bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Search for Magnetotail Twisting at Mercury: Comparing MESSENGER Observations With the Terrestrial Case
Authors: Romanelli N. , DiBraccio G. A. , Slavin J. , Bowers C. , Weber T. 
Published: December 2022

AbstractPrevious studies reported that the terrestrial and Martian magnetotails can become twisted due to the solar wind‐planetary interaction; however, the associated physical processes proper of intrinsic and induced magnetospheres are still under debate. In particular, there is evidence that the Interplanetary Magnetic Field (IMF) dawn‐dusk component (By) plays a major role in both environments, affecting the sense of twist. Here, we analyze all MErcury, Surface, Space ENvironment, GEochemistry and Ranging Magnetometer observations to investigate the IMF By influence on Mercury's magnetotail. We find that Mercury's tail twist is very small (≲3°), for a median downtail distance of ∼2 Mercury radii. We also identify a correlation between the IMF By and the local By component around the magnetotail current sheet. These results suggest the small (or lack of) twist may be explained by the dipolar field strength in the near‐magnetotail. We examine this hypothesis by putting these observations into context with studies on the terrestrial magnetotail.
Mitochondrial PARP1 regulates NAD+-dependent poly ADP-ribosylation of mitochondrial nucleoids
Authors: Lee Jong-Hyuk , Hussain Mansoor , Kim Edward W. , Cheng Shang-Jung , Leung Anthony K. L. , Fakouri Nima Borhan , Croteau Deborah L. , Bohr Vilhelm A. 
Published: December 2022

AbstractPARPs play fundamental roles in multiple DNA damage recognition and repair pathways. Persistent nuclear PARP activation causes cellular NAD+ depletion and exacerbates cellular aging. However, very little is known about mitochondrial PARP (mtPARP) and poly ADP-ribosylation (PARylation). The existence of mtPARP is controversial, and the biological roles of mtPARP-induced mitochondrial PARylation are unclear. Here, we demonstrate the presence of PARP1 and PARylation in purified mitochondria. The addition of the PARP1 substrate NAD+ to isolated mitochondria induced PARylation, which was suppressed by treatment with the inhibitor olaparib. Mitochondrial PARylation was also evaluated by enzymatic labeling of terminal ADP-ribose (ELTA). To further confirm the presence of mtPARP1, we evaluated mitochondrial nucleoid PARylation by ADP ribose-chromatin affinity purification (ADPr-ChAP) and PARP1 chromatin immunoprecipitation (ChIP). We observed that NAD+ stimulated PARylation and TFAM occupancy on the mtDNA regulatory region D-loop, inducing mtDNA transcription. These findings suggest that PARP1 is integrally involved in mitochondrial PARylation and that NAD+-dependent mtPARP1 activity contributes to mtDNA transcriptional regulation.
Inflammation promotes synucleinopathy propagation
Authors: Kim Tae-Kyung , Bae Eun-Jin , Jung Byung Chul , Choi Minsun , Shin Soo Jean , Park Sung Jun , Kim Jeong Tae , Jung Min Kyo , Ulusoy Ayse , Song Mi-Young , Lee Jun Sung , Lee He-Jin , Di Monte Donato A. , Lee Seung-Jae 
Published: December 2022

AbstractThe clinical progression of neurodegenerative diseases correlates with the spread of proteinopathy in the brain. The current understanding of the mechanism of proteinopathy spread is far from complete. Here, we propose that inflammation is fundamental to proteinopathy spread. A sequence variant of α-synuclein (V40G) was much less capable of fibril formation than wild-type α-synuclein (WT-syn) and, when mixed with WT-syn, interfered with its fibrillation. However, when V40G was injected intracerebrally into mice, it induced aggregate spreading even more effectively than WT-syn. Aggregate spreading was preceded by sustained microgliosis and inflammatory responses, which were more robust with V40G than with WT-syn. Oral administration of an anti-inflammatory agent suppressed aggregate spreading, inflammation, and behavioral deficits in mice. Furthermore, exposure of cells to inflammatory cytokines increased the cell-to-cell propagation of α-synuclein. These results suggest that the inflammatory microenvironment is the major driver of the spread of synucleinopathy in the brain.
Neuroinflammation is independently associated with brain network dysfunction in Alzheimer’s disease
Authors: Leng Fangda , Hinz Rainer , Gentleman Steve , Hampshire Adam , Dani Melanie , Brooks David J. , Edison Paul 
Published: December 2022

AbstractBrain network dysfunction is increasingly recognised in Alzheimer’s disease (AD). However, the causes of brain connectivity disruption are still poorly understood. Recently, neuroinflammation has been identified as an important factor in AD pathogenesis. Microglia participate in the construction and maintenance of healthy neuronal networks, but pro-inflammatory microglia can also damage these circuits. We hypothesised that microglial activation is independently associated with brain connectivity disruption in AD. We performed a cross-sectional multimodal imaging study and interrogated the relationship between imaging biomarkers of neuroinflammation, Aβ deposition, brain connectivity and cognition. 42 participants (12 Aβ-positive MCI, 14 Aβ-positive AD and 16 Aβ-negative healthy controls) were recruited. Participants had 11C-PBR28 and 18F-flutemetamol PET to quantify Aβ deposition and microglial activation, T1-weighted, diffusion tensor and resting-state functional MRI to assess structural network and functional network. 11C-PBR28 uptake, structural network integrity and functional network orgnisation were compared across diagnostic groups and the relationship between neuroinflammation and brain network was tested in 26 Aβ-positive patients. Increased 11C-PBR28 uptake, decreased FA, network small-worldness and local efficiency were observed in AD patients. Cortical 11C-PBR28 uptake correlated negatively with structural integrity (standardised β = −0.375, p = 0.037) and network local efficiency (standardised β = −0.468, p < 0.001), independent of cortical thickness and Aβ deposition, while Aβ was not. Network structural integrity, small-worldness and local efficiency, and cortical thickness were positively associated with cognition. Our findings suggest cortical neuroinflammation coincide with structural and functional network disruption independent of Aβ and cortical atrophy. These findings link the brain connectivity change and pathological process in Alzheimer’s disease, and suggest a pathway from neuroinflammation to systemic brain dysfunction.
Negotiation and honesty in artificial intelligence methods for the board game of Diplomacy
Authors: Kramár János , Eccles Tom , Gemp Ian , Tacchetti Andrea , McKee Kevin R. , Malinowski Mateusz , Graepel Thore , Bachrach Yoram 
Published: December 2022

AbstractThe success of human civilization is rooted in our ability to cooperate by communicating and making joint plans. We study how artificial agents may use communication to better cooperate in Diplomacy, a long-standing AI challenge. We propose negotiation algorithms allowing agents to agree on contracts regarding joint plans, and show they outperform agents lacking this ability. For humans, misleading others about our intentions forms a barrier to cooperation. Diplomacy requires reasoning about our opponents’ future plans, enabling us to study broken commitments between agents and the conditions for honest cooperation. We find that artificial agents face a similar problem as humans: communities of communicating agents are susceptible to peers who deviate from agreements. To defend against this, we show that the inclination to sanction peers who break contracts dramatically reduces the advantage of such deviators. Hence, sanctioning helps foster mostly truthful communication, despite conditions that initially favor deviations from agreements.
The gut microbiota and depressive symptoms across ethnic groups
Authors: Bosch Jos A. , Nieuwdorp Max , Zwinderman Aeilko H. , Deschasaux Mélanie , Radjabzadeh Djawad , Kraaij Robert , Davids Mark , de Rooij Susanne R. , Lok Anja 
Published: December 2022

AbstractThe gut microbiome is thought to play a role in depressive disorders, which makes it an attractive target for interventions. Both the microbiome and depressive symptom levels vary substantially across ethnic groups. Thus, any intervention for depression targeting the microbiome requires understanding of microbiome-depression associations across ethnicities. Analysing data from the HELIUS cohort, we characterize the gut microbiota and its associations with depressive symptoms in 6 ethnic groups (Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, Moroccan;N = 3211), living in the same urban area. Diversity of the gut microbiota, both within (α-diversity) and between individuals (β-diversity), predicts depressive symptom levels, taking into account demographic, behavioural, and medical differences. These associations do not differ between ethnic groups. Further, β-diversity explains 29%–18% of the ethnic differences in depressive symptoms. Bacterial genera associated with depressive symptoms belong to mulitple families, prominently including the familiesChristensenellaceae, Lachnospiraceae, andRuminococcaceae. In summary, the results show that the gut microbiota are linked to depressive symptom levels and that this association generalizes across ethnic groups. Moreover, the results suggest that ethnic differences in the gut microbiota may partly explain parallel disparities in depression.
The role of auxiliary domains in modulating CHD4 activity suggests mechanistic commonality between enzyme families
Authors: Zhong Yichen , Moghaddas Sani Hakimeh , Paudel Bishnu P. , Low Jason K. K. , Silva Ana P. G. , Mueller Stefan , Deshpande Chandrika , Panjikar Santosh , Reid Xavier J. , Bedward Max J. , van Oijen Antoine M. , Mackay Joel P. 
Published: December 2022

AbstractCHD4 is an essential, widely conserved ATP-dependent translocase that is also a broad tumour dependency. In common with other SF2-family chromatin remodelling enzymes, it alters chromatin accessibility by repositioning histone octamers. Besides the helicase and adjacent tandem chromodomains and PHD domains, CHD4 features 1000 residues of N- and C-terminal sequence with unknown structure and function. We demonstrate that these regions regulate CHD4 activity through different mechanisms. An N-terminal intrinsically disordered region (IDR) promotes remodelling integrity in a manner that depends on the composition but not sequence of the IDR. The C-terminal region harbours an auto-inhibitory region that contacts the helicase domain. Auto-inhibition is relieved by a previously unrecognized C-terminal SANT-SLIDE domain split by ~150 residues of disordered sequence, most likely by binding of this domain to substrate DNA. Our data shed light on CHD4 regulation and reveal strong mechanistic commonality between CHD family members, as well as with ISWI-family remodellers.
Subduction-related oxidation of the sublithospheric mantle evidenced by ferropericlase and magnesiowüstite diamond inclusions
Authors: Kiseeva Ekaterina S. , Korolev Nester , Koemets Iuliia , Zedgenizov Dmitry A. , Unitt Richard , McCammon Catherine , Aslandukova Alena , Khandarkhaeva Saiana , Fedotenko Timofey , Glazyrin Konstantin , Bessas Dimitrios , Aprilis Georgios , Chumakov Alexandr I. , Kagi Hiroyuki , Dubrovinsky Leonid 
Published: December 2022

AbstractFerropericlase (Mg,Fe)O is the second most abundant mineral in Earth’s lower mantle and a common inclusion found in subcratonic diamonds. Pyrolitic mantle has Mg# (100 × Mg/(Mg+Fe)) ~89. However, ferropericlase inclusions in diamonds show a broad range of Mg# between 12 and 93. Here we use Synchrotron Mössbauer Source (SMS) spectroscopy and single-crystal X-ray diffraction to determine the iron oxidation state and structure of two magnesiowüstite and three ferropericlase inclusions in diamonds from São Luiz, Brazil. Inclusion Mg#s vary between 16.1 and 84.5. Ferropericlase inclusions contain no ferric iron within the detection limit of SMS, while both magnesiowüstite inclusions show the presence of monocrystalline magnesioferrite ((Mg,Fe)Fe3+2O4) with an estimated 47–53 wt% Fe2O3. We argue that the wide range of Fe concentrations observed in (Mg,Fe)O inclusions in diamonds and the appearance of magnesioferrite result from oxidation of ferropericlase triggered by the introduction of subducted material into sublithospheric mantle.
Backbone amides are determinants of Cl− selectivity in CLC ion channels
Authors: Leisle Lilia , Lam Kin , Dehghani-Ghahnaviyeh Sepehr , Fortea Eva , Galpin Jason D. , Ahern Christopher A. , Tajkhorshid Emad , Accardi Alessio 
Published: December 2022

AbstractChloride homeostasis is regulated in all cellular compartments. CLC-type channels selectively transport Cl− across biological membranes. It is proposed that side-chains of pore-lining residues determine Cl− selectivity in CLC-type channels, but their spatial orientation and contributions to selectivity are not conserved. This suggests a possible role for mainchain amides in selectivity. We use nonsense suppression to insert α-hydroxy acids at pore-lining positions in two CLC-type channels, CLC-0 and bCLC-k, thus exchanging peptide-bond amides with ester-bond oxygens which are incapable of hydrogen-bonding. Backbone substitutions functionally degrade inter-anion discrimination in a site-specific manner. The presence of a pore-occupying glutamate side chain modulates these effects. Molecular dynamics simulations show backbone amides determine ion energetics within the bCLC-k pore and how insertion of an α-hydroxy acid alters selectivity. We propose that backbone-ion interactions are determinants of Cl− specificity in CLC channels in a mechanism reminiscent of that described for K+ channels.
Cascade of transitions in twisted and non-twisted graphene layers within the van Hove scenario
Authors: Chichinadze Dmitry V. , Classen Laura , Wang Yuxuan , Chubukov Andrey V. 
Published: December 2022

AbstractMotivated by measurements of compressibility and STM spectra in twisted bilayer graphene, we analyze the pattern of symmetry breaking for itinerant fermions near a van Hove singularity. Making use of an approximate SU(4) symmetry of the Landau functional, we show that the structure of the spin/isospin order parameter changes with increasing filling via a cascade of transitions. We compute the feedback from different spin/isospin orders on fermions and argue that each order splits the initially 4-fold degenerate van Hove peak in a particular fashion, consistent with the STM data and compressibility measurements, providing a unified interpretation of the cascade of transitions in twisted bilayer graphene. Our results follow from a generic analysis of an SU(4)-symmetric Landau functional and are valid beyond a specific underlying fermionic model. We argue that an analogous van Hove scenario explains the cascade of phase transitions in non-twisted Bernal bilayer and rhombohedral trilayer graphene.
Antibody feedback regulates immune memory after SARS-CoV-2 mRNA vaccination
Authors: Schaefer-Babajew Dennis , Wang Zijun , Muecksch Frauke , Cho Alice , Loewe Maximilian , Cipolla Melissa , Raspe Raphael , Johnson Brianna , Canis Marie , DaSilva Justin , Ramos Victor , Turroja Martina , Millard Katrina G. , Schmidt Fabian , Witte Leander , Dizon Juan , Shimeliovich Irina , Yao Kai-Hui , Oliveira Thiago Y. , Gazumyan Anna , Gaebler Christian , Bieniasz Paul D. , Hatziioannou Theodora , Caskey Marina , Nussenzweig Michel C. 
Published: December 2022

AbstractFeedback inhibition of humoral immunity by antibodies was first documented in 19091. Subsequent studies showed that, depending on the context, antibodies can enhance or inhibit immune responses2,3. However, little is known about how pre-existing antibodies influence the development of memory B cells. Here we examined the memory B cell response in individuals who received two high-affinity anti-SARS-CoV-2 monoclonal antibodies and subsequently two doses of an mRNA vaccine4–8. We found that the recipients of the monoclonal antibodies produced antigen-binding and neutralizing titres that were only fractionally lower compared than in control individuals. However, the memory B cells of the individuals who received the monoclonal antibodies differed from those of control individuals in that they predominantly expressed low-affinity IgM antibodies that carried small numbers of somatic mutations and showed altered receptor binding domain (RBD) target specificity, consistent with epitope masking. Moreover, only 1 out of 77 anti-RBD memory antibodies tested neutralized the virus. The mechanism underlying these findings was examined in experiments in mice that showed that germinal centres formed in the presence of the same antibodies were dominated by low-affinity B cells. Our results indicate that pre-existing high-affinity antibodies bias germinal centre and memory B cell selection through two distinct mechanisms: (1) by lowering the activation threshold for B cells, thereby permitting abundant lower-affinity clones to participate in the immune response; and (2) through direct masking of their cognate epitopes. This may in part explain the shifting target profile of memory antibodies elicited by booster vaccinations9.
The dynamics of extracellular DNA associates with treatment response in patients with rheumatoid arthritis
Authors: Macáková Kristína , Illésová Júlia , Mlynáriková Vanda , Lesayová Alexandra , Konečná Barbora , Vlková Barbora , Celec Peter , Šteňová Emöke 
Published: December 2022

AbstractRheumatoid arthritis (RA) as a chronic autoimmune inflammatory disease increases extracellular DNA (ecDNA). Our previous study has shown that anti-inflammatory treatment reduces ecDNA, but it is unclear whether there is an association with treatment response. The aim of this study was to analyze the changes of ecDNA induced by biological disease-modifying antirheumatic drugs (bDMARDs) in RA patients with an emphasis on the subcellular origin of ecDNA. Plasma samples from 40 RA patients were collected in three different time-points: before treatment with bDMARDs as well as 3 and 12 months following treatment initiation. Total, nuclear and mitochondrial ecDNA was quantified using fluorometry and real-time PCR. Disease activity score (DAS28) and C-reactive protein (CRP) were used to monitor the clinical status and the response to treatment. Treatment with bDMARDs elicited an overall improvement of the clinical status: DAS28 and CRP showed a significant decrease by 54% and 43%, respectively, after 3 months of treatment. A significant decrease of total ecDNA by 60% and nuclear ecDNA by 58% was detected only in good responders after 3 months of bDMARDs treatment. No significant changes of plasma ecDNA concentration were observed in moderate and non-responders. Deoxyribonuclease activity was not affected by the treatment. None of the analyzed biomarkers differed between the groups at baseline. Plasma ecDNA especially of nuclear origin could potentially be useful to monitor the treatment response in RA. Further studies should shed light on disease-treatment interplay implicated in ecDNA origin potentially linked to neutrophil extracellular traps.
Risk assessment of pollen allergy in urban environments
Authors: Dbouk Talib , Visez Nicolas , Ali Samer , Shahrour Isam , Drikakis Dimitris 
Published: December 2022

AbstractAccording to WHO, by 2050, at least one person out of two will suffer from an allergy disorder resulting from the accelerating air pollution associated with toxic gas emissions and climate change. Airborne pollen, and associated allergies, are major public health topics during the pollination season, and their effects are further strengthened due to climate change. Therefore, assessing the airborne pollen allergy risk is essential for improving public health. This study presents a new computational fluid dynamics methodology for risk assessment of local airborne pollen transport in an urban environment. Specifically, we investigate the local airborne pollen transport from trees on a university campus in the north of France. We produce risk assessment maps for pollen allergy for five consecutive days during the pollination season. The proposed methodology could be extended to larger built-up areas for different weather conditions. The risk assessment maps may also be integrated with smart devices, thus leading to decision-aid tools to better guide and protect the public against airborne pollen allergy.
Assessing metabolic syndrome prediction quality using seven anthropometric indices among Jordanian adults: a cross-sectional study
Authors: Al-Shami Islam , Alkhalidy Hana , Alnaser Khadeejah , Mukattash Tareq L. , Al Hourani Huda , Alzboun Tamara , Orabi Aliaa , Liu Dongmin 
Published: December 2022

AbstractMetabolic syndrome (MSyn) is a considerable health concern in developing and developed countries, and it is a critical predictor of all-cause mortality. Obesity, specifically central obesity, is highly associated with MSyn incidence and development. In this study, seven anthropometric indices (Body Mass Index (BMI), Waist circumference (WC), Waist-to-Height Ratio (WHtR), A Body Shape Index (ABSI), Body Roundness Index (BRI), conicity index (CI), and the Visceral Adiposity Index (VAI)) were used to identify individuals with MSyn among the Jordanian population. These indices were assessed to identify their superiority in predicting the risk of MSyn. A total of 756 subjects (410 were male and 346 were female) were met between May 2018 and September 2019 and enrolled in this study. Height, weight, and waist circumferences were measured and BMI, WHtR, ABSI, BRI, CI, and VAI were calculated. Fasting plasma glucose level, lipid profile, and blood pressure were measured. Receiver-operating characteristic (ROC) curve was used to determine the discriminatory power of the anthropometric indices as classifiers for MSyn presence using the Third Adult Treatment Panel III (ATP III) definition. MSyn prevalence was 42.5%, and obese women and men have a significantly higher prevalence. BRI and WHtR showed the highest ability to predict MSyn (AUC = 0.83 for both indices). The optimal cutoff point for an early diagnosis of MSyn was > 28.4 kg/m2 for BMI, > 98.5 cm for WC, > 5.13 for BRI, > 0.09 m11/6 kg−2/3 for ABSI, > 5.55 cm2 for AVI, > 1.33 m3/2 kg−1/2 for CI, and > 0.59 for WHtR with males having higher cutoff points for MSyn early detection than females. In conclusion, we found that WHtR and BRI may be the best-suggested indices for MSyn prediction among Jordanian adults. These indices are affordable and might result in better early detection for MSyn and thereby may be helpful in the prevention of MSyn and its complications.