bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutraligands of C5a can potentially occlude the interaction of C5a with the complement receptors C5aR1 and C5aR2
Authors: Das Aurosikha , Ghosh Manaswini , Gupta Pulkit Kr. , Rana Soumendra 
Published: December 2022

AbstractThe complement system is central to the rapid immune response witnessed in vertebrates and invertebrates, which plays a crucial role in physiology and pathophysiology. Complement activation fuels the proteolytic cascade, which produces several complement fragments that interacts with a distinct set of complement receptors. Among all the complement fragments, C5a is one of the most potent anaphylatoxins, which exerts solid pro‐inflammatory responses in a myriad of tissues by binding to the complement receptors such as C5aR1 (CD88, C5aR) and C5aR2 (GPR77, C5L2), which are part of the rhodopsin subfamily of G‐protein coupled receptors. In terms of signaling cascade, recruitment of C5aR1 or C5aR2 by C5a triggers the association of either G‐proteins or β‐arrestins, providing a protective response under normal physiological conditions and a destructive response under pathophysiological conditions. As a result, both deficiency and unregulated activation of the complement lead to clinical conditions that require therapeutic intervention. Indeed, complement therapeutics targeting either the complement fragments or the complement receptors are being actively pursued by both industry and academia. In this context, the model structural complex of C5a–C5aR1 interactions, followed by a biophysical evaluation of the model complex, has been elaborated on earlier. In addition, through the drug repurposing strategy, we have shown that small molecule drugs such as raloxifene and prednisone may act as neutraligands of C5a by effectively binding to C5a and altering its biologically active molecular conformation. Very recently, structural models illustrating the intermolecular interaction of C5a with C5aR2 have also been elaborated by our group. In the current study, we provide the biophysical validation of the C5a‐C5aR2 model complex by recruiting major synthetic peptide fragments of C5aR2 against C5a. In addition, the ability of the selected neutraligands to hinder the interaction of C5a with the peptide fragments derived from both C5aR1 and C5aR2 has also been explored. Overall, the computational and experimental data provided in the current study supports the idea that small molecule drugs targeting C5a can potentially neutralize C5a's ability to interact effectively with its cognate complement receptors, which can be beneficial in modulating the destructive signaling response of C5a under pathological conditions.
Mechanisms of radioresistance and the underlying signaling pathways in colorectal cancer cells
Authors: Tessmann Josiane W. , Rocha Murilo R. , Morgado‐Díaz Jose A. 
Published: December 2022

AbstractRadiotherapy is one of the most common modalities for the treatment of a wide range of tumors, including colorectal cancer (CRC); however, radioresistance of cancer cells remains a major limitation for this treatment. Following radiotherapy, the activities of various cellular mechanisms and cell signaling pathways are altered, resulting in the development of radioresistance, which leads to therapeutic failure and poor prognosis in patients with cancer. Furthermore, even though several inhibitors have been developed to target tumor resistance, these molecules can induce side effects in nontumor cells due to low specificity and efficiency. However, the role of these mechanisms in CRC has not been extensively studied. This review discusses recent studies regarding the relationship between radioresistance and the alterations in a series of cellular mechanisms and cell signaling pathways that lead to therapeutic failure and tumor recurrence. Our review also presents recent advances in the in vitro/in vivo study models aimed at investigating the radioresistance mechanism in CRC. Furthermore, it provides a relevant biochemical basis in theory, which can be useful to improve radiotherapy sensitivity and prolong patient survival.
Implementation of real‐time TDDFT for periodic systems in the open‐source PySCF software package
Authors: Hanasaki Kota , Ali Zulfikhar A. , Choi Min , Del Ben Mauro , Wong Bryan M. 
Published: December 2022

AbstractWe present a new implementation of real‐time time‐dependent density functional theory (RT‐TDDFT) for calculating excited‐state dynamics of periodic systems in the open‐source Python‐based PySCF software package. Our implementation uses Gaussian basis functions in a velocity gauge formalism and can be applied to periodic surfaces, condensed‐phase, and molecular systems. As representative benchmark applications, we present optical absorption calculations of various molecular and bulk systems and a real‐time simulation of field‐induced dynamics of a (ZnO)4 molecular cluster on a periodic graphene sheet. We present representative calculations on optical response of solids to infinitesimal external fields as well as real‐time charge‐transfer dynamics induced by strong pulsed laser fields. Due to the widespread use of the Python language, our RT‐TDDFT implementation can be easily modified and provides a new capability in the PySCF code for real‐time excited‐state calculations of chemical and material systems.
p62/SQSTM1 indirectly mediates remote multipotent mesenchymal cells and rescues bone loss and bone marrow integrity in ovariectomized rats
Authors: Agas Dimitrios , Marchegiani Andrea , Laus Fulvio , Gabai Vladimir , Sufianov Albert A. , Shneider Alexander , Sabbieti Maria Giovanna 
Published: December 2022

AbstractIntramuscular administration of p62/SQSTM1 (sequestosome1)‐encoding plasmid demonstrated an anticancer effect in rodent models and dogs as well as a high safety profile and the first evidence of clinical benefits in humans. Also, an anti‐inflammatory effect of the plasmid was reported in several rodent disease models. Yet, the mechanisms of action for the p62 plasmid remain unknown. Here, we tested a hypothesis that the p62‐plasmid can act through the modulation of bone marrow multipotent mesenchymal cells (MSCs). We demonstrated that a p62 plasmid can affect MSCs indirectly by stimulating p62‐transfected cells to secrete an active ingredient(s) sensed by untransfected MSCs. When we transfected MSCs with the p62‐plasmid, collected their supernatant, and added it to an untransfected MSCs culture, it switched the differentiation state and prompt osteogenic responses of the untransfected MSCs. According to an accepted viewpoint, ovariectomy leads to bone pathology via dysregulation of MSCs, and restoring the MSC homeostasis would restore ovariectomy‐induced bone damage. To validate our in vitro observations in a clinically relevant in vivo model, we administered the p62 plasmid to ovariectomized rats. It partially reversed bone loss and notably reduced adipogenesis with concurrent reestablishing of the MSC subpopulation pool within the bone marrow. Overall, our study suggests that remote modulation of progenitor MSCs via administering a p62‐encoding plasmid may constitute a mechanism for its previously reported effects and presents a feasible disease‐preventing and/or therapeutic strategy.
Androgen and prolactin manipulation do not induce changes in immunocompetence measures in a fish with male parental care
Authors: Cunha Adriano A. P. , Garner Shawn R. , Ingoldsby Erin , Dixon Brian , MacDougall‐Shackleton Scott A. , Knapp Rosemary , Neff Bryan D. 
Published: December 2022

AbstractProlactin and 11‐ketotestosterone (11‐KT) are important reproductive hormones in fishes, which may also influence immunocompetence. The immunocompetence handicap hypothesis states that higher androgen concentrations that support secondary sex traits are traded off against a decrease in immune system function. To test the relationships between these hormones and immunocompetence, we experimentally manipulated 11‐ketotestosterone and prolactin in the freshwater fish, bluegill (Lepomis macrochirus) during parental care using implants that contained either 11‐KT, prolactin, or an inert control. We vaccinated individuals to stimulate the acquired immune response, then measured immunocompetence as the number of granulocytes, lymphocytes and monocytes, and the expression of interleukin 8 in each sample. We did not observe any significant differences in the immune measures among the hormone treatments. Our results indicate that in bluegill, there is no trade‐off between androgens or prolactin and immunocompetence.
Brain response in allergic rhinitis: Profile and proposal
Authors: Wang Yao , Song Xiao‐Yu , Wei Shi‐Zhuang , Wang Han‐Rui , Zhang Wen‐Bin , Li Yu‐Mei , Mou Ya‐Kui , Ren Chao , Song Xi‐Cheng 
Published: December 2022

AbstractIn addition to typical nasal symptoms, patients with allergic rhinitis (AR) will further lead to symptoms related to brain function such as hyposmia, anxiety, depression, cognitive impairment, memory loss, etc., which seriously affect the quality of life of patients and bring a heavy burden to the patient's family and society. Some scholars have speculated that there may be potential “nose‐brain communication” mechanism in AR that rely on neuro‐immunity. This mechanism plays an important role in AR‐associated brain response process. However, no study has directly demonstrated which neural circuits will change in the connection between the nose and brain during the onset of AR, and the mechanism which underlines this question is also lack. Focusing on the topic of “nose‐brain communication”, this paper systematically summarizes the latest research progress between AR and related brain responses and discusses the mechanism of AR‐related neurological phenotypes. Hope new diagnostic and therapeutic targets to ameliorate the brain function‐related symptoms and improve the quality of life of AR patients will be developed.
The combined influences of Amazon deforestation and Pacific Decadal Oscillation on the South America climate variability
Authors: Silva Maria Elisa Siqueira , da Rocha Rosmeri Porfírio , Pereira Gabriel , Medeiros Rocha Andre , Mendes Daniel , da Silva Carlos Batista 
Published: December 2022

AbstractIn this study we analyse the climatic impact over South America due to Amazon deforestation for positive (PDO+) and negative (PDO−) PDO phases. The regional climatic model RegCM4 was run from 1968 to 2003 for the domain including a great area of the Pacific Ocean and South America, using 50 km as spatial resolution. The Amazon deforestation scenario is that one extrapolated to the 2050 year. Under deforestation, the results show precipitation depletion over the extreme northern South America and precipitation increase over areas to the south, including deforested pixels and east‐southern sectors. These changes are more intense and occupy larger areas during the rainy season. Simulations also indicate that deforestation may impose a drier corridor following the Andes Mountains oriental slopes, from northwestern to south‐southeastern South America, in the rainy season. The impact from deforestation in distinct PDO phases presents the greatest signals over central‐southern South America, in a northwest–southeast direction. Over southeast Brazil, deforestation presents a slightly northeastward displacement of the PDO+ positive precipitation anomalies, intensifying the precipitation anomalies in the north sector and weakening over the south sector. The deforestation effects are more intense in the rainy season and have opposite signals between PDO+ and PDO−. Over the southeast South America, deforestation provides a weaker signal on PDO+ negative precipitation than in PDO−. The increased air temperature over the northern South America, near the northern coast, due to the joint effect of deforestation and PDO variability is more evident during PDO+ dry season than PDO− rainy season. This study illustrates the importance of considering long‐term climate simulations to better understand the role of deforestation in the lower frequency variability over South America.
Persistent and nonpersistent regional extreme total, daytime, and night‐time precipitation events over southwest China (1961–2019)
Authors: Cheng Qingping , Jin Hanyu , Ren Yitong 
Published: December 2022

AbstractExtreme persistent precipitation is becoming increasingly common globally, and persistent extreme regional precipitation events (PERPEs) pose a particularly serious threat to humans and environmental systems. This study investigated total precipitation (TP), daytime precipitation (DP), and night‐time precipitation (NP) in southwest China (SWC) during 1961–2019. The occurrence of TP, DP, and NP was analysed under the conditions of persistence over 1–5 days, temporal persistence over >2 days, and temporal nonpersistence over ≤2 days, and spatiotemporal overlap for at least 3 days (i.e., a PERPE) using the objective identification technique for regional extreme events. The results indicated the following. (a) Annual maximum daily precipitation ≥200 (100) mm in terms of TP (NP) was recorded mainly in the Sichuan Basin (SCB) and eastern parts of the Yunnan–Guizhou Plateau (YGP), and it occurred mostly in summer. For DP, annual maximum daily precipitation of ≥100 mm was recorded throughout SWC, and it occurred mainly in winter in the Henduan Mountains, summer in the SCB, and spring in western parts of the YGP. (b) The magnitudes of NP and DP differed for events persisting for 1–5 days. The average amount of precipitation with temporal persistence increased during 1961–2019 for TP, DP, and NP. However, the frequency of occurrence of events with temporal persistence increased more in comparison with that of events with temporal nonpersistence. Overall, the frequency of occurrence of events with temporal persistence or temporal nonpersistence in the western SCB and eastern YGP increased more for TP and NP than for DP. (c) In the study period, 22, 44, and 4 PERPEs were detected for TP, NP, and DP, respectively, occurring mainly in the SCB, indicating that TP was dominated by night‐time PERPEs. These findings improve understanding of PERPEs changes in SWC and provide scientific support for implementation of measures intended to prevent and mitigate extreme flood events and waterlogging.
Regional changes of surface air temperature annual cycle in the Northern Hemisphere land areas
Authors: Deng Qimin , Fu Zuntao 
Published: December 2022

AbstractThe regional amplitude and phase characteristics of surface (2 m) air temperature (SAT) annual cycle (AC) over the Northern Hemisphere land area are analysed by the clustering method for the period 1953–2018. The five clusters are found in the nonlinear changes of AC amplitude and the six clusters are found in the AC phase. The spatial distributions of clusters are not the same for amplitude and phase, but the similarity is that both the amplitude and phase have remarkably different trends in the mainland of Eurasia and North America, even though these two regions locate over the similar latitudinal zone. Descending trends of AC amplitude are found for the whole period 1953–2018 in most areas, except in and around Greenland. However, when checking the nonlinear variation and making a piece‐wise linear fit, the abnormal increasing trend (stronger seasonality) appears in the major part of Eurasia after the year 1990. The comparisons of surface radiation fluxes in Eurasia and North America indicate that the long‐term reduction of the reflection and absorption of clouds and aerosols with the declined surface albedo after 1980–1985 may lead to the amplitude amplification after 1990 in Eurasia. In contrast, the variation of surface radiation in North America remains unchanged, where the decreasing trend of amplitude may result from other causes. The overall phase trend is increasing (toward earlier season), but in North America after 1990, the phase shift becomes delayed. The phase variations are correlated to North Atlantic Oscillation (NAO) cold season index over almost all regions, especially in Europe.
Predictability of China winter temperature under different intensities of La Niña events in seasonal climate forecast models
Authors: Guo Zengyuan , Ke Zongjian , Chen Lijuan 
Published: December 2022

AbstractIn this study, we focus on the features and predictability of winter 2‐m air temperature (t2m) over China under different intensities of La Niña events. The seasonal and intraseasonal prediction skills of winter t2m over China are examined by four state‐of‐art seasonal climate forecast models. The results show that the China winter t2m anomaly is sensitive to the intensity of La Niña. Strong and moderate (S/M) La Niña events are often accompanied by cold winter over China, while a positive anomaly of mean t2m over China frequently occurs in the weak La Niña events. The intensity difference of the East Asian winter monsoon (EAWM) results in this discrepancy. All models have a slightly higher anomaly correlation coefficient (ACC) for the S/M La Niña than that for the weak La Niña in leading 1 month (LT1). Both individual models and MME exhibit higher skills of anomaly sign consistency rate (ASCR) for the S/M La Niña, which implies that models predict t2m anomaly over China more accurately in the S/M La Niña events. Furthermore, the winter t2m over China presents larger intraseasonal variability for the S/M La Niña than that for the weak La Niña. Models can capture the t2m anomaly over China more accurately when the temperature varies gently with small intraseasonal variability during winter for the S/M La Niña.
Monthly variation of local land–atmosphere coupling over the Tibetan Plateau in the rainy season and its relationship with the South Asian summer monsoon
Authors: Sun Genhou , Sun Fanglin , Wei Wei , Yang Song , Hu Zeyong , Ma Yaoming , Xie Zhipeng , Wang Jiemin 
Published: December 2022

AbstractThe local land–atmosphere coupling (LoCo) over the Tibetan Plateau (TP) in the rainy season and the possible influence of the South Asian monsoon (SAM) on LoCo characteristics are investigated by applying two LoCo diagnostic metrics to 12‐year observational data at six stations over the TP and the ERA5 from June to September (JJAS) from 1980 to 2018. The validation of ERA5 in estimating monthly mean diurnal evolutions of T2m, q2m, and surface fluxes (Hsfc and LEsfc) at the six stations reveals that these variables in the ERA5 are relatively reliable for the LoCo analysis. The mixing diagram analysis based on the observational data and ERA5 suggests that the monthly variations in the planetary boundary layer (PBL) energy budget are strong and vary from station to station, revealing the complexity of the influence of the SAM on the PBL energy budget over TP. The relationship between Hsfc and PBL height (PBLH) and lifted condensation level (LCL) deficit at the six stations based on the ERA5 reveal a strong influence of soil moisture on PBL growth and convective cloud formation, although the topography may also exert its influence. Analyses of the correlations of the PBL energy budget, PBLH, and LCL deficit over the TP with the SAM in JJAS indicate that the LoCo characteristics over the TP show large spatial variability between the southeastern and central‐western parts of the TP. Such spatial variability can be attributed to the spatial differences in monthly mean soil moisture and rainfall closely related to the evolution of SAM's influence and the complex topography of the TP. The topography of the TP can also affect the LoCo characteristics in JJAS, but the mechanisms in the areas dominated by SAM and by the westerly winds are different.
Raman and synchrotron X‐ray diffraction studies of 4‐azidobenzoic acid under high pressures
Authors: Yang Wen , Wei Hui‐li , Yu Tian‐yi , Ding Jie , Jiang Jun‐ru , Wang Jian , He Zhi‐jun , Zhu Hong‐yang 
Published: December 2022

AbstractHere, we report the distinct behaviors of 4‐azidobenzoic acid (C7H5N3O2, 4‐ABA) in diamond anvil cells with the pressure up to ∼18 GPa at room temperature by in situ Raman scattering and synchrotron angle‐dispersive X‐ray diffraction (ADXRD) measurements. The analyses of Raman spectra revealed that 4‐ABA underwent a phase transition in the pressure range of 0.8–1.3 GPa and a conformational change at 6.3 GPa, which were supported by XRD results. The phase transition is attributed to the distortion of the benzene ring, and the change of hydrogen bonds results in the conformational change. Above 11.2 GPa, the (112) Bragg peak moved toward a low angle, indicating the increase of the interplanar distance of 4‐ABA. Upon compression to 18.0 GPa, 4‐ABA transformed into amorphous phase that the low amorphization pressure is helpful for nitrogen polymerization. This study provides an effective route for understanding the evolution of the azide group under high pressure, which is beneficial to studying the mechanism of forming polymeric nitrogen.
Particulate and dissolved metabolite distributions along a latitudinal transect of the western Atlantic Ocean
Authors: Johnson Winifred M. , Kido Soule Melissa C. , Longnecker Krista , Bhatia Maya P. , Hallam Steven J. , Lomas Michael W. , Kujawinski Elizabeth B. 
Published: December 2022

AbstractMetabolites, or the small organic molecules that are synthesized by cells during metabolism, comprise a complex and dynamic pool of carbon in the ocean. They are an essential currency in interactions at the population and community levels of biological organization. Characterizing metabolite distributions inside microbial cells and dissolved in seawater is essential to understanding the controls on their production and fate, as well as their roles in shaping marine microbial food webs. Here, we apply a targeted metabolomics method to quantify particulate and dissolved distributions of a suite of biologically relevant metabolites including vitamins, amino acids, nucleic acids, osmolytes, and intermediates in biosynthetic pathways along a latitudinal transect in the western Atlantic Ocean. We find that, in the upper 200 m of the water column, most particulate or intracellular metabolites positively covary with the most abundant microbial taxa. In contrast, dissolved metabolites exhibited greater variability with differences in distribution between ocean regions. Although fewer particulate metabolites were detected below 200 m, the particulate metabolites identified in the deep ocean may be linked to adaptive physiological strategies of deep‐sea microbes. Based on the identified metabolite distributions, we propose relationships between certain metabolites and microbial populations, and find that dissolved metabolite distributions are not directly related to their particulate abundances.
Side Chain Dynamics of Poly(norbornene)‐g‐Poly(propylene oxide) Bottlebrush Polymers
Authors: Bichler Karin J. , Jakobi Bruno , Klapproth Alice , Tominaga Taiki , Mole Richard A. , Schneider Gerald J. 
Published: December 2022

AbstractThe segmental dynamics of the side chains of poly(norbornene)‐g‐poly(propylene oxide) (PNB‐g‐PPO) bottlebrush polymer in comparison to PPO is studied by quasi‐elastic neutron scattering. Having experimental time and length scale information simultaneously allows to extract spatial information in addition to relaxation time. Tethering one end of the PPO side chain onto a stiff PNB backbone slows down the segmental relaxation, over the length and time scales investigated. The power law dependence of the relaxation time on the momentum transfer,Q, indicates a more heterogeneous relaxation pattern for the bottlebrush polymer, whereas the linear PPO has less deviations from a homogenous relaxation. Similar conclusions can be drawn from the time dependent mean square displacement, 〈r2(t)〉, and the non‐Gaussian parameter,α2(t). Herein, the bottlebrush polymer shows a more restricted dynamics, whereas the linear PPO reaches 〈r2(t)〉∝t0.5at the highest temperature. The deviations from Gaussian behavior are evident at theα2(t). Both samples show a decayingα2(t). The non‐Gaussian parameter supports the results from the power law dependence of the relaxation times, with lowerα2(t) values for PPO compared to those for PNB‐g‐PPO, pointing to less deviations from Gaussian behavior.