bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactors and effects of overexpressing YlxR/RpnM, a conserved RNA binding protein in cyanobacteria
Authors: Hemm Luisa , Miucci Anna , Riediger Matthias , Tholen Stefan , Kraus Alexander , Georg Jens , Schilling Oliver , Hess Wolfgang R. 
Published: January 2024

AbstractThroughout the tree of life RNA-binding proteins play important roles, but they are poorly characterized in cyanobacteria. Structural prediction suggests an RNA-binding interface for the protein YlxR/Ssr1238 in the cyanobacteriumSynechocystis6803. Two pairs of cysteine residues are arranged as possibly coordinating an Fe-S cluster and appear widely conserved in the homologous proteins of other cyanobacteria. Overexpression of Ssr1238 for 24 h led to higher levels of RNase P RNA, tRNAs, and stress-related mRNAs. Co-immunoprecipitation of proteins followed by MS analysis and sequencing of UV crosslinked, co-immunoprecipitated RNA samples identified potential interaction partners of Ssr1238. The most enriched transcript was RNase P RNA, and RnpA, the protein component of RNase P, was among the most highly enriched proteins. A second highly enriched transcript derived from genessl3177, which encodes a central enzyme in cell wall remodeling during cell division. The data also showed a strong connection to the RNA maturation and modification system indicated by co-precipitation of RNA modifying enzymes, riboendonuclease E and enolase. Surprisingly, cyanophycin synthetase and urease were highly enriched as well. In conclusion, Ssr1238 specifically binds to two different transcripts and participates in the coordination of RNA maturation, translation, cell division, and aspects of nitrogen metabolism. Our results are consistent with recent findings that theB. subtilisYlxR protein functions as an RNase P modulator (RnpM), but suggest additional functionalities and extend its proposed role to the phylum cyanobacteria.
Demonstration of chemotherapeutic mediated lymphatic changes in meningeal lymphatics in vitro, ex vivo, and in vivo
Authors: Roberts L. Monet , Hammel Jennifer H , Azar Francesca , Feng Tzu-Yu (Alkaid) , Cunningham Jessica J. , Rutkowski Melanie , Munson Jennifer 
Published: January 2024

AbstractSystemic chemotherapeutics target cancer cells but are also known to impact other cells away from the tumor. Questions remain whether systemic chemotherapy crosses the blood-brain barrier and causes inflammation in the periphery that impacts the central nervous system (CNS) downstream. The meningeal lymphatics are a critical component that drain cerebrospinal fluid from the CNS to the cervical lymph nodes for immunosurveillence. To develop new tools for understanding chemotherapy-mediated effects on the meningeal lymphatics, we present two novel models that examine cellular and tissue level changes. Our in vitro tissue engineered model of a meningeal lymphatic vessel lumen, using a simple tissue culture insert system with both lymphatic endothelial and meningeal cells, examines cell disruption. Our ex vivo model culturing mouse meningeal layers probes structural changes and remodeling, correlating to an explant tissue level. To gain a holistic understanding, we compare our in vitro and ex vivo models to in vivo studies for validation and a three-tier methodology for examining the chemotherapeutic response of the meningeal lymphatics. We have demonstrated that the meningeal lymphatics can be disrupted by systemic chemotherapy but show differential responses to platinum and taxane chemotherapies, emphasizing the need for further study of off-target impacts in the CNS.
Behaviour-based movement cut-off points in 3-year old children comparing wrist- with hip-worn actigraphs MW8 and GT3X
Authors: Jansson Daniel , Westlander Rikard , Sandlund Jonas , West Christina E. , Domellöf Magnus , Wulff Katharina 
Published: January 2024

ABSTRACTIntroductionBehaviour-based physical intensities have not undergone rigorous calibration in long-term recordings of 3-year-old children’s sleep/activity patterns. This study aimed at (i) calibrating activity counts of motor behaviour measured simultaneously with MotionWatch 8 (MW8) and ActiGraph (GT3X) in 3-year-old children, (ii) documenting movement intensities in 30s-epochs at wrist/hip positions, and (iii) evaluating the accuracy of cut-off agreements between different behavioural activities.MethodsThirty 3-year-old children of the NorthPop cohort performed six directed behavioural activities individually, each for 8-10 minutes while wearing two pairs of devices at hip and wrist position. Directly observed naturally-occurring behaviours included: watching cartoons, recumbent story listening, sit and handcraft, floor play with toys, engaging in a walk and a sprinting game. Receiver-Operating-Curve classification was applied to determine activity count thresholds and to assign context-guided, physical activity composite classes.ResultsActivity counts of MW8 and GT3X pairs of wrist-worn (r = 0.94) and hip-worn (r = 0.79) devices correlated significantly (p < 0.001). Activity counts at hip position were significantly lower compared to those at the wrist position (p < 0.001), irrespective of device type. Sprinting, floorball/walk and floorplay assigned as ‘physicallymobile’classes achieved outstanding accuracy (AUC >0.9) and two sedentary and a motionless activities assigned into ‘physicallystationary’classes achieved excellent accuracy (AUC >0.8).ConclusionThis study provides useful cut-offs for physical activity levels of preschool children using two different devices. Contextual information of behaviour is advantageous over intensity classifications only, because interventions reallocate time among behaviours, which allows to establish dose-response relationships between behavioural changes and health outcomes. Our comparative calibration is one step forward to inform behaviour-based public health guidelines for 3-year-old children.
Predicting Serotonin Detection with DNA-Carbon Nanotube Sensors Across Multiple Spectral Wavelengths
Authors: Kelich Payam , Adams Jaquesta , Jeong Sanghwa , Navarro Nicole , Landry Markita P. , Vuković Lela 
Published: January 2024

AbstractOwing to the value of DNA-wrapped single-walled carbon nanotube (SWNT) based sensors for chemically-specific imaging in biology, we explore machine learning (ML) predictions DNA-SWNT serotonin sensor responsivity as a function of DNA sequence based on the whole SWNT fluorescence spectra. Our analysis reveals the crucial role of DNA sequence in the binding modes of DNA-SWNTs to serotonin, with a smaller influence of SWNT chirality. Regression ML models trained on existing datasets predict the change in the fluorescence emission in response to serotonin, ΔF/F, at over a hundred wavelengths for new DNA-SWNT conjugates, successfully identifying some high- and low-response DNA sequences. Despite successful predictions, we also show that the finite size of the training dataset leads to limitations on prediction accuracy. Nevertheless, incorporating entire spectra into ML models enhances prediction robustness and facilitates the discovery of novel DNA-SWNT sensors. Our approaches show promise for identifying new chemical systems with specific sensing response characteristics, marking a valuable advancement in DNA-based system discovery.
Synthetase and Hydrolase Specificity Collectively Excludes 2’-Deoxyguanosine from Bacterial Alarmone
Authors: Zhou Rich W. , Gordon Isis J. , Hei Yuanyuan , Wang Boyuan 
Published: January 2024

AbstractIn response to starvation, virtually all bacteria pyrophosphorylate the 3’-hydroxy group of GTP or GDP to produce two messenger nucleotides collectively denoted as (p)ppGpp. Also known as alarmones, (p)ppGpp reprograms bacterial physiology to arrest growth and promote survival. Intriguingly, although cellular concentration of dGTP is two orders of magnitude lower than that of GTP, alarmone synthetases are highly selective against using 2’-deoxyguanosine (2dG) nucleotides as substrates. We thus hypothesize that production of 2dG alarmone, (p)pp(dG)pp, is highly deleterious, which drives a strong negative selection to exclude 2dG nucleotides from alarmone signaling. In this work, we show that theB. subtilisSasB synthetase prefers GDP over dGDP with 65,000-fold higherkcat/Km, a specificity stricter than RNA polymerase selecting against 2’-deoxynucleotides. Using comparative chemical proteomics, we found that although most known alarmone-binding proteins inEscherichia colicannot distinguish ppGpp from pp(dG)pp, hydrolysis of pp(dG)pp by the essential hydrolase, SpoT, is 1,000-fold slower. This inability to degrade 2’-deoxy-3’-pyrophosphorylated substrate is a common feature of the alarmone hydrolase family. We further show that SpoT is a binuclear metallopyrophoshohydrolase and that hydrolysis of ppGpp and pp(dG)pp shares the same metal dependence. Our results support a model in which 2’-OH directly coordinates the Mn2+at SpoT active center to stabilize the hydrolysis-productive conformation of ppGpp. Taken together, our study reveals a vital role of 2’-OH in alarmone degradation, provides new insight on the catalytic mechanism of alarmone hydrolases, and leads to the conclusion that 2dG nucleotides must be strictly excluded from alarmone synthesis because bacteria lack the key machinery to down-regulate such products.
Acquisition phase-specific contribution of climbing fiber transmission to cerebellum-dependent motor memory
Authors: Seo Jewoo , Kim Seung Ha , Lee Jaegeon , Kim Min Seok , Lee Yong-Seok , Kim Sang Jeong 
Published: January 2024

AbstractClimbing fiber (CF) transmission from the inferior olivary triggers complex spikes (Cs) in Purkinje cells (PCs) driven by a burst of calcium spikes. In the context of motor learning, especially the compensatory optic response, CF transmission serves as instructive signals selectively conveyed to PCs. While the significance of CF input in motor memory formation is widely acknowledged, a comprehensive understanding of its distinct contribution across different temporal windows, spanning from the initial learning phase to the retrieval period, remains incomplete. Therefore, we aimed to investigate the necessity of CF-induced instructive signals in motor learning by assessing their roles in memory acquisition, consolidation, and retrieval. We employed optogenetics to selectively inhibit CF transmission during targeted time windows. Consequently, the absence of CF-induced instructive signals during motor learning impairs memory acquisition. However, when these signals were suppressed during the consolidation and retrieval period, there was neither a loss of long-term memory nor prevention of memory retrieval. Our results highlight that CF transmission plays a specialized and critical role primarily in memory acquisition, rather than subsequent processes.
Capsaicin acts as a novel NRF2 agonist to suppress ethanol induced gastric mucosa oxidative damage by directly disrupting the KEAP1-NRF2 interaction
Authors: Gao Xiaoning , Guo WuYan , Liu Peiyuan , Yuwen Mingyue , Liu Zixiang , Tan Ruyang , Liu Kairui , Yang Zhiru , Ba Junli , Bai Xue , Shama Shiti , Tang Cong , Miao Kai , Pei Haozhi , Liu Liren , Zhu Cheng , Wang Tao , Zhang Bo , Kang Jun 
Published: January 2024

AbstractExcessive drinking poses serious health risks and is closely associated with oxidative damage. The KEAP1-NRF2-ARE axis serves as the primary antioxidant system. However, the existing small molecule inhibitors are all covalently bound to KEAP1, meaning that once bound, they are not easily dissociated, while continuous inhibition of KEAP1 exhibits severe side effects. In this study, BLI, CETSA, Pull-down, Co-IP and HDX-MS assay analysis were conducted to detect the KEAP1 binding behavior of natural product, capsaicin (CAP), bothin vitroand in GES-1 cells. The ethanol-induced acute gastric mucosal damage rat model was also established to determine the therapeutic effect of CAP. We demonstrated that CAP ameliorated mitochondrial damage, facilitated the nuclear translocation of NRF2, thereby promoting the expression of downstream antioxidant response elements, HO-1, Trx, GSS and NQO1 in GES-1 cells. Subsequently, CAP could directly bind to KEAP1 and inhibit the interaction between KEAP1 and NRF2. While in the KEAP1-knockout 293T cells, CAP failed to activate NRF2 expression. It was also found that CAP non-covalently bound to Kelch domain and allosterically regulated three regions of KEAP1:L342-L355, D394-G423 and N482-N495. To enhance drug solubility and delivery efficiency, we designed IR-Dye800 modified albumin coated CAP nanoparticle. The nanoparticles significantly alleviated the gastric mucosal inflammation and activated the NRF2 downstream genesin vivo. Finally, we further verified our hypothesis in Nfe2l2-knockout mice. Our work provided new insights that CAP is a safe and novel NRF2 agonist by allosterically regulating KEAP1, which may contribute to the development of lead drugs for oxidative stress-related illness, e.g. aging, cancer, neurodegenerative and cardiovascular diseases.Graphic diagram
Label-free long-term measurements of adipocyte differentiation from patient-driven fibroblasts and quantitative analyses of in situ lipid droplet generation
Authors: Jeong Eun Young , Kim Hye-Jin , Lee Sumin , Park Yongkeun , Kim Young Mo 
Published: January 2024

AbstractThe visualization and tracking of adipocytes and their lipid droplets (LDs) during differentiation are pivotal in developmental biology and regenerative medicine studies. Traditional staining or labeling methods, however, pose significant challenges due to their labor-intensive sample preparation, potential disruption of intrinsic cellular physiology, and limited observation timeframe. This study introduces a novel method for long-term visualization and quantification of biophysical parameters of LDs in unlabeled adipocytes, utilizing the refractive index (RI) distributions of LDs and cells. We employ low-coherence holotomography (HT) to systematically investigate and quantitatively analyze the 42-day redifferentiation process of fat cells into adipocytes. This technique yields three-dimensional, high-resolution refractive tomograms of adipocytes, enabling precise segmentation of LDs based on their elevated RI values. Subsequent automated analysis quantifies the mean concentration, volume, projected area, and dry mass of individual LDs, revealing a gradual increase corresponding with adipocyte maturation. Our findings demonstrate that HT is a potent tool for non-invasively monitoring live adipocyte differentiation and analyzing LD accumulation. This study, therefore, offers valuable insights into adipogenesis and lipid research, establishing HT and image-based analysis as a promising approach in these fields.
Impact of high fat diet and exercise on bone and bile acid metabolism in rats
Authors: Alonso Nerea , Almer Gunter , Semeraro Maria Donatella , Rodriguez-Blanco Giovanny , Fauler Günter , Anders Ines , Ritter Gerald , vom Scheidt Annika , Hammer Niels , Gruber Hans Jürgen , Herrmann Markus 
Published: January 2024

AbstractBackgroundBile acids help facilitate the intestinal lipids absorption, and have endocrine activity in glucose, lipid and bone metabolism. Obesity and exercise influence bile acid metabolism and have opposite effects in bone. This given study investigates if regular exercise helps mitigate the adverse effects of obesity on bone, potentially by reversing alterations in bile acid metabolism.MethodsFour-month-old female Sprague Dawley rats either received high fat diet (HFD) or chow-based standard diet (lean controls). During the 10-month study period, half of the animals performed 30 min of running at moderate speed on five consecutive days followed by two days of rest. The other half was kept inactive (inactive controls). At study end, bone quality was assessed by micro computed tomography and biomechanical testing. Bile acids were measured in serum and stool.ResultsHFD feeding was related to reduced trabecular (−33%, p=1.14×10-7) and cortical (−21%, p=2.9×10-8) bone mass, and lowered femoral stiffness (12-41%, p=0.005). Furthermore, HFD decreased total bile acids in serum (−37%, p=1.0×10-6), but increased bile acids in stool (+2-fold, p=7.3×10-9). These quantitative effects were accompanied by changes in the relative abundance of individual bile acids. The concentration of serum bile acids correlated positively with all cortical bone parameters (r=0.593 - 0.708), whilst stool levels showed inverse correlations at cortical (r=-0.651 - −0.805) and trabecular level (r=-0.656 - −0.750). Exercise improved some trabecular and cortical bone quality parameters (+11-31%, p=0.043 to 0.001) in lean controls, but failed to revert the bone loss related to HFD. Similarly, changes in bile acid metabolism were not mitigated by exercise.ConclusionProlonged HFD consumption induced quantitative and qualitative alterations in bile acid metabolism, accompanied by bone loss. Tight correlations between bile acids and structural indices of bone quality support further functional analyses on the potential role of bile acids in bone metabolism. Regular moderate exercise improved trabecular and cortical bone quality in lean controls but failed mitigating the effects related to HFD in bone and bile acid metabolism.
The Emerging Role of 3-Hydroxyanthranilic Acid onC. elegansAging Immune Function
Authors: Espejo Luis S. , DeNicola Destiny , Chang Leah M. , Hofschneider Vanessa , Haskins Anne E. , Balsa Jonah , Freitas Samuel S. , Antenor Angelo , Hamming Sage , Hull Bradford , Castro-Portuguez Raul , Dang Hope , Sutphin George L. 
Published: January 2024

Abstract3-hydroxyanthranilic acid (3HAA) is considered to be a fleeting metabolic intermediate along tryptophan catabolism through the kynurenine pathway. 3HAA and the rest of the kynurenine pathway have been linked to immune response in mammals yet whether it is detrimental or advantageous is a point of contention. Recently we have shown that accumulation of this metabolite, either through supplementation or prevention of its degradation, extends healthy lifespan inC. elegansand mice, while the mechanism remained unknown. UtilizingC. elegansas a model we investigate how 3HAA andhaao-1inhibition impact the host and the potential pathogens. What we find is that 3HAA improves host immune function with aging and serves as an antimicrobial against gram-negative bacteria. Regulation of 3HAA’s antimicrobial activity is accomplished via tissue separation. 3HAA is synthesized in theC. eleganshypodermal tissue, localized to the site of pathogen interaction within the gut granules, and degraded in the neuronal cells. This tissue separation creates a new possible function for 3HAA that may give insight to a larger evolutionarily conserved function within the immune response.Graphical Abstract
Allostery at a protein-protein interface harboring an intermolecular dynamic network
Authors: Gomez Sara Medina , Vasa Suresh Kumar , Linser Rasmus 
Published: January 2024

AbstractMotional properties of individual amino acids in proteins are strongly modulated by their specific surrounding. The dynamics of tightly interacting residues can formintramolecular dynamic networks, which influence various features of protein function and serve as an access point for their modulation within signaling cascades. However, the possible formation ofintermolecular networks shared between natural or constructed interaction partners has escaped thorough experimental assessment. Here, using fast-MAS solid-state NMR spectroscopy, we contrast the absence of a cross-talk between different residues in an apo protein with a recoupling of μs timescale dynamics effective via a mediating crystal-crystal contact. The data show that dynamic allostery is not necessarily restricted to motionally coupled elements within a single protein but can traverse molecular boundaries. Interrogation of intermolecular dynamic networks by the strategies proposed here may shed light on the mechanisms underlying allosteric modulation of protein function in biological, pharmacological, and biotechnological studies.
The holocephalan ratfish endoskeleton shares trabecular and areolar mineralization patterns, but not tesserae, with elasmobranchs little skate and catshark, and appears paedomorphic
Authors: Atake Oghenevwogaga J. , Berio Fidji , Debiais-Thibaud Melanie , Eames B. Frank 
Published: January 2024

AbstractSpecific character traits of mineralized endoskeletal tissues need to be clearly defined and comprehensively examined among extant chondrichthyans (elasmobranchs, such as sharks and skates, and holocephalans, such as chimaeras) to understand their evolution. For example, tiles of mineralized polygonal structures called tesserae occur at cartilage surfaces in chondrichthyans, but recent studies showing trabecular mineralization at elasmobranch cartilage surfaces suggest that tesserae are not as common as previously thought. Also, while areolar mineralized tissue in elasmobranchs is generally considered a unique, shared chondrichthyan feature, some chondrichthyan species demonstrate bone-like tissues in both a specific region of tesserae termed the cap zone and continuous (not tiled) mineralized neural arches. To clarify the distribution of specific endoskeletal features among extant chondrichthyans, adult skeletal tissues in a holocephalan chimaera (spotted ratfish) and two elasmobranchs (small-spotted catshark and little skate) were characterized using synchrotron radiation and desktop micro-CT imaging, and histological and immunofluorescent assays. Endoskeletal mineralization in the ratfish, catshark, and little skate varied both quantitively in tissue mineral density (TMD), and qualitatively in the morphology and localization of mineralized structures and tissues. For example, TMD of several skeletal elements was significantly lower in ratfish, compared to catshark and little skate. Trabecular and areolar mineralization were shared among these extant chondrichthyan species, but tesserae and bone-like tissues were not. Interestingly, three separate analyses argued that the chimaera endoskeleton retains embryonic features (i.e., paedomorphic with respect to elasmobranchs). This study further proposes general terminology for character states of the extant chondrichthyan endoskeleton and infers those states in ancestral chondrichthyans with reference to fossil data.