bluuebunny/crossref_metadata_2025 huggingface dataset:
Late Paleozoic oxygenation of marine environments supported by dolomite U-Pb dating
Authors: Ben-Israel Michal , Holder Robert M. , Nelson Lyle L. , Smith Emily F. , Kylander-Clark Andrew R. C. , Ryb Uri
Published: April 2024

Understanding causal relationships between evolution and ocean oxygenation hinges on reliable reconstructions of marine oxygen levels, typically from redox-sensitive geochemical proxies. Here, we develop a proxy, using dolomite U–Pb geochronology, to reconstruct seawater U/Pb ratios. Dolomite samples consistently give U–Pb dates and initial 207Pb/206Pb ratios lower than expected from their stratigraphic ages. These observations are explained by resetting of the U–Pb system long after deposition; the magnitude of deviations from expected initial 207Pb/206Pb are a function of the redox-sensitive U/Pb ratios during deposition. Reconstructed initial U/Pb ratios increased notably in the late-Paleozoic, reflecting an increase in oxygenation of marine environments at that time. This timeline is consistent with documented shifts in some other redox proxies and supports evolution-driven mechanisms for the oxygenation of late-Paleozoic marine environments, as well as suggestions that early animals thrived in oceans that on long time scales were oxygen-limited compared to today.
Intrinsic exchange biased anomalous Hall effect in an uncompensated antiferromagnet MnBi2Te4
Authors: Chong Su Kong , Cheng Yang , Man Huiyuan , Lee Seng Huat , Wang Yu , Dai Bingqian , Tanabe Masaki , Yang Ting-Hsun , Mao Zhiqiang , Moler Kathryn A. , Wang Kang L.
Published: April 2024

Achieving spin-pinning at the interface of hetero-bilayer ferromagnet/antiferromagnet structures in conventional exchange bias systems can be challenging due to difficulties in interface control and the weakening of spin-pinning caused by poor interface quality. In this work, we propose an alternative approach to stabilize the exchange interaction at the interface of an uncompensated antiferromagnet by utilizing a gradient of interlayer exchange coupling. We demonstrate this exchange interaction through a designed field training protocol in the odd-layer topological antiferromagnet MnBi2Te4. Our results reveal a remarkable field-trained exchange bias of up to ~ 400 mT, which exhibits high repeatability and can be easily reset by a large training field. Notably, this field-trained exchange bias effect persists even with zero-field initialization, presenting a stark contrast to the traditional field-cooled exchange bias. The highly tunable exchange bias observed in this single antiferromagnet compound, without the need for an additional magnetic layer, provides valuable insight into the exchange interaction mechanism. These findings pave the way for the systematic design of topological antiferromagnetic spintronics.
Genomic language model predicts protein co-regulation and function
Authors: Hwang Yunha , Cornman Andre L. , Kellogg Elizabeth H. , Ovchinnikov Sergey , Girguis Peter R.
Published: April 2024

Abstract

Deciphering the relationship between a gene and its genomic context is fundamental to understanding and engineering biological systems. Machine learning has shown promise in learning latent relationships underlying the sequence-structure-function paradigm from massive protein sequence datasets. However, to date, limited attempts have been made in extending this continuum to include higher order genomic context information. Evolutionary processes dictate the specificity of genomic contexts in which a gene is found across phylogenetic distances, and these emergent genomic patterns can be leveraged to uncover functional relationships between gene products. Here, we train a genomic language model (gLM) on millions of metagenomic scaffolds to learn the latent functional and regulatory relationships between genes. gLM learns contextualized protein embeddings that capture the genomic context as well as the protein sequence itself, and encode biologically meaningful and functionally relevant information (e.g. enzymatic function, taxonomy). Our analysis of the attention patterns demonstrates that gLM is learning co-regulated functional modules (i.e. operons). Our findings illustrate that gLM’s unsupervised deep learning of the metagenomic corpus is an effective and promising approach to encode functional semantics and regulatory syntax of genes in their genomic contexts and uncover complex relationships between genes in a genomic region.
Dbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination
Authors: Galanti Lorenzo , Peritore Martina , Gnügge Robert , Cannavo Elda , Heipke Johannes , Palumbieri Maria Dilia , Steigenberger Barbara , Symington Lorraine S. , Cejka Petr , Pfander Boris
Published: April 2024

DNA double-strand breaks (DSBs) can be repaired by several pathways. In eukaryotes, DSB repair pathway choice occurs at the level of DNA end resection and is controlled by the cell cycle. Upon cell cycle-dependent activation, cyclin-dependent kinases (CDKs) phosphorylate resection proteins and thereby stimulate end resection and repair by homologous recombination (HR). However, inability of CDK phospho-mimetic mutants to bypass this cell cycle regulation, suggests that additional cell cycle regulators may be important. Here, we identify Dbf4-dependent kinase (DDK) as a second major cell cycle regulator of DNA end resection. Using inducible genetic and chemical inhibition of DDK in budding yeast and human cells, we show that end resection and HR require activation by DDK. Mechanistically, DDK phosphorylates at least two resection nucleases in budding yeast: the Mre11 activator Sae2, which promotes resection initiation, as well as the Dna2 nuclease, which promotes resection elongation. Notably, synthetic activation of DDK allows limited resection and HR in G1 cells, suggesting that DDK is a key component of DSB repair pathway selection.
Loss of CREBBP and KMT2D cooperate to accelerate lymphomagenesis and shape the lymphoma immune microenvironment
Authors: Li Jie , Chin Christopher R. , Ying Hsia-Yuan , Meydan Cem , Teater Matthew R. , Xia Min , Farinha Pedro , Takata Katsuyoshi , Chu Chi-Shuen , Jiang Yiyue , Eagles Jenna , Passerini Verena , Tang Zhanyun , Rivas Martin A. , Weigert Oliver , Pugh Trevor J. , Chadburn Amy , Steidl Christian , Scott David W. , Roeder Robert G. , Mason Christopher E. , Zappasodi Roberta , Béguelin Wendy , Melnick Ari M.
Published: April 2024

Despite regulating overlapping gene enhancers and pathways, CREBBP and KMT2D mutations recurrently co-occur in germinal center (GC) B cell-derived lymphomas, suggesting potential oncogenic cooperation. Herein, we report that combined haploinsufficiency of Crebbp and Kmt2d induces a more severe mouse lymphoma phenotype (vs either allele alone) and unexpectedly confers an immune evasive microenvironment manifesting as CD8+ T-cell exhaustion and reduced infiltration. This is linked to profound repression of immune synapse genes that mediate crosstalk with T-cells, resulting in aberrant GC B cell fate decisions. From the epigenetic perspective, we observe interaction and mutually dependent binding and function of CREBBP and KMT2D on chromatin. Their combined deficiency preferentially impairs activation of immune synapse-responsive super-enhancers, pointing to a particular dependency for both co-activators at these specialized regulatory elements. Together, our data provide an example where chromatin modifier mutations cooperatively shape and induce an immune-evasive microenvironment to facilitate lymphomagenesis.
Hidden impacts of ocean warming and acidification on biological responses of marine animals revealed through meta-analysis
Authors: Alter Katharina , Jacquemont Juliette , Claudet Joachim , Lattuca María E. , Barrantes María E. , Marras Stefano , Manríquez Patricio H. , González Claudio P. , Fernández Daniel A. , Peck Myron A. , Cattano Carlo , Milazzo Marco , Mark Felix C. , Domenici Paolo
Published: April 2024

Conflicting results remain on the impacts of climate change on marine organisms, hindering our capacity to predict the future state of marine ecosystems. To account for species-specific responses and for the ambiguous relation of most metrics to fitness, we develop a meta-analytical approach based on the deviation of responses from reference values (absolute change) to complement meta-analyses of directional (relative) changes in responses. Using this approach, we evaluate responses of fish and invertebrates to warming and acidification. We find that climate drivers induce directional changes in calcification, survival, and metabolism, and significant deviations in twice as many biological responses, including physiology, reproduction, behavior, and development. Widespread deviations of responses are detected even under moderate intensity levels of warming and acidification, while directional changes are mostly limited to more severe intensity levels. Because such deviations may result in ecological shifts impacting ecosystem structures and processes, our results suggest that climate change will likely have stronger impacts than those previously predicted based on directional changes alone.
Enhanced polarization switching characteristics of HfO2 ultrathin films via acceptor-donor co-doping
Authors: Zhou Chao , Ma Liyang , Feng Yanpeng , Kuo Chang-Yang , Ku Yu-Chieh , Liu Cheng-En , Cheng Xianlong , Li Jingxuan , Si Yangyang , Huang Haoliang , Huang Yan , Zhao Hongjian , Chang Chun-Fu , Das Sujit , Liu Shi , Chen Zuhuang
Published: April 2024

In the realm of ferroelectric memories, HfO2-based ferroelectrics stand out because of their exceptional CMOS compatibility and scalability. Nevertheless, their switchable polarization and switching speed are not on par with those of perovskite ferroelectrics. It is widely acknowledged that defects play a crucial role in stabilizing the metastable polar phase of HfO2. Simultaneously, defects also pin the domain walls and impede the switching process, ultimately rendering the sluggish switching of HfO2. Herein, we present an effective strategy involving acceptor-donor co-doping to effectively tackle this dilemma. Remarkably enhanced ferroelectricity and the fastest switching process ever reported among HfO2 polar devices are observed in La3+-Ta5+ co-doped HfO2 ultrathin films. Moreover, robust macro-electrical characteristics of co-doped films persist even at a thickness as low as 3 nm, expanding potential applications of HfO2 in ultrathin devices. Our systematic investigations further demonstrate that synergistic effects of uniform microstructure and smaller switching barrier introduced by co-doping ensure the enhanced ferroelectricity and shortened switching time. The co-doping strategy offers an effective avenue to control the defect state and improve the ferroelectric properties of HfO2 films.
A modular organic neuromorphic spiking circuit for retina-inspired sensory coding and neurotransmitter-mediated neural pathways
Authors: Matrone Giovanni Maria , van Doremaele Eveline R. W. , Surendran Abhijith , Laswick Zachary , Griggs Sophie , Ye Gang , McCulloch Iain , Santoro Francesca , Rivnay Jonathan , van de Burgt Yoeri
Published: April 2024

Signal communication mechanisms within the human body rely on the transmission and modulation of action potentials. Replicating the interdependent functions of receptors, neurons and synapses with organic artificial neurons and biohybrid synapses is an essential first step towards merging neuromorphic circuits and biological systems, crucial for computing at the biological interface. However, most organic neuromorphic systems are based on simple circuits which exhibit limited adaptability to both external and internal biological cues, and are restricted to emulate only specific the functions of an individual neuron/synapse. Here, we present a modular neuromorphic system which combines organic spiking neurons and biohybrid synapses to replicate a neural pathway. The spiking neuron mimics the sensory coding function of afferent neurons from light stimuli, while the neuromodulatory activity of interneurons is emulated by neurotransmitters-mediated biohybrid synapses. Combining these functions, we create a modular connection between multiple neurons to establish a pre-processing retinal pathway primitive.
ReLo is a simple and rapid colocalization assay to identify and characterize direct protein–protein interactions
Authors: Salgania Harpreet Kaur , Metz Jutta , Jeske Mandy
Published: April 2024

The characterization of protein-protein interactions (PPIs) is fundamental to the understanding of biochemical processes. Many methods have been established to identify and study direct PPIs; however, screening and investigating PPIs involving large or poorly soluble proteins remains challenging. Here, we introduce ReLo, a simple, rapid, and versatile cell culture-based method for detecting and investigating interactions in a cellular context. Our experiments demonstrate that ReLo specifically detects direct binary PPIs. Furthermore, we show that ReLo bridging experiments can also be used to determine the binding topology of subunits within multiprotein complexes. In addition, ReLo facilitates the identification of protein domains that mediate complex formation, allows screening for interfering point mutations, and it is sensitive to drugs that mediate or disrupt an interaction. In summary, ReLo is a simple and rapid alternative for the study of PPIs, especially when studying structurally complex proteins or when established methods fail.
Inverse relationship between species competitiveness and intraspecific trait variability may enable species coexistence in experimental seedling communities
Authors: Yang Jing , Wang Xiya , Carmona Carlos P. , Wang Xihua , Shen Guochun
Published: April 2024

Theory suggests that intraspecific trait variability may promote species coexistence when competitively inferior species have higher intraspecific trait variability than their superior competitors. Here, we provide empirical evidence for this phenomenon in tree seedlings. We evaluated intraspecific variability and plastic response of ten traits in 6750 seedlings of ten species in a three-year greenhouse experiment. While we observed no relationship between intraspecific trait variability and species competitiveness in competition-free homogeneous environments, an inverse relationship emerged under interspecific competition and in spatially heterogeneous environments. We showed that this relationship is driven by the plastic response of the competitively inferior species: Compared to their competitively superior counterparts, they exhibited a greater increase in trait variability, particularly in fine-root traits, in response to competition, environmental heterogeneity and their combination. Our findings contribute to understanding how interspecific competition and intraspecific trait variability together structure plant communities.
RNA-seq analysis in simulated microgravity unveils down-regulation of the beta-rhizobial siderophore phymabactin
Authors: Golaz Daphné , Papenfuhs Chad K. , Bellés-Sancho Paula , Eberl Leo , Egli Marcel , Pessi Gabriella
Published: April 2024

Exploiting the symbiotic interaction between crops and nitrogen-fixing bacteria is a simple and ecological method to promote plant growth in prospective extraterrestrial human outposts. In this study, we performed an RNA-seq analysis to investigate the adaptation of the legume symbiont Paraburkholderia phymatum STM815T to simulated microgravity (s0-g) at the transcriptome level. The results revealed a drastic effect on gene expression, with roughly 23% of P. phymatum genes being differentially regulated in s0-g. Among those, 951 genes were upregulated and 858 downregulated in the cells grown in s0-g compared to terrestrial gravity (1 g). Several genes involved in posttranslational modification, protein turnover or chaperones encoding were upregulated in s0-g, while those involved in translation, ribosomal structure and biosynthesis, motility or inorganic ions transport were downregulated. Specifically, the whole phm gene cluster, previously bioinformatically predicted to be involved in the production of a hypothetical malleobactin-like siderophore, phymabactin, was 20-fold downregulated in microgravity. By constructing a mutant strain (ΔphmJK) we confirmed that the phm gene cluster codes for the only siderophore secreted by P. phymatum as assessed by the complete lack of iron chelating activity of the P. phymatum ΔphmJK mutant on chrome azurol S (CAS) agar plates. These results not only provide a deeper understanding of the physiology of symbiotic organisms exposed to space-like conditions, but also increase our knowledge of iron acquisition mechanisms in rhizobia.
Wireless pressure monitoring system utilizing a 3D-printed Origami pressure sensor array
Authors: Moeinnia Hadi , Agron Danielle Jaye , Ganzert Carl , Schubert Loren , Kim Woo Soo
Published: April 2024

We present here a 3D-printed pressure mapping mat, equipped with customizable architecture sensors, that offers a cost-effective and adaptable solution, overcoming the size constraints and sensing accuracy issues commonly associated with existing commercial pressure mats across various fields, such as healthcare and sports applications. Leveraging a pillar-origami structure, the demonstrated sensor offers multifaceted stiffness properties, effectively filtering skin deformations and enabling capacitive pressure sensing. Notably, the sensor’s detection range can be finely tuned, spanning from 70 to 2500 kPa, with a sensitivity range between 0.01 kPa-1 and 0.0002 kPa-1, and an impressive response time of just 800 milliseconds. Furthermore, the inclusion of a modular sensor array enhances maintenance and allows for greater flexibility in shaping and enhancing the device’s resolution. This technology finds practical applications in wireless foot pressure mapping and sports protection pads, marking a significant milestone in the advancement of flexible and custom-shaped pressure sensor technology.
Influences of amyloid-β and tau on white matter neurite alterations in dementia with Lewy bodies
Authors: Mak Elijah , Reid Robert I. , Przybelski Scott A. , Lesnick Timothy G. , Schwarz Christopher G. , Senjem Matthew L. , Raghavan Sheelakumari , Vemuri Prashanthi , Jack Clifford R. , Min Hoon Ki , Jain Manoj K. , Miyagawa Toji , Forsberg Leah K. , Fields Julie A. , Savica Rodolfo , Graff-Radford Jonathan , Jones David T. , Botha Hugo , St. Louis Erik K. , Knopman David S. , Ramanan Vijay K. , Dickson Dennis W. , Graff-Radford Neill R. , Ferman Tanis J. , Petersen Ronald C. , Lowe Val J. , Boeve Bradley F. , O’Brien John T. , Kantarci Kejal
Published: April 2024

Dementia with Lewy bodies (DLB) is a neurodegenerative condition often co-occurring with Alzheimer’s disease (AD) pathology. Characterizing white matter tissue microstructure using Neurite Orientation Dispersion and Density Imaging (NODDI) may help elucidate the biological underpinnings of white matter injury in individuals with DLB. In this study, diffusion tensor imaging (DTI) and NODDI metrics were compared in 45 patients within the dementia with Lewy bodies spectrum (mild cognitive impairment with Lewy bodies (n = 13) and probable dementia with Lewy bodies (n = 32)) against 45 matched controls using conditional logistic models. We evaluated the associations of tau and amyloid-β with DTI and NODDI parameters and examined the correlations of AD-related white matter injury with Clinical Dementia Rating (CDR). Structural equation models (SEM) explored relationships among age, APOE ε4, amyloid-β, tau, and white matter injury. The DLB spectrum group exhibited widespread white matter abnormalities, including reduced fractional anisotropy, increased mean diffusivity, and decreased neurite density index. Tau was significantly associated with limbic and temporal white matter injury, which was, in turn, associated with worse CDR. SEM revealed that amyloid-β exerted indirect effects on white matter injury through tau. We observed widespread disruptions in white matter tracts in DLB that were not attributed to AD pathologies, likely due to α-synuclein-related injury. However, a fraction of the white matter injury could be attributed to AD pathology. Our findings underscore the impact of AD pathology on white matter integrity in DLB and highlight the utility of NODDI in elucidating the biological basis of white matter injury in DLB.
Reverse development of vaccines against antimicrobial-resistant pathogens
Authors: Bagnoli Fabio , Galgani Ilaria , Vadivelu V. Kumaran , Phogat Sanjay
Published: April 2024

Vaccine R&D is typically a lengthy process taking >10 years. However, vaccines still fail in clinical development because of unreliable animal models or absent immunological correlates of protection. Without a correlate of protection, phase-1 and -2 studies of safety and immunogenicity can fail to predict phase-3 efficacy. Indeed, the history of vaccine development is replete with promising phase-1 and -2 results and failed phase-3 efficacy trials. To avoid this misfortune, we present Reverse Vaccine Development for vaccines against antimicrobial-resistant (AMR) pathogens. In this approach, instead of evaluating efficacy in phase 3, proof-of-principle efficacy is evaluated as early as possible in a population with a high incidence of disease, which may differ from the population intended for registration, and can be a controlled human infection population. To identify a correlate of protection in these populations, the vaccine-elicited immune response is compared between protected and unprotected subjects. If a correlate is identified, it can help to refine the vaccine dosage, schedule, and formulation, and facilitate the assessment of vaccine efficacy in other populations with different attack rates, subject characteristics, and disease manifestations. This may be the only way to provide life-saving vaccines to populations affected by AMR-pathogen diseases at incidences that are typically low and unsuited to phase-3 efficacy trials. The availability of a correlate of protection early in clinical development can potentially prevent failures of large phase-3 trials and unnecessary exposures of populations to inefficacious vaccines that have resulted in disinvestment in the development of vaccines against AMR pathogens.
An air- and moisture-stable ruthenium precatalyst for diverse reactivity
Authors: McArthur Gillian , Docherty Jamie H. , Hareram Mishra Deepak , Simonetti Marco , Vitorica-Yrezabal Iñigo J. , Douglas James J. , Larrosa Igor
Published: April 2024

Versatile, efficient and robust (pre)catalysts are pivotal in accelerating the discovery and optimization of chemical reactions, shaping diverse synthetic fields such as cross-coupling, C–H functionalization and polymer chemistry. Yet, their scarcity in certain domains has hindered the advancement and adoption of new applications. Here we present a highly reactive air- and moisture-stable ruthenium precatalyst [(tBuCN)5Ru(H2O)](BF4)2, featuring a key exchangeable water ligand. This versatile precatalyst drives an array of transformations, including late-stage C(sp2)–H arylation, primary/secondary alkylation, methylation, hydrogen/deuterium exchange, C(sp3)–H oxidation, alkene isomerization and oxidative cleavage, consistently outperforming conventionally used ruthenium (pre)catalysts. The generality and applicability of this precatalyst is exemplified through the potential for rapid screening and optimization of photocatalytic reactions with a suite of in situ generated ruthenium photocatalysts containing hitherto unknown complexes, and through the rapid discovery of reactivities previously unreported for ruthenium. The diverse applicability observed is suggestive of a generic platform for reaction simplification and accelerated synthetic discovery that will enable broader applicability and accessibility to state-of-the-art ruthenium catalysis.
Nobiletin alleviates cisplatin-induced ototoxicity via activating autophagy and inhibiting NRF2/GPX4-mediated ferroptosis
Authors: Song Wenao , Zhang Li , Cui Xiaolin , Wang Rongrong , Ma Jingyu , Xu Yue , Jin Yan , Wang Dawei , Lu Zhiming
Published: April 2024

Nobiletin, a citrus polymethoxy flavonoid with antiapoptotic and antioxidative properties, could safeguard against cisplatin-induced nephrotoxicity and neurotoxicity. Cisplatin, as the pioneer of anti-cancer drug, the severe ototoxicity limits its clinical applications, while the effect of nobiletin on cisplatin-induced ototoxicity has not been identified. The current study investigated the alleviating effect of nobiletin on cisplatin-induced ototoxicity and the underlying mechanisms. Apoptosis and ROS formation were evaluated using the CCK-8 assay, Western blotting, and immunofluorescence, indicating that nobiletin attenuated cisplatin-induced apoptosis and oxidative stress. LC3B and SQSTM1/p62 were determined by Western blotting, qPCR, and immunofluorescence, indicating that nobiletin significantly activated autophagy. Nobiletin promoted the nuclear translocation of NRF2 and the transcription of its target genes, including Hmox1, Nqo1, and ferroptosis markers (Gpx4, Slc7a11, Fth, and Ftl), thereby inhibiting ferroptosis. Furthermore, RNA sequencing analysis verified that autophagy, ferroptosis, and the NRF2 signaling pathway served as crucial points for the protection of nobiletin against ototoxicity caused by cisplatin. Collectively, these results indicated, for the first time, that nobiletin alleviated cisplatin-elicited ototoxicity through suppressing apoptosis and oxidative stress, which were attributed to the activation of autophagy and the inhibition of NRF2/GPX4-mediated ferroptosis. Our study suggested that nobiletin could be a prospective agent for preventing cisplatin-induced hearing loss.
Immune checkpoint inhibitors for metastatic uveal melanoma: a meta-analysis
Authors: Yamada Kayoko , Takeuchi Masaki , Fukumoto Takeshi , Suzuki Minako , Kato Ai , Mizuki Yuki , Yamada Norihiro , Kaneko Takeshi , Mizuki Nobuhisa , Horita Nobuyuki
Published: April 2024

Several studies have evaluated immune checkpoint inhibitors (ICIs) for metastatic uveal melanoma; however, the efficacy of ICIs in the previous studies varied greatly. In this systematic review, we searched for prospective or retrospective studies on single or dual-ICIs for metastatic uveal melanoma treatment. A random-effect model meta-analysis with generic inverse-variance was conducted, and 36 articles representing 41 cohorts of 1414 patients with metastatic uveal melanoma were included. The pooled outcomes were as follows: objective response rate (ORR) was 5.6% (95% confidence interval [95%CI] 3.7–7.5%; I2, 36%), disease control rate (DCR) was 32.5% (95% CI 27.2–37.7%; I2, 73%), median progression-free survival was 2.8 months (95% CI 2.7–2.9 months; I2, 26%), and median overall survival (OS) was 11.2 months (95% CI 9.6–13.2 months; I2, 74%). Compared to single-agent ICI, dual ICI led to better ORR (single-agent: 3.4% [95% CI 1.8–5.1]; dual-agent: 12.4% [95% CI 8.0–16.9]; P < 0.001), DCR (single-agent: 29.3%, [95% CI 23.4–35.2]; dual-agent: 44.3% [95% CI 31.7–56.8]; P = 0.03), and OS (single-agent: 9.8 months [95% CI 8.0–12.2]; dual-agent: 16.3 months [95% CI 13.5–19.7]; P < 0.001). Our analysis provided treatment outcomes as described above. Dual-ICIs appear better than single-agent ICIs for the treatment of metastatic uveal melanoma.
Pulsar glitches from quantum vortex networks
Authors: Marmorini Giacomo , Yasui Shigehiro , Nitta Muneto
Published: April 2024

Neutron stars or pulsars are very rapidly rotating compact stars with extremely high density. One of the unsolved long-standing problems of these enigmatic celestial bodies is the origin of pulsars’ glitches, i.e., the sudden rapid deceleration in the rotation speed of neutron stars. Although many glitch events have been reported, there is no consensus on the microscopic mechanism responsible for them. One of the important characterizations of the glitches is the scaling law $$P(E) \sim E^{-\alpha }$$

P

(
E
)

∼

E

-
α

of the probability distribution for a glitch with energy E. Here, we reanalyse the accumulated up-to-date observation data to obtain the exponent $$\alpha \approx 0.88$$

α
≈
0.88

for the scaling law, and propose a simple microscopic model that naturally deduces this scaling law without any free parameters. Our model explains the appearance of these glitches in terms of the presence of quantum vortex networks arising at the interface of two different kinds of superfluids in the core of neutron stars; a p-wave neutron superfluid in the inner core which interfaces with the s-wave neutron superfluid in the outer core, where each integer vortex in the s-wave superfluid connects to two half-quantized vortices in the p-wave superfluid through structures called “boojums”.
Particle Swarm Optimization for exploring Darcy–Forchheimer flow of Casson fluid between co-axial rotating disks with the Cattaneo–Christov model
Authors: Uddin Ziya , Upreti Himanshu , Ganga Sai , Ibrahim Wubshet
Published: April 2024

In this paper, we carried out a numerical analysis of the fluid dynamics and heat transfer occurring between two parallel disks. The study accounts for the impact of temperature-dependent fluid viscosity and thermal conductivity. We systematically investigated various parameters, including viscosity, thermal conductivity, rotational behavior (rotation or counter-rotation), and the presence of stretching, aiming to comprehend their effects on fluid velocity, temperature profiles, and pressure distributions. Our research constructs a mathematical model that intricately couples fluid heat transfer and pressure distribution within the rotating system. To solve this model, we employed the 'Particle Swarm Optimization' method in tandem with the finite difference approach. The results are presented through visual representations of fluid flow profiles, temperature, and pressure distributions along the rotational axis. The findings revealed that the change in Casson factor from 2.5 to 1.5 resulted in a reduction of skin friction by up to 65%, while the change in local Nusselt number was minimal. Furthermore, both the viscosity variation parameter and thermal conductivity parameters were found to play significant roles in regulating both skin friction and local Nusselt number. These findings will have practical relevance to scientists and engineers working in fields related to heat management, such as those involved in rotating gas turbines, computer storage devices, medical equipment, space vehicles, and various other applications.
Exploring the electrical robustness of conductive textile fasteners for wearable devices in different human motion conditions
Authors: Fortes Ferreira Afonso , Alves Helena , da Silva Hugo Plácido , Marques Nuno , Fred Ana
Published: April 2024

Conventional snap fasteners used in clothing are often used as electrical connectors in e-textile and wearable applications for signal transmission due to their wide availability and ease of use. Nonetheless, limited research exists on the validation of these fasteners, regarding the impact of contact-induced high-amplitude artefacts, especially under motion conditions. In this work, three types of fasteners were used as electromechanical connectors, establishing the interface between a regular sock and an acquisition device. The tested fasteners have different shapes and sizes, as well as have different mechanisms of attachment between the plug and receptacle counterparts. Experimental evaluation was performed under static conditions, slow walking, and rope jumping at a high cadence. The tests were also performed with a test mass of 140 g. Magnetic fasteners presented excellent electromechanical robustness under highly dynamic human movement with and without the additional mass. On the other hand, it was demonstrated that the Spring snap buttons (with a spring-based engaging mechanism) presented a sub-optimal performance under high motion and load conditions, followed by the Prong snap fasteners (without spring), which revealed a high susceptibility to artefacts. Overall, this work provides further evidence on the importance and reliability of clothing fasteners as electrical connectors in wearable systems.
Attenuation of spatial bias with target template variation
Authors: Hong Injae , Kim Min-Shik
Published: April 2024

This study investigated the impact of target template variation or consistency on attentional bias in location probability learning. Participants conducted a visual search task to find a heterogeneous shape among a homogeneous set of distractors. The target and distractor shapes were either fixed throughout the experiment (target-consistent group) or unpredictably varied on each trial (target-variant group). The target was often presented in one possible search region, unbeknownst to the participants. When the target template was consistent throughout the biased visual search, spatial attention was persistently biased toward the frequent target location. However, when the target template was inconsistent and varied during the biased search, the spatial bias was attenuated so that attention was less prioritized to a frequent target location. The results suggest that the alternative use of target templates may interfere with the emergence of a persistent spatial bias. The regularity-based spatial bias depends on the number of attentional shifts to the frequent target location, but also on search-relevant contexts.
Real-time cortical dynamics during motor inhibition
Authors: Casula Elias Paolo , Pezzopane Valentina , Roncaioli Andrea , Battaglini Luca , Rumiati Raffaella , Rothwell John , Rocchi Lorenzo , Koch Giacomo
Published: April 2024

The inhibition of action is a fundamental executive mechanism of human behaviour that involve a complex neural network. In spite of the progresses made so far, many questions regarding the brain dynamics occurring during action inhibition are still unsolved. Here, we used a novel approach optimized to investigate real-time effective brain dynamics, which combines transcranial magnetic stimulation (TMS) with simultaneous electroencephalographic (EEG) recordings. 22 healthy volunteers performed a motor Go/NoGo task during TMS of the hand-hotspot of the primary motor cortex (M1) and whole-scalp EEG recordings. We reconstructed source-based real-time spatiotemporal dynamics of cortical activity and cortico-cortical connectivity throughout the task. Our results showed a task-dependent bi-directional change in theta/gamma supplementary motor cortex (SMA) and M1 connectivity that, when participants were instructed to inhibit their response, resulted in an increase of a specific TMS-evoked EEG potential (N100), likely due to a GABA-mediated inhibition. Interestingly, these changes were linearly related to reaction times, when participants were asked to produce a motor response. In addition, TMS perturbation revealed a task-dependent long-lasting modulation of SMA–M1 natural frequencies, i.e. alpha/beta activity. Some of these results are shared by animal models and shed new light on the physiological mechanisms of motor inhibition in humans.
Impact of a virtual reality-based simulation training for shoulder dystocia on human and technical skills among caregivers: a randomized-controlled trial
Authors: Falcone Veronica , Catic Anja , Heinzl Florian , Steinbauer Philipp , Wagner Michael , Mikula Fanny , Dorittke Tim , Roessler Bernhard , Farr Alex
Published: April 2024

This study analyzed the adherence to the modified Advanced Life Support in Obstetrics (ALSO) algorithm (HELP-RER) for handling shoulder dystocia (SD) using a virtual reality (VR) training modality. Secondary outcomes were improvements in the post-training diagnosis-to-delivery time, human skills factors (HuFSHI), and perceived task-load index (TLX). Prospective, case–control, single-blind, 1:1 randomized crossover study. Participants were shown a 360° VR video of SD management. The control group was briefed theoretically. Both groups underwent HuFSHI and HELP-RER score assessments at baseline and after the manikin-based training. The TLX questionnaire was then administered. After a washout phase of 12 weeks, we performed a crossover, and groups were switched. There were similar outcomes between groups during the first training session. However, after crossover, the control group yielded significantly higher HELP-RER scores [7 vs. 6.5; (p = 0.01)], with lower diagnosis-to-delivery-time [85.5 vs. 99 s; (p = 0.02)], and TLX scores [57 vs. 68; (p = 0.04)]. In the multivariable linear regression analysis, VR training was independently associated with improved HELP-RER scores (p = 0.003). The HuFSHI scores were comparable between groups. Our data demonstrated the feasibility of a VR simulation training of SD management for caregivers. Considering the drawbacks of common high-fidelity trainings, VR-based simulations offer new perspectives.
RETRACTED ARTICLE: Bio synthesis, comprehensive
characterization, and multifaceted therapeutic applications of BSA-Resveratrol coated
platinum nanoparticles
Authors: Faisal Shah , Tariq Muhammad Hamza , Abdullah  , Zafar Sania , Un Nisa Zaib , Ullah Riaz , Ur Rahman Anees , Bari Ahmed , Ullah Khair , Khan Rahat Ullah
Published: April 2024

This study examines the manufacturing, characterization, and biological
evaluation of platinum nanoparticles, which were synthesized by Enterobacter cloacae and coated with Bovine Serum Albumin (BSA) and
Resveratrol (RSV). The formation of PtNPs was confirmed with the change of color from
dark yellow to black, which was due to the bioreduction of platinum chloride by
E. cloacae. BSA and RSV functionalization enhanced
these nanoparticles' biocompatibility and therapeutic potential. TGA, SEM, XRD, and FTIR
were employed for characterization, where PtNPs and drug conjugation-related functional
groups were studied by FTIR. XRD confirmed the crystalline nature of PtNPs and
Pt-BSA-RSV NPs, while TGA and SEM showed thermal stability and post-drug coating
morphological changes. Designed composite was also found to be biocompatible in nature
in hemolytic testing, indicating their potential in Biomedical applications. After
confirmation of PtNPs based nanocaompsite synthesis, they were examined for
anti-bacterial, anti-oxidant, anti-inflammatory, and anti-cancer properties. Pt-BSA-RSV
NPs showed higher concentration-dependent DPPH scavenging activity, which measured
antioxidant capability. Enzyme inhibition tests demonstrated considerable
anti-inflammatory activity against COX-2 and 15-LOX enzymes. In in vitro anticancer
studies, Pt-BSA-RSV NPs effectively killed human ovarian cancer cells. This phenomenon
was demonstrated to be facilitated by the acidic environment of cancer, as the drug
release assay confirmed the release of RSV from the NP formulation in the acidic
environment. Finally, Molecular docking also demonstrated that RSV has strong potential
as an anti-oxidant, antibacterial, anti-inflammatory, and anticancer agent. Overall, in
silico and in vitro investigations in the current study showed good medicinal
applications for designed nanocomposites, however, further in-vivo experiments must be
conducted to validate our findings.
A comprehensive approach to characterize navigation instruments for magnetic guidance in biological systems
Authors: Blümler Peter , Raudzus Fabian , Schmid Friederike
Published: April 2024

Achieving non-invasive spatiotemporal control over cellular functions, tissue organization, and behavior is a desirable aim for advanced therapies. Magnetic fields, due to their negligible interaction with biological matter, are promising for in vitro and in vivo applications, even in deep tissues. Particularly, the remote manipulation of paramagnetic (including superparamagnetic and ferromagnetic, all with a positive magnetic susceptibility) entities through magnetic instruments has emerged as a promising approach across various biological contexts. However, variations in the properties and descriptions of these instruments have led to a lack of reproducibility and comparability among studies. This article addresses the need for standardizing the characterization of magnetic instruments, with a specific focus on their ability to control the movement of paramagnetic objects within organisms. While it is well known that the force exerted on magnetic particles depends on the spatial variation (gradient) of the magnetic field, the magnitude of the field is often overlooked in the literature. Therefore, we comprehensively analyze and discuss both actors and propose a novel descriptor, termed ‘effective gradient’, which combines both dependencies. To illustrate the importance of both factors, we characterize different magnet systems and relate them to experiments involving superparamagnetic nanoparticles. This standardization effort aims to enhance the reproducibility and comparability of studies utilizing magnetic instruments for biological applications.
RPA-CRISPR/Cas12a assay for the diagnosis of bovine Anaplasma marginale infection
Authors: Sutipatanasomboon Arpaporn , Wongsantichon Jantana , Sakdee Somsri , Naksith Piyaporn , Watthanadirek Amaya , Anuracpreeda Panat , Blacksell Stuart D. , Saisawang Chonticha
Published: April 2024

Anaplasma marginale infection is one of the most common tick-borne diseases, causing a substantial loss in the beef and dairy production industries. Once infected, the pathogen remains in the cattle for life, allowing the parasites to spread to healthy animals. Since clinical manifestations of anaplasmosis occur late in the disease, a sensitive, accurate, and affordable pathogen identification is crucial in preventing and controlling the infection. To this end, we developed an RPA-CRISPR/Cas12a assay specific to A. marginale infection in bovines targeting the msp4 gene. Our assay is performed at one moderately high temperature, producing fluorescent signals or positive readout of a lateral flow dipstick, which is as sensitive as conventional PCR-based DNA amplification. This RPA-CRISPR/Cas12a assay can detect as few as 4 copies/μl of Anaplasma using msp4 marker without cross-reactivity to other common bovine pathogens. Lyophilized components of the assay can be stored at room temperature for an extended period, indicating its potential for field diagnosis and low-resource settings of anaplasmosis in bovines.
SOX11/PRDX2 axis modulates redox homeostasis and chemoresistance in aggressive mantle cell lymphoma
Authors: De Bolòs Anna , Sureda-Gómez Marta , Carreras-Caballé Maria , Rodríguez Marta-Leonor , Clot Guillem , Beà Silvia , Giné Eva , Campo Elias , Balsas Patricia , Amador Virginia
Published: April 2024

Mantle cell lymphoma (MCL) is an incurable B-cell neoplasm characterized by an aggressive behavior, short responses to conventional therapies and SOX11 overexpression, which is associated with aggressive disease features and inferior clinical outcome of patients. Oxidative stress is known to induce tumorigenesis and tumor progression, whereas high expression levels of antioxidant genes have been associated with chemoresistance in different cancers. However, the role of oxidative stress in MCL pathogenesis and the involvement of SOX11 regulating redox homeostasis in MCL cells are largely unknown. Here, by integrating gene set enrichment analysis of two independent series of MCL, we observed that SOX11+ MCL had higher reactive oxygen species (ROS) levels compared to SOX11− MCL primary tumors and increased expression of Peredoxine2 (PRDX2), which upregulation significantly correlated with SOX11 overexpression, higher ROS production and worse overall survival of patients. SOX11 knockout (SOX11KO) significantly reduced PRDX2 expression, and SOX11KO and PRDX2 knockdown (PRDX2KD) had increased ROS levels and ROS-mediated tumor cell death upon treatment with drugs, compared to control MCL cell lines. Our results suggest an aberrant redox homeostasis associated with chemoresistance in aggressive MCL through SOX11-mediated PRDX2 upregulation, highlighting PRDX2 as promising target for new therapeutic strategies to overcome chemoresistance in aggressive MCLs.
Cloning, functional expression, and pharmacological characterization of inwardly rectifying potassium channels (Kir) from Apis mellifera
Authors: Sourisseau Fabien , Chahine Chaimaa , Pouliot Valérie , Cens Thierry , Charnet Pierre , Chahine Mohamed
Published: April 2024

Potassium channels belong to the super family of ion channels and play a fundamental role in cell excitability. Kir channels are potassium channels with an inwardly rectifying property. They play a role in setting the resting membrane potential of many excitable cells including neurons. Although putative Kir channel family genes can be found in the Apis mellifera genome, their functional expression, biophysical properties, and sensitivity to small molecules with insecticidal activity remain to be investigated. We cloned six Kir channel isoforms from Apis mellifera that derive from two Kir genes, AmKir1 and AmKir2, which are present in the Apis mellifera genome. We studied the tissue distribution, the electrophysiological and pharmacological characteristics of three isoforms that expressed functional currents (AmKir1.1, AmKir2.2, and AmKir2.3). AmKir1.1, AmKir2.2, and AmKir2.3 isoforms exhibited distinct characteristics when expressed in Xenopus oocytes. AmKir1.1 exhibited the largest potassium currents and was impermeable to cesium whereas AmKir2.2 and AmKir2.3 exhibited smaller currents but allowed cesium to permeate. AmKir1 exhibited faster opening kinetics than AmKir2. Pharmacological experiments revealed that both AmKir1.1 and AmKir2.2 are blocked by the divalent ion barium, with IC50 values of 10−5 and 10−6 M, respectively. The concentrations of VU041, a small molecule with insecticidal properties required to achieve a 50% current blockade for all three channels were higher than those needed to block Kir channels in other arthropods, such as the aphid Aphis gossypii and the mosquito Aedes aegypti. From this, we conclude that Apis mellifera AmKir channels exhibit lower sensitivity to VU041.
Orthotopic model for the analysis of melanoma circulating tumor cells
Authors: Pícková Markéta , Kahounová Zuzana , Radaszkiewicz Tomasz , Procházková Jiřina , Fedr Radek , Nosková Michaela , Radaszkiewicz Katarzyna Anna , Ovesná Petra , Bryja Vítězslav , Souček Karel
Published: April 2024

Metastatic melanoma, a highly lethal form of skin cancer, presents significant clinical challenges due to limited therapeutic options and high metastatic capacity. Recent studies have demonstrated that cancer dissemination can occur earlier, before the diagnosis of the primary tumor. The progress in understanding the kinetics of cancer dissemination is limited by the lack of animal models that accurately mimic disease progression. We have established a xenograft model of human melanoma that spontaneously metastasizes to lymph nodes and lungs. This model allows precise monitoring of melanoma progression and is suitable for the quantitative and qualitative analysis of circulating tumor cells (CTCs). We have validated a flow cytometry-based protocol for CTCs enumeration and isolation. We could demonstrate that (i) CTCs were detectable in the bloodstream from the fourth week after tumor initiation, coinciding with the lymph node metastases appearance, (ii) excision of the primary tumor accelerated the formation of metastases in lymph nodes and lungs as early as one-week post-surgery, accompanied by the increased numbers of CTCs, and (iii) CTCs change their surface protein signature. In summary, we present a model of human melanoma that can be effectively utilized for future drug efficacy studies.