bluuebunny/crossref_metadata_2025_split huggingface dataset:
Base preference for inosine 3′-riboendonuclease activity of human endonuclease V: implications for cleavage of poly-A tails containing inosine
Authors: Mitsuoka Kazuma , Kim Jung In , Yoshida Aya , Matsumoto Akane , Aoki-Shioi Narumi , Iwai Shigenori , Kuraoka Isao 
Published: July 2024

AbstractDeamination of bases is a form of DNA damage that occurs spontaneously via the hydrolysis and nitrosation of living cells, generating hypoxanthine from adenine. E. coli endonuclease V (eEndoV) cleaves hypoxanthine-containing double-stranded DNA, whereas human endonuclease V (hEndoV) cleaves hypoxanthine-containing RNA; however, hEndoV in vivo function remains unclear. To date, hEndoV has only been examined using hypoxanthine, because it binds closely to the base located at the cleavage site. Here, we examined whether hEndoV cleaves other lesions (e.g., AP site, 6-methyladenine, xanthine) to reveal its function and whether 2′-nucleoside modification affects its cleavage activity. We observed that hEndoV is hypoxanthine-specific; its activity was the highest with 2′-OH modification in ribose. The cleavage activity of hEndoV was compared based on its base sequence. We observed that it has specificity for adenine located on the 3′-end of hypoxanthine at the cleavage site, both before and after cleavage. These data suggest that hEndoV recognizes and cleaves the inosine generated on the poly A tail to maintain RNA quality. Our results provide mechanistic insight into the role of hEndoV in vivo.
Viable eco-efficiency targets for waste collection communities
Authors: Daraio Cinzia , Di Leo Simone , Simar Léopold 
Published: July 2024

AbstractWaste management is crucial for advancing the circular economy, and Italy has begun to address this issue by organizing municipalities into collaborative communities of municipalities, named ATOs. In this paper, we propose a quantitative approach based on conditional efficiency analysis to estimate viable eco-efficiency targets for these waste collection communities. The proposed targets are both eco-efficient, because they reflect optimal resource allocation within the eco-efficiency framework, and viable, because they consider the unique specificities of each waste community. The methodology determines a pathway or direction for municipalities to reach the eco-efficiency frontier based on specific external factors, ensuring that each municipality is benchmarked against others with similar contexts within the same community. Our analysis focuses on 89 Italian municipalities within the ATO “Città metropolitana di Roma Capitale” in 2021, revealing that size and economic development significantly contributed to viable eco-efficiency within the community during this period. The proposed approach is general and flexible and can be applied to other municipalities in Italy or across Europe. It can also be extended to meso (regional) or macro (country) levels of analysis.
Continent-wide genomic analysis of the African buffalo (Syncerus caffer)
Authors: Talenti Andrea , Wilkinson Toby , Cook Elizabeth A. , Hemmink Johanneke D. , Paxton Edith , Mutinda Matthew , Ngulu Stephen D. , Jayaraman Siddharth , Bishop Richard P. , Obara Isaiah , Hourlier Thibaut , Garcia Giron Carlos , Martin Fergal J. , Labuschagne Michel , Atimnedi Patrick , Nanteza Anne , Keyyu Julius D. , Mramba Furaha , Caron Alexandre , Cornelis Daniel , Chardonnet Philippe , Fyumagwa Robert , Lembo Tiziana , Auty Harriet K. , Michaux Johan , Smitz Nathalie , Toye Philip , Robert Christelle , Prendergast James G. D. , Morrison Liam J. 
Published: July 2024

AbstractThe African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest quality de novo genome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided little support for the currently described four subspecies. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management.
Tracing nerve fibers with volume electron microscopy to quantitatively analyze brain connectivity
Authors: Turegano-Lopez Marta , de las Pozas Felix , Santuy Andrea , Rodriguez Jose-Rodrigo , DeFelipe Javier , Merchan-Perez Angel 
Published: July 2024

AbstractThe highly complex structure of the brain requires an approach that can unravel its connectivity. Using volume electron microscopy and a dedicated software we can trace and measure all nerve fibers present within different samples of brain tissue. With this software tool, individual dendrites and axons are traced, obtaining a simplified “skeleton” of each fiber, which is linked to its corresponding synaptic contacts. The result is an intricate meshwork of axons and dendrites interconnected by a cloud of synaptic junctions. To test this methodology, we apply it to the stratum radiatum of the hippocampus and layers 1 and 3 of the somatosensory cortex of the mouse. We find that nerve fibers are densely packed in the neuropil, reaching up to 9 kilometers per cubic mm. We obtain the number of synapses, the number and lengths of dendrites and axons, the linear densities of synapses established by dendrites and axons, and their location on dendritic spines and shafts. The quantitative data obtained through this method enable us to identify subtle traits and differences in the synaptic organization of the samples, which might have been overlooked in a qualitative analysis.
[18F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue
Authors: Levi Jelena , Guglielmetti Caroline , Henrich Timothy J. , Yoon John C. , Gokhale Prafulla C. , Reardon David A. , Packiasamy Juliet , Huynh Lyna , Cabrera Hilda , Ruzevich Marisa , Blecha Joseph , Peluso Michael J. , Huynh Tony L. , An Sung-Min , Dornan Mark , Belanger Anthony P. , Nguyen Quang-Dé , Seo Youngho , Song Hong , Chaumeil Myriam M. , VanBrocklin Henry F. , Chae Hee-Don 
Published: July 2024

AbstractBrown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [18F]F-AraG, a mitochondrial metabolic tracer capable of tracking activated lymphocytes and adipocytes simultaneously, we demonstrate, in models of glioblastoma and multiple sclerosis, the correlation between intracerebral immune infiltration and changes in brown- and bone marrow adipose tissue. Significantly, we show initial evidence that a neuroinflammation-adipose tissue link may also exist in humans. This study proposes the concept of an intricate immuno-neuro-adipose circuit, and highlights brown- and bone marrow adipose tissue as an intermediary in the communication between the immune and nervous systems. Understanding the interconnectedness within this circuitry may lead to advancements in the treatment and management of various conditions, including cancer, neurodegenerative diseases and metabolic disorders.
Development of Nurr1 agonists from amodiaquine by scaffold hopping and fragment growing
Authors: Sai Minh , Hank Emily C. , Tai Hin-Man , Kasch Till , Lewandowski Max , Vincendeau Michelle , Marschner Julian A. , Merk Daniel 
Published: July 2024

AbstractThe neuroprotective transcription factor nuclear receptor-related 1 (Nurr1) has shown great promise as a therapeutic target in Parkinson’s and Alzheimer’s disease as well as multiple sclerosis but high-quality chemical tools for pharmacological target validation of Nurr1 are rare. We have employed the weak Nurr1 modulator amodiaquine (AQ) and AQ-derived fragments as templates to design a new Nurr1 agonist chemotype by scaffold hopping and fragment growing strategies. Systematic structural optimization of this scaffold yielded Nurr1 agonists with nanomolar potency and binding affinity. Comprehensive in vitro profiling revealed efficient cellular target engagement and compliance with the highest probe criteria. In human midbrain organoids bearing a Parkinson-driving LRRK2 mutation, a novel Nurr1 agonist rescued tyrosine hydroxylase expression highlighting the potential of the new Nurr1 modulator chemotype as lead and as a chemical tool for biological studies.
Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice
Authors: Zumerle Sara , Sarill Miles , Saponaro Miriam , Colucci Manuel , Contu Liliana , Lazzarini Edoardo , Sartori Roberta , Pezzini Camilla , Rinaldi Anna , Scanu Anna , Sgrignani Jacopo , Locatelli Patrizia , Sabbadin Marianna , Valdata Aurora , Brina Daniela , Giacomini Isabella , Rizzo Beatrice , Pierantoni Alessandra , Sharifi Saman , Bressan Silvia , Altomare Claudia , Goshovska Yulia , Giraudo Chiara , Luisetto Roberto , Iaccarino Luca , Torcasio Cristina , Mosole Simone , Pasquini Emiliano , Rinaldi Andrea , Pellegrini Laura , Peron Gregorio , Fassan Matteo , Masiero Stefano , Giori Andrea Maria , Dall’Acqua Stefano , Auwerx Johan , Cippà Pietro , Cavalli Andrea , Bolis Marco , Sandri Marco , Barile Lucio , Montopoli Monica , Alimonti Andrea 
Published: July 2024

AbstractAccumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence and thus improve healthspan. Here, we show that daily oral administration of a standardized extract of Salvia haenkei (Haenkenium (HK)) extended lifespan and healthspan of naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis and senescence markers across several tissues, as well as increased muscle strength and fur thickness compared with age-matched controls. We also found that HK treatment reduced acutely induced senescence by the chemotherapeutic agent doxorubicin, using p16LUC reporter mice. We profiled the constituent components of HK by mass spectrometry, and identified luteolin—the most concentrated flavonoid in HK—as a senomorphic compound. Mechanistically, by performing surface plasmon resonance and in situ proximity ligation assay, we found that luteolin disrupted the p16–CDK6 interaction. This work demonstrates that administration of HK promotes longevity in mice, possibly by modulating cellular senescence and by disrupting the p16–CDK6 interaction.
Functionalization of Position 7 of Pyrazolo[1,5-a]pyrazines
Authors: Kostyuk Aleksandr , Koidan Georgyi , Tsyzoryk Nazar , Rusanov Eduard B. , Shishkina Svitlana V. , Vovk Mykhailo 
Published: July 2024

AbstractWe report a straightforward formylation at position 7 of pyrazolo[1,5-a]pyrazine derivatives featuring substituents at the 2,3,4 positions. N,N,N′,1,1,1-Hexamethylsilanecarboximidamide exists in equilibrium with its carbene form due to 1,2-migration of the silyl group. The ensuing carbene can be inserted into the most acidic C–H group of the pyrazolo[1,5-a]pyrazines. The most acidic calculated pK
a (DMSO) C–H group is at position 7 and does not depend significantly on the substituents. The reactions proceed in high yields affording aminals that can be hydrolyzed to the corresponding aldehydes. Methanolysis of the aminals affords the corresponding methylimines. The constitution of the aminals was unambiguously proved by X-ray crystal structure analysis of a set of derivatives. The method is simple, often does not require even solvents, and can be extended to other heterocyclic compounds.
Patient-Reported Outcomes and Complications of Simultaneous versus Staged Surgical Decompression for Tandem Spinal Stenosis
Authors: Hussain Mustafa Mushtaq , Khalil Mujtaba , Suleman Fatima , Ali Iqra Fatima Munawar , Masroor Mehar , Shamim Muhammad Shahzad 
Published: July 2024

Abstract
Introduction Tandem spinal stenosis (TSS) refers to the narrowing of the spinal canal at two distinct anatomic areas. Symptoms can present due to either cervical myelopathy or lumbar stenosis. Consequently, determining the symptomatic anatomical levels requiring surgery can pose a challenge. We sought to identify the surgical approach associated with better patient-reported outcomes.
Materials and Methods The Information Management System was queried using the International Classification of Diseases Ninth and Tenth Edition codes to identify patients who underwent simultaneous or staged decompression surgery for TSS between 2011 and 2020. Patient records were reviewed to collect data on age, sex, comorbidities, surgical approach, modified Japanese Orthopedic Association (mJOA) score, and complications. The mJOA is a validated composite assessment used to quantify postoperative neurological status. Multivariable regression models were utilized to identify factors associated with better postoperative neurological recovery.
Results Among 42 patients included in the analytical cohort, 33 (78.6%) underwent simultaneous cervical and lumbar decompression, while 9 (21.4%) underwent staged decompression (cervical followed by lumbar). The patient's age, sex, comorbid conditions, and American Society of Anesthesiologists level were similar between the two groups. Furthermore, simultaneous decompression was associated with higher blood loss (676.97 vs. 584.44 mL) and an increased need for transfusion (259.09 vs. 111.11 mL) compared with staged decompression. Moreover, patients who underwent simultaneous decompression experienced a higher number of postoperative complications (10 vs. 1; p = 0.024). Notably, postoperative mJOA scores improved in both groups; however, the improvement was more pronounced in the staged group (mJOA score: 15.16% [ ± 2.18] vs. 16.56% [ ± 1.59]). On follow-up visits, patients who underwent staged decompression showed better recovery rates (mJOA score: 78.20% [ ± 24.45] vs. 59.75% [ ± 25.05]).
Conclusion The patient's clinical history and examination findings should be the main determinants of surgical decision-making. Our study showed a slightly higher postoperative mJOA score and a recovery rate with fewer complications in staged decompression of TSS.
A netnographic study to understand the determinants of experiential tourism destinations
Authors: Küster Inés , Vila Natalia 
Published: July 2024

AbstractConsidering the Social Identity Theory in an experiential tourism destination and using a netnoghaphic perspective, this paper (i) analyses the main topics associated with an experiential tourism destination and (ii) studies the relationships among destination determinants (i.e., destination attachment, hedonic emotions, spiritual experiences, and information, satisfaction, and loyalty). Camino de Santiago 518 effective post titles published on TripAdvisor were scrapped and analysed using a netnographic and correspondence analyses. Results show that there are three main topics associated with an experiential destination: (1) experiences and emotions, (2) information about Camino de Santiago, and (3) destination-brand recommendations. There is a main cluster where destination loyalty, destination identity, hedonic emotions, and negative experiences/aspects are close to the 5-score. A second cluster focused on information comments is not associated with other variables or scores. This article adds value to previous work because (1) it adopts a netnographic point of view, (2) it uses social media and user-generated content in the tourism industry, and (3) it provides strategies for experiential marketing in the tourism industry.
High-temperature setup for infrared reflection spectroscopy
Authors: Steigleder Marc , Dressel Martin 
Published: July 2024

We have designed an oven for optical reflection measurements at temperatures as high as 1000 K. The compact setup can be attached to any Fourier-transform infrared spectrometer using a microscope. The details of the layout, operation, and performance are discussed as well as ways for reference measurements and data correction. Finally, the high-temperature setup is utilized to determine the infrared reflectivity of tungsten up to T = 1000 K, which can serve as a reference mirror for future experiments.
Modeling of collision-induced excitation and quenching of atomic nitrogen
Authors: Wu Yanze , Hochlaf Majdi , Schatz George C. 
Published: July 2024

Excited atomic nitrogen atoms play an important role in plasma formation in hypersonic shock-waves, as happens during spacecraft reentry and other high velocity vehicle applications. In this study, we have thoroughly studied collision induced excitation associated with two colliding nitrogen atoms in the N(4S), N(2D), and N(2P) states at collision energies up to 6 eV, using time-independent scattering calculations to determine cross sections and temperature-dependent rate coefficients. The calculations are based on potential curves and couplings determined in earlier multireference configuration interaction calculations with large basis sets, and the results are in good agreement with experiments where comparisons are possible. To properly consider the spin–orbit coupling matrix, we have developed a scaling method for treating transitions between different fine-structure components that only require calculations with two coupled states, and with this, we define accurate degeneracy factors for determining cross sections and rate coefficients that include all states. The results indicate that both spin–orbit and derivative coupling effects can play important roles in collisional excitation and quenching, and that although derivative coupling is always much stronger than spin–orbit, there are many transitions where only spin–orbit can contribute. As part of this, we identify two distinct pathways associated with N(2P) relaxation and one Auger-like mechanism leading to two N(2D) that could be important at high temperatures.
DNA polymerase κ participates in early S-phase DNA replication in human cells
Authors: Tang Feng , Wang Yinan , Zhao Ting , Yuan Jun , Kellum Andrew H. , Wang Yinsheng 
Published: July 2024

Cycling cells replicate their DNA during the S phase through a defined temporal program known as replication timing. Mutation frequencies, epigenetic chromatin states, and transcriptional activities are different for genomic regions that are replicated early and late in the S phase. Here, we found from ChIP-Seq analysis that DNA polymerase (Pol) κ is enriched in early-replicating genomic regions in HEK293T cells. In addition, by feeding cells with
N
2
-heptynyl-2′-deoxyguanosine followed by click chemistry–based enrichment and high-throughput sequencing, we observed elevated Pol κ activities in genomic regions that are replicated early in the S phase. On the basis of the established functions of Pol κ in accurate and efficient nucleotide insertion opposite endogenously induced
N
2
-modified dG lesions, our work suggests that active engagement of Pol κ may contribute to diminished mutation rates observed in early-replicating regions of the human genome, including cancer genomes. Together, our work expands the functions of Pol κ and offered a plausible mechanism underlying replication timing–dependent mutation accrual in the human genome.
Impact of various DIII-D diagnostics on the accuracy of neural network surrogates for kinetic EFIT reconstructions
Authors: Sun Xuan , Akçay Cihan , Bechtel Amara Torrin , Kruger Scott E , Lao Lang L , Liu Yueqiang , Madireddy Sandeep , McClenaghan Joseph ,   the EFIT-AI Team
Published: July 2024

Abstract
Kinetic equilibrium reconstructions make use of profile information such as particle density and temperature measurements in addition to magnetics data to compute a self-consistent equilibrium. They are used in a multitude of physics-based modeling. This work develops a multi-layer perceptron (MLP) neural network (NN) model as a surrogate for kinetic Equilibrium Fitting (EFITs) and trains on the 2019 DIII-D discharge campaign database of kinetic equilibrium reconstructions. We investigate the impact of including various diagnostic data and machine actuator controls as input into the NN. When giving various categories of data as input into NN models that have been trained using those same categories of data, the predictions on multiple equilibrium reconstruction solutions (poloidal magnetic flux, global scalars, pressure profile, current profile) are highly accurate. When comparing different models with different diagnostics as input, the magnetics-only model outputs accurate kinetic profiles and the inclusion of additional data does not significantly impact the accuracy. When the NN is tasked with inferring only a single target such as the EFIT pressure profile or EFIT current profile, we see a large increase in the accuracy of the prediction of the kinetic profiles as more data is included. These results indicate that certain MLP NN configurations can be reasonably robust to different burning-plasma-relevant diagnostics depending on the accuracy requirements for equilibrium reconstruction tasks.
Joint associations of diet and physical activity with incident type 2 diabetes and hypertension: an analysis of 144 288 UK Biobank participants
Authors: Inan-Eroglu Elif , Ahmadi Matthew , Sainsbury Amanda , Leitzmann Michael , Khunti Kamlesh , Yates Thomas , Stamatakis Emmanuel 
Published: July 2024

Abstract
Studies examining the joint associations of lifestyle exposures can reveal novel synergistic and joint effects, but no study has examined the joint association of diet and physical activity (PA) with type 2 diabetes (T2D) and hypertension. The aim of this study is to examine the joint associations of PA and diet with incidence of type T2D and hypertension, as a combined outcome and separately in a large sample of adults in the United Kingdom. This prospective cohort study included 144 288 UK Biobank participants aged 40-69. Moderate to vigorous PA (MVPA) was measured using the International Physical Activity Questionnaire and a wrist accelerometer. We categorized PA and diet indicators (diet quality score [DQS] and energy intake [EI]) based on tertiles and derived joint PA and diet variables. Outcome was major cardiometabolic disease incidence (combination of T2D and hypertension). A total of 14 003 (7.1%) participants developed T2D, 28 075 (19.2%) developed hypertension, and 30 529 (21.2%) developed T2D or hypertension over a mean follow-up of 10.9 (3.7) years. Participants with middle and high self-reported MVPA levels had lower risk of major cardiometabolic disease regardless of diet (eg, among high DQS group, hazard ratios [HRs] in middle and high MVPA group were 0.90; 95% CI, 0.86-0.94), and 0.88 (95% CI, 0.84-0.92), respectively. Participants with jointly high device-measured MVPA and high DQS levels had lower major cardiometabolic disease risk (HR, 0.84; 95% CI, 0.71-0.99). The equivalent joint device-measured MVPA and EI exposure analyses showed no clear pattern of associations with the outcomes. Higher PA is an important component in cardiometabolic disease prevention across all diet quality and total EI groups. The observed lack of association between diet health outcomes may stem from a lower DQS.