bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postnatal supplementation with alarmins S100a8/a9 ameliorates malnutrition-induced neonate enteropathy in mice
Authors: Perruzza Lisa , Heckmann Julia , Rezzonico Jost Tanja , Raneri Matteo , Guglielmetti Simone , Gargari Giorgio , Palatella Martina , Willers Maike , Fehlhaber Beate , Werlein Christopher , Vogl Thomas , Roth Johannes , Grassi Fabio , Viemann Dorothee 
Published: October 2024

AbstractMalnutrition is linked to 45% of global childhood mortality, however, the impact of maternal malnutrition on the child’s health remains elusive. Previous studies suggested that maternal malnutrition does not affect breast milk composition. Yet, malnourished children often develop a so-called environmental enteropathy, assumed to be triggered by frequent pathogen uptake and unfavorable gut colonization. Here, we show in a murine model that maternal malnutrition induces a persistent inflammatory gut dysfunction in the offspring that establishes during nursing and does not recover after weaning onto standard diet. Early intestinal influx of neutrophils, impaired postnatal development of gut-regulatory functions, and expansion of Enterobacteriaceae were hallmarks of this enteropathy. This gut phenotype resembled those developing under deficient S100a8/a9-supply via breast milk, which is a known key factor for the postnatal development of gut homeostasis. We could confirm that S100a8/a9 is lacking in the breast milk of malnourished mothers and the offspring’s intestine. Nutritional supply of S100a8 to neonates of malnourished mothers abrogated the aberrant development of gut mucosal immunity and microbiota colonization and protected them lifelong against severe enteric infections and non-infectious bowel diseases. S100a8 supplementation after birth might be a promising measure to counteract deleterious imprinting of gut immunity by maternal malnutrition.
Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy
Authors: Hutchings Amy-Jayne , Hambrecht Bita , Veh Alexander , Giridhar Neha Jadhav , Zare Abdolhossein , Angerer Christina , Ohnesorge Thorben , Schenke Maren , Selvaraj Bhuvaneish T. , Chandran Siddharthan , Sterneckert Jared , Petri Susanne , Seeger Bettina , Briese Michael , Stigloher Christian , Bischler Thorsten , Hermann Andreas , Damme Markus , Sendtner Michael , Lüningschrör Patrick 
Published: October 2024

AbstractIncreasing evidence suggests an essential function for autophagy in unconventional protein secretion (UPS). However, despite its relevance for the secretion of aggregate-prone proteins, the mechanisms of secretory autophagy in neurons have remained elusive. Here we show that the lower motoneuron disease-associated guanine exchange factor Plekhg5 drives the UPS of Sod1. Mechanistically, Sod1 is sequestered into autophagosomal carriers, which subsequently fuse with secretory lysosomal-related organelles (LROs). Exocytosis of LROs to release Sod1 into the extracellular milieu requires the activation of the small GTPase Rab26 by Plekhg5. Deletion of Plekhg5 in mice leads to the accumulation of Sod1 in LROs at swollen presynaptic sites. A reduced secretion of toxic ALS-linked SOD1G93A following deletion of Plekhg5 in SOD1G93A mice accelerated disease onset while prolonging survival due to an attenuated microglia activation. Using human iPSC-derived motoneurons we show that reduced levels of PLEKHG5 cause an impaired secretion of ALS-linked SOD1. Our findings highlight an unexpected pathophysiological mechanism that converges two motoneuron disease-associated proteins into a common pathway.
Dynamic gain and frequency comb formation in exceptional-point lasers
Authors: Gao Xingwei , He Hao , Sobolewski Scott , Cerjan Alexander , Hsu Chia Wei 
Published: October 2024

AbstractExceptional points (EPs)—singularities in the parameter space of non-Hermitian systems where two nearby eigenmodes coalesce—feature unique properties with applications such as sensitivity enhancement and chiral emission. Existing realizations of EP lasers operate with static populations in the gain medium. By analyzing the full-wave Maxwell–Bloch equations, here we show that in a laser operating sufficiently close to an EP, the nonlinear gain will spontaneously induce a multi-spectral multi-modal instability above a pump threshold, which initiates an oscillating population inversion and generates a frequency comb. The efficiency of comb generation is enhanced by both the spectral degeneracy and the spatial coalescence of modes near an EP. Such an “EP comb” has a widely tunable repetition rate, self-starts without external modulators or a continuous-wave pump, and can be realized with an ultra-compact footprint. We develop an exact solution of the Maxwell–Bloch equations with an oscillating inversion, describing all spatiotemporal properties of the EP comb as a limit cycle. We numerically illustrate this phenomenon in a 5-μm-long gain-loss coupled AlGaAs cavity and adjust the EP comb repetition rate from 20 to 27 GHz. This work provides a rigorous spatiotemporal description of the rich laser behaviors that arise from the interplay between the non-Hermiticity, nonlinearity, and dynamics of a gain medium.
Evolution of the conformational dynamics of the molecular chaperone Hsp90
Authors: Riedl Stefan , Bilgen Ecenaz , Agam Ganesh , Hirvonen Viivi , Jussupow Alexander , Tippl Franziska , Riedl Maximilian , Maier Andreas , Becker Christian F. W. , Kaila Ville R. I. , Lamb Don C. , Buchner Johannes 
Published: October 2024

AbstractHsp90 is a molecular chaperone of central importance for protein homeostasis in the cytosol of eukaryotic cells, with key functional and structural traits conserved from yeast to man. During evolution, Hsp90 has gained additional functional importance, leading to an increased number of interacting co-chaperones and client proteins. Here, we show that the overall conformational transitions coupled to the ATPase cycle of Hsp90 are conserved from yeast to humans, but cycle timing as well as the dynamics are significantly altered. In contrast to yeast Hsp90, the human Hsp90 is characterized by broad ensembles of conformational states, irrespective of the absence or presence of ATP. The differences in the ATPase rate and conformational transitions between yeast and human Hsp90 are based on two residues in otherwise conserved structural elements that are involved in triggering structural changes in response to ATP binding. The exchange of these two mutations allows swapping of the ATPase rate and of the conformational transitions between human and yeast Hsp90. Our combined results show that Hsp90 evolved to a protein with increased conformational dynamics that populates ensembles of different states with strong preferences for the N-terminally open, client-accepting states.
Resource availability enhances positive tree functional diversity effects on carbon and nitrogen accrual in natural forests
Authors: Chen Xinli , Reich Peter B. , Taylor Anthony R. , An Zhengfeng , Chang Scott X. 
Published: October 2024

AbstractForests harbor extensive biodiversity and act as a strong global carbon and nitrogen sink. Although enhancing tree diversity has been shown to mitigate climate change by sequestering more carbon and nitrogen in biomass and soils in manipulative experiments, it is still unknown how varying environmental gradients, such as gradients in resource availability, mediate the effects of tree diversity on carbon and nitrogen accrual in natural forests. Here, we use Canada’s National Forest Inventory data to explore how the relationships between tree diversity and the accumulation of carbon and nitrogen in tree biomass and soils vary with resource availability and environmental stressors in natural forests. We find that the positive relationship between tree functional diversity (rather than species richness) and the accumulation of carbon in tree biomass strengthens with increasing light and soil nutrient availability. Moreover, the positive relationship between tree functional diversity and the accumulation of carbon and nitrogen in both organic and mineral soil horizons is more pronounced at sites with greater water and nutrient availabilities. Our results highlight that conserving and promoting functionally diverse forests in resource-rich environments could play a greater role than in resource-poor environments in enhancing carbon and nitrogen sequestration in Canada’s forests.
Coexistence of ferroelectricity and antiferroelectricity in 2D van der Waals multiferroic
Authors: Wu Yangliu , Zeng Zhaozhuo , Lu Haipeng , Han Xiaocang , Yang Chendi , Liu Nanshu , Zhao Xiaoxu , Qiao Liang , Ji Wei , Che Renchao , Deng Longjiang , Yan Peng , Peng Bo 
Published: October 2024

AbstractMultiferroic materials have been intensively pursued to achieve the mutual control of electric and magnetic properties. The breakthrough progress in 2D magnets and ferroelectrics encourages the exploration of low-dimensional multiferroics, which holds the promise of understanding inscrutable magnetoelectric coupling and inventing advanced spintronic devices. However, confirming ferroelectricity with optical techniques is challenging in 2D materials, particularly in conjunction with antiferromagnetic orders in single- and few-layer multiferroics. Here, we report the discovery of 2D vdW multiferroic with out-of-plane ferroelectric polarization in trilayer NiI2 device, as revealed by scanning reflective magnetic circular dichroism microscopy and ferroelectric hysteresis loops. The evolution between ferroelectric and antiferroelectric phases has been unambiguously observed. Moreover, the magnetoelectric interaction is directly probed by magnetic control of the multiferroic domain switching. This work opens up opportunities for exploring multiferroic orders and multiferroic physics at the limit of single or few atomic layers, and for creating advanced magnetoelectronic devices.
Structural elucidation of recombinant Trichomonas vaginalis 20S proteasome bound to covalent inhibitors
Authors: Silhan Jan , Fajtova Pavla , Bartosova Jitka , Hurysz Brianna M. , Almaliti Jehad , Miyamoto Yukiko , Eckmann Lars , Gerwick William H. , O’Donoghue Anthony J. , Boura Evzen 
Published: October 2024

AbstractThe proteasome is a proteolytic enzyme complex essential for protein homeostasis in mammalian cells and protozoan parasites like Trichomonas vaginalis (Tv), the cause of the most common, non-viral sexually transmitted disease. Tv and other protozoan 20S proteasomes have been validated as druggable targets for antimicrobials. However, low yields and purity of the native proteasome have hindered studies of the Tv 20S proteasome (Tv20S). We address this challenge by creating a recombinant protozoan proteasome by expressing all seven α and seven β subunits of Tv20S alongside the Ump-1 chaperone in insect cells. The recombinant Tv20S displays biochemical equivalence to its native counterpart, confirmed by various assays. Notably, the marizomib (MZB) inhibits all catalytic subunits of Tv20S, while the peptide inhibitor carmaphycin-17 (CP-17) specifically targets β2 and β5. Cryo-electron microscopy (cryo-EM) unveils the structures of Tv20S bound to MZB and CP-17 at 2.8 Å. These findings explain MZB’s low specificity for Tv20S compared to the human proteasome and demonstrate CP-17’s higher specificity. Overall, these data provide a structure-based strategy for the development of specific Tv20S inhibitors to treat trichomoniasis.
Inhibition of phototrophic iron oxidation by nitric oxide in ferruginous environments
Authors: Nikeleit Verena , Mellage Adrian , Bianchini Giorgio , Sauter Lea , Buessecker Steffen , Gotterbarm Stefanie , Schad Manuel , Konhauser Kurt , Zerkle Aubrey L. , Sánchez-Baracaldo Patricia , Kappler Andreas , Bryce Casey 
Published: October 2024

AbstractAnoxygenic phototrophic Fe(II) oxidizers (photoferrotrophs) are thought to have thrived in Earth’s ancient ferruginous oceans and played a primary role in the precipitation of Archaean and Palaeoproterozoic (3.8–1.85-billion-year-old) banded iron formations (BIFs). The end of BIF deposition by photoferrotrophs has been interpreted as the result of a deepening of water-column oxygenation below the photic zone, concomitant with the proliferation of cyanobacteria. However, photoferrotrophs may have experienced competition from other anaerobic Fe(II)-oxidizing microorganisms, altering the formation mechanism of BIFs. Here we utilize microbial incubations to show that nitrate-reducing Fe(II) oxidizers metabolically outcompete photoferrotrophs for dissolved Fe(II). Moreover, both experiments and numerical modelling show that the nitrate-reducing Fe(II) oxidizers inhibit photoferrotrophy via the production of toxic intermediates. Four different photoferrotrophs, representing both green sulfur and purple non-sulfur bacteria, are susceptible to this toxic effect despite having genomic capabilities for nitric oxide detoxification. Indeed, despite nitric oxide detoxification mechanisms being ubiquitous in some groups of phototrophs at the genomic level (for example, Chlorobi and Cyanobacteria) it is likely that they would still be affected. We suggest that the production of reactive nitrogen species during nitrate-reducing Fe(II) oxidation in ferruginous environments may have inhibited the activity of photoferrotrophs in the ancient oceans and thus impeded their role in the precipitation of BIFs.
Multi-parameter simultaneous extraction with a novel microwave sensor based on coupled resonators
Authors: Juan Carlos G. , Potelon Benjamin , Aquino Anyela , García-Martínez Héctor , Quendo Cédric 
Published: October 2024

AbstractThis work presents a microwave resonant multi-parameter sensor devoted to the simultaneous extraction of three characteristics of a homogeneous solid sample: its dielectric permittivity, its loss tangent and its thickness. The device is composed of three coupled resonators in two different substrate boards, having the sample between the boards, in a sandwich configuration. Presence of the sample impacts the electrical response of the device, not only influencing resonators, but also by affecting inter-resonator couplings. A method to analyse the response of the device, allowing for the extraction of the desired characteristics of the sample is proposed, as well as an experimental calibration procedure. The model is built upon 990 simulations, calibrated with three reference-samples measurements and then tested over 18 experimental measurements, with good results, thereby validating the multi-parameter sensing approach.
Design, synthesis, and biological evaluation of novel imidazole derivatives as analgesic and anti-inflammatory agents: experimental and molecular docking insights
Authors: Muheyuddeen Gulam , Khan Mohd Yaqub , Ahmad Tanzeem , Srivastava Shriyansh , Verma Stuti , Ansari Mo. Suheb , Sahu Nilanchala 
Published: October 2024

AbstractImidazole moieties exhibit a broad range of biological activities, including analgesic, anti-depressant, anticancer, anti-fungal, anti-tubercular, anti-inflammatory, antimicrobial, antiviral, and antifungal properties. In this study, we explored the use of Schiff base for the synthesis of new imidazole derivatives as anti-inflammatory and pain-relieving agents. A series of eight novel imidazole analogues (2a–h) were prepared in three steps with excellent yields. All compounds were characterized using IR, NMR, and mass spectral data. Their analgesic and anti-inflammatory activities were evaluated using hot plate and paw oedema methods. Compound 2 g (1-(2,3-dichlorophenyl)-2-(3-nitrophenyl)-4,5-diphenyl-1H-imidazole) showed significant analgesic activity (89% at 100 mg/kg b.w.), while compounds 2a (2-(2,6-dichlorophenyl)-1-(4-ethoxyphenyl)-4,5-diphenyl-1H-imidazole) and 2b (2-(2,3-dichlorophenyl)-1-(2-chlorophenyl)-4,5-diphenyl-1H-imidazole) exhibited good anti-inflammatory activity (100% at 100 mg/kg b.w.), comparable to diclofenac salt (100% at 50 mg/kg b.w.). Molecular docking studies were conducted using Schrödinger software version 2021-2, employing the OPLS4 force field for both receptor and ligand preparation. The results were visualized using molecular visualization software such as PyMOL. These studies revealed that compound 2g exhibited the highest binding affinity with the COX-2 receptor (−5.516 kcal/mol). Compound 2g formed three conventional hydrogen bonds with residues GLN-242 (bond length: 2.3 Å) and ARG-343 (bond lengths: 2.2 Å & 2.4 Å). This binding affinity was comparable to that of Diclofenac salt, which showed the highest binding affinity of −5.627 kcal/mol with the COX-2 receptor. Diclofenac salt formed two conventional hydrogen bonds with the residues ARG-344 (bond length: 2.0 Å) and TRP-140 (bond length: 1.7 Å). Later, molecular dynamic simulations confirmed the stable binding affinity of compound 2g with the protein. Furthermore, other compounds also demonstrated potential binding to the receptor-binding pocket region. The anti-inflammatory potential of the synthesized compounds was evaluated using the carrageenan-induced rat hind paw oedema model, while the analgesic potential was assessed using the hot plate method. These evaluations were conducted in comparison with Diclofenac sodium, serving as the standard compound. However, compound 2g stood out for its superior analgesic activity, as confirmed by in-vivo examination. These findings suggest that these novel imidazole derivatives have potential as anti-inflammatory and analgesic agents.
Innervation pattern and fiber counts of the human dorsal nerve of clitoris
Authors: Tunçkol Elçin , Heim Christine , Brunk Irene , Vida Imre , Brecht Michael 
Published: October 2024

AbstractEven tough clitoris plays a critical role in female sexuality, we lack a precise understanding of qualitative and quantitative aspects of the innervation of the human clitoris. To address this issue, we dissected human clitorides from body donors and imaged them after staining with iodine with microCT for a macroscopic analysis. To resolve innervation patterns at the microscopic level we prepared thin sections of clitorides and stained them with trichrome azan to reveal the tissue structure combined with immunocytochemistry against Neurofilament H antibodies to reveal all axons and luxol blue labeling to reveal myelinated axons. We find the clitoral branch of pudendal nerve that innervates the clitoris not as single nerve, but as number of loose bundles. In the crus of the clitoris, about 12 such bundles can be recognized while about 32 bundles are present in the clitoral hemi-body. We counted on avarage 2917 axons in the crus of the clitoris (76% of which are myelinated) and 3137 axons in the hemibody of the clitoris (71% of which are myelinated). While the human clitoris receives only one third of the number of axons that innervate the human penis, an estimate of innervation density (per surface area) revealed that clitoris has approximately 6 times denser innervation compared to the penis. Thus, our study combines histology with microCT analysis provides detailed information on the number, myelination and innervation density of dorsal nerve of clitoris.
Quercetin as a therapeutic agent activate the Nrf2/Keap1 pathway to alleviate lung ischemia-reperfusion injury
Authors: Yousefi Zardak Mohammad , Keshavarz Fatemeh , Mahyaei Ali , Gholami Morteza , Moosavi Fatemeh Sadat , Abbasloo Elham , Abdollahi Farzaneh , Hossein Rezaei Maryam , Madadizadeh Elham , Soltani Nasrin , Bejeshk Fatemeh , Salehi Niyan , Rostamabadi Fahimeh , Bagheri Fatemeh , Jafaraghae Mahla , Ranjbar Zeydabadi Mahdiyeh , Baghgoli Meraj , Sepehri Gholamreza , Bejeshk Mohammad Abbas 
Published: October 2024

AbstractLung ischemia-reperfusion injury (LIRI) causes oxidative stress, inflammation, and immune system activation. The Nrf2/Keap1/HO-1 pathway is important in cellular defense against these effects. Quercetin, a flavonoid with antioxidant, anti-inflammatory, and anti-cancer properties, has been investigated. Our aim in this study was to investigate the effect of quercetin on preventing lung ischemia-reperfusion injury and the role of the Nrf2/Keap1/HO-1 pathway. Sixty-four male Wistar rats were divided into four distinct groups(n = 16). Sham, lung ischemia-reperfusion (LIR), Saline + LIR, Quercetin + LIR (30 mg/kg i.p for a week before LIR). LIR groups were subjected to 60 min of ischemia (left pulmonary artery, vein, and bronchus) and 120 min of reperfusion. Our assessment encompassed a comprehensive analysis of various factors, including the evaluation of expression Nrf2, Keap1, and Heme Oxygenase-1 (HO-1) levels and NF-κB protein. Furthermore, we examined markers related to inflammation (interleukin-1β and tumor necrosis factor alpha), oxidative stress (malondialdehyde, total oxidant status, superoxide dismutase, glutathione peroxidase, total antioxidant capacity), lung edema (Wet/dry lung weight ratio and total protein concentration), apoptosis (Bax and Bcl2 protein), and histopathological alterations (intra-alveolar edema, alveolar hemorrhage, and neutrophil infiltration). Our results show that ischemia-reperfusion results in heightened inflammation, oxidative stress, apoptosis, lung edema, and histopathological damage. Quercetin showed preventive effects by reducing these markers, acting through modulation of the Nrf2/Keap1 pathway and inhibiting the NF-κB pathway. This anti-inflammatory effect, complementary to the antioxidant effects of quercetin, provides a multifaceted approach to cell protection that is important for developing therapeutic strategies against ischemia-reperfusion injury and could be helpful in preventive strategies against ischemia-reperfusion.
Rational design based on multi-monomer simultaneous docking for epitope imprinting of SARS-CoV-2 spike protein
Authors: Rajpal Soumya , Batista Alex D. , Groß Rüdiger , Münch Jan , Mizaikoff Boris , Mishra Prashant 
Published: October 2024

AbstractAmong biomimetic strategies shaping engineering designs, molecularly imprinted polymer (MIP) technology stands out, involving chemically synthesised receptors emulating natural antigen-antibody interactions. These versatile ‘designer polymers’ with remarkable stability and low cost, are pivotal for in vitro diagnostics. Amid the recent global health crisis, we probed MIPs’ potential to capture SARS-CoV-2 virions. Large biotemplates complicate MIP design, influencing generated binding site specificity. To precisely structure recognition sites within polymers, we innovated an epitope imprinting method supplemented by in silico polymerization component screening. A viral surface Spike protein informed epitope selection was targeted for MIP development. A novel multi-monomer docking approach (MMSD) was employed to simulate classical receptor-ligand interactions, mimicking binding reinforcement across multiple amino acids. Around 40 monomer combinations were docked to the epitope sequence and top performers experimentally validated via rapid fluorescence binding assays. Notably, high imprinting factor polymers correlated with MMSD predictions, promising rational MIP design applicable to diverse viral pathologies.