bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the reliability of T2measurement in magnetic resonance imaging
Authors: Yang Xiuli 
Published: June 2024

AbstractMagnetic resonance imaging (MRI) is a versatile technique broadly utilized in research and clinic. Among the information available from MRI measurements, transversal relaxation time (T2) is a basic but critical one to reflect the microstructure and microenvironment at the molecular level. A popular method to estimate T2is employing a series of evolution time (TE) values and, thereafter, fitting with the exponential model (termed as T2fitting). Despite of the popularity in using T2fitting, there is a lack of knowledge how related experimental parameters, such as signal-to-noise (SNR), number of TE utilized, dynamic range of TE, and repetition number of each TE, affect the measurement reproducibility. In this study, we performed Monte Carlo simulations to investigate how SNR, TE number, TE range, and repetition number influence the reliability of T2measurement, which was indexed by coefficient of variations. Good reliability with ≤5.0% variation can be achieved when the normalized noise level is below 2.2%. Optimal TE range for measuring T2is related to the T2under evaluation. TE number and repetition number can be increased to reduce measurement variations.
Intragenomic conflict underlies extreme phenotypic plasticity in queen-worker caste determination in honey bees (Apis mellifera)
Authors: Bresnahan Sean T. , Mahony Shaun , Anton Kate , Harpur Brock , Grozinger Christina M. 
Published: June 2024

AbstractCaste determination of honey bees (Apis mellifera) is a prime example of developmental plasticity, where differences in larval diet will result in identical genotypes yielding either long-lived, reproductive queens or short-lived, facultatively sterile workers. Beyond environmental factors, intragenomic conflict between genes inherited from the mother (matrigenes) versus the father (patrigenes) is also hypothesized to generate this plasticity. In honey bees, the Kinship Theory of Intragenomic Conflict predicts selection on patrigenes to enhance traits that result in fitness gained through reproduction, and thus patrigenes should favor the queen caste fate. Here, we conducted allele-specific transcriptome analyses on queen-destined larvae (QL) and worker-destined larvae (WL) at 192 hours post-fertilization (hpf), a critical stage for caste determination. Our findings reveal hundreds of genes with parent-of-origin effects (POEs), with significant patrigene-biased transcription in QL. Genes with POEs in honey bees resemble imprinted genes in other taxa in terms of genomic clustering, recombination rate, intron length and CpG density, and a subset are maintained from 24hpf eggs. Previous studies demonstrated that DNA methylation, the canonical regulatory mechanism underlying transcriptional POEs in placental mammals, angiosperms, and some insects, is not operating in honey bees or other social insects. We use allele-specific ChIP-seq analyses to demonstrate that POEs on caste-specific histone post-translational modification (HPTM) profiles of H3K27me3, H3K4me3 and H3K27ac are associated with POEs on transcription. Together, these findings suggest that parent-of-origin intragenomic conflicts may contribute broadly to phenotypic plasticity and may be associated with HPTMs, suggesting a “non-canonical” genomic imprinting-like system in social insects.
Olfactory facilitation of visual categorization in the 4-month-old brain depends on visual demand
Authors: Kiseleva Anna , Rekow Diane , Schaal Benoist , Leleu Arnaud 
Published: June 2024

AbstractTo navigate their environment, infants rely on intersensory facilitation when unisensory perceptual demand is high, a principle known as inverse effectiveness. Given that this principle was mainly documented in the context of audiovisual stimulations, here we aim to determine whether it applies to olfactory-to-visual facilitation. We build on previous evidence that the mother’s body odor facilitates face categorization in the 4-month-old brain, and investigate whether this effect depends on visual demand. Scalp electroencephalogram (EEG) was recorded in 2 groups of 4-month-old infants while they watched 6-Hz streams of visual stimuli with faces displayed every 6thstimulus to tag a face-selective response at 1 Hz. We used variable natural stimuli in one group (NatGroup), while stimuli were simplified in the other group (SimpGroup) to reduce perceptual categorization demand. During visual stimulation, infants were alternatively exposed to their mother’svs. a baseline odor. For both groups, we found an occipito-temporal face-selective response, but with a larger amplitude for the simplified stimuli, reflecting less demanding visual categorization. Importantly, the mother’s body odor enhances the response to natural, but not to simplified, face stimuli, indicating that maternal odor improves face categorization when it is most demanding for the 4-month-old brain. Overall, this study demonstrates that the inverse effectiveness of intersensory facilitation applies to the sense of smell during early perceptual development.Highlights- Intersensory facilitation is a function of unisensory perceptual demand in infants (inverse effectiveness).- This inverse relation between multisensory and unisensory perception has been mainly documented using audiovisual stimulations.- Here we show that olfactory-to-visual facilitation depends on visual demand in 4-month-old infants.- The inverse effectiveness of intersensory facilitation during early perceptual development applies to the sense of smell.
ATP Citrate Lyase Supports Cardiac Function and NAD+/NADH Balance And Is Depressed in Human Heart Failure
Authors: Meddeb Mariam , Koleini Navid , Jun Seungho , Keykhaei Mohammad , Farshidfar Farnaz , Zhao Liang , Kwon Seoyoung , Lin Brian , Keceli Gizem , Paolocci Nazareno , Hahn Virginia , Sharma Kavita , Pearce Erika L. , Kass David A. 
Published: June 2024

AbstractBackgroundATP-citrate lyase (ACLY) converts citrate into acetyl-CoA and oxaloacetate in the cytosol. It plays a prominent role in lipogenesis and fat accumulation coupled to excess glucose, and its inhibition is approved for treating hyperlipidemia. In RNAseq analysis of human failing myocardium, we foundACLYgene expression is reduced; however the impact this might have on cardiac function and/or metabolism has not been previously studied. As new ACLY inhibitors are in development for cancer and other disorders, such understanding has added importance.MethodsCardiomyocytes,ex-vivobeating hearts, andin vivohearts with ACLY inhibited by selective pharmacologic (BMS303141, ACLYi) or genetic suppression, were studied. Regulation of ACLY gene/protein expression, and effects of ACLYi on function, cytotoxicity, tricarboxylic acid (TCA)-cycle metabolism, and redox and NAD+/NADH balance were assessed. Mice with cardiac ACLY knockdown induced by AAV9-acly-shRNA or cardiomyocyte tamoxifen-inducibleAclyknockdown were studied.ResultsAclygene expression was reduced more in obese patients with heart failure and preserved EF (HFpEF) than HF with reduced EF.In vivopressure-overload andin vitrohormonal stress increased ACLY protein expression, whereas it declined upon fatty-acid exposure. Acute ACLYi (1-hr) dose-dependently induced cytotoxicity in adult and neonatal cardiomyocytes, and caused substantial reduction of systolic and diastolic function in myocytes andex-vivobeating hearts. In the latter, ATP/ADP ratio also fell and lactate increased. U13C-glucose tracing revealed an ACLY-dependent TCA-bypass circuit in myocytes, where citrate generated in mitochondria is transported to the cytosol, metabolized by ACLY and then converted to malate to re-enter mitochondria, bypassing several NADH-generating steps. ACLYi lowered NAD+/NADH ratio and restoring this balance ameliorated cardiomyocyte toxicity. Oxidative stress was undetected with ACLYi. Adult hearts following 8-weeks of reduced cardiac and/or cardiomyocyte ACLY downregulation exhibited ventricular dilation and reduced function that was prevented by NAD augmentation. Cardiac dysfunction from ACLY knockdown was worse in hearts subjected to sustained pressure-overload, supporting a role in stress responses.ConclusionsACLY supports normal cardiac function through maintenance of the NAD+/NADH balance and is upregulated by hemodynamic and hormonal stress, but depressed by lipid excess. ACLY levels are most reduced in human HFpEF with obesity potentially worsening cardio-metabolic reserve.
Ratios in Disguise, Truths Arise: Glycomics Meets Compositional Data Analysis
Authors: Bennett Alexander R. , Lundstrøm Jon , Chatterjee Sayantani , Thaysen-Andersen Morten , Bojar Daniel 
Published: June 2024

AbstractComparative glycomics data are an instance of compositional data defined by the Aitchison simplex, where measured glycans are parts of a whole, indicated by relative abundances, which are then compared between conditions. Applying traditional statistical analyses to this type of data often results in misleading conclusions, such as spurious “decreases” of glycans between conditions when other structures sharply increase in abundance, or routine false-positive rates of >25% for differential abundance. Our work introduces a compositional data analysis framework, specifically tailored to comparative glycomics, to account for these data dependencies. We employ center log-ratio (CLR) and additive log-ratio (ALR) transformations, augmented with a model incorporating scale uncertainty/information, to introduce the most robust and sensitive glycomics data analysis pipeline. Applied to many publicly available comparative glycomics datasets, we show that this model controls false-positive rates and results in new biological findings. Additionally, we present new modalities to analyze comparative glycomics data with this framework. Alpha- and beta-diversity enable exploration of glycan distributions within and between biological samples, while cross-class glycan correlations shed light on complex and previously undetected interdependencies. These new approaches have revealed deeper insights into glycome variations that are critical to understanding the roles of glycans in health and disease.
A Second Drug Binding Site in P2X3
Authors: Thach Trung , Dhanabalan KanagaVijayan , Nandekar Prajwal Prabhakarrao , Stauffer Seth , Heisler Iring , Alvarado Sarah , Snyder Jonathan , Subramanian Ramaswamy 
Published: June 2024

AbstractPurinergic P2X3 receptors form trimeric cation-gated channels, which are activated by extracellular ATP. P2X3 plays a crucial role in chronic cough and affects over 10% of the population. Despite considerable efforts to develop drugs targeting P2X3, the highly conserved structure within the P2X receptor family presents obstacles for achieving selectivity. Camlipixant, a potent and selective P2X3 antagonist, is currently in phase III clinical trials. However, the mechanisms underlying receptor desensitization, ion permeation, principles governing antagonism, and the structure of P2X3 when bound to camlipixant remain elusive. In this study, we established a stable cell line expressing homotrimeric P2X3 and utilized a peptide scaffold to purify the complex and determine its structure using cryo-electron microscopy (cryo-EM). P2X3 binds to camlipixant at a previously unidentified drug-binding site and functions as an allosteric inhibitor. Structure-activity studies combined with modeling and simulations have shed light on the mechanisms underlying the selective targeting and inhibition of P2X3 by camlipixant, distinguishing it from other members of the P2X receptor family.
Molecular tension authenticates apoptotic cells being phagocytosed
Authors: Min Chanhyuk , Cho Hyeokjin , Yu Jeongmin , Moon Byeongjin , Jeon Jaeseon , Shahdab Nafeesa , Moon Hyunji , Yang Susumin , Lee Juyeon , Jin Jaeseong , Hong Mingi , Chung Won-jin , Park Jihwan , Lee Gwangrog , Park Daeho 
Published: June 2024

AbstractProfound cytoskeletal reorganization and plasma membrane deformation in phagocytes is indispensable for phagocytosis of massive apoptotic cells, but whether these dynamics accompany a mechanical signal modulating signaling during efferocytosis remains largely unexplored. Here, we report that tension between phosphatidylserine (PS) and PS receptors (PSR) generated at the phagocytic synapse serves as a signal to determine whether PS-exposing cells should be phagocytosed. Mechanistically, increased membrane tension of phagocytes via Rac1-dependent actin polymerization and membrane stiffness of apoptotic cells caused tension between PS and PSRs, leading to phosphoinositide 3-kinase recruitment to PSRs, which resulted in Rac1 inactivation and myosin II phosphorylation required for phagocytic cup closure. Our observations imply that tension between PS and PSRs acts as a mechanical fail-safe to prevent removal of all PS-exposing cells for the integrity of efferocytosis.One-Sentence SummaryTension between phosphatidylserine and its receptors acts as a final decision-maker determining phagocytosis of apoptotic cells.
Signal Antagonists SuppressPseudomonas syringaePathogenicity
Authors: Mas-Roselló Josep , Mathew Anugraha , Avramenko Veronika , Ren Jiajun , Steiner Till , Sieber Simon , Eberl Leo , Gademann Karl 
Published: June 2024

AbstractThe bacterial plant pathogenPseudomonas syringaecauses significant damage to economically important crops worldwide. These bacteria coordinate their behavior and virulence through specific signaling compounds, such as the diazeniumdiolate leudiazen. Conventional antibacterial treatments enable the development of resistant strains. A more attractive treatment strategy would involve antagonists that suppress the expression of virulence factors without killing the pathogen, potentially reducing the risk of resistance development. Herein, we present the design and synthesis of analogs of leudiazen, which positively regulates the production of mangotoxin inP. syringaepv.syringae(Pss). Several compounds display inhibitory activity towards mangotoxin production, and a lead compound abolishes necrosis in infected tomato leaves, without significantly affecting bacterial growth. Thus, this study represents a promising advance towards developing effective and sustainable methods for bacterial disease control.
A proteome-wide yeast degron collection for the dynamic study of protein function
Authors: Valenti Rosario , David Yotam , Edilbi Dunya , Dubreuil Benjamin , Asraf Yeynit , Meir-Salame Tomer , Sass Ehud , Schuldiner Maya 
Published: June 2024

AbstractGenome-wide collections of yeast strains, known as libraries, revolutionized the way systematic studies are carried out. Specifically, libraries that involve a cellular perturbation, such as the deletion collection, have facilitated key biological discoveries. However, short-term rewiring and long-term accumulation of suppressor mutations often obscure the functional consequences of such perturbations. We present the AID library which supplies “on demand” protein depletion to overcome these limitations. Here, each protein is tagged with a Green Fluorescent Protein (GFP) and an Auxin inducible degron (AID), enabling rapid protein depletion that can be quantified systematically using the GFP element. We characterized the degradation response of all strains and demonstrated its utility by revisiting seminal yeast screens for genes involved in cell cycle progression as well as mitochondrial distribution and morphology. In addition to recapitulating known phenotypes, we also uncovered proteins with previously unrecognized roles in these central processes. Hence, our tool expands our knowledge of cellular biology and physiology by enabling access to phenotypes that are central to cellular physiology and therefore rapidly equilibrated.
Morphometric Analysis of Actin Networks
Authors: Akenuwa Oghosa H. , Gu Jinmo , Nebenführ Andreas , Abel Steven M. 
Published: June 2024

AbstractThe organization of cytoskeletal elements is pivotal for coordinating intracellular transport in eukaryotic cells. Several quantitative measures based on image analysis have been proposed to characterize morphometric features of fluorescently labeled actin networks. While helpful in detecting differences in actin organization between treatments or genotypes, the accuracy of these measures could not be rigorously assessed due to a lack of ground-truth data to which they could be compared. To overcome this limitation, we utilized coarse-grained computer simulations of actin filaments and crosslinkers to generate synthetic actin networks with varying levels of bundling. We converted the simulated networks into pseudo-fluorescence images similar to images obtained using confocal microscopy. Using both published and novel analysis procedures, we extracted a series of morphometric parameters and benchmarked them against analogous measures based on the ground-truth actin configurations. Our analysis revealed a set of parameters that reliably reports on actin network density, orientation, ordering, and bundling. Application of these morphometric parameters to root epidermal cells ofArabidopsis thalianarevealed subtle changes in network organization between wild-type and mutant cells. This work provides robust measures that can be used to quantify features of actin networks and characterize changes in actin organization for different experimental conditions.
Dark matter and spacetime symmetry restoration
Authors: Magueijo João 
Published: June 2024

We examine local physics in the presence of variables: variables associated with the whole of the spacelike surfaces of a foliation. These could be the (pseudo)constants of nature and their conjugate times, but our statements are more general. Interactions between the local and the global (for example, dependence of the local action on global times dual to constants) degrades full space-time diffeomorphism invariance down to spatial diffeomorphism invariance, and so an extra degree of freedom appears. When these presumably primordial global interactions switch off, the local action recovers full invariance and so the usual two gravitons, but a legacy matter component is left over, bearing the extra degree of freedom. Under the assumption that the preferred foliation is geodesic, this component behaves like dark matter, except that 3 of its 4 local degrees of freedom are frozen, forcing its rest frame to coincide with the preferred foliation. The nonfrozen degree of freedom (the number density of the effective fluid) is the survivor of the extra “graviton” present in the initial theory and keeps memory of all the past global interactions that took place in a given location in the preferred foliation. Such “painted-on” dark matter is best distinguished from the conventional one in situations where the preferred frame would be preposterous if all 4 degrees of freedom of dark matter were available. We provide one example: an outflowing halo of legacy matter with exact escape speed at each point and a very specific profile, surrounding a condensed structure made of normal matter.

Published by the American Physical Society
2024
In Situ
Magnetometry of Iron in Human Dopaminergic Neurons Using Superresolution MRI and Ion-Beam Microscopy
Authors: Brammerloh Malte , Sibgatulin Renat , Herrmann Karl-Heinz , Morawski Markus , Reinert Tilo , Jäger Carsten , Müller Roland , Falkenberg Gerald , Brückner Dennis , Pine Kerrin J. , Deistung Andreas , Kiselev Valerij G. , Reichenbach Jürgen R. , Weiskopf Nikolaus , Kirilina Evgeniya 
Published: June 2024

Paramagnetic transition metals play a crucial role as cofactors in various cellular catalytic processes. However, their high concentrations in reactive oxidation states can induce oxidative stress, resulting in cell dysfunction or death. Hence, it is vital to have methods to monitor metal concentrations and paramagnetic properties in cells for medicine and cell biology. Here we present a novel multimodal method for in-cell magnetometry enabling direct measurement of metal magnetic properties within individual cells in tissue, without prior isolation and at room temperature. Individual cell magnetic moments are measured using superresolution magnetic resonance imaging (MRI) microscopy at 9.4 T by detecting microscopic magnetic-field perturbations around the cells. The cellular metal content is quantified using ion-beam microscopy or synchrotron micro-x-ray fluorescence for the same cells. The metal magnetic susceptibility at 9.4 T is then obtained from the slope of the cell magnetic moments’ dependence on cell metal content. To estimate the susceptibility at lower fields, multifield MR relaxometry and biophysical modeling are employed, extrapolating the 9.4-T susceptibility values to fields as low as 3 T. We apply the new method to determine the susceptibility of iron accumulated in human dopaminergic neurons inside neuromelanin, the by-product of dopamine synthesis. The susceptibility of iron in neuromelanin is measured to be χρ=(2.98±0.19)×10−6  m3/kg providing unique insights into the biochemistry of iron inside dopaminergic neurons. The obtained value reveals a predominant monoatomic low-affinity iron-binding site within neuromelanin, indicating a higher neurotoxicity of iron than previously suggested. Furthermore, the measured susceptibility value establishes a quantitative relationship between cellular iron concentration and iron-sensitive MRI parameters, which can be noninvasively measured . This breakthrough paves the way for the detection of dopaminergic neuron density and iron load, requiring a standard clinical MRI scanner only. It promises to facilitate early diagnosis of Parkinson’s disease. In conclusion, our presented novel method enables the direct measurements of magnetic properties of paramagnetic metals within single cells with high sensitivity and across large cell groups within a macroscopic volume, providing invaluable information about the cellular biology of metals.

Published by the American Physical Society
2024
Lost in translation: is Taiwan’s bilingual policy in graduate school a myth?
Authors: Feng Kuo-Zheng 
Published: June 2024

PurposeThis study intended to bridge this gap by investigating the perspectives of international students regarding Taiwan’s bilingual education policy and its impact on their willingness to enroll in graduate programs in Taiwan. Additionally, the comparisons among international students from diverse backgrounds were examined.Design/methodology/approachEmploying a qualitative research design, the study included nine participants from three countries, with each country contributing three students. Three sessions of semi-structured interviews were conducted, supplemented by the analysis of 15 documents from 8 organizations and universities.FindingsResults indicated predominantly negative views toward Taiwan’s bilingual education policy, with little impact reported by two participants and none by others. Furthermore, themes derived from document analysis deviated from participants' viewpoints.Originality/valueA focus on students from southern Asia, which was the major source of international students in Taiwan, becomes critical. In the same vein, little literature has been found concerning graduate students' perceptions toward bilingual education policy, which should be thoroughly explored as well.