bluuebunny/crossref_metadata_2025_split huggingface dataset:
Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions
Authors: Lu Peilin , Ruan Dongxue , Huang Meiqi , Tian Mi , Zhu Kangshun , Gan Ziqi , Xiao Zecong 
Published: July 2024

AbstractThe applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements and the potential of hydrogels in therapeutic applications, focusing primarily on two areas: emerging cell-based therapies and promising non-cell therapeutic modalities. Within the context of cell therapy, we discuss the capacity of hydrogels to overcome the existing translational challenges faced by mainstream cell therapy paradigms, provide a detailed discussion on the advantages and principal design considerations of hydrogels for boosting the efficacy of cell therapy, as well as list specific examples of their applications in different disease scenarios. We then explore the potential of hydrogels in drug delivery, physical intervention therapies, and other non-cell therapeutic areas (e.g., bioadhesives, artificial tissues, and biosensors), emphasizing their utility beyond mere delivery vehicles. Additionally, we complement our discussion on the latest progress and challenges in the clinical application of hydrogels and outline future research directions, particularly in terms of integration with advanced biomanufacturing technologies. This review aims to present a comprehensive view and critical insights into the design and selection of hydrogels for both cell therapy and non-cell therapies, tailored to meet the therapeutic requirements of diverse diseases and situations.
Dynamicity of brain network organization & their community architecture as characterizing features for classification of common mental disorders from whole-brain connectome
Authors: Sastry Nisha Chetana , Banerjee Arpan 
Published: July 2024

AbstractThe urgency of addressing common mental disorders (bipolar disorder, attention-deficit hyperactivity disorder (ADHD), and schizophrenia) arises from their significant societal impact. Developing strategies to support psychiatrists is crucial. Previous studies focused on the relationship between these disorders and changes in the resting-state functional connectome’s modularity, often using static functional connectivity (sFC) estimation. However, understanding the dynamic reconfiguration of resting-state brain networks with rich temporal structure is essential for comprehending neural activity and addressing mental health disorders. This study proposes an unsupervised approach combining spatial and temporal characterization of brain networks to classify common mental disorders using fMRI timeseries data from two cohorts (N = 408 participants). We employ the weighted stochastic block model to uncover mesoscale community architecture differences, providing insights into network organization. Our approach overcomes sFC limitations and biases in community detection algorithms by modelling the functional connectome’s temporal dynamics as a landscape, quantifying temporal stability at whole-brain and network levels. Findings reveal individuals with schizophrenia exhibit less assortative community structure and participate in multiple motif classes, indicating less specialized network organization. Patients with schizophrenia and ADHD demonstrate significantly reduced temporal stability compared to healthy controls. This study offers insights into functional connectivity (FC) patterns’ spatiotemporal organization and their alterations in common mental disorders, highlighting the potential of temporal stability as a biomarker.
Semiautomated experiment with a robotic system and data generation by foundation models for synthesis of polyamic acid particles
Authors: Hatakeyama-Sato Kan , Ishikawa Hiroki , Takaishi Shinya , Igarashi Yasuhiko , Nabae Yuta , Hayakawa Teruaki 
Published: July 2024

AbstractA semiautomated system for synthesizing polyamic acid particles using a custom liquid-handling device and a robotic arm is proposed in this study. Integration of cameras and a multimodal large language model facilitates continuous monitoring and documentation, enhancing objectivity in synthetic experiments and enabling future advancements in experimental research.
Asset-level assessment of climate physical risk matters for adaptation finance
Authors: Bressan Giacomo , Đuranović Anja , Monasterolo Irene , Battiston Stefano 
Published: July 2024

AbstractClimate physical risk assessment is crucial to inform adaptation policies and finance. However, science-based and transparent solutions to assess climate physical risks are limited, compounding the adaptation gap. This is a main limitation to fill the adaptation gap. We provide a methodology that quantifies physical risks on geolocalized productive assets, considering their exposure to chronic and acute impacts (hurricanes) across the scenarios of the Intergovernmental Panel on Climate Change. Then, we translate asset-level shocks into economic and financial losses. We apply the methodology to Mexico, a country highly exposed to physical risks, recipient of adaptation finance and foreign investments. We show that investor losses are underestimated up to 70% when neglecting asset-level information, and up to 82% when neglecting tail acute risks. Therefore, neglecting the asset-level and acute dimensions of physical risks leads to large errors in the identification of adaptation policy responses, investments and finance tools aimed to build resilience to climate change.
The chromatin regulator Ankrd11 controls cardiac neural crest cell-mediated outflow tract remodeling and heart function
Authors: Kibalnyk Yana , Afanasiev Elia , Noble Ronan M. N. , Watson Adrianne E. S. , Poverennaya Irina , Dittmann Nicole L. , Alexiou Maria , Goodkey Kara , Greenwell Amanda A. , Ussher John R. , Adameyko Igor , Massey James , Graf Daniel , Bourque Stephane L. , Stratton Jo Anne , Voronova Anastassia 
Published: July 2024

AbstractANKRD11 (Ankyrin Repeat Domain 11) is a chromatin regulator and a causative gene for KBG syndrome, a rare developmental disorder characterized by multiple organ abnormalities, including cardiac defects. However, the role of ANKRD11 in heart development is unknown. The neural crest plays a leading role in embryonic heart development, and its dysfunction is implicated in congenital heart defects. We demonstrate that conditional knockout of Ankrd11 in the murine embryonic neural crest results in persistent truncus arteriosus, ventricular dilation, and impaired ventricular contractility. We further show these defects occur due to aberrant cardiac neural crest cell organization leading to outflow tract septation failure. Lastly, knockout of Ankrd11 in the neural crest leads to impaired expression of various transcription factors, chromatin remodelers and signaling pathways, including mTOR, BMP and TGF-β in the cardiac neural crest cells. In this work, we identify Ankrd11 as a regulator of neural crest-mediated heart development and function.
An outside individual option increases optimism and facilitates collaboration when groups form flexibly
Authors: Mori Ryutaro , Hanaki Nobuyuki , Kameda Tatsuya 
Published: July 2024

AbstractVoluntary participation is a central yet understudied aspect of collaboration. Here, we model collaboration as people’s voluntary choices between joining an uncertain public goods provisioning in groups and pursuing a less profitable but certain individual option. First, we find that voluntariness in collaboration increases the likelihood of group success via two pathways, both contributing to form more optimistic groups: pessimistic defectors are filtered out from groups, and some individuals update their beliefs to become cooperative. Second, we reconcile these findings with existing literature that highlights the detrimental effects of an individual option. We argue that the impact of an outside individual option on collaboration depends on the “externality” of loners — the influence that those leaving the group still exert on group endeavors. Theoretically and experimentally, we show that if collaboration allows for flexible group formation, the negative externality of loners remains limited, and the presence of an individual option robustly aids collaborative success.
Linear ubiquitination regulates the KSHV replication and transcription activator protein to control infection
Authors: Luan Yi , Long Wenying , Dai Lisi , Tao Panfeng , Deng Zhifen , Xia Zongping 
Published: July 2024

AbstractLike many other viruses, KSHV has two life cycle modes: the latent phase and the lytic phase. The RTA protein from KSHV is essential for lytic reactivation, but how this protein’s activity is regulated is not fully understood. Here, we report that linear ubiquitination regulates the activity of RTA during KSHV lytic reactivation and de novo infection. Overexpressing OTULIN inhibits KSHV lytic reactivation, whereas knocking down OTULIN or overexpressing HOIP enhances it. Intriguingly, we found that RTA is linearly polyubiquitinated by HOIP at K516 and K518, and these modifications control the RTA’s nuclear localization. OTULIN removes linear polyubiquitin chains from cytoplasmic RTA, preventing its nuclear import. The RTA orthologs encoded by the EB and MHV68 viruses are also linearly polyubiquitinated and regulated by OTULIN. Our study establishes that linear polyubiquitination plays a critically regulatory role in herpesvirus infection, adding virus infection to the list of biological processes known to be controlled by linear polyubiquitination.
Single-base tiled screen unveils design principles of PspCas13b for potent and off-target-free RNA silencing
Authors: Hu Wenxin , Kumar Amit , Ahmed Syed Faraz , Qi Shijiao , Ma David K. G. , Chen Honglin , Singh Gurjeet J. , Casan Joshua M. L. , Haber Michelle , Voskoboinik Ilia , McKay Matthew R. , Trapani Joseph A. , Ekert Paul G. , Fareh Mohamed 
Published: July 2024

AbstractThe development of precise RNA-editing tools is essential for the advancement of RNA therapeutics. CRISPR (clustered regularly interspaced short palindromic repeats) PspCas13b is a programmable RNA nuclease predicted to offer superior specificity because of its 30-nucleotide spacer sequence. However, its design principles and its on-target, off-target and collateral activities remain poorly characterized. Here, we present single-base tiled screening and computational analyses that identify key design principles for potent and highly selective RNA recognition and cleavage in human cells. We show that the de novo design of spacers containing guanosine bases at precise positions can greatly enhance the catalytic activity of inefficient CRISPR RNAs (crRNAs). These validated design principles (integrated into an online tool, https://cas13target.azurewebsites.net/) can predict highly effective crRNAs with ~90% accuracy. Furthermore, the comprehensive spacer–target mutagenesis revealed that PspCas13b can tolerate only up to four mismatches and requires ~26-nucleotide base pairing with the target to activate its nuclease domains, highlighting its superior specificity compared to other RNA or DNA interference tools. On the basis of this targeting resolution, we predict an extremely low probability of PspCas13b having off-target effects on other cellular transcripts. Proteomic analysis validated this prediction and showed that, unlike other Cas13 orthologs, PspCas13b exhibits potent on-target activity and lacks collateral effects.
Asymmetric apical domain states of mitochondrial Hsp60 coordinate substrate engagement and chaperonin assembly
Authors: Braxton Julian R. , Shao Hao , Tse Eric , Gestwicki Jason E. , Southworth Daniel R. 
Published: July 2024

AbstractThe mitochondrial chaperonin, mitochondrial heat shock protein 60 (mtHsp60), promotes the folding of newly imported and transiently misfolded proteins in the mitochondrial matrix, assisted by its co-chaperone mtHsp10. Despite its essential role in mitochondrial proteostasis, structural insights into how this chaperonin progresses through its ATP-dependent client folding cycle are not clear. Here, we determined cryo-EM structures of a hyperstable disease-associated human mtHsp60 mutant, V72I. Client density is identified in three distinct states, revealing interactions with the mtHsp60 apical domains and C termini that coordinate client positioning in the folding chamber. We further identify an asymmetric arrangement of the apical domains in the ATP state, in which an alternating up/down configuration positions interaction surfaces for simultaneous recruitment of mtHsp10 and client retention. Client is then fully encapsulated in mtHsp60–10, revealing prominent contacts at two discrete sites that potentially support maturation. These results identify distinct roles for the apical domains in coordinating client capture and progression through the chaperone cycle, supporting a conserved mechanism of group I chaperonin function.
Effect of temperature on the biological parameters of pink bollworm, Pectinophora gossypiella Saunders (Lepidoptera: Gelechiidae)
Authors: Nagaraju Madhu Tadagavadi , Mohan Kamanur Murali , Keerthi Manikyanahalli Chandrashekara , Prabhulinga Tenguri , Thube Shivaji , Shah Vivek , Elansary Hosam O. , Mousa Ihab Mohamed , El-Sheikh Mohamed A. 
Published: July 2024

AbstractPink bollworm (PBW) Pectinophora gossypiella is an important pest cotton worldwide. There are multiple factors which determines the occurrence and distribution of P. gossypiella across different cotton growing regions of the world, and one such key factor is ‘temperature’. The aim was to analyze the life history traits of PBW across varying temperature conditions. We systematically explored the biological and demographic parameters of P. gossypiella at five distinct temperatures; 20, 25, 30, 35 and 40 ± 1 °C maintaining a photoperiod of LD 16:8 h. The results revealed that the total developmental period of PBW shortens with rising temperatures, and the highest larval survival rates were observed between 30 °C and 35 °C, reaching 86.66% and 80.67%, respectively. Moreover, significant impacts were observed as the pupal weight, percent mating success, and fecundity exhibited higher values at 30 °C and 35 °C. Conversely, percent egg hatching, larval survival, and adult emergence were notably lower at 20 °C and 40 °C, respectively. Adult longevity decreased with rising temperatures, with females outliving males across all treatments. Notably, thermal stress had a persistent effect on the F1 generation, significantly affecting immature stages (egg and larvae), while its impact on reproductive potential was minimal. These findings offer valuable insights for predicting the population dynamics of P. gossypiella at the field level and developing climate-resilient management strategies in cotton.
ToF-SIMS evaluation of PEG-related mass peaks and applications in PEG detection in cosmetic products
Authors: Shen Yanjie , Son Jiyoung , Yu Xiao-Ying 
Published: July 2024

AbstractPolyethylene glycols (PEGs) are used in industrial, medical, health care, and personal care applications. The cycling and disposal of synthetic polymers like PEGs pose significant environmental concerns. Detecting and monitoring PEGs in the real world calls for immediate attention. This study unveils the efficacy of time-of-flight secondary ion mass spectrometry (ToF-SIMS) as a reliable approach for precise analysis and identification of reference PEGs and PEGs used in cosmetic products. By comparing SIMS spectra, we show remarkable sensitivity in pinpointing distinctive ion peaks inherent to various PEG compounds. Moreover, the employment of principal component analysis effectively discriminates compositions among different samples. Notably, the application of SIMS two-dimensional image analysis visually portrays the spatial distribution of various PEGs as reference materials. The same is observed in authentic cosmetic products. The application of ToF-SIMS underscores its potential in distinguishing PEGs within intricate environmental context. ToF-SIMS provides an effective solution to studying emerging environmental challenges, offering straightforward sample preparation and superior detection of synthetic organics in mass spectral analysis. These features show that SIMS can serve as a promising alternative for evaluation and assessment of PEGs in terms of the source, emission, and transport of anthropogenic organics.
sUPRa is a dual-color reporter for unbiased quantification of the unfolded protein response with cellular resolution
Authors: Chakrabarty Atreyi , Newey Sarah E. , Promi Maisha M. , Agbetiameh Belinda K. , Munro Daniella , Brodersen Paul J. N. , Gothard Gemma , Mahfooz Kashif , Mengual Jose P. , Vyazovskiy Vladyslav V. , Akerman Colin J. 
Published: July 2024

AbstractThe unfolded protein response (UPR) maintains proteostasis upon endoplasmic reticulum (ER) stress, and is initiated by a range of physiological and pathological processes. While there have been advances in developing fluorescent reporters for monitoring individual signaling pathways of the UPR, this approach may not capture a cell’s overall UPR activity. Here we describe a novel sensor of UPR activity, sUPRa, which is designed to report the global UPR. sUPRa displays excellent response characteristics, outperforms reporters of individual UPR pathways in terms of sensitivity and kinetics, and responds to a range of different ER stress stimuli. Furthermore, sUPRa’s dual promoter and fluorescent protein design ensures that both UPR-active and inactive cells are detected, and controls for reporter copy number. Using sUPRa, we reveal UPR activation in layer 2/3 pyramidal neurons of mouse cerebral cortex following a period of sleep deprivation. sUPRa affords new opportunities for quantifying physiological UPR activity with cellular resolution.
Efficient handling of ACL policy change in SDN using reactive and proactive flow rule installation
Authors: Hussain Mudassar , Amin Rashid , Gantassi Rahma , Alshehri Asma Hassan , Frnda Jaroslav , Raza Syed Mohsan 
Published: July 2024

AbstractSoftware-defined networking (SDN) is a pioneering network paradigm that strategically decouples the control plane from the data and management planes, thereby streamlining network administration. SDN's centralized network management makes configuring access control list (ACL) policies easier, which is important as these policies frequently change due to network application needs and topology modifications. Consequently, this action may trigger modifications at the SDN controller. In response, the controller performs computational tasks to generate updated flow rules in accordance with modified ACL policies and installs flow rules at the data plane. Existing research has investigated reactive flow rules installation that changes in ACL policies result in packet violations and network inefficiencies. Network management becomes difficult due to deleting inconsistent flow rules and computing new flow rules per modified ACL policies. The proposed solution efficiently handles ACL policy change phenomena by automatically detecting ACL policy change and accordingly detecting and deleting inconsistent flow rules along with the caching at the controller and adding new flow rules at the data plane. A comprehensive analysis of both proactive and reactive mechanisms in SDN is carried out to achieve this. To facilitate the evaluation of these mechanisms, the ACL policies are modeled using a 5-tuple structure comprising Source, Destination, Protocol, Ports, and Action. The resulting policies are then translated into a policy implementation file and transmitted to the controller. Subsequently, the controller utilizes the network topology and the ACL policies to calculate the necessary flow rules and caches these flow rules in hash table in addition to installing them at the switches. The proposed solution is simulated in Mininet Emulator using a set of ACL policies, hosts, and switches. The results are presented by varying the ACL policy at different time instances, inter-packet delay and flow timeout value. The simulation results show that the reactive flow rule installation performs better than the proactive mechanism with respect to network throughput, packet violations, successful packet delivery, normalized overhead, policy change detection time and end-to-end delay. The proposed solution, designed to be directly used on SDN controllers that support the Pyretic language, provides a flexible and efficient approach for flow rule installation. The proposed mechanism can be employed to facilitate network administrators in implementing ACL policies. It may also be integrated with network monitoring and debugging tools to analyze the effectiveness of the policy change mechanism.
DUSP1 and SOX2 expression determine squamous cell carcinoma of the salivary gland progression
Authors: Acero-Riaguas Lucía , Griso-Acevedo Ana Belén , SanLorenzo-Vaquero Alejandro , Ibáñez-Herrera Blanca , Fernandez-Diaz Sara María , Mascaraque Marta , Sánchez-Siles Rocío , López-García Iván , Benítez-Buelga Carlos , Bravo-Burguillos Elena Ruiz , Castelo Beatriz , Cebrián-Carretero José Luis , Perona Rosario , Sastre Leandro , Sastre-Perona Ana 
Published: July 2024

AbstractSalivary gland squamous cell carcinomas (SG-SCCs) constitute a rare type of head and neck cancer which is linked to poor prognosis. Due to their low frequency, the molecular mechanisms responsible for their aggressiveness are poorly understood. In this work we studied the role of the phosphatase DUSP1, a negative regulator of MAPK activity, in controlling SG-SCC progression. We generated DUSP1 KO clones in A253 human cells. These clones showed a reduced ability to grow in 2D, self-renew in ECM matrices and to form tumors in immunodeficient mice. This was caused by an overactivation of the stress and apoptosis kinase JNK1/2 in DUSP1−/+ clones. Interestingly, RNAseq analysis revealed that the expression of SOX2, a well-known self-renewal gene was decreased at the mRNA and protein levels in DUSP1−/+ cells. Unexpectedly, CRISPR-KO of SOX2 did not recapitulate DUSP1−/+ phenotype, and SOX2-null cells had an enhanced ability to self-renew and to form tumors in mice. Gene expression analysis demonstrated that SOX2-null cells have a decreased squamous differentiation profile -losing TP63 expression- and an increased migratory phenotype, with an enhanced epithelial to mesenchymal transition signature. In summary, our data indicates that DUSP1 and SOX2 have opposite functions in SG-SCC, being DUSP1 necessary for tumor growth and SOX2 dispensable showing a tumor suppressor function. Our data suggest that the combined expression of SOX2 and DUSP1 could be a useful biomarker to predict progression in patients with SG-SCCs.