bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrodin combined with electroacupuncture prevents the development of cerebral ischemia via rebalance of brain-derived neurotrophic factor and interleukin-6 in stroke model rats
Authors: Liu Min , Gong Rujie , Ding Lina , Zhao Yingdi , Yan Xili , Shi Liangbin , Zhang Yegui , Xu Zhiliang
Published: May 2024

Traditional Chinese medicine (TCM) has long been used to treat various diseases, including cerebral ischemia. The specific molecular mechanism of TCM in the treatment of cerebral ischemia, however, is still unclear. This study investigated the effects of gastrodin, electroacupuncture and their combination on cerebral ischemic rats. We used Nissl staining, immunohistochemical staining and immunoblotting to detect the expression changes of brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) in the frontal cortex. The results showed that the combination therapy of gastrodin and electroacupuncture significantly increased the number of Nissl-positive neurons and improved cell morphology compared with other groups. Mechanistically, we found that the combination of gastrodin and electroacupuncture treatment group can restore the abnormal morphology of neuronal cells caused by cerebral ischemia by rebalancing the expression levels of BDNF and IL-6. Our research indicates that gastrodin combined with electroacupuncture has a significant protective effect on cerebral ischemic injury in rats, possibly by regulating the expression of BDNF and IL-6. This combination therapy is superior to single-drug or electroacupuncture therapy.
CCfrag: Scanning folding potential of coiled-coil fragments with AlphaFold
Authors: Martinez-Goikoetxea Mikel
Published: May 2024

Structured abstract

Motivation

Coiled coils are a widespread structural motif consisting of multiple α-helices that wind around a central axis to bury their hydrophobic core. Although their backbone can be uniquely described by the Crick parametric equations, these have little practical application in structural prediction, given that most coiled coils in nature feature non-canonical repeats that locally distort their geometry. While AlphaFold has emerged as an effective coiled-coil modeling tool, capable of accurately predicting changes in periodicity and core geometry along coiled-coil stalks, it is not without limitations. These include the generation of spuriously bent models and the inability to effectively model globally non-canonical coiled coils. In an effort to overcome these limitations, we investigated whether dividing full-length sequences into fragments would result in better models.

Results

We developed CCfrag to leverage AlphaFold for the piece-wise modeling of coiled coils. The user can create a specification, defined by window size, length of overlap, and oligomerization state, and the program produces the files necessary to run structural predictions with AlphaFold. Then, the structural models and their scores are integrated into a rich per-residue representation defined by sequence-or structure-based features, which can be visualized or employed for further analysis. Our results suggest that removing coiled-coil sequences from their native context can in some case improve the prediction confidence and avoids bent models with spurious contacts. In this paper, we present various use cases of CCfrag, and propose that fragment-based prediction is useful for understanding the properties of long, fibrous coiled coils, by showing local features not seen in full-length models.

Availability and Implementation

The program is implemented as a Python module. The code and its documentation are available athttps://github.com/Mikel-MG/CCfrag.

Contact

mikel.martinez@tuebingen.mpg.de
Emergent patterns of patchiness reflect decoupling between ocean physics and biology
Authors: Gray Patrick Clifton , Boss Emmanuel , Bourdin Guillaume ,   Mission Microbiomes AtlantECO,   Tara Pacific Consortium, Lehahn Yoav
Published: May 2024

While a rich history of patchiness research has explored spatial structure in the ocean, there is still no consensus over the controls on biological patchiness and how biogeochemical processes and patchiness relate. The prevailing thought is that physics structures biology, but this has not been tested at the basin scale with consistentin situmeasurements. Here we show that the patchiness of physics and biology are decoupled at the global scale through analysis of a global dataset of in situ surface optical properties from the S/VTaraand using the slope of spatial scale vs variance to quantify patchiness. Based on analysis of ∼650,000 nearly continuous (dx∼150m) measurements from an underway sampling system - representing five years of consistently collected data across the Atlantic, Pacific, and Southern Oceans - we find the patchiness of physical and biological parameters are uncorrelated. We show that variance slope is an emergent property with unique patterns in biogeochemical properties that are distinct from physical tracers, yet connected to other biological tracers. These results provide context for decades of discrepancy betweenin situstudies, could support new tests of biogeochemical model parameterizations, and open the way for new insight into processes regulating the observed patterns.
In vivotracking ofex vivogenerated89Zr-oxine labeled plasma cells by PET in a non-human primate model
Authors: Young David J , Edwards Abigail J , Quiroz Caceda Kevin G , Liberzon Ella , Barrientos Johana , Hong Sogun , Turner Jacob , Choyke Peter L. , Arlauckas Sean , Lazorchak Adam S , Morgan Richard A , Sato Noriko , Dunbar Cynthia E
Published: May 2024

B cells are an attractive platform for engineering to produce protein-based biologics absent in genetic disorders, and potentially for the treatment of metabolic diseases and cancer. As part of pre-clinical development of B cell medicines, we demonstrate a method to collect,ex vivoexpand, differentiate, radioactively label, and track adoptively transferred non-human primate (NHP) B cells. These cells underwent 10- to 15-fold expansion, initiated IgG class switching, and differentiated into antibody secreting cells. Zirconium-89-oxine labeled cells were infused into autologous donors without any preconditioning and tracked by PET/CT imaging. Within 24 hours of infusion, 20% of the initial dose homed to the bone marrow and spleen and distributed stably and equally between the two. Interestingly, approximately half of the dose homed to the liver. Image analysis of the bone marrow demonstrated inhomogeneous distribution of the cells. The subjects experienced no clinically significant side effects or laboratory abnormalities. A second infusion of B cells into one of the subjects resulted in an almost identical distribution of cells, suggesting a non-limiting engraftment niche and feasibility of repeated infusions. This work supports the NHP as a valuable model to assess the potential of B cell medicines as potential treatment for human diseases.
Evaluating ARG-estimation methods in the context of estimating population-mean polygenic score histories
Authors: Peng Dandan , Mulder Obadiah J. , Edge Michael D.
Published: May 2024

Scalable methods for estimating marginal coalescent trees across the genome present new opportunities for studying evolution and have generated considerable excitement, with new methods extending scalability to thousands of samples. Benchmarking of the available methods has revealed general tradeoffs between accuracy and scalability, but performance in downstream applications has not always been easily predictable from general performance measures, suggesting that specific features of the ARG may be important for specific downstream applications of estimated ARGs. To exemplify this point, we benchmark ARG estimation methods with respect to a specific set of methods for estimating the historical time course of a population-mean polygenic score (PGS) using the marginal coalescent trees encoded by the ancestral recombination graph (ARG). Here we examine the performance in simulation of seven ARG estimation methods:ARGweaver, RENT+, Relate, tsinfer+tsdate, ARG-Needle, ASMC-clust, andSINGER, using their estimated coalescent trees and examining bias, mean squared error (MSE), confidence interval coverage, and Type I and II error rates of the downstream methods. Although it does not scale to the sample sizes attainable by other new methods,SINGERproduced the most accurate estimated PGS histories in many instances, even whenRelate, tsinfer+tsdate, ARG-NeedleandASMC-clustused samples ten or more times as large as those used bySINGER. In general, the best choice of method depends on the number of samples available and the historical time period of interest. In particular, the unprecedented sample sizes allowed byRelate, tsinfer+tsdate, ARG-Needle, andASMC-clustare of greatest importance when the recent past is of interest—further back in time, most of the tree has coalesced, and differences in contemporary sample size are less salient.
Likelihood Ratios for physical traits in forensic investigations
Authors: Marsico Franco , Egeland Thore
Published: May 2024

Recent years have seen significant advances in DNA phenotyping, which predicts the physical traits of an unknown person, such as hair, eyes, and skin color, using DNA data. This technique is increasingly used in forensic investigations to identify missing persons, disaster victims, and suspects of crimes. A key contribution of DNA phenotyping is that it allows researchers to search through lists of individuals with similar characteristics, often gathered from testimonies, photographs, and social media data. However, despite their growing relevance, current methods lack comprehensive mathematical models to calculate likelihood ratios that accurately assess the statistical weight of evidence. Our work bridges this gap by developing new likelihood ratio models, validated through computational simulations. In addition, we demonstrate the ability of these models to improve forensic investigations in real-world scenarios. Furthermore, we introduce the R packageforensicolors, freely available on CRAN, to facilitate the application of the methodologies developed.
Skeleton-forming responses of reef-building corals under ocean acidification
Authors: Li Yixin , Zhao Hongwei , Zhao Yunpeng , Liao Xin , Chen J.-Y. , He Chunpeng , Lu Zuhong
Published: May 2024

Ocean acidification is increasing in frequency and is considered one of the most important causes of severe damage to global coral reefs. Therefore, there is an urgent need to study the impact of acid stress on the growth patterns of major reef-building corals. Here, we studied the skeleton forming strategies of four widely distributed coral species in a simulated acidified habitat with a pH of 7.6–7.8. We reconstructed and visualized the skeleton building process, quantified elemental calcium loss, and determined gene expression changes. The results suggest that different reef-building corals have diverse growing strategies in acidified seawater. A unique ‘cavity-like’ forming process starts from the inside of the skeletons ofAcropora muricata, which sacrifices skeleton density to protect its polyp-canal system. The forming patterns inPocillopora damicornis,Montipora capricornis, andM. foliosawere characterized by ‘osteoporosis’, exhibiting disordered skeletal structures, insufficient synthesis of adhesion proteins, and low bone mass, correspondingly. In addition, we found that skeletal areas near coral polyps suffered less and had later acidified damage than other skeletal areas in the colony. These results help to understand the skeleton-forming strategies of several major coral species under acid stress, thereby laying a foundation for coral reef protection and restoration under increasing ocean acidification.
Ancient eukaryotic protein interactions illuminate modern genetic traits and disorders
Authors: Cox Rachael M. , Papoulas Ophelia , Shril Shirlee , Lee Chanjae , Gardner Tynan , Battenhouse Anna M. , Lee Muyoung , Drew Kevin , McWhite Claire D. , Yang David , Leggere Janelle C. , Durand Dannie , Hildebrandt Friedhelm , Wallingford John B. , Marcotte Edward M.
Published: May 2024

All eukaryotes share a common ancestor from roughly 1.5 – 1.8 billion years ago, a single-celled, swimming microbe known as LECA, the Last Eukaryotic Common Ancestor. Nearly half of the genes in modern eukaryotes were present in LECA, and many current genetic diseases and traits stem from these ancient molecular systems. To better understand these systems, we compared genes across modern organisms and identified a core set of 10,092 shared protein-coding gene families likely present in LECA, a quarter of which are uncharacterized. We then integrated >26,000 mass spectrometry proteomics analyses from 31 species to infer how these proteins interact in higher-order complexes. The resulting interactome describes the biochemical organization of LECA, revealing both known and new assemblies. We analyzed these ancient protein interactions to find new human gene-disease relationships for bone density and congenital birth defects, demonstrating the value of ancestral protein interactions for guiding functional genetics today.
Identification of Spared and Proportionally Controllable Hand Motor Dimensions in Motor Complete Spinal Cord Injuries Using Latent Manifold Analysis
Authors: Sîmpetru Raul C , Souza de Oliveira Daniela , Ponfick Matthias , Del Vecchio Alessandro
Published: May 2024

The loss of bilateral hand function is a debilitating challenge for millions of individuals that suffered a motor-complete spinal cord injury (SCI). We have recently demonstrated in eight tetraplegic individuals the presence of highly functional spared spinal motor neurons in the extrinsic muscles of the hand that are still capable of generating proportional flexion and extension signals. In this work, we hypothesized that an artificial intelligence (AI) system could automatically learn the spared electromyographic (EMG) patterns that encode the attempted movements of the paralyzed digits. We constrained the AI to continuously output the attempted movements in the form of a digital hand so that this signal could be used to control any assistive system (e.g., exoskeletons, electrical stimulation). We trained a convolutional neural network using data from 13 uninjured (control) participants and 8 motor-complete tetraplegic participants to study the latent space learned by the AI. Our model can automatically differentiate between eight different hand movements, including individual finger flexions, grasps, and pinches, achieving a mean accuracy of 98.3% within the SCI group. Moreover, the model could distinguish with 100% accuracy whether a participant had an injury or not, and it could also facilitate proportional control of certain movements after the injury. Analysis of the latent space of the model revealed that proportionally controllable movements exhibited an elliptical path, while movements lacking proportional control followed a chaotic trajectory. We found that proportional control of a movement can only be correctly estimated if the latent space embedding of the movement follows an elliptical path (correlation = 0.73; p < 0.001). These findings emphasize the reliability of the proposed system for closed-loop applications that require an accurate estimate of the spinal cord motor output.
Scoping Review of Maternal Monocytes and the Syncytiotrophoblast: Bi-Directional Communication in the Intervillous Space
Authors: Yankello Hannah , Smith Caroline , Daniel Kristin , Megli Christina J , Wayne Elizabeth C
Published: May 2024

The relationship between maternal monocytes and the placenta is crucial for successful pregnancy. As existing reviews focus on the research on decidual macrophages or Hofbauer cells (fetal macrophages), we conducted a scoping review of literature studies examining the relationship between circulating maternal monocytes and the villous trophoblast. The goal of this review was to outline existing research within the field, disseminate further information, and to identify current knowledge gaps within the field. We searched the PubMed (MEDLINE) database for relevant articles published since 1995 that studied human tissue or cell lines. Our results showed clear trends in the type of monocyte and placental primary tissues and cell lines used. Further classification of these articles revealed four primary categories of monocyte-trophoblast interaction research: monocyte presence or recruitment to the placenta, monocyte phenotype in the intervillous space, monocyte-placental adhesion, and monocyte interaction with syncytiotrophoblast-derived extracellular vesicles (STBEVs). Although limited in scope and number, these studies implicate the importance of monocyte-trophoblast interactions, and their significant roles in maternal disease.
MARK2 regulates Golgi apparatus reorientation by phosphorylation of CAMSAP2 in directional cell migration
Authors: Xu Peipei , Zhang Rui , Zhou Zhengrong , Xu Honglin , Li Yuejia , Yang Mengge , Lin Ruifan , Wang Yingchun , Huang Xiahe , Xie Qi , Meng Wenxiang
Published: May 2024

The reorientation of the Golgi apparatus is crucial for cell migration and is regulated by multi-polarity signals. A number of non-centrosomal microtubules anchor at the surface of the Golgi apparatus and play a vital role in the Golgi reorientation, but how the Golgi are regulated by polarity signals remains unclear. Calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) is a protein that anchors microtubules to the Golgi, a cellular organelle. Our research indicates that CAMSAP2 is dynamically localized at the Golgi during its reorientation processing. Further research shows that CAMSAP2 is potentially regulated by a polarity signaling molecule called MARK2, which interacts with CAMSAP2. We used mass spectrometry to find that MARK2 phosphorylates CAMSAP2 at serine 835, which affects its interaction with the Golgi associated protein USO1 but not with CG-NAP or CLASPs. This interaction is critical for anchoring microtubules to the Golgi during cell migration, altering microtubule polarity distribution, and aiding Golgi reorientation. Our study reveals an important signaling pathway in Golgi reorientation during cell migration, which can provide insights for research in cancer cell migration, immune response, and targeted drug development.
Effects of Ca2+on the Structure and Dynamics of PIP3 in Model Membranes Containing PC and PS
Authors: Bernstein Ashley D. , Yang Yanxing , Osborn Popp Thomas M. , Ampadu Gertrude Asante , Acharya Gobin Raj , Nieuwkoop Andrew J.
Published: May 2024

Phosphatidylinositol phosphates (PIPs) are a family of seven different eukaryotic membrane lipids that have a large role in cell viability, despite their minor concentration in eukaryotic cellular membranes. PIPs tightly regulate cellular processes such as cellular growth, metabolism, immunity, and development through direct interactions with partner proteins. Understanding the biophysical properties of PIPs in the complex membrane environment is important to understand how PIPs selectively regulate a partner protein. Here we investigate the structure and dynamics of PIP3 in lipid bilayers that are simplified models of the natural membrane environment. We probe the effects of the anionic lipid phosphatidylserine (PS) and the divalent cation Ca2+. We use solution and solid-state1H,31P, and13C NMR all at natural abundance combined with MD simulations to characterize the structure and dynamics of PIPs.1H and31P 1D spectra show good resolution at high temperatures with isolated peaks in the headgroup, interfacial, and bilayer regions. Site specific assignment of these 1D reporters were made and used to measure the effects of Ca2+and PS. In particular, the resolved31P signals of the PIP3 headgroup allowed for extremely well localized information about PIP3 phosphate dynamics, which the MD simulations were able to help explain. Cross polarization kinetics provided additional site-specific dynamics measurements for the PIP3 headgroups.
Modular, inducible, and titratable expression systems forEscherichia coliandAcinetobacter baumannii
Authors: Bacon Emily E. , Tran Jennifer S. , Nadig Nischala , Peters Jason M.
Published: May 2024

Gene expression systems that transcend species barriers are needed for cross-species analysis of gene function. In particular, expression systems that can be utilized in both model and pathogenic bacteria underpin comparative functional approaches that inform conserved and variable features of bacterial physiology. Here, we develop replicative and integrative vectors alongside a novel, IPTG-inducible promoter that can be used in the model bacteriumEscherichia coliK-12 as well as strains of the antibiotic-resistant pathogen,Acinetobacter baumannii. We generate modular vectors that transfer by conjugation at high efficiency and either replicate or integrate into the genome, depending on design. Embedded in these vectors, we also developed a synthetic, IPTG-inducible promoter, PabstBR, that induces to a high level, but is less leaky than the commonly usedtrcpromoter. We show that PabstBRis titratable at both the population and single cell level, regardless of species, highlighting the utility of our expression systems for cross-species functional studies. Finally, as a proof of principle, we use our integrating vector to develop a reporter for theE. colienvelope stress σ factor, RpoE, and deploy the reporter inE. coliandA. baumannii, finding thatA. baumanniidoes not recognize RpoE-dependent promoters unless RpoE is heterologously expressed. We envision that these vector and promoter tools will be valuable for the community of researchers that study fundamental biology ofE. coliandA. baumannii.

Importance

Acinetobacter baumanniiis a multidrug-resistant, hospital-acquired pathogen with the ability to cause severe infections. Understanding the unique biology of this non-model bacterium may lead to the discovery of new weaknesses that can be targeted to treat antibiotic-resistant infections. Here, we provide expression tools that can be used to study gene function inA. baumannii, including in drug-resistant clinical isolates. These tools are also compatible with the model bacterium,Escherichia coli, enabling cross-species comparisons of gene function. We anticipate that the use of these tools by the scientific community will accelerate our understanding ofAcinetobacterbiology.
Endocannabinoid regulation of inward rectifier potassium (Kir) channels
Authors: Mayar Sultan , Borbuliak Mariia , Zoumpoulakis Andreas , Bouceba Tahar , Labonté Madeleine M. , Ahrari Ameneh , Sinniah Niveny , Memarpoor-Yazdi Mina , Vénien-Bryan Catherine , Tieleman D. Peter , D’Avanzo Nazzareno
Published: May 2024

The inward rectifier potassium channel Kir2.1 (KCNJ2) is an important regulator of resting membrane potential in both excitable and non-excitable cells. The functions of Kir2.1 channels are dependent on their lipid environment, including the availability of PI(4,5)P2, secondary anionic lipids, cholesterol and long-chain fatty acids acyl coenzyme A (LC-CoA). Endocannabinoids are a class of lipids that are naturally expressed in a variety of cells, including cardiac, neuronal, and immune cells. While these lipids are identified as ligands for cannabinoid receptors (CBRs), there is a growing body of evidence that they can directly regulate the function of numerous ion channels independently of CBRs. Here we examine the effects of a panel of endocannabinoids on Kir2.1 function and demonstrate that a subset of endocannabinoids can alter Kir2.1 conductance to varying degrees independently of CBRs. Using computational and SPR analysis, endocannabinoid regulation of Kir2.1 channels appears to be the result of altered membrane properties, rather than through direct protein-lipid interactions. Furthermore, differences in endocannabinoid effects on Kir4.1 and Kir7.1 channels, indicating that endocannabinoid regulation is not conserved among Kir family members. These findings may have broader implications on the function of cardiac, neuronal and/or immune cells.
Structural and Biophysical Dynamics of Fungal Plasma Membrane Proteins and Implications for Echinocandin Action inCandida glabrata
Authors: Jiang Jennifer , Keniya Mikhail V. , Puri Anusha , Zhan Xueying , Cheng Jeff , Wang Huan , Lin Gigi , Lee Yun-Kyung , Jaber Nora , Hassoun Yasmine , Shor Erika , Shi Zheng , Lee Sang-Hyuk , Xu Min , Perlin David S. , Dai Wei
Published: May 2024

Fungal plasma membrane proteins represent key therapeutic targets for antifungal agents, yet their structure and spatial distribution in the native context remain poorly characterized. Herein, we employ an integrative multimodal approach to elucidate the structural and functional organization of plasma membrane protein complexes inCandida glabrata, focusing on prominent and essential membrane proteins, the polysaccharide synthase β-(1,3)-glucan synthase (GS) and the proton pump Pma1. Cryo-electron tomography (cryo-ET) and live cell imaging reveal that GS and Pma1 are heterogeneously distributed into distinct plasma membrane microdomains. Treatment with caspofungin, an echinocandin antifungal that targets GS, alters the plasma membrane and disrupts the native distribution of GS and Pma1. Based on these findings, we propose a model for echinocandin action that considers how drug interactions with the plasma membrane environment lead to inhibition of GS. Our work underscores the importance of interrogating the structural and dynamic characteristics of fungal plasma membrane proteinsin situto understand function and facilitate precisely targeted development of novel antifungal therapies.
Non-enzymatic oxylipin production in a mudflat microphytobenthic biofilm: evidence of a diatom response to light
Authors: Doose Caroline , Oger Camille , Mas-Normand Lindsay , Durand Thierry , Hubas Cédric
Published: May 2024

The microphytobenthos (MPB) is a diatom dominated microbial community of primary producers inhabiting the mudflat sediments. In one hand, the benthic diatoms display photo-protective strategies to face extreme light variations susceptible to generate cellular oxidative stress. In the other hand, oxidative stress induces the production of reactive oxygen species (ROS) that generate oxylipins, oxygenated metabolites of polyunsaturated fatty acids (PUFAs), which are among the known chemical mediators in diatoms. However, non-enzymatically generated oxylipins known as isoprostanoids or isofuranoids are poorly studied in diatoms. To better understand the roles of the latter in migrational MPB light response, we investigated the effect of different light irradiances corresponding to dark (D), low light (LL, 50 and 100 µmol. photons. m−2. s−1PAR), medium light (ML, 250 µmol. photons. m−2. s−1PAR), high light (HL, 500, 750 and 1000 µmol. photons. m−2. s−1PAR), on the isoprostanoids production by the biofilm’s organisms. The PUFAs precursors of the varying oxylipins evidenced a diatoms response to light irradiance. Under 1000 PAR condition, the total amount of isoprotanoids increased, indicating an oxidative stress response. Isoprostanes (IsoPs) and prostaglandins (PGs) characterized the HL conditions and evidenced lipid peroxidation probably linked to the higher generation of ROS by the photosynthesis. On the contrary, the phytoprostanes (PhytoPs) characterized the LL and ML where the de-epoxidation state was low and ROS scavengers probably not overwhelmed. This first investigation of non-enzymatic oxylipin production by a microphytobenthic biofilm under different light irradiances highlighted the interest to explore their potential signaling roles related to MPB light responses.
The effects of iron deficient and high iron diets on SARS-CoV-2 lung infection and disease
Authors: Carolin Agnes , Frazer David , Yan Kexin , Bishop Cameron R. , Tang Bing , Nguyen Wilson , Helman Sheridan L. , Horvat Jay , Larcher Thibaut , Rawle Daniel J. , Suhrbier Andreas
Published: May 2024

The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated by a range of comorbidities. A considerable literature suggests iron deficiency and iron overload may contribute to increased infection, inflammation and disease severity, although direct causal relationships have been difficult to establish. Here we generate iron deficient and iron loaded C57BL/6J mice by feeding low and high iron diets, with mice on a normal iron diet representing controls. All mice were infected with a primary omicron XXB SARS-CoV-2 isolate and lung inflammatory responses were analyzed by histology, immunohistochemistry and RNA-Seq. Compared with controls, iron deficient mice showed no significant changes in lung viral loads or histopathology, whereas, iron loaded mice showed slightly, but significantly, reduced lung viral loads and histopathology. Transcriptional changes were modest, but illustrated widespread dysregulation of inflammation signatures for both iron deficient vs. controls, and iron loaded vs. controls. Some of these changes could be associated with detrimental outcomes, whereas others would be viewed as beneficial. Diet-associated iron deficiency or overload thus induced modest modulations of inflammatory signatures, but no significant histopathologically detectable disease exacerbations.

Author summary

A diet deficient in iron can lead to anemia, a widespread problem worldwide. A diet with excessive iron is less common, but can be associated with excessive consumption of iron supplements. We investigate herein using a mouse model, whether low or high iron diets predispose to detrimental outcomes in the lungs after infection with SARS-CoV-2. A considerable literature suggests iron dysregulation would promote infection and inflammation. However, we found, although inflammatory responses showed modest modulations, viral loads were unaffected or slightly reduced, and lung histopathology was either unaffected or indicated slightly less severe disease. These findings do not support a view that low or high iron diets represent comorbidities predisposing to overt detrimental outcomes for acute COVID-19 lung disease.
Attentional propagation of conceptual information in the human brain
Authors: Acunzo David , Grignolio Damiano , Hickey Clayton
Published: May 2024

The visual environment is complicated, and humans and other animals accordingly prioritise some sources of information over others through the deployment of spatial attention. We presume that attention has the ultimate purpose of guiding the abstraction of information from perceptual experience in the development of concepts and categories. However, neuroscientific investigation has focussed closely on identification of the systems and algorithms that support attentional control, or that instantiate the effect of attention on sensation and perception. Much less is known about how attention impacts the acquisition and activation of high-level information in the brain. Here, we use machine learning of EEG and concurrently-recorded EEG/MRI to temporally and anatomically characterise the neural network that abstracts from attended perceptual information to activate and construct semantic and conceptual representations. We find that the trial-wise amplitude of N2pc - an ERP component closely linked to selective attention - predicts the rapid emergence of information about semantic categories in EEG. Similar analysis of EEG/MRI shows that N2pc predicts MRI-derived category information in a network including VMPFC, posterior parietal cortex, and anterior insula. These brain areas appear critically involved in the attention-mediated translation of perceptual information to concepts, semantics, and action plans.
Dual Mechanism of Action: Exosomes from Human iPSC-Cardiomyocytes and Mesenchymal Stem Cells Restore Injured Myocardium
Authors: Tzng Eileen , Bayardo Nathan , Ikeda Gentaro , Takashima Hiroyuki , Lyons Jennifer , Bennett Mihoko , O’Brien Connor G , Yang Phillip C.
Published: May 2024

Background

Transplantation of mesenchymal stem cells or induced pluripotent stem cell derived cardiomyocytes improve heart function after myocardial infarction in pre-clinical models. Exosomes are extracellular vesicles, 30-150nm in size, which regulate the paracrine signal of the stem cells. We investigated the functional outcomes and biological effects of exosomes from pure populations of human bone marrow derived mesenchymal stem cells (MSCs) and induced pluripotent stem cell derived cardiomyocytes (iCMs) in a porcine acute myocardial infarction model.

Methods

Yorkshire swine were subject to proximal left anterior descending artery occlusion with a catheter balloon for 1 hour for ischemia-reperfusion injury. Ten 500ul injections containing 5 x 1011exosomes isolated from the tissue culture media of iCMs or MSCs were delivered transendocardially into the peri-infarct region. Cardiac function was assessed by magnetic resonance imaging (MRI). Multi-omic analyses were performed in theex vivoswine peri-infarct specimen to delineate the mechanism of action.

Results

Cardiac MRI at weeks 2 and 4 showed significant improvement in heart function in iCM-derived exosomes while MSC-derived exosomes showed a trend towards improvement. A comparative analysis of transcriptomic sequencing of the porcine peri-infarct tissue and Next Generation Sequencing of the exosome cargo confirmed the dual mechanism of action. The marked improvements seen in cardiac function are conferred by miRNA carried by the exosomes, particularly by cardioprotective reduction in metabolism during acute myocardial injury while promoting concurrent cardiomyocyte cell cycle re-entry and proliferation.

Conclusions

Significant reduction in myocardial metabolism and increase in proliferation signal pathways were found in both exosome treatment groups; however, distinct sets of microRNAs were found to underlie the mechanism of action in each population of exosomes.
scRNA-seq reveals transcriptional dynamics ofEncephalitozoon intestinalisparasites in human macrophages
Authors: Jaroenlak Pattana , McCarty Kacie L. , Xia Bo , Lam Cherry , Zwack Erin E. , Yanai Itai , Bhabha Gira , Ekiert Damian C.
Published: May 2024

Microsporidia are single-celled intracellular parasites that cause opportunistic diseases in humans.Encephalitozoon intestinalisis a prevalent human-infecting species that invades the small intestine. Dissemination to other organ systems is also observed, and is potentially facilitated by macrophages. The macrophage response to infection and the developmental trajectory of the parasite are not well studied. Here we use single cell RNA sequencing to investigate transcriptional changes in both the host and parasite during infection. While a small population of infected macrophages mount a response, most remain transcriptionally unchanged, suggesting that the majority of parasites may avoid host detection. The parasite transcriptome reveals large transcriptional changes throughout the life cycle, providing a blueprint for parasite development. The stealthy microsporidian lifestyle likely allows these parasites to harness macrophages for replication and dissemination. Together, our data provide insights into the host response in primary human macrophages and theE. intestinalisdevelopmental program.
Study of weak radiative decays of
D0→Vγ
Authors: Cao Ye , Zhao Qiang
Published: May 2024

The weak radiative decay of D0→Vγ with V=K¯0, and ϕ, ρ0, and ω, is systematically studied in the vector meson dominance model. It allows us to distinguish the short-distance mechanisms which can be described by the tree-level transitions in the nonrelativistic constituent quark model, and the long-distance mechanisms which are related to the final-state interactions (FSIs). We find that the FSI effects play a crucial role in D0→Vγ and the SU(3) flavor symmetry can provide a natural constraint on the relative phase between the short and long-distance transition amplitudes. Our analysis suggests that the D-meson weak radiative decays can serve as a good case for investigating the nonperturbative QCD mechanisms at the charm quark mass region.

Published by the American Physical Society
2024
Fourier calculus from intersection theory
Authors: Brunello Giacomo , Crisanti Giulio , Giroux Mathieu , Mastrolia Pierpaolo , Smith Sid
Published: May 2024

Building on recent advances in studying the cohomological properties of Feynman integrals, we apply intersection theory to the computation of Fourier integrals. We discuss applications pertinent to gravitational bremsstrahlung and deep inelastic scattering in the saturation regime. After identifying the bases of master integrals, the latter are evaluated by means of the differential equation method. Finally, new results with exact dependence on the spacetime dimension D are presented.

Published by the American Physical Society
2024
Orbifold modular GUT of flavor
Authors: de Anda Francisco J. , King Stephen F.
Published: May 2024

We discuss an SU(5) grand unified theory based on the 10d orbifold (T2)3/(Z4×Z2) plus three modular

S

4

groups with moduli at respective fixed points i,i+2,ω=e2iπ/3. The resulting model has hierarchical quark and charged-lepton mass matrices, arising from a double weighton mechanism, and reproduces the highly predictive littlest seesaw mechanism in the neutrino sector. The down-quark mass matrix has an upper triangular form, contributing to Cabibbo-Kobayashi-Maskawa mixing, while the charged-lepton mass matrix has a lower-triangular form with suppressed contributions to Pontecorvo-Maki-Nakagawa-Sakata mixing. The orbifold yields successful SU(5) breaking with doublet-triplet splitting of the Higgs multiplets.

Published by the American Physical Society
2024
Understanding Inner-Shell Excitations in Molecules through Spectroscopy of the
4f
Hole States of YbF
Authors: Popa S. , Schaller S. , Fielicke A. , Lim J. , Sartakov B. G. , Tarbutt M. R. , Meijer G.
Published: May 2024

Molecules containing a lanthanide atom have sets of electronic states arising from excitation of an inner-shell electron. These states have received little attention but are thought to play an important role in laser cooling of such molecules and may be a useful resource for testing fundamental physics. We study a series of inner-shell excited states in YbF using resonance-enhanced multiphoton ionization spectroscopy. We investigate the excited states of lowest energy, 8474, 9013, and 9090  cm−1 above the ground state, all corresponding to the configuration 4f136s2  F27/2 of the Yb+ ion. They are metastable, since they have no electric dipole allowed transitions to the ground state. We also characterize a state at 31 050  cm−1 that is easily excited from both the ground and metastable states, which makes it especially useful for this spectroscopic study. Finally, we study two states at 48 720 and 48 729  cm−1, which are above the ionization limit and feature strong autoionizing resonances that prove useful for efficient detection of the molecules and for identifying the rotational quantum number of each line in the spectrum. We resolve the rotational structures of all these states and find that they can all be described by a very simple model based on Hund’s case (c). Our study provides information necessary for laser slowing and magneto-optical trapping of YbF, which is an important species for testing fundamental physics. We also consider whether the low-lying inner-shell states may themselves be useful as probes of the electron’s electric dipole moment or of varying fundamental constants, since they are long-lived states in a laser-coolable molecule featuring closely spaced levels of opposite parity.

Published by the American Physical Society
2024
Multiscale stochastic optimal control of hysteretic structures based on wavelet transform and probability density evolution method
Authors: Chha Haylim , Peng Yongbo
Published: May 2024

Purpose

Contemporary stochastic optimal control by synergy of the probability density evolution method (PDEM) and conventional optimal controller exhibits less capability to guarantee economical energy consumption versus control efficacy when non-stationary stochastic excitations drive hysteretic structures. In this regard, a novel multiscale stochastic optimal controller is invented based on the wavelet transform and the PDEM.

Design/methodology/approach

For a representative point, a conventional control law is decomposed into sub-control laws by deploying the multiresolution analysis. Then, the sub-control laws are classified into two generic control laws using resonant and non-resonant bands. Both frequency bands are established by employing actual natural frequency(ies) of structure, making computed efforts depend on actual structural properties and time-frequency effect of non-stationary stochastic excitations. Gain matrices in both bands are then acquired by a probabilistic criterion pertaining to system second-order statistics assessment. A multi-degree-of-freedom hysteretic structure driven by non-stationary and non-Gaussian stochastic ground accelerations is numerically studied, in which three distortion scenarios describing uncertainties in structural properties are considered.

Findings

Time-frequency-dependent gain matrices sophisticatedly address non-stationary stochastic excitations, providing efficient ways to independently suppress vibrations between resonant and non-resonant bands. Wavelet level, natural frequency(ies), and ratio of control forces in both bands influence the scheme’s outcomes. Presented approach outperforms existing approach in ensuring trade-off under uncertainty and randomness in system and excitations.

Originality/value

Presented control law generates control efforts relying upon resonant and non-resonant bands, and deploys actual structural properties. Cost-function weights and probabilistic criterion are promisingly developed, achieving cost-effectiveness of energy demand versus controlled structural performance.
Enhancing employees’ quality of work life and engagement to foster corporate social responsibility: a data mining approach
Authors: Sareminia Saba , Sajedi Haji Fatemeh
Published: May 2024

Purpose

This paper aims to present a dynamic model for strategic and personalized decision-making in human resources (HR), using data mining techniques to enhance corporate social sustainability (CSS). The focus is on the interconnectedness of employee engagement (EE), enablement and the quality of work life.

Design/methodology/approach

The proposed model integrates various HR data, including demographic information, job specifications, payment and rewards, attendance and absence, alongside employees’ perceptions of their work-life quality, engagement and enablement. Data mining processes are applied to generate meaningful insights for senior and middle managers.

Findings

The study implemented the model within a production organization, revealing that factors influencing EE and enablement differ based on gender, marital status and occupational group. Performance-based rewards play a significant role in enhancing engagement, regardless of the reward amount. Factors such as “being recognized for competency” influence engagement for women, while payment has a greater impact on men. Engagement does not directly influence the quality of work life, but subcomponents like perceived transparency and the organization’s processes, particularly the “employee performance evaluation system,” improve work-life quality.

Research limitations/implications

The findings are specific to the studied organization, limiting generalizability. Future research should explore the model’s effectiveness in different cultural and organizational settings.

Practical implications

The proposed model provides practical implications for organizations that enhance CSS. Organizations can gain insights into factors influencing EE and enablement by using data mining techniques, enabling informed decision-making and tailored human resource management practices.

Social implications

This research addresses the societal concern regarding the impact of business activities on sustainability. Organizations can contribute to a more socially responsible and sustainable business environment by focusing on work-life quality and EE.

Originality/value

This paper offers a dynamic model using data mining and machine learning techniques for sustainable human resource management. It emphasizes the importance of customization to align practices with the unique needs of the workforce.
Built environment of community enterprise and culture against odds-the case of Kochi on the west coast of India
Authors: Rao Vidya , Nandineni Rama Devi , Panicker Shaji Kananchira
Published: May 2024

Purpose

This study aims to read ritual performances, built forms and cultural undertones of traumatic migration in the settlements of people at the periphery of mainstream history at Mattancherry in Kochi, India. Interactions between their culture, faith, location, ethnicity and community enterprise are explored. This study is essential in the context of negative social perceptions of internal migration and migrants.

Design/methodology/approach

The methodology is ethnography and includes interdisciplinary fieldwork of transect walks, participant observations, unstructured interviews and architectural documentation. Secondary references were community publications and scholarly journals.

Findings

Constant resilient rebuilding was possible through shared identity and community enterprise. Community temples, monastic institutions, volunteer groups and emerging high-net-worth individuals contributed to nurturing this identity. The temple rituals encouraged an egalitarian outlook. Throughout the settlement’s existence, the centrality of the temple and its religious activities remained constant. Community cohesion and endogamous practices create a cultural island distinct from the general population. Community enterprise also meant contribution to prosperity as productive citizens in the region and beyond.

Originality/value

Religion and shared history-based ethnic community enterprise for survival and prosperity postmigration are observed in this settlement. The conducive entrepreneurial atmosphere is set in its historical, cultural and religious context. This study can, therefore, provide insights for policymakers and academia about the interactions between culture, faith and history during the entrepreneurial process. The cultural context is explored as a backdrop of community enterprise posttraumatic migration, informing societal perceptions about migration and migrants.
Clothing disposal in Ethiopia: methods and motives
Authors: Woldeyohanis Yilma Geletu , Berndt Adele , Elifneh Yohannes Workeaferahu
Published: May 2024

Purpose

This study explores clothing disposal in a developing economy. It focuses on how consumers dispose of clothing and what motives influence them to use a specific disposal method.

Design/methodology/approach

Semi-structured interviews, a qualitative research method, were conducted with a purposive sample of 27 participants from diverse demographic backgrounds within the developing economy of Ethiopia. The interviews were coded and analysed using thematic analysis to identify categories and themes.

Findings

The findings reveal various clothing disposal methods, such as bartering, donating, gifting, repurposing and reusing, and discarding. Different motives drive consumers to use these methods, including economic benefits, altruism, and convenience.

Originality/value

The study bridges an important knowledge gap in literature mainly on three aspects, as highlighted by previous research. Theoretically, in addition to proposing a different perspective of bartering as a disposal method, the study investigates the motives behind clothing disposal methods from diverse consumer groups and proposes a conceptual framework to illustrate the link between clothing disposal methods and motives. Methodologically, the study addresses the call for a more inclusive and diverse sample, considering gender and varied socio-economic groups. Contextually, while previous research has focused on developed economies, this study explains clothing disposal methods and motives from a developing economy context, specifically Ethiopia.