bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylobone: a comprehensive database of bone extracellular matrix proteins in human and model organisms
Authors: Fontcuberta-Rigo Margalida , Nakamura Miho , Puigbò Pere 
Published: August 2023

AbstractThe bone extracellular matrix (ECM) contains minerals deposited on highly crosslinked collagen fibrils and hundreds of non-collagenous proteins. Some of these proteins are key to the regulation of bone formation and regeneration via signaling pathways, and play important regulatory and structural roles. However, the complete list of bone extracellular matrix proteins, their roles, and the extent of individual and cross-species variations have not been fully captured in both humans and model organisms. Here, we introduce the most comprehensive resource of bone extracellular matrix (ECM) proteins that can be used in research fields such as bone regeneration, osteoporosis, and mechanobiology. The Phylobone database (available at https://phylobone.com) includes 255 proteins potentially expressed in the bone extracellular matrix (ECM) of humans and 30 species of vertebrates. A bioinformatics pipeline was used to identify the evolutionary relationships of bone ECM proteins. The analysis facilitated the identification of potential model organisms to study the molecular mechanisms of bone regeneration. A network analysis showed high connectivity of bone ECM proteins. A total of 214 functional protein domains were identified, including collagen and the domains involved in bone formation and resorption. Information from public drug repositories was used to identify potential repurposing of existing drugs. The Phylobone database provides a platform to study bone regeneration and osteoporosis in light of (biological) evolution, and will substantially contribute to the identification of molecular mechanisms and drug targets.
HDAC1/2/3 are major histone desuccinylases critical for promoter desuccinylation
Authors: Li Jialun , Lu Lu , Liu Lingling , Ren Xuelian , Chen Jiwei , Yin Xingzhi , Xiao Yanhui , Li Jiwen , Wei Gang , Huang He , Wei Wei , Wong Jiemin 
Published: August 2023

AbstractLysine succinylation is one of the major post-translational modifications occurring on histones and is believed to have significant roles in regulating chromatin structure and function. Currently, histone desuccinylation is widely believed to be catalyzed by members of the SIRT family deacetylases. Here, we report that histone desuccinylation is in fact primarily catalyzed by the class I HDAC1/2/3. Inhibition or depletion of HDAC1/2/3 resulted in a marked increase of global histone succinylation, whereas ectopic expression of HDAC1/2/3 but not their deacetylase inactive mutants downregulated global histone succinylation. We demonstrated that the class I HDAC1/2/3 complexes have robust histone desuccinylase activity in vitro. Genomic landscape analysis revealed that histone succinylation is highly enriched at gene promoters and inhibition of HDAC activity results in marked elevation of promoter histone succinylation. Furthermore, our integrated analysis revealed that promoter histone succinylation positively correlates with gene transcriptional activity. Collectively, we demonstrate that the class I HDAC1/2/3 but not the SIRT family proteins are the major histone desuccinylases particularly important for promoter histone desuccinylation. Our study thus sheds new light on the role of histone succinylation in transcriptional regulation.
Immune regulatory networks coordinated by glycans and glycan-binding proteins in autoimmunity and infection
Authors: Pinho Salomé S. , Alves Inês , Gaifem Joana , Rabinovich Gabriel A. 
Published: August 2023

AbstractThe immune system is coordinated by an intricate network of stimulatory and inhibitory circuits that regulate host responses against endogenous and exogenous insults. Disruption of these safeguard and homeostatic mechanisms can lead to unpredictable inflammatory and autoimmune responses, whereas deficiency of immune stimulatory pathways may orchestrate immunosuppressive programs that contribute to perpetuate chronic infections, but also influence cancer development and progression. Glycans have emerged as essential components of homeostatic circuits, acting as fine-tuners of immunological responses and potential molecular targets for manipulation of immune tolerance and activation in a wide range of pathologic settings. Cell surface glycans, present in cells, tissues and the extracellular matrix, have been proposed to serve as “self-associated molecular patterns” that store structurally relevant biological data. The responsibility of deciphering this information relies on different families of glycan-binding proteins (including galectins, siglecs and C-type lectins) which, upon recognition of specific carbohydrate structures, can recalibrate the magnitude, nature and fate of immune responses. This process is tightly regulated by the diversity of glycan structures and the establishment of multivalent interactions on cell surface receptors and the extracellular matrix. Here we review the spatiotemporal regulation of selected glycan-modifying processes including mannosylation, complex N-glycan branching, core 2 O-glycan elongation, LacNAc extension, as well as terminal sialylation and fucosylation. Moreover, we illustrate examples that highlight the contribution of these processes to the control of immune responses and their integration with canonical tolerogenic pathways. Finally, we discuss the power of glycans and glycan-binding proteins as a source of immunomodulatory signals that could be leveraged for the treatment of autoimmune inflammation and chronic infection.
Association between vmPFC gray matter volume and smoking initiation in adolescents
Authors: Xiang Shitong , Jia Tianye , Xie Chao , Cheng Wei , Chaarani Bader , Banaschewski Tobias , Barker Gareth J. , Bokde Arun L. W. , Büchel Christian , Desrivières Sylvane , Flor Herta , Grigis Antoine , Gowland Penny A. , Brühl Rüdiger , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Nees Frauke , Orfanos Dimitri Papadopoulos , Poustka Luise , Hohmann Sarah , Fröhner Juliane H. , Smolka Michael N. , Vaidya Nilakshi , Walter Henrik , Whelan Robert , Garavan Hugh , Schumann Gunter , Sahakian Barbara J. , Robbins Trevor W. , Feng Jianfeng ,   IMAGEN Consortium
Published: August 2023

AbstractSmoking of cigarettes among young adolescents is a pressing public health issue. However, the neural mechanisms underlying smoking initiation and sustenance during adolescence, especially the potential causal interactions between altered brain development and smoking behaviour, remain elusive. Here, using large longitudinal adolescence imaging genetic cohorts, we identify associations between left ventromedial prefrontal cortex (vmPFC) gray matter volume (GMV) and subsequent self-reported smoking initiation, and between right vmPFC GMV and the maintenance of smoking behaviour. Rule-breaking behaviour mediates the association between smaller left vmPFC GMV and smoking behaviour based on longitudinal cross-lagged analysis and Mendelian randomisation. In contrast, smoking behaviour associated longitudinal covariation of right vmPFC GMV and sensation seeking (especially hedonic experience) highlights a potential reward-based mechanism for sustaining addictive behaviour. Taken together, our findings reveal vmPFC GMV as a possible biomarker for the early stages of nicotine addiction, with implications for its prevention and treatment.
Quantitative real-time in-cell imaging reveals heterogeneous clusters of proteins prior to condensation
Authors: Lan Chenyang , Kim Juhyeong , Ulferts Svenja , Aprile-Garcia Fernando , Weyrauch Sophie , Anandamurugan Abhinaya , Grosse Robert , Sawarkar Ritwick , Reinhardt Aleks , Hugel Thorsten 
Published: August 2023

AbstractOur current understanding of biomolecular condensate formation is largely based on observing the final near-equilibrium condensate state. Despite expectations from classical nucleation theory, pre-critical protein clusters were recently shown to form under subsaturation conditions in vitro; if similar long-lived clusters comprising more than a few molecules are also present in cells, our understanding of the physical basis of biological phase separation may fundamentally change. Here, we combine fluorescence microscopy with photobleaching analysis to quantify the formation of clusters of NELF proteins in living, stressed cells. We categorise small and large clusters based on their dynamics and their response to p38 kinase inhibition. We find a broad distribution of pre-condensate cluster sizes and show that NELF protein cluster formation can be explained as non-classical nucleation with a surprisingly flat free-energy landscape for a wide range of sizes and an inhibition of condensation in unstressed cells.
Diversity-oriented synthesis encoded by deoxyoligonucleotides
Authors: Hudson Liam , Mason Jeremy W. , Westphal Matthias V. , Richter Matthieu J. R. , Thielman Jonathan R. , Hua Bruce K. , Gerry Christopher J. , Xia Guoqin , Osswald Heather L. , Knapp John M. , Tan Zher Yin , Kokkonda Praveen , Tresco Ben I. C. , Liu Shuang , Reidenbach Andrew G. , Lim Katherine S. , Poirier Jennifer , Capece John , Bonazzi Simone , Gampe Christian M. , Smith Nichola J. , Bradner James E. , Coley Connor W. , Clemons Paul A. , Melillo Bruno , Hon C. Suk-Yee , Ottl Johannes , Dumelin Christoph E. , Schaefer Jonas V. , Faust Ann Marie E. , Berst Frédéric , Schreiber Stuart L. , Zécri Frédéric J. , Briner Karin 
Published: August 2023

AbstractDiversity-oriented synthesis (DOS) is a powerful strategy to prepare molecules with underrepresented features in commercial screening collections, resulting in the elucidation of novel biological mechanisms. In parallel to the development of DOS, DNA-encoded libraries (DELs) have emerged as an effective, efficient screening strategy to identify protein binders. Despite recent advancements in this field, most DEL syntheses are limited by the presence of sensitive DNA-based constructs. Here, we describe the design, synthesis, and validation experiments performed for a 3.7 million-member DEL, generated using diverse skeleton architectures with varying exit vectors and derived from DOS, to achieve structural diversity beyond what is possible by varying appendages alone. We also show screening results for three diverse protein targets. We will make this DEL available to the academic scientific community to increase access to novel structural features and accelerate early-phase drug discovery.
Pillararene incorporated metal–organic frameworks for supramolecular recognition and selective separation
Authors: Wu Yitao , Tang Meiqi , Wang Zeju , Shi Le , Xiong Zhangyi , Chen Zhijie , Sessler Jonathan L. , Huang Feihe 
Published: August 2023

AbstractCrystalline frameworks containing incorporated flexible macrocycle units can afford new opportunities in molecular recognition and selective separation. However, such functionalized frameworks are difficult to prepare and challenging to characterize due to the flexible nature of macrocycles, which limits the development of macrocycle-based crystalline frameworks. Herein, we report the design and synthesis of a set of metal–organic frameworks (MOFs) containing pillar[5]arene units. The pillar[5]arene units were uniformly embedded in the periodic frameworks. Single crystal X-ray diffraction analysis revealed an interpenetrated network that appears to hinder the rotation of the pillar[5]arene repeating units in the frameworks, and it therefore resulted in the successful determination of the precise pillar[5]arene host structure in a MOF crystal. These MOFs can recognize paraquat and 1,2,4,5-tetracyanobenzene in solution and selectively remove trace pyridine from toluene with relative ease. The work presented here represents a critical step towards the synthesis of macrocycle-incorporated crystalline frameworks with well-defined structures and functional utility.
Combined PARP and WEE1 inhibition triggers anti-tumor immune response in BRCA1/2 wildtype triple-negative breast cancer
Authors: Teo Zhi Ling , O’Connor Mark J. , Versaci Stephanie , Clarke Kylie A. , Brown Emmaline R. , Percy Luke W. , Kuykhoven Keilly , Mintoff Christopher P. , Savas Peter , Virassamy Balaji , Luen Stephen J. , Byrne Ann , Sant Sneha , Lindeman Geoffrey J. , Darcy Phillip K. , Loi Sherene 
Published: August 2023

AbstractNovel therapeutic strategies that can effectively combine with immunotherapies are needed in the treatment of triple-negative breast cancer (TNBC). We demonstrate that combined PARP and WEE1 inhibition are synergistic in controlling tumour growth in BRCA1/2 wild-type TNBC preclinical models. The PARP inhibitor (PARPi) olaparib combined with the WEE1 inhibitor (WEE1i) adavosertib triggered increases in anti-tumour immune responses, including STING pathway activation. Combinations with a STING agonist resulted in further improved durable tumour regression and significant improvements in survival outcomes in murine tumour models of BRCA1/2 wild-type TNBC. In addition, we have identified baseline tumour-infiltrating lymphocyte (TIL) levels as a potential predictive biomarker of response to PARPi, WEE1i and immunotherapies in BRCA1/2 wild-type TNBC.
Interaction of BMI and respiratory status in obstructive sleep apnea, a cross-sectional COPD study
Authors: Hashiguchi Mizuha Haraguchi , Chubachi Shotaro , Yamasawa Wakako , Otsuka Kengo , Harada Naoko , Miyao Naoki , Nakamura Hidetoshi , Asano Koichiro , Yamaguchi Kazuhiro , Fukunaga Koichi 
Published: August 2023

AbstractThis cross-sectional study of 136 patients with chronic obstructive pulmonary disease (COPD) investigated the mechanism underlying overlap syndrome, defined as coexisting COPD and obstructive sleep apnea (OSA). OSA was defined as a respiratory event index (REI) ≥ 5 events/h, determined using type-3 portable monitors. The mean REI was 12.8 events/h. Most participants (60.1%) had mild OSA (REI: 5–15 events/h). The REI was positively correlated with forced expiratory volume in one second (%FEV1) (r = 0.33, p < 0.001), body mass index (BMI) (r = 0.24, p = 0.005), and fat-free mass index (r = 0.31, p = 0.005), and negatively correlated with residual volume divided by total lung capacity (r = −0.27, p = 0.003). Receiver-operating characteristic curve analysis revealed an optimal BMI cutoff of 21.96 kg/m2 for predicting moderate/severe OSA. A BMI ≥ 21.96 kg/m2 was associated with OSA among participants with %FEV1 ≥ 50%, but not those with %FEV1 < 50%. This study revealed an interaction between airflow limitation and hyperinflation, nutritional status, and OSA.
Investigation of vertical and horizontal transmission of Spiroplasma in ticks under laboratory conditions
Authors: Ogata Shohei , Umemiya-Shirafuji Rika , Kusakisako Kodai , Kakisaka Keita , Chatanga Elisha , Hayashi Naoki , Taya Yurie , Ohari Yuma , Pandey Gita Sadaula , Abdelbaset Abdelbaset Eweda , Qiu Yongjin , Matsuno Keita , Nonaka Nariaki , Nakao Ryo 
Published: August 2023

AbstractMany arthropods harbour bacterial symbionts, which are maintained by vertical and/or horizontal transmission. Spiroplasma is one of the most well-known symbionts of ticks and other arthropods. It is still unclear how Spiroplasma infections have spread in tick populations despite its high prevalence in some tick species. In this study, Ixodes ovatus, which has been reported to harbour Spiroplasma ixodetis at high frequencies, was examined for its vertical transmission potential under experimental conditions. Next, two isolates of tick-derived Spiroplasma, S. ixodetis and Spiroplasma mirum, were experimentally inoculated into Spiroplasma-free Haemaphysalis longicornis colonies and the presence of Spiroplasma in their eggs and larvae was tested. Our experimental data confirmed that S. ixodetis was transmitted to eggs and larvae in a vertical manner in the original host I. ovatus. In the second experiment, there was no significant difference in engorged weight, egg weight, and hatching rate between Spiroplasma-inoculated and control H. longicornis groups. This suggested that Spiroplasma infection does not affect tick reproduction. Spiroplasma DNA was only detected in the eggs and larvae derived from some individuals of S. ixodetis-inoculated groups. This has demonstrated the potential of horizontal transmission between different tick species. These findings may help understand the transmission dynamics of Spiroplasma in nature and its adaptation mechanism to host arthropod species.
The association between dietary pattern and visceral adiposity index, triglyceride-glucose index, inflammation, and body composition among Iranian overweight and obese women
Authors: Gholami Fatemeh , Karimi Zahra , Samadi Mahsa , Sovied Neda , Yekaninejad Mir Saeid , Keshavarz Seyed Ali , Javdan Gholamali , Bahrampour Niki , Wong Alexei , Clark Cain C. T. , Mirzaei Khadijeh 
Published: August 2023

AbstractThe aim of the present study was to investigate the association between dietary patterns, derived through latent class analysis (LCA), with visceral adiposity index (VAI), Triglyceride-Glucose Index (TyG), inflammation biomarkers, and body composition in overweight and obese Iranian women. For this cross-sectional study, dietary exposure was assessed using a validated 147-item semi-quantitative food frequency questionnaire (FFQ). Dietary patterns were derived through LCA. Binary logistic was performed to test the associations of dietary patterns with VAI, TyG, inflammation biomarkers, and body composition. Health centers in Tehran, Iran. 376 obese and overweight women, aged > 18 years. Two dietary patterns were identified using LCA modeling: healthy and unhealthy. Women in the unhealthy class were characterized by higher consumption of fast food, sweetened beverages, grains, unhealthy oils, butter and margarine, and snacks. Compared with the healthy class, the unhealthy class was associated with an increased risk of higher fasting blood sugar (FBS) (OR = 6.07; 95% CI: 1.33–27.74, P value = 0.02), c-reactive protein (CRP) (OR = 1.72; 95% CI: 1.05–2.80; P value = 0.02), and lower fat free mass index (FFMI) (OR = 0.56; 95% CI: 0.35–0.88, P value = 0.01), after adjusting for confounders. We found that adherence to an unhealthy dietary pattern was associated with decreased FFMI and increased FBS and CRP using LCA, but not with the rest of the variables. Further studies should be conducted to confirm the veracity of these findings.
A two-stage dominance-based surrogate-assisted evolution algorithm for high-dimensional expensive multi-objective optimization
Authors: Yu Mengjiao , Wang Zheng , Dai Rui , Chen Zhongkui , Ye Qianlin , Wang Wanliang 
Published: August 2023

AbstractIn the past decades, surrogate-assisted evolutionary algorithms (SAEAs) have become one of the most popular methods to solve expensive multi-objective optimization problems (EMOPs). However, most existing methods focus on low-dimensional EMOPs because a large number of training samples are required to build accurate surrogate models, which is unrealistic for high-dimensional EMOPs. Therefore, this paper develops a two-stage dominance-based surrogate-assisted evolution algorithm (TSDEA) for high-dimensional EMOPs which utilizes the RBF model to approximate each objective function. First, a two-stage selection strategy is applied to select individuals for re-evaluation. Then considering the training time of the model, proposing a novel archive updating strategy to limit the number of individuals for updating. Experimental results show that the proposed algorithm has promising performance and computational efficiency compared to the state-of-the-art five SAEAs.
Effect of diotic versus dichotic presentation on the pitch perception of tone complexes at medium and very high frequencies
Authors: Gockel Hedwig E. , Carlyon Robert P. 
Published: August 2023

AbstractDifference limens for fundamental frequency (F0), F0DLs, are usually small for complex tones containing low harmonics that are resolved in the auditory periphery, but worsen when the rank of the lowest harmonic increases above about 6–8 and harmonics become less resolved. The traditional explanation for this, in terms of resolvability, has been challenged and an alternative explanation in terms of harmonic rank was suggested. Here, to disentangle the effects of resolvability and harmonic rank the complex tones were presented either diotically (all harmonics to both ears) or dichotically (even and odd harmonics to opposite ears); the latter increases resolvability but does not affect harmonic rank. F0DLs were measured for 14 listeners for complex tones containing harmonics 6–10 with F0s of 280 and 1400 Hz, presented diotically or dichotically. For the low F0, F0DLs were significantly lower for the dichotic than for the diotic condition. This is consistent with a benefit of increased resolvability of harmonics for F0 discrimination and extends previous results to harmonics as low as the sixth. In contrast, for the high F0, F0DLs were similar for the two presentation modes, adding to evidence for differences in pitch perception between tones with low-to-medium and very-high frequency content.
Virtual reality for assessing stereopsis performance and eye characteristics in Post-COVID
Authors: Mehringer Wolfgang , Stoeve Maike , Krauss Daniel , Ring Matthias , Steussloff Fritz , Güttes Moritz , Zott Julia , Hohberger Bettina , Michelson Georg , Eskofier Bjoern 
Published: August 2023

AbstractIn 2019, we faced a pandemic due to the coronavirus disease (COVID-19), with millions of confirmed cases and reported deaths. Even in recovered patients, symptoms can be persistent over weeks, termed Post-COVID. In addition to common symptoms of fatigue, muscle weakness, and cognitive impairments, visual impairments have been reported. Automatic classification of COVID and Post-COVID is researched based on blood samples and radiation-based procedures, among others. However, a symptom-oriented assessment for visual impairments is still missing. Thus, we propose a Virtual Reality environment in which stereoscopic stimuli are displayed to test the patient’s stereopsis performance. While performing the visual tasks, the eyes’ gaze and pupil diameter are recorded. We collected data from 15 controls and 20 Post-COVID patients in a study. Therefrom, we extracted features of three main data groups, stereopsis performance, pupil diameter, and gaze behavior, and trained various classifiers. The Random Forest classifier achieved the best result with 71% accuracy. The recorded data support the classification result showing worse stereopsis performance and eye movement alterations in Post-COVID. There are limitations in the study design, comprising a small sample size and the use of an eye tracking system.
Tailor-designed nanoparticle-based PdNiSn catalyst as a potential anode for glycerol fuel cells
Authors: El-Nowihy Ghada H. 
Published: August 2023

AbstractIn order to effectively use glycerol as a fuel in direct glycerol fuel cells, a catalyst that can break the C–C bond and enhance the electro-oxidation of glycerol to CO2 is necessary. In this particular investigation, a palladium-nickel-tin nanocomposite electrodeposited on a glassy carbon electrode (PdNiSn/GC) exhibited excellent activity towards the electro-oxidation of glycerol, thanks to the synergistic effect of the catalyst composition. The PdNiSn/GC surface generated a peak current (Ip) that was 2.5 times higher than that obtained at a Pd/GC electrode, with a cathodic shift in the onset potential (Eonset) of approximately 300 mV. Additionally, the current obtained at the PdNiSn/GC surface remained stable during continuous electrolysis. Capacitance measurements were used to interpret the results of the electrocatalytic activity, and high-performance liquid chromatography indicated that the products of the glycerol electro-oxidation reaction were oxalic acid and formic acid, which were subsequently oxidized to CO2, as revealed by the charge calculations. The results depict that the synergy between Pd, β-Ni(OH)2, and SnO2 is crucial for boosting GEOR through enhancing the C–C bond cleavage and completely oxidize the reaction intermediates to CO2.