without systematic power optimization. Our work represents the first step in deploying efficient machine learning algorithms to the computing “edge.”
Predicting vaccine effectiveness for mpox
Authors: Berry Matthew T. , Khan Shanchita R. , Schlub Timothy E. , Notaras Adriana , Kunasekaran Mohana , Grulich Andrew E. , MacIntyre C. Raina , Davenport Miles P. , Khoury David S.
Published: May 2024

The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was initially approved for mpox based on its reported immunogenicity (from phase I/II trials) and effectiveness in animal models, rather than evidence of clinical efficacy. However, no validated correlate of protection after vaccination has been identified. Here we performed a systematic search and meta-analysis of the available data to test whether vaccinia-binding ELISA endpoint titer is predictive of vaccine effectiveness against mpox. We observe a significant correlation between vaccine effectiveness and vaccinia-binding antibody titers, consistent with the existing assumption that antibody levels may be a correlate of protection. Combining this data with analysis of antibody kinetics after vaccination, we predict the durability of protection after vaccination and the impact of dose spacing. We find that delaying the second dose of MVA-BN vaccination will provide more durable protection and may be optimal in an outbreak with limited vaccine stock. Although further work is required to validate this correlate, this study provides a quantitative evidence-based approach for using antibody measurements to predict the effectiveness of mpox vaccination.
Probing the activated complex of the F + NH3 reaction via a dipole-bound state
Authors: Zhang Rui , Yan Shuaiting , Song Hongwei , Guo Hua , Ning Chuangang
Published: May 2024

Experimental characterization of the transition state poses a significant challenge due to its fleeting nature. Negative ion photodetachment offers a unique tool for probing transition states and their vicinity. However, this approach is usually limited to Franck-Condon regions. For example, high-lying Feshbach resonances with an excited HF stretching mode (vHF = 2-4) were recently identified in the transition-state region of the F + NH3 → HF + NH2 reaction through photo-detaching FNH3− anions, but the direct photodetachment failed to observe the lower-lying vHF = 0,1 resonances and bound states due apparently to negligible Franck-Condon factors. Indeed, these weak transitions can be resonantly enhanced via a dipole-bound state (DBS) formed between an electron and the polar FNH3 species. In this study, we unveil a series of Feshbach resonances and bound states along the F + NH3 reaction path via a DBS by combining high-resolution photoelectron spectroscopy with high-level quantum dynamical computations. This study presents an approach for probing the activated complex in a reaction by negative ion photodetachment through a DBS.
General strategy for developing thick-film micro-thermoelectric coolers from material fabrication to device integration
Authors: Sun Xiaowen , Yan Yuedong , Kang Man , Zhao Weiyun , Yan Kaifen , Wang He , Li Ranran , Zhao Shijie , Hua Xiaoshe , Wang Boyi , Zhang Weifeng , Deng Yuan
Published: May 2024

Micro-thermoelectric coolers are emerging as a promising solution for high-density cooling applications in confined spaces. Unlike thin-film micro-thermoelectric coolers with high cooling flux at the expense of cooling temperature difference due to very short thermoelectric legs, thick-film micro-thermoelectric coolers can achieve better comprehensive cooling performance. However, they still face significant challenges in both material preparation and device integration. Herein, we propose a design strategy which combines Bi2Te3-based thick film prepared by powder direct molding with micro-thermoelectric cooler integrated via phase-change batch transfer. Accurate thickness control and relatively high thermoelectric performance can be achieved for the thick film, and the high-density-integrated thick-film micro-thermoelectric cooler exhibits excellent performance with maximum cooling temperature difference of 40.6 K and maximum cooling flux of 56.5 W·cm−2at room temperature. The micro-thermoelectric cooler also shows high temperature control accuracy (0.01 K) and reliability (over 30000 cooling cycles). Moreover, the device demonstrates remarkable capacity in power generation with normalized power density up to 214.0 μW · cm−2 · K−2. This study provides a general and scalable route for developing high-performance thick-film micro-thermoelectric cooler, benefiting widespread applications in thermal management of microsystems.
Common conditions of use elements. Atomic concepts for consistent and effective information governance
Authors: Sanchez Gonzalez Maria del Carmen , Kamerling Pim , Iermito Mariapia , Casati Sara , Riaz Umar , Veal Colin D. , Maini Monika , Jeanson Francis , Benhamed Oussama Mohammed , van Enckevort Esther , Landi Annalisa , Mimouni Yanis , Le Cornec Clèmence , Coviello Domenico A. , Franchin Tiziana , Fusco Francesca , Ramírez García Jose Antonio , van der Zanden Loes F. M. , Bernier Alexander , Wilkinson Mark D. , Mueller Heimo , Gibson Spencer J. , Brookes Anthony J.
Published: May 2024

Myriad policy, ethical and legal considerations underpin the sharing of biological resources, implying the need for standardised and yet flexible ways to digitally represent diverse ‘use conditions’. We report a core lexicon of terms that are atomic, non-directional ‘concepts of use’, called Common Conditions of use Elements. This work engaged biobanks and registries relevant to the European Joint Programme for Rare Diseases and aimed to produce a lexicon that would have generalised utility. Seventy-six concepts were initially identified from diverse real-world settings, and via iterative rounds of deliberation and user-testing these were optimised and condensed down to 20 items. To validate utility, support software and training information was provided to biobanks and registries who were asked to create Sharing Policy Profiles. This succeeded and involved adding standardised directionality and scope annotations to the employed terms. The addition of free-text parameters was also explored. The approach is now being adopted by several real-world projects, enabling this standard to evolve progressively into a universal basis for representing and managing conditions of use.
Beyond NGS data sharing for plant ecological resilience and improvement of agronomic traits
Authors: Kwon Ji-Su , Shilpha Jayabalan , Lee Junesung , Yeom Seon-In
Published: May 2024

Decoding complex plant omics is essential for advancing our understanding of plant biology, evolution, and breeding as well as for practical applications in agriculture, conservation, and biotechnology. The advent of Next-Generation Sequencing (NGS) has revolutionized global plant genomic research, offering high-throughput, cost-effective, and accurate methods for generating genomic data. However, challenges still exist that suggest an entirely unresolved genome characterized by high heterozygosity, extensive repetitive sequences, and complex ploidy features. In addition, individual investigation of genomic information from various genetic resources is essential for omics research, as there are differences in traits within a single breed beyond a species due to the uniqueness of sequence variation. This article provides high-quality genomic and transcriptomic insights targeted at the agronomical background.
A study on nickel application methods for optimizing soybean growth
Authors: Rodak Bruna Wurr , Freitas Douglas Siqueira , Rossi Monica Lanzoni , Linhares Francisco Scaglia , Moro Edemar , Campos Cid Naudi Silva , Reis André Rodrigues , Guilherme Luiz Roberto Guimarães , Lavres José
Published: May 2024

Fertilization with nickel (Ni) can positively affect plant development due to the role of this micronutrient in nitrogen (N) metabolism, namely, through urease and NiFe-hydrogenase. Although the application of Ni is an emerging practice in modern agriculture, its effectiveness strongly depends on the chosen application method, making further research in this area essential. The individual and combined effects of different Ni application methods—seed treatment, leaf spraying and/or soil fertilization—were investigated in soybean plants under different edaphoclimatic conditions (field and greenhouse). Beneficial effects of the Soil, Soil + Leaf and Seed + Leaf treatments were observed, with gains of 7 to 20% in biological nitrogen fixation, 1.5-fold in ureides, 14% in shoot dry weight and yield increases of up to 1161 kg ha−1. All the Ni application methods resulted in a 1.1-fold increase in the SPAD index, a 1.2-fold increase in photosynthesis, a 1.4-fold increase in nitrogenase, and a 3.9-fold increase in urease activity. Edaphoclimatic conditions exerted a significant influence on the treatments. The integrated approaches, namely, leaf application in conjunction with soil or seed fertilization, were more effective for enhancing yield in soybean cultivation systems. The determination of the ideal method is crucial for ensuring optimal absorption and utilization of this micronutrient and thus a feasible and sustainable management technology. Further research is warranted to establish official guidelines for the application of Ni in agricultural practices.
Cold hypersensitivity in the hands and feet is associated with erectile dysfunction in young Taiwanese men
Authors: Chang Che-Jui , Fan Yu-Hua , Chiu Yi-Chun , Cheng Wei-Ming
Published: May 2024

Cold hypersensitivity in the hands and feet (CHHF) is a protective or predisposing factor for many diseases; however, the relationship between CHHF and erectile dysfunction (ED) remains unclear. We aimed to investigate associations between CHHF and ED among young men of Southeast Asian origin. In this cross-sectional study, sexually active Taiwanese men aged 20–40 years were enrolled via an online questionnaire comprising general demographic information, comorbidities, subjective thermal sensations of their hands and feet in the past 6 months, and their erectile function using the International Index of Erectile Function-5 (IIEF-5). Participants who reported cold sensation of hands and feet were classified to have CHHF; those with IIEF-5 score ≤ 21 were considered to have ED. Total 54.2% and 27.9% of participants had ED and CHHF, respectively. Men with CHHF were significantly younger, had lower body mass index and IIEF-5 scores (p < 0.001), and a lower prevalence of diabetes mellitus (p = 0.033) along with higher prevalence of ED, psychiatric disorders, and insomnia (p < 0.001). After adjusting for predisposing factors of ED, CHHF (odds ratio 1.410, 95% confidence interval 1.159–1.714; p = 0.001) remained an independent predictor of ED. Thus, CHHF is independently associated with ED, affecting more than a quarter of young Taiwanese men. Autonomic dysregulation and subclinical endothelial dysfunction may be common pathophysiologies of CHHF and ED.
The impact of mobility costs on cooperation and welfare in spatial social dilemmas
Authors: Bara Jacques , Santos Fernando P. , Turrini Paolo
Published: May 2024

From over-exploitation of resources to urban pollution, sustaining well-being requires solving social dilemmas of cooperation. Often such dilemmas are studied assuming that individuals occupy fixed positions in a network or lattice. In spatial settings, however, agents can move, and such movements involve costs. Here we investigate how mobility costs impact cooperation dynamics. To this end, we study cooperation dilemmas where individuals are located in a two-dimensional space and can be of two types: cooperators–or cleaners, who pay an individual cost to have a positive impact on their neighbours–and defectors–or polluters, free-riding on others’ effort to sustain a clean environment. Importantly, agents can pay a cost to move to a cleaner site. Both analytically and through agent-based simulations we find that, in general, introducing mobility costs increases pollution felt in the limit of fast movement (equivalently slow strategy revision). The effect on cooperation of increasing mobility costs is non-monotonic when mobility co-occurs with strategy revision. In such scenarios, low (yet non-zero) mobility costs minimise cooperation in low density environments; whereas high costs can promote cooperation even when a minority of agents initially defect. Finally, we find that heterogeneity in mobility cost affects the final distribution of strategies, leading to differences in who supports the burden of having a clean environment.
Comparative analysis of infected cassava root transcriptomics reveals candidate genes for root rot disease resistance
Authors: Hohenfeld Camila Santiago , de Oliveira Saulo Alves Santos , Ferreira Claudia Fortes , Mello Victor Hugo , Margarido Gabriel Rodrigues Alves , Passos Adriana Rodrigues , de Oliveira Eder Jorge
Published: May 2024

Cassava root-rot incited by soil-borne pathogens is one of the major diseases that reduces root yield. Although the use of resistant cultivars is the most effective method of management, the genetic basis for root-rot resistance remains poorly understood. Therefore, our work analyzed the transcriptome of two contrasting genotypes (BRS Kiriris/resistant and BGM-1345/susceptible) using RNA-Seq to understand the molecular response and identify candidate genes for resistance. Cassava seedlings (resistant and susceptible to root-rot) were both planted in infested and sterilized soil and samples from Initial-time and Final-time periods, pooled. Two controls were used: (i) seedlings collected before planting in infested soil (absolute control) and, (ii) plants grown in sterilized soil (mock treatments). For the differentially expressed genes (DEGs) analysis 23.912 were expressed in the resistant genotype, where 10.307 were differentially expressed in the control treatment, 15 DEGs in the Initial Time-period and 366 DEGs in the Final Time-period. Eighteen candidate genes from the resistant genotype were related to plant defense, such as the MLP-like protein 31 and the peroxidase A2-like gene. This is the first model of resistance at the transcriptional level proposed for the cassava × root-rot pathosystem. Gene validation will contribute to screening for resistance of germplasm, segregating populations and/or use in gene editing in the pursuit to develop most promising cassava clones with resistance to root-rot.
Characterizing the blood microbiota in healthy and febrile domestic cats via 16s rRNA sequencing
Authors: Kitson Liam , Becker Anne A. M. J. , Hartmann Katrin , Bergmann Michèle , Sepulveda-Garcia Paulina , Canales Nivia , Muller Ananda
Published: May 2024

This study aimed to evaluate the blood bacterial microbiota in healthy and febrile cats. High-quality sequencing reads from the 16S rRNA gene variable region V3-V4 were obtained from genomic blood DNA belonging to 145 healthy cats, and 140 febrile cats. Comparisons between the blood microbiota of healthy and febrile cats revealed dominant presence of Actinobacteria, followed by Firmicutes and Proteobacteria, and a lower relative abundance of Bacteroidetes. Upon lower taxonomic levels, the bacterial composition was significantly different between healthy and febrile cats. The families Faecalibacterium and Kineothrix (Firmicutes), and Phyllobacterium (Proteobacteria) experienced increased abundance in febrile samples. Whereas Thioprofundum (Proteobacteria) demonstrated a significant decrease in abundance in febrile. The bacterial composition and beta diversity within febrile cats was different according to the affected body system (Oral/GI, systemic, skin, and respiratory) at both family and genus levels. Sex and age were not significant factors affecting the blood microbiota of febrile cats nor healthy ones. Age was different between young adult and mature adult healthy cats. Alpha diversity was unaffected by any factors. Overall, the findings suggest that age, health status and nature of disease are significant factors affecting blood microbiota diversity and composition in cats, but sex is not.
Structural investigation of interactions between halogenated flavonoids and the lipid membrane along with their role as cytotoxic agents
Authors: Dudek Anita , Szulc Natalia , Pawlak Aleksandra , Strugała-Danak Paulina , Krawczyk-Łebek Agnieszka , Perz Martyna , Kostrzewa-Susłow Edyta , Pruchnik Hanna
Published: May 2024

This study focuses on understanding the structural and molecular changes in lipid membranes under the influence of six halogenated flavonoid derivatives differing in the number and position of substitution of chlorine and bromine atoms (D1–D6). Utilizing various analytical techniques, including fluorometric methods, dynamic light scattering (DLS), attenuated Fourier transform infrared spectroscopy (ATR- FTIR), and FT-Raman spectroscopy, the research aims to elucidate the mechanisms underlying the interaction of flavonoids with cell membranes. Additionally, the study includes in silico analyses to explore the physicochemical properties of these compounds and their potential pharmaceutical applications, along with toxicity studies to assess their effects on cancer, normal, and red blood cells. Our study showed the ability of halogenated derivatives to interact mostly with the outer part of the membrane, especially in the lipid heads region however, some of them were able to penetrate deeper into the membrane and affect the fluidity of hydrocarbon chains. The potential to reduce cancer cell viability, the lack of toxicity towards erythrocytes, and the favourable physicochemical and pharmacokinetic properties suggest these halogenated flavonoids potential candidates for exploring their potential for medical use.
Selective but not pan-CDK inhibition abrogates 5-FU-driven tissue factor upregulation in colon cancer
Authors: Kayser Annika , Wolff Annabell , Berlin Peggy , Duehring Lara , Henze Larissa , Mundkowski Ralf , Bergmann Wendy , Müller-Hilke Brigitte , Wagner Charlotte , Huehns Maja , Oehmcke-Hecht Sonja , Maletzki Claudia
Published: May 2024

Thromboembolic events are complications in cancer patients and hypercoagulability has been linked to the tissue factor (TF) pathway, making this an attractive target. Here, we investigated the effects of chemotherapeutics and CDK inhibitors (CDKI) abemaciclib/palbociclib (CDK4/6), THZ-1 (CDK7/12/13), and dinaciclib (CDK1/2/5/9) alone and in combination regimens on TF abundance and coagulation. The human colorectal cancer (CRC) cell line HROC173 was treated with 5-FU or gemcitabine to stimulate TF expression. TF+ cells were sorted, recultured, and re-analyzed. The effect of treatment alone or in combination was assessed by functional assays. Low-dose chemotherapy induced a hypercoagulable state and significantly upregulated TF, even after reculture without treatment. Cells exhibited characteristics of epithelial-mesenchymal transition, including high expression of vimentin and mucin. Dinaciclib and THZ-1 also upregulated TF, while abemaciclib and palbociclib downregulated it. Similar results were observed in coagulation assays. The same anticoagulant activity of abemaciclib was seen after incubation with peripheral immune cells from healthy donors and CRC patients. Abemaciclib reversed 5-FU-induced TF upregulation and prolonged clotting times in second-line treatment. Effects were independent of cytotoxicity, senescence, and p27kip1 induction. TF-antibody blocking experiments confirmed the importance of TF in plasma coagulation, with Factor XII playing a minor role. Short-term abemaciclib counteracts 5-FU-induced hypercoagulation and eventually even prevents thromboembolic events.
Identification of master regulator genes controlling pathogenic CD4+ T cell fate in inflammatory bowel disease through transcriptional network analysis
Authors: Jiménez José M. , Contreras-Riquelme J. Sebastián , Vidal Pía M. , Prado Carolina , Bastías Macarena , Meneses Claudio , Martín Alberto J. M. , Perez-Acle Tomás , Pacheco Rodrigo
Published: May 2024

Inflammatory bowel diseases (IBD) are a group of chronic inflammatory conditions of the gastrointestinal tract associated with multiple pathogenic factors, including dysregulation of the immune response. Effector CD4+ T cells and regulatory CD4+ T cells (Treg) are central players in maintaining the balance between tolerance and inflammation. Interestingly, genetic modifications in these cells have been implicated in regulating the commitment of specific phenotypes and immune functions. However, the transcriptional program controlling the pathogenic behavior of T helper cells in IBD progression is still unknown. In this study, we aimed to find master transcription regulators controlling the pathogenic behavior of effector CD4+ T cells upon gut inflammation. To achieve this goal, we used an animal model of IBD induced by the transfer of naïve CD4+ T cells into recombination-activating gene 1 (Rag1) deficient mice, which are devoid of lymphocytes. As a control, a group of Rag1−/− mice received the transfer of the whole CD4+ T cells population, which includes both effector T cells and Treg. When gut inflammation progressed, we isolated CD4+ T cells from the colonic lamina propria and spleen tissue, and performed bulk RNA-seq. We identified differentially up- and down-regulated genes by comparing samples from both experimental groups. We found 532 differentially expressed genes (DEGs) in the colon and 30 DEGs in the spleen, mostly related to Th1 response, leukocyte migration, and response to cytokines in lamina propria T-cells. We integrated these data into Gene Regulatory Networks to identify Master Regulators, identifying four up-regulated master gene regulators (Lef1, Dnmt1, Mybl2, and Jup) and only one down-regulated master regulator (Foxo3). The altered expression of master regulators observed in the transcriptomic analysis was confirmed by qRT-PCR analysis and found an up-regulation of Lef1 and Mybl2, but without differences on Dnmt1, Jup, and Foxo3. These two master regulators have been involved in T cells function and cell cycle progression, respectively. We identified two master regulator genes associated with the pathogenic behavior of effector CD4+ T cells in an animal model of IBD. These findings provide two new potential molecular targets for treating IBD.
Graph semantic similarity-based automatic assessment for programming exercises
Authors: Xiang Chengguan , Wang Ying , Zhou Qiyun , Yu Zhen
Published: May 2024

This paper proposes an algorithm for the automatic assessment of programming exercises. The algorithm assigns assessment scores based on the program dependency graph structure and the program semantic similarity, but does not actually need to run the student’s program. By calculating the node similarity between the student’s program and the teacher’s reference programs in terms of structure and program semantics, a similarity matrix is generated and the optimal similarity node path of this matrix is identified. The proposed algorithm achieves improved computational efficiency, with a time complexity of $$O(n^2)$$

O
(

n
2

)

for a graph with n nodes. The experimental results show that the assessment algorithm proposed in this paper is more reliable and accurate than several comparison algorithms, and can be used for scoring programming exercises in C/C++, Java, Python, and other languages.
Development of a new affinity maturation protocol for the construction of an internalizing anti-nucleolin antibody library
Authors: Ribeiro Rita , Moreira João N. , Goncalves João
Published: May 2024

Over the last decades, monoclonal antibodies have substantially improved the treatment of several conditions. The continuous search for novel therapeutic targets and improvements in antibody’s structure, demands for a constant optimization of their development. In this regard, modulation of an antibody’s affinity to its target has been largely explored and culminated in the discovery and optimization of a variety of molecules. It involves the creation of antibody libraries and selection against the target of interest. In this work, we aimed at developing a novel protocol to be used for the affinity maturation of an antibody previously developed by our group. An antibody library was constructed using an in vivo random mutagenesis approach that, to our knowledge, has not been used before for antibody development. Then, a cell-based phage display selection protocol was designed to allow the fast and simple screening of antibody clones capable of being internalized by target cells. Next generation sequencing coupled with computer analysis provided an extensive characterization of the created library and post-selection pool, that can be used as a guide for future antibody development. With a single selection step, an enrichment in the mutated antibody library, given by a decrease in almost 50% in sequence diversity, was achieved, and structural information useful in the study of the antibody-target interaction in the future was obtained.
Insights into phage-bacteria interaction in cold seep Gigantidas platifrons through metagenomics and transcriptome analyses
Authors: Zhang Yan , Chen Hao , Lian Chao , Cao Lei , Guo Yang , Wang Minxiao , Zhong Zhaoshan , Li Mengna , Zhang Huan , Li Chaolun
Published: May 2024

Viruses are crucial for regulating deep-sea microbial communities and biogeochemical cycles. However, their roles are still less characterized in deep-sea holobionts. Bathymodioline mussels are endemic species inhabiting cold seeps and harboring endosymbionts in gill epithelial cells for nutrition. This study unveiled a diverse array of viruses in the gill tissues of Gigantidas platifrons mussels and analyzed the viral metagenome and transcriptome from the gill tissues of Gigantidas platifrons mussels collected from a cold seep in the South Sea. The mussel gills contained various viruses including Baculoviridae, Rountreeviridae, Myoviridae and Siphovirdae, but the active viromes were Myoviridae, Siphoviridae, and Podoviridae belonging to the order Caudovirales. The overall viral community structure showed significant variation among environments with different methane concentrations. Transcriptome analysis indicated high expression of viral structural genes, integrase, and restriction endonuclease genes in a high methane concentration environment, suggesting frequent virus infection and replication. Furthermore, two viruses (GP-phage-contig14 and GP-phage-contig72) interacted with Gigantidas platifrons methanotrophic gill symbionts (bathymodiolin mussels host intracellular methanotrophic Gammaproteobacteria in their gills), showing high expression levels, and have huge different expression in different methane concentrations. Additionally, single-stranded DNA viruses may play a potential auxiliary role in the virus–host interaction using indirect bioinformatics methods. Moreover, the Cro and DNA methylase genes had phylogenetic similarity between the virus and Gigantidas platifrons methanotrophic gill symbionts. This study also explored a variety of viruses in the gill tissues of Gigantidas platifrons and revealed that bacteria interacted with the viruses during the symbiosis with Gigantidas platifrons. This study provides fundamental insights into the interplay of microorganisms within Gigantidas platifrons mussels in deep sea.
Multispectral optoacoustic tomography of benign parotid tumors in vivo: a prospective observational pilot study
Authors: Kouka Mussab , Waldner Maximilian , Guntinas-Lichius Orlando
Published: May 2024

Parotid lumps are a heterogeneous group of mainly benign but also malignant tumors. Preoperative imaging does not allow a differentiation between tumor types. Multispectral optoacoustic tomography (MSOT) may improve the preoperative diagnostics. In this first prospective pilot trial the ability of MSOT to discriminate between the two most frequent benign parotid tumors, pleomorphic adenoma (PA) and Warthin tumor (WT) as well as to normal parotid tissue was explored. Six wavelengths (700, 730, 760, 800, 850, 900 nm) and the parameters deoxygenated (HbR), oxygenated (HbO2), total hemoglobin (HbT), and saturation of hemoglobin (sO2) were analyzed. Ten patients with PA and fourteen with WT were included (12/12 female/male; median age: 51 years). For PA, the mean values for all measured wave lengths as well as for the hemoglobin parameters were different for the tumors compared to the healthy parotid (all p < 0.05). The mean MSOT parameters were all significantly higher (all p < 0.05) in the WT compared to healthy parotid gland except for HbT and sO2. Comparing both tumors directly, the mean values of MSOT parameters were not different between PA and WT (all p > 0.05). Differences were seen for the maximal MSOT parameters. The maximal tumor values for 900 nm, HbR, HbT, and sO2 were lower in PA than in WT (all p < 0.05). This preliminary MSOT parotid tumor imaging study showed clear differences for PA or WT compared to healthy parotid tissue. Some MSOT characteristics of PA and WT were different but needed to be explored in larger studies.