bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect and mechanism of liraglutide on the biological functions of BMSCs in diabetic patients
Authors: Wang Yao , Sun Yujie , Yang Bo , Li Jun , Liang Chao 
Published: March 2024

AbstractObjectivesTo investigate the effect of liraglutide on osteogenesis in human alveolar bone marrow mesenchymal stem cells (BMSCs) and the influence of liraglutide on implant–bone integration in rats with T2DM.Subjects and methodsExtracting BMSCs from the alveoli of diabetic patients treated with insulin. BMSCs were treated with different concentrations of liraglutide. Osteogenesis and the underlying mechanism were investigated via ALP detection, ALP staining, Alizarin Red S staining, Western blotting, and RT‐PCR. Liraglutide was given to Wistar and GK rats after implantation, and new bone formation around the implants was analyzed via micro‐CT. Implant–bone integration in rats was investigated via toluidine blue staining.ResultsLiraglutide enhanced osteogenesis in BMSCs via the BMP2/Smad/Runx2 signaling pathway. The optimal concentration of liraglutide that promoted osteogenesis was 10−8 mol/L. At concentrations higher than 10−7 mol/L, liraglutide had a negative effect on BMSCs. At a concentration of 10−8 mol/L liraglutide, BMSCs and diabetes mellitus–bone marrow stromal cells (DM‐BMSCs) showed optimal osteogenesis. Liraglutide promoted implant–bone integration and new bone formation in Wistar and GK rats.ConclusionsLiraglutide not only promotes osteogenesis of BMSCs in normoglycemic individuals but also enhances osteogenesis of BMSCs in diabetic patients treated with insulin and enhances osseointegration in rats.
Tilletia horrida glycoside hydrolase family 128 protein, designated ThGhd_7, modulates plant immunity by blocking reactive oxygen species production
Authors: Shu Xinyue , Yin Desuo , Liang Juan , Xiang Ting , Zhang Chao , Li Honglian , Zheng Aiping , Li Ping , Wang Aijun 
Published: March 2024

AbstractTilletia horrida is an important soilborne fungal pathogen that causes rice kernel smut worldwide. We found a glycoside hydrolase family 128 protein, designated ThGhd_7, caused cell death in Nicotiana benthamiana leaves. The predicted signal peptide (SP) of ThGhd_7 targets it for secretion. However, loss of the SP did not affect its ability to induce cell death. The 23–201 amino acid sequence of ThGhd_7 was sufficient to trigger cell death in N. benthamiana. ThGhd_7 expression was induced and upregulated during T. horrida infection. ThGhd_7 localised to both the cytoplasm and nucleus of plant cells, and nuclear localisation was required to induce cell death. The ability of ThGhd_7 to trigger cell death in N. benthamiana depends on RAR1 (required for Mla12 resistance), SGT1 (suppressor of G2 allele of Skp1), and BAK1/SERK3 (somatic embryogenesis receptor‐like kinase 3). Heterologous overexpression of ThGhd_7 in rice reduced reactive oxygen species (ROS) production and enhanced susceptibility to T. horrida. Further research revealed that ThGhd_7 interacted with and destabilised OsSGT1, which is required for ROS production and is a positive regulator of rice resistance to T. horrida. Taken together, these findings suggest that T. horrida employs ThGhd_7 to disrupt ROS production and thereby promote infection.
The roots of Euroscepticism: Affective, behavioural and cognitive anti‐EU attitudes in Hungary
Authors: Bíró‐Nagy András , Szászi Áron József 
Published: March 2024

AbstractThis paper has put forward a new indicator based on the “ABC‐model” of attitudes designed to capture individual‐level Euroscepticism. We constructed a composite anti‐EU score based on affective, behavioural and cognitive sub‐indices. The study analyses data from a representative, countrywide Hungarian public opinion research. Looking for the drivers of anti‐EU attitudes, we took an integrative approach linking various theories of voting behaviour, Euroscepticism and populism studies. Our research showed that subjective well‐being significantly reduces anti‐EU attitudes. We found some empirical support for the “left behind thesis” in the Hungarian context, as severe economic grievances and fear of losing social status explained anti‐EU attitudes. Authoritarian traits turned out to be a major driver of Euroscepticism in Hungary. We proved that cosmopolitan values reduce affective and cognitive anti‐EU attitudes, but foreign experience and some international ties significantly correlated with anti‐EU stance. We confirmed that being a supporter of the governing Fidesz party and sharing culturally right‐wing political views significantly increase anti‐EU attitudes. We also revealed that partisanship's effect is strengthened by affective polarization and political interest.
Reimagining Theological Education in an Interreligious Setting: A Hindu Perspective
Authors: Rodrigues Pravina 
Published: March 2024

ABSTRACTHindu sacred scriptures are a rich interweave of cosmological revelation that is embedded in melopoeia (melodic poetry) and sung in designated meters during rituals, liturgical services, festivals, and personal prayers. Revelation is conveyed through enigmatic dialogues, debates, parables, anecdotes, legends, and narratives. These occur between mendicants and saints, kings and mystics, and sometimes fables that include the natural world. These narrative accounts appeal to the young and the old and influence the body–mind–sense complex. A growing body of evidence attests to the positive effects of music and storytelling in the classroom setting. Drawing from these data and Hindu understandings of sacred mantric sound and storytelling, I discuss my experiments with musical frameworks and storytelling in my classes at the Graduate Theological Union, the Jesuit School of Theology of Santa Clara University, and Starr King School for the Ministry in California. I contend that the incorporation of parables, tales, legends, and narratives within a musical melodic framework, as is used in Hindu texts, is an effective means of imparting Hindu–Christian theological education.
Cardiac output‐mediated regulation of cerebral blood flow during exercise: Clinical perspectives on the indirect impact of muscle metaboreflex
Authors: Ogoh Shigehiko 
Published: March 2024

AbstractThe muscle metaboreflex stimulates the elevation of arterial blood pressure, aiming to rectify the oxygen deficit by enhancing oxygen delivery to support muscle activity. Moreover, activating the muscle metaboreflex significantly increases cardiac output (CO) by increasing factors such as heart rate, ventricular contractility, preload, stroke volume and mobilization of central blood volume. Previous studies indicate that ageing and cardiovascular diseases modify the muscle metaboreflex during exercise, limiting the ability to increase CO during physical activity. Alongside reduced exercise capacity, the attenuated rise in CO due to abnormal muscle metaboreflex in these patients impedes the increase in cerebral blood flow during exercise. Considering that CO plays a pivotal role in regulating cerebral blood flow adequately during exercise, this occurrence might contribute to an elevated risk of cerebral diseases, and it could also, at least, reduce the effective role of exercise in preventing cerebral disease and dementia among elderly individuals and patients with cardiovascular conditions. Therefore, it is important to consider this phenomenon when optimizing the effectiveness of exercise rehabilitation in patients with cardiovascular disease to prevent cerebral diseases and dementia.
Antagonism of 5‐HT2 receptors attenuates self‐sustained firing of human motor units
Authors: Goodlich Benjamin I. , Pearcey Gregory E. P. , Del Vecchio Alessandro , Horan Sean A. , Kavanagh Justin J. 
Published: March 2024

Abstract5‐HT2 receptors on motoneurones play a critical role in facilitating persistent inward currents (PICs). Although facilitation of PICs can enhance self‐sustained firing after periods of excitation, the relationship between 5‐HT2 receptor activity and self‐sustained firing in human motor units (MUs) has not been resolved. MU activity was assessed from the tibialis anterior of 10 healthy adults (24.9 ± 2.8 years) during two contraction protocols. Both protocols featured steady‐state isometric contractions with constant descending drive to the motoneurone pool. However, one protocol also included an additional phase of superimposed descending drive. Adding and then removing descending drive in the middle of steady‐state contractions altered MU firing behaviour across the motor pool, where newly recruited units in the superimposed phase were unable to switch off (P = 0.0002), and units recruited prior to additional descending drive reduced their discharge rates (P < 0.0001, difference in estimated marginal means (∆) = 2.24 pulses/s). The 5‐HT2 receptor antagonist, cyproheptadine, was then administered to determine whether changes in MU firing were mediated by serotonergic mechanisms. 5‐HT2 receptor antagonism caused reductions in MU discharge rate (P < 0.001, ∆ = 1.65 pulses/s), recruitment threshold (P = 0.00112, ∆ = 1.09% maximal voluntary contraction) and self‐sustained firing duration (P < 0.0001, ∆ = 1.77s) after the additional descending drive was removed in the middle of the steady‐state contraction. These findings indicate that serotonergic neuromodulation plays a key role in facilitating discharge and self‐sustained firing of human motoneurones, where adaptive changes in MU recruitment must occur to meet the demands of the contraction.
imageKey points
Animal and cellular preparations indicate that somato‐dendritic 5‐HT2 receptors regulate the intrinsic excitability of motoneurones.
5‐HT2 receptor antagonism reduces estimates of persistent inward currents in motoneurones, which contribute to self‐sustained firing when synaptic inputs are reduced or removed.
This human study employed a contraction task that slowly increased (and then removed) the additional descending drive in the middle of a steady‐state contraction where marked self‐sustained firing occurred when the descending drive was removed.
5‐HT2 receptor antagonism caused widespread reductions in motor unit (MU) discharge rates during contractions, which was accompanied by reduced recruitment threshold and attenuation of self‐sustained firing duration after the removal of the additional descending drive to motoneurones.
These findings support the role that serotonergic neuromodulation is a key facilitator of MU discharge and self‐sustained firing of human motoneurones, where adaptative changes in MU recruitment must occur to meet the demands of the contraction.
Functional dissection of the spike glycoprotein S1 subunit and identification of cellular cofactors for regulation of swine acute diarrhea syndrome coronavirus entry
Authors: Yang Yong-Le , Wang Bin , Li Wentao , Cai Hou-Li , Qian Qian-Yu , Qin Yu , Shi Fang-Shu , Bosch Berend-Jan , Huang Yao-Wei 
Published: March 2024

ABSTRACT

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus, and the broad interspecies infection of SADS-CoV poses a potential threat to human health. This study provides experimental evidence to dissect the roles of distinct domains within the SADS-CoV spike S1 subunit in cellular entry. Specifically, we expressed the S1 and its subdomains, S1
A
and S1
B
. Cell binding and invasion inhibition assays revealed a preference for the S1
B
subdomain in binding to the receptors on the cell surface, and this unknown receptor is not utilized by the porcine epidemic diarrhea virus. Nanoparticle display demonstrated hemagglutination of erythrocytes from pigs, humans, and mice, linking the S1
A
subdomain to the binding of sialic acid (Sia) involved in virus attachment. We successfully rescued GFP-labeled SADS-CoV (rSADS-GFP) from a recombinant cDNA clone to track viral infection. Antisera raised against S1, S1
A
, or S1
B
contained highly potent neutralizing antibodies, with anti-S1
B
showing better efficiency in neutralizing rSADS-GFP infection compared to anti-S1
A
. Furthermore, depletion of heparan sulfate (HS) by heparinase treatment or pre-incubation of rSADS-GFP with HS or constituent monosaccharides could inhibit SADS-CoV entry. Finally, we demonstrated that active furin cleavage of S glycoprotein and the presence of type II transmembrane serine protease (TMPRSS2) are essential for SADS-CoV infection. These combined observations suggest that the wide cell tropism of SADS-CoV may be related to the distribution of Sia or HS on the cell surface, whereas the S1
B
contains the main protein receptor binding site. Specific host proteases also play important roles in facilitating SADS-CoV entry.

IMPORTANCE

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel pathogen infecting piglet, and its unique genetic evolution characteristics and broad species tropism suggest the potential for cross-species transmission. The virus enters cells through its spike (S) glycoprotein. In this study, we identify the receptor binding domain on the C-terminal part of the S1 subunit (S1
B
) of SADS-CoV, whereas the sugar-binding domain located at the S1 N-terminal part of S1 (S1
A
). Sialic acid, heparan sulfate, and specific host proteases play essential roles in viral attachment and entry. The dissection of SADS-CoV S1 subunit’s functional domains and identification of cellular entry cofactors will help to explore the receptors used by SADS-CoV, which may contribute to exploring the mechanisms behind cross-species transmission and host tropism.
Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways
Authors: Wang Tongtong , Hu Leyu , Li Ruibo , Ren Huiying , Li Shuwen , Sun Qi , Ding Xiangdan , Li Yubao , Wang Changfa , Li Liangliang 
Published: March 2024

ABSTRACT

Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry. Currently, there is no effective vaccine or drug against EHV-8 infection, underscoring the need for a novel antiviral drug to prevent EHV-8-induced latent infection and decrease the pathogenicity of this virus. The present study demonstrated that hyperoside can exert antiviral effects against EHV-8 infection in RK-13 (rabbit kidney cells), MDBK (Madin–Darby bovine kidney), and NBL-6 cells (E. Derm cells). Mechanistic investigations revealed that hyperoside induces heme oxygenase-1 expression by activating the c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis, alleviating oxidative stress and triggering a downstream antiviral interferon response. Accordingly, hyperoside inhibits EHV-8 infection. Meanwhile, hyperoside can also mitigate EHV-8-induced injury in the lungs of infected mice. These results indicate that hyperoside may serve as a novel antiviral agent against EHV-8 infection.

IMPORTANCE
Hyperoside has been reported to suppress viral infections, including herpesvirus, hepatitis B virus, infectious bronchitis virus, and severe acute respiratory syndrome coronavirus 2 infection. However, its mechanism of action against equine herpesvirus type 8 (EHV-8) is currently unknown. Here, we demonstrated that hyperoside significantly inhibits EHV-8 adsorption and internalization in susceptible cells. This process induces HO-1 expression via c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis activation, alleviating oxidative stress and triggering an antiviral interferon response. These findings indicate that hyperoside could be very effective as a drug against EHV-8.
Evolutionary dynamics of the accessory genomes of
Staphylococcus aureus
Authors: Piper Kathryn R. , Ikhimiukor Odion O. , Souza Stephanie S. R. , Garcia-Aroca Teddy , Andam Cheryl P. 
Published: March 2024

ABSTRACT

Staphylococcus aureus
is a ubiquitous commensal and opportunistic bacterial pathogen that can cause a wide gamut of infections, which are exacerbated by the presence of multidrug-resistant and methicillin-resistant
S. aureus
.
S. aureus
is genetically heterogeneous and consists of numerous distinct lineages. Using 558 complete genomes of
S. aureus
, we aim to determine how the accessory genome content among phylogenetic lineages of
S. aureus
is structured and has evolved. Bayesian hierarchical clustering identified 10 sequence clusters, of which seven contained major sequence types (ST 1, 5, 8, 30, 59, 239, and 398). The seven sequence clusters differed in their accessory gene content, including genes associated with antimicrobial resistance and virulence. Focusing on the two largest clusters, BAPS8 and BAPS10, and each consisting mostly of ST5 and ST8, respectively, we found that the structure and connected components in the co-occurrence networks of accessory genomes varied between them. These differences are explained, in part, by the variation in the rates at which the two sequence clusters gained and lost accessory genes, with the highest rate of gene accumulation occurring recently in their evolutionary histories. We also identified a divergent group within BAPS10 that has experienced high gene gain and loss early in its history. Together, our results show highly variable and dynamic accessory genomes in
S. aureus
that are structured by the history of the specific lineages that carry them.

IMPORTANCE

Staphylococcus aureus
is an opportunistic, multi-host pathogen that can cause a variety of benign and life-threatening infections. Our results revealed considerable differences in the structure and evolution of the accessory genomes of major lineages within
S. aureus
. Such genomic variation within a species can have important implications on disease epidemiology, pathogenesis of infection, and interactions with the vertebrate host. Our findings provide important insights into the underlying genetic basis for the success of
S. aureus
as a highly adaptable and resistant pathogen, which will inform current efforts to control and treat staphylococcal diseases.
Structural implications of BK polyomavirus sequence variations in the major viral capsid protein Vp1 and large T-antigen: a computational study
Authors: Durairaj Janani , Follonier Océane M. , Leuzinger Karoline , Alexander Leila T. , Wilhelm Maud , Pereira Joana , Hillenbrand Caroline A. , Weissbach Fabian H. , Schwede Torsten , Hirsch Hans H. 
Published: March 2024

ABSTRACT

BK polyomavirus (BKPyV) is a double-stranded DNA virus causing nephropathy, hemorrhagic cystitis, and urothelial cancer in transplant patients. The BKPyV-encoded capsid protein Vp1 and large T-antigen (LTag) are key targets of neutralizing antibodies and cytotoxic T-cells, respectively. Our single-center data suggested that variability in Vp1 and LTag may contribute to failing BKPyV-specific immune control and impact vaccine design. We, therefore, analyzed all available entries in GenBank (1516
VP1
; 742
LTAG
) and explored potential structural effects using computational approaches. BKPyV-genotype (gt)1 was found in 71.18% of entries, followed by BKPyV-gt4 (19.26%), BKPyV-gt2 (8.11%), and BKPyV-gt3 (1.45%), but rates differed according to country and specimen type. Vp1-mutations matched a serotype different than the assigned one or were serotype-independent in 43%, 18% affected more than one amino acid. Notable Vp1-mutations altered antibody-binding domains, interactions with sialic acid receptors, or were predicted to change conformation. LTag-sequences were more conserved, with only 16 mutations detectable in more than one entry and without significant effects on LTag-structure or interaction domains. However, LTag changes were predicted to affect HLA-class I presentation of immunodominant 9mers to cytotoxic T-cells. These global data strengthen single center observations and specifically our earlier findings revealing mutant 9mer epitopes conferring immune escape from HLA-I cytotoxic T cells. We conclude that variability of BKPyV-Vp1 and LTag may have important implications for diagnostic assays assessing BKPyV-specific immune control and for vaccine design.

IMPORTANCE
Type and rate of amino acid variations in BKPyV may provide important insights into BKPyV diversity in human populations and an important step toward defining determinants of BKPyV-specific immunity needed to protect vulnerable patients from BKPyV diseases. Our analysis of BKPyV sequences obtained from human specimens reveals an unexpectedly high genetic variability for this double-stranded DNA virus that strongly relies on host cell DNA replication machinery with its proof reading and error correction mechanisms. BKPyV variability and immune escape should be taken into account when designing further approaches to antivirals, monoclonal antibodies, and vaccines for patients at risk of BKPyV diseases.
Supplemental Material: Late Triassic paleogeography of southern Laurentia and its fringing arcs: Insights from detrital zircon U-Pb geochronology and Hf isotope geochemistry, Auld Lang Syne basin (Nevada, USA)
Authors: Schwartz Theresa M. , al. et 
Published: March 2024

<p>Figure S1: Schematic stratigraphic columns of different parts of the Auld Lang Syne basin. Figure S2: Normalized KDEs and histograms for all new detrital zircon samples from the Auld Lang Syne basin that emphasize the distributions of Permian and Triassic ages in each sample. Table S1: Detailed sample information. Table S2: New detrital zircon U-Pb data for sandstones of the Auld Lang Syne basin, western Nevada, USA. Table S3: LA-MC-ICP-MS Lu-Hf isotopic analyses of detrital zircons younger than 600 Ma from the Auld Lang Syne basin, Nevada, USA. Table S4: Information for Upper Triassic (Norian) samples comprising the four “interpretation groups” discussed throughout the text. Table S5: Information for samples comprising the various source proxies discussed throughout the text, including DZmix inputs and results. Table S6: Information for εHf reference data used in Figure 11 of the main text. </p>
Evaluation of degree of blending and its effect on performance of recycled hot-mix asphalt under different preheating conditions
Authors: Zhang Yining , Chen Hengjin 
Published: March 2024

This research comprehensively explored the function of preheating temperature and quantified the contribution of degree of blending (DoB) to performance of recycled hot-mix asphalt (HMAs). Five groups were designed, including no blending group, full blending group, and three experimental groups at preheating temperatures of 60, 110, and 160 °C. It can be found that the preheating temperature played a positive impact on DoB and performance of recycled HMAs. As the preheating temperature increased by 50 °C, about 0.13%–0.2% of reclaimed asphalt binder can be additionally activated, and the tensile strength ratio, shear strength, and fracture energy of recycled HMAs can improve by around 6%–8%, 0.07–0.15 MPa, and 304.2–335.4 J·m2, respectively. Moreover, the results showed that the performance of recycled mixes designed at preheating temperature of 60 °C was close to that of no blending group, while the mixes designed at a preheating temperature of 160 °C can reach to those of full blending group.